Article: "Evolution machine: Genetic engineering on fast forward

[Giovanni Lostumbo]

http://www.newscientist.com/article/mg21028181.700-evolution-machine-genetic-engineering-on-fast-forward.html?full=true

[JonathanCline]

On Jul 2, 12:15 pm, Giovanni Lostumbo <giovanni.lostu...@gmail.com>
wrote:
> http://www.newscientist.com/article/mg21028181.700-evolution-machine-...


"Church calls this bold approach multiplex automated genome
engineering, or MAGE."

He also mentioned to me at SB5 that a MAGE device isn't worth
building; to paraphrase: 'it doesn't get much use in the lab, it
mostly sits idle.'
The conclusion is that non-researchers are better off ordering
standardized biological parts (ala BIOFAB) and combining them
rather than performing synthesis directly, or using some
combination of standard assembly techniques.
At least that was my understanding of Church's comments.

--
## Jonathan Cline
## jcl...@ieee.org
## Mobile: +1-805-617-0223
########################

[John Griessen]

On 07/08/11 19:07, JonathanCline wrote:
> The conclusion is that non-researchers are better off ordering
> standardized biological parts (ala BIOFAB) and combining them
> rather than performing synthesis directly, or using some
> combination of standard assembly techniques.
> At least that was my understanding of Church's comments.

Could you still get enough freedom of choice to discover anything
that way?

John

[JonathanCline]

That is what I wonder. I guess the assumption is that the
productivity (=results/(cost+time)) is still better.

Personally it would be a great branch of DIY to engineer plants
for enhanced taste. Currently plants are ag-engineered for
fastest ripening and longest shelf life, which is at the expense
of taste. This harkens to the demonstration of the MAGE device
which evolved the tomato for more redness.

[Phil]

From the Dec. 15 Science:

"Some experts are worried not so much about academic and company
synthetic biologists but about amateurs tinkering in their garages.
Harvard University's George Church told the bioethics panel that these
"do-it-yourselfers" should be licensed and surveilled."

So, we're dangerous and should be surveilled - but it's okay for
George to mix up 15 billion random new strains of E. coli?

[Cathal Garvey]

Yea, that stung. Harsh, George. Harsh.

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[General Oya]

Nothing new from George, there. He pretty much took that position during the discussions with the Presidential Commission last year.
What do you expect from the antiquated academics?

Ryan

[Cathal Garvey]

It's really sad to see genuine cognitive power trapped by a small mind.

letters.cunningprojects.com
twitter.com/onetruecathal
http://www.indiebiotech.com

[george church]

Note that the Dec 15 Science did not quote me. To be clear, I have
recommended (consistently since 2004) that anyone practicing synthetic
biology (academics, companies, DIY) be equally surveilled -- including
my own lab. My analogy is with licenses for driving cars. Just about
anyone can get one and everyone on the road is subject to surveillance
of speed limits, DUI, etc. I am a big fan and supporter of DIYbio.

On Jul 9, 4:13 pm, Phil <philgo...@gmail.com> wrote:
> From the Dec. 15 Science:
>
> "Some experts are worried not so much about academic and company
> synthetic biologists but about amateurs tinkering in their garages.

> Harvard University's GeorgeChurchtold the bioethics panel that these

[Cathal Garvey]

Ah, then I owe you an apology. Sorry, the material I had seen suggested a double standard against amateurs.

Personally I'm open to the idea of a carefully done licensing system, as long as it's accessible to all and permits certain safe experiments for beginners without a license. Sadly I'm not sure that's possible without damage due to implementation concerns..

Ireland's law superficially looks like the above, but it's being crippled by the agency responsible for enforcing it so that it's very forbidding to science. They "interpret" the unambiguous text so that all the reasonable exemptions are impossible to use, abuse the system for extending the application response deadline, and won't consider the 50% discount that's part of the text for low-capital applicants.

Really sad for us in Ireland, it makes DIY synbio very challenging, and it's cost me months of wasted time and 250 euro. And we're among the less science-hating countries in Europe.. If my experience of a SynBio license hadn't been such an ordeal, I'd agree with you more. Implementation of a great law by a disinterested agency can lead to crippling pressure on DIYs, startups and nonprofits.

On 14 Jul 2011 21:41, "george church" <geoc...@gmail.com> wrote:

[Meredith L. Patterson]

On Fri, Jul 15, 2011 at 11:13 AM, Cathal Garvey <cathal...@gmail.com> wrote:

Really sad for us in Ireland, it makes DIY synbio very challenging, and it's cost me months of wasted time and 250 euro. And we're among the less science-hating countries in Europe.. If my experience of a SynBio license hadn't been such an ordeal, I'd agree with you more. Implementation of a great law by a disinterested agency can lead to crippling pressure on DIYs, startups and nonprofits.

Furthermore, variations in legal standards among nation-level actors historically produce a race to the bottom in terms of protection of individual freedom, usually motivated by actors with a fiscal interest in curtailing those freedoms. We're seeing this already with the proliferation of "three strikes" Internet laws (thanks, France). 

We already have perfectly good biosafety guidelines for pathogens; the question of whether synthetic biology requires extra regulation is still open, and it's going to take a lot of work and PR on our part to ensure that any regulations that do emerge aren't preferential toward large labs like George's but exclusionary toward amateurs. Nothing against you personally, George -- but your lab is a hell of a lot better funded and staffed than my basement or Cathal's attic. A major lab can task some poor bastard with all the compliance paperwork. We can't.

--mlp

[Cathal Garvey]

FYI, I'm not in an attic anymore! :) I'm in a spare bedroom, retrofitted with a proper MDF lab bench. Less hazard of falling through the hatch in the floor, and more space to work with. Also, I don't have to have a HEPA-rated air purifier on all the time to keep the air clear..

Although the attic had a certain rustic charm. I'd call it an "underground" charm but it's sort of contradictory.

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[george church]

Great points. I'll lobby internationally for very low costs and
complexity for synbio licenses especially DIYbio (same standards and
surveillance as everyone else). DIYbio could save us some day (and
someone untrained/unlicensed could hurt us).

On Jul 15, 6:15 am, "Meredith L. Patterson" <clonea...@gmail.com>
wrote:

[Ashley Heath]

Watching the "licensing" discussion with interest, and definitely from a no government intervention perspective. But the thought arises, how is synbio defined exactly, in order to apply this licensing idea? If I run a simple PCR reaction at home I suppose it is not synbio. But if I pop the product into a plasmid, then it is?

[Cathal Garvey]

In Ireland, recombinant technology is unregulated but transgenics is. So hack DNA all you like but if you want to out it into a cell, you need a license.

There is a specific exemption for cases where the DNA comes from the species originally. The reasoning is that you're not adding any new new DNA just new context. However, I specifically designed my plasmid to fit that exemption, only to be told I'd need a license.

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[Ronin]

Georgie Churchie the Wyssy guy

Dissed the BioHackers and made us cry

When the boys came out to play,

Georgie Churchie did not run away!

You don't tug on Superman's cape

You don't spit into the wind

You don't pull the mask off the old Lone Ranger

And you don't mess around with Churchie.

Sent from my iPhone

[Arthur Kuan]

+1 

[Simon Quellen Field]

How far does the car license analogy go?

I don't need a license to drive on my own property.

I don't need a license to operate farm equipment.

Amateur radio operators need a license to use certain frequencies and

wattages, but there are Part 15 regulations that allow unlicensed operation

on open frequencies with realistic but limited power. Those regulations led

to things like WiFi that have changed the way we work and communicate.

Are there kinds of DIYBio research (or play) that you would see regulated

in a similar fashion?

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[Phil]

On Jul 14, 4:30 pm, george church <geochu...@gmail.com> wrote:
> Note that the Dec 15 Science did not quote me. To be clear, I have
> recommended (consistently since 2004) that anyone practicing synthetic
> biology (academics, companies, DIY) be equally surveilled -- including
> my own lab. My analogy is with licenses for driving cars.  Just about
> anyone can get one and everyone on the road is subject to surveillance
> of speed limits, DUI, etc.  I am a big fan and supporter of DIYbio.

Dr. Church, I respect your many achievements a great deal.
The problem I have here is that I think that running your
high-throughput evolution machine, on E. coli of all things,
is more dangerous than a hundred thousand unlicensed DIY labs.
It is scientifically interesting, and it's probably worth
the risk to do it, since E. coli is already doing basically
the same thing on its own in my gut right now anyway.
But the risk of generating billions of randomly-mutated
variants of E. coli is many orders of magnitude greater
than the risk from a DIY lab, where doing just one such
mutation and selection would take an entire day.

When you say regulation is like licenses for cars,
that sounds like applying a simple rule,
rather than doing a cost-benefit analysis.
There's a great cost asymmetry here
that doesn't exist in the case of cars.
Being licensed and monitored isn't a big additional burden on your
lab;
you probably already have people on staff whose job
is to comply with government regulation.
And you can afford to buy whatever facilities and
equipment and reagents the regulations stipulate should be used.

So, I would say your analogy would be more
appropriate if we had a situation where only
large corporations had cars, which were already
under so many regulations that every car
had a chauffeur whose only purpose
was to ensure compliance with the regulations;
and the government asked the large corporations'
advice on how to bring individuals and small
corporations who also wanted cars
into the regulatory system.

(The main impact of regulation would be to
discourage hobbyists and start-ups.
So I would rather debate the question,
Would increasing the number of hobbyists
be helpful, or harmful, to existing laboratories
and corporations? Because I think that if
everyone were convinced that having more
hobbyists would benefit them, rather than just
provide more competition, regulating them would
be less appealing. If, for instance, there were
a good way to farm work out to hobbyists the way
we farm it out to grad students, it could be very helpful.)

[Patrik]

If we agree for a moment that there should be licensing and
regulations at a very minimum for work on human pathogens etc. - then
the question becomes: where should we draw the line for what type of
work does and does not require such a license for DIYbio?

If we show some kids at MakerFaire how to extract DNA from a
strawberry, we obviously shouldn't have to require a DIYBio license
for them. How about for typing one of your own genes? Inserting GFP
into E.coli? The average iGEM experiments?

What are the criteria we should use to determine where to draw the
line? Transgenics might be fairly rational boundary. After all, if
you know how to insert GFP into E.coli, you also know how to insert a
toxin gene into E.coli. Of course, that would put the "Hello World" of
synthetic biology out of reach of anyone without a license.

We'd also need to define more clearly what settings DIYBio
encompasses. Obviously, learning some of these techniques as part of a
degree wouldn't fall under DIYBio. How about a class at a community
college? How about a class at a hackerspace? How about showing your
friend how to do it in your basement? Do we need a separate teacher's
license to allow you to supervise nonlicensed people doing DIYbio, or
would that be included in the standard DIYBio license?

[lianchao han]

I am afraid that I don't agree with Dr. Church's driver license analogy. The licensed drivers kill about 50,000 each year in America. More importantly, this idea assumes that synthetic biology is fundamentally more harmful than any other sciences. by requiring licenses for practicing synthetic biology it singles this field out . Why not require a license for a computer scientist who could potentially hack into and disable a national power grid, or an economist who puts forward a risk formula that creates an enormous financial crisis for that matter. Besides who's there to decide the qualifications of synthetic biology practitioners. My view is, a license requirement will damper the movement rather than advance it at this early stage.

A better way to self-regulate the field is a transparent community. Everyone knows what everyone else has in his or her refrigerators and what projects he or she is working on through an open community registration process.    

[Tom Randall]

> Really sad for us in Ireland, it makes DIY synbio very challenging, and it's
> cost me months of wasted time and 250 euro. And we're among the less
> science-hating countries in Europe.. If my experience of a SynBio license
> hadn't been such an ordeal, I'd agree with you more. Implementation of a
> great law by a disinterested agency can lead to crippling pressure on DIYs,
> startups and nonprofits.

At least you finally did get a license, that is a good precedent.

[Matt DiLeo]

I think that's a good point to keep in mind, Lianchao.

I don't know if there's every been demonstrable harm arising from
genetic engineering, but there CERTAINLY has from programming/hacking
and no one's trying (or thinks it's possible!) to control programming
with licenses. The analogy is particularly apt as programs also self-
replicate with unexpected consequences...

We should also keep in mind that humans, pathogens and other creatures
have been evolving for millions and millions of years. It's not a
trivial thing to create a new organism/pathogen that can outperform
existing ones. Yeah, it may be straightforward to resurrect small pox
or polio, but despite huge investments from state and non-state
entities, biological warfare has almost never been successful. It
grabs a lot of headlines to suggest some garage malcontent is going to
unleash a plague on the world but it's really very hard to grow and
distribute microbes in a way that they do what you intend. There's a
reason why governments, warlords and terrorists (even in 2011) still
rely on very old fashioned bullets, explosives and intimidation.

[Matt DiLeo]

I don't see a problem - there are no shortage of companies that will
synthesize any DNA sequence you want cheaper than you can make (or
often clone) them yourself (and these capabilities will on increase).
If you were building a motorcycle, you'd use cheap, effective
standardized parts as much as you could - then you'd machine (or
outsource) novel parts as required.

I wouldn't worry about your ability to discover or create something
new - all science and engineering are derivative.

[Bryan Bishop]

On Fri, Jul 15, 2011 at 9:15 AM, george church wrote:

Great points.  I'll lobby internationally for very low costs and
complexity for synbio licenses especially DIYbio (same standards and
surveillance as everyone else).  DIYbio could save us some day (and
someone untrained/unlicensed could hurt us).

I don't remember the formal name for this phenomenon (like "Streissand effect"), but "when you outlaw something, only the outlaws will have that something". Of course, outlawing is only an extreme type of regulation. But the effects of regulation are the same: when you regulate something, you're largely focusing on those who choose to abide by the regulations and not those who choose to avoid them (which are presumably the people you are concerned about).

Okay, so I bet your next step would be then to come up with regulatory incentives to convince people to opt-in to regulation, like hefty fines, criminal law, etc. But that still won't get what you're desiring, since biohackers won't submit to negative incentives. If you're willing to go all the way to making negative incentives, what about positive incentives instead? For instance, amateur biology licensing would provide net benefits like tax breaks, "first responder oops sorry i told local hazmat that you are a terrorist" insurance, government grants, etc.

As it is right now, anonymous biohackers have very little to gain from going public (like affiliating themselves with DIYbio), and everything to lose because of people's urges for negative/coercive regulation. But by an incentive-based framework you could not only attract biohackers but you could entice them to be involved in a positive community and work on projects in a safe, secure, sane manner. The alternative, of being required/coerced into being licensed to be allowed to make, play, create-- all natural human activities- gives me the creeps. This is a group primarily interested in expressing, promoting and protecting our biological tendency to experiment, engineer and build. Hopefully this isn't surprising to anyone.

We've been having these discussions for years now, and there's tons of good threads in the archives. Anyone who sincerely believes in strongly regulating or licensing amateurized, anonymized, non-institutionalized biohacking should read this history of our discussion and thoughts on these topics. There's certainly no universal opinion on these topics, although I'd argue that us biohackers do have opinions that align more often than not. I'd also like to point out that nobody has done a comprehensive survey of our past discussions on this topic, in case anyone jumps for joy at the idea of sorting through thousands of emails. Ahem..

What's also interesting is that the cypherpunks proved that cryptography and anonymization works (in the social sense; we already had theoretical proofs of validity); so if biohackers get scared off, we'll just go do our own thing and won't be stoppable anyway. So that's cool... but I don't think anyone has the intention of spawning an international crypto-biopunk trend.

- Bryan
http://heybryan.org/
1 512 203 0507

[Patrik]

On Jul 16, 10:01 am, Bryan Bishop <kanz...@gmail.com> wrote:
>
> Okay, so I bet your next step would be then to come up with regulatory
> incentives to convince people to opt-in to regulation, like hefty fines,
> criminal law, etc. But that still won't get what you're desiring, since
> biohackers won't submit to negative incentives. If you're willing to go all
> the way to making negative incentives, what about positive incentives
> instead?

One obvious positive incentive would be to get access to commercial
suppliers, DNA synthesis services, etc. As Cathal and others can
testify, most companies right now don't want to sell to individuals,
because they just don't want to deal with the legal headache if
something were to go wrong (and frankly, because it's not a big enough
market segment for them to care about). However, if there were a
formal DIYBio license that also provided some legal guarantees for the
suppliers, I'm sure that would change. Heck, maybe some of the
suppliers might throw in an academic discount.

Other incentives could include some small innovation grants from NSF,
NIH, or DARPA - a million dollars doesn't go very far at a national
lab, but split that into 100 $10K grants to amateur scientists, and
you might get something exciting.

[Simon Quellen Field]

A driver's license does not guarantee that the driver will operate the car properly.

An amateur radio license does not guarantee the radio operator will obey the rules.

These licenses do two things. They require that the licensee pass a test about

the rules, so they can be presumed to know the rules (laws). And they give the

government something to take away if the laws are not obeyed.

The driving laws are policed by traffic officers, who watch for violations on the public

highways. The amateur radio laws are policed by the FCC, but more often by the

other amateurs, who watch for violations on the public airwaves.

What is missing from an amateur genetic engineering license are the laws themselves,

the test for knowledge of the laws, a public arena in which the actions of the licensees

are visible, and a policing body, or at least someone who watches the amateurs and

reports violations.

People operating in their basements are not as visible as people driving poorly on

public highways, or people interfering with communications on the public airwaves.

What might be similar to a public arena is the purchase of genes from a supplier.

But this looks more like a prescription drug model than a driver's license model.

Do we want to require genetic engineers to have doctoral degrees and the equivalent

of a medical license? That would definitely force the movement underground, and

slow the momentum of amateur discoveries and inventions.

But if we had a handbook of rules, and a test that showed we knew the rules, and that

got us a license to buy genes, devices, cultures, etc. from suppliers, and the license came

with an invitation for a government inspector to visit our home labs at any time, and could

be revoked by that inspector, would that satisfy the people who think I am dangerous?

We can build the handbook ourselves. We can set up a web page that issues the test,

and a public key signing protocol that gives some assurance that we are who we say we

are when we order something, and when we interact with authorities. The first authorities

could be Stanford, Harvard, and MIT, just as an example.

Once we have that infrastructure in place, suppliers can voluntarily use it, and governments

can use it as a model. We don't need to wait for laws to be passed. In fact, if we wait, the

laws that are passed will likely not be to our liking.

-----

Get a free science project every week! "http://scitoys.com/newsletter.html"

[JonathanCline]

BTW

There is a solid 1-hour podcast-interview with
George Church here:

"An Hour with Dr. George Church, Harvard Medical School"
http://mendelspod.com/podcast

[julie.e....@gmail.com]

I just wanted to point out here that although this technology allows one to apply elements of randomness, one would typically apply them in a very targeted way. Overall there are misconceptions about genetic engineering by the general populace that perhaps individuals in DIYbio can help to clear up. One of these misconceptions is that one instance of genetic engineering, even a manipulation as simple as adding gfp is likely to create a cancer causing agent, grey goo, or Frankenstein. The reality is that this doesn't happen (otherwise you would read in you local paper about the large annual death tolls of practicing biologists at your local university--complete with images of sobbing parents and quotes like "we told her not to work in a biology lab.") For reference, take a look at the original MAGE paper, where the randomness is being applied, and try to estimate the probability that the specific manipulations described in the paper will create a bug that will kill you.

Now, however, imagine someone using this technology for evil by applying it to genetic circuit that has been designed to harm humans. It is possible that such a venture could succeed, but note that harmful intent is a characteristic of the second situation.

Individuals can use all manner of technologies to kill other people from cars to chemicals to electricity. However, on a given day most people do not use these technologies for intentional harm. Creating transparent systems to allow synthetic biology, while making it easier to observe and eliminate harmful may make it possible that the field can benefit from the contributions of DIYbiologists while minimizing risks generated by both that community and individuals in ordinary labs (though the risk there seems to be small using historical measures--much, much lower than inadvertent driver error.).

On the other hand, the rise of antibiotic resistant bacteria is a real problem, basically because we are selecting bacteria that can outwit our best defenses and potentially kill us. The selection factor here isn't typically scientists inadvertently creating grey goo, but rather the more pedestrian problems of overprescribed antibiotics and individuals who fail to take them in the prescribed fashion.

Sent from my iPhone

[Patrik]

On Jul 16, 4:25 pm, Simon Quellen Field <sfi...@scitoys.com> wrote:
> But if we had a handbook of rules, and a test that showed we knew the rules,
> and that got us a license to buy genes, devices, cultures, etc. from suppliers,
> and the license came with an invitation for a government inspector to visit
> our home labs at any time, and could be revoked by that inspector, would
> that satisfy the people who think I am dangerous?

Yes, I think that would go very far towards satisfying those
concerned. We will never be able to satisfy all the paranoiacs, but I
think the rational majority will be satisfied with a show of good
faith.

I don't think we even need the government inspector, although checks
by a trusted authority may indeed be needed to allow for some
independent verification. I think this could be a faculty member at a
local university though. As long as we're talking about imposing some
rules upon ourselves, no need to make them more onerous than
necessary.

I love the idea of having some distributed, self-governing licensing
authority. As long as we keep everything as transparent and verifiable
as possible, there may be no need to get any government officials at
all.

[Cathal Garvey]

At the European coding workshop we discussed peer-to-peer validation and inspections. I.e. the Manchester DIYbioers might travel to London Hackerspace or BiologiGaragen to check out their space, run a safety checklist, and offer specifically tailored advice on areas that could be improved. If each major DIYbio lab, whether individual or community, were able to give their own individual "Stamp of approval" according to community approved guidelines, perhaps coupled with individual additions, it would have two effects:
1) It would help generate a web-of-trust, because any given diybioer could boast safety validation from X established members, and there would be a reciprocal social pressure not to tarnish those validations by disrespecting the safety and ethics they represent;
2) It would help draw the community together in realspace by offering a social frame that justifies and endorses visits.

If you then assert that two validations equals "license" and push the idea to cagey suppliers, you have an incentive for a system that's not even negative to begin with.

[Cathal Garvey]

The proactive way to end that email would be a general offer;

If anyone does want me to give their lab a gym badge, I'd be happy to help provided I could afford to reach them. Also, not for the next three months until my role as a father is realised and well established.

Towards having a set of criteria, I'll draw up a checklist that'll cover the draft code, general biosafety and general Bioethics. It won't cover legalities of biohacking because I'm not a "Competent Authority" in the EU jargon, but I'll happily offer an audit within my understanding of the EU directive and my experience of procuring a license.

[Matt DiLeo]

RE: regulation

In the US it costs MILLIONS of dollars and typically takes 10 years
for a (very well prepared + professional) organization to get
regulatory approval for a new GM crop (not including the costs of
inventing and validating the new crop).

So only giant multinational chemical companies can afford to play (and
only can justify the expense for huge market industrial traits).

And then everyone complains that they have a "monopoly" on genetic
engineering and that GMOs aren't helping Africa.

> - Bryanhttp://heybryan.org/
> 1 512 203 0507

[General Oya]

I wonder what palms get greased to release crappy products like the "Eat this ad" campaign, I was hearing about on NPR Marketplace 2 months ago. Apparently they've utilized synbio to create thermophilic bacterium that paint heat reactive ads onto YOUR FOOD. So that a prepressed hamburger lights up while you grill it, with a lil Mr. Pickle waving. Or even the use of bacteriophage bioplastics that are sprayed onto deli meats to keep them from being exposed to the air.
Seems like the commercial realm could use a whole lot more policing to me.

Ryan

[General Oya]

http://marketplace.publicradio.org/display/web/2011/04/01/pm-firms-cash-in-on-edible-advertising/

http://www.intralytix.com/

Ryan

[Matt DiLeo]

Let me quote the last line of your citation for you:

"RYSSDAL: Crazy story, huh? What's the date today?

*This is our April Fool's Day story."


NPR tricks me EVERY april 4th ;)

On Jul 17, 10:26 am, General Oya <general...@gmail.com> wrote:
> I wonder what palms get greased to release crappy products like the "Eat
> this ad" campaign, I was hearing about on NPR Marketplace 2 months ago.
> Apparently they've utilized synbio to create thermophilic bacterium that
> paint heat reactive ads onto YOUR FOOD. So that a prepressed hamburger
> lights up while you grill it, with a lil Mr. Pickle waving. Or even the use
> of bacteriophage bioplastics that are sprayed onto deli meats to keep them
> from being exposed to the air.
> Seems like the commercial realm could use a whole lot more policing to me.
>
> Ryan

[General Oya]

No sh*t. When I googled it, at least 4 or 5 other places were quoting it online, but I must have headed into work before they announced that. Thanks for the clarification.

Ryan