bioethics.gov July 8th meeting on synthetic biology in DC
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Bryan Bishop
Jul 1, 2010, 1:42:49 PM7/1/10
to diybio, kan...@gmail.com
I found this agenda item interesting.
http://bioethics.gov/meetings/070810/
- Bryan
http://heybryan.org/
1 512 203 0507
http://bioethics.gov/meetings/070810/
Agenda for July 8-9, 2010
The Ritz-Carlton Washington, D.C.
1150 22nd St. NW
Washington, DC 20037
202-835-0500
No Registration Required
Topic: Synthetic Biology
Thursday, July 8
9-9:30 a.m.
Welcome and Introductions
9:30-10:30 a.m.
Session 1: Overview and Context of the Science and Technology
-
Drew Endy, Ph.D.
- Terman Fellow & Asst. Professor of Bioengineering
Stanford University - Director
BIOFAB: International Open Facility Advancing Biotechnology - President
The BioBricks Foundation
- Terman Fellow & Asst. Professor of Bioengineering
-
Bonnie L. Bassler, Ph.D.
- Howard Hughes Medical Institute Investigator
- Squibb Professor
Dept. of Molecular Biology
Princeton University - President
American Society for Microbiology
-
Robert Carlson, Ph.D.
- Principal
Biodesic
- Principal
10:30-10:45 a.m.
Break
10:45 a.m.-12:30 p.m.
Session 2: Applications
-
J. Craig Venter, Ph.D.
- Founder and President
J. Craig Venter Institute
- Founder and President
-
George Church, Ph.D.
- Professor of Genetics
Harvard Medical School
- Professor of Genetics
-
Kristala L. J. Prather, Ph.D.
- Assistant Professor
Dept. of Chemical Engineering
Massachusetts Institute of Technology
- Assistant Professor
12:30-1:45 p.m.
Lunch
1:45-3 p.m.
Session 3: Benefits and Risks
-
Allison Snow, Ph.D.
- Professor
Dept. of Evolution, Ecology & Organismal Biology
Ohio State University
- Professor
-
Jim Thomas
- Programme Manager
ETC Group
- Programme Manager
-
Nancy M.P. King, J.D.
- Professor
Dept. of Social Sciences and Health Policy
Wake Forest University School of Medicine - Co-Director
WFU Center for Bioethics, Health, and Society
- Professor
3-4 p.m.
Session 4: Ethics
-
Gregory Kaebnick, Ph.D.
- Research Scholar
The Hastings Center - Editor
The Hastings Center Report
- Research Scholar
-
Allen Buchanan, Ph.D.
- James B. Duke Professor of Philosophy
Duke University - Investigator
Institute for Genome Sciences and Policy
Duke University - Distinguished Research Associate
Uehiro Centre for Practical Ethics, University of Oxford
- James B. Duke Professor of Philosophy
4-4:15 p.m.
Break
4:15-5:15 p.m.
Session 5: Plenary
Speakers Roundtable Moderated by Amy Gutmann, Ph.D.
Friday, July 9
9-10:30 a.m.
Session 6: Ethics
-
David Rejeski
- Director
Science and Technology Innovation Program
Woodrow Wilson International Center for Scholars
- Director
-
Markus Schmidt, Ph.D.
- Co-founder
Organisation for International Dialogue and Conflict Management
Vienna, Austria
- Co-founder
-
Paul Root Wolpe, Ph.D.
- Asa Griggs Candler Professor of Bioethics
Director
Center for Ethics
Emory University
- Asa Griggs Candler Professor of Bioethics
10:30-10:45 a.m.
Break
10:45 a.m.-12:15 p.m.
Session 7: Federal Oversight
-
Amy Patterson, M.D.
- Acting Director
Office of Science Policy - Director
Office of Biotechnology Activities
National Institutes of Health
- Acting Director
-
Michael Rodemeyer, J.D.
- Lecturer
Dept. of Science, Technology & Society
School of Engineering and Applied Science
University of Virginia
- Lecturer
-
Edward H. You
- Supervisory Special Agent
Federal Bureau of Investigation
Weapons of Mass Destruction Directorate
Countermeasures Unit I
Bioterrorism Prevention Program
- Supervisory Special Agent
http://heybryan.org/
1 512 203 0507
Bryan Bishop
Jul 8, 2010, 12:45:47 PM7/8/10
to diybio, kan...@gmail.com
I was watching the video, and there was a transcription going on below the stream, but honestly the transcriber wasn't too good (i.e. missing entire sentences). So I decided to try my hand at transcribing the video.
There are components in the cell, uh, George Church and others are going to be using those components, and we think we will as well. They have cell-free systems that can be reconstructed. It's interesting science, but it's irrelevant to these arguments for booting up a new piece of chemical software. One of the most important experiments was in 2007 where we isolated the DNA and chromosome from one species, transplated it into another cell, replacing the DNA in that cell. And it converted the cell into the species that we isolated the DNA from. So it's like putting different DNA into you, and converting you into an other species. We can do that at the single cell level. Doing it at the multiple cell level is uh perhaps decades off, but not centuries away. So these are important concepts about starting with digital code and DNA. It is software. It does build its own hardware. That's an interesting science question: what do we need? We need some ribosomes, a few tRNAs, some other things, some lipids, can we get some cells booted up from that? I think that's going to be important about understanding origins of life. But we are in fact building upon 3.5 billion years of evolution. Um. The arguments that because we're using genes that we discovered, versus inventing new genes, it's kind of spurious, like saying Tesla did not build a new electric car because they bought the batteries from one source, and they bought the electric motor from another source, they combined that to make a Tesla. Um, which is a pretty exciting electric car. My team has discovered the majority of genes known to science. We're up to 40M, there were less than 1M when we started. These are going to be the future design components. Biobricks are important teaching tools. It's great for getting students involved, but the number of genes will top out over the number of 200 or 300 million. We're dealing with a lot of design components. Nobody is going to patent them, and combining them in new ways, now using these tools that we had, the proof of concept experiment, that's the future of this field.
We couldn't do any of this until we did this study that was just published in Science. We're able to make these really large pieces of DNA, but until you can boot them up in a cell, it was just an interesting academic exercise. So, it's very different from what has happened before in molecular biology. This is a new set of tools, starting from a new vantage point. It changes a lot of the rules. Scientists sort of controlled uh who got what, whether they sent them their cell line or DNA clone for their gene. Now, anybody who has access to the internet, that information is in the public databases, you can download and make those genes, now any virus sequence that's in the public databases, can be pretty readily re-made, fortunately not all of them are the DNA-effective. Smallpox is one of them, where just having the DNA from smallpox on its own can't just boot up readily. But these tools are there, and it's a different starting point. All you need is the general information and a DNA synthesizer.
So, building the pieces of DNA was an interesting technological challenge. Getting it booted it up was straight-forward biology and molecular biology. None of it is cloning. So these are totally misuses.. cloning means anything and everything to biologists that sort of collects terms. It's making copies of cell, copies of DNA, splicing DNA, so, we think it's an irrelevant term for what we do. We used the term synthetic cell, because every protein in the cell all the constructions in the cell are derived from the synthetic DNA.
The cell that we used as the recipient cell, all its characteristics are 100% gone after a few replications, so everything in the cell that we have is from that synthetic DNA and therefore we defined it as a synthetic cell. It's a cell that never existed before, uh, of course we used copies of existing genomes. I agree with the very statements- that we're very early on in our knowledge of biology. But we definitely have new tools now to get there. We're using somebody's tools to make new vaccines, so we have a program that is funded by the NIH, to make synthetic components of every flu vaccine that we and others have sequenced, and we can combine these and make a new flu vaccine candidate in less than 24 hours. We're working with Norvartis (?), and it's possible that the flu vaccine that you get next year will be from these synthetic DNA and synthetic genomic technologies.
It was announced last year that we have a program with Exxon Mobile to get cells to capture CO2 and make uh basically a biocrude that can go into refineries. We have not found any cells that can do this naturally at the levels that are required. At the very minimum it is going to need extensive engineering. I am absolutely certain that by the time we get to version 2.0 of these cells they will be completely synthetic as will most things going forward in an industrial environment. Definitions are important, the definitions can be found in our scientific publications. I think this is an area that Drew Endy's students show are more limited by our imagination.
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Back to our early recommendations on licensing being, .. ecosystem of synthetic biology, is important, we need to have surveillance and testing of systems that are proposed to go in. This is just not restricted to bacteria. We have a very active synthetic biology community and human DIY community. Some of my undergraduates have gone and sequenced parts of their genome on their own without FDA approval and without special equipment. This is a whole-nother subject that we are not going to talk about, DIY, do it ourself, do it yourself, bioweathermap and so on. We've studied vaccination, that's another topic for another day, genomic engineering, some success stories, Artimesomeeon, Dupont .. million dollar project, very successful, 90% of the theoretical yield only inolved 8 foreign gene plus 13 up and .. Methylelososne from .. Methyleleosene. 27 changes was a lot of work back then. I am going to talk about 100s of changes that we've incorporated. These are two other companies that I helped start, that are.. not in the future, but are already making 1000s of liters of production-scale fuels either from biomass or carbon dioxide and light. These are making alkanes, diesel and gasoline. The success of comparative genomics, you can look at algae and .. to find those genes, you can take, look at .. and over.. produce them.
Rob Carlson elluded to this, .. this exponential curve from 1.5 to 10 fold. More importantly this is a gap between our recent huge increase due to the second generation sequencing and synthesis. We're still stuck in the first generation for gene synthesis and those four companies, and genome synthesis. We're using first generation sequencing and synthesis for the most part. There are 21 next generation sequencing technologies and 21 companies that go with it, and I am an advisor for about 16 of them. There's also next generation synthesis off of chips, since around 2004, this has lagged a little bit behind for making genes and genomes, but it's certainly terrific for making very short constructs.
* A conformational switch controls the DNA cleavage activity of lambda integrase
* Design, activity and structure of a highly specific artificial endonuclease
Getting those, and working in cells; it's one thing to make DNA, getting it to work in cells; there are protein-based specificity tools, and more general tools which are DNA based and homology based, they do not require particular tools to put it in precise locations in the genome. Some of these require ssDNA, we've automated this in order to bring down the cost. This is multi-plexed automated genome engineering (MAGE) this has one particular implementation shown on this slide, it's a catch-all phrase, this one uses single stranded oligonucleotides, that use CAD to optimize secondary structure and to optimize the position and length, um, you have to have mismatch repair turned off for some of these, and there are special proteins, but the key point is that in a few years we moved from an efficiency of 1e-4 (1 in 10,000) to 25%, 100%, and now we can get up to 8 mutations per 2 hour cycle and we can just continue to cycle 8 changes precisely in the genome where-ever you want. You can make up to a billion different changes in a population. I'll show you an example of where we did 100,000. This is Harrison's prototype, CAD of the upgrade, this is the actual upgrade, this is applying it where we made 100,000 genomes (not one by one but in a mixture), but it shows the awesome power of accelerated evolution in a laboratory where we can make these 100,000 genomes focusing all of the changes in the known pathways including putting in some genes from other organisms, and in three days we can get the highest yields that we have ever seen for this hydrocarbon lipipine, which makes tomatoes red. It evolved (involved?) the order of 24 genes.
Another project that we have done which is less combinatorial, less evolutionary-based, where we wanted to make a precise gneome more resistant to particular viruses, and allowing nucleotides to incorporate efficiently. Here we changed all of the codons for examples of codons (TAG) into TAA (?? i got this wrong) in order to free up that codon and allow us to delete the cellular factor that recognizes it.
SynBERC - Synthetic Biology Engineering Research Center
This can be generalized, there are 64 codons of these triplets, and we've targeted nine of them. This allows us to do three things: multi-virus resistance, safety features,
There are 64 codons of these tirplets, we've targeted nine of them. This allows us to do three things: new amino acids, safety features, and multivirus resistance which itself is a safety feature. We've done one of these nine codons that we are targetting out of 64, we've synthesized all of the DNA to do the remaining eight, at least a proof of concept on the essential genes, and there's another topic- another project- where we are making new ribosomes which is an in vitro system which has interesting commercial applications. Just changing these nine codons would require 2.7% of the genome, but if we're making these 90-mers, we have to tile the genome 2 and a half fold over, we're essentially changing the genome, even though it's just 2.7% of it. Doing it more efficient, all synthesis all at once, where we will probably have multiple failures, doing it one at a time.
Just as a last slide or two, is this issue of safety in terms of isolation. You can have physical isolation, biological isolation. The changing of a genetic code gives you biological isolation- genes can neither go in or out that are functioning. Critics of GM organisms..
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New characteristics. That's part of synthetic biology that has been different from genetic engineering. It's not entirely distinct from systems biology- math, the ability to predict and design what we do. DNA synthesis is an enabling technology. You'll see from the first few slides, if we're talking about biology as engineering and getting easier, Drew Endy was talking about the tech gap between writing DNA and knowing what to write. Under the umbrella of synthetic iology, there's DNA synthesis using it at a mirnimal level. In that vain, this goal of engineering biology, what's our biological workspace? Microbes being a substrate of choice, because of its relative simplicity? It's less complex than a mammalian cell, and also plants, and from an applications perspective, if these are the biological substrates that we want to work with, the applications become pretty clear: therapeutics including pharmaceuticals, small-scale pharma, biologics, protein-therapeutics or more complex therapeutic agents, fuels and energy, not restricted to fuels, chemicals which may be part of the pharmaceuticals, new ways for materials to have renewable materials, get rid of the polyproplyene bottles, agriculture as we go from plants, the biological progression from plants, the potential to expand even what we've seen before with GMO for agricultural.
Controlling transgene expression in subctaneous implants using a skin lotion containing the apple metabolite phloretin
This has been funding, 42.5M from the Gates foundation, and Amyris, and the Keasling lab to develop this technology. One of the interesting things is that the University of California has to agree jadto agree to make the licenses basically free, and the commitment would be that they would develop this at-cost production, this would be a ... Amyris has transitioned this, it's in the hands of industrial manufacturing. They have switched their focus to fuels, so it's an example of how the basic technology of these achievements, synthetic biology and
Non-fermattive pathways for synthesis of branched-chain higher alcohols as biofuels
.. as it applies to fuels. We've talked about microbes, there are efforts and achievements in synthetic biology that are going into more complex systems. This is a paper from Martin Fueznegger groups, from PNAS a year ago, about a circuit for controlling gene expression for implants. So the idea is that they were able to take pieces from bacterial cells in order to put together a regulatory element that would respond to an element, that would respond to a skin lotion, they could have subcutaneous implants, and if you applied this lotion, you would get gene expression. Again this notion of a circuit where you can control expression of a gene from the introduction of a small molecule. Activating gene expression with perhaps novel forms of gene therapy, subcutaneous implant, not modifying the genome with more I would say complex perspectives of gene therapy where you're looking at examples of removing stem cells, re-engineering them, putting them back in, this would be an implant that would be distinct from the native or human chromosome.
LS9, Inc.
Biologically templated photocatlytic nanostructures for sustained light-driven water oxidation
Synthetic protein scaffolds provide modular control over metabolic flux.
A synthetic oscillatory netwrok of transcriptional regulation.
A synthetic gene-metabolic oscillator
A tunable synthetic mammalian oscillator
A synchronized quorum of genetic clocks
Creation of a Bacterial Cell Controlled by a Chemically Synthesized Gneome
Moving on to fuels, I've already mentioned Amyris, this is from the University of California Los Angeles published in Nature. This has been licensed by Gevo. Scale, optimzation and getting something really industrial viable. This is a case where this work was licensed by a company and they are actively working to commercialize this process, similar to the work done with.
.. This is just a screenshot from their website. They really do talk about themselves as being a synthetic biology company, being able to take advantage of all of the extensive information from genome sequencing projects, but increasingly the tools and technologies that we are developing for synthesis and construction of biology. They are relying and focusing on fuels, but they are also focusing on biochemicals.
This is an example of what I mentioned before: energy but not being fuels related. This was a paper released in April of this year from a lab at MIT where again because of the multiple definitions of synthetic biology.. They used M13 phage as a templating device, so they were able to use them to form self-assembled structures, and the phage actually integrated with the inorganic often metals, and they are able to form higher-order structures. This is a case of using biological inspiration, or using biology as a template to make these nanostructures. But we can certainly think about how to expand this about having the power of synthetic biology and constructive biology, to be able to re-design these phages in different ways, so that the types of structures that we get are a little more complex.
One particular application was putting together a strructure that allows you to get photosynthesis. So they had light-driven water splitting, with the idea of using this for energy storage because you could capture now the hydrogen that comes from the splitting of water, and that the hydrogen could be stored and used at a later time. Whereas if we think about traditional solar energy, you have it available when the sun is out, and not available when the sun is not out.
This is from my lab, in collaboration with Keasling. They have the ability to make a pathway for gluceric cid...
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No, thank you very much for that list, and also for ending with the challenge that we have ahead. Keeping with the format that we have used before, I ask the commissioners to get their thoughts together, but I would return the favor and if anyone would like to fofer the first question.
Thank you all. Let me begin with a question to Craig, if I may. Uh, the potential power of synthetic biology creates hopes and it creates fears, and we're all too well aware now of the fears and I want to begin with the fears, as well. So, you mentioned a one-day production of vaccines for a flu, for example. Here's my question to you. What is the single hope that we should most believe in from synthetic biology moving forward? And, it would only be in incumbetent of me, to ask the same question as regard to fear. What is the single fear that we should take most seriously?
Venter: They both give me wide latitude, so I appreciate that. Don't make it too wide. On the hope side, obviously our own teams and others are trying to do as well, we need new tools to make new medicines a lot faster. Particularly with vaccines. It took quite a while with H1N1 the proper response, in part because the rate of building and deciding on seed stocks and in part because we're using 100 year old technology with chicken eggs to produce vaccines. Both need to change and quickly, but with rapid sequencing and all of these changes in reading the genetic code, and now the ability to quickly write the genetic code, it's now hours instead of weeks and months to make new seed stocks. The potential applications, because we can design cells with hundreds to thousands of energetic variation.. diseases like HIV that we're chatting about with that change in their genetic code very rapidly. Things like rhinovirus, we don't have a vaccine against the common cold because the virus evolves very rapidly. Designing things with the same rate of evolution or covering the spectrum of energetic variations gives us whole new ways to approach vaccines that never existed before. On the environmental side, I think it's clear that we need to do something different as we go from 6.5 to 9 to 10 billion people. We can't keep doing what we're doing. All of these different attempts need to be successful in creating new sources of fuel and energy and food or humanity will be irreversibly damaged and altered. We're a society dependent on science now, for our future. Biology is a key part of that future science. Synthetic biology, synthetic genomics are key, I hope, components of altering that future. On the fear side, the worst scenario is what happened in computing because we're talking about software: people make computer viruses that cause a lot of economic damage, but we don't want the same mentality going into making new animal or plant viruses either inadvertently or purposefully, and some of that can be readily prevented by straight-forward regulations, but obviously nobody develops new tech ever produce harm to others, we just would like to see the benefits. I think the molecular biology community has a pretty good track record from the last several decades because of the guidelines and rules that we've all been working under.
I also want to direct this question to Dr. Venter. Um, I've heard both you use and the literature, people have talked about the publication of science as a proof of concept. What is it exactly that it is proving? In part, because as I understand it, the cell wall of the bacteria was used in the first generation, and it's a natural organism that has been synthesized, what is it that it proves, how significant is that proof of concept, but second, building on that, looking forward, you might be working on algae or other multi-cellular organism where the genetic information is in the nucleus of the cell, rather than as a single strand. How far away are we from that? is that the proof of concept that would propel the field forward?
So, what's been possible in molecular biology is what several people described this morning as changing one or two things in a cell, and inserting that into plasmids. While we have evidence in evolution that many bacteria evolved by taking up entire chromosomes, and there are two chromosomes from two very different.. very clearly different origins, so they probably hapepned through these processes. But never before have we molecular biologists been able to take an entire bacterial chromosome, an entire chromosome of anything more than a small virus, transpl,ant it into a cell of one type and convert that cell into another type. Then you add to that, the digital code in the cfomputer, making the entire chromosome from scratch. Means now that we have the means to start with that digital code, make dramatic changes, while we have the basis of an existing organism, we made substantial changes to it, we inserted the names of 46 authors, several quotations, it's the first genome with its first built-in website, web address, these may seem like trivial changes, but uh they clearly identify it as a synthetically made chromosome, something we think is critical for this field and activated that, and completely transformed that one cell into a new cell. It was not just trivial.. one base pair set us back 3mo, one error in 3M bp did not enable this to happen. So, it's now because it's a proof of concept, we do know how to do it, and now we can make much more extensive modifications. We're building a robot to do combinatorial synthesis, where instead of making one chromosome over ten years, our goal is to make a million or so per day by randomly sorting genes or selecting the very specific ones and selecting for living cells that you can't get.. it's not a species that existed before. It's very similar to a pre-existing cell, but it grows substantially faster because of the 14 genes that we elliminated. "And on the multicellular front?" So that we don't get the negative consequences or the unintended ones of that..
"George, you've written on this way or not." I don't know if this is an ethical or policy issue, but many of the previous discussions, the conclusions have been that we're having more discussions. I actually think this is a place where we can do more than this, we can focus on licensing and surveillance, I don't know if this is ethics or not. What has hapepned since 1999 si that this exponential curve has gotten steeper. I would say that it's time to go beyond more discussions.
Following on that, it seems that we have heard a lot from the previous panel and the three of you, about the wide-spread availability, the ability to do it in your garage, that seems to be about obtaining the sequences and the synthesis. And that generates worries, and my question is how big a step is it from having the sequence to actually getting it to work in a biological system, and is that gap big enough that we shouldn't be as fearful of this being misused, or the possibility of regulation or safeguards at that step that would be helpful? True or false?
That wasn't a yes no question, sorry. Then I would say, false. I think that with each new cellular system, and by the way, the Mycoplasma do not have a cell wall, and that's why we chose them - they had a simple plasma membrane which made it simple to make the DNA get across. At the JCVI, we're using spheroplasts that had a plasma membrane. We are at the earliest stages, we need to figure out how these tools are. Getting DNA past cell walls are tough. The two areas go in parallel. The design and synthesis and booting it up. Our worry was that we were going to have a large macromolecu.le, the largest man-made structure ever, and we couldn't activate it, because of one single error. It would have to be optimized for each individual biological systems. It's totally different with cell walls, without cell walls, plants and bacteria. This is going to be a very rapidly expanding research- regulation will be hard. Guidelines at the ... tough.. there's other ways to get around things.
This is going to be a very rapidly expanding area of research and probably difficult to regulate, the guidelines that get set up for approving projects at the institutional level with broader-guidelines at the funding level, and even though our work was not federally funded because our institution is a major federal grant recipient, we have to follow the rules regardless of the funded project that the government chooses. This has been a wonderful example of how to proceed, expanding the repetoire and expanding the way we go on with this.
I might be misinterpreting the question. The information is free. You can go to the NCBI database and get as much sequence as you want. It is cheaper, but still not trivial to pay for synthesis. My lab does not yet, we do not synthesis everything. We do a tremendous amount of PCR, I just had a meeting with a student a day ago, we can get these things synthesized, because it's $3k, but you can't get the 12 other variants that you want, because it's $36k. Some of it is access. Certainly we are not at $10 per base, but we're still under a $1/base, and we're not at a dime per base. At the levels of small amounts of orders, you can get negotations to get 10 cents to 25 cents a base if you want a lot of sequence. I might be misunderstanding your question. Whether or not you're talking about institutional access versus not, skilled labor versus not. Access in terms of cost, the things that may invoke a lot of fear and apprehension are beyond the cost of most non-institutional players, and then because we're talking about difficult biology, and one base pair setting you back three months, there's still a lot to do based on a skilled or unskilled.
Just to follow-up, I appreciate hearing that it is a little more difficult than just doing it in your garage to get the sequencing done, but I was talking about the next step, and whether or not people could do it in their garage, to get it to replicate in their cells, and whether or not that is an impoprtant place that regulation safeguards should be placed to make sure it doesn't get into the wrong hands.
if you read the blogs, everyone wants things to glow with green fluorescent protein. It's relatively easily to order a gene, order a plasmid that has a promoter and a terminator on one end, and transform that in your garage and say hey, it glows. It's very difficult to get your dog to glow. There's a level of complexity there, getting one gene to work in a garage with a junior high school is pretty close to trivial. The types of things that Venter and I did, are not going to happen in the garage with 14 year-olds. It's very expensive.
Thank you very much for your presentations. You talked about some need for regulation, and I was wondering if you could comment on whether all of these things that would fall under the definition of synthetic biology are covered under existing regulations, because of certainly we have regulations on how to handle anthrax, ebola, or do you feel that we need to have new and different types of regulations to deal with issues in synthetic biology.
We certainly have recombinant DNA regulations, but most of this is dependent on federal grants, or in some other way being a responsible citizen. What we don't really have is surveillance that the regulations are being obeyed, by all citizens, not just the standard members of society. WE do not have many regulations on safety testing, even for things that might get into the environment. We take safety testing for granted, there's relatively little of that in biology. There are some gaps that we need to pay attention to.
There are no limitations on what you can order from an oligonucleotide synthesis company. They are not required to list or screen against volatile agents. DNA synthesis is a global effort. If you can't get what you want here, you can order it in Germany or India or China, you can buy DNA synthesizers off of ebay, so maybe there are, people earlier, four companies that are probably 90% of the synthesis in the US even though they are not all in the US, getting them to require a screening against, ordering institution that could go towards the frivulous use. There is a lot of home-brew biology being done in kitchens, it's a new trend, Drew Endy has been in the past, it's great to see, he's stopped encouraging biohacking. We want some reasonable restraints on that, without destroying the wonderful creativity that these kids are doing, to come up with new circuitry that the kids can come up with. I don't think it's covered with existing regulations.
It would be possible to take 100-mers, to recognize that they may come from a pathogenic organism, order a bunch from one company, and be able to put them together. At the level of 100-mers, and anything over an 18-mer, you could get a pretty good trend of what someone is trying to do. The signatures are pretty clear-cut. Also these companies are beginning to coordinate voluntarily, this would be nice to be backed up with regulation. They are voluntarily doing this- splitting an order over four companies would be an alarming event, which combining with sequences that could be recognized, you could put the story together. There will be on-going efforts to get around this.
Entirely based on computational algorithsm, and testing, you could put that story together in hours. Government agencies that are willing to act in hours, that would be great.
I think you've gotten to the heart of a lot of my concerns, as you know. Asymitrio Cult, had an irreavalent strain of anthra, however that is a low hurdle to overcome in the ongoing biological processes, so I've heard a couple of different things. This is still difficult to do, very difficult, but the second part is that it is getting easier. I think that Rahj brought up an interesting point. There are regulations in place now, for traditional biology, being able to reproduce organisms that are on the toxins list or select agents list. But we are talking more about biobricks now, which are quite frankly not part of the regulation for BSAT, so what concerns, and I think you've expressed them, this evolving technology, and getting around the BSAT, the security measures that we would need to take to make sure these would not happen, and what is the balance, you've been prevvied of the latest BSAT, in balancing scientific discovery versus the security for the american people.
I don't actually think that this is a trade-off between security and science discovery. If this is properly implemented, where most of the effort is in developing computer software and getting compliance at the company level and surveillance at the government level. The researchers shouldn't even see it, and they could get on their work. If you require them to sign a piece of paper every few minutes, every time they pipette something, I think that's unlikely. I think some serious computational efforts are in order.
I'm interested in the money behind it all. It's a very expensive proposition to come up with a new cell as you did with over 40M dollars, or new products, and mostly funded now by often small biotech companies, with venture capital kind of money. Are there recommendations for encouraging the entrepreneurship, or not having so tight control or getting a payback on the amount of money you put into a project? Getting that payback quickly, and encouraging entrepreneurs to work on projects. There are huge profits in this if this works out in biofuels or energy, if it continues. Do you have thoughts or recommendations?
In my opinion, this current system is quite healthy to the contrast the one that Rob Carlson described. Most of my experience with dozens of companies, they can get the job done without spending tons of money on lawyers. You don't need the patents, you need the know-how. I have very few examples of patents getting in the way of academic research, and generally not getting in the way of startups. This is such a vibrant field, people are inventing so quickly, they invent around patents, or don't even concern themselves about patents. Going from small to large is quite quickly. LS9 and Exxron, they have Proctor and Gamble and Shevron, this is all in a short number of years. This is healthy.
It's healthy and critical- to get an ecological benefit of taking carbon out of the ground and putting it into the atmosphere, we need that to work out. There have been some recent changes in the stock market; stepped in where the government hasn't. Genentech and private investment, the majority comes from private investment. In our case, we would have been stuck in 2003 with a small synthetic virus if we did not have independent money to start synthetic genomics.
I would only add to that, I agree with what's been said, I think one of the impediments to progress if you will, that can arise if the all of the achievements are done individually, is one of the very big goals of synthetic biology is to have standardization and interoperability. one of the ways that the federal government can help with this is to promote something in the community to organize on a reuglar basis around what should those standards should be, so that you don't have innovation happening in isolation, so that we have technologies evolving independently, and netwroking those becomes difficult. As we dream about synthetic biology, and ...
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Pubsliehd a paper in Science, it's great for understanding the concepts, converting it into the reality, where you can buy the fuel at the gas pump, that could only work in an economically competitive environment. All of these companies like LS9 will only survive if they have an economically competitive product. Any new fuels have to be available and they have to be cheaper than existing fuels, or at least cost-competitive. We need economic driving forces to pull this stuff much more rapidly. I don't see limitation of access, we need access pretty rapidly to CO2-based fuels as an example.
Before I go to NIDA and Anitya, I had a thought that was dropped. In connecting to something that you said. It's the flip side of regulation. Stimulation. one of the ways to insure safety, and in a gressykq-eseuqe way, have the ability to skate ahead of the puck, were you suggesting, or leave it open, the question that we had sort of posed in the prior panel, what would be the very next thing to be funded? Where would we like to see, in view of having a knowledge base and an ability to advance the kinds, and have the deeper knowledge to help ensure, that we can recognize, as Dr. Church mentioned, some of the sinister or potentially sinister application of these things? What would you fund, standardization?
It's a difficult question. So, I think about for example the BIOFAB which Drew Endy is funding and directing. It has an ambitious goal of being a focal point where you can develop parts to use a term in synthetic biology, some discrete pieces of DNA that encode for biological function, characterize them, composability, what happens when you put this thing with another thing, and it's an ambitious goal, and it's great, and they have $2M in 2 years, what happens when that is gone? There is a need for an effort that is more ambitious in scope, much bigger in scope, let's bring, that does two things: (1) serve as a forum or fora for bringing different players together and brainstorming and saying, here's what we're doing, ehre's what this person is doing, how do we interface this for setting a standard, so that new tech will fit in very well. Then how do we set priorities and safely, and so, I'll jumep ahead to a thought- the Synberc experience, we had discussions all along, we had a .. human practices, biosafety and biosecurity and intellectual property and silo applications. So, but that's a small number of people, and an increasingly populated academic field. If you look at the number of people associating with synthetic biology, it's grown astronomically over the past few years. If you take NSF's investment into synberc, and DOE's investment in the joint bio.. institute.. It's real money, it's not trivial, but it's a very small number of people that it impacts. But I would like to see efforts that are designed to bring the community together, and so that we could be more progressive and as opposed to re-active. We're in the midst now where we go with this, here's how it's all wrong, and I'm not saying it's not going to get us where we're going, if we want to bridge the technological divide, where we have the potentials and exciting technologies that have a real impact on humanity, we need to bring this forward quickly.
The two questions that I get most often, people are worried about bioterrorism, and environmental release. It depends on where you are, which one is first or second. George gave some wonderful examples of safety mechanisms that would be built in. It would be nice to have orders of magnitude more, suicide genes, large algae plants, modified organisms, they need to not be able to survive in the environment, suicide genes, artificial amino acids, chemical toxins, expanding the reepertorie of what safe and secure means, that would be a very beneficial thing.
Just quickly- I think it's coupling this question about small versusl arge. Large has some certain safety advantages, when we get to large manufacturing of automobiles did we start to get high levels of safety, as technology gets to a certain point, amateurs stop making it. I made a computer when I was young, the know-how starts to fade away, which is a mixed blessing, but from a safety standpoint, it's important.
It made me very proud of my heritage, engineering. One of the things that has been demonstrated in physical systems is that it is far more effective to design-in safety rather than regulate safety. Anita is next.
>> Thank you. I really have appreciated all these remarks. I wanted to ask Dr. Prather a very specific question about something that you said toward the end of your slides. You had a slide in which you made the intriguing point our synthesis capabilities exceed our design capabilities. We know how, but not what. Can you elaborate on this? The reason I want you to elaborate, we know how but not what, does that point to limitations of the applications that might be forth coming from this science?
It absolutely does.
Bryan Bishop
Jul 8, 2010, 12:58:26 PM7/8/10
to diybio, kan...@gmail.com
On Thu, Jul 8, 2010 at 11:45 AM, Bryan Bishop wrote:
I was watching the video, and there was a transcription going on below the stream, but honestly the transcriber wasn't too good (i.e. missing entire sentences). So I decided to try my hand at transcribing the video.
... starting with digital code and starting with DNA. It is software and it does build its own hardware. I think that's an interesting science question. What do we need? Do we need some ribosomes and TRNAs and lipids and can we get some cells bootup. I think that's going to be important about understanding origins of life. But we are in fact building upon 3.5 billion years of evolution. The argument is because we're using genes that we have discovered versus inventing a new gene is a spurious one. It's like they didn't create a new car because they built a battery from one source and they combined that to make the Tesla, a pretty exciting electric car. My team has discovered a variety of genes known to science. We're up to 40 million. There were less than 1 million when we started. These are going to be the future design components.
I think biobricks are an important teaching tool. It's great for getting students involved but the number of genes on this planet I'm sure will top out somewhere over 200 or 300 million. We're dealing with a lot of design components. Nobody is going to patent them. And I think combining those in new ways, now using these tools we had in the proof of context experiment is what the future of this field is going to be. We couldn't do any of this until we did the study that was just published in science. We were able to make these really large pieces of DNA. But until you can boot them up in a cell and get them activated, it was an interesting academic exercise. So it's very different from what's happened before in molecular biology. This is a new set of tools starting from a new vantage point. And as Drew said, it changes a lot of the rules. Scientists sort of controlled who got what, whether they sent them their cell line or their DNA clone for a gene. Now anybody who has access to the Internet, if that information is in the public databases, you can download it and you can make those genes. Now, any virus sequence that's in the public databases can be pretty readily remade. Fortunately, not all of them is the DNA ineffective. Smallpox is one of them where having the DNA from smallpox on its own can't just boot up readily. But these tools are there. It's a different startling point -- startingd point. All you need is the digital information in a DNA synthesizer. So building the pieces of DNA was an interesting technological challenge. Getting booted up was straightforward biology and molecular biology. None of it is cloning. These are totally misuses of terms. Cloning means everything and anything to biologiesists and it's sort of a collecting term and making copies of cells. It's making copies of DNA. It's splicing DNA. So we think it's an irrelevant term for what we do. We use the term synthetic cell because every protein in the cell, all the constructions in the cell are derived from the synthetic DNA. The cell that we use as the recipient cell, all its characteristics are 100% gone after a few replications. So everything in the cell that we have is from that synthetic DNA and, therefore, we define it as a synthetic cell. It's a cell that never existed before. Of course, we use copies of existing genomes. I agree with the very statements we're very early on in our knowledge of biology, but we definitely have new tools now to get there. We're using some of these tools to make new vaccines so we have a program that is funded by the NIH to make synthetic components of every flu vaccine that we and others have ever sequenced. And we can recombine these and make a new flu vaccine candidate in less than 24 hours that we're working with no virus and it's very possible the flu vaccine you get next year will be from these synthetic DNA, synthetic genomic technologies. It was announced last year that we have a program with ExxonMobil to try and get cells to capture CO2 and make basically a biocrude that can go into refineries. We still have not found any cells that can do this naturally at the levels that are required. So at the very minimum, it's going to need extensive engineering, but I'm absolutely certain, at least by the time we get to version 2.0 of the cells, they will be completely synthetic as will most things going forward in an industrial environment. Definitions are important. The definitions can be found in our scientific publication. I think this is an area that Drew Endy's students show we are limited more by our imaginations now than any technological limitations. I think having an intelligent ethical framework for this new science to emerge in is absolutely critical. Thank you very much.
>> Thank you. We appreciate your views and clarification on the definition. And also impressing upon us the value of the technology coupling with the science. Dr. George Church is our next presenter. Professor of genetickic at Harvard med. He has spineered innovations in reading and writing DNA, he directs personal genomes.org with a goal of enabling open access integration of full genome sequences, environmental and trait data goal of working toward 100,000 individuals. Very interesting application. Again, this session being on applications, very eager. And Dr. George to hear what you have to say. Thanks for being here.
>> So thank you for the time here. As soon as my slides come up, I'm going to talk almost entirely about application. And it's going to different a little bit from previous talks in that I'm not going to talk about introductory definitions and in particular about what we can't do or having done but what we are doing. So this is my thank you slide. And my conflict of interest slide.
[LAUGHTER]
Next slide, please. Can I control this? There we go. Perfect. Okay. Sorry. And so as a graduate student, I work with Greg sutCliff, which we did a ridiculously high cost even though we were students, this has been used in many recombinant DNA efforts that some of them are listed here that we're really single gene efforts. What's wrong with this picture? This fellow is not using safety goggles. He's not properly grounded for electropouration. But the main thing is we've gone well beyond main genome engineering I had in the last slide. We have gone beyond minimal slides to these fast robust useful cells. We're focusing on lower costs. We have talked a lot about scaling up, but not lowering costs. I will focus on that. We look forward to whole genomes, but most of what I'll talk about is doing a little bit less than a whole genome but on a genome scale. And the question is, why do we do things on a genome scale? And then there's safety and security for the reason for doing things on a genome scale. And evolution is a unique capability that we have that most other fields in engineering do not have. And my major takeoff for all this is that we are going much faster than it appears. And we should not be reassured that biology is not capable of engineering and there's no difference between what we're doing and what I did as a graduate student. Why, genome-wide? We need to know why. Genome engineering is a commonly used term and is also a couple of genes done in the chromosome rather than on a plasma. Big deal.
Metabolic you might have a pathway or small network. 30 genes or less. But genetic code offers us multi-virus resistance and safety measures and some use of new amino acid and this is genome wide and one of the few articulated goals that is genome wide. The safety component is incredibly important. This is not meant to just be an analogy or images. But we have interoperable parts. These are all from cars but the same thing applied in biological design. Cost effectiveness, standards and isolation. We need to -- is it sufficient to have a set of rules and guidelines if there isn't testing, if there isn't surveillance? You can do licensing like driver's license but you have to do surveillance to make sure people are obeying the laws. And then again evolution is something that's new. There have been recommendations in 2006 and the next slide 2007 which I think don't go far enough. We talk about preferred practices. We pragmatically talk about federal grantees and contractors. There's a lot more out there than federal grantees and contractors. The Sloan 2007 went a little further than this. But we need to have surveillance and enforcement. And so back to my earlier recommendations on really licensing the entire ecosystem in synthetic biology, it's important. We need to have surveillance and testing of systems that are proposed to go in. And this is not restricted to bacteria. We have a very active human synthetic biology community and human do-it-yourself community. Some of my undergraduates have gone and sequenced part of their genomes on their own without F.D.A. approval and without really using any special equipment. And this is a whole another subject we're not going to talk about. But do it yourself or do it ourself biology and bio weather map and so on. We have studied vaccinations. Genome engineering, some success stories, we already mentioned one but also propane from DuPont to a $400 million project 90% successful. It only involved eight foreign genes plus 13 -- I'm sorry 13 down and six up regulations in the e.coli genome. 27 changes was a lot of work back then. I'm going to talk about hundreds of changes that we have incorporated. These are two other companies that I helped start that are not in the future but are already making thousands of liters of production scale fuels, either from biomass or from carbon dioxide and light. These are making alcanes, diesel and gasoline. Part of this is the success of comparative genomics. You can look through the bacteria for those that make trace amounts, Greg sort of alluded to trace amounts of the alcanes by taking fatty acids and reducing and decarbonnallating them. You can look at the genomes that produced and those that didn't produce these trace amounts and then you can identify the genes and overproduce them. Rob Carlson alluded to this exponential curve. This is actually quite different than his curves, although basically the same. What's different is that around 2004 or 2005, there was an increase in the rate of this exponential curve from 1.5 to 10 fold. And more importantly, this is a gap between the -- thank you. Between our recent huge increase in second generation or next generation sequencing and synthesis. And we're still stuck in the first generation for gene synthesis in the companies and genome synthesis that we're using first generation sequencing and synthesis for the most part.
There are 21 next generation sequencing technologies and 21 companies that go with it. And I am an advisor for about 16 of them. And similarly, there's a next generation synthesis off of chips that we've been doing since around 2004. This has lagged a little bit behind from making agains and genomes but it's certainly terrific for making short constructs.
Working in the cells, it's one thing to make DNA but getting the work in the cells, there are many tools. These are protein based specificity tools. And more general tools which are DNA based, they don't require specific proteins to put it in precise locations in the genome to make precise changes. But some of these involve single stranded DNA number 3 and number 4 in particular. And we have automated this in order to bring down the cost and extend our capabilities industrially. One of these is called -- or the general term is multiplex genome engineering or MAGE. And this has one particular implementation shown on this slide but there are many others. You can see it's a catch-all phrase. This one uses single strand nucleotides that use computer aided design to optimize secondary structures, optimize the position and length. You have to have a mismatch repair turned off for some of these. And there's a special proteins. But the key point is in a few years, we move from an efficiency around 10 to minus 4, 1 in 10,000 to 25% to 100%. And now we can get up to 8 mutations per two-hour cycle and we can just continue the cycle, 8 changes precisely in the genome wherever you want. And I'm sorry. You can make up to 1 billion different changes in a population. I'll show you an example where we did 100,000. This is Harris' prototype. A computer aided design of the upgrade. This is the sphul upgrade. This is applying it where we made 100,000 genomes, not one by one, but in a mixture. And it shows the awesome power of accelerated evolution in the laboratory, where we could make these 100,000 genomes focusing all of the changes in the known path ways, including putting in some genes from other organisms. And in three days, we can get the highest yields we have ever seen for this hydrocarbon lycopene which makes tomatoes red involved on the order of 24 genes. Another project that we have done which is less commonna torial and allows new amino acids and has safety features, here we changed all of the codons into TAA genome wide in order to free up that codon and allow us to delete the cellular factor that recognizes it. This can be generalized. There are 64 codons of these triplets and we have targeted nine of them. This allows us to do three things. New amino acids, safety features and multi-virus resistant which itself is a safety feature. We have these nine. We have done one of these nine codons that we're targeting out of 64. We have synthesized all the DNA to do the remaining eight, at least proof of concept on the essential genes. And another topic that is far beyond what we can talk about today probably is the project where we're making ribosomes and Greg aleaded to an in-vitro system which has interesting commercial applications. The key thing here is just changing these nine codons would require changing just 2.7% of the genome, not the whole genome. But if we're making these optimal 90, we have compiled the genome two and a half fold over and we essentially have remade the genome, even though we've only changed 2.7% of it. And that lies in the future, and it remains to be seen which is more efficient. Doing it all synthesis all at once where we'll probably have multiple failures or doing it one at a time. And just as a quick last slide or two is this issue of safety in terms of isolation. You can have physical isolation or you can have biological isolation. The changes of the genetic code, the genes can neither go out or come in that are functioning. The critics of the genetically manufactured organisms have wanted it.
A third way that it's isolated is physical and genetic and it's this metabolic dating back to the early days of recombinant DNA there was this acid that was used by deleting the biosynthetic pathway that you made the bacterium dependent upon that. It's not common in the environment, but it does occur. And that's one of the down sides. Some of these other SACB or tox-antitox pairs are used but as counter selections. But they are ways of having the cell self-destruct but they have the problem that they can be lost just before you need them. So they are not ideal. So we think going forward using the new genetic code to allow us to design multiple essential genes to have multiple dependencies that have been used in Peter Schultz's group. So in conclusion, just to remind you, you know, where we think we need genome engineering and synthetic biology, it's in making biology safer than it already is and this involves really using some of the lessons of other engineering disciplines, interoperable parts, hierarchyial designs, cost effectiveness, standards, isolation, testing, redundant systems, surveillance very important, not just surveillance of government grantees. Licensing at every part of the ecosystem. And focusing on this ability to evolve both in the lab and outside the lab. Thank you.
>> George, thank you for that. Your message is loud and clear in the face of advancement and technology advancement is astounding. And some near-term applications are very exciting. And also clarifies and I appreciate your last slide. And it was used before to help clarify for us what some engineering challenges are going forward. Our final speaker in this panel is Kristala Jones Prather. Dr. Prather is an Assistant Professor of chemical engineering at MIT and worked in industry as well as academia. Has been recognized for her work with numerous awards and investments. She is a research young investigator and received technology reviews TR35 young investigator award. She has also the NSF investing in her through an NSF career award. She's an investigator in the multiple institutional synthetic biology engineering research center funded by NSF. Welcome, we're pleased to have you here.
>> Thank you very much. Let me start by thanking the commission for an opportunity to come and speak to you today. The title of this panel is applications in synthetic biology. And what I'm going to do is try to give an overview in the field have been. And I hope what we can learn by that is both what we have done today and we can start to think about how that may project forward into what potential achievements or applications of synthetic biology might be in the future. Unlike George, I am going to start with a definition. You have heard a lot of them and you have heard -- I think what's clear is there is I will say lack of universal agreement on what synthetic biology is and how it should be defined. I'm going to give a practical definition, one we use within the research center. It's very simple and it says that synthetic biology is about making biology easier to engineer. You have heard some of these things before, particularly this morning. And in the first session about the relationship between biology and engineering and how they react with each other. For us in particular, it's about applying engineering principles to biological testimonies and it involves words like design, modeling and characterization. I was raised by Jay Keasling and there's a well-known cartoon that Greg Stephanopoulos used to show that there's a group of students in the class and the student raises their hand and says what's the difference between metabolic engineering and genetic engineering and there's a professor that says lots and lots of math. And then there's a picture of the professor and no students. There is this idea that we like to have models of systems that are numerical and mathematical. And it's an attempt so we can have this loop back and change your model and see what the new characteristics are. So I think that is a part of synthetic biology, which has traditionally been different from genetic engineering. But it's not wholly distinct from what you may know as systems biology. Again this effort to include math and the ability to predict and design and what we do.
And we'll highlight DNA synthesis as an enabling technology. You'll see from the first few slides that if we're talking about making biology easier to engineer and we want to get started with that now and based on I thought what Drew gave was a very good slide of the technology gap, if you will, between the ability to write DNA and to know what to write on DNA. Much of what's happening now under the umbrella of synthetic biology is using DNA synthesis at a very minimal level because we have to start with some existing biological substrate. In that vein, if we think of this goal of synthetic biology and what is our biological workspace, we heard about microbes being the substrate of choice because of their relative simplicity and I'll use relative quite intentionally because we're still talking about very complex organisms although they are less complex than the million cells which you see there and also plants. And if you think about now from an applications perspective, the biological substrates we work with, the applications I think become pretty clear in terms of extrapolating. We can think of therapeutics including pharmaceuticals as well as biologics or biopharmaceuticals and protein therapeutic fields, energies and I'll give a brief slide on that. Chemicals which may be part of the pharmaceuticals but leading toward thinking of new ways for materials to have renewable materials, things to get rid of other polypropylene bottles which will fill landfills if we can't figure out good ways to recycle. And agriculture when we think about the biological works of plants and the potential to expand with genetically engineered organisms for agriculture. Wrong button. Too many buttons. With this paper here that we have heard about already, which is the work from the Keasling lab from the University of California at Berkeley, producing the antimalarial drug which can be used for an antimalarial, this was funned as the numbers have come up. I am sure we can all recite them. $42.5 million from the gates foundation as something of a public-private partnership between UC Berkeley and Amyris which was a company founded by folks from the Keasling lab to develop this technology. One of the unique aspects, intellectual property came up previously. There were lots of issues because the University of California had to agree to make the licenses available essentially free and the commitment by all parties involved is that they would develop this as a remedy for at-cost production. This was to be a non-profit generating venture as far as the company is concerned. Amyris, if you have been keeping up with the literature, has sort of transitioned this process. It's now in the hands of industrial manufacturing and they have switched their focus almost exclusively to fuels. So it's an example of how the basic technology of these achievements and what we're able to do with engineering of biology with synthetic biology, with metabolic engineering, whatever particular phase you want to use, builds a repository of intellectual information and intellectual properties that can be then converted into other downstream applications and in this case from therapeutics to fuel. We have talked a lot about microbes. That work was done in microbes. There are efforts and achievements in synthetic biology going into increasingly more complex systems. This is a paper from Martin fussnegger's group about developing effectively a circuit to control gene expression for implants. So the idea was they were able to take pieces from microbial cells to respond to a particular molecule they put into a skin lotion. They could have subcutaneous implants. If you applied this lotion, you would get gene expression. This notion of a circuit to control expression of a gene from the introduction of a small molecule, this is now an example where we can think about how that actually has potential applications in medicine in terms of being able to activate gene expression perhaps with novel forms of gene therapy that would be a subcutaneous implant so you're not talking about trying to modify the genome with more I would say complex perspectives of gene therapy where you're looking at, for example, removing some cells and reengineering them and putting them back into the cell. This would be a separate implant that would be distinct from the native or the human chromosome. Moving on to the field, I have already mentioned Amyris work. This is work from the University of California in Los Angeles that was published in "Nature" a couple of years ago for making higher order branched alcohols as biofuels. This is technology licensed by GeeBo. Dr. Bassler mentioned and if I can paraphrase from going to scale and optimization and getting something industrially viable, this is the case where this work was licensed by a company and they are actively working to commercialize this process. Similar to the work done that we have heard about before, these are pathways to a certain extent are all natural. The molecules being produced were ones being identified as minor products in wine fermentation so the enzymes or the genes needed in order to convert what ends up being intermediate amino acid synthesis were optimized in the most promising was 22 grams per liter of iso buttenol being produced. This is a screen shot from a website. I wanted to highlight the fact that they really do talk about themselves as being a synthetic biology company, being able to take advantage as one has already referred to of all the extensive information that's come to us from genome sequencing projects and increasingly the tools and technologies that we're developing and being able to take advantage of that had have to do with synthesis and construction of biology. They are focusing on fuels, but also on biochemicals. This is an example I mentioned before in terms of energy but not being fuels. This is a paper from April of this year from a lab at MIT where again because of the multiple definitions of synthetic biology we may or may not think of this as synthetic biology. But it just describes briefly what was done here. The Belcher lab at MIT used M-13FHAGE as biotemplating devices. They were able to use them and the PHAGE interact with inorganic often metals and able to form these higher order structures. This is a case of biological expression and biology as a template for making these nanostructures. We could certainly think about how to expand that towards now having the power of synthetic biology and constructive biology to be able to redesign these PHAGEs so the structures are complex. And the particular application was to be able to put together a structure that would allow you to have effectively photosynthesis. And they had the idea you could use this for energy storage and capture the hydrogen from the splitting of water and that hydrogen can be stored and used at a later time. And solar energy you have available when the sun is out and don't have it available when the sun is not out. This is work from my own lab in collaboration. In the chemical space what we were looking at is being able to make a pathway for a compound acid where we don't actually have a natural metabolic pathway for this compound. This is different from the work I presented previously on the branch of alcohols where we weren't starting from a pathway and trying to reconstruct. We started here's a compound we want to make, how do we think about doing that? The particular innovation in this case was to be able to use these novel synthetic scaffolds. And Dr. Bassler mentioned the wonderful spatial organization that happens with a naturally occurring system. This was a synthetic device designed to introduce this spatial organization into a microbial cell. And the result was to have increased productivity for the compounds we were interested in. And I want to refer to biological computing or a lot of the analogies to programmability. The first of which was a program about 10 years that described the repress later. And also from Jim's group, the first was from Princeton and Mike Elowitz and the oscillator called the retabbilator, which is often a fluorescent protein this is oscillation in the metabolite. Now going from again microbial systems and mammalian cells and this was referred to by Dr. Bassler and is now looking at these oscillators and genetic clocks taking advantage of intercellular communication. And this is often discussed and deresided as toy applications and you're just making cells blink. What is that good for? From my own perspective from making these that make high quantities of synthetic chemicals, we're interested in these because we know that timing of gene expression is important for some systems that we're looking at. So we can look at oscillators that have been designed even with clean production proteins and think about how do we extend those into practical applications of systems where we're using them either in therapeutic purposes in order to have time expression of genes, for example, in development, talking about stem cell biology or even in like a large bioreactor talking about chemicals. The last sort of screen set I have is the paper that again was sort of the impetus for this particular discussion from the Venter group which you have already heard about. And I just -- my comment I wanted to make sure is all the things I have talked about so far, you may be thinking what does that have to do with synthetic genomics and the ability to completely synthesize the bacterial genome, what I would say is this is about trying to bridge this
technological divide. What we currently have is the capacity to do very extensive reengineering of genomes from existing cells, taking out lots of genes. Putting in lots of genes. Beyond that, where the challenges often arise or how do you precisely control them, temporally, spatially, these other issues about natural biology, they are complex and very confusing for us. What you have here is now this very clear synthetic capability. And where I see this bridging is that as we get better and better at understanding how to do the kinds of engineering we're doing, then it really is about the differences in scale that Dr. Bassler referred to this morning, that we can think about now going from making these manipulations at the level of an existing genome towards designing them in de novo and starting from scratch with a genome that works the way we want it to work. The final comments is there are, of course, lots of challenges. Biology is complex as we have heard over and over again. I'll add it's often context dependent. We do have the stream of having interchangeable interoperable parts. I'll say from personal experience, you move them from one cell to the other, they don't work the same way. And that's exciting. It's a challenge. It's something that we have to become better at understanding. The synthesis capabilities as you've already heard far exceed the technological capabilities and that's a gap that does in some way point at what our future ambitions are but indicate what our current limitations are. The potential benefits I think are enormous. I indicated a few of these, but, you know, we can think about this in any way where we think about biology being important. At the same time, the risks are real. Because there is this information gap between what we really understand about biology and what our capabilities are, it's impossible for us to really predict what's going to happen in every single experiment. And so I do think it's very worthwhile to think about being as careful as possible as we do this to minimize those risks. And two seconds over, I'll stop.
[LAUGHTER]
>> Very impressive. Thank you very much for that list. And also ending with a challenge that we have ahead. Keeping with the format we used before, I have asked the commissioners to get their thoughts together. But I'll return the favor, Amy, if you would like to offer the first question.
>> Thank you very much. And thank you all. Let me begin with a question to Craig, if I may. The potential power of synthetic biology creates hopes and it creates fears. And we're all too well aware now of the fears. But I want to begin with the hopes as well. So you mentioned the one-day production of a vaccine for flu, for example. So here's my question to you. What is the single hope that we should most believe in from synthetic biology moving forward? And it would only be incumbent on me to ask you the same question with regard to fear. What is the single fear that we should take most seriously?
>> Well, they both give me wide latitude, so I appreciate that. I think --
>> Don't make it too wide.
>> So I also want to direct this question to Dr. Venter. I heard both your views and in the literature people have talked about the publication of science and the proof of concept. And I wanted to understand exactly what it is that it is proving. In part, as I understand it, the cell wall of the bacteria was used in the first generation and it's a natural organism that has been synthesized. I'd like to understand what it is that it proves and how significant that proof of concept is. And second, building on that, looking forward, I understand that you may be working on algae and other multi-cellular organisms where the genetic information is in the nucleus of the cell rather than a single strand.
How far away from that are we? Is that the proof of concept that will propel this field forward?
>> What's been possible in molecular biology is what several people have described this morning. Changing one or a few genes in the cell by inserting the genes in plasmics. Although some evolve by taking up chromosomes, for example, color has two chromosomes from two very clearly different origins so they probably happen through these kind of processes. But never before have we molecular biologists been able to take an entire bacterial chromosome, an entire chromosome of anything other than a small virus and transplant into a cell of one type and convert that cell into another. Then you add to that, starting with the digital code in the computer making the entire compromise from scratch means now we have the means to start with that digital code, make gramattic changes. While we'd the basis of an existing organism, we made changes to it and inserted the names of 46 authors, several quotations. It's the first genome with its first built-in website and web address. These may seem like trivial changes but identify it as a synthetically made chromosome something we think is critical for this field. And activated that and completely transformed that one cell into a new cell. It was not trivial. One base pair being wrong set us back three months. One error out of a million base pairs did not enable this to happen. So it's now, because it's a proof of concept, we do know how to do it. And now we can make much more extensive modifications. So we're building a robot to do common synthesis instead of making one chromosome over 10 years, our goal is to make 1 million or so a day by randomly sorting genes or selecting very specific ones, selecting living cells that you can't get. It's not a species that existed. It's very closely similar to a pre-existing cell, but it grows substantially faster because of the 14 genes we eliminated.
>> And on the multi-cellular front.
>> There are a lot of eukaryotes, moving nuclei around has been done 50 years or more, changing the DNA in the nuclei and replacing the DNA we don't think will be a huge challenge. It's probably usier to replace the chromosomes and eukaryote yeast by replacing them one at a time with synthetic DNA.
>> Thank you.
>> Dr. Venter, do you think it's fair to say that, you know, in the very elegant transformation experiment, that really that's how I read your paper first on that day, I saw it as, you know, probably the world's most elegant bacterial transportation formation that had been done to date.
>> Thank you.
>> I think maybe trying to clarify what Nita was driving at, you need today collaborate with existing life in order to make that transformation experiment work. And whiem it's true that after after several replications that all components, not just the proteins of that cell, were obviously derived from what you had produced in sillico and printed out, it did require a collaboration with existing life that had been derived by natural selection.
>> Absolutely. So we're starting, as I said, with the 3.5 billion years of evolution. We used that starting system to read the new genetic code and start making all the new proteins. As I said earlier, I think it's an interesting scientific question how few of those components we can get away with. As I said, perhaps just a ribosome, some polymerase, a few lipids. So, you know, when people evoke that you start with existing life, it takes us back to vitalism, that people try and amazingly, the "New York Times" has tried to reovoc vitalism. Most scientists view it disappeared 8 years ago as a concept and certainly with DNA being the material coding for everything, there's nothing vital in the cell other than the ability to read that new software. So we are clearly software-driven machines. That software is DNA.
>> First, thank you all very much for your comments. I would like to ask Dr. Venter, this is an important scientific step, but as you described what you have been working on for many years, you also described a process of thinking about the ethical issues right from the very beginning. So I am wondering if you could say from your perspective, what has changed now ethically, if anything. And where you think building on Dr. Atkinson's question earlier, where you think -- I think you mentioned we need an intelligent ethical-legal framework. Where are we lacking in that regard? What do you think we can do to help in that regard? I'd love to hear others' opinions on that as well.
>> I think it's a very critical question. It's not clear that anything has changed so dramatically as what some people describe as minor changes in biology with minor but significant changes in the ethical and legal framework, primarily because the way we control who has, for example, A-list agents and has been controlling who has access to these agents. Now, if all you need is the genetic code in the computer, it totally changes who has access and how you get access to them. If students can order anything from a DNA synthesis company and there's no tracking of what they order, some could try and make ebola virus which is only 8 genes or at least the DNA. The DNA is not ineffective but I'm sure if Homeland Security started detecting an ebola virus DNA, they'd probably get upset. Those would be the kind of hacking things that we don't want to occur. I think those can be pretty much eliminated by requiring companies to screen against A-list agents and requiring bona fide institutions to be doing this work versus being done in somebody's garage. I think creating new life forms -- I think what we did is as much a philosophical step as a scientific-technical one. Because it now opens the window for literally merging the digital world with the biology world. And because anything that's totally open-ended, we think there's some guidelines that are needed. I think it's sensible to start in that framework, so that we don't get the negative consequences are unintended ones from lack of paying proper attention.
>> George, you have written on this as well. Would you weigh in, please?
>> Yeah, I'm not sure whether this is an ethical or policy issue. But many of the previous discussions, the conclusions have been we should have more discussion. And I think that we are actually in a place that we can do more than that, which is to focus on licensing and surveillance. And I don't know whether that's a new -- whether that's ethics at all, much less a new one. What's happened since 1999 is this exponential curve has gotten steeper. And I think that's something you can't ignore. So I would say that it's time to go beyond having more discussions.
>> Following actually on that, it seems to me we have heard a lot both from the previous panel and from the three of you about the widespread availability of various codes, the quote-unquote ability to do it in your garage, unquote. But that seems to me to refer to the obtaining of the sequences and perhaps the synthesizing of those and that generates worries for people. But the question I have is, how big a step is it -- and you have alluded to this, I think, Dr. Venter -- from having the sequence to actually getting it to work in a biological system? And is that gap big enough that we shouldn't be as fearful as we are of the possibility of this being misused because we could in fact have regulation or safeguards at that step that would be very helpful? True or false.
>> That wasn't a yes-no question. I'm sorry.
>> You have a 50% chance of getting it right.
[LAUGHTER]
>> Then I'll say false. I think with each new cellular system and the micro plasmas don't have a membrane which made it simple to get the DNA across. What we are trying to do with the algae right now is maybe using a plasma membrane to transform things. We're at the earliest stages. We need to see how extendible these tools are. Getting DNA past cell walls may be very tough, but there are other ways to get around things. The two areas go in parallel. One is the design and the synthesis and the two booting it up. The biggest worry was we were going to have this really nice macro molecule, the largest one of a defined structure ever made and we couldn't activate it in the cell. We were there for a long time because of one single error in the genetic code. So I think it's going to have to be optimized for each individual biological system. It's totally different getting DNA into plants than it is to bacteria and totally different with cell walls, without cell walls. What I think this is going to be a rapid expanding area of research and probably difficult to regulate. I think the guidelines that get set up for approving projects at the institutional level with broader guidelines at the funding level and even though our work was not federally funded because my institution is a major federal grant recipient, we have to follow the federal rules regardless of whether it's funding that particular research. So I think the way molecular biology has been practiced, particularly in this country, has been I think a wonderful example of how to proceed, but expanding the repertoire and expanding some of the ways we monitor things.
>> Go ahead.
>> Yeah. I may be misinterpreting the question. So the information is free. You go to the database and get as much sequence as you want. It is cheaper, but still not trivial to actually pay for synthesis. So my lab does not yet, as a matter of pract tis, synthesis everything. We still do a tremendous amount of PCR. I just had a meeting with a student a couple of days ago and said, okay, you can get these things synthesized and it's going to cost about 3 thowshd but you can't get the 12 other variants of it synthesized that you want. Now, we're talking about $36,000. So as far as access, some of it is thinking to the future in terms of if we go -- certainly we're not at $10 a base as George showed but we're under $1 per base but not at a dime per base, at the level of small amounts of orders. So you can do negotiations with some companies to get things on the order of 10 cents to 25 cents a base if you want a lot of sequence. So because of that, I think again I may be misunderstanding your question. But I think there are different answers in terms of whether or not you're talking about institutional access versus noninstitutional access, skilled labor versus unskilled labor. In terms of access because of the cost, I still think that a lot of the more fear was the word used earlier but the things that may evoke fear and apprehension are still beyond the cost of most noninstitutional players. And then because we're really talking about difficult biology and one base pair mistake setting you back three months, there's still a big difference between what you can do as a skilled practitioner versus an unskilled practitioner.
>> Just to follow up, I appreciate hearing that it's a little more difficult than just doing it quote-unquote in your garage to get the sequencing done. But I was talking about the next step and whether people can do that in their garages quote-unquote, of getting that to replicate inside a cell and how difficult that is and what material is needed there and whether that's an important place in which regulatory safeguards could be placed to make sure this doesn't get into the wrong hands.
>> So, at the simplest level, and if you read some of the blogs and the popular press, everybody wants to make things glow. You want fish that glow. And it's like let's put protein in anything you think about. It is relatively inexpensive and on a skill level relatively easy to order a gene that would affectively be a plasma that encodes for green fluorescent with motor on one end and terminator on one end and transform a bacterium in your garage and say, hey, it glows. It's very difficult to make your dog glow. So again, we're still talking about a level of complexity there. And the one gene being able to transfer one gene and getting that to work in a garage with a junior high school student, pretty close to trivial. The types of things that the Venter lab did, not going to happen in the garage with 14-year-olds.
[LAUGHTER]
>> Thank you very much for your presentations. All three of you really talked about the need for some level of regulation. And I wonder if you could comment on whether all of these different things that fall under the definition of synthetic biology are already covered under existing regulations because certainly we have regulations of how to handle anthrax or ebola or other this process of things. Do you feel we need to have different and new types of regulations to deal with the issues of synthetic biology?
>> We certainly have recombinant DNA regulations. Many of these depend on the person practicing and having federal grants or in some other way being a responsible citizen. I think what we don't really have is surveillance that the regulations are being obeyed by all citizens, not just the standard members of society. And I think we also don't really have many regulations about safety testing as we make things that either are intended or could accidentally get into the environment. I think as safety testing, we take for granted in many other engineering disciplines, there's relatively little of that in biology. It probably doesn't require major overhauls but I think there are some gaps that we need to pay attention to.
>> There are really no limitations on what you can order from a nucleotide synthesis company. At the present time, they are not required to screen against any list of agents. Some are voluntarily doing it now. And it's not just a U.S. problem. DNA synthesis is a global effort. If you can't get what you want here, you can order it in Germany or you can order it in India or get things made in China. You can buy DNA synthesizers off of eBay. So maybe there are, as people said earlier, four companies that are probably 90% of the synthesis in the U.S., even though they are not all in the U.S., requiring them to screen against A-list agents, requiring them to have bona fide credentials of the ordering institution, I think are things that could go towards preventing the frivolous use. There is a lot of home-brewed biology being done in kitchens. It's a new trend. Drew Endy has been in the past -- I was pleased to see he stopped doing it and encouraging biohacking. You know, we want some reasonable restraints on that, without destroying this wonderful creativity that these kids are doing to come up with some new circuitry that could totally change what we work on. But I don't think it's covered by any of the existing regulations.
>> Just as a follow-up, you know, in the kinds of experiments that you published, it is possible to be able to take what nobody may be able to recognize and may come from an organism and you could order a bunch from one company and a bunch from another company and be able to put together.
>> At the level of 100 meres or anything over probably an 18 mer or something, you could get a pretty good trend of what somebody was trying to do. The signatures are pretty clear-cut.
>> Also, these companies are beginning to coordinate voluntarily. This is something that would be nice to be backed up with regulation. But they are voluntarily coordinating their efforts. So if someone split their order over four companies, that in and of itself would be an alarming event, which combined with the sequences that could be recognized, I think you could put the story together. But it will be ongoing efforts to get around that.
>> How quickly will you put the story together realistically?
>> Well, if it's entirely based on computational algorithms pretested -- and I emphasize the importance of testing. You could put it together in hours. The computers, especially if you have got government agencies that are willing to act in hours.
>> I think you have gotten to the heart of a lot of my concerns. As you probably all know, I'm there was a strain of anthrax that seems to be becoming a low hurdle to overcome in the ongoing biological processes.
I have heard a couple of different things. One is that this is still difficult to do, very difficult to do. But the second part is that it's getting easier. And so I think that raj brought up an excellent point. There are regulations in place now for I think what we would consider traditional biology being able to reproduce organisms that are on the biological toxins list. However, we're talking more about the biobricks now which, quite frankly, are not part of the regulation. So what concerns -- and I think you have expressed them here. So your concerns about this evolving technology and getting around the B-sat, the security measures that we would need to take to make sure that these would not happen, and what is the balance? You have probably been privy to the discussions of the latest B-sat. In balancing scientific discovery versus security for the American people.
>> I don't actually think that this is a trade-off between security and scientific discovery. I think if this is properly implemented, where most of the effort is in developing computer software and getting compliance at the company level and getting surveillance at the government level, the researchers in a certain sense shouldn't even see it. It should be transparent to them and they can get on with their work. On the other hand, if you require them to sign a piece of paper every few minutes and every time they type something, you could interfere. I think that's unlikely that's where we would be going with this. I think some serious computational efforts are in order.
>> I am interested in the money behind it all. It's a very expensive proposition now to come up with a new cell, as you did over $40 million or new products. And mostly funded now in often small biotech companies and with venture capital kinds of money. Are there recommendations for being able to encourage the entrepreneurship, while not having so tight control on it that you can't get a payback to the amount of money you spend putting into a project and can't get ta payback fairly quickly? Versus being able to also encourage entrepreneurs to work on projects. I mean there's going to be huge profits in this, if it would work out the way it is looking like it might work out in biofuels or energy and so on. I just wondered if you had recommendations or thoughts on what the commission should recommend on those issues.
>> Just my opinion is the current system is actually quite healthy. In contrast to the one that Rob Carlson described, most of my experience with dozens of companies is they can get the job done without spending a lot of money on lawyers. Very often you don't really even need the patents in the end. It's the know-how that's incredibly important. I have very few examples of a patent getting in the way of academic research. And generally, not even in the getting in the way of start-ups as well. This is such a vibrant field that people are inventing so quickly, that they invent around or don't even concern themselves. I think it's actually quite healthy and going from small to large is happening quite quickly, too. Craig mentioned Exxon and the case of LS9 and they have Procter & Gamble and Chevron. This is in theory a authority number of years. I think in my opinion it's healthy.
>> In fact, if I can add briefly to it, it's healthy and critical. I think if all these bets are right that everybody is placing to get proper ecological benefit and change the use and dependency on taking carbon out of the ground and burning it and putting it into the atmosphere, we need things to work economically. And I think there's a healthy investment climate in the U.S. despite the stock market. Better step in where the government hasn't.
Most of the advancements in biotechnology have come with companies like Genentech. In our case, we would have been stuck back in 2003 with a small synthetic virus if we did not have independent money from starting synthetic genomics to fund this work at the not-for-profit institute.
>> I would only add to that I think one -- so I agree with what's been said. I think one of the impediments to progress, if you will, that can arise if all of the achievements are done individually, is one of the very big goals of synthetic biology is to have standardization and interoperability. One of the ways the federal government can help with that is promote in some tangible way an effort for the community to be able to organize on a regular basis around what should those standards be, so that you don't have innovation happening in isolation in a way that you have very great technologies evolving independently and to network those and interface those becomes very difficult. As we dream about synthetic biologies and you see the leggo kits all over the place as a good analogy, that works because you have standardization and you know you can get leggos from anywhere and they are going to work together. That's an effort I think has been more difficult to get real support for. Because it's not -- it's fundamental. It's foundational. And it's enabling, but it doesn't in and of itself get you biofuels and it doesn't in and of itself get you new vaccines. It facilitates all those things and sometimes there is a gap between the foundational more engineering-oriented standardization work and the applications-oriented things which can be very interesting and attractive to investors.
>> I want to begin by thanking all of you three for excellent presentations. I have got a couple of concerns or questions for you. One has to do with the fact this is all now accessible on the Internet and it's international. So if we're a commission set up to think about regulations here in the United States, I'm wondering what the context of our deliberations should be. If these activities are really taking place all over the world. So, you know, I mean what sort of international collaboration has to take place for U.S. regulations to have any real effective bite. That's the first question.
>> I think it's a critical question because science is international. These tools are international. The Internet is international. And I think first and foremost, the U.S. can set a good positive example. That didn't happen with stem cells in the recent past. And research expanded overseas at the expense of research in the U.S. I think we can do the opposite here if we do it intelligently. The same concerns that we have here have been expressed in the EU and basically every country I visited around the world. So I think if there's a positive example of how to deal with things, that would be a good start. But it has to be international ultimately to have any impact.
>> Thank you. A follow-up has to -- it's really a follow-up question about the role of industry. There has been some talk around the table about the movement from small to large, right. So listening to all the panelists, you get that picture that we're currently living through, the kind of biological Woodstock with people experimenting in their garages and so forth. But the movement will be, as it's been in the pharmaceutical industry and computer industry, from small to large. And so I'm wondering what the implications of that might be with regard to access to the goods produced by the industry. We have seen in the area of pharmaceuticals, a lot of public concern about the patent system and the rules and regulations relating to access, particularly with regard to access to life-saving drugs for diseases like HIV, where it's perceived by many people that the patent system is working against access to life-saving medications. So I'm wondering if we have anything to worry about that's analogous in this area, right. In other words, should we be worrying now about the synthetic bio analogs of Microsoft and Pfizer limiting access to knowledge and limiting access to the goods that are produced.
>> My answer is quite simple, no. I don't think there's any worry at all. In fact, the worry is in the opposite direction. If we don't get the things that really work at a commercial level, this is an interesting academic field. Published in a paper like my team did in science is great for understanding the concepts, converting it into reality where you can buy fuel at the gas pump made from carbon dioxide instead of from oil out of the ground will only work if that's done in an economically competitive environment. LS9 and these companies, synthetic genomics will only survive if they have economically competitive products. Most people aren't going to buy things just because it's better for the environment unfortunately. So any new fuels, for example, have to be available and they have to be cheaper than existing fuels or at least cost competitive with it. So we need economic driving forces to pull this stuff much more rapidly than is currently happening. I don't see any limitation of access. We need access pretty rapidly to CO2-based fuels as an example.
>> Before I go to Nita, I don't want a thought that was dropped, Kristala, that you brought up and connected with something to George. There's the flip side of regulation. And that's stimulation. Will one of the effective ways to ensure safety to be the sort of a way to be able to skate ahead of the puck, know where the puck was going? Were you suggesting Dr. Prather -- maybe I should leave it open. The question that we had sort of posed in the prior panel to you.
What would be the very next thing to be funded? In view of being able to have a knowledge base and an ability both to advance the applications of the kinds you have all been talking about, but have a deeper knowledge to help ensure that we can recognize as Dr. Church mentioned some of the sinister potentially sinister applications of these things. What would you fund next? Would it be your standardization?
>> You're not allowed to answer your own lab.
>> Yeah. That's fair enough.
>> What's the second thing?
>> No. It's a difficult question. So I think about, for example, the biofab which Drew Endy is directing which has the ambitious goal of being a focal point where you can develop parts to use a term in synthetic biology, discreet pieces of DNA in code for some biological function. And you can characterize them and see how they behave and see things like composability, what happens this this thing and the other thing. And I think it's a very ambitious goal and I think it's great. And they have got like $2 million in two years. And so what happens when that's gone? So I think that there's a need for an effort that is more ambitious in scope and much bigger in scope to say, okay, let's bring -- it does two things. One is that it can serve as a forum, if you will, for bringing different players together and brainstorming and saying, okay, here's what I'm doing, here's what you're doing. Here's what this person is doing. How do we get those to interface in a way that we can actually set a standard moving forward so that as new technologies are developed, we know they are going to fit in very well? And then how do we set priorities for -- and safely, yes. And so I'll jump ahead to a thought. You know, I think one of the things that's been very nice about the sinberg experience is we have had discussions all along about discussions and the thrust called human practices that deals with biosafety and biosecurity and intellectual processes. But that is a very, very small number of people. And what's becoming an increasingly populated academic field.
If you look at the number of people associating themselves with synthetic biology, it's grown astronomically over the past few years. And so there are questions in terms of if you are focusing and if you take NSF's investment into synberg and take DOE into the joint bioenergy institute, you're talking about real money. We're not giving it back. It's not trivial but a very small number of people it's impacting. I'd like to see efforts to bring the community together in a way that we can think about what the next steps are going forward and that we can be more progressive and proactive as opposed to reactive in saying, well, you did it wrong, so here's my other way to do better. We're in that midst now where it's a bunch of you go back and forth between I did it this way, that way is all wrong. Here's why it's all wrong. And I'm not saying that won't eventually get us to where we're going. But if we want to be able to bridge this technological divide and say we have exciting technology and the potentials for the impact it can actually have on human existence are very real, we need to be able to move that forward more quickly.
>> Thank you. Craig, did you have a comment?
>> The two questions I get more often, most often when I give lectures on this topic is people are worried about bioterrorism and environmental release. And it depends where you are which one is first or second. And so George gave some wonderful examples of safety mechanisms that could be built in. It would be nice to have orders of magnitude more. We're trying to build in suicide genes to organisms. If we're going to have large algae plants made from genetically synthesized or modified organisms, they need to not be able to survive in the environment on their own. Suicide genes, chemical dependencies, using artificial amino acids so they couldn't possibly grow in different environments, expanding the repertoire of what is safe and secure I think would be the sing the most beneficial thing out of any government funding.
>> I'll just quickly -- and I think coupling this question to the previous small versus large. Small has safety advantages. It's only once we got to the large manufacturing of automobiles that we really started getting very high levels of safety. And furthermore, as the technology gets to a certain point, amateurs stop making it. So, you know, I made a computer when I was young. I wouldn't bother to make one today. The know-how starts to fade away at the grassroots level which is a mixed blessing. But from a safety standpoint I think it's incredibly important.
>> Certainly since we're taking so much of a lead from engineering, it made me very proud of my heritage actually today. But one thing that has been demonstrated in so many physical systems is that it is far more effective to design in safety than it is to try to regulate in safety. That was the basis for those questions and very responsive. Thank you. Nita, I think you're next. Anita is next?
>> Thank you. I really have appreciated all these remarks. I wanted to ask Dr. Prather a very specific question about something that you said toward the end of your slides. You had a slide in which you made the intriguing point that our synthesis capabilities exceed our design capabilities. We know how, but not what. Could you elaborate? The reason why I want you to elaborate is because I'm wondering if we know how but not what points to some limitations on the applications that may be forthcoming from this science.
>> It absolutely does. Simply put, this is all back to comments that Bonnie Bassler made earlier that these are really complex systems that we're talking about. I don't yet know anyone in the field for whom their design works the first time they implement it. And the question is always -- I describe when I am sort of giving my pitch to first-year graduate students, they say what we do is to pick molecules we want to build and then we have problems. And your thesis research is all about how do you solve those problems and what do you learn from solving those problems. And we often learn things we didn't expect to learn. Sometimes we run into problems and they go, yeah, we figured that was coming eventually. There is two different aspects of it. One is that biology even for very simple organisms is still very complex. So being able to predictably know what's going to happen if you make a single perti vaition is difficult to do. That's one aspect of it. The other part is the type of manipulations that we're talking about doing are in and of themselves somewhat different from what we see in nature. We are mimicking nature but trying to take natural components and stream them together in ways that haven't been done before. There are no some cases a lack of fundamental knowledge of how that's going to behave. So there's a need for experimentation, to actually have the observation that says, okay, this is what I observed when I did this particular configuration. Let me make four or five different variants and see those observations and then put it on a graph and see if it's just a random set of points orphic then draw some conclusion that if I have these specific changes, here's the effect I'm going to get from that. What the Venter lab group I think has shown that the capability, the capacity to go from sequence on a computer into something that is physical DNA is there. But if you ask anybody, okay, you're free to write 500,000 base pairs, DNA, what would you do? Most of us are going to copy something that already exists because we just don't know how to make it all work together. And even the stuff that's working together, we don't know why it's working the way it's working.
>> How can we get better at knowing what -- given our genius at knowing how, how do we get to the knowing what.
>> There are two parts that also came through this morning. Some of it is more information about biology. As an engineer, I have no desire to interfere with the biologist doing what he or she does on a day-to-day basis to uncover fundamental knowledge of biology. I applaud it and we steal as much of it as we can with proper credit that we took it from somebody. We need biology to have the freedom to continue and the investment in biology to learn this. At the same time, this was alluded to previously.
Because we have these synthetic capabilities, we have the possibility of doing kinds of experiments we didn't have before. And it's mostly at a pace and scale we couldn't access before. So we can use the tools of synthetic biology to help us actually understand fundamental biology, to have rewiring, if you will, of the cells and see if I make this pertvaition what does the change in the input tell me about the change in the output. There are numerous mathematical algorithms and more to help fill in the black box between what you put in and what you can measure. The other thing I think honestly that's a little more difficult, but it's about understanding. So there is, you know, sometimes a little bit of lack of respect for biologists and engineers and vice versa. Sometimes they think they don't care about making anything work and engineers say scientists don't care about how it works but just care about it working. So bridging that divide and having the understanding, especially for this field, where they really are very interdependent upon each other, moves that forward as well.
If we start to have conversations and say here are the tools and techniques and methodologies I'm developing, how does that help you in understanding fundamental biology? And biologists are saying here are things that we have uncovered, parts we have called them. What can you do with those? If we are able to have those conversations in a way that's respectful and appreciative of each other's stream I think the whole field moves forward.
>> I agree. Thank you. Genetic deconvolution.
>> I want to folks on a couple of comments by Dr. Church and Dr. Prather about the role for government in regulation and promoting the development in this field. In particular, I was hoping that Dr. Church, you could expand on what you mean by surveillance. You mentioned a few times you think the government could play a role in surveillance. I'm not sure if you mean active or passive or what specifically you had in mind. Dr. Prather, when you mentioned standardization and the government could play a role in standardization, I'm wondering what you are envisioning. Is it funding or setting up a large initiative like the human genome project like a standardization project. If you could expand on that as well.
>> Yes. In terms of surveillance, I think one thing that was hard for the government to act until industry had shown what it was planning on doing. But at this point, I think they could tune into that and help it along and make it law and work internationally. I know that both secretary generals of the United Nations have been in favor of this. So it's a key time while there's still this bottleneck on synthesis. And not just to regulate, I'm sorry, to allow computer surveillance of orders of synthetic genes, but if you license the entire industry, then if someone wants to go around it, it's not just a matter of going to another shop or even going to an earlier step. They have to go around the entire system, obtaining the know-how to make the phosphoramidite chemicals all the way through in the idea of getting DNA to work in a cell. I think that's a great opportunity. And I think it actually plays into what Kristala will say about a genome project scale. I think it is certainly appropriate in this case. As a beneficiary of the human genome project, I saw just how great it was in terms of stimulating community and industry. So I think there is a huge opportunity there that will also result in greater responsibility.
>> Thank you.
>> I'll give a very simple answer. You said funding or project. I would say both, which is basically to set a priority and say we think this is really important and we're going to organize a project around that. And You how you do projects without funding. I think they go together.
>> Thank you. Are there questions from the audience? Yes, sir.
>> Terry Taylor from the international council for life sciences. My question is about the international environment, that being an excellent discussion about the fact that anything we might do in the United States has to be fitted into an international context if it's all to be in any way successful in regard to regulation or ethical conduct. And I have two questions really. One for our excellent speakers, first-class presentations, you're at the leading edge of the development of a science, whether in academia and, of course, experienced in commercial industry. Where would you start in terms of the global environment? Is it best left to various networks which are academic, which are in commercial industry? Dr. Venter mentioned the industry is already trying to do some of these things like the international association for synthetic biology based in Germany attempting codes of conduct and some really quite successfully. Or should there be some central, more top-down approach? Is it a networking approach, multiple networks? Should we be doing something or encouraging the development of top-down and globally? That's question number one. Second question really I suppose is for the commission, to what extent are you going to consult internationally on this subject in order to set whatever recommendations you might make in a global context? Thank you very much.
>> Let's begin with the second one because I can answer that very quickly. We are going to consult internationally, not only are we going to, we have already begun to consult internationally. And we will have here as a presenter somebody, Markus Schmidt who represents an international voice in this. And we will continue to consult internationally. So I now push it back to our presenters to answer the substantive question which is an important one.
>> I think the only way to start is in two ways, simultaneously. But it certainly has happened with molecular biology and international code of standards, that we all agree upon, such as simple things like labeling the DNA of synthetic by watermarking it, as we tried to set the standard for trying to make sure no organisms are released to the environment unless they have these critical biological controls. We suggested early on no human pathogens but two out of the three first viruses were made were human pathogens with polio and the 1980 flu virus but the flu virus was done in the right way and down in the C.D.C. with extreme controls and was a critical experiment for understanding why the 1918 flu was so lethal because we couldn't tell from looking at the sequence.
I think it has to happen at the government and society levels as well in the key countries where the activities are going, starting with the EU, China, India and the U.S. would be great starting points.
>> I can't help myself here. As tempted as I am to weigh in on licensing and regulation, I won't do that. I wanted to look at the small versus large conversation.
>> Introduce yourself.
>> Rob Carlson, sorry. Previous speaker. That more than 50% of the jobs in this country are in small businesses, a little bit less than 50% of the payroll is in small businesses. And that's where a lot of our technology comes from. And there's also an example of small-scale distributed biological manufacturing being highly successful in this country. And if you look at the size of breweries over the last 100 years, officially the number one to zero during prohibition, officially. After prohibition, brewing was dominated by very large-scale brewers around the world until 1980 roughly. And although a small number of very large brewers control most of the U.S. market, those number in the -- you can count them on your one hand basically. There are 1500 craft brewers in the U.S. that supply about 5% of the volume but 9% of the revenue or take home 9% of the revenue. That is distributing biological manufacturing and it works just fine and they are covered by a regulatory regime to the extent that alcohol is still regulated in this country. That's all I wanted to throw into the discussion.
>> Thanks, Rob. Since you have brought it back to the commission.
>> Yes. I have a follow-up question, since this panel, we really wanted to focus on application. And here's the question. I'll try to make it as vivid as possible. Next flu season, the most virulent flu begins. And there is real fear of how much it's going to spread and the lives lost and so on. Next flu season, could we have a one-day production through synthetic biology of a flu vaccine?
>> Well, the seed stock for that vaccine could have been produced in probably about 12 hours. And because all the surveillance now with the rapid DNA sequencing, we can predict, we think, well in advance what the changes will be for next year's flu before WHO makes the decision as to the vaccine stocks. I think the biggest limitation going forward is how we actually produce the vaccine. Is it going to be in chicken eggs? Are we going to go to modern cellular systems? Or is the magnitude faster and under much better control? The second step is much better in producing the doses for the individuals. Well, other companies are tooled up for it in part because of government funding, waiting mostly for F.D.A. approval.
>> If I'm right, the answer is no, we're not yet ready to do it in a day.
>> No. Actually, I think we are ready. Depends on who the we is. If we're the F.D.A., we're not ready.
>> So we're the public. We're the American public and we want to know, next flu season, if there's some virulent flu strain, can synthetic biology come to the rescue?? And I don't mean if it were in theory possible. But will it happen?
>> It's very likely, as I said, the vaccine you get next year will be from synthetic genomic technologies.
>> So the answer is yes?
>> The answer is definitely yes. NIH is funding us to make synthetic segments of every virus. It's easy just to put them together in a very rapid synthesis process to make any seed stock or any change we see for tracking new emerging infections.
>> Thank you for that.
>> There is a corollary to that. And the corollary to that question is, can it be done only by synthetic biology? Or are there other approaches that could equally effectively produce the kind of vaccine that you are talking about?
>> And what's the answer to that next flu season?
>> The answer is yes, but nowhere near as fast.
>> And speed matters.
>> Speed definitely matters.
>> And nowhere near as cost effective?
>> I mean the cost is a trivial part at that stage.
>> Great to know.
>> I don't want to gloss over the manufacturing issues here because Dr. Venter made this point of if you are still making it in chicken eggs, it's not going to happen in a day. There's a difference between the tools of synthetic biology being able to give you what that starting material is.
If we're stuck with chicken eggs, it's not going to happen. If you go to chicken cell culture, it's going to be faster. If the DNA vaccine technology proves out and you can do it in microbes, you can do it in a day.
>> What do we need for that?
>> That's not a synthetic biology problem. That's an immunology problem.
>> The final question is yours, ma'am.
>> Nancy Jones from NIH. So my question is we have talked a lot about external regulations for the government in this. As trainers of the future scientists and engineers in this, what are you all's obligations? What do you teach your engineers and scientists about what the ethical considerations are for moving this field forward?
>> Well, at the Venter Institute in synthetic genomics we have internal IRB committees, that any scientific experiments have to be approved in advance along guidelines published in the past by NIH. And also just a commonsense approach. We wouldn't be testing new microbes to see if they survive in the environment. The micro plasma that we made and changed was initially a goat pathogen.
We have eliminated 14 genes that were originally associated with that pathogennity. There's a common sense level to all this work that I think most labs -- it's a reason with millions of experiments in molecular biology, there's been no fundamental levels or accidents in part, the ethics of the scientists doing this and how they train scientists and the simple guidelines that are out there. I think they work very effectively.
>> So I teach a course on responsible conduct of science, which is based on some of the NIH literature. In addition, in every other standard course that I teach, I inject some both lectures and exercises, where they have to seriously understand it in order to do well in the course. I would say in addition, iGEM and SynBERC as part of our training includes what's called a human practices component where really they are judged in their competition as to how well they conquer that particular knowledge base as well. So I think there's certainly room for improvement, but there's some hope as well.
>> I want to say thank you for the question, because I made a comment earlier to someone that I am here to learn myself. I didn't realize until recently -- I don't have an IH funding, therefore, my students aren't required to have any training in ethics. Because of our affiliation with SynBERC, they have exposure to it in a way that I think very few other students who are trained as engineers traditionally have. And it's a gap, I think, in terms of how we think about training the next generation of engineers to have a focus on what our responsibilities are beyond the science. So certainly, it's something to think about.
>> Yes. Actually, I think we need to adjourn. As we adjourn to reconvene at 1:45, I believe.
Please join me in thanking Drs. Prather, Church and Venter.
[APPLAUSE]
Bryan Bishop
Jul 8, 2010, 4:16:52 PM7/8/10
to diybio, Bryan Bishop
On Thu, Jul 1, 2010 at 12:42 PM, Bryan Bishop wrote:
> I found this agenda item interesting.
More transcripts.. this is from the after-lunch session with Allen Buchanan et al.> I found this agenda item interesting.
>> Let me invite Dr. Kaebnick and Dr. Buchanan to come to the table. We're not going to take a break. We're hardly going to breathe as we move into the fourth and final panel of the day. As they are getting in place, the fourth panel deals very specifically with ethical issues of synthetic biology. Our commission is, of course, ultimately charged with looking at these ethical implications so we have two different panels of speakers, one today and the first one tomorrow to help us focus on these issues. We have asked the speakers of today's ethics panel to tell us what they consider to be the most important ethical issues raised by current and foreseeable developments in the field, to help us understand if we have already or how much we are in danger of crossing any ethical boundaries owing to the unique methods and applications associated with synthetic biology and not common perhaps to other scientific endeavors. Welcome to both of you. And our first speaker will be Dr. Gregory Kaebnick, a research center at the Hastings Center, coinvestigator in a research project on ethical issues in synthetic biology funded by the Alfred P. Sloan foundation. Dr. Kaebnick, welcome. There's only room for so many words in my brain, unfortunately. It's really great to have you here. Look forward to your presentation.
>> Thank you very much for inviting me here. It's a big honor to be here. So my goal, my charge, as I understand it, is to set the table for these next two sessions in these two meetings by giving you an overview and also comment on how these issues might translate into a governmental response. And I should say both by way of giving credit where its due and by way of offering a kind of caveat, that what I'm going to say is informed by and comes out of this Sloan-funded project you mentioned. But it's not anything like a consensus statement of that body. We have brought together a lot of people and I have benefited from a lot of input. I'm certain that not everyone would participate and sign on to what I'm going to say here today. Anything I say that is particularly silly is very much my own. So I group ethical issues raised by syn biointo two categories that perhaps runs counter to one of the premises of this session essentially. One of these has to do with whether synthesizing organisms is bad in itself, intrinsically bad aside from the consequences for human welfare. But the other set of ethical issues does have to do with these consequences. When I talk about the ethical issues, I mean to have both on the table. The harms and benefits as well as the intrinsic concerns. I'll start with the intrinsic concerns which is what our work at the Hastings Center has to date focused on. I believe these come in related, but different forms. And there are related, but somewhat different things to say about each of them. First off, maybe the classic way of articulating concerns about synthetic biology suggests a kind of religious or metaphysical claim. One might worry, for example, that synthetic biology puts scientists in the role in the COSMOS that would be properly held by God. Scientists are playing God is a phrase we have seen over and over again on TV about this. Or slightly different point, one might hold that synbio has an inappropriate degradation of life. Prince Charles seems to have something like this in mind when he lamented that biotechnology was leading to the industrial of life in a capital element. My guess, though is that people mostly don't view the question of what humans may do to life as sort of this single uni tarry. Sacredness might be attributed to some but not all living things and synthetic biology in its current form, though we have heard a little bit and there's been some in the media but getting human reproduction under control, synbio is what we can do with microbes. If you did object to synbio along these lines, it would turn out to have fairly limited force in the public sphere. It's an objection that cannot be fully articulated without appealing to one's faith or world view. Not everyone will share that world view. In fact, we know from one of the readings sent around for this meeting, not everyone would share the objection within the faith of world view. Some will celebrate science as an aspect of human creativity that we are meant to develop and put to use. Finally, there is also an important question whether this kind of concern may legitimately ground public policy in a liberal society. Governments in liberal societies are widely thought to have to maintain some level, some kind of neutrality concerning religious belief. They shouldn't be forced to believe. If I can just offer a little side note here. Some thought the NOI in May that a synthetic cell had been created established once and for all some of the religious world views are false. They climb science that is finally definitively shown that life is just a well organized puddle of chemicals. There's no greater being, no spiritual core and no vital essence by which life is sacred. I don't really see how that reasoning goes. I don't think that's quite right. Seems to me if there's a god who gives microbes, even microbes, some special vital essence, it would be well within that God's powers to endow a synthetic microbe with vital essence as well. A somewhat similar question came before one of the predecessors to this commission, the national bioethics advisory commission. Whether people created through cloning would have souls. Submit that it's extremely difficult to resist the conclusion that they would. And by analogy, it seems that microbes created in the lab would have whatever special soul-like properties there are that characterize microbes generally. Another way to develop intrinsic observations to synbio would be to couch them not at metaphysical claims but as concerns that the field somehow conflicts with important moral conflicts. A number of commentators have suggested that synthetic biology my conflict with the concepts of human agency and life and maybe it promotes a kind of grandiosity about human powers or dismissiveness about the specialness of life. These are sort of low-key versions of the metaphysical claim of human beings in the cosmos of life and what some may see as grandiosity some may see as commendable inventiveness and desirable industry. Also the fact that an organism has been created in the lab doesn't necessarily settle what its moral value is. This also was a point offered in the readings. And finally, again, synbio is still about life and deeply implicated by what we do, as long as we're just doing it with microbes. Another more promising way of saying that synbio conflicts with shared moral concepts to hold it raises questions about the human treatment of nature. To see it is an environmentalist concern. A goal of environmentalism isn't just to make nature a safe place for human beings but to make nature safe to some degree from human beings. We should treat the natural world with the kind of acceptance or even reverence and that seems to saving endangered species or wildernesses and forests and so on. Maybe synbio doesn't square quite with this value. The obvious rejoinedder is that human beings have been altering nature throughout history so the issue has got to be at the very least where to draw the line, even determined preservationists will accept that there's some sort of balance to be struck between protecting trees and harvesting them, so there might also be a balance when it comes to biotechnology. Furthermore, many, at least of the nearer term, potential synbio applications are fairly limited from an environmental standpoint and could be if they worked out right. In many cases, we're not talking about intentional ecological changes. We're talking about creating limited microbes to be contained in a laboratory or factory and would maybe partially displace the petro chemical industry. The classic concerns about the human relationship to nature are about environmental destruction. The demolition of species in wildernesses. Part of the promise any way of synbio is that it will be beneficial to the environment. If that can be achieved and note the conditional obviously, many environmental Is might find at least some applications of synbio aattractive. And I mean this actually from the standpoint of intrinsic values. The kind of deliberate release into the environment that professor Snow was talking about would be another category of protection. So my concluding thought about the intrinsic concerns, I take them very seriously. I'm not inclined to write them off at the outset as illegitimate, as many people with my kind of degree are. But I think that once we study them, they don't point toward a need to restrict synthetic biology. Not now anyway. It seems possible that the intrinsic considerations would change as the details change. If environmental damage looked to be likely or if we began to apply the technology to complex organisms. The second category has to do about the consequences. I'm not going to talk about what these are in any details. So these are more economy at that than I. I want to say a little bit more about the process of assessing them, a conversation that was begun in the last session about professor King. An overarching point I want to make, there was a legitimate question whether current strategies for evaluating possible outcomes are actually up to the task. As has been stressed especially in the last session, the potential benefits and risks of synbio are particularly difficult to assess. It's very easy to be dazzled by futuristic stories of how technology is going to remake the world for the better. It's hard to think hard about the kinds of risks, kinds of potential harms that synbio presents. Some of these appear to me to be very low probability, but very high impact, which is a confounding for us. We blow risks out of proportion. We also weigh them too lightly as happened to very bad effect in the Gulf of Mexico, nor is it clear as many have stressed now how much we can learn about it the risks of synbio with older biotechnologies. Synbio is on a continuum with older work which can be seen as a form of the older work and significant advance on it. And frankly, the testimony at the house energy and commerce committee on this point in May tended to make both these points, emphasizing the respect in advance when discussing the benefits and the familiarity when discussing the harms. Second, we have to negotiate this tension between benefits and harms, sort these out, just as their a debate going on about how to assess technologies, how to weigh benefits and harms. This debate is basically over the approach known as risk assessment and cost benefit analysis on one hand and the precautionary principle on the other hand. One side favors objective scientific and economic analyses, tends to down play the enormive assumptions it makes as when applying a discount rate to future risks and benefits. And according to its critics anyway, it gives too much weight to potential benefits. The other side invokes an expressly enormive stance and according to critics gives too much weight to potential harms. The point I want to make, there are at issue here a series of difficult questions about values and how to operationalize them and it's easy to bury these decisions and equations without really attending to them carefully. I think a good public assessment of synthetic biology ought to be ex-ples it -- explicit to these and open to reassessing them. So in conclusion, I think a case can be made for pushing the field forward. I think there's also reason for caution. I think we should guard against overconfidence in looking at the outcomes. And I'd offer four general recommendations. I think we need much more careful study of the emergent possibility and the impact of the potential harms. I think we need a strategy that is grounded in good science, is flexible enough to look for the unexpected. I think we need a strategy for studying the risks that brings together different disciplines and different perspectives on the risks. And I'd add that is clearer about the enormive assumptions at stake. And then it seems to me that then we need to go on and on the basis of that conduct an analysis of whether our current regulatory framework is adequate to deal with these risks and how that framework should be augmented. And, of course, the sessions tomorrow will carry that forward. Thank you.
>> Thank you so much. Our second speaker is Dr. Allen Buchanan who is Duke's university distinguished Professor of Philosophy and investigator for the university's Institute for Genome Science and policy. He's also a distinguished research associate at the Uehiro Centre for practical ethics at the University of Oxford. He's worked on or been consultant to past bioethics commissions. He's a veteran.
>> Very happy to be here but I haven't been equipped with any means of changing the slides.
>> We would like to remedy that.
>> It's going to be a problem.
>> In the meantime.
>> There ya go.
>> I'm having a feeling of deja vu. 28 years ago, I was working on the first president's on genetic testing and the other on splicing life, genetic engineering with human beings. In a moment, I'm going to explain why I'm a little depressed because I think some of the language used in the debate about synthetic biology is depressingly similar to some of the language used 28 years ago. I think we need to get beyond that language and the prime suspect here is talk about playing God as Dr. Cade knick has pointed out. There's lots of better ways of talking about the risk of unintended consequences and the risk of overreaching our knowledge than using these slogans like playing God.
I'll say we a number of times during this presentation. It's because I'm presenting work that was done by myself and Russell Powell who is actually at the back of the room here. An earlier speaker said that he was wearing a button that said it's the bioeconomy stupid something to remind him of that. And I'll wearing a tie that depects the anthrax pathogen to remind me of a point that will come up later on.
[LAUGHTER]
Well, let's see. What should the commission do? Well, obviously, we should consider the benefits. And this seems like a no-brainer. But I think that with some past Presidential Commissions, including the last one, there really hasn't been a sympathetic enough explanation to the public of what the full range of potential benefits of new technologies has been. And this sort of stacks the deck because people are very aware of possible risk, but the potential social benefits of synthetic biology need to be thoroughly explored, both in terms of advances in basic sciences and in practical applications. And this last item on the list there is something that's come up a couple of times. Namely, it's important to determine which benefits can only be obtained or only be obtained at reasonable costs through synthetic biology. Because I think that's going to be very relevant to trying to weigh risk and potential benefits. There needs to be a classification of the risks. It's not productivive to talk about the risks in the blanket clumping way. The comprehensive classification needs to try to distinguish the severity of harm, probability of occurrence and immunability to management of the risk and in particular to try to determine which risks, if any, are peculiar to synthetic biology. And it's been suggested earlier today in a couple of talks and comments that there are perhaps peculiar risk of synthetic biology because of the technology is so easily accessible and people can order nucleotides and buy gene synthesizer or use the services of one. They can download the information from the Internet. Well, again, I'm not sure that's so different because 28 or 30 years ago, people were saying exactly the same thing about gene splicing. It was incredibly easy. And in one sense, they were right. I'm not convinced that there's an order of magnitude difference with synthetic biology, at this point at least. In tems of ranking the risk, in our judgment, the most are the risk of unintended bad consequences which people talk quite a lot about today and the so-called dual use risk. Now, the other supposed risks have been mentioned by Dr. Kaebnick and they include the so-called playing God idea and in a moment I'll say why I don't think that's a productive way to label that risk. Worry about devaluing life which Dr. Kaebnick also talked about. And the idea of encouraging unwholesome attitudes toward humankind's relationship to nature. Now, there are in fact two dual use problems, not one. First is the one that everybody talks about, the risk of misuse of synthetic biology by bad non-state actors or rogue states. That's very important. But there's also dual use 2. The risk of quote, good governments using synthetic biology, including research and techniques developed in antiterrorism or defensive bioweapons programs for offensive purposes and the risk of so-called bioweapons arms race. I think it's important for the commission to squarely admit this is a risk and also to admit that efforts to reduce the risk of dual use 1 may not be effective for dual use 2, but they may actually exacerbate dual use 2 risks. Let me just mention something to try to bring home this last point. Look, if you have a big antibioterrorism initiative to try to reduce dual use 1, the first effect is you're going to be training a lot more people who are capable of doing bad things with the technology. The second risk is that you may be creating government agencies which will in their function of doing surveillance over new research will be in a position to get hold of that research, use it for their own purposes and restrict everybody else from using it. Now, I mentioned this point at a meeting on antibioterrorism initiatives a few years ago in Baltimore. There was a member of the NSSAB there. And he said, oh, you know, professor Buchanan, I don't mean to be impolite but you're being paranoid about this dual risk 2. I asked him if he had read the president's advisory commission report on human radiation experiments. He said he hadn't. And I suggested that he should read that before he commented further on my paranoid tendencies. I served on a staff commission and a couple of people in the room worked actively on that. And for those of you who aren't familiar, this is a very sad story of pernicious complicity between leading figures in science and the U.S. Government conducting grossly unethical experiments over a period from about 1944 to 1973. And they were people just like you and just like me. So I think dual risk 2 is something we really need to think about and don't just focus on dual risk 1, although dual risk 1 is extremely important. Now, I don't want to try to assess what the risk of bad unintended consequences is. I'll leave that to people who have more technical expertise than I. But I want to suggest that there are good ways of framing that problem and bad ways of framing it. And one bad way of framing it is to rely either explicitly or tacitly on very misleading metaphors about what evolution is like or what nature is like. People talk about the benevolent balance of nature or in President Bush's report biotherapy they likened natural selection or evolution working through natural selection to the work of a master engineer that produces complete, stable, harmonious master products. Now, from the standpoint of evolutionary biology, this is just bunk. This is not what evolution does. It produces Jerry rigged contraptions that respond to short-term design problems with no forethought for what will happen down the line. And at most, it fleetingly proximates biological fitness. Human well-being is not about biological fitness. We have goals in life that are a little more ambitious than maximizing the number of genes we pass on to the next generation. The problem as I see it is that to a large extent, the public and even many members of the bioethics community have a few of nature that's really preDfew of nature that's really preDarwinnian. It's a view of nature as this kind of stable, harmonious largely benign thing. And if you have that view, you will automatically stack the deck against any biotechnologies. You will automatically think that the situation is like this. Everything is humming along just fine. The status quo will continue indefinitely, so long as we don't intervene and mess it up. That's simply not true. As Dr. Venter pointed out earlier, we have already intervened in this planet quite a lot. We have created a lot of problems. We're not just individuals who react with preestablished niches. We create niches. We are constantly changing the environment. And we create problems. And some of those problems we may need synthetic biology to cope with. We can't know which and we can't know whether there are other means but we have to keep that open. I'm not making a pitch for let's go to be synthetic biology full throttle, yahoo. Instead, I'm saying it's very important how we think about the status quo. And part of that is how we think about nature or evolution and our relationship to it. And my sense is that this commission could do a huge amount of good by educating the public and the bioethics community with a more accurate scientifically informed view about nature and evolution. Now, another point, in managing the risk -- of course, the idea is to manual, not to eliminate risk. Life is not riskless.
There's no way to eliminate risk. You need to emphasize that risk reduction is costly and often the marginal costs of risk reduction are rising. That is, additional incrementals of reduction of risk may come at great cost, including the opportunity cost of foregoing benefits that you might have. In terms of institutional design, it's very important in thinking about how to develop practices or, as one of the previous speakers said, social technologies for dealing with this biological technology. It's important to think in terms of institutional design and to note how different incentives apply to different individuals depending on their roles and these incentives can lead them to overestimate or underestimate risk and the cost of risk reduction. It's important to develop cautionary rules of thumb and practices that have the following characteristics. They are knowledge sensitive. That is, we should expect them to change as our knowledge changes and our knowledge increases in particular. Our way of approaching risk should encourage relevant knowledge acquisition. It should take the costs of risk reduction seriously. It should have effective provisions for ongoing critical revision of risk assessment and management practices. And it should not rely on a single risk reduction or prevention principle. Especially for het a hetero genus biology. Now, if you want an example of a cautionary heuristic or risk reduction principle that violates all of those, think of the precautionary principle as it's usually formulated. It's not knowledge sensitive. It doesn't encourage knowledge acquisition. In fact, it discourages it. It doesn't count the cost of risk reduction at all. It doesn't recognize that our situations are dynamic. It doesn't have provisions for ongoing critical revision of how it assesses risk. And it commits the fallacy of thinking there's a magic bullet, a single principle for all the hetero genus areas in which risk may arise. Now, a lot of this has already been gone over today so I don't think it's really important. But let me just mention one thing. Some people think -- and I think this is not unreasonable -- that there may be greater risk to synthetic biology because you may be creating a really novel organisms. And so they worry about the sort of virgin population problem in the case of infectious diseases. We don't have resistance because this is really new. On the other hand, I think there are a couple of considerations on the other side that need to be taken into account. One is that in general, dangerous biological agents like pathogens like the anthrax pathogen coevolved with their prey. So if you have something that's really, really different, it may not, as it were, have a purchase on us. It may be a more matter of ships passing in the night. That's another consideration to weigh in. The other is something mentioned a bit earlier also. And that is the very fact that you're creating more novel organisms, starting with more basic building blocks, means that you have in principle the opportunity to design in more safety features. You don't have that with less radical technologies including sort of conventional genetic engineering. You can do some things by regulating expression of genes. But synthetic biology, at least in principle, you have a wider range of opportunities for risk reduction by designing risk reduction factors into the product itself, rather than trying to provide fences and safeguards after it's developed. I think that's worth thinking a lot about. Now, this is something that Dr. Kaebnick mentioned also. And that is in thinking about risk benefit, cost benefit and cost effective analysis, it's very important to recognize both that these are valuable and that what their limitations are. There's been a lot of work on what their limitations are. And I think the commission could do a great deal of good by helping to educate the public about both the usefulness and the limitations on the usefulness of these risk assessment technologies. Also, I think it's very important to point out that taking consequences seriously doesn't mean you're adopting what moral philosophers call a consequentialist moral framework. There's a lot of misleading talk to that effect in some of the bioethics literature that needs to be dispelled as well. I'm not going to go over thereth -- this because I think Dr. Kaebnick did a good job of it. It's two degree indications.
I really think it's the second version that we need to worry about. I'd like to dispense with talk about playing God because it's so ambiguous and misleading. Also I think if you ask people doing this kind of work, whether playing God, they will say they are not playing at anything. They are deadly serious. Now, what about this idea of humankind's relationship to nature? Well, again, I think we need to avoid misleading metaphors about the living world and talk about the wisdom of nature, benevolent balance of nature, master engineer of nature or talk about genetic pollution or breaching species barriers, all these are very loaded terms. And they are not really conducive to a reasonable assessment of the risk. They get in the way of a reasonable assessment of the risk. Here's another example. This last item. Beware of controversial enormative assumptions being smuggled in under the nature or human nature or nature. I have worked a lot in the ethics of enhancing normal human capacities by biotechnologies, biomedical enhancement. And the debate there has been infected by veryishy and prejudicial talk about not interfering with the natural, not destroying human nature.
And all of that talk needs to be translated into more hard-headed concerns about risks and benefits. It doesn't help. I mean anybody who has looked at the sad progress of the concept of human nature over the last several hundred years knows that some of the best minds have said foolish things about what human nature is and isn't. It's a huge ongoing debate. And instead of smuggling in your moral premises under the supposedly neutral heading of a description of what human nature is, it's much better just to confront these moral issues. Again, that has to do with framing. So let me just -- I tried to go even more quickly than the other speakers. And I'm able to do that because so much of what I said has already been covered. Let me just make one last pitch summarizing. I think the two critical issues are the risk of unintended bad consequences and the two -- not the one, but the two dual use risks. And I really would like to see the commission focus on those issues and rather quickly set aside but in a respectful way towards those who still hold these kinds of views what Dr. Kaebnick referred to as the more intrinsic concerns. Let me just -- it may sound a little harsh, the last thing I said. Take the idea of creating life or of, let's say, reductionism. In your briefing book, there was an article by Cho et al. on synthetic biology and ethical and concerns and raised the concern about reductionism. Many people worry that synthetic biology is going to show that life is nothing but a bunch of molecules or something like that. Well, that's a misunderstanding of what reductionism is. There are a number of different senses of reductionism. No matter what you are able to do with synthetic biology, it's not going to tell us that we're not really moral agents. It's not going to tell us that there's no such thing as wrongness and rightness. It's not going to tell us that there's no meaning of life in any sense of the phrase meaning of life that we're interested in. And I think the commission could do a really good job of pointing this out and then moving on. Moving on to the real questions about unintended bad consequences and the two -- not the one, but the two dual use problems. And thinking about what sort of concrete recommendations can be made both to move the handling of the safety considerations forward and to help educate the public how to think about these issues better. And for today, in terms of the safety issues, the concrete issues of reducing the risk of harm, there's a lot that can be done. Commission Farahany has pointed out we need to think in terms of prohibition and in terms of licensing and tracking and surveillance. And as Dr. Venter said, engaging people in certain kinds of synthetic biology work to have institutional affiliations so that there is some kind of oversight and control. This is what we need to do. And we especially need to do this at the international level. Otherwise you'll have unregulated research in countries that aren't going along with an effort to make the technology safe.
>> Allen, I know the commission is dying to ask you a bench of questions.
>> Perfect. Good timing.
>> I do need, John, to make certain that our chair has an opportunity.
>> I'm going to take it that Allen Buchanan -- I have ceded my time to Allen Buchanan. Seriously, I would like to give my fellow commissioners a chance to ask questions. Jim, if you would.
>> John, you're number one.
>> Okay. Again, thank you. The bar was set very high this morning and it just keeps getting higher and higher as we progress through the day. As Amy Gutmann our chair has pointed out again and again, this is a deliberative body. Okay? And that entails that we need to ask questions like, who is going to be invited to the discussion and what sort of weight we will accord to what they say? These words of argument that they give. So both Greg and Allen have alluded, you know -- Greg at the start and Allen at the end, to how we should deal with questions of religious or metaphysical nature. And I just want to press this question a little bit harder because it does raise difficult and really important questions for any sort of deliberative body like our own. So, Greg, the way you put it originally was that you can respect the views of people who believe that this involves playing God and so forth, but we should sort of discount arguments that are based on sort of sectarian, religious views or on, as you put it, various world views. Now, I can easily understand how we should respond if somebody says, well, we should oppose synthetic biology because that's what Jesus would want us to do. Okay? Because that's clearly a kind of argument that not everybody can, you know, agree to. But if you widen the circle of suspect dialogue to include world views, that would include a lot. It may include Francis bacon's notion of teaming nature for human good, which most scientists would be guilty of. John Stewart Mill will have a similar view of science. And it would also I think include sort of deep ecologists who have a world view that views with suspicion sort of monkeying around in nature or, you know, adding synthetic genes to the natural world. So I'd like you to both really sort of circle back over this question a little bit and help us get a grip on exactly what's at stake here and exactly what your position is on this. Okay? In other words, are you saying that, you know, certain sorts of arguments should be ventilated, but not really given a whole lot of credit. Or what's the position?
>> Just a quick reply. I think if you together come to a conclusion to make a certain recommendation, you should not water it down in deference to views that you think are false. Now, that doesn't mean that you should sort of go out of your way to try to show up people's views as irrational or somehow inappropriate. But I think you just have to be courageous enough to say, look, in the parts of our documents where we are drawing conclusions about this technology, we're going to call it as we see it. And we will have a full ventilating of a wide range of views. Nobody should be stifled. But that's not the same as saying that you should sort of view your conclusions as having to track the majority view of the public or that they should even reflect some substantial minority of the public's views if you think those views of the public are simply not supportable. Easy for me to say, but I think that's what you should do.
>> So, Dr. Kaebnick, I wanted to press you about your view of the evolutionary claims and the highlight of the arguments developed now are based perhaps on a flawed view of evolutionary and nature claims. I wonder if there's a version of the claim that you might agree with. And that is that it seems like at least with the types of fixes that you refer to in evolution, some quick fixes that are brought together to solve immediate concerns, that the process is a slow one, right. So evolutionary fixes happen over time which allows the rest of the environment to adapt to those fixes potentially as well. In synthetic biology, we may be talking about faster changes. So you're both right in that we can develop much more efficient solutions, but potentially then the impact on the environment may be much greater, such that nature is able to achieve potentially a slower and more balanced approach than sudden, introduction of drastic changes goes.
>> Well, I think there are actually some sudden and drastic changes that occur in nature without human intervention. I guess what I'd like to say is I think that the important thing is to recognize the complexity of evolved organisms and ecosystems. But recognizing that they are complex is quite different from saying that they are optimal and stable. That's the mistake. That's the mistake that people make. When they talk about a master engineer, they are attributing much more competence to evolution. Organisms are always in danger of intervene you prematurely because we don't know enough and don't understand the complexity. That's quite different from saying we shouldn't intervene because it's perfect and stable. A brief quote from Darwin here. What a book a devil's chaplain could write on the blundering low abhor I hadly cruel works of nature Darwin.
>> I'm not saying that you would say organisms are perfect. But I'm wondering if the rate of change is different than the type of organism.
>> It all depends upon whether the rapid changes we might be trying to make through synthetic biology or other means are ones that are likely to have a large impact on a fairly large ecosystem. And that's where all of these questions about containment and reversibility come in, right? And I think that's extremely important, you know.
Those are the technologies you have to think about. Those are the risk reduction technologies that have to be thought about. You have to try to find out from the scientists which of the containment and reversibility techniques already developed in molecular biology and in the traditional genetic engineering are applicable to synthetic biology. Which ones aren't. Which ones have worked in the former case, which ones are problematic and which new ones you need. That seems to me to be the answer. I'm not denying this is a problem. You're right. If you make some profound change in organism that has fairly dense interconnections with a larger ecological sphere, then the recalibration of the rest of the elements of ecology of that may be pretty Rocky. That's true. Thought all the more reason to think about limited, contained kinds of interventions.
>> Thank you.
>> Anita, why don't we have your question? And then in the interest of time, go out to the audience.
>> Thank you. I have two relative quick ones. For Greg, I was interested in the fact that you mentioned religion in connection with the intrinsic value arguments, and not in connection with the consequencialist arguments. Many people of faith coming out of religious traditionals are not just concerned with vague metaphysical respect for nature of the sacred or inappropriately playing God. They are also concerned about social justice and the kinds of issues we heard from the previous panel about the bioeconomy that the potential result from pursuing a synthetic biology. So I just want you to agree with me that --
[LAUGHTER]
>> Done.
>> Okay, great. Then for Allen, my question is a little more complicated. You made the point along the way that maybe we can manage some of the risk involved in synthetic biology by designing in safety, like the suicide gene or something of that nature. It occurs to me that is an often reassuring folk and engineer in safety. But hasn't experience taught us that we have to be a little bit careful there? Because, for example, with fast cars. Oh, we'll just engineer safety into fast cars. But then the corporate guys decide that it's too expensive to put that extra tough bumper on the back of a car so cars aren't as safe as they could be. Or in the data protection field, we all heard for the whole 1990s, we'll just engineer into the Internet privacy proposals. But then it turned out the website guys, they want to create a market of new information and not going to engineer privacy into the Internet.
So we can do it, but whence comes the will to do it? And should the public feel safe that we're in fact going to get those safety devices engineered into the product?
>> You're absolutely right, obviously, saying in principle, looks like there are greater resources for synthetic biology for designing in safety features. That's in principle. What happens in the real world? That depends on what the incentives are and the regive regime can test those limits. I think that's a crucial question. I wouldn't want somebody to overrely on the idea we can design the safety in. It's a combination of sort of external controls and some designing in. And the question is, how can you ensure that the designing in safety really gets done and gets periodically reevaluated and works in a complementary fashion with other kinds of safety measures that have to do with the environment that the product operates in? You mentioned the notion of justice, too. I just want to mention that the slide presentation is just a fragment of a larger piece that Russell Powell and I wrote for the commission that's about seven pages long. And in it, we do spend some considerable time on the justice issues. I'd like to say one thing about that. I don't think there's a peculiar part of justice in synthetic biologies, it's part of innovation. We live in a world in which innovation is very important.
And our theorizing about justice and institutions have to take into account the problems with justice and innovation. For the most part, there really are problems about the slow diffusion of beneficial innovations. Okay? It's that we need to learn how to reduce the gap between when some people get a beneficial innovation and when the bulk of people get it. For some technologies, that gap is very small. Cell phone technology is the best example. Diffusion of cell phones has been quite incredible. Poor peasants in south Asia are revitalizing their economic life with cell phones. The political life of cell phones has been incredible, too. You can't assume a technology is going to diffuse quickly. We need to think about how to speed up the diffusion of beneficial technologies and don't be a synthetic biology exceptionalist and think this is just a problem for this area. The solution to the problem for synthetic biology has to be part of a larger problem of thinking about new practices and institutioning for justice in the diffusion of innovations.
>> Why don't we take one question from the audience? If there is one. With the reminder to others that when we reconvene after this session, we will have a plenary that will involve all of our speakers so we can have more questions. Really just one at this time. I'm sorry. Hang on for the plenary session. Yes, sir.
>> Good afternoon. My name is Sal hajarski and I'm a student.
My question goes back to degrading life and you addressed this and I understood your counter arguments in regard to the subjectivity. But I have to be reminded of something that Mr. Thomas, the previous speaker who was up here, kind of brought up about the economics of the biology industry. What I was really wondering is what you think using life as a means of production would do in terms of devaluing life. I understand we use living things, obviously, as products. We have agriculture, etc. But we haven't really used it in itself as a means of production. I mean to the scale that we would be using biotechnology or synthetic biology, rather. So I was kind of wondering about that.
>> Well, briefly, I'm just a little uncomfortable at talking about using life as a means of production. Life is just too big a term. Okay? If you get more specific, I think most of your concerns will dissipate. Okay? If you are using living things, you said it. We use living things as a means of production all the time. We are a living thing. We use ourselves. So I would worry about this kind of redefining talk of using life or people saying you can't patent life. That's not a very useful entry into the very complicated debate about intellectual properties to say let's don't patent life. Talk specifically about what you're talking about patenting and why you object to it. And talk about which biological processes you think shouldn't be used in which ways for which kinds of production. Be much more comfortable with that kind of talk. I just don't think it's very productive. You are clearly on to something. We don't want to treat everything as if it only had instrumental value. We can all agree on that. We need to get down to particulars, if we're going to get very far with that.
>> Did you want to comment, Greg?
>> No. I think that's exactly right. I think that the concern is a serious one.
>> One of the things the commission has learned that in certain sessions, we need to allow a little bit more time. But what we will do is reconvene in just 10 minutes. This is quarter past 4:00. For the plenary session, we have all of our speakers with us and we can engage them in further conversation. Thank you, Dr. Buchanan, thank you, Dr. Kaebnick.
[APPLAUSE]
Bryan Bishop
Jul 8, 2010, 5:24:11 PM7/8/10
to diybio, kan...@gmail.com
On Thu, Jul 1, 2010 at 12:42 PM, Bryan Bishop wrote:
> http://bioethics.gov/meetings/070810/And now the plenary session transcript..
>> Would everyone take their seats? We're going to get started in a moment.
>> I want to thank our panelists. We have had a terrific first day so far of preparations, questions. As someone once said, good questions outrank easy answers. Nobody tried to give us easy answers and I thought all the questions from commission members and public were really excellent and will help us a lot. Today's presentations and the questions and answers, I have spoken to all our commission members at our break. And they have really helped us. One possible answer to the question of how we're going to process different world views, faith-based views, non-faith-based views is quite -- let me just answer that quite directly from my own perspective. It's that we would be unwise to think we have the answers now before listening to different perspectives and listening to the arguments and reasons that they give. When it comes to writing our report, we will write what we think is the best advice and recommendations to the President, given what our charge is. And we will do so with all respect to the views we have heard, but not in entire agreement with all the views we have heard. That would be impossible. It may be that we don't entirely agree with any of the views we have heard. But we will do our very best. But only arriving at conclusions after we hear more. And this is the beginning. And so far an excellent beginning. That said, I don't want to lose any time. And I'm going to open it up to the --
Oh.
There you go.
>> I'm sorry.
>> No, you have no apologies. Thank you very much for the heroic effort to get another microphone here. So the question I want to lead off with is a very direct question. And I want direct and succinct answers for the presenters. And that is if there's one recommendation you could make to us for what we should include in our report, what would it be? Just one. I know it's hard to pick just one. But it would be helpful for us to know what you think is really important that we address. Bonnie.
>> I would say you have to be very careful not to restrict the creativity, the ingenuity and the innovation of scientists going forward in this field.
>> Others. Let me just read, if I can, the charge to the commission in the letter that I received, May 20th letter. Do we have the letter?
>> Yes, right here.
>> I did have it because I think it outlines our charge very well. Here we go. Let me just give you a moment. So it asks us. And when you are asked by the President to do something, it's my philosophy that one does it. Especially when it is as reasonable as this is. In its study, the commission should consider the potential medical, environmental, security and other benefits of this field of research, as well as any potential health, security or other risks. Further, the commission should develop recommendations about any actions the federal government should take to ensure that America reaps the benefits of this developing field of science, while identifying appropriate ethical boundaries and minimizing identified risks. Now, the one interesting fact about this charge is that it asks us to develop recommendations that ensure that America reaps the benefits of this developing field of science, while identifying ethical boundaries and minimizing risk. And I say that because, Bonnie, your recommendation to us is absolutely consistent with this charge. Jim, would you like to chime in, in absolute agreement or counter point perhaps?
>> No, no. I think an appropriate boundary is the laboratory door. And this technology kept within the laboratory door is an opportunity for the creativity and imagination of scientists to further understand the frontier of knowledge. But that's the boundary that shouldn't be crossed at this time. So no environmental or commercial release.
>> And let me just say that several people mentioned the precautionary principle without defining it. But the definition that I have seen in the literature of the precautionary principle is don't go ahead until one can prove there are no risks. Is that too strong, Jim?
>> There are several definitions of the precautionary principle.
>> Just so we have --
>> Where there is evidence of risk of harm, even when that harm isn't yet proven, that shouldn't be a basis of not moving ahead.
>> Okay.
>> So it's not as straightforward as don't do it until you can profits safe. You can never prove everything in the world as safe. But where there are concerns, you don't need overwhelming evidence of lack of safety of risk to stop something. You can stop something with just some risk.
>> That's good. Because in something that ETC wrote, it was even stronger than that. I'll take that. Allen, I don't want to get sidetracked.
>> I would emphasize not just benefits to the U.S.A. but to mankind, to humankind. I don't think this should be a sort of -- I know you're not saying it, sort of rah-rah, let's get ahead on synthetic biology for the U.S. I think you need to think about the benefits to human beings and the distribution of benefits and risks. Because the people benefiting the most may not be the people bearing the greatest risk. So I would take a more cosmopolitan view.
>> Two points you made. One is we don't need to stop at the boundaries of this country. But the second point is to think about the distribution of the benefits and the risks and the harm. And that I think is something that nobody here has disagreed with. I mean people may have different views of that. But it's very important for us that is part of what we see as the charge of ethics and social responsibility. We're really in the charge. It's interpreted quite broadly. And I think legitimately so. Yes.
>> There are many different mechanisms you can use to regulate a technology. And I think the commission has to think seriously about which regulatory mechanisms they are going to recommend in so far as they need to recommend a mechanism that is flexible enough to be nimble in a rapidly changing technology that's going to be different five years from now than it is now, so you don't want Draconian or overarching regulations that stifle innovation and can also respond to new situations, to limit or stop things that might actually end up being dangerous. You need more of an oversight committee kind of way of thinking about it, though that oversight committee may not be the exact correct mechanism. Then you need a set of laws on the books that right now create boundaries of this technology.
>> Yes.
>> Hi. Yeah. As I have said before, I don't think there has been enough discussion of specific cases of environmental risk and what they involve and harm. And I feel that it may be time for the national academy of sciences to put out a report on, you know, what are the potential harms that we need to be concerned about. And this could serve a double purpose. I almost said dual use. But a double purpose of educating the public and also moving the conversation forward to be away from soundbytes, which I don't like, like we're going to save the environment and have biofields that are wonderful with no consequences. I feel like a more deep analysis by, for example, a committee at the National Academy of Sciences, an NRC committee would be a very good outcome.
>> Jim. Go ahead.
>> I think looking back at what we did for the past 10 or 15 years on nanotech, I think if there's interesting lessons there, it's not a perfect analogy. As Jim said, I think the thing that we didn't do early enough and seriously enough was look at implications research. Okay? So there's a tendency to push the gas ahead on the applications and the brake on the implications. Now, there's three things that have to happen, to sort of send the message to the world that you're serious about implications. The government needs a strategy that goes beyond biosecurity and execute basically the biosafety issues. You need more agencies involved, E.P.A., OSHA, F.D.A., the forest service, they all have to be in the room. You have to have some serious money funding research going to the right agencies and right research institutions. We're talking tens of millions. Right now we're nickel and diming the research. In the case of nanotech we use P-cast and the General Accountability Office. So I think that whole piece of being able to say we're doing the applications, but we're also very aware of the implications, not just the environmental ones but some of the social ones Jim was talking about. And we're serious enough to put serious money behind it. We have a strategy. We're making sure that's evaluated on a regular, periodic basis.
>> And this underlines the point that we really take seriously that it's much better to do things proactively.
>> Correct.
>> And to really assess risks and take the measures that are needed ahead of time, rather than waiting.
>> And I think this is something that the public wants. They expect it. I think the idea of being able to get the research ahead of public concerns is extremely important, even if you don't have the answers, to be able to say there's a serious effort there to get them.
>> Yeah. Yes.
>> If I can just follow up on that, I think -- and I'm sure David would agree with this. A key element of that is transparency. In our typical regulatory regime now, risk is generated by private companies that are going to an agency for an approval process. Very little of that information is made publicly available. And one of the great debates on genetically engineered organisms because of confidentiality and other restrictions, those risk assessment decisions get made essentially behind closed doors so if we can have a publicly funded research effort that looks at risk assessment methodologies, looks at implications research, makes that transparent as good science should be done, I think it will go a long way not obviously only to developing this body of knowledge but in parallel with technology and helping to build public confidence that the technology is being discussed in the open and to build a knowledge base for the regulatory agencies when they need to use it.
>> Got it. George.
>> Yeah. So I'll try to frame this as the one recommendation, but it's also quite -- I'm being quite reactive to what's going on in a positive way, hopefully here. But I would actually and this will sound ironic, I would go further than Jim is going in the sense that I actually that the drawing the line between commercial and academic is dangerous in the sense I think the academics are capable of releasing things in the environment much more problematic than what a company would do because of the extra steps that go into approval and investors and so forth while academic, especially in unrestricted and creative one as Bonnie would have. Now, I'm not saying --
[LAUGHTER]
No, as Bonnie would like to have us all about. So I also would like us to be unrestricted and creative. But I think drawing this line with commercial is not. And so what we need is something not just one NAS report, but an ongoing report that's going on all the time where we're constantly doing cost-benefit analysis. And I think that is best done in the context of a larger project. And, for example, the genome project set aside a considerable fraction of its sums to ethical, legal and social implications. I would add policy and economic considerations. That would be my one recommendation.
>> Good. And that actually picks up on Nancy's and Allison's continual reassessment and a mechanism in place.
>> But it has to be integrated.
>> Right. Other one suggestions? Yes.
>> This is the best conversation I have seen on synthetic biology since I have been involved with it. And I think that has to do with the fact that it's coupled to the President and it is coupled to executive leadership. And to complement the two remarks around sustaining what leadership can do in this field, you are unlikely, even in the best case scenario to get everything sorted as the world is today within the deadlines you've got. And it's certainly the case that things will change. So there can be no question there has to be some sustaining activity. But I think what we're finding here and I guess it would be my one amendment to sustaining activity, is to enable one to be ethical in this field, one has to also consider how to enable the field. And so it's not a typical discussion of bioethics. It's a discussion of how investments and technology development and the science and the law and the ethics all come together. I don't know. I've never seen a sustaining venue that enables all of that to happen. But you've sort of captured it here somehow. Right. So maybe it's this group of people or the next version of us with a different name. But let me encourage it to not just be a sustaining consideration of benefits, dangers, costs. But how we actually make this all work.
>> Well, we have captured it. And there needs to be a "We" going forward that doesn't simply issue a report into a black hole. We need some ongoing -- it came up education and understanding of whatever turns out to be a set of reasonable recommendations for how we can both benefit from and minimize identifiable risks.
>> Let me try and say something more clearly.
>> Go ahead.
>> I think it's very significant to have executive leadership on this topic. And I think whenever you are trying to do something new, there's skepticism about utility. There's concern about risk. And there's a disbelief. And so I think there are logjams all over the place where people want to be working together on this in different agencies at different levels. But they are not enabled. And there is something very powerful and special and essential about having executive leadership associated with leading.
>> Good. We've got it. Kristala.
>> One of the things that's come up over the course of today is how exciting this technology is and particularly how it is percolating down to younger and younger people and perhaps in a distributed way to people outside of institutions. So the one recommendation I would like to see -- I don't know the answer to this. I'll say this up-front. But I think there needs to be considerable thought as we go forward thinking about risks and regulations and how all those play and interplay with one another and interact with one another. How do you have that conversation in the context of extra institutional or noninstitutional players or participants. And figuring out a way to be educated about that and to be as constructive as possible to still have the surveillance that George has talked about and the monitoring that others have talked about. But to not automatically think that immediately goes to what our federally funded researchers at academic universities are doing.
>> So this I think raises to the higher level what drew earlier said about wanting it to do it together rather than do it yourself. That's very good.
I'm going to just invite not only the presenters but anybody and just urge you, anyone who is interested to send us comments. We, the commission, will read them and I'm urging you to think about the one thing that you want us to address in the report because we'll read whatever you send us, but I'm telling you what would be really helpful, if we just discovered what is truly important to you, rather than a long, long list. Which we would also read, but it won't be as helpful as this kind of really focusing on what we need to do to make our recommendations and these deliberations most productive. And with that, I'm going to ask Jim if he wants to ask.
>> Yeah, I'm dying to ask some questions. But I also know -- would you mind if we intersperse some of the public questions? I know I saw some people stand up. They almost charged the microphone.
>> Why doesn't someone pop up but I want to give commission members time. We will intersperse it. I was going to do it in order.
>> I feel like I short changed them in the last session. It's guilt.
>> We will compensate. I have a lot of Jewish guilt, too.
[LAUGHTER]
Here we go.
>> I'm at the American association for the advancement of science. My one recommendation is to be clear about implicit assumptions that you may be building into something you say. The demand of the study is synthetic biology, but lots of the things we talked about pertain to innovation as a whole or biotechnology or social equity as a whole. To the extent synthetic biology cannot make the problems worse, it's certainly worth bringing these up. If the net effect to focus on synthetic biology when your goal is much broader than that is to distort the innovation claim and not solve the bigger problem, that's a concern. One example might be -- pardon me for picking on you, Jim. The criticism about going to a bioeconomy and the consequences, there's four things that are the alternative to that. One, you love fossil fuels. That's great. Two, there's a new kind of technology that's going to solve the problem outside of our domain and we'll hope that takes care of it. Three, we'll go global lip to a lower energy intensity or four, find some way to get rid of a couple of billion people because the planet can't support all of them. Be clear of the assumptions you're making.
>> We will definitely do that. And we are not going to -- I can assure you we're not going to pick on synthetic biology and blame it for all of the world's problems or see it as a cure or its prohibition as a cure for all of the world's problems. So that point was not lost on us. I'm glad that you made it, but it's also our charge to look at synthetic biology broadly, not only for what it has done to date but what its implications are moving forward and how it relates to other field, hence the kind --
>> Connected to that, it comes on my head, if we can't get this answered, let's give it two minutes to see if it converges. But I do wonder if one of the contributions the committee could make might actually propose a comment just made to be able to give a better definition to what we understand synthetic biology to be. I went back over my notes. I have five definitions we were offered and not necessarily complementary ranging from DNA construction to be the number one technology of the 21st Century to having it defined as synthetic genomics that must exist in digital code and processed in the genome and activated in a living system to others saying this is really just an extension of genetic engineering and in fact one person saying there's no clear distinction between synthetic biology and genetic engineering. We had one definition offered saying it was making biology easier to engineer. If all of those are true and you're just asking the commission to kind of sweep them into a hole, we can try to do that. But I hate to have all these scientists leave the room without my having asked have I missed the definition for synthetic biology.
>> You haven't gotten them all.
[LAUGHTER]
>> You're probably right.
>> Well, I remember Dr. Prather told us if you had five in the room, we'd get six definitions. So let's see if we can get another one.
>> Well, I refuse.
[LAUGHTER]
>> And my counsel to be would you don't stress out about it too much. I have seen particularly in Europe meeting after meeting creating meeting after meeting with the primary agenda item being to come to a definition.
>> Then I suggest we don't discuss it further.
>> I can reach a consensus on that one. Let me just say I've got a note here that says next time you invite commentary, you can mention our public email address. So I'm going to invite commentary again in order to mention our public email address. In...@bioethics.gov. Nita.
>> This may not be a fruitful question in light of the abandonment of having any definition of synthetic biology. What I'm hoping is for some idea of what the unique risks are that are posed by synthetic biology as opposed to any of the other fields that we have discussed today. And, you know, this may not -- this may be difficult to characterize if we don't have a clear sense of what's included and what isn't. Really, what's different in the risk that this field poses as opposed to previous fields or previous kinds of biotechnology?
>> The answer can be nothing.
>> I can't speak to this comprehensively. But in the Sloan foundation study done with Dr. Epstein and garFinkel and freedman, on synthesis of DNA, we face the same challenge. What's unique about the tools processed science of synthetic biology from the risk perspective. In this case we're looking at oftentimes security risks. To give you a specific example, we identified three types of viruses from which direct synthesis of information would be the best available technology for providing access. So things that weren't available that didn't exist at this time, the 1918 influenza and ebola and it seems there wasn't a specific Delta increase in risk due to the tools within the arbitrary ambiguous definition of the field. I haven't seen it done beyond security and human pathogens but I'm sure you could quickly work that up and sketch out how big a puzzle it is.
>> Yeah. The parallel question, by the way, is what are some of the unique benefits of the field. Jim.
>> I just wanted to throw an extra of what I think is an example of a sort of unique thing that comes out of synthetic biology, although an extension of an existing problem, it's unique in how it plays out. And that's in the ability to enable digital biopiracy. Up until now, ever since the 16th century, if you wanted to take biological materials from communities, say, in the global south, you'd have to go there and take them and physically remove them. Now, we have an international regime being put in place to try and prevent that movement of the biological materials. Synthetic biology means that in fact you don't have to go there at all. You can download it from the Internet. You can upload it to the Internet and send the information. That's a difference in-kind I think is unique.
>> Commission members questions. Raju.
>> I was struck by a couple of comments. One made by Allen Buchanan and the one by David about sort of deja vu from 25 years ago and thinking about, you know, issues dealing with the genetic engineering or dealing with the nanotechnology. So the question that I have is that, are there lessons we have learned either from the process or the outcomes of those discussions that would be very helpful for us in thinking about this issue?
>> Allen, do you want to take a stab at that? You have been there before. Put your red light on. Counter intuitive, the red light means go.
>> You shouldn't assume that the commission report is the same as making an impact on public opinion or public knowledge. That's one thing I would say. And the other is I think there's a danger brought up a minute ago of doing a report on synthetic biology without making it clear that it's just part and parcel of much larger issues of scientific innovation. Those are two lessons I think you can learn.
>> If I could respond to that, too.
>> Yeah.
>> I think one of the other lessons is that applications matter. The way the particular trajectory and the development of the biotechnology, particularly with respect to genetically modified crops and food ended up being an enormously polarizing debate that we still have repercussions from today. You could envision a different rollout of that technology that would have had a very different kind of worldwide greeting, I think. I think the other issue from a regulatory perspective is that I think we certainly have learned particularly with the regulation of plants that the goal of having 100% segregation of the genetically engineered plants does not work. It's just not a feasible goal. Now, again, that goes back to the issue of containment and control. You may have a different opportunity here, but that issue has in fact created -- while not environmental or health issues, has created some economic challenges for farmers, especially.
>> Public questions. You need the microphone. Go ahead.
>> Yes. Gameon Bennett, the director of human processes at the biofab. Comment and then question. First on the question of what I think that this commission should be focused on, we have heard a lot today about biosafety and questions of contamination. And a little bit about biosecurity and the question of malicious action. I think the third agenda that Dr. Endy raised on his slides is the question of preparedness. If something negative happens either unintentionally or intentionally, how are we prepared to respond? I think the question of preparedness is particularly useful for this kind of a commission because it goes to practices, habits and dispositions which are really the heart of ethical matters. That was my comment. The question I would like to pose to Drs. Kaebnick and Buchanan was the question that was actually raised in the morning in both sessions in the morning. And I would like them to answer the question, but in light of comments that Professor King made in the afternoon, the question is what is distinctive about synthetic biology today relative to other moments in the development of biotechnology and genetic engineering in particular? And I took that question to mean what's really significant about it today.
>> Okay.
>> And this morning when the question was posed, the response came on what was distinctive about the technology. Professor King invited us to think in the way of which context makes it significant and relevant. I'd like to ask Dr. Kaebnick and Dr. Buchanan the context in which synthetic biology is emerging that might tell us something about the ethical calculus.
>> Greg and Allen. Greg, you want to begin? Allen, you want to begin?
>> Well, I think the ethical context is people are very worried about environmental damage and global warming in particular, so there might be a tendency to have unduly high expectations for synthetic biology doing away with the need for fossil fuels or something. So that could distort the debate. But, otherwise, I can't think of anything that's peculiar about the context that's different from the context in which genetic engineering has been evolving for the last couple of decades.
>> Thanks. Greg.
>> I feel like anything I say about this is going to be very speculative and ill founded. But synthetic biology is sometimes described as the beginning of the new Industrial Revolution. We have had one Industrial Revolution and now that's sort of coming to an end and we have an opportunity maybe to get in front of this whole new wave that might, as Jim has pointed out, completely overturn existing modes of production and distribution of a lot of basic goods. And so that strikes me as consideration here.
>> Let me just turn the comment about preparedness into a question for any of the presenters because we didn't really address that. We'll take some deep dives later into some of these. But does anybody have some insight on the preparedness issue and how we should approach it? Yes. Rob.
>> I have a bunch of stuff in my head that is the result of listening to many provocative comments throughout the day. I'll do my best to stick with that. When the 1918 flu virus was accomplished and we constructed, there were a number of vitryial public comments about how we have given bioterrorists the best weapon they have ever had forgetting how hard it was to rebuild the virus. If you talk to people who build viruses for a living, pathogens particularly for a living, they fail most of the time. Whether it's SARS or the 1918 flu, what not, the funding, the tens of millions of dollars of funding that goes into efforts to rebuild pathogens, to figure out how they work results in success a small fraction of the time. So I find it unlikely in the near-term that any amateur is going to pull that off successfully. In the median term, long-term, it's going -- I don't know it's going to get easier. I think it was Terrance selfy, partially responsible for reconstructing the 1918 flu. When the public comments, yes it's true it's becoming easier to write pathogens from scratch.
But our real problem right now is nature is the best bioterrorist. And I would just go back to my comments about SARS this morning. If SARS were to come back today, we would have no better response capability than we did the first time. There's no human vaccine for it. We would be better at diagnosing it and finding it at the beginning, but it's unclear we would have any better clinical response to it. And I suggest that's probably true for most emerging pathogens. I hope that in fact we get some vaccines in the next year for the flu. That would be fantastic. My suspicion is that issues will arise, as they have for the last five to 10 years, thinking about synthetic vaccines that will stand in the way.
>> There was a question. Yes. Question.
>> This is a question to give you some historical perspective that you may not. In view of the fact that most, if not all reports of Presidential Commissions in the last half century have gone to the dead-letter office, and in view of the polarizing issues that you are discussing, you have a difficult task of finding a way to make your act of deliberations consequential.
>> We do indeed. Let me point out --
[LAUGHTER]
-- that is the chaul of -- challenge of anybody who wants to make anything consequential in government. We are an advisory body. But let me just point out that President Clinton's end back was asked shortly after it was formed, like we have been asked by President Obama shortly after we have been formed in the case of N-back, it was asked to issue a report on cloning after dolly was cloned. And shortly after that report it was issued, President Clinton actually agreed to some of the major recommendations of the report.
Congress never acted on those recommendations, but several states did. And the report was quite influential. And aside from the fact that, as Drew has pointed out, the President has actually asked for recommendations and been very specific in our not only asking for recommendations, but constituting a commission that includes three members of relevant agencies that might be asked to consider some of these considerations, the value of our report, if we write it clearly, is that it is far from going into the dust bin of history, it's actually there for the concerned public to read, as a possible antidote to the immediate soundbyte reactions that are almost always more extreme and more simplistic than the educated public and the concerned public, both here and abroad, would like. So that is our hope, expectation and challenge. Thank you very much for expressing what I'm sure you are not unique in holding.
>> Hello. My name is Brian wells, I'm the chief technology officer at Penn medicine. I help the clinicians and researchers in the pursuit of benefits of personalized medicine. Personalized medicine is the treatment of disease in a person based on genotype and not phenotype. Are we too soon for the benefits of that technology in that realm? Do we have decades to go? Are we on the verge of using synthetic biology for treating individual patient problems?
>> Doctors, including doctors on the commission.
>> My sense is personalized medicine has decades to go with respect and the contribution of synthetic biology is probably around personalized pharmaceuticals and the ability to manufacture individually-tailored drugs in context on demand.
>> Nelson.
>> Let me just say that our state of understanding of genomics and genome research is still quite in its infancy. So I think that the public concern which is rightful about personalized medicine is not going to be realized by cogent work in the laboratory for quite sometime.
>> Thank you. I'm going to respectfully disagree a little bit here. I think personalized medicine is not necessarily about just going from a genome. You can integrate everything you currently have in medicine, plus the genome. And secondly, I don't think it's so far away. We already have 1800 genetic tests that are considered predictive and actionable. And personalized medicine is already having a huge impact in pharmacogenetics and in cancer. So synthetic biology plus personal genomics I think is uncertain, but I wouldn't say it's necessarily that far in the future.
>> Interesting. Drew.
>> I wanted to return to the public question from Dr. Bennett about context and just having the benefit of a couple of minutes to reflect upon what's new.
>> Could I just get Raj first? He has an answer on the personalized medicine.
>> I think that you pointed out, you know, right now we are utilizing genetic and genomic information to make diagnosis and prognosis and treatment decisions and that's what personalized medicine is. And many of the technologies to accomplish that are also technologies also used in many other aspects, including synthetic biology. So even though I do not see any direct, you know, relevance to what we are talking about today in terms of synthetic biology, the technologies are very, very similar.
>> Drew, you're on.
>> Again, just returning to the question of, are there changes in context regarding ethics, and very practically, if I arbitrarily go back to circumstanca 1975 and start with the early applications of recombinant DNA, security as a topic was not considered at Pacific growth. The scientists thought following the Nixon administration with the biological weapons that would be a soft problem. And if you talk to David now, he will admit that's a naive mistake. We live in a different world.
We live in a world people are concerned about security and terror. That's a significant difference to the ethical landscape. I think another point of significance that we're one human generation past the invention of genetic engineering. So Paul Berg is a distinguished colleague at Stanford and I'm honored to learn from him. He's an emeritus faculty. That means as a new generation comes up after the synthetic engineering generation, we have to pass along the information with it and discard some baggage that is dysfunctional.
I think we're at a very interesting point in time. 35-plus years post genetic engineering. And the third thing that's quite significant that wasn't true when a lot of these earlier conversations in bioethics happened, the Internet exists. Not to make a cliche of that, but people interact in many different ways. There's new types of communities and new types of representation and new types of dialogue. And I haven't seen -- it may exist, but I haven't seen a study of how this impacts the deliberation or practice of bioethics, but that it matters greatly.
>> Questions from commission members? Nelson.
>> So there was several wide-range of opinions from a number of you in terms of what the role of governments and I'll use the term instead of our single government, but of governments and their stewardship of this process would be. On one hand, there's been some discussion of having an executive agent or executive process where there would be stewards from multiple agencies that would have allowed there to be a public and transparent discourse that might replicate this kind of forum, but do it in perpetuity that may transcend the political nature of the appointment lengths for this kind of process. On the other hand, you know, we heard that there are some concerns about being sure the choke point of information in the hands of governments, that even under best of intentions, in the absence of some degree of transparency, the consolidation of that oversight could turn into something else. That was your dual use 2. So what maybe would be the recommendations for what role governments should play, so that you don't end up running afoul of either end of that spectrum?
>> Allen.
>> I think you minimize the last risk that you mentioned, dual use 2. If you think about international governments, it's less likely that one country will be able to sort of get ahold of the good information and use it for nefarious purposes. I think one difference in context Dr. Endy has mentioned several, we now live as opposed to say in 1975, we live in a world where international institutions are much more robustly developed than they have ever been. And I think that gives us an opportunity for international oversight and encouragement of the good uses of this technology that didn't exist before. So I would think about that. Think about which existing international institutions are such that you could piggyback some efforts for synthetic lab.
>> Allen, which would you put on your list?
>> I hadn't really thought about that question. I'm not sure whether it's a matter of piggybacking on something in the world health organization as sort of a starting point, or whether some other sort of international venue is needed. But this just leads to another thing. I really think that you need somebody advising you. Not me because I'm not qualified to do it. But somebody advising you on institutional design with respect to recommendations you make that have implications for either how new institutions should be created and existing institutions should be modified to deal with these issues. I think you really need somebody who is an expert on institutional design to think about incentive compatibility and when to piggyback on an existing level domestic or internationally, when you need a new institution. Actually, your colleague, Bob Cohen is the person I wish we could go to first for advice on this.
>> I think, Allison, you said this. As one of your recommendations, you would ask the national academy board of life sciences to make one of their reports. It's actually a really good idea. That's what they sit around and do. And also all of the funding agencies, the government agencies are invested in those reports. So you can have the executive level recommendation, but if you want this to filter out to the science community, right, those reports many of which end up on a shelf, but some of them are highly influential if they are timed right. And I think to couple those two reports together could really give you some umph.
>> And you agree the subject should be potential risks only?
>> What's really good about the NRC reports, they help you craft the question so you get maximum answers back. You know, it's not like you just get to give a question. They help and they are very good at refining it to make the question bigger, better, broader, if that's appropriate. Or to say you need two reports, one on risk, one on, I don't know, technology. But I think to explore that avenue is just one little line in your report to give it lasting -- that gives you much more than your six-month time frame, too. Because those reports, you know, take a year.
>> We don't expect our report to be immortal. It's just the recommendations will -- we want them to be self-replicating like the cell, right.
>> Right, right. Automatically, yeah, in the spirit. But to give yourself traction. Like automatic extra traction.
>> Got it. Raj and then Christine.
>> I want to ask a question but I want to preface this by a little history. The many issues we talked about are indeed very similar to what happened in the mid 1970s when recombinant DNA and the ability to splice molecules became available. At that time, first the in the meeting there was a call for, you know, a moratorium on doing additional work. And then indeed, some parts of the country that I know very well, Princeton and Cambridge, for example, in the cities, they completely banned the use of any of those kinds of technologies. And then as a result of that, the National Institutes of Health formed the recombinant advisory committee. And they developed guidelines to how we would be able to do research. And over the years, that has evolved. And over these last -- all of these years, they have continued to evolve. And we began to recognize that it wasn't as dangerous as people thought that it was going to be. And that we were able to reap the benefits from it, despite the social issues that we have with regard to the use of recombinant DNA technology with plants and so on. And that was sort of considered as an example of how scientists are capable of regulating themselves in a reasonable fashion. Is that an example of a good model of how to do that? Or there are other things we have learned that say that is not a good model?
>> Yes. Rob.
>> I can't address that question directly and I've been sort of mulling with it. But I have a bit of a revisionist view of summar and what happened there. That comes from spending time with Sidney Brenner. I was not there but Sidney was. His perspective has changed over the years. He said that summar was motivated by desire to be just like the physicists. To have the power to destroy the world. And looking back on that, he says clearly, that was not correct. That the power of recombinant DNA then and today does not confer upon biologists the capacity they sort of hoped to have to compete culturally with physicists. The second thing I would say about it is summar brought to the fore a great number of promises, many of which have been born out, not all of which about the possibilities recombinant DNA provides. It was also a chance to air a great many concerns and potential threats that the technology might bring forward. And I would observe that both the promise and the peril will there were listed by the same individuals, by the scientists who went. As we have just heard, many of the potential threats didn't turn out to be there. So summar is a model for something. And I'm not sure it's the model to follow here because the potential for self-promotion is pretty strong.
>> Christine.
>> I wanted to ask -- seems like we have spent a lot of time talking about assessing risks and thinking about security and preparedness and all that. But we have had a couple of comments that were more along the lines of recommendations that we might be able to make that would support or maybe enable responsible progress in this area. And I think the funding for implications research is one of those, the letting scientists be creative is one of those. But maybe there are others that we should think about. One of the ones I wondered about -- let me throw it out here. I sensed this morning that the integrating engineering and biology is something unique and that maybe some kind of more disciplinary something or other, education or ongoing dialogue or something might be along the lines of what I'm thinking about. But anything like that, things that we might think about recommending that would support or enable responsible progress, rather than just putting brakes on.
>> Can I just build on that question?
>> Sure.
>> So Dr. Prather had raised the idea earlier potentially of something like the synthetic biology standardization project or something akin to like the human genome research project which Dr. Venter disagreed with. I wonder as you're answering that question if that's something like a standardization project or something, something that would be useful in a way to enable the science and the useful role for the government or not.
>> Yes.
[LAUGHTER]
And there should be good discussion about what such projects might be. So if you can build a genome, can you build -- and its software that makes its own hardware burdened with those metaphors, why not just call it wet ware. If we use those metaphors, howan operating system in how about we make the engineering version of a genome project? And its standardization and sharing and international and brings many people together and it's really challenging. So I think there's tremendous opportunities around that. I tried to mention very quickly this morning what I considered to be a very important opportunity to have public investment sustained in tools investment. And in particular, DNA construction, but you could go into many different directions with that. So I think there are tremendous opportunities there. No one person should have the privilege of figuring that all out, but we have good mechanisms for research and technology communities to come together with public policy groups to figure that out.
>> David, on this point.
>> I think one of the things the government could do is constantly monitor the changing structure of the industry as it grows. And we were doing this with nano tech because a lot of the work spun out of universities. All of a sudden, you had thousands of small businesses. The kinds of intervenses you make and kinds of government agencies to get involved with small businesses, the kinds of things that small businesses use are quite often very different than the Dow chemicals. So I think there's a tremendous need for something like the Department of Commerce to sort of say, what is the structure of this industry look like at this point in time? How can we support them? Whether they need capital. Whether they need support promotion. Whether they need help with biosafety. There's a different set of innovations and strategies. And it's going to change. They all have very different needs and those needs will have to be answered quite often by different agencies and different outreach arms of different agencies.
>> Yes.
>> There are two ways the government can support something like this. One way is through the development of tools. And the other way is through directing the technology towards goals. So the government can support the creation of certain synthetic biology tools or it can say we're giving "X" amount of money for the creation, you know, for cures to the following disease or orphan diseases by synthetic biology means. So we have to differentiate the kind of incentives that we're talking about to move it forward.
It's probably premature for the latter, to start. It's still basic enough that probably the most productive thing the government can do at this point right now is to support tools, rather than goals. But it's probably not that much in the future where goals will become far more important and where there's an opportunity for this society as a whole through governmental agents to say given this enormously diverse set of activities, here are some of the places where we as a society want to put our resources to encourage you to accomplish the following things that are important to us.
>> So we have heard loud and clear, and I'm not going to sum up today. We have tomorrow as well. But I am going to draw this session to a close, simply by saying we have heard loud and clear, albeit sometimes from different people, that we need to think about the potential benefits as well as the risks and harms. And let me just sum that point up by saying going back to the social justice issue. There are people today and people who are not yet here today whose lives can be saved and enhanced by what science today often unpredictably tomorrow creates. There are also concomitant risks and harms we need to take into account. And I think it was a wise charge that we received to take both into account. And all of the presenters together have addressed some of the benefits and the harms. And we will continue to pursue them and think about the institutional ways, domestic and international, in which those on the one hand harms, minimizes risks, minimizes but not going to zero, and benefits maximized. I know enough since I started as a mathematician to know you can't maximize and minimize at the same time. But we're going to think hard about this. And I really want to conclude by saying thank you to everybody who has attended, to the presenters today. And we look forward to the presenters tomorrow. And above all, to my fellow commission members who have already shown that we have a commitment to this common Enterprise, thank you all for coming. And enjoy your evening.
[APPLAUSE]
Josh Perfetto
Jul 8, 2010, 5:58:29 PM7/8/10
to diy...@googlegroups.com, kan...@gmail.com
There are also archives of these sessions that are slowly being populated: http://www.tvworldwide.com/events/bioethics/100708/ . Many are well-worth watching.
-Josh
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Bryan Bishop
Jul 9, 2010, 12:33:13 PM7/9/10
to diybio, kan...@gmail.com
On Thu, Jul 1, 2010 at 12:42 PM, Bryan Bishop wrote:
http://bioethics.gov/meetings/070810/
>> Thank you. Thank you, Amy. Good morning to everyone. Good morning to our commissioners, to our experts. Thank you all for being here. Excited to get this second day going. Hope it will be marked with the same frank and eager level of discussion that we enjoyed yesterday. This morning, as Amy has said, our first session is on ethics. We ended with a session on ethics yesterday and we'll start today's panel hearing from David Rejeski who directs the Woodrow Wilson center for science and technology innovation. Innovation program, excuse me. As well as synthetic biology project. And before he joined the Wilson center, Mr. Rejeski worked for the White House Office of Science and technology on a variety of technology-related issues. David, welcome this morning. We look forward to your comments.
>> Well, thank you. It's a pleasure to be here. I'd like to thank Dr. Gutmann and the whole commission and also thank your staff which I think have done a great job in terms of supporting everyone that was involved. I have some slides that I'm going to go through. Let me just start by saying that we have devoted about six years of our time into my project trying to essentially bring the voice or voices of the public into the conversation about science policy on emerging technologies. We started with nanotechnology and have now added synthetic biology. In terms of how we do this, it's pretty easy. We talk to them. We go out with a fairly intensive and structured discussions with people all around the country. We have run lots of focus groups in Spokane, Washington, Dallas, Texas, Cleveland, Ohio, Baltimore. Every year we do an annual survey with heart research. We'll be doing a new one in August on synthetic biology in which we'll be asking questions about what happens if next year we produce our flu vaccine with synthetic biology. It might be interesting to get public input on that question. We also do a lot of partnering with other groups that are doing similar kinds of research in the space. And some work on media. Let me yump in and give you a sense of what we found out. Big question, what is this? We have been grappling with this for two days. We ask people, how much have you ever heard about synthetic biology? These are the figures from 2008 and 2009. They have actually increased somewhat. At this point in time, 80% of the American public has heard little or nothing about synthetic biology. So who they hear from and what the message is and how they hear it could have a huge impact on future trajectories of the technology and our ability to use it. So you're in this I think very interesting space right now where people don't know much. Having said that, this is a complex word and it tends to, I think, elicit a lot of concerns as soon as people hear it. It's different than nanotechnology. People are, what is that? Synthetic biology, people think about this through analogy. And the train goes something like this. Synthetic biology is that like artificial life? Is that cloning? Is that stem cells? Is that GMOs? Within 15 seconds, you have hit every third reel issue that you might possibly hit. The term synthetic biology makes me think of genetic engineering and something lab grown. Cloning is the image I think of. I think about molecular compounds and playing God. This is the public speaking right now. So this is kind of how you're starting off. In order to kind of get around this, what we have tried to do is immediately focus people on applications. We go past the science right into application. Last year we did a lot of work on biofuels because that seems to be coming down the track very quickly. And the people's reactions to biofuels and the use of synthetic organisms and metabolic pathways is initially optimism. I think it's pretty good "But." The "Buts" are interesting. My concern is maybe we'll create something that we can't control. Here's another but. Once you start doing this, you open a Pandora's box and you might do things I don't approve of.
When you break it down, you find about a 30/30 split. People have concerns about the leakage into bioweapons, the moral issues about artificial life. There are a lot of concerns about these environmental issues. Could it move in horizontal gene transfer? The other thing we played with last year was it seemed inevitable almost that somebody was going to create some form of synthetic life. We weren't sure who would do it and when it would happen. So we played with that question. Here's what came out. Almost 100% of the people said more should be done to inform the public about this research. So you've got a fairly strong mandate. The federal government should regulate this research. 2/3 of the people said that. I'm worried about this. Over 1/2. I'm excited about it, less than 1/2. This tracks fairly well with what's going on in Europe. Here's a recent statement that came in "Nature" magazine. Without effective public engagement there will be no synthetic biology in Europe. Pretty strong statement I think. Artificial life needs regulation. So this will give you some idea. I think there's a huge, huge hunger for public dialogue on this issue. The dark horse in synthetic biology's future is trust, and whether we will trust the people that are essentially developing the technology, promoting the technology or doing oversight on the technology. So for the past three years, we have actually tracked trust in agencies. You can see where the government agencies are kind of oscillating in the 50% to 60% range. This is a broad question about whether they trust these agencies to maximize benefits and minimize risks, which is kind of what the commission is about. We added the DOE last year because of the biofuels work. The agencies beat the businesses. So this issue of who wins in a global race I think with synthetic biology, it will have a lot to do with how much social capital you have in your society. There's huge variations. There's much more trust, for instance, in government and corporations in China right now than there is in the U.S. So this trust issue is sort of lurking in the background, but it's something we'll look at again this year. We have asked people, well, how do we build trust? With nano tech, we'll be doing this in August. We found no public support for a moratorium on research. It always comes up, let's shut the system down. But we also found no public support really for self-regulation by industry. So this idea that industry is going to just look after itself and everything will be fine, there's just not a lot of public belief that's going to happen. When we asked people very specifically how can we build public confidence, the thing that happens is 80% of their responses converge around three answers. They want greater transparency and disclosure about science, they want free market testing. There's this feeling, this fear that we're taking technologies and pushing them into the market without doing the due diligence. The government isn't doing it, corporations aren't doing it. And they also like the idea of third-party testing. So they bring up issues and they bring up examples like consumer's union or underwriters lab or people above the fray or the National Academy of Sciences. Having industry do the testing is probably not going to work here. Okay. So then we sort of asked, where are people getting these ideas? Because they certainly aren't reading peer-reviewed literature, at least most people aren't. So here's the great filter. Some of you might know this Gary Larson cartoon. This is a scientist on the top and the media on the bottom. Now, if you think this is an exaggeration, this is what came out a few weeks ago. This was the institute of research and this is an analysis we did on the headlines in major press outlets in the U.S. The size of the words essentially represent the frequency of their use. A lot of people just skim the headlines anyway. So this is what they kind of got out of this. Craig creates synthetic life.
[LAUGHTER]
Now, if you think this is just an American phenomenon, we went back a few weeks ago and took a bigger sample.
We looked at the U.S., the U.K. and Germany. That was the U.S. It's about synthetic life, folks. This is the U.K. It's about synthetic life. This is Germany, artificial life and Craig Venter. So this is working constantly. I'll come book to this a little later in terms of whether this is problematic and how to fix it. The other thing that happens is there's very different ways of covering it we found in the U.S. and in the European union. This is work that my colleague has done. We basically looked at press for five years. This is the U.S. press. We seem to be very bullish on benefits. It's the same problem we had with nanotechnology and GMOs. A lot of the articles talk about the benefits. Very few talk about the risks. This is the European press, a little bit more balanced. The thing that's quite surprising is then you break the things down into issues. These are the issues that appeared in the American press. Synthetic biology has largely been framed here as a biosecurity issue. It's all about biosecurity. This is Europe. Biosecurity actually falls behind biosafety. There's a lot of discussion about the ethics and a lot of discussion about what we call business issues, the I.P. issues and who owns this. Much more balanced I think coverage. And one can imagine a divergence of public opinion and public policy between the two countries. Now, in the end, science has very little impact on public perceptions. Culture does. The late novelist David foster Wallace made the comment that human beings are narrative animals. That's how we understand science. So the sphere of public concern usually forms around threats, rather than benefits. This is one of my favorite set of comments in the 1950s, Captain marvel and the wonderful world of Mr. Atom. The narrative there was the U.S. Government really isn't paying attention to atomic energy and it falls into the hands of various evil-doers. These are deep, deep narratives. And they are powerful because science is essentially presented in the context of society and the people that do the oversight, the people who want to get at it for bad purposes, it's a story. We are story-tellers. When we have gone back and we have sort of thought about the focus groups, there's a bunch of narratives that are incredibly powerful that come up again and again. I'll give you three of them. Dr. Strangelove. This is dual use 1, corruption of scientists. This was in spiderman 2. If you've got teenagers, they probably watched agent Cody banks. If you have gamers, there's an Xbox 360 game called bioshock. Very powerful and built into every single media. The Trojan horse, very, very powerful again. We accept these technologies into society and we learn later that it's probably a mistake. DDT, CFC, Vioxx, this is a game called nano breaker, same thing. The last one is oops. The accidental release of harmful substances or technological error, there's a wonderful book "Prey," the release of nano Bots from a laboratory in the desert and "splice" where they have combined animal and human DNA. So the thing that scientists have to understand is people will fall back on these narratives long before they will ever pick up a biology book. And they are incredibly pervasive, ubiquitous and powerful. So let me close up with some communication challenges. What is it? What is synthetic biology? We actually have 11 or 12 definitions on our website so I think five or six is an underestimate. Let me make a comment. The scientists, industry or government have no communication strategy about this at all. We are mumbling in real-time. So it's wrong quite often to blame the media. The media that is problems. But the scientific community has difficult communicating what this is. Conversely, we haven't told them what it isn't. We had a discussion yesterday about whether this was cloning and we never reached a conclusion. So it's kind of open space for people's imaginations to operate in. And they will operate. The other thing, is this a big deal? Who knows? I mean if you look at the responses to Venter's research you go from freeman Dyson who thinks it's a turning point and another thinks Craig has overplayed this. Is this a big deal? Do we have any way of knowing? How do we communicate? How does this impact individuals and society? I think we went through that a lot yesterday. Jim Thomas awakened us a little bit to the larger impacts we have to think about. Let me just tell you that people always impress me. In the social context in which the public thinks is much broader than the social context in which most scientists think. They are going to ask very hard questions about who is developing this, who is promoting this, who wins, who loses and what can go wrong. Those are nagging questions for which we have quite often no answers. I'm always impressed about how intelligent people are about this. What can go wrong? They constantly ask us what can go wrong. And if something goes wrong, who's in charge. Where is the 800 number? Who do I call? Is it the White House, the F.D.A., the E.P.A.? The other question because of what's going on in the Gulf of Mexico is, can we fix it? Can you plug the hole, daddy? As Obama's daughter has been asking. Is there a biological blowout preventer? We heard a lot of stuff about suicide genes and phenotypical handicapping. Can you do this and guarantee it? And the public will ask questions like that. I think we need to be prepared with answers. So just some final thoughts. I think it makes sense potentially to launch a bigger national dialogue on synthetic biology. This is the one that the U.K. just did, which ran for eight or nine months. Might be able to build off of the lessons they learned. I think there's a need to actually set up a very visible coordinating office and body in the U.S. Government. With nanotechnology, we had something called the national nanotech coordinating office which did a lot of outreach and inreach. And so there's a place to go to. It's not clear kind of where you go here. This is going to happen soon. I predict in one year, someone in the Congress will ask the General Accountability Office to examine the adequacy of our regulatory system to address synthetic biology. And they should. The GAO would provide an independent assessment. They have the capacity to do that. They have moved into technology assessment. And I think we need to do this sooner rather than later. This was preempted because somebody actually suggested this the National Academy of Science undertake a new study of the environmental impacts. The last time the academy looked at bio containment was 2004. The chapter on synthetic organisms is relatively weak because they were very focused on animals, transgenic animals and plants. So it's time to take a hard look at this. I also think people have to look at potential for extremely low probability but high-impact events. At the beginning of the nuclear age Hermann Kahn at the Rand social said we need to look at people called black swans, people that could be game changers that we're not thinking about. And finally, I think it's time to really engage in greater international collaboration, not just around biosecurity. I think a lot of that is happening. But issues like risk research, international property issues and this one kind of coming up again and again as we talk is the biosafety issues. So that's my comments. All of the things that I have referred to are up on our website. The work we do is funded by the Sloan Foundation.
>> David, thank you very, very much. Let's move right along. We'll get to Q and A later. Our next speaker is Markus Schmidt. Dr. Schmidt is the cofounder and board member and project leader at the Organisation for dialogue and conflict management in Vienna Austria. We certainly welcome you and look forward to hearing from you.
>> Thank you. First of all, I would like to thank the commission for inviting me. It's an honor to be here. I think it shows the commitment of the commission to have this discussion and on synthetic biology on the international level. I will not try to hide my lovely Austrian accent during the presentation. You have asked me to give an introduction in Europe. I have 15 minutes for that and I will try my best. As an overview, I will try to give you an idea of what we think falls under the umbrella term of synthetic biology, rather than to give a definition to just see what's going on and who is doing what. And it's a little bit about the role of Europe, compared to U.S. and the funding, what the European ethics councils are doing and what recommendations they are giving and some examples of projects in Europe. We have heard something about maybe a different definition than what this included in synthetic biology. Cloning, stem cells. So it took me quite a long time. I'm working in synthetic biology for five years now. And it took me a little bit in order to grasp that. I think we can make out five different sub fields or under the umbrella of synthetic biology. The first one is DNA synthesis or genomes. The reason this has been put in place by Barack Obama and what Craig Venter is doing. I think you can maybe call that synthetic genomes. And maybe the step ahead, you can say that if synthetic genomics can create life, it's pertinent to ask if gutenberg has created the Bible. He was not a Shakespeare. This was attempts by the second group category which is DNA-based biocircuits and the creation of a system made of parts of genes. And we have heard we still have limitations in doing so, but it is going on. The third group is working on the minimal genome to reduce the genome in a living cell to the extent it can barely survive to know about the least complex living systems, and to be used as a chassis for the second type. The first three types are actually you can say this is life as we know it. Right? So they are using more or less similar principles of natural organisms. The second and next two parts are actually descriptions and attempts to make life as we don't know it. Protocells are trying to make cells from scratch and putting together in a way one point in the future this will have all the characteristics of life. I think this would be the category you can say they are trying to make real synthetic life, synthetic cells. The last part is chemical synthetic biology. There are attempts to diversify the biochemicals of life and to have six or eight or 12 bases instead of four and to replace chemicals and these things would be octagonal or different from other organisms and have a genetic enclave for biology firewall as a safety system. All right. Comparing Europe to the U.S., there are many ways to do that. I went to the department website and found it as well. The U.S. is ahead in terms of publications and also in terms of receiving funding for the work, but Europe is second to the United States. So I think together we might have 80% or 90% of the synthetic biology volume, capacity in the world. But Europe is very diverse. There is on the one hand European commission funding and initiatives but there are different. In some communities there is the research community but lack of funding. In Austria we have the community but very few scientists working on that the. The benchmark is in Europe. And they are required to work together and to collaborate. So they set a good example for Europe. All these publications, work and funding in Europe on synthetic biology have drawn to the attention the fact that there might be biological issues and a couple of bioethics working in this or not working. In the U.K., the Council on Bioethics has repeatedly decided not to work on it in 2006, 2007 and 2008, but other countries have. In Germany, there were different ethics council and the council in the German parliament and the German ethics council.at first the term said it was not relevant and they Dant want to work in that but the ethics and German parliament said it might be relevant. And now I think the German ethics council is doing something in it as well. Switzerland, actually a very interesting publication coming out. The federal ethics committee on non-human biotechnology, a long word in German, they look especially on the nonphysical harm part of the synthetic biology. So the dignity of microbes. Looking at microbes and if we can treat microbes as a machine and if they have positions like egocentric and they came to the conclusion that the majority of people in this have a biocentric view and say microbes are not a machine. This dignity is less and not as important as other higher animals and organisms and we can use them in any way we want. It's a green light for scientists. Also in the Netherlands, there was the cochairman made a statement, but I would like to say a little bit about the European commission itself. In 2008, the President asked his European guEp on science and new technologies to also have an organized recommendations or to come up with an opinion paper which stated and published in November last year. We are interested and they asked what is our one recommendation to you, it could be you want to look at their recommendations and see if there is something you can use. As I mentioned before, biosafety is really an important topic in Europe. Much more than biosecurity. I think we are one major difference between the U.S. and Europe. There are several points in biosafety, especially we need to be aware of risk assessment methods so that we can in the future try to assess the risks of new synthetic biology tools and methods, otherwise it would run into a situation with just uncertainties. They also ascertain there are products that come out of synthetic biology and it's an idea that they could do. Include the biosafety standard when doing import-export with synthetic biology products. And promote public support for basic research and ELSI work. Here is a timeline of different projects dealing with societal aspects in Europe. The color doesn't have any meaning. It's just more colorful. Some are stand-alone and others are parts. So in order to map the different projects in this world, you know that Europe has a history of colonizing and we do that and have this virtual world here. Five different areas of synthetic biology and different ELSI aspects, okay. Also try to map the different projects into this world. You see that most of the activities are going on in biosafety and ethics and most of them regarding DNA biocircuits and those are initiatives and and there are some activities on science and society. And socioeconomics. My last couple of slides, I'd like to present some of these projects I know best and have been part of. The first one is synbio save. It was in the way of a pilot study to map fields and see if there's anything new in safety and ethics. And we did this in our ethical part and found out that the ethical aspects that may come up in the project can be attributed to three different areas, whether it's about applications like human enhancement. For example, we can do synthetic human chromosomes that can be useddor gene therapy that would be an issue or related to its distribution. It's the bioeconomy and what is the effect of synthetic biology on the global justice and the distribution and benefit in order the procedure is the international status of living machines. Regarding biosafety, we have three questions or challenges. The first one is we need to find new methods in risk assessments in order that we can have some certainty about the risks of new products in biotechnology. And second is what are the ways to improve synthetic biology, to improve the biosafety by using tools of synthetic biology, for example, I mentioned before the different DNA with different chemicals. We would have different forms and feed nature and so forth. The third one is what happens if nonprofessionals, amateurs and people start using that. In addition to some publications, we also thought it was necessary to produce some material for the general public so that more and more people are interested and motivated to enter the discussion. We did this documentary film. I brought a few copies for the commission here. You can get more information on this website. Starting from this more general assessment of risk and benefits, another project here, TARPOL which is the targeting environmental pollution with microbial systems a la carte from the framer program, we're looking into specific applications where synthetic biology could make contribution and try to find out what its economic and environmental and social impact would be. Okay? So this is going to be accomplished in September. So this is a draft. If you want, I can send you the final version so we have, for example, in biofuels and looking to ethanol, non-ethanol kind of fuels, algae based fuels, biohydrogen and try to evaluate the different aspects. This is a way to go away from the general assessment to a more case by case assessment. Another project that we have done in Austria is where we wanted to know more about public perception. This is in the light of a certain lack of knowledge about synthetic biology, although we have in the last couple of years more and more press articles, in this case the German language but very similar in other cases in Europe. But there are certainly most of the people haven't heard about this German in the United States. And it can give you another hint in September, the Europe study is going to be released. And this is every three years the European commission is doing a massive poll, opinion poll in Europe asking a total of 30,000 people in Europe on different aspects of biotechnology. And for the first time, we were able to slip in some questions on synthetic biology. And it's going to be -- I have seen the results but I can't tell you yet because it's published in September. It's going to be useful for you. Doing this and this lack of knowledge and awareness, we're doing a real-time experiment, asking scientists to write press releases, asking journalists to write articles and give that to eight focus groups consisting of different parts of the public. And what we found was that -- these are the eight groups, right? And the scale is if the people would be the positive link line or negative or neutral. In the beginning because they didn't know anything, they are more or less neutral and don't have any opinion on synthetic biology. Actually, the name should be here as well. And it turns out that after they received the articles, we see that like the majority, like half of the groups that didn't change their opinion, they still didn't feel -- seem to engulf them a lot, but two groups had the suddenly negative opinion and two groups suddenly get a quite positive opinion on this. So this group on the left was an environmental and this group was a Christian NGO and here we have students and these are members from the economic chapters. It turns out synthetic biology has the potential to polarize parts of the public while we have a silent mass of people that don't care a lot. But, of course, there are people on the fringe of interesting. We also found that in this communication process from science to media to the public, actually the very essence of synthetic biology got lost. So while they beginning the sign tichts were talking about why it was different from genetic engineering and they had the standardization and the engineering principles, this got lost. And in favor of a more application focused kind of information that was conveyed. And this is important from the point of view of journalists because they want to write something that is relevant for people and it's about applications. So because they just talk about applications and about the method behind it, people cannot make a difference between synthetic biology, genetic engineering or bioculture, so they put it together. And the research from this communication process, the nuances get totally lost. This is my last slide. We heard yesterday if synthetic biology is successful, imagination will be the limit. If this is really the case, I think we should invite people that are experts in imagination and maybe not only engineers. And so we are inviting filmmakers and artists to give us their version of what synthetic biology could change our society in the future and we are going to do the science and art and film festival at the museum of natural history in Vienna and we're still inviting people to send us short films. I think it's going to be a very interesting festival. With that, I'd like to thank the commission for your time.
>> Thank you, Dr. Schmidt. Very interesting to see the sort of European response to the challenge and challenge for public dialogue that David Rejeski issued to us. Our final speaker in this morning's Pam, I have a special pleasure to introduce, Dr. Paul wonpy, the aa Griggs Candler professor for bioethics at Emory. He sits on the editorial board of a dozen professional journals, the past President of the American Society for bioethics and humanities. His work focuses primarily on the social, religious and ideological impact on the human condition. I am delighted to welcome you here, Paul. We look forward to what you have to say.
>> Thanks very much. It's a great pleasure for me to be here. I'm a sociologist and social scientist and very atypical for me, I will not be using slides. You know how some people can't talk without their hands, we'll see if I can't talk without a PowerPoint presentation. I was pleased with the breadth of ethical concerns expressed yesterday because it freed me up to talk about what I think are some often less considered and underlying and deeper ethical concerns that I have. Concerns that are troubling in some ways as ecological or pathogenic concerns but much more difficult to know how to address. My assignment today, what I was asked to do was talk about religious perspectives on synbio. And I spent a few weeks reading the literature. I spoke to people from a variety of faith traditions, from Buddhism with Emory's wonderful Emory Tibet program that we have, people from Islam, Christianity and Judaism, Hinduism. And what I discovered was there was remarkable agreement about synbio. And that is at this point, they are unconcerned. Fundamentally, their objections or their concerns were those of all of us in this room. What are the potential harms? What might happen if these things are released into the environment? And they expressed a concern that synbio keep its eye on maximizing human good and reducing sferg. And if it does that, it's acceptable. And that was reflected, I think, in the Vatican's response, for example, to synbio where they said that the recent creation of Venter's cell can be a positive development if correctly used. And then there was a warning afterwards, but scientists should be careful about playing God, creating life, remembering that only God can do that. I found the questions that we typically ask of religious traditions about bioethical issues to be relatively uninteresting. We focus on asking for them to sanction what science is doing but I don't really think that's the right question we should be asking of religious traditions. It's not where they can make their greatest contributions in telling us what we should or should not do. Rather, I think that modern science is simply the newest means of trying to struggle with eternal questions about how to minimize human suffering, what our proper relationship is to the natural world, what are the important problems we as a species must solve and so on. Religious traditions have had centuries to think about these questions. And the smartest people of their age throughout most of human history drifted into religious dialogue. And so those traditions hold wisdom that we can draw from. We know that the role of science is generating knowledge. What I think the most valuable role of religious troishes, what I think we should ask of them is how to generate wisdom, which is a different quality than knowledge alone. And so for a few minutes, I want to talk about what kind of wisdom might we glean about synbio and similar biotechnologies. These aren't going to be the points that are usually made explicitly by religious traditions or religious spokesmen, nor do they come from particular religious traditions. They come from a generalized religious sensibility, a positive that asks what might be positions be if we start from the premise, there's something sacred about our lives even if you define the word sacred in its most secular sense. Religious sensibility that I mean is shared by a variety of people by faith and people of no particular religious faith, by both the theis and agnostic and atheist. Begins with the premise that life is rare and precious, our biosphere is fragile and sing lar. And we have evolved to be the stewards of the planet and very powerful stewards at that. One last point before I move on to the specific points I want to make, I don't think wisdom is at all an exclusive domain of religion. We find it in art. We find it in literature and we find it in science as well. In fact, if you look at science's impact on religion over the last 100 years or more, we see as profound an impact going in that direction as we do in religion's influence on science. I'm interested in that dialogue between science and religion to some degree and how they can mutually inform each other. And that is a dialogue of longer duration and greater productivity than is generally appreciated. I want to give four examples of ethical issues that are difficult and perhaps retractible and might reflect this generalized sense that I've referring to. First is the idea that human beings are cocreated by technology. We think of ourselves as the creators of technology, which we then somehow send into the world and then we create the next technology and send it into the world. We pay far less attention to the way that the technologies we create then reciprocally recreate us, recreate human beings and recreate human society. The invention of the plow shaped human societies, modern civilization itself was largely a product of plow-based agriculture. The automobile made suburban life possible, moved industry out of the cities. And even perhaps ended the era when people had to keep animals for transportation and thus estranged us from the natural world even more. Computers, we don't have to mention how they have fundamentally changed us not just the socioeconomic and the computer power and even parents being unable these days to figure out how to communicate with their own children. We have a whole different system of communication than many parents do. Yesterday we heard some speculations of how synbio might contribute to bioeconomic dislocation. Powerful technologies can change social relationships. Change how we think about problems. New technologies create new problems that call for even newer technologies to solve them and create their own challenges which we address with even newer technologies which is why we always seem to have both too much technology and not enough technology at the same time. So how will synbio change us? I have no idea. I don't think anybody does. Perhaps it will accelerate the biomedicalization of life where by diverse human phenomena are recast and redefined primarily by their biomedical nature. Perhaps it will change our personal self-conception from one that thought of individuality as a variation on our commonality to one emphasizing our polymorphic diverges and idiosyncrasies. Perhaps it will be all biological forms will be taught of primarily in terms of their utility. I don't know. It's too early to tell and premature probably for the commission to speculate on. But I think we all agree that looking at technology in isolation from the economic, social, philosophical implications of future development is to fail to fulfill the deepest meaning of the President's charge to explore the implications of the field. The second issue is speed. And this is a point that I think is often overlooked in talking about technological change. Speed itself is an ethical issue. We live in a society that explicitly and implicitly presents speed as an ethical value, taking longer time to achieve similar results is see as less desirable, as wasting time, doing something faster is doing it better. Synthetic biology and genetic engineering as well justify the utility in part as we heard yesterday on how they have dramatically collapsed the time horizon of evolutionary change. Yet speed is a problematic value. Selective breeding, for example, is limited, difficult and time consuming. And so in that sense, genetic technologies are an improvement. Because it plays out over long periods of time, it allows for reflection and self-correction. Change happens slowly which offers a large range of choices at new increment of intervention. Synbio makes that in one step. It may take many generations to understand the single gene change on the integrity of an organism as a whole. It may take many generations to understand the impact of alterations on the environment. Even transgenic have changes that differ from selective breeding. Speed has an impact in two senses. One in the ways that synbio speeds up natural processes and second in the explosive development, and dissemination of synthetic biology, technologies and methodologies themselves. How do we think about, accommodate and understand the ethical implications of speed? The third is incrementalism. It's a difficult dilemma. We can follow a path where every step is examined individually and found to be ethically unobjectionable and yet 100 steps later we found ourself in a place that no one wants to be. The idea is also captured by the fact that most synbio research findings advance our knowledge incrementally and yet somehow we see the enterprise as a whole as transformative. One of the reasons for behavior-based religious systems like Judaism or sharia in Islam or for the vennia of Buddhism is to guard against incrementalism and what is seen in these religious traditions as keen of pernicious potential to drift slowly away from what each tradition sees as right paths. I think in fact it is actually a kind of incrementalism that people are trying to combat when they resist biotechnical change or resist an enterprise like synbio or nanotechnology. Perhaps it's even what underlying the playing God objection to some degree, so when we respond that we have been playing God since homo hablus produced tools, yes, we have been playing God along the way, is there some way in which changes to our natural environment, our changes to our physiological integrity, our changes to fellow creatures has crossed some line, though the line is obscured by the fact that this step really isn't that much advanced from the step before us. It presents a real policy challenge. How do I say that step "A" is okay and "B" is okay and "C" is okay, but "D" isn't okay when "D" is really indistinguishable in many ways from "C" and the real reason I want to stop at "D" is because I see "H" down the line? How do you create a policy that captures the subtlety of incrementalism. It's very difficult and perhaps the best way is to address in a positive way creating goals and incentives rather than trying to stop things. And the fourth point is what I call the fedishization of progress. And this is something that is often expressed by religious traditions. A fedish is defined as any object, idea, etc. illicitting unquestioning reverence, respect or devotion. Got that right out of the dictionary. I submit that description countizes the general cultural posture of many people and most scientists toward scientific progress. Here religions have a lot to say. A report of the executive committee of the European ecumenical commission for church and society wrote our Christian heritage teaches us to be skeptical of romantic notions in scientific progress that prevail in some parts of the scientific and political communities, our support for scientific research is moderated by our awareness of human finiteness and fallibility. Modern biotechnological science has a history of failed prediction and I verbally from predictions of gene therapy that I was very involved in early in my career to the claims early on that nanotechnology is going to solve hunger and our energy problems and virtually everything else. While the cautions of some temperists are easy to dismiss, there's wisdom in pausing periodically to question scientific utopianism, the argument of urgency and other arguments of some biotechnical advocacy. Programs here it might be instructive to conclude, as both the previous speakers alluded to drawing from two narrative traditions or two narrative tales, one from secular Christian tradition and the other from my own Jewish tradition. There are two tales in addition to Dr. Strangelove and oops and the other thing that they were saying which are in this area. The first is the tale of Frankenstein. The tale is a product of a Christian cultural view that had underpinnings of suspicion about technology. By the way, what isn't usually commented on is this idea of playing God is a Christian idea. It doesn't exist in Judaism, Hinduism, Islam or Buddhism. All of which are much, much more historically predisposed to science than certain strains of Christianity. That's not true, of course, of all strains of Christianity. The story of Frankenstein is a scientific one. Anyone can manipulate life and create it. Some may remember Mel Brooks "Young Franen Stein" where gene wilder broke in and figured he could do it too. Dr. Frankenstein transgresses and European thought condemns him. It is a monster, a freak. The story of goalem is quite different. He's created to safeguard his people. The talmud accepts it. There's stories of creating goats and they consider the goalum part of the co-creation with God. Unlike Frankenstein created by putting together biological parts. The goalum is a synbio creation. He writes three letters of a religious genetic code on his forehead and then he's alive. There are two differences in the last second between these stories I want to leave us with. Victor Frankenstein is portrayed by Shelly as a driven man, arrogant to displays personal cowardice. His temper is violent, passions strong. When the monster disappears, he is relieved and flees rather than taking responsibility. In contrast, only the most righteous can create a goalum and manipulate life. And the agree of success is correlated with their degree of righteousness, by breathing life into the clay, rabbi Lowe emulates God and sees his responsibility to emulate other qualities. And in the pact, you will see one of the biggest concerns were the most vaition and disposition of scientists making the research, whether they could afford dignity and respect in the natural world. And finally, the second and last point I want to make about these two stories is Dr. Frankenstein loses control of his namesake. There is no safety mechanism built into the monster. And ultimately Frankenstein must pursue his creation and he dies trying unsuccessfully to end the monster's life while the goalum always remains under control of its creator, rabbi Lowe builds a safety valve into the goalum. When he gets out of control, he has to move one letter off the forehead and it turns back into clay. And it is hard to see the leaders of synbio have taken the safety valve seriously and built it into the products. To the commission, I have tried to highlight three or four what I think are very difficult issues. And I think the challenge to the commission seems to me is to take the extraordinary knowledge presented us by synbio and temper it with wisdom. Thank you.
>> Thank you. Appreciate it. I do want to defer first to the chair but we have questions from the commission.
>> I'll wait for my question and go straight to the commission and ask mine later.
>> I don't know. Thank you all very much. Paul, I want to reassure you that it's perfectly okay not to use PowerPoint. I believe that PowerPoint is the spawn of Satan.
[LAUGHTER]
I actually applaud you for not using it.
>> The commission will not take a position on the use of PowerPoint.
[LAUGHTER]
>> But I'll be working on you all. So I want to begin with this reflection on the absence of trust with regard to these sorts of scientific developments. I think that Dr. Rejeski is correct that this is the social environment in which we are working here. It's an environment marked by an absence of trust. And we see this all around us with regard to BP, with regard to climate gate and so on where there's just a high degree of suspicion with regard to all of our major institutions. The church, science, business, government, everything. So in this kind of environment, I think you're right that some kind of public outreach, public engagement will be absolutely crucial. And I have read your excellent article, David, in the reader which does talk about the importance of engagement with the public. But I think we need to probe that a little bit deeper to get at the rationale for doing so. I mean one rationale could simply be to sort of work on the public, you know, to sort of massage the public or tweak the public in various ways in order to make the world safe for scientific development. Another way of thinking about it, which I think is much more plausible and philosophically appropriate is to view public engagement as a way to obtain public legitimacy. In other words, if the public sees itself as having a role in the formulation of public policy, that bestows a certain amount of legitimacy on the project. I think we can see this. We have and tick dotes so far. We have a couple of case studies in this. One of my favorites is the rationing program in the state of Oregon, where public officials in Oregon basically reached out to the public, engaged them in a prolonged discussion. And it turns out in the state of Oregon, people can -- the state can ration healthcare in a rational transparent and effective way that gained public acceptance. I wonder what you think about this process of public engagement in the area of synthetic biology. Is there any evidence that this kind of engagement will indeed engender and increase legitimacy? Or is it a theoretical notion that, you know, involves a lot of hand waving?
>> I think there's always a certain amount of askepticism and fear of doing this. I think the scientific community is often used as a deficiency model which the public simply doesn't get it. If they only got the science, they'd get on board. And part of the problem is, of course, this public is asking a different set of questions. I think one of the problems that you run into immediately, if you wait too long, it appears disingenuous. This happened to a large public engagement process in the U.K. called GMO Nation where it really started after -- essentially, it looked to the public like the train had left the station.
>> It is their worst fear.
>> Recently the French conducted a large engagement process on nanotech and it was shut down by protests, again because people felt nanotech products are on the market and we have essentially done this before. So I think part of it, there is a timing issue. I think if you really are serious about this, it has to be done fairly soon. The report we just put out on participatory assessment says there are ways of doing this that are extremely well tested. We have done 16 of these types of exercises in the U.S. alone. And they are used pretty widely in Europe. This is just a matter of getting a representative sample. One of the things you'll grapple with and I'm sure you'll be asked, are the people you're talking to representative? That's a statistical question and methodical question you'll have to deal with. There was an interesting process that was run on biomonitoring in Boston. This was done a few years ago and brought in a wide range of people from the public, fairly representative sample to talk about monitoring. And it was visited at the same time by the head of the national academy panel that was doing essentially an investigation on biomonitoring for the U.S. Government. His response was he was stunned at sort of the level of conversation by an informed public because you actually have to inform the people what's going on. And the fact that they actually came up with new ideas. I think it goes beyond legitimacy. I think people can generate new ideas, new ideas for policy, things you hadn't thought about. So I think it's not just sort of educating and dumping knowledge, it's not just trying to get some legitimacy by having a dialogue. It's also the fact people are smart. They get this stuff. And that's why when we have done our public focus groups, we float a lot of public policy ideas. People come back and say what do you think about labeling? What do you think about a moratorium? What should the F.D.A. do? What can they do to build your trust? For me, I come from a policy world. So I think the use of these as ways of informing public policy is actually very, very critical. So I would push you to actually go beyond the legitimacy issue and just having the dialogue and say how can I learn something from millions of people, at least a representative sample of those.
>> I have two questions. I want to thank Mr. Rejeski for your enlightment. And your questions are critical as well. My questions are directed to Dr. Wolpe. I was quite surprised when you said there was no religious perspective or difference at least within the religious community. And I wonder if that was a representative population that you spoke to. I would suspect there may be some differences particularly around the questions of life, dualistic versus materialistic concerns about the creation of life. And so I wonder if the question of awareness and the degree to which synthetic biology is being included under the large umbrella and whether or not you think there may be concerns develop. Let me ask you the second question next. Your answer to incrementalism and to the rate of change is we should create goals and incentives to keep in mind as a way to direct this. And I wonder if you have specific ideas of what the goals and incentives are and if they would address the shifting rate of change in the environment.
>> Thank you. I wasn't trying to say there wasn't religious objections to synthetic biology. There are some religious groups that object to virtually the entire modern scientific enterprise. I spoke to mostly official or high-place spokesmen for religion and these religious traditions asking them what their religious traditions say specifically about this particular case of the creation of the artificial cell. What I got in response from almost all of them was at this point the actual act of creating a synthetic genome and inserting into a cell that replicates is not one that we have any particular ideological or theological objection to. I asked a very narrow question.
>> It was not about synthetic biology generally or views about this.
>> Right. In so far as the conversation, it went on to where their problems lie, they tended to all be down the rolled or they tended -- down the road or in this intrinsic issue of Huberis or human intervention or humidity and -- humility and issues like that. Part of that is synthetic biology is an enterprise and like us we don't know the implications. And there's a let's wait-and-see attitude. But religious traditions outside Christian religious traditions tend to see the use of other forms of life to better human life as a legitimate enterprise within certain limits.
So creation of synthetic biology products that would cure disease or help with things like mitigating pollution are seen as legitimate scientific goals. The issue of incrementalism, the reason that I'm suggesting positive incentives rather than regulatory limits is because nobody knows and I certainly don't know where to put regulatory limits. As I say, it always seems arbitrary. Therefore, in some sense, it is very practical difficulty that leads me to suggest that positive incentives are a better policy strategy. At this point, I think it's premature to suggest where the proper goals of synthetic biology are. That needs a little more time. But it is exactly what we do in medicine, of course. So we create the NIH. And the NIH is the steward of public funds. It looks at all the possible places that it could invest public funds. And it makes value decisions about what kinds of medical products, goals, cures, preventions are in the best public interest and incentivizes the system to move in those directions. That's what NSF and what our public funding agencies and private funding agencies do. I was suggesting, it's such an intractable problem, the problem of incrementalism, that is a better strategy, even though I don't have a specific recommendation at this point about what specific goals that incentive program should pursue.
>> I'd like to ask Dr. Rejeski to perhaps be a little more granular in your thoughts about how you would organize the lack of a communication plan certainly in this country compared to Dr. Schmidt's presentation which is fairly I think stark support for that comment. How would you suggest, based on your comments of yesterday, you wanted more government agencies to be in the room and to be part of this process? And yet when you went through your five specific recommendations, you suggested a coordinating body or office within the U.S. Government. Where in your view should that bully pulpit be? And what would you recommend for its composition outside of U.S. Government agencies? How would you interdigitate with the international approach that you did mention at the very end? But Dr. Schmidt showed with great granularity. How would you bring in a community advisory process so that this would not be a deliberative process that would seem to be in the hands of just policy or wonky people?
>> Well, the last thing is obviously the big danger. I think logically, it should be at a White House level. You know, it could be worked down at the national science and technology council. The national nanotech coordinating office was set up as an independent body that reported up through the White House and was funded essentially by the different agencies. I think that is one model. I think they were consistently underfunded so you have to figure out a way of kind of levying a certain tax on the agencies to make sure there was enough money there. So one of the tasks that office was given was to actually have a national dialogue on nanotechnology. And that never really happened. There really wasn't enough money, enough umph there. If you did it, you have to come up with some way of making sure that there's enough funding go into the coordinating function. The agencies have to be able to pony up some money to make that happen. In terms of advisory bodies, you know you're going to run into FACA issues in terms of the federal advisory act. But it may be worth going through the process to actually set up a FACA that would bring in the wide swath of population and communities to be able to sort of get ideas off of. The other option, there's nothing that would stop government and the agencies from going on the road. When I was in the White House, we did work on the national environmental technology strategy and we had 25 meetings around the country. They were just the kind of thing you're doing but again focused on a specific technology and science area. We ended up also with a White House conference which is another thing that attracted 1400 people. So we were constantly bouncing ideas off, ideas that had been taken from the government and getting lots of different feedback. I would say that one of the things that came out of that was exponential improvement in our strategies because we were able to really interact with stakeholders. I think there's a bunch of different ways. The level matters. It has to have White House support. That's where it belongs. If you have a coordinating body, you have to have essentially enough money behind it to make it work. There has to be some leadership there. I would certainly recommend the use of potentially putting FACA in place. It might help.
>> Thanks again. I think we were treated to three very different, but very, very good presentations. My question would be for Dr. Wolpe. Paul, you probably know there are sort of two ways we can think about religious voices participating in public dialogues like the one this commission is conducting. One strategy is to sort of only give publicly accessible reasons. And the second is to allow people of religious communities to speak out of the fullness of their traditions. You seem to have allowed a broader sense of the second kind of participation in a dialogue like this. I was wondering what you think the actual -- if that's true, what the actual value is of allowing people to speak out of the thickness of their own traditions as part of a public debate about a contentious issue like this.
>> Religious traditions don't get to talk about why they really believe what they believe. If you get up in front of Congress or a commission and you say I think this is wrong because the Koran tells me it's wrong or the Torah or whatever your sacred scriptures are, it's the end of the conversation, not the beginning of the conversation. You have to translate parochial religious ideas into universal principles if you want to be convincing about why you should take actions. But I think underlying the parochial reasons that religious traditions think things are often very deep principles that can be universally expressed. And I think that in our society, that is the greatest contribution of religious traditions because these are well thought out, centuries old, much debated, much very nuanced positions. So that's what I tried to do here, rather than reiterating what I think are very easily accessible and commonly discussed religious positions about technological issues. I was trying to get underneath the surface and ask what is the font of concern from which religious objections spring?
>> Well, thank you all three. This has been enormously insightful and informative. I think it will help us moving forward. I really like the idea, if you would mind my changing one word. Instead of knowledge, tempered by wisdom, knowledge coupled with wisdom. And I think we, as a commission, would like to issue a report that is informed by the facts, knowledge, and driven by values, wisdom. To elevate it a bit. And I'd like to ask any of you to share -- we can start, if you want, with Paul. What are the values that you see us having to deal with? What are the values that are most relevant to the issue of where synthetic biology is likely to go? The values that we need to deal with as a Presidential Commission. Just I know this is a big question. But if you can give us one answer.
>> My answer would be that it isn't a single values question. It is a balancing of values problem. That is, when I talked about the fedishization of scientific progress, I wasn't trying to say I was against scientific progress. I am extraordinarily for it. I live my life in a medical environment and celebrate medical advances but there are other values that have to be brought in. I think your challenge is not so much what is the value we should represent in our support that will be the value that synthetic biology needs, but rather how do we create a report -- and I think temperance might be the right word -- that takes all of these competing values and balances them in a way that makes policy valuable.
>> I should say that why I asked about values, there was a famous philosopher who said that values without facts are lame. Facts without values are blind. So we take both sides of this. You can speak to either one.
>> I would like to refer to this Swiss bioethics commission with the positions one would have and from that different values are entertained. There were, for example, thinking about people that believe in the kind of -- that every organism can be explained or reduced and the properties can be lost. And there are a lot of people that have the point of view that doesn't know there's something special in life. There is some X-factor that cannot be controlled. I think many in synthetic biology, they come from this monism concept and there's a misunderstanding of this idea to think the two positions can get in the way, in a way that it's a direct attack, so to say, that there's some specialness of life. And this carries a lot of value. It is the position as unfounded as the other one, but it's a way we view life. And if we attack that, or if this is an attack by synthetic biology, it could trigger some strong reactions to that.
>> I would think that one of the things that would be very useful in the report was a sense of the sensitivity and celebration of plurality. We are a very plural hetero genus society. One of the things that's so striking when we do focus groups is the huge difference. We talked about religion. There are huge differences between men and women. There are huge differences between whites and people of color and how they view this and the trust issues. And I think it would be phenomenal if the report could kind of reflect that. We have a plural society and we have gone out and we have kind of looked at that. And we have gone deeply into the little pockets of society. And I think that's something that is what gave rise to quite often resistance in the environmental justice movement. I think that's something you have to do. There's going to be the sense of how deep have we gone. How sensitive have we been to the plurality of the society? I think it can be dealt with on the basis that links values with facts.
>> Thank you. And thanks to the panel. I might ask David Rejeski a question, but also open it to the other panelists. There are certainly unique capabilities of synthetic biology. But one of the issues we spoke about yesterday is the overlap in the issues that are raised between this new technology and other technologies, genetic engineering, stem cell biology, even nanotechnology. And my question is in terms of the public debate and also the oversight framework, are we better isolating synthetic biology? Or addressing these issues in the larger context of emerging biotechnologies?
>> Well, I'll give you my opinion. I think there actually is a certain danger in creating different-ologies. 20 years ago, the U.S. Government made a conscious or unconscious decision, that our goal was to basically build another Industrial Revolution by gaining control of matter in a nano scale in a biologically relevant scale. We started with nanotech focused on inorganic matter and now moved to organic matter. This is about precision control of matter. That's going to change the way we make everything the next 100 years. This idea of separating things, one thing that was striking when you saw the slides, it mentioned nanotechnology. And so there's people up at MIT that actually reengineered viruses to make batteries. So the nano folks, they have been talking 10 years about self-replicating nano. Biology does that and we're in the position to program it. Drew mentioned this ability to recouple bits from atoms and program the bits and address them back to the world of atoms. So I think the national science foundation has talked for years about converging technologies, the nano and info and bio world. There is some value in thinking about the fact these are all coming together now and asking the question about, well, how will the regulatory system work? And will the toxic substance control act work well with nanotech and nano biotech because they are getting more complex. And you can do the same exercise through most of the U.S. statutes and U.S. agencies. I think there's attention there. Quite often it essential conceptually easier to break it down. But I don't think that's where we're going to end up in 20 years.
You are already seeing a tremendous kind of convergence. And there's also lessons to be learned, as we have already talked about I think.
>> Let me ask the audience if there is a question or two. Wow. A large number of questions. I'll tell you what. Why don't you collect your questions and then let them run through them? Give me your question and I'll note it down. Introduce yourself and then we'll turn our panelists loose on you. Please.
>> My question was for Dr. Schmidt. And it was basically is there a need for international standard for synthetic biology? But biotechnology in general as well.
>> Introduce yourself.
>> I'm sarhath Josey a student.
>> I am Gerald Epstein, I guess this is for David Rejeski. I have a pocket hobby of collecting policy studies whose recommendations include the president needs to make this a personal mission. In terms of the U.S. office or U.S. Government wide office, maybe related to the last. Does it need a special office? Or should it get in line behind other U.S. offices.
>> And what would be the priority of that?
>> Do we need a special one?
>> I am Nicole Gaddis from the University of Pennsylvania. My question is for Mr. Rejeski and Dr. Schmidt. I was wondering if there's been the ability to investigate educating young people before college and the impact of public perception on science advancing technologies or synthetic biology in particular?
>> Got it.
>> I'm Heather latey from the University of Ed inboro and I have a question from Mr. Rejeski and Dr. Schmidt as well. I enjoyed your focus on comparisons from Europe and the U.S. What do you think can be learned from what has arisen between Europe and the U.S. because this technology is going to fit into existing frameworks. What do we need to learn from what happens happened in the case of --
>> I'm very sorry. I didn't get good notes on that one. Slow down so I make sure I understand the question, please.
>> I was asking what could be learned from treating what has been learned between the U.S. and Europe as well in the case of genetic modification technologies and what can be learned going forward?
>> I have it.
>> Jim just wanted to hear you speak.
>> It was beautiful. Just beautiful.
[LAUGHTER]
Front microphone.
>> Hi, my name is Colleen Lyons. I have two questions. First is around the Belmont report as a values discussion. So I thought it was appropriate or I'd ask you how appropriate is that as a jumping point to investigate values in today's social context. The second thing is regarding education. What role can the House of Representatives play as a platform for educating their constituents? That's a general question.
>> Thank you. And finally in the back.
>> My name is Donald braman, a professor of law at George Washington university.
>> Yes.
>> And I'm a member of the Cultural Cognition Project and actually got to participate and collaborate with David Rejeski as part of the project and other work they have done. I wanted to second what they said with David and Markus said about the potential for polarization and the need for evidence-based science communication and deliberation strategies. Maybe I'll make it a little starker than David and Markus did. Deliberation can work and bring people together if done right. But done wrong, it can really push people to the polls and create a lot of conflict and polarization. So we're lucky to have generous funding from the national science foundation as they are doing research on just this sort of thing. There are plenty of researchers out there looking at how to do science-based education. I just urge the commission to make evidence-based science communication a deliberate and a formal part of their report to the President.
>> Appreciate ta.
You're with G.W. law?
>> Yes.
>> That's how we can find them. I was hoping they would converge into bins. There's at least one bin around communication and education. Thoughts about young people and focusing education toward them. The role of our Congress in educating constituents. And I think the comment there at the end. What about the education dimension of communications, gentlemen? Yes, Markus.
>> In one of our projects, in synthetic biology, we have one work package where we take film clips from Hollywood blockbuster movie that is have something to do with synthetic biology like forensic Jurassic park to find the sequence of DNA and make the dinosaur. It was science fiction in 1993 but not totally science fiction now. We took this and tried to combine it with scientific facts, what is possible right now, what could be possible in the future. Should it be done? What are the consequences? And make high school packages for teachers to be used in school. I think it's one way to engage people below university grade in this area. This is a general strategy in any new technology and also people that work in climate change and trying to to schools and inform young people. They are still open. A couple of weeks ago I was invited at a school, 14 years old high school students. And it was very interesting. I gave a presentation about the synthetic genome in the cell and the children were they interested. For them it was new. But as new as any other thing that was new. Actually, it was more surprised with the teachers, why are you talking to me? Is it real or is it a joke? The children understood it's not a joke. But the teachers didn't. They were more smart in grasping this.
>> Exactly. Wonderful. And options for educating Congress. And let's couple that with this question for a need for the White House level. Is that the right level? Should it have high priority here?
>> I think there is a tremendous need to obviously get Congress up to speed on lots of emerging technologies. I think before the congressional folks can educate their constituencies, they need to get educated themselves. So the Congress uses a system called caucuses. So for years, they had the nanotechnology caucus. We worked with them pretty intensively. And basically, they bring people in to brief members that are in the caucus. And I think that's a model that can be used with synthetic biology. One might even be able to build off the nano caucus. So I think that's a starting point. That gets the staff involved. It gets the members involved. And the caucus model is well-known in the Congress.
>> Thank you.
>> I mean I agree that we probably don't need another White House office. But one option, since we talked about this issue of things coming together, would be to build off the coordinating office of nanotech and do nano bio so we're not actually doing another office. We're kind of admitting this is where the science and technology is going. And we kind of expand that to take on some of the synthetic bio issues so we're not putting in place another White House entity, but just expanding it around this idea of converging technologies.
>> Final thing we heard from the audience was the international theme and the need for -- the question around the need for international standards. What can we learn about the existing conflict resolutions and agreements for genetic modification between U.S. and Europe. Perhaps we can even ask you to comment on the values of the report in this last grouping. Who wants to go?
>> I think what you find when you look internationally and not just the United States and Europe, both the biotechnology in general is certain areas of convergence of values in certain areas of divergence. So you have activities, you know, for example, this exhibit synbio, but you have in China the genetic engineering of human nucleus into a rabbit ovum and then taking a certain number of cells, which is something that wouldn't happen in the United States.
I think it is crucial as these technologies progress that we try to come to some set of international standards. While we can impose standards in our own countries and we can have multi-country agreement, it is undermined in these particular kinds of technologies, if there are rogue states, so to speak, that are doing things that are completely outside the bounds of the regulatory system set up by treaty or by agreement or even by some kind of international regulation. And so we have a very, very difficult problem of trying to figure out how to universalize a set of standards for scientific progress, as these technologies get so much more powerful.
>> In terms of technical standards, it is incredibly important. May I remind you one of the NASA Mars landers collapsed and they couldn't go to Mars because there was a misunderstanding between inches and centimeters which is very important. And the TARPOL project organized a meeting, a workshop earlier this year where representatives from the U.S. and Europe were sitting together in order to talk about standards and technical standards. But if you talk about biosafety standards, I think it's also important to have these. Also in relation to international trade, I mentioned one of the recommendations by the European group on ethics, the things that got imported or exported from outside the European union, they should be acceptable and fall under the European kind of laws and regulations. They have some countries that want to import or export into the European union have to adopt the standards and it would make incredible sense. On the other hand, I think I agree with you that standards should not limit exploration of new ideas and there should be some kind of diversity as well.
>> I agree with the need for the international standard setting. Let me take you in the other direction. We live in a large country and quite often, when there is some hesitancy by the federal government, state and local governments move, so the first municipality that put in place a biotechnology ordinance was Cambridge, Massachusetts. It's been in place since 1976. And there's 55 biotech companies in Cambridge. Cambridge put in place a nanotech ordinance, so did Berkeley in California, setting up their own system to take care of nanotech issues. We know from air pollution control, water, whatever topic you pick, you have a huge system. We have our own E.U. here. One of the things you have to be sensitive to is the fact some money may decide to move ahead of you. That drives industry crazy because not only do they have to deal with this aggregation at an international level but disaggregated markets at a local level. It's important to keep your eye on local government and states.
>> You're absolutely right. Can you get your questions answered at break time? I'd appreciate that. Let us, first of all, thank Dr. Wolpe and Schmidt. Thank you so for your contribution.
[APPLAUSE]
Wonderful. We will reconvene in 10 minutes, at quarter to the hour for the final session.
[Recess]
Commission members if you would please take your seats. We now move to our final panel of this day which will focus on current federal oersight and regulatory activities regarding synthetic biology and potential actions that the government could take in response to recent developments. This is the beginning of an overview. We will have time for deeper dives into this. As a commission, we will not be able to reach any conclusions about this part of our report until we have a chance to digest more of the science and ethics and social responsibility issues. This will at least begin to give us a sense of where our presenters see federal oversight as it is now. And will give us a window on to the state of federal regulation and oversight and give the commission members and the public to ask some initial questions. So let us begin. First up is Amy Patterson (NIH). (patterson intro goes here)
Thank you very much. Good morning commissioners and good morning everyone here today. I was asked to speak here today about the role of the federal government and the role of NIH in the oversight of synthetic biology research. I would like to spend a few moments on how science and policy have evolved over the last few decades and have brought us to the current oversight framework, and I'll spend a few moments talking about its relevance, the technological challenges for oversight, and some parting thoughts.
The caveat, before we turn back the hands of time. This timeline is in no way comprehensive, but it does present some of the key tech highlights and oversight relevant to synbio research. With the advent of recombinant DNA, we moved beyond the structure and sequence of DNA to the manipulation of that structure. The technology gave us new tools for understanding the avenues of life and developments of therapeutics and beneficial applications. The tech also prompted concerns among the scientific community and general public about unintended consequences, in particular on short term and long term effects on health. The tech also raised questions about boundaries between species and appropriateness of human kind manipulating the genetic code. During this time, a national dialog grew, about the role of public, society and legislature shaping the discourse in a free society. Several bills were almost passed, which would have placed restraints. This proved unnecessary. The scientific community, recognizing the depth of public cocern, and so on, they called for a moratorium on future research pending the development of an oversight framework. They assembled in 1975 and began the work of articulating the principles and practices that might govern the future of this research. There emerged one: the recognition of the inherit promise, and two the importance of an ongoing dialog and a development of public input and dialog. Three, the importance of careful risk assessment and oversight. Thus the foundation was layed for the oversight framework that was layed, and would touch on key points.
A national advisory body- the NIH recombinant DNA committee (RAC). It was to review each and every recombinant DNA suggestion at that time, and to articulate overarching principles and practices and biology and physical containment of recombinant DNA agents. The rpoceedings were published. A very deliberate decision was made to publish these as guidelines. In despite of the name guidelines, compliance was one and is a term and condition of federal funding.
In the emerging ease with which DNA can be manipulated and sequenced, and the coupling of this to human disease; a prior's president commission determined that the benefits of recombinant DNA tech also warranted continued exploration, but with thoughtful forward-thinking about the ethical considerations of recombinant technology and how it might be developed in the future. In an effort to embed genomics in day-to-day research, a program was established to adderess the ethical and legal research, and ELSI was an integral part of that. In anticipation of the first application of recombinant DNA in humans, the NIH guidelines underwent an extensive revision, and also to put in place a review process for each and every protocol that proposed hteu se of recombinant DNA in humans.
In 1986, the federal government issued a document on basic policy on the regulation of biotechnology products. Among a number of things, it articulates a principle that might be relevant here: the notion that genetic engineering products should be regulated by their intrinsic features, not their method of production.
The 1990s also expressed concerns about bioterrorism, select agents and toxins; the regulations for travel and transport; natural as well as recombinant toxins. The past decades have seen advances in our understanding of the human genome, but also our ability to design and synthesize larger fragments of nucleic acids. These experiments represent a continuum of research, and they enable important advances in vaccine development. They also raise profound questions. These advancements took place in the shadow of 9/11 and the dissementation of spores through the U.S. postal system. Concerns crescendoed through the misuse of biotechnology as a way to harm human health and national security. These concerns prompted a national policy dialog, and a national advisory board for biosecurity (NSABB). They have issued several reports about minimizing the misuses of biotech, including a code of conduct for scientists, and strategies for minimizing the risks of synthetic select agents.
The scientific community has again stepped up to the plate on a number of occassions. One case is synbio- they have convened in a series of ongoing meetings not only to discuss the advances in the tech, but also the important societal issues raised by this tech. From the 1970s to the present day, we've been probing and structuring DNA through genovo-synthesis techniques and other technologies. This has been a continuum of incremental steps, and coupled with the oversight evolution that encompasses synthetic biology.
I wanted to touch on the principles and attributes over the oversight principle. While biotech offers benefits, the potential risks must be assessed and addressed. Oversight must be predicated on risks. The framework is designed to reflect advances in science and advancements in our understanding of risks. But it is also designed to accept input from the public. The oversight framework is designed to account for accidental pathogen exposure risks, the general public and plants/animals/environment, biosecurity risks from the deliberate misuse of tech to cause harms; risks to human subjects, risks from adverse clinical administration; risks to societal norms, controversial uses or consequences of biotech, like germline gene transfer, or using GE to alter human traits rather than using it to treat human disease.
We don't have time to review these tables item by item. I will briefly touch on the overall categories. Biosafety risks are addressed by a variety of federal regulations and policies; essentially they speak to the handling and transfer of infectious agents. Biosecurity risks are addressed in statutess that are about minimizing the misuse of knowledge and the theft of biological materials that could threaten national security. There is also protection of clinical research; risk to society are to some extent addressed by these same policies. The NIH guidelines prehibit the use of germline research for in utero administration. The biologics and toxic weapons convention bans the use of this for mass destruction weapons.
The oversight framework acknowledges the responsible conduct of science rests on the behavior of individuals. Federal oversight can help cultivate a culture of responsibility. At the end of the day, this is fostered and nurtured at the local level. This oversight is also predicated on the biological characteristics of agents, hosts and environments. Be it recombinant DNA or synthetic biology, the important point is that it has the ability to grow new compounds and new species, and therefore brings difficulties in assessment. With synthetic biology in particular, the capacity to create increasingly novel organisms is at least in theory possible.
Another problem is the increasing ease with which you can order DNA over the internet. You can also purchase it on the web; but also reagents and automated equipment. The demographics of the practicioners of synthetic biologists include people from multiple scientific disciplines but also high school students. Synthetic biology is democritized, it's a globalized and commercialized industry. All of these features present scientific progress. It's a very open access environment, offering the hope for therapeutics and also presentation of major challenges for oversight.
We need to expand our ability to do risk assessment, characterization of biological properties, in the context of the tech. The U.S. Government is continuing to refine the oversight framework. We are very visibly at owrk, we have a lot of work to do. We are all on the slippery slope of the learning curve.
The NIH guidelines are currently under revision to improve basic and clinical research about nucleic acids. This would be an oversight framework for the local and federal level for the review of these experiments.
Also guidance for the providers of double stranded DNA, how to screen orders, and policy on the local and federal level for the dual-use of knowledge, the potential misuse of these techniques. This is well underway, based on the NAASB recommendations, which will be applicable to certain types of synthetic biology experiments. The US govt recently tasked NAASB on strategies on outreach to practicioners on synthetic biology, enhancing the culture of responsibility and engage the international community.
The U.S. government is exploring the way that the framework could be enhanced ,to reliabily predict the action of agents and associated risks. We have commissioned a study from the National Academy on this very topic. And as recently as last week, our president issued an executive order to strike a critical balance between biosecurity and scientists engaged in legitimate research on select agents.
The oversight framework has evolved. The field of synthetic biology continues to present new challenges to oversight. Oversight can never be "business as usual". And scientific progress is predicated on trust- open, transparent dialog that encompasses frank deliberations about uncertainty, unintended consequences, and societal norms. This committee can provide a forum for enhanced understanding, applications of this tech, future uses, and what it may mean for society, and the future of the oversight framework and its evolution will require this.
The price of scientific freedom is eternal vigilance and scientific responsibility.
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Michael Rodemeyer
Thank you very much. It's a great privleedge to be here with you this morning to talk with you about the current regulatory system and how it would likely apply to the first generation of syn bio products. As Dr. Gutmann recognizes, this is largely from the work for the Woodrow Wilson Center, which was from work with Pew.
In general, since it's difficult for a lawyer to say anything in 15min, my concluding thoughts are: the existing laws and regulations that cover biotech products are likely to apply to the first products of synthetic biology. SInce the first generation of syn bio products are expected to be very simple, and not different from the genetically engineered products that agencies are familiar with, it is not likely to present new challenges at first. As the organisms become more complex, artificial and novel, the challenge will be to assess the risks of the organisms in advance, especially for organisms in the environment. Regulatory agencies will be in a difficult position to make decisions that balance benefits, uncertainties and potential harms.
There is a deja vu quality to all of these discussions. Much of this happened in 1976 following the development of recombinant DNA tech. While there are differences between the tools in synthetic biology and recombinant DNA technology, the kind of risks that regulators are interested in (when it comes to biosafety), that's what we're talking. We're talking about biosafety in the lab, like the accidental release of a pathogenic organism, that might infect laboratory workers, we're talking about the environmental concerns that Dr. Snow talked about, like in unintentional as well as intentional release in the environment. Also concerns about final products, like using synthetic microbes to manufacture chemicals, drugs and foods, how do we know those final products are going to be safe?
I will be talking about the existing systme of biotechnology regulation. As Dr. Patterson has indicated, the NIH plays a critical role in regulation of biosafety conduct in research labs. This is not unique to engineered organisms. We need to deal with a huge range of infectious and dangerous organisms. Engineered organisms pose particular issues. How do you determine in advance the potential risk of the organism in order to know which level of biosafety you need to put in place?
For recombinant DNA tech, that's pretty simple. You find the gene segment, you determine the function based on natural knowledge. Synthetic biology makes this more complicated: synthetic microbes could be assembled from synthetic genomic parts that were constructed in a lab or from multiple other organisms. The engineered microbe could show emergent behaviors. While unlikely, an engineered organism might have riskier behavior than just the sum of the parts. Dr. Patterson has guided people at the NIH over risk characterization. Commedably, they are moving ahead to cover synthetic biology research as well. The challenge will be to develop guidelines that are cautionary, without hindering research with expensive regulatory requirements. Whether these guidelines work will depend on insitutional biosafety committees at research labs that have the responsibility for implementing them.
The research not covered by NIH guidelines - privately funded researhc- is this a problem or not? In 1980s, as the first products of genetic engineering began to move out of the lab and into the production. The oversight framework was wondering what to do about this. So, as a result, the office of science and tech policy in 1986 led an inter-agency process to develop a framework forbiotechnology products. These policies are still in place today.
There were three basic findings of that group that are relevant to us here: (1) the decision that the process of biotechnology process itself is not inherently risky, no more riskier than conventional breeding, and therefore (2) regulation should be based on the characteristics of the final product and not the process that it was made. (3) Given that, the existing laws could be used by US regulatory agencies could be used to regulate anticipated risks from the products of biotech. The question of course is, how well has this regulatory system been put into place?
The way that it has evolved is (1) the US and this is not a model that has not been followed around the world (it has not been followed, I mean). The drugs are regulated by the FDA regardless of how they are made; pesticides by the EPA. Microbes and plants for environment are reviewed for pest problems by the department of agriculture. Despite this general principle, regulatory agencies have had to engage in legal slight of hand to fit biotech products into existing regulatory schemes, which were written before biotech came along. In some cases, agencies are still trying to adapt regulations to fit new tech. EPA had to figure out how to regulate a corn plant as a pesiticde. The FDA had to regulate a genetically engineered salmon under animal laws. The USDA had to figure out how to regulate a soy bean as a plant pest.
Some of these creative legal interprretations could be challenged. The ability of the agencies to regulate this under these regulatory committees. Biotech companies have every reason to cooperate with these agencies rather than confront them. This tech-neutral issue is interesting. Under US law, some products are viewed as inherently risky, and are therefore required to go through a pre-market approval process (agencies must find this to be safe before marketing). Animal/human drugs, pesticides, food additives. Most products intorduced into the market get little to no pre-market regulatory review. Manufacturers have to be responsible for safety. If you want to make a dietary supplement via synthetic biology, you get the same regulations as other dietary supplements (which is very little).
Different products get different levels of scrutiny. There is still a difference of opinion over the last 30 years. A number of groups believe that the system is not rigorous enough. While others believe that biotech products are over-regulated, and keep beneficial products off of the market.
If you had a blank slate, you would not design this system. On the whole, the system works. Valuable products have been introduced without evidence of harm or environmental problems. One could argue that we're just lucky, or we're just not looking hard enough for problems. That's probably true, but overall the system seems to be working. The US is unlikely to change its policy positions that have been in place for 30 years. How would this framework apply for synthetic microbes and drugs and biofuels?
Do the laws give agencies authority to cover this? Other agencies have had to stretch their legal authority. The USDA and EPA will need to revise their regulations in order to cover synthetic biology products. Existing laws are likely to provide agencies with sufficient authority for new products developed through synthetic biology. The FDA has been allowed to look at the process of manufacturing of these products. The real issue, the more important question is, whether or not the agencies have the resources and tools they need to both assess the risks and to also manage the risks as well.
The first microbes from synthetic biology are not likely to be appreciably different, and there's no reason to think they are more risky than products before. As the tech develops, it will be more difficult to assess the risk of potential impacts. Risk assessment is critical for regulatory agencies, which determines the level of containment, monitoring and control for commercialization of a product. Getting this right, by over-regulation and neither under-regulation, is a major challenge.
It may be a difficult thing for the EPA under the toxic control act. There are some laws pending in congress. It might make it difficult for the EPA to attain the information it needs for more assesment. Since risk assessment is more likely to become difficult, there needs to be controls for the unintended control of spread ... unintended spread of the microbes in the environment. Actual function of these microbes in the environment. Our experience to date has not been good: it's hard to keep biologically active materials separate in the environment, we've had instances of finding widespread gene flow from GM crops, etc. It's critical that such tools be developed publically, tested publically, and tested widely, in order to avoid controversies of terminator technologies in the context of GM crops.
Everything that I have talked about this is irrelevant to the garage biology phenomena. Regulations that I am talking about presume an industry that has the capacity to comply. In the case of people doing work in their backyards or garages will be likely to not know that they need to file a permit or something. We do not have a satisfactory model for this.
(1) The federal government needs to conduct a full and transparent review of the authoritoes, tools and resources to assess and manage the risks of synthetic biology. The recent DOE grant to the Venter Institute hopefully can provide a process for beginning that assessment.
(2) Federal funding agencies should fund robust risk research on synthetic microbes so that regulatory agencies have an independent basis on making regulatory decisions. Funding is also needed for developing and testing the conditional releases of organisms. Unless the risk research keeps pace with tech development, agencies are likely to respond to this by over-regulation, and keeping beneficial products off the market. Such research needs to be done in an open way.
(3) Finally I would recommend that the government needs to meet with stake holders- local governments, the do-it-together community, to begin to discuss rules and regulatios and so on that applies to all players.
Synthetic biology and synthetic genomics offers a lot of promises about our health needs. Providing a regulatory regime is a key part in assuring that society receives maximal benefit.
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Edward You. Weapons of Mass Destruction Unit.
Thank you very much. I want to thank the commission for inviting the FBI to present today. Being last, I have the advantage of building on the previous presenters. Let me start on building on Dr. Patterson on the AASB recommendations. These are very relevant. They have reports on biosecurity concerns related to synthetic biology, dual-use issues, and most importantly, the outreach and education component of it all.
I would like to bring to the commission's attention, the national strategy for countering biological threats. I have included some of the highlights: norms for responsible conduct, emergent risks, taking reasonable steps to reduce the potential for exploitation, and also international progress.
I do want to caveat right now that the FBI is not a regulatory body, but a law enforcement agency. In light of 9/11 and the anthrax mailings, we have taken a pro-active stance now. Through the consolidation of the WMD units, we have countermeasures/preparendess, intelligence for chemical/biological/nuclear threats. From the bioterrorism prevention program, these are our goals here, mostly operational to address bioterrorism.
Scientific industry and academic outreach. Why is this the case? When it comes to synthetic biology, how do you engage the different communities about biosecurity? The commission has seen that synthetic biology is difficult to define- academic to your amateur biologist. They are very different cultures.
You're dealing with advancement in technology on different levels. Not just the agencies, but also the participants. While the FBI has a responsibility for maintaining homeland security, we understand that any biosecurity program has to ensure there is not a negative impact that impedes research on all of these different fronts. That would present a national security risk, because you could impede countermeasure and biodefense research and more important entrepreneurial efforts that are going on as well. Striking that balance.
In 2006, the NAASB came up with a report on the illicit acquisition of DNA sequences coding for dangerous toxins or pathogens. The synthetic DNA companies in the US and actually instituted best practices in looking at how do you screen your customers and incoming sequences to make sure that risk is addressed. The FBI took the NAASB recommendations and ran with them, and conducted outreach with these companies. Although they do their due-diligence, if they come up with the red flag, what do they do? By conducting the outreach, the FBI engaged the WMD core, these are special agents dedicated to this- there's one in every one of our 56 offices. You can contact your local coordinator, where we have some subject matter experts at HQ, so we can contact the CDC and so on.
As I highlighted there, the industry was very happy about the question of "who to call" was resolved. Dr. Patterson just mentioned that recently the draft for screening guidance was released in November. This came out of NIH. Screening recommendations, government notification recommendations. This gives some DNA providers some recourse for what to look up and who to contact, the FBI, or export considerations (like Dept. of Commerce). This is all voluntary as well too.
The FBI hosted in August 2009 the first synthetic biology conference in San Francisco. We did this with the state department, AAAS, and at this event we had communities like diybio, academia, to come together and talk about the state of the art, but by having a law enforcement presence, can we come up with a meeting of the minds, can we come up with the risks, and managing or mitigating those risks, without impacting their efforts? It was overwhelmingly received. The FBI gained a better understanding of what the different communities represented.
This also on an international level, Dr. Schmidt mentioned the International Association Synthetic BIology. They instituted a best practices workshop in November 2009 to look at customer and sequencing matters, and a code of conduct to codify these best practices. The UN Biological Weapons Convention and US State Department were in attendance, and they looked at how we could assist in perhaps translating this notification process of the FBI to an international level.
And then we talked about iGEM, it's an undergrad competition hosted by MIT, and this past year in 2009, there were 1022 attendees, 26 countries. It's an undergrad competition and the director of this competition (Ruttberg) - I can't state this enough. It's fun. It is fun. It is all about synthetic biology. It's amazing what these teenagers can do in a 3mo time period. They come to MIT and showcase their summer projects. The FBI was at this last igem. Because of the national component.
Why is the FBI here? That was the first question. But because the international representation, we invited the UN to bring representatives. We hosted a workshop and had an outreach booth. To promote responsible research. In this instance, it was outreach, not oversight, and it was blue genes, not men in black. And then, DIYbio had a formal conference at UCLA. They talked about their state of the art, where they stood, citizen science and the expansion of the community.
And they got the .. and to the credit, they invited the FBI to come in and give a presentation and promote some career opportunities as well. Just recently, the UN Inter-regional Crime and Justice Unit (UNICREET), had a nanotech/synbio response. It is a parallel of what the commission is doing here. They brought on board all sorts of people, and the UWNBC, to look at biosecurity implications, and then hopefully come to some possible response measures or policy recommendations.
The report is due out this September, so that might be something the commission might want to take into consideration. Also, just recently, the FBI co-hosted with the Massaschussets Society for Medical Research its first biosecurity conference. This is a conference that had academia attendees, and representatives from institutional biosafety committees, institutional animal care and abuse committees. These are the gate-keepers, they are the ones who make sure the NIH guidelines are followed. They look at ethical issues on grant proposals. At this conference, and all of the conference people, we brought to the academic level, what do we mean by biosecurity?
By working together with the research community, can we come up with ways addressing biosecurity and so on? In a way that is not impacting research and commensurate with the identified researchs? The majority of the attendees said that any future biosecurity trainings should definitely have FBI or federal participation. It was really great. Um, and as we talke dabout over the case of a day and a half are terms like dual use, physical security, exploitation, material handling, all of the FBI activities are looking at fostering a culture of responsibility. It's empowering the community members themselves, what do we mean by biosecurity, help them to self-identify what some of the risks and harms could be? And working together to manage those risks.
I want to share an anecdote. It is not difficult toe ngage these communities. One professor - Jean Preclude from Virgina Tech. He's a professor in biotech. When he received an invitation to synthetic biology with the FBI, and he figured that he would go, and he listened to the message, took it to heart, and at Virginia Tech, he invited the FBI to come down and give a biosecurity workshop but not just for the bioinformatics college, but for the entire campus and four other universities, and undergrads all the way up to faculty and administration like vice president of research and compliance. It was a great success. It was a great success story. At the end of the day, I will never forget this, there was a sophomore student, and at the end of the message, she stood up and asked "I udnerstand, what can I do?" Through iGEM, the outreach that we have for the faculty members, we are equipping them to become the next generation of synthetic biology researchers and entrepereurs to understand that these issues should address.
We're fostering the development of this culture. On the facutly side, we're helping them become good advisors for these areas. What's the role of the FBI? As I said, there are certain identified and yet-to-beidentified threats. The FBI addressing the threats, that's our job. Engaging the scientific community, our job is to engage them and provide them the education to have situational awareness, to empower them from industry academia all the way down to DIYbio, to address these threats and that they are out there, and within the community potentially, but it doesn't stop there. It's a two way street, there's communication back to the FBI, not just a 911 call, but basically to help us, and as we mentioned, this is - syunthetic biology is screaming forwartd into the future. Not only from the FBI side, but from a policy making side, it's going to be difficult to keep up with the state of the art. We're helping to guide them, and make sure that we're aligning our resources commensurate with the risks, not only makes sense to national security but also the constituents that make up the scientific community.
Mitigating the risks, conducting our reach, partnerships not oversight. Effective policy making. The FBI and our federal partners can advise bodies like yourselves to make policy recommendations. More importantly, to get engagement from the scientific community, to get them toa divse you.
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I have a vivid imagine of agents in jeans advocating teens to do DIYbio. I am going to ask Jim Wagner to ask our first question. Wonderful presentations, thank you. I have a quick question. Dr. Patterson, I understand, and it was re-iterated, this notion of basing regulatory focus and activity on product, performance, and several other words, organisms, the objects. I am comforted that you feel that in the near term, with a little bit of extension with our current regulatory regime, we're in pretty good shape. I found it striking that it was Agent You who focused on something we heard yesterday: part of the distinguishing element of synthetic biology apparently is that so much of it is information, coded sequences. It's not in product.
Do we imagine that the other dimension that needs to be added to the regulatory regime, using your language, is something that would address not just product and performance, but also early stage information and its exchange?
I think that this is in terms of where the regulatory agencies come into play. Again, it's a reactive system. Essentially, the agencies wait for industry to develop products, that they need to move forward with to get regulatory approval. So, agencies are not generally in the position of going out and trying to get, even though there is an effort to track what's going on, so they can anticipate what is about to happen, unless there is a legal requirement to come to them for some regulatory review, the fact that there is previous work beigng done is not something likely to engage the agencies. This would fall within the NIH.
I would like to add a couple of comments. First of all, genetic sequences are overseen. Let me give you a few examples. On the biosafety side, genetic sequences are looked at for their capacity to replicate or encode. The constructs themselves, there is an oversight framework for how they are used, handled and distributed. On the biosecurity side, the select agent rules have a genetic section. There is regulatory oversight for genetic sequence. What can that genetic encode? Can it encode an infectious form of one of the pathogens that we are concerned about? Can it encode one of the highly lethal toxins? It's the subset which could potentially encode a pathogen.
Follow-up question. You were very I thought clear and open in your presentation that we have a set of regulations in place and practices but to quote, the American philosopher Will Rogers, even if you're on the right track, if you just stand there, you will get run over. We need to think about where we have to move, where the gaps are. Can you just say a little bit about the gaps? I know you can't be comprehensive, but where are the gaps when you look at synthetic biology?
I think many of the speakers have touched on the major issues - the notion of uncertainty, and as the constructs become more novel, we are unable to extrapolate from what we know to what these are. The question becomes, is the construct or the new entity guilty of being pathogenic, or being innocent until we have data? How do you treat it in the interim where you don't have data? Will you treat it with maximum controls? It's a conceptaul framework for how we think about these things, and move forward in a responsible way.
I want to follow-up on that question. Both Patterson and Rodemeyer have made the case that synthetic biology is part of the continuum of what has been happening with recombinant DNA and so on, for the past 35 years, and also talked about how the NIH pomigigated guidelines for using recombinant DNA. How other agencies came in and began to implement a strategy for even those institutions not funded by the NIH. One of the questions I have is, do you feel, based on what we're hearing, that we have an adequate infrastructure to examine these issues in synthetic biology, and do we have the ability to promulgate the right guidelines, or do we need a new infrastructure that lead to synthetic biology?
I don't think it's a politically realstici thing to talk about a new regulatory system for synthetic biology. I think this is the system that we have. How do we improve the system to make sure the challenges by synthetic biology- how do we build in better capacity for this system to be able to deal with it? There are any numbers of relatively small things that could be done in terms of agencies writing regulations that making sure that information is obtained, and incentives for industires to develop this kind of information as these products are being developed as well. So that information is made available. The system is adequate in thes sense that the real concerns - the real concerns about the resources and tools that the agencies have. It's difficult enough for them to deal iwth the fires that they have to put out today, having them think about 5 to 10 years down the road is really asking too much. The system is adaptable enough for them to grow and change as they learn. I think that we shouldn't throw out the baby and the bath water.
I would agree with what Michael has said. I would also remark that if one were to take the blank slate and design an oversight system, in my view, again, the three attributes would be (1) the ability to foster the beneficial applications of technology while minimizing the risks and managing the risks, that there would be a role for society in input into that infrastructure, and to cultivate public awareness and understanding, and (3) that the system could evolve. While I think that the government isn't good at cultivating public awareness and understanding, we're not always the best but we try, those three components are present in the current system. But it needs to evolve. The most important things it needs are the tools for appropriate risk assessment. Another question to ask is the applicability across all sectors, we see this technology is widely available, it's practiced on academia, not just dependent on streams of federal funding, but it's also privatized. Our relationship to other countries, and our citizenship in the world, is the question of how or what position the US takes with oversight with respect to other countries, and the degree of international engagements on these issues.
My question to the three of you is the follow-on. It seems to me, based on all three of your presentations, that you discribe a similar context that has been evolving over 40 years, you describe in your presentation that you thought there was adequacy, even though you wouldn't choose to build this particular framework, and that it has stood up to challenges. The FBI seems to be the answer to a question raised yesterday- who is the 911? They are actively engaged so that the 911 entity will stay up with the state of the science. It's definitely improving its ability to survey and become part of the field.
What I am wondering is if the existing regulatory or federal bodies that need to exist simply need to add this as a mission, perhaps not creating a new office, or adding this mission to their existing federal system so that there can be a quick learning period and the ability to make the quickest impact in a field that is evolving quickly? Adding a mission, or creating a new framewrok?
I think it's evidenced by the fact that the FBI as I mentioned, we are foremost a law-enforcement agency. In criminal investigations, it's reactive. If anything is better testimony, is the fact that we're proactive, as adding a mission. As evidenced, it is possible. I cannot comment on from a regulatory standpoint, but at least from the FBI standpoint, the mission has changed and has adapted.
Two comments. First of all, I think we have underscored a theme, a continuum here, but also the caveat that should not make us complacent. I think I can speak on the behalf of my colleagues at other federal agencies. We think a lot about these issues. We look forward to the input to the commission; complacency and turning a blind eye to what might be novel would be a mistake. Synthetic biology is within the mission of biomedical research and much of the oversight framework that we have today we've tried to bring togehter, the NAASB, the recombinatn DNA advisory committee for a joint meeting for examining the state of the science, top-down and bottom-up, and examine current issues, horizons, and what we can't see - biosecurity and biosafety risks. We are actively trying to engage an international dialog, we have 11-enrs, the first one was in the Americas with PAHO. We're just about to do one-- these are webinars. Online interactive sessions where the notions of dual-use synthetic biology are discussed and people could log-in and call in, we have one coming up based in Europe in the fall, it features synthetic biology. We have one later on in the year in China. I just say that to try to underscore that we're trying to address these issues. I think they are very much within the current mission of many offices and agencies either implicitly or explicitly and increasingly explicitly.
I have - I would go to Anitya then Christine then Barbara. Thank you. Uh, assuming that proactive government and law-enforcement oversight is appropriate, I want to ask a friendly version of a question, which you might get as unfriendly. My intention is friendly. What concerns or push-back or resistance might you expect or have you gotten from the idea of govbernment oversight from researchers? Concerns about academic freedom, intellectual freedom, industrial business secrets, civil liberties like freedom from surveillance. The push-back from the academic setting, when the government began to regulate encryption controls and so on. What sort of push back have you gotten or do you anticipate about academic freedom and intellectual property?
I guess that's my question. Again, our outreach activities have been relatively new. There has been some initial pushback. But I think that when we come in, and I addressed this in my first slide, how do you engage the different communities? The industry representatives- not the same way to approach someone in the DIYbio community. The message is still the same. There are some inherent risks and potential threats, but by working together, can we manage and mitigate those risks, what's the flipside? If there is an accidental release and so on, that's probably going to happen.. but engaging with academic, they understand it. One of our engagements is where we have a table top hypothetical scenario set, with hypothetical release and so on. WE have someone from academia and someone from law enforcement. The representative from academia now understands the role of law enforcement. It makes the message that much more understandable, but then it doesn't stop there, it's that- for instance, an accidental release from a law-enforcement side, from a criminal standpoint, we're done, if it's an accident. But we gain the appreciation, if you're the university, now your funding might be at risk, all the liability issues, that's just the very first step. So, there's an appreciation from both communities, both from the intentional aspects and also from the accidental aspects. The different scenarios, by gaining an understanding by different communities is vital. The pushback decreases.
I am hearing proactive education, proactive risk assessment, and question as to whether we can do that, whether you all can do that, without a crisis, before a crisis happens. Christine?
I wanted to ask a question in light of the questions before. Do we need to change regulations? One of the things Amy said is that the ideal situation would be a system that is easily evolvable. Being a federal employee, we work hard to make things respondi, but the federal government is not known for speed and changing or reacting to new fields. This synthetic biology depending on how you think about it, is moving pretty fast, maybe not as fast as some would like to think, and speed is an important thing to think about. Is there anything to think about in terms of how the federal government would think about having to evolve faster than it currently does given the current structures? And slightly different, how about coverage? Who do we reach out to, but what else can be done at the governmental level to reach constituents that it doesn't normally reach.
For your first question Christine, the strategy of embedding in law and regulation the overarching principles, like the products of biotechnology or pathogens should not be misused to threaten public health, or regulations that ensure the safe conduct of research, and then setting forth the specific procedures and guidance and practice, so you have the standard, but the way it is achieved can be more rapidly evolved and tweaked as new data comes in, our data is enriched, how we go about embodying that goal and statue is achieved. We need the flexibility to have oversight tools that change in that fashion and yet uphold the principles. We see this in the select agent rules that speak to knowing what you possess, transfering it, and registering it, but the voluntarily guidance to synthetic double stranded DNA providers, how do they go about screening or knowing what they made? That's embedded in guidance rather than embedding it in regulations. That would be my thoughts on that balance.
We heard yesterday about licensing at various steps along the process as a way to monitor. I am not concerned about the NIH- they have a fair number of areas of scrutiny- but by industrial uses - and amateur uses. Would it be valuable or not valuable to have licensing of products or steps along the way and the bioterrorism issues and the ones who are not licensed therefore being subject to some other ergulation?
With our engagement with the DIYbio engagement, they are taking that into serious consideration. Some of the things they have considered is model rocketry for instance. There are over-the-counter products, where you can just take it and launch it, and there are more - the example they show, last year, an amateur rocketry enthusiast built a 1/5th scale model rocket and had to get FAA clearance, and all of the permits and licenses. They are likening a safety and security framework around this. Drew Endy mentioned amateur radio. They understand what the impact could be, if something could go wrong, they understand how it could effect not just the community but the perception of the community. They are taking into serious consideration, how it would flesh out would be where it's extremely important that we engage the different communities. It will not be a one-size fits all, it might not work for amateur communities but maybe the industrial communities.
I am going to. It's a testament to everything that you have told us, and we are going to engage you more. We are going to the members of the public now for questions so we can address some questions to our presenters. And, um, go ahead. Yes, go ahead. We should take a few, htis is our last session, it's our last session for this meeting, it's not our last session. Please introduce yourself and ask a question, and I will keep track.
I am with Friends of the Earth. I am going to go with Dr. Patterson and Rodelemeryer says with moving forward with the synthetic organisms. Where does the burden of proof lie with analyzing risks, to prove research, do we let them go forward and be reactive if something bad happens?
Rob Carlson. I am concerned of two comments. I am concerned that the words of regulations and licensing have been used casually these past two days. And would observe that the press coverage would lean on regulation and not bioethical issues. The reason I am conferned about this is that nobody has talked about the costs. It is assumed that regulation and licensing equals safety, and it is demonstrably the case that safety and security are reduced with regulation. This issue has two sides, and we don't want to make it worse. The final comment is that the national strategy for countering biological threats that Agent You put up[, the first sentence of the second document says that garage biology is good.
I am director of Texas Tech University law for public policy or something. I would like to address a question about gaps. Many of these that come to mind are a lot of the things are oversight mechanisms but they apply only to people who have government contracts, they are spending the money as part of the oversight. The broader picture and broader public, that should probably be addressed. If we can learn lessons from legal history, the governments and states may fill in regulating at that level, it would be a point to good to address. Another point is the speed, and that's a relevant question when you have a technology emerging as quickly as this one, and if I had the opportunity to ask the agencies to look at this, I would ask them to inventory what existing regulations apply, and then secondly issue a guidance about how synthetic biology applies, guidance can be non-binding for the regulated community. So I would suggest two things that I might say would be really good steps forward, assess what regulations exist, and then issue a letter of guidance. The big picture, I think, also, I learn from lessons, and I had a walkthrough the legal and scientific history of biotech. The tension that we have explored in the last two days is the need between regulatory oversight and against the need to optimize development without unnecessary impedance. So also ethical and value constraints. This is not a luxury but a necessity, it's doing exactly what should be done today.
I have a question for Mr. Rodemeyer. I am an environmental journalist that has written on genetic resource access. All of the presentations were nelightening, I have a question on federal review. The international connects or disconnects. For instance, gene flow from GM crops, that's an important management issue, and it's an international issue. Within this question, implicit international agreements.
Where does the burden of proof lie? What do we take the costs of regulations into account? And international- how do we factor the international community I'll leave that to anyone who takes that.
The burden of proof is really set out by the various laws that apply to products. For instance, if you are a drug manufacturing, the burden of proof to safety is on you. The agency will deny it until it is proven to be safe. In other areas, the government is burdened to prove risk to justify regulation and enforcement. It is an open question, as to where in the variouis risks, where synthetic biology, what would apply? Good.
When it comes to the oversight of research, assuming that there is a standard or regulatory standard is in place, then the burden of proof is on the researcher to prove that they have adequate evidence and proof of concept that supports for moving forward. So, as to hte cost of regulation. When regulations are promulgated, there is an economic analysis that is done with them. The burden of regulation is assessed and published with the recommendation. One could quibble about whether the assessments are accurate,do they capture the costs, or do they overlook costs? So the costs of regulation are important, so I agree with the gentleman who offered that. There is a cost in not regulating. Both need to be considered.
The commission's perspective: we will not assume that regulation is justified or not justified regardless of the cost. That to us is an open question. Rob has been reading the news articles more than we have probably, since we haven't had a moment in the past two days, whatever they say, I want to put it on record that this is something that we would definitely consider, the cost factor is something that we would consider. These are really important questions, when we're not going to do the deep dive today, but perhaps the question on the international community.
There are two aspects: biosecurity issues are critical and I will ask my colleagues to respond to that. On the regulatory side, this is has been a real challenge because we have a global controversy about genetically modified crops and foods. Other regulatory systems are based on process-based, and we have this problem of asynchronous regulatory approvals, where products are legal here, but not in another part of the world. This is difficult with a commodity like corn. These issues are engaged at international levels, there have been efforts to harmonize efforts between the nations. It's a complicated answer. There is no clear response, no clear one place where you can kind of bring all of those issues together.
Mr. You. I would comment that the FBI does have intenrational engagement such as through INTERPOL and the UN, but also the US State Dept. has an interntational bioengagement strategy, and that question could be addressed through that level.
We have reached the end of our time for our first inaugural session. First, I just want to say, uh, a simple observation, uh, the number and diversity of members of the public who have turned out, is truly heartening for anyone like myself that believes education first and foremost is at the heart of a lot of the issues that we face in our democracy and secondly it's a testament to how many members of the public stayed till we are adjourned. Let me just say a few words and ask Jim if he would like to say anything. FIrst, we have issued a call for commentary on the topic of synthetic biology. Any group or individual that would like to offer opinions on the topic, we will read them. Check our website, our website is www.bioethics.gov and our email address is in...@bioethics.gov - so, on behalf of the commission, I want to thank you all for coming. Our next meeting is being held September 13th and 14th at the University of Pennsylavnia in Philadelphia. All of our meetings are open to the public and free, and our meeting after that is in Atlanta at Emory. I will now turn it over to Jim.
Let me thank everyone and our experts throughout this session. This has been fabulous. Thank you to the public and please contribute through the mechanisms provided. Thank you for two days of excellent discussion and deliberation, it will serve us very well. Thank our three presenters who did a marvelous job.
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