Might as well post this for reactions
Roger
Would be interested in reactions or comments. I don't personally
expect anything bad
to come from DIY bio as it is presently constituted. And I would be
extremely interested
in credible "fun apps" or "useful apps" that offered capabilities or
quantitative levels of
functionality that one could not get otherwise, even if we all
understood that these were
just ideas.
Best,
Roger
----------
Power and responsibility
Roger Brent
Director and President
The Molecular Sciences Institute
Berkeley, California
The introduction
Peter Parker and Uncle Ben are on my mind. The reason is that is
that a month ago I was jumped by Craig Venter. There were TV cameras
around. The live audience was an interesting, edgy mix, on the
interface between "technology", meaning computer technology, and
culture/ media/ journalism; I had just given a closely prepared talk
on the history, promises, and perils of biology, 20 minutes from solar
ignition to origin of life to photosynthesis to agriculture to
Asilomar to now; and I had paid particular attention to the existing
threat from remade and lightly engineered viruses, to the various
technology-empowered approaches that could contribute to a defense
against such unpredictable pathogens. The whole set of ways the
defense strategy needs to shift.
For whatever reasons, Craig came prepared to take the talk as an
attack on himself and his agendas. As if review of human use of
biology in historical context, and talk about real risks, somehow
threatened his ability to mobilize resources toward his goals:
removing nonessential genes from Mycoplasma genitalium, synthesizing
hydrogen and methane, cruising around the world in boats, etc.. The
word "fearmonger" came up, multiple times. "Chicken Little" came up
too, afterwards. And one terrific sound bite, which is that more
people were killed by lightning last year than by anthrax attacks
during the past 50 (see below).
Of course, nobody likes being jumped, but being jumped happens, I
think I held my own, and when it's up on YouTube under Creative
Commons, I hope it at least makes decent television. More to the
point, Craig happens. Complaining that the man can go off half-
cocked, or that he can conflate attempts at analysis with personal
attacks...isn't relevant. Might as well complain that hurricanes are
wet and full of wind. Because Craig is a force of nature, and, what's
more, he's one of those forces that is usually a force for good. It
is very largely due to him that we had large scale shotgun sequencing
as soon as we did. And it's very largely due to his efforts and those
of the extraordinary people he attracted that the fly genome, and then
the human genome, were delivered so fast; had Craig not acted, it
might have taken years more. Craig's sense of scientific celebrity
and his adroit use of it bespeak a deeply intuitive understanding of
our culture. His current work to focus attention on the genomic
analysis of microbial ecologies and energy production is igniting
imaginations and no doubt helping recruit the next generation of
genomic scientists and engineers all over the world. So this isn't
about Craig. Still less about the anomie of the contemporary US
scientific intellectual (misunderstood... yet again... shall we
cry?).
Rather, this is about asking people who identify as members of a
synthetic biology community to take a few next steps toward coming of
age.
The facts on the ground
The first starting point is that certain kinds of biological
engineering, including making pathogens drug resistant, and recovering
live viruses from transfected recombinant DNA, are technically
feasible and have been so for a very long time. The recovery of
poliovirus from cDNA was accomplished by Baltimore and coworkers in
1982. To restate that, a generation ago, a lab (albeit one of the
best virology and recombinant DNA labs in the world at the time) made
infectious virus from DNA. If one needed a demonstration that one
could remake viruses, this was it. Nowadays, remaking viruses is a
matter of making appropriate DNA constructions that encode the viral
genome and that provide any other functions needed to get live virus
out. Polio is one of the simple ones. To remake many other DNA and
RNA viruses requires helper functions-- for example, protein hardware
to make negative RNA strands into positive RNA strands, or to start
viral transcription going. So, to remake viruses, one transfects with
DNA that is the viral genome or (for RNA viruses) directs the
synthesis of the viral genome, together with DNA that directs the
synthesis of the helper functions. You don't need to provide the
helper functions from DNA constructs, you can also co-transfect genome-
encoding DNA into cells co-infected with a related "helper virus" that
you have screwed up so that it cannot replicate. Depending on the
virus one is re-making, the ways one goes about getting live virus
back from DNA used to construct it range from really simple (mix 12
things, wait 24 hours) to relatively gnarly (some classes of viruses
have not even been done yet, so would require new construction work
and troubleshooting). To calibrate "gnarly", I mean "might take one
of the 5,000 most skilled research groups in the world as much as a
year to carry out". For any given family of virus, I (or any of more
than a thousand scientists) can be a great deal more specific about
how one would perform any given construction job, and what technical
hurdles might still exist and how one would overcome them. But given
that this page will be crawled by Google within a week after it goes
up, this is as specific as I'm now going to get.
The second starting point is to imagine two circles in a Venn
diagram. One circle is the set of people who know how to perform
various manipulations and pieces of construction work, who could for
example make the DNA, or troubleshoot what was wrong in a co-
transfection setup as above. The second circle is the set of people
who might be motivated to build and release a self-replicating
organism that hurts people. The number of people in the first circle
has been growing steadily, at a guess at around 10% per year, for many
decades since 1973. At the moment, the number in the second circle is
large, and is affected by international political attitudes (I am
guessing that it has grown significantly in the past 5 years). If we
are in luck, there might now be no people in the intersection of those
two circles. But even if we are lucky now, there is no reason to think
we will stay lucky in the future, because the number of people in the
first circle will continue to grow.
To run the calculation for the first circle, let's ask, if there
are 20,000 undergraduates at UC Berkeley, how many possess the
technical skills and access to labs to make a gram positive organism,
anthrax, resistant to the first line antibiotic fluoroquinilone
antibiotic, ciprofloxin? Let's guess that one tenth of them do. 2,000
UC Berkeley undergraduates. Now, let's try to guess how many have the
DNA manipulative skills needed to construct the plasmids and perform
the transfections needed to follow recipes to recover animal viruses?
Surely, more than 20? Maybe 200? Now, given that techniques keep
getting easier, and more people keep getting trained in their use, how
many past and present UC Berkeley undergraduates will have those
skills in 2016?
How synthetic biology interacts impacts this existing strategic
situation
Now, the group of people who call themselves synthetic biologists
did not make this situation. But up to now, the community of
synthetic biologists has been poorly defined and has staked out
boundaries, that, from outside, seem weird and artificial. To be
provocative, I am going to call the community a self-made ghetto, with
an arbitrary line drawn to wall off a group from a much greater
community of related activities (I am imagining the sacred cord, the
eruv, that the faithful can place at the perimeter of orthodox Jewish
neighborhoods, thus enabling those within the cord to perform certain
activities on the Sabbath). Inside the ghetto, good work on
fabrication, abstraction hierarchies and (in the US but not in Europe
where it is considered to be chemical engineering) on microbe-powered
chemical synthesis. At the same time, the overwhelming majority of
the real genetic engineering work of the world, such as engineering of
crop plants, the applications of genetic engineering to scientific
research, to pharmaceuticals, and to medicine, and most of the complex
applications of recombinant DNA to microbial synthesis of organic
chemicals, has been going on for 3 decades, outside the boundaries and
largely unaware of ghetto activities.
So I would like to stipulate some things. I believe that most
reasonable people can agree with Venter that the applications of
synthetic biology within the current ghetto boundaries pose no
significant risk. Hold a gun to my head, and I say: "zero risk".
Zero, zip, nada, none. To say this again, there is no reason anyone
should fear a minimal Mycoplasma genome, or a bug that makes plastic,
or methane, or artemisinin. Period. Full stop.
But I also submit that most reasonable people can fear drug
resistant anthrax, or smallpox, or a revenant 1918 flu that carries a
point mutation that makes it resistant to the first line antiviral,
tamiflu.
I also submit that the increased attention, capital investment,
and sheer technical ingenuity now being deployed to developed chemical
synthesis of long pieces of double-stranded DNA provides another path
to making DNA constructions. It joins other schemes, ligation in
vitro and PCR and various methods perform homologous recombination in
vivo, but, yes, it does add yet another path. For that reason, the
widening capability to synthesize long pieces of DNA directly,
increases the incremental risk for biological attack. I can't
quantify that risk but suspect that it is low.
I further submit that developing an additional class of DNA
hackers via an undergraduate engineering route (as opposed to the
existing scientific or biomedical communities) also provides some
increment of risk. I can't quantify that risk, either, although I
suspect it is not high, but it will become very much higher if we
permit an outlaw hacker culture to come into being and are foolish
enough to glamorize it.
Finally, I submit that the synthetic biology community has been
extremely proactive in recognizing those incremental risks introduced
by large scale synthesis of double stranded DNA and attempting to
address them. The general approach has been to identify those
activities specific to self-identified Synthetic Biology, then, to the
extent possible, seek to zero them out. This ghetto will police
itself, at least a little. Call it a "Hippocratic" approach: within
the eruv, the boundary defined by the consecrated string, we will
address our risks.
The issue
The trouble is, that if one doesn't understand or recognize the
boundaries defined by the sacred string, things immediately start
seeming a little, um, Talmudic. Asking for help in screening long
double stranded pieces of chemically synthesized DNA to see they don't
encode pathogens? Look at how responsible we ghetto members are! The
fact that this screen won't apply to shorter, single stranded
synthetic DNA, the fact that ligation in vitro, PCR and serial
recombination in yeast and E. coli all provide perfectly good
alternative ways to make any DNA construction? Not our problem! We
synthetic biologists only police our ghetto -- and we reserve the
right to move the string that defines the boundary whenever we like.
Even though nobody else even understands the string, or insofar as
they do understand it, takes the string with any seriousness.
The reason the boundaries and self-policing can't work anymore is
that the multiple and reasonable connotations of the term "synthetic
biology" naturally mean that anybody not of the ghetto will
immediately associate it with the entirety of recombinant DNA work in
general. And this is a time when discussions about recombinant DNA
powered work are breaking surface again. For all sorts of reasons,
including the ones above On November 18th, Kofi Annan of the UN
called for a world discussion about the dangers arising from the
ability to resynthesize viruses. In the US, visibility is only likely
to increase, because the country in a runup to elections in 2008 that
will probably drag both energy policy and climate change into
political discourse. In fact, it's not too far a stretch to imagine
we might hear about hemicellulose and lignin, microbial fermentation
of higher alcohols and hydrogen, during the 2008 US Presidential
debates. So, for biology, we may once again be coming into an
"Asilomar moment". If this is true, then people who know how to make
DNA constructions, from the very top of the celebrity chain (ie,
Craig) all the way down to the 11th grade student who has just
finished a high school science fair project, are going to be asked for
their opinions as to whether and how organisms created by recombinant
DNA work should be regulated.
And I guess this is the place to recall the postmodern mythology.
Long ago, there was a time when Peter Parker was a freshly minted (as
opposed to veteran) adolescent superhero. Parker's Uncle, Ben, told
him that "with great powers come great responsibilities". Soon after
that helpful pronouncement, Ben was killed by a criminal. The same
miscreant whom Parker, as Spiderman, who had been earning money as a
wrestler, had refused to help the police apprehend. Because collaring
perps wasn't Spiderman's job.
The responsibilities
So I am urging members of the synthetic biology community to
acknowledge three responsibilities.
Responsibility to not screw up the defense. The argument that
more people are killed by lightning than anthrax will get every bit of
the respect it deserves. But it isn't enough to let fatuousness
collapse under its own weight. Much of what needs doing requires
complex and thoughtful action. In particular, the "Maginot line
problem", that an attacker will want to outflank fixed defenses, means
that we will need to move to agile detection and response to pathogens
we cannot now predict. Development and deployment of the needed
technical measures constitutes a set of hard problems that will take
brains, money, and time to solve. Synthetic biologists can help with
these problems if they are willing to learn enough to contribute to
their solution. The complementary need to invent, and implement
appropriate social controls, be those criminal penalties,
stigmatization, or licensing regimes, constitutes a set of equally
hard problems that again will require creative brainpower to address.
Synthetic biologists can at least help explain these issues to other
stakeholders, and can help input into these schemes to make sure that
they do more good than harm. The US and Europe being as they are, it
now seems unlikely that the world will get meaningful defenses into
place before an attack, but some of us feel duty to act as if that is
possible and prepare the ground for the needed work. Denial and
evasion are not our friends here. People who are refusing to
acknowledge that that there is a problem while other people are
working to envision 21st century public health systems... such people
are just not helping Uncle Ben.
Responsibility to tell the truth. I admit that "truth" here can
be slippery, especially for those of us whose jobs involve helping
bring the future into being through their dreams. But when synthetic
biologists step outside their ghetto, the people on the outside tend
to ask questions on topics other than the oscillators, switches,
minimal bacterial genomes and synthesis of fine chemicals by
fermentation that the synthetic biologists dream about. This is the
place where it's easy to slip up.
For example, journalists ask: what's new? (and they will ask
this, that question being such a large part of their jobs). Suppose a
journalist asks a synthetic biologist what distinguishes her field
from previous genetic engineering, and our synthetic biologist replies
that in the past genetic engineers did not create assemblies of
multiple parts to carry out desired functions, whereas synthetic
biologists do. That statement is utterly counterfactual, 30 years out
of date, but your basic science or business journalist cannot be
expected to vett it, and it appeared in all over print media in 2005
and 2006. Better to make the case for standardized parts and
attention to abstraction hierarchies than to speak falsehood with
authority.
Responsibility to the truth can also take other forms. If Craig,
in order to help advance the idea that building synthetic bacterial
genomes is safe, says that more people were killed by lightning in the
last year than by anthrax attack in the last 50, it's of course true,
just as it for people killed by exploding hydrogen warheads. But even
though it's true, it's just not especially relevant. Call that... a
"designed to distract" kind of true, an "Exxon-Mobil" kind of true.
Now imagine that, to decouple fears of microbial fermentation from
fears of biological attack, a synthetic biologist finds herself
asserting that it's not easy to remake measles, or influenza with
synthetic DNA. Or simply that there is a legitimate scientific
uncertainty around that point, so that the prudent next step is...
further study. Plead uncertainty, or assert that there is
controversy, where none exists, and there we are back at Exxon-Mobil
again. Unless some readers believe that governments, corporations and
foundations should be staging scientific meetings in 2010 to address
an alleged lack of consensus as to whether human-generated CO2
emissions are contributing to a rise in average planetary
temperature?
Finally, responsibility to the truth can take the form of
admitting ignorance. This summer there were interviews in which self-
identified synthetic biologists were asked, among other things, about
"experiments of concern". Now, "experiments of concern" is what one
calls a "term of art". It was coined in the Fink report, where it
refers to 7 highly specific classes of activities (for example,
deliberately making a pathogen resistant to a therapeutic drug).
Reading the transcripts, it is hard to shake the impression that, in
some of the interviews, neither the graduate student interviewers
(public policy students) nor the young leaders being interviewed
(often, engineers, and in any case not infectious disease researchers)
had any idea that the term had a specific meaning, much less what it
did mean. Is it too much to ask that at least one of the parties in
these conversations have been able to admit that they didn't know
exactly what it was they were discussing?
Responsibility to articulate and help bring about positive
consequences. I suspect that most people who read this will share the
belief that biological engineering, recombinant DNA work, and
synthetic biology have a great deal to contribute to a better human
future. And that the current ghetto boundaries, the focus on devices,
minimal bacterial genomes, microbial chemical synthesis, and ability
to make long pieces of double stranded DNA, do not capture all the
good that needs to be done. But, although I am very sympathetic to
the ideas that hacking and playfulness are good for their own sake,
I'm pretty sure that for hacking in biology, the public is not going
to buy in without a positive vision. So, I suspect that to give the
field traction, it will be necessary to articulate and work toward
achievable positive goals.
I've already mentioned defense. There is a lot to do here, and
I'd like to see students of biological engineering make more
contributions than they have to problems of disease detection,
diagnosis, prophylaxis, and treatment. But defense isn't the half of
it. There are tremendous human needs during this century, including
but not limited to food, energy, health, housing, water, cleanup, and,
for all we know, emergency fixation of carbon. Why should the next
election not feature a proposal to spend 50 million dollars by 2010 on
open source standard parts, genes encoding enzymes relevant to
anabolism (carbon fixation, alcohol synthesis, energy storage
materials, plant derived materials and functions) and catabolism
(chemical remediation, recycling)? Couple this with social norms and
condign punishment of pathogen-makers and you have a bridge you might
be able to sell.
Protecting Uncle Ben
Precisely because it has attained a measure of prominence,
synthetic biology has attained a measure of power. At the very least,
it has increased its power to influence people's thoughts and
opinions, and so affect public debate. At the same time, technical
trends that predate synthetic biology but will inevitably be
associated with it have brought about the current risky landscape.
The consequence is pretty clear. On some day in the future, they are
going to hit us. Fill in your own "they"; remember that "they" in
2006 may not be the same "they" as in 2016; remember that "they" in
2006 could be "he" or "she" in 2016; and fill in your own "us". On
the day that they hit us, significant numbers of Uncle Bens are going
to die. Fill in your own "Uncle Bens"
With greater powers come greater responsibilities.
Technical publication information
Power and Responsibility
Version 3
Copyright 21 November 2006 to Roger Brent
CC deed Attribution-NoDerivs 2.5
Fair use permitted
Some rights reserved
DOI version 2
1721.1/34913
MIT Synthetic Biology Archive
Bryan Bishop
> Dear DIY Biology people,
Weren't you the person who said that you don't trust us?
> Rather, this is about asking people who identify as members of a
> synthetic biology community to take a few next steps toward coming of
> age.
>
> The facts on the ground
>
> The second starting point is to imagine two circles in a Venn
> diagram. One circle is the set of people who know how to perform
> various manipulations and pieces of construction work, who could for
> example make the DNA, or troubleshoot what was wrong in a co-
> transfection setup as above. The second circle is the set of people
> who might be motivated to build and release a self-replicating
> organism that hurts people. The number of people in the first circle
> has been growing steadily, at a guess at around 10% per year, for many
> decades since 1973. At the moment, the number in the second circle is
> large, and is affected by international political attitudes (I am
> guessing that it has grown significantly in the past 5 years). If we
> are in luck, there might now be no people in the intersection of those
> two circles. But even if we are lucky now, there is no reason to think
> we will stay lucky in the future, because the number of people in the
> first circle will continue to grow.
How about you just go use a separated habitat/environment if you're
going to be a hypochondriac and hikikomori about viruses?
> To run the calculation for the first circle, let's ask, if there
> are 20,000 undergraduates at UC Berkeley, how many possess the
> technical skills and access to labs to make a gram positive organism,
> anthrax, resistant to the first line antibiotic fluoroquinilone
> antibiotic, ciprofloxin? Let's guess that one tenth of them do. 2,000
> UC Berkeley undergraduates. Now, let's try to guess how many have the
> DNA manipulative skills needed to construct the plasmids and perform
> the transfections needed to follow recipes to recover animal viruses?
> Surely, more than 20? Maybe 200? Now, given that techniques keep
> getting easier, and more people keep getting trained in their use, how
> many past and present UC Berkeley undergraduates will have those
> skills in 2016?
>
> So I would like to stipulate some things. I believe that most
> reasonable people can agree with Venter that the applications of
> synthetic biology within the current ghetto boundaries pose no
> significant risk. Hold a gun to my head, and I say: "zero risk".
> Zero, zip, nada, none. To say this again, there is no reason anyone
> should fear a minimal Mycoplasma genome, or a bug that makes plastic,
> or methane, or artemisinin. Period. Full stop.
>
> I further submit that developing an additional class of DNA
> hackers via an undergraduate engineering route (as opposed to the
> existing scientific or biomedical communities) also provides some
> increment of risk. I can't quantify that risk, either, although I
> suspect it is not high, but it will become very much higher if we
> permit an outlaw hacker culture to come into being and are foolish
> enough to glamorize it.
So, whenever I see people talking about risks, I always refer to the
concise Wikipedia article on SPOFs, or Single Points of Failure. In
any network system, a SPOF is where you have this node spontaneously
fail or do something terrible, which might be a cascading black swan,
completely unpredictable and turns everything upside down. For
instance, if you only have your very important document on one
computer, that's a SPOF, because if that point fails, then all of the
other things that you were going to do with that one document will now
be generally undoable.
http://en.wikipedia.org/wiki/Single_point_of_failure
"""
The strategy to prevent from total systems failure is
1) Reduced Complexity
Complex systems shall be designed according to principles decomposing
complexity to the required level.
2) Redundancy
Redundant systems include a double instance for any critical
component with an automatic and robust switch or handle to turn
control over to the other well functioning unit (failover)
3) Diversity
Diversity design is a special redundancy concept that cares for the
doubling of functionality in completely different design setups of
components to decrease the probability that redundant components might
fail both at the same time under identical conditions.
4) Transparency
Whatever systems design will deliver, long term reliability is based
on transparent and comprehensive documentation.
"""
So, I see DIYbio as implementing a few of these, especially #4 and #1.
But when it comes to risks of total system failure due to viruses, I
see we're completely failing at #3 with having only one single
atmosphere, and thus a possible medium for harmful biological agents.
I mean, it's just a bad idea. It's nice though. I really do like
everything, but I hardly think it's fair to play the blame game and
act like viruses are the cause for how much that possibility sucks-
it's also partly due to just the way that the world has historically
worked.
> The reason the boundaries and self-policing can't work anymore is
> that the multiple and reasonable connotations of the term "synthetic
> biology" naturally mean that anybody not of the ghetto will
> immediately associate it with the entirety of recombinant DNA work in
> general. And this is a time when discussions about recombinant DNA
> powered work are breaking surface again. For all sorts of reasons,
> including the ones above On November 18th, Kofi Annan of the UN
> called for a world discussion about the dangers arising from the
Global problems need global solutions- habitats are one way if you
want to do the environmental isolation from viruses gig. I mean, let's
be honest here. You're looking at the problem of viral infection, so
let's solve *that* problem. Viruses are easy to replicate. Habitats
aren't- that's where the actual effort needs to go into, if you really
are worried about these viral infections.
<snip>
> possible and prepare the ground for the needed work. Denial and
> evasion are not our friends here. People who are refusing to
> acknowledge that that there is a problem while other people are
> working to envision 21st century public health systems... such people
> are just not helping Uncle Ben.
Because Uncle Ben really isn't a person. Now, if the government wants
to contribute, stay active in these matters, increase infrastructure
for new research and so on, that's fantastic and I am sure many people
on this list would find that a worthwhile use of their time.
> Responsibility to articulate and help bring about positive
> consequences. I suspect that most people who read this will share the
I agree. There is a strong need for clear articulation of topics and
issues. I suspect that there is a problem of 'institutional
boundaries' however- some of us might be articulating thoughts from a
point of view that government bodies simply can't address, such as the
idea of passing university and corporate boundaries for labwork, which
for a while now has been the norm.
"Why should the next election not feature a proposal .. on open source
standard parts?" I'd be happy to support open source standard parts
for just about anything. An election might not be the best place for
that topic though- technical things should happen for technical
reasons- which you gave a good list of (food, energy, health, housing,
water, cleanup, ..).
Jason Bobe
Safeguarding Biology by George Church • Posted February 2, 2009 11:03 AM
http://www.seedmagazine.com/news/2009/02/safeguarding_biology.php
I like that George offered opinions on practical steps to evaluate safety of GEOs:
<snip>
But actions speak louder than words. These safety features will be accepted and used only if they undergo rigorous testing in physical isolation and review by a diversity of critics. The battery of necessary tests is formidable, and includes ensuring that GEOs are not toxic to immunocompromised lab animals, as well as lab examinations of ecological challenges like unwanted gene transfer and harmful mutations. If we can construct safety measures that pass all these tests, the door will be opened to potentially allow more sophisticated biotechnological interventions in areas like human health.
</snip>
Jason Bobe
Andrew Hessel
I have to admit to being skeptical of work to reengineer the genetic code, though. Nature to me is one giant combinatorial engine, leading to diversity we are just now beginning to comprehend on a molecular/genetic level. (The macroscopic understanding is pretty weak, too, in many environments.)
Ever stop to consider why alternative or species-specific genetic codes did not widely result, after billions of years of evolution?
Andrew Hessel
Biostrategy consultant
780.868.3169
ahe...@gmail.com
Meredith L. Patterson
> Ever stop to consider why alternative or species-specific genetic codes did
> not widely result, after billions of years of evolution?
Um, dude, what do you think speciation is?
There are thousands, perhaps millions of species-specific proteins and
metabolic pathways out there. Countless more existed in species that
are now extinct. Certainly there's a laundry-list of machinery that's
common across species -- heritability and parallel evolution at work
(thanks, selection pressure!) -- but the innumerable variation already
extant in nature is precisely the result of species-specific genes.
Even common functionality has subtle differences from one species to
another, DNA-wise.
Cheers,
--mlp
Guido D. Núñez-Mujica
nucleotides to protein.
AAA codes for lysine pretty much in every animal, plant and fungus.
There are exceptions, however. Our Mithocondria uses a slightly
different code. But the exceptions are not that different from the
standard and there are only two extra aminoacids from literally
thousands of possibilities.
Here there is more about the variations:
http://www.ncbi.nlm.nih.gov/Taxonomy/Utils/wprintgc.cgi?mode=c
William Heath
-Tim
Guido D. Núñez-Mujica
and expressed there and fulfill functions on cellular metabolism.
However, why is a different question of which I ignore the answer.
Bryan Bishop
> Why does mitochonrdria have dna? Does it use it somehow?
Yes, in humans it encodes the use of 13 proteins which have caused
Aubrey quite a headache. There have been some who have suggested
attempting to port the proteins into the nucleic DNA instead of
mitochondrial DNA.
http://www.mfoundation.org/research/adgpubs#allo
http://www.mfoundation.org/research/adgpubs#mtmut
See also MitoSENS. I'm sure there's other more interesting
mitochondrial DNA research out there that I am failing to remember to
cite.
Ingrid Swanson
Ingrid
Why does mitochonrdria have dna? Does it use it somehow?
-Tim
Lora
restricting *either* knowledge of how-to *or* access to cooties *or*
having lots of angry disenfranchised people, Elvis has left the
building.
So far all the approaches to biohazard control I have seen are sort of
built on the precedent set by the nuclear industry: The same basic
premise that uranium is hard to come across, that manipulating it into
things that go boom is a difficult skill to master, that the knowledge
is arcane and mysterious.
This is just not the case w/ biology. Limiting access to nasty
pathogens? What are you going to do, quarantine every squirrel and
prairie dog in the Southwest US and Pacific coast? Ban sheep farming?
For that matter, you better start paying nursing aides in the old
folks' homes a LOT better and putting them through serious background
checks--nursing homes are prime breeding grounds for antibiotic-
resistant pathogens of all sorts.
Limit access to the knowledge? How? Burn every undergrad text and open
access article on transfection techniques published since 1950? Close
every public library? Good luck with that.
I'm probably dating myself here, but when I was an undergrad, the
first step in setting up a blot was going to the grocery store to buy
Brillo pads. The first step in making a DNA gel was boiling potatoes
and cutting up strips of blotter paper. (Yes, I am a dinosaur,
thanks.) Kits and Invitrogen toys don't actually enable anyone to do
anything they couldn't do before, they just make it faster and more
efficient. *waves cane at Roger* You whipper-snappers don't know how
good you have it!
Look, when it comes to the issue of Horrible Pathogens That Will Kill
Us All, synthetic bio is about the LAST thing I worry about. I'm more
worried about idiots who run factory farms that drown entire towns in
several feet of raw sewage, feedlot operations that use massive
amounts of antibiotics and hormones in food, lack of infection control
in hospitals / schools / workplaces that don't give sufficient sick
days, prion diseases, farm labor pooping Salmonella in the spinach
fields for lack of toilets, dumping raw sewage into rivers and lakes
used as drinking water and recreation, lack of public health
infrastructure, poor vaccination rates due to fear-mongering, and
using halogen-based disinfection in water systems when we know just
about every water bug is chlorine-resistant at this point. Those are
things which are proven, over and over, to create disease and death,
*and which we already know how to fix*. It should tell you something
when we know without debate that those things are hazardous to life
and humanity, and we have the technology in hand to fix those things,
*yet we don't fix them anyway*. I'd suggest that when it comes to
making the world safer, we work on things we already are sure of,
before going off half-cocked on the WhatIfs. We got enough problems,
let's not go imagining more.
On Feb 4, 7:33 pm, Ingrid Swanson <iswan...@u.washington.edu> wrote:
> The why: Mitochondria have DNA by virtue of being derived from
> bacteria. Some mitochondrial proteins are made from this DNA (they
> have their own ribosomes too) while others are encoded in the
> chromosomal DNA (or the "extracellular plasmid" from the point of view
> of the mitochondria, as coined by mitochondrial expert Dr. Douglas
> Wallace). These proteins are imported into the mitochondria from the
> cytoplasm.
>
> Ingrid
>
>
> > Why does mitochonrdria have dna? Does it use it somehow?
>
> > -Tim
>
>
> > Meredith, as I see it, Andrew means the code for translating
> > nucleotides to protein.
>
> > AAA codes for lysine pretty much in every animal, plant and fungus.
> > There are exceptions, however. Our Mithocondria uses a slightly
> > different code. But the exceptions are not that different from the
> > standard and there are only two extra aminoacids from literally
> > thousands of possibilities.
>
> > Here there is more about the variations:
> >http://www.ncbi.nlm.nih.gov/Taxonomy/Utils/wprintgc.cgi?mode=c
>
> > On Thu, Feb 5, 2009 at 7:25 PM, Meredith L. Patterson
>
> > > On Thu, Feb 5, 2009 at 12:28 AM, Andrew Hessel <ahes...@gmail.com>
Len Sassaman
subscribe to your newsletter.
Mackenzie Cowell
I think Roger would agree with you about the difficulty of biological
material control. As he wrote, it is unlike the nuclear situation,
which is amenable to material and process control. Instead, it is:
"the "Maginot line problem", that an attacker will want to outflank
fixed defenses, means that we will need to move to agile detection and
response to pathogens we cannot now predict."
a stockpiling of hepa gas masks, but rather that synthetic biologists,
and larger society in general, are not devoting enough effort to
developing strategic defenses to biological disaster. Roger argues
that the intersecting area of the venn diagram of expertise + ill-will
is increasing, and hence the chance of disaster is as well. As people
who are contributing to that increase by developing the first circle
in that diagram, it is our responsibility to also spend effort
developing the safeguards and defenses.
A practical step forward would be for iGEM (igem.org) to launch a
biological defense track for the 2009 competition. In this way, at
least some of the newest echelon of synthetic biologists would be
devoted to inventing the defenses Roger is wishing for.
Mac
Julie Norville
-----------------------------------------------------------------------------------------
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show details 8:38 PM (3 minutes ago)
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Yes, I would definitely be up for that. I'm sure Jason B would as well.
When can we introduce Roger Brent?
Mac
On Wed, Feb 4, 2009 at 8:32 PM, Julie Norville
> Jason and Mac, would you like to introduce Travis and Nils at a lunch at
> MIT, most likely on March 4th. I'll send out more info about it later.
> Julie
JonathanCline
> Dear DIY Biology people,
>
> Would be interested in reactions or comments. I don't personally
> expect anything bad
> to come from DIY bio as it is presently constituted. And I would be
> extremely interested
> in credible "fun apps" or "useful apps" that offered capabilities or
> quantitative levels of
> functionality that one could not get otherwise, even if we all
> understood that these were
> just ideas.
>
> Best,
>
> Roger
community of related activities (I am imagining the sacred cord, the
eruv, that the faithful can place at the perimeter of orthodox Jewish
neighborhoods, thus enabling those within the cord to perform certain
activities on the Sabbath)."
ghetto |ˈgetō|
noun ( pl. -tos or -toes)
a part of a city, esp. a slum area, occupied by a minority group or
groups.
Why would you want to allude that "the group of people who call
themselves synthetic biologists" is a slum?
slum |sləm|
noun
a squalid and overcrowded urban street or district inhabited by very
poor people.
• a house or building unfit for human habitation.
(And then you ask for the opinion of this list? That's so bizarre!)
## Jonathan Cline
## jcl...@ieee.org
## Mobile: +1-805-617-0223
########################
Nick Taylor
This post gives me a fairly massive sense of relief tbh - someone actually attempting to address the risk at a systemic level rather than just trying to downplay it.
I think I'd add something to that list... something that Jason's microbial-birdwatching addresses I think - I haven't quite put my finger on it yet, but it's got something to do with an network-based, over-arching awareness of what's going on. Everywhere.
I mean transparency is one thing, but you've still got to have people who can read - and having networks of on-the-ground trend/change-spotters would create a lot of resilience in the system overall - with regards early warnings etc.
That algal bloom up the road from me for example wasn't dealt with until it had gone really toxic and was leaching ammonia everywhere. I think informed bio-citizen-journalists are probably fairly crucial if Craig Ventor's predictions of a Cambrian-era style explosion of species hit anywhere near the truth.
Nick Taylor
> Look, when it comes to the issue of Horrible Pathogens That Will Kill
> Us All, synthetic bio is about the LAST thing I worry about.
> It should tell you something when we know without debate that those
> things are hazardous to life and humanity, and we have the technology
> in hand to fix those things, *yet we don't fix them anyway*.
> I'd suggest that when it comes to making the world safer, we work on
> things we already are sure of, before going off half-cocked on the
> WhatIfs. We got enough problems, let's not go imagining more.
Bryan Bishop
>> http://en.wikipedia.org/wiki/Single_point_of_failure
>>
>> """
>> The strategy to prevent from total systems failure is
>>
>> 1) Reduced Complexity
>> Complex systems shall be designed according to principles decomposing
>> complexity to the required level.
>>
>> 2) Redundancy
>> Redundant systems include a double instance for any critical
>> component with an automatic and robust switch or handle to turn
>> control over to the other well functioning unit (failover)
>>
>> 3) Diversity
>> Diversity design is a special redundancy concept that cares for the
>> doubling of functionality in completely different design setups of
>> components to decrease the probability that redundant components might
>> fail both at the same time under identical conditions.
>>
>> 4) Transparency
>> Whatever systems design will deliver, long term reliability is based
>> on transparent and comprehensive documentation.
>> """
>
> attempting to address the risk at a systemic level rather than just trying
> to downplay it.
Thank you. :-) Strategies for preventing total system failure are
important, and another aspect of it is a constructive or
creation-based approach. Anyway, check out this too:
http://constructal.org/ "According to the Constructal law, every
system is destined to remain imperfect, i.e. with flow resistances.
The natural constructal tendency then is to distribute the
imperfections of the system, and this distribution of imperfection
generates the shape and structure of the system."
http://en.wikipedia.org/wiki/Systemantics
"""
* The Primal Scenario or Basic Datum of Experience: Systems in general
work poorly or not at all. (Complicated systems seldom exceed five
percent efficiency.)
* The Fundamental Theorem: New systems generate new problems.
* The Law of Conservation of Anergy [sic]: The total amount of anergy
in the universe is constant. ("Anergy" = 'human energy')
* Laws of Growth: Systems tend to grow, and as they grow, they encroach.
* The Generalized Uncertainty Principle: Systems display antics.
(Complicated systems produce unexpected outcomes. The total behavior
of large systems cannot be predicted.)
* Le Chatelier's Principle: Complex systems tend to oppose their own
proper function. As systems grow in complexity, they tend to oppose
their stated function.
* Functionary's Falsity: People in systems do not actually do what the
system says they are doing.
* The Operational Fallacy: The system itself does not actually do what
it says it is doing.
* The Fundamental Law of Administrative Workings (F.L.A.W.): Things
are what they are reported to be. The real world is what it is
reported to be. (That is, the system takes as given that things are as
reported, regardless of the true state of affairs.)
* Systems attract systems-people. (For every human system, there is a
type of person adapted to thrive on it or in it.)
* The bigger the system, the narrower and more specialized the
interface with individuals.
* A complex system cannot be "made" to work. It either works or it doesn't.
* A simple system, designed from scratch, sometimes works.
* Some complex systems actually work.
* A complex system that works is invariably found to have evolved from
a simple system that works.
* A complex system designed from scratch never works and cannot be
patched up to make it work. You have to start over, beginning with a
working simple system.
* The Functional Indeterminacy Theorem (F.I.T.): In complex systems,
malfunction and even total non-function may not be detectable for long
periods, if ever.
* The Newtonian Law of Systems Inertia: A system that performs a
certain way will continue to operate in that way regardless of the
need or of changed conditions.
* Systems develop goals of their own the instant they come into being.
* Intrasystem [sic] goals come first.
* The Fundamental Failure-Mode Theorem (F.F.T.): Complex systems
usually operate in failure mode.
* A complex system can fail in an infinite number of ways. (If
anything can go wrong, it will.) (See Murphy's law.)
* The mode of failure of a complex system cannot ordinarily be
predicted from its structure.
* The crucial variables are discovered by accident.
* The larger the system, the greater the probability of unexpected failure.
* "Success" or "Function" in any system may be failure in the larger
or smaller systems to which the system is connected.
* The Fail-Safe Theorem: When a Fail-Safe system fails, it fails by
failing to fail safe.
* Complex systems tend to produce complex responses (not solutions) to problems.
* Great advances are not produced by systems designed to produce great advances.
* The Vector Theory of Systems: Systems run better when designed to
run downhill.
* Loose systems last longer and work better. (Efficient systems are
dangerous to themselves and to others.)
* As systems grow in size, they tend to lose basic functions.
* The larger the system, the less the variety in the product.
* Control of a system is exercised by the element with the greatest
variety of behavioral responses.
* Colossal systems foster colossal errors.
* Choose your systems with care.
"""
> I think I'd add something to that list... something that Jason's
> microbial-birdwatching addresses I think - I haven't quite put my finger on
> it yet, but it's got something to do with an network-based, over-arching
> awareness of what's going on. Everywhere.
That's interesting, could you elaborate some more on this over-arching
awareness?
> I mean transparency is one thing, but you've still got to have people who
> can read - and having networks of on-the-ground trend/change-spotters would
> create a lot of resilience in the system overall - with regards early
> warnings etc.
Neil Gershenfeld has mentioned that there is a new type of literacy,
which largely surpasses the basics of reading/writing and is more in
tune with microcontroller programming, or basic stuffhacking.
"From this combination of passion and inventiveness I began to get a
sense that what these students are really doing is reinventing
literacy. Literacy in the modern sense emerged in the Renaissance as
mastery of the liberal arts. This is liberal in the sense of
liberation, not politically liberal. The trivium and the quadrivium
represented the available means of expression. Since then we've boiled
that down to just reading and writing, but the means have changed
quite a bit since the Renaissance. In a very real sense post-digital
literacy now includes 3D machining and microcontroller programming.
I've even been taking my twins, now 6, in to use MIT's workshops; they
talk about going to MIT to make things they think of rather than going
to a toy store to buy what someone else has designed. The World Bank
is trying to close the digital divide by bringing IT to the masses.
The message coming back for the fab labs is that rather than IT for
the masses the real story is IT development for the masses. Rather
than the digital divide, the real story is that there's a fabrication
and an instrumentation divide. Computing for the rest of the world
only secondarily means browsing the Web; it demands rich means of
input and output to interface computing to their worlds. There was an
amazing moment as I was talking to these Army generals about how the
most profound implication of emerging technology for them might not
lie in designing a better weapon to win a war, but rather in giving
more people something else to do. So we're now at a cusp where
personal fabrication is poised to reinvent literacy in the developed
world, and to engage the intellectual capacity of the rest of the
world."
Roger
Brian requested a reply to some of the thoughtful comments
on this question, and that's more than fair. Right now,
I can't do them justice, so will be brief. Might have done
this better earlier, but will welcome further guidance as
to what might be appropriate etiquette on discussion
forums of this type.
In no particular order.
Am impressed with the many eyes arguments and
of course with the brio and idealism of this community.
We all understand that controls of material and knowledge
here are impossible. I suspect that everybody also would
agree that the spread is a good thing.
The use of the word "ghetto" was, as said, deliberately
intended to provoke. Not the meaning of "slum"
but rather the earlier meaning, but neighborhood
full of weirdly religious people. Who might
for example have run a string
around the boundaries of the neighborhood and
nobody not of the neighborhood can possibly
take the string seriously. I did not mean to be too
sharp. In the essay, however, I did mean to
try to push for intellectually defensible boundaries
(in Europe, the 100s of people making bugs to
make materials call themselves microbial
chemical engineers). And I especially wanted
to see if it was possible to diminish the drumbeat
of false claims of novelty. None of the above
is at issue here in the DIY community.
Would love to talk with people about the security
issues in person on a trip to Boston or wherever.
Am not sure I will be able to participate consistently
in this, but I will try, and am grateful to Brian and others
for past or future pointers for proper behavior.
Roger
>
> read more »
Lora
profoundly, qualitatively different ground.
pathogens definitely replicate. For sure, they acquire fitness from
the selective pressures in their environments (antibiotics, heavy
metals, etc.). I agree that there's a HUGE difference between a
naturally occurring antibiotic-resistant Clostridium that happens to
live in a biofilm in garden soil with Acinetobacter neighbors, vs. a
Clostridium that has specifically adapted to life in a Zithromax-
saturated hospital, and that the latter is much more hazardous, having
already acquired other pathogenic characteristics from its
environment, but I don't see that cloning antibiotic resistance is
necessarily more hazardous or worse than the hospital pathogen
adaptation. If anything, the nosocomial infection adaptations should
be worse--able to acquire Staph toxin genes, already selected for
pathogenicity in humans (as opposed to mice or whatever the Evildoers
are using), already surviving every precaution and treatment humanity
can throw at it in the bestest of medical facilities. Cloning that
sort of thing is technically much more challenging and likely to
result in many disappointing failures.
Well, OK, it's only the Evildoers who would be disappointed. But you
know what I mean.
> >You can persuade humans line up for
> vaccinations. Honey bees not so much.
outbreaks all over the Western world due to that Wakefield fool who
couldn't do math (or immunology, but that's another rant), polio all
over Nigeria and north African countries because of the politics of
the war in Iraq, and so on and so forth.
>
> It's not a question of imagining more, it's a question of making more.
Henrik Schoen, Malcolm Pearce, Thereza Imanishi-Kari, Charles Dawson,
Luk van Parijs, Pons & Fleischmann...?
We've got the Geneva Convention of course, which already forbids
bioweapons, although I hear that's not working out so hot these days
either. I mean, if international treaties don't do the trick, what
other ideas did you have?
I'm sorry you're scared, but honestly, I don't know what to do for
you--I don't see that there's a whole lot more to be done. I already
vote for the "diplomacy first" hippie politicians when I can. I could
make you a nice cup of tea and give you a hug, that's about it.
Nick Taylor
>> I think I'd add something to that list... something that Jason's
>> microbial-birdwatching addresses I think - I haven't quite put my finger on
>> it yet, but it's got something to do with an network-based, over-arching
>> awareness of what's going on. Everywhere.
>
> That's interesting, could you elaborate some more on this over-arching
> awareness?
Something like that. Something akin to the web's extraordinary sensitivity to censorship.
I have a feeling that a type of no-single-person, group-awareness might actually be an emergent behaviour of networks - not everyone can keep their eye on everything that concerns them all the time, so everyone keeps an eye on their little corner of the world... twittering happily to their neighbours... and if something that concerns the whole network crops up, the whole network responds.
George Orwell was at least partly wrong... the surveillance society isn't (generally) a top down thing, it's a bottom up thing. Everyone carries a camera that can upload into the mass-consciousness. Strangely enough, the way our govts (especially the British) seem to be reacting to this network-empowerment is to use 1984 as an instruction manual. Weird.
To (ahem) illustrate: I used to be terrified of being filmed on CCTV drunk out of my mind in Soho, London. Last time I was there I found myself (as you invariably do) singing Lost Highway* in the middle of the road at 4am... being filmed by people with fucking cellphones.
Anyway - the network-response-effect was what I was on about yesterday (in the point-missing that I apparently did) when I said that Obama's campaign was about resilience. When attacked by a hierarchy, the response wasn't hierarchical - instead of saying "oooh, but I'm not a muslim", his entire base responded by donating money.
This is an observation I've pinched from Umair Haque, who's a genius (kindof) and who's blog caused me to blurt "holy crap" and to right there and then read the whole thing from start to finish.
http://discussionleader.hbsp.com/haque/2008/11/obamas_seven_lessons_for_radic.html
http://www.bubblegeneration.com/ (though he's mostly on a Harvard blog now)
So. DIYbbio. What I'd like to do... me, personally... (and this is for Jason if he's listening), is collect algae/pond samples from the various places that I live, microscopically photograph them and upload them to the web, for people who know what they're talking about, to identify... so I can learn how to identify them too.
I also want to do this as an artistic endeavour. I think a series of green circular plates on a website would look cool.
Every node doesn't need to be a smart node in other words - the thing is to crowd-source the collection of data, and in a decoupled sort of way, crowd-source the analysis of it.
There's probably a way of automating this - but it's also a good way of giving people something to do... or to be more specific, of giving people value, within an economic system that's geared to reducing their worth.
Sorry. Long post.
Nick
* http://www.youtube.com/watch?v=2PGTEk2ESCU
You can't make an omelette without breaking a few eggs.
Nick Taylor
re: http://en.wikipedia.org/wiki/Systemantics
My dad would agree with this one:
* Le Chatelier's Principle: Complex systems tend to oppose their own proper function. As systems grow in complexity, they tend to oppose their stated function.
He's a school teacher - and has long held that every new "measure" instituted within the educational system always has the exact opposite effect to the one intended.
I'd add one to that list I think :
* Complexity is the fractaline manifestation of flawed assumptions.
A bit like 80s haircuts etc.
Nick Taylor
> Would love to talk with people about the security
> issues in person on a trip to Boston or wherever.
... we already have these problems and we aren't fixing them now.
I think what needs to happen is that we need to become much better at building resilient ecosystems - we need this regardless of whether 100 million neo-alchemists trying to find the elixir of life (in their potting sheds) are suddenly unleashed upon the world at once. As an aside, I prefer the word "quarantine" to"security". The etymological feng-shui of the word rests a little easier. Security is a state of mind, and is impossible. Quarantine isn't.
Anyway, maybe solving the problems we've got now will go a long way towards solving the ones we create.
Nick
* http://www.aceshowbiz.com/images/news/00016210.jpg
Lora
> I think security is impossible. It's a fear-response, and isn't the issue -
> and as someone (who I can't (dear God, please forgive me) help but picture
> as looking a bit like the clairvoyance one off Harry Potter*) said
> yesterday...
>
> ... we already have these problems and we aren't fixing them now.
>
not far off--picture Professor Trelawney in jeans, a t shirt with a
caffeine molecule on it, and a tweed jacket, and that's about right.
And now, my husband, who is reading this over my shoulder, is
sniggering. Thank you...