Garage Biology Project: Melamine-detection Bugs

Worried about whether your yogurt is safe?  Drop in some of  Meredith Patterson's home-brew bugs and see if they turn green.  The AP has a short story about Patterson and DIYBio: "Amateurs are trying genetic engineering at home".  No surprise that it is a bit short on details.

This story made it as far (temporarily) as the front page of The Huffington Post, which I find interesting.  I wonder whether the editors put it there out of genuine interest or to scare the crap out of their readers.

It's only been eight years since I first speculated about garage biology (PDF), and only three since the topic appeared in Wired (Splice it yourself).  iGEM has only been around since 2004.  Biology, for the most part, remains Open (See, "Thoughts on Open Biology"):

As in 2000, I remain today most interested in maintaining, andenhancing, the ability to innovate.  In particular, I feel that safe and secure innovation is likely to be best achieved through distributed research and through distributed biological manufacturing.  By "Open Biology" I mean access to the tools and skills necessary to participate in that innovation and distributed economy.

I find myself a bit surprised to feel a bit surprised that this is this is all going just as I expected (PDF).  (Aside: if there isn't a name for that, there should be; I predicted X, and not only am I surprised that it is coming true, I am surprised to feel surprised that it is coming true...because I really believed it was going to come true.  I think.)  From the AP story:

[Patterson]  learned about genetic engineering by reading scientific papers and getting tips from online forums. She ordered jellyfish DNA for a green fluorescent protein from a biological supply company for less than $100. And she built her own lab equipment, including a gel electrophoresis chamber, or DNA analyzer, which she constructed for less than $25, versus more than $200 for a low-end off-the-shelf model.

Frankly, I don't know whether to feel relieved or uneasy.  That ambivalence will probably characterize my response to this technology from here on out.  Whether we like it or not, we are about to find out what role garage biology will play in our physical and economic security (Journal article, PDF).

Cheery Reading: "WORLD AT RISK The Report of the Commission on the Prevention of WMD Proliferation and Terrorism"

In case you haven't seen the headlines the lase couple of days, Bob Graham and Jim Talent say we are doomed.  Mostly.  Sort of.  Maybe?

Here is the page to download the report.  In summary, the commission predicts an attack using a weapon of mass destruction with in the next five years.  They are more worried about biological weapons than nuclear ones.

Despite the grim tone of most of the text, here is something useful to squawk back at Chicken Little:

...One should not oversimplify or exaggerate the threat of bioterrorism. Developing a biological weapon that can inflict mass casualties is an intricate undertaking, both technically and operationally complex. 

That is among the more optimistic statements in the entire document.

I caught Bob Graham on the Colbert Report last night, and the interview helped me figure out what has been bugging me about the language used by the report and its authors as they talk to the press.  No, not the part where Graham and Colbert -- two grown men in suit and tie -- used copies of the report like GI Joe figures in desktop combat (see 2:30 -- that brief interlude was enlightening in a different way):

The lightbulb went off when Graham said "The most important thing we can do is make sure that we, and the rest of the world, are locking down all the nuclear and biological material so that it is not capable of leaking into the hands of terrorists."

That sounds great, and the report goes on at length about securing BSL-3 and -4 facilities here in the US so that nasty bugs are kept behind locked doors, doors that are guarded by guys with visible guns.  That constitutes a particular kind of deterrence, which is fine.  As I have spent far too much of my life working in clean rooms trussed up in bunny suits, I can only feel sympathy for the folks who will have to deal with that security and suit up to work in the lab every day.  But those bugs are dangerous, and biosafety in those facilities is no joke.  The near-term threat is undoubtedly from bugs that already exist in labs.

But this is where things start to go off the rails for me.  Graham didn't have a lot of time with Colbert, but his language was disturbingly absolute.  I am concerned the Commission's views on biological technologies aredysfunctionally bipolar.  Here is what I mean: Even though the text of report reassures me that the people who actually put words on the page have a sense of how far and how fast biological technologies are proliferating (which I get to below), the language used by the official spokesman involves "locking down all the biological materials".  I worry that "locking down" anything might be construed in Washington DC, or by the populace, as constituting sufficient security measures.  See my article from last year "Laying the foundations for a bio-economy" for an update on what has happened as a result trying to "lock down" methamphetamine production in the US.  Short summary: There is more meth available on the streets, and the DEA acknowledges that its efforts have created an environment in which it actually has worse intelligence about who is making the drug and how it gets distributed.

Frankly, I haven't quite sorted out all of the things that bother me about the report, the way we talk about security in this country, and the inevitable spread of powerful biological technologies.  What follows are some additional notes and ruminations on the matter.   

Here is what the text of the report has to say about the threat from DNA synthesis technologies:

The only way to rule out the harmful use of advances in biotechnology would be to stifle their beneficial applications as well--and that is not a realistic option. Instead, the dual-use dilemma associated with the revolution in biology must be managed on an ongoing basis. As long as rapid innovations in biological science and the malevolent intentions of terrorists and proliferators continue on trajectories that are likely to intersect sooner or later, the risk that biological weapons pose to humanity must not be minimized or ignored.

Hmm...well, yes.  I'm glad they acknowledge the fact that in order to benefit from the technology it must be developed further, and that security through proscription will retard that innovation.  I am relieved that this part of the report's recommendations do not include measures I believe would be immediately counterproductive.  The authors later write:

The more that sophisticated capabilities, including genetic engineering and gene synthesis, spread around the globe, the greater the potential that terrorists will use them to develop biological weapons. The challenge for U.S. policymakers is to prevent that potential from becoming a reality by keeping dangerous pathogens--and the equipment, technology, and know-how needed to weaponize them--out of the hands of criminals, terrorists, and proliferant states. 

The charge in the last sentence sounds rather infeasible to me.  Anyway, the Commission then puts responsibility for security on the heads of scientists and engineers working in the life sciences: 

The choice is stark. The life sciences community can wait until a catastrophic biological attack occurs before it steps up to its security responsibilities. Or it can act proactively in its own enlightened self-interest, aware that the reaction of the political system to a major bioterrorist event would likely be extreme and even draconian, resulting in significant harm to the scientific enterprise.

...ACTION: The Department of Health and Human Services and Congress should promote a culture of security awareness in the life sciences community.

Members of the life sciences community--universities, medical and veterinary schools, nongovernmental biomedical research institutes, trade associations, and biotechnology and pharmaceutical companies--must foster a bottom-up effort to sensitize researchers to biosecurity issues and concerns. Scientists should understand the ethical imperative to "do no harm," strive to anticipate the potential consequences of their research, and design and conduct experiments in a way that minimizes safety and security risks.

(This bit sounds like the Commission heard from Drew Endy.)

...The currently separate concepts of biosafety and biosecurity should be combined into a unified conceptual framework of laboratory risk management. This framework should be integrated into a program of mandatory education and training for scientists and technicians in the life sciences field, whether they are working in the academy or in industry. Such training should begin with advanced college and graduate students andextend to career scientists. The U.S. government should also fund the development of educational materials and reference manuals on biosafety and biosecurity issues. At the same time, the responsibilities of laboratory biosafety officers should be expanded to include laboratory security and oversight of select agents, and all biosafety officers should be tested and certified by a competent government authority.

The phrase "culture of security awareness" appears frequently.  This creeps me out more than a bit, particularly given our government's recent exhortations to keep an eye on our neighbors.  You never know who might be a sleeper.  Or a sleep-walking bioterrorist.  I make this point not entirely in jest.  Who wants to live in such a paranoid culture?  Particularly when it is not at all clear that such paranoia makes us safer.

To be fair, I called for something not too dissimilar in 2003 in The Pace and Proliferation of Biological Technologies.  It only makes sense to keep an eye out for potential bioterror and bioerror, and we should have some sort of educational framework to make sure that people are aware of the potential hazards as they hack DNA.  But seeing that language in a report from a legislatively-established body makes me start imagining Orwellian propaganda posters on the walls of labs around the country.  Ick.  That is no way to foster communication and innovation.

On a different topic, here is something that opened my eyes. The report contains a story about a Russian -- someone in charge of weighing out uranium for his coworkers -- who was able to continuously steal small amounts of fissile materiel because the scales were officially recognized to be calibrated only to within 3%.  By withholding a little each time, he amassed a stash of 1.6 kg of "90 percent enriched uranium", while the official books showed no missing materiel.  Fortunately the fellow was caught, because while he was a clever thief he was a not-so-clever salesman.  As part of subsequent non-proliferation efforts, the US government paid for more accurate scales in order to prevent another incident of stealing "a bomb's worth of uranium, bit by bit".  Holy shit.

It is nice to hear that this sort of leak has been plugged for the nuclear threat.  I hope our government clearly understands that such plugs are few and far between for biological threats.

Update on Plans for GM Crop Research in Britain

Last year I pointed out the complexities of arguments about GM food through the continuing debate in Europe and the U.K. about animal feed.  The diminishing availability of GM-free feed grain could lead to significant shortages, which in turn could drastically reduce the amount of meat in European markets.  (See "Re-Inventing The Food Chain (or "On Food Prices, In Vitro Meat, and GM Livestock Feed")."

Now the Independent reports that the U.K. is considering protecting GM crop research from domestic protest and attack.  The government may go so far as to bring that research onto defense installations in order to protect it better, as suggested by Andrew Grice in a story provocatively titled "Government to defy critics with secret GM crop trials".

Here is one 'graph from the article:

Professor Tim Benton, research dean at [the Leeds University] Faculty of Biological Science, said yesterday: "We need to find a way to do crop trials in a safe way and to minimise the environmental risk. We cannot carry on for the next 20 or 30 years saying it's too scary, the public is too frightened, it is politically too dangerous. There is absolutely no way we can move towards a world with food security without using GM technology. The amount of food we need could double because the population is growing, climate change will reduce yields and we will take land out of food production for biofuels."

iGEM 2008: Surprise -- The Future is Here Already.

I'm back from a weekend at MIT serving as a judge for the International Genetically Engineered Machines Competition.  Here are a few thoughts on the competition.

The "international" flavor continues to strengthen.  Of the six finalists, three were from the U.S., two from Europe, and one from Asia.  There were 85 teams registered, almost all of whom showed up.  I was hoping for more biofuels/energy projects, but perhaps that fad is already past.

The top three teams were (here are the full results): 1) Slovenia 2) Freiburg 3) Caltech.

First, a couple of slightly blurry iPhotos (when the hell is Apple going to upgrade that camera?):

IMG_0138 Tom Knight receives the BioBrick from the 2007 winner, Peking University.

IMG_0140 A collective dance party while the competitors wait for the judges.

IMG_0141 Tom Knight awards the BioBrick to the 2008 winners, Slovenia.

Several of the 2008 projects implement ideas that have appeared in science fiction stories and in my own speculations about the future of biological technologies:

UCSF characterized a fusion protein that enables epigenetic control of gene expression through chromatin silencing.  This, in effect, gives the user (which could be the cell itself) a new control knob for building memory circuits in eukaryotes.  I seem to recall that this is the basic innovation in Greg Bear's Blood Music that brings about the end of the world through Green Goo.  Go UCSF!

Caltech and NYMU-Taipei (check out the killer Wiki) both modified commensal E. coli strains to serve as therapeutics.  Caltech built a bunch of new functionality into the probiotic strain Nissle 1917, including microbicidal circuits, Vitamin B supplements, and lactase production (big kudos to Christina Smolke, here).  Taipei built a "Bactokidney" for people with kidney failure: cells that attach to the lining of the small intestine and absorb nasty substances that would otherwise need to be removed via dialysis.  These are both very cool ideas.

Seeing these projects brought back shades of a scenario published in Bio-era's "Genome Synthesis and Design Futures: Implications for the U.S. Economy".  (I wrote the original story, which was less complicated but slightly more nefarious than the Bio-era version, in 2005 as a short, provocative piece of a larger report for a TLA -- a three letter agency.)  Almost all the technology described below has been published in bits and pieces -- fortunately, it has not yet been put together in one microbe.

In 2008, the North Korean government launches a secret program to develop biological tools that can be used to pacify target populations for crowd control or military purposes. North Korea's research draws on Soviet work on modifying pathogens to express mood-altering peptides, and the demonstration by U.S. scientists at the National Institutes of Health that common commensal strains of E. coli could be modified to secrete specialized peptides in human intestines.  Modifying the same strain used by the NIH, available in an over-the-counter probiotic pill, the North Koreans secretly produce an organism that produces peptide hormones easily absorbed through the intestinal wall.

With further modifications to allow the peptides to enter the brain, the new strain produces a calming, almost sedative, effect on colonized individuals. Combined with a genetic circuit that confers both antibiotic resistance and upregulation of the peptides upon exposure to a chemical that can be dispersed like teargas, these modifications enable the government to pacify crowds in times of crisis. The E. coli can be distributed via food and water to target populations.

To maintain the presence of the genetic circuit within the population, the new strain is equipped with an antibiotic resistance mechanism from V. cholera that causes plasmids containing the entire genetic circuit, including the regulatory genes and the mood modification genes, to be horizontally transferred to other bacteria upon treatment with common antibiotics.

In 2009, Pyongyang uses military forces to suppress a widening political uprising against the regime. Reports of a "pacifying gas" quickly emerge, raising allegations about the use of chemical weapons. U.S. intelligence agencies claim that North Korea has used a novel combination of biological and chemical weapons against rioters, leading the U.S. to declare that Pyongyang has violated the international treaty on bioweapons. Pacifist biohackers undertake to recreate the microbe , or to invent new versions to use as "peace weapons" against armies.

When a U.S.-led coalition attempts to impose an economic embargo against North Korea, the Chinese government uses its military to secure supply lines to North Korea. A military standoff between U.S. and Chinese forces ensues.

Here is the original inspiration: "Toward a live microbial microbicide for HIV: Commensal bacteria secreting an HIV fusion inhibitor peptide". (I'd completely forgotten that I blogged the original paper.)

Slovenia won (again) with "Immunobricks" by engineering new vaccines. The technology they used forms the basis of arguments about rapid, distributed vaccine production we made in Genome Synthesis and Design Futures (Section 4.3, in particular), which I've also written about extensively here on this blog, and which will show up in my book.  Yet all of a sudden it's real, all the more so because it was an iGEM project.

From Slovenia's Wiki abstract:

Using synthetic biology approaches we managed to assemble functional "immunobricks" into a designer vaccine with a goal to activate both innate and acquired immune response to H. pylori. We successfully developed two forms of such designer vaccines. One was based on modifying H. pylori component (flagellin) such that it can now be recognized by the immune system. The other relied upon linking H. pylori components to certain molecules of the innate immune response (so called Toll-like receptors) to activate and guide H. pylori proteins to relevant compartments within the immune cell causing optimal innate and acquired immune response. Both types of vaccines have been thoroughly characterized in vitro (in test tubes or cells) as well as in vivo (laboratory mice) exhibiting substantial antibody response. Our strategy of both vaccines' design is not limited to H. pylori and can be applied to other pathogens. Additionally, our vaccines can be delivered using simple and inexpensive vaccination routes, which could be suitable also in third world countries.

If you've read this far into the post, you should definitely spend some time on Slovenia's Wiki.

Here's the short, pithy version: There is presently no vaccine for H. pylori.  Between June and October this year, seven undergraduates built and tested three kinds of brand new vaccines against H. pylori.  (They also put a whole mess of Biobrick parts into the Registry, which means those parts are all in the public domain.)

Yes, yes -- it's true, getting something to work in a mouse and in mammalian cell culture is a long way from getting it to work in humans, or even in ferrets.  But the skill level and speed of this work should make everyone sit up and take notice.

So it is worth pondering the broader implications of these projects.

The Slovenian team clearly has access to very high quality labs and protocols.  Mammalian cell culture can be very fiddly unless you know what you are doing and have the right equipment (I speak from painful experience, lo those many years ago in grad school).  The Caltech and Taipei teams also clearly have a great deal of support and mentoring.  Yet while bashing DNA and growing E. coli are not particularly hard, the design and testing of the coli projects is very impressive.

Despite all the support and money evident in the projects, there is absolutely no reason this work could not be done in a garage.  And all of the parts for these projects are now available from the Registry.

Over the past couple of years, in various venues, I have tried to point out both the utility and inevitability of proliferating biological technologies.  iGEM 2008 drives home the point yet again.  In particular, the ability to rapidly create vaccines and biological therapeutics points the way to increased participation by "amateurs", whether the professionals (and policy makers...and security types) are ready or not.  I'm also thinking back to "peer reviews" in which I was excoriated for suggesting this kind of work was within the reach of people with minimal formal training.  Because, really, you need a PhD, and an NIH grant, and tenure, to even think of taking on anything like a synthetic vaccine.  Oh, wait...

Although I've predicted in writing that this sort of thing would happen, I frankly expected practical implementation of both the rapid, synthetic vaccines and the modified commensal bacteria to take a few more years. Yet undergraduates are already building these things as summer projects.

It didn't really hit me until I started writing this post earlier this afternoon, but as I ponder the results from this year's iGEM only one thought comes to mind: "Holy crap -- hold on to your knickers."

The world is changing very, very quickly.

Synthetic Biology 4.0 – Not so live blog, part 1

What a difference a few years makes.  SB 1.0 was mostly a bunch of professors and grad students in a relatively small, stuffy lecture hall at MIT.  SB 2.0 in Berkeley expanded a bit to include a few lawyers, sociologists, and venture capitalists.  (I skipped 3.0 in Zurich.)

At just over 600 attendees, SB 4.0 is more than twice as big as even 3.0, with just under half the roster from Asia.  The venue, at the Hong Kong University of Science and Technology, is absurdly nice, with a view over the ocean that beats even UCSB and UCSD.  Kudos also to the organizers here.  They worked very hard to make sure the meeting came off well, and it is clear they are interested in synthetic biology, and biotech in general, as a long term proposition.  The Finance Minister of Hong Kong, John Tsang, spoke one evening, and he was very clear that HK is planning to put quite a lot of money and effort into biology.

Which brings me to a general observation that Hong Kong really cares about the future, and is investing to bring it along that much sooner.  I arrived a day early in order to acclimate a bit and wander around the city, as my previous visit was somewhat hectic.  Even amid the financial crisis, the city feels more optimistic and energetic than most American cities I visit.

I will have to write up the rest of the meeting when I get back to the States later this week.  But here are a few thoughts:

As of the last few days, I have now seen all the pieces necessary to build a desktop gene printer.  I don’t have prediction when such a thing will arrive on the market, but there is no doubt in my mind that it is technically feasible.  With appropriate resources, I think it would take about 8 weeks to build a prototype.  It is that close.

Ralph Baric continues to do work on SARS that completely scares the shit out of me.  And I am really glad it is getting done, and also that he is the one doing it.  His work clearly demonstrates how real the threat from natural pathogens is, and how poorly prepared we are to deal with it.

Jian Xu, who is better known for his efforts to understand the human gut microbiome, spoke on the soup-to-nuts plant engineering and biofuels effort at the Qingdao Institute of Bioenergy and Bioprocess Technology, run by the Chinese Academy of Sciences (QIBEBT).   The Chinese are serious about putting GM plants into the field and deriving massive amounts of energy from biomass.

Daphne Prauss from Chromatin gave a great talk about artificial chromosomes in plants and how they speed up genetic modification.  I’ll have to understand this a bit better before I write about it.

Zach Serber from Amyris spoke about on their biofuels efforts, and Amyris is on schedule to get aviation fuel, diesel, and biogasoline into the market within the next couple of years.  All three fuels have equivalent or better characteristic as petro-fuels when it comes to vapor pressure, cloud point, cetane number, octane, energy density, etc.

More soon.

"Laying the foundations for a bio-economy"

My new commentary, "Laying the foundations for a bio-economy", will be appearing in a upcoming issue of Systems and Synthetic Biology.  The piece is freely available online as both text and PDF.  Thanks to Springer for supporting the Open Access option.  Here are the abstract, the first two paragraphs, and the last two paragraphs:

Abstract  Biologicaltechnologies are becoming an important part of the economy. Biotechnology already contributes at least 1% of US GDP, with revenues growing as much as 20% annually. The introduction of composable biological parts will enable an engineering discipline similar to the ones that resulted in modern aviation and information technology. As the sophistication of biological engineering increases, it will provide new goods and services at lower costs and higher efficiencies. Broad access to foundational engineering technologies is seen by some as a threat to physical and economic security. However, regulation of access will serve to suppress the innovation required to produce new vaccines and other countermeasures as well as limiting general economic growth.          

Welcome to the Paleobiotic Age. Just as today we look back somewhat wistfully on our quaint Paleolithic--literally "old stone"--ancestors, so will our descendants see the present age as that of "old biology", inhabited by Paleobiotic Man. The technologies we use to manipulate biological systems are experiencing dramatic improvement, and as a result are driving change throughout human economies.       

In order to understand the impact of our growing economic dependence on biological technologies it is worth taking a moment to consider the meaning of economy. "Economy" is variously thought of as, "the management of the resources of a country, especially with a view to its productivity" and "the disposition or regulation of the parts or functions of any organic whole; an organized system or method"  Amid a constantly increasing demand for resources, we look to technology to improve the productivity of labor, to improve the efficiency of industrial process and energy production, and to improve the yield of agriculture. Very tritely, we look to technological innovation within our economy to provide more stuff at lower cost. Biological technologies are increasingly playing that role.

...

In this, the Paleobiotic Age, our society is only just beginning to struggle with all the social and technical questions that arise from a fundamental transformation of the economy. History holds many lessons for those of us involved in creating new tools and new organisms and in trying to safely integrate these new technologies into an already complex socio-economic system. Alas, history also fails to provide examples of any technological system as powerful as rational engineering of biology. We have precious little guidance concerning how our socio-economic system might be changed in the Neobiotic Age to come. We can only attempt to minimize our mistakes and rapidly correct those we and others do make.

The coming bio-economy will be based on fundamentally less expensive and more distributed technologies than those that shaped the course of the 20th Century. Our choices about how to structure the system around biological technologies will determine the pace and effectiveness of innovation. As with the rest of the natural and human built world, the development of this system is decidedly in human hands. To paraphrase Stewart Brand: We are as engineers, and we'd better get good at it in a hurry.          

Thoughts on Open Biology

A story at LinuxDevices last year on a report from the Committee for Economic Development (CED), recommending government use of "open source" and "open research", prompted me to collect the following thoughts on Open Biology.

I've changed the entry in my category list for this blog from "Open Source Biology" to "Open Biology".  Despite unleashing the phrase "Open Source Biology" on the world six years ago, at this point I no longer know what Open Source Biology might be.  Perhaps Drew Endy still has a  useful definition in mind, but as I try to understand how to maintain progress, improve safety, and keep the door open for economic growth, I think the analogy between software and biology just doesn't go far enough.  Biology isn't software, and DNA isn't code.  As I study the historical development of railroads, electricity, aviation, computer hardware, computer software, and of the availability of computation itself (distributed, to desktop, and back to distributed; or ARPANet to Microsoft Office to Google Apps), I am still trying to sort out what lessons can be applied to biological technologies.  I have only limited conclusions about how any such lessons will help us plan for the future of biology.

When I first heard Drew Endy utter the phrase "Open Source Biology", it was within the broader context of living in Berkeley, trying to understand the future of biology as technology, and working in an environment (the then embryonic Molecular Sciences Institute) that encouraged thinking anything was possible.  It was also within the context of Microsoft's domination of the OS market, the general technology boom in the San Francisco Bay area, the skyrocketing cost of drug development coupled to a stagnation of investment return on those dollars, and the obvious gap in our capabilities in designing and building biological systems.  OSB seemed the right strategy to get to where I thought we ought to be in the future, which is to create the ability to tinker effectively,  perhaps someday even to engineer biology, and to employ biology as technology for solving some of the many problems humans face, and that humans have created.

As in 2000, I remain today most interested in maintaining, and enhancing, the ability to innovate.  In particular, I feel that safe and secure innovation is likely to be best achieved through distributed research and through distributed biological manufacturing.  By "Open Biology" I mean access to the tools and skills necessary to participate in that innovation and distributed economy.

"Open source biology" and "open source biotechnology" are catchy phrases, but they have little if any content for the moment.  As various non-profits get up and running (e.g., CAMBIA and the BioBrick Foundation), some of the vagaries will be defined, and at least we will have some structure to talk about and test in the real world.  When there is a real license a la the GPL, or the Lesser License, and when it is finally tested in court we will have some sense of how this will all work out.

I am by no means saying work should stop on OSB, or on figuring out the licenses, just that I don't understand how it fits into helping innovation at the moment.  A great deal of the innovation we need to see will not come from academia or existing corporations, but from people noodling around in their garages or in start-ups yet to be founded.  These are the customers for Biobricks, these are the people who want the ability to build biological systems without needing an NIH grant.

But Drew Endy (Biobricks) and Richard Jefferson (CAMBIA) have as primary customers not corporations, hobbyists, or tinkerers, but large foundations and governments.  The marketplace in which Biobricks and CAMBIA compete for funding values innovation and the promise of changing the world.  At present, they do not derive the majority of their funding from actually selling parts or licenses on the open market, and thus do not rely on sales to fund their work.  Nor should they.  But the rest of our economy operates on exchanges of money for goods and services.  Synthetic Biology will get there some day, too, but the transition is still a bit murky for me.  The Bio-era research report, "Genome Synthesis and Design Futures: Implications for the U.S. Economy", of which I am a co-author, points to the utility of Synthetic Biology and Biobricks in producing biofuels, vaccines, and new materials.  However, the implementation of the new technological framework of genome design, enabled by large scale gene synthesis and composable parts with defined properties, is still in the offing.

Janet Hope has made an initial study of the state of Open Source Biotechnology in her Ph.D. dissertation at Australia National University.  Janet gives the following definition for her project:

"Open Source Biotechnology" refers to the possibility of extending the principles of commerce-friendly, commons-based peer production exemplified by Open Source software development to the development of research tools in biomedical and agricultural biotechnology.

This project examines the feasibility of Open Source Biotechnology in the current industry environment. In particular, it explores:       

1. Whether it would be possible to run a viable biotechnology business on Open Source principles, and

2. What such a business might look like, including the application of specific Open Source-style licences to particular classes of biotechnology research tools.

Janet's book on the subject is due out later this year from Harvard Press.  My book on all of this stuff is, um, not finished.

The CED report  "concludes that openness should be promoted as a matter of public policy, in order to foster innovation and economic growth in the U.S. and world economies."  I think this bit, in particular, is very interesting (quoting from the LinuxDevices story):

  • Open Innovation (such as 'peer production' systems like WikiPedia and eBay user ratings)

    • To foster open innovation, federally funded, non-classified research should be widely disseminated, following the example of the NIH (National Institute of Health)
    • "Any legislation or regulation regarding intellectual property rights [should be] weighed with a presumption against the granting of new rights ... because of the benefits to society of further innovation through greater access to technology."
    • The NSF (National Science Foundation) should fund research into "alternative compensation methods, similar to those created to facilitate the growth of radio, to reward creators of digital information products"

The first point is a bit off, since most NIH sponsored research, as a practical matter, available only through subscriptions to the journals in which it is published.  This will slowly get fixed, however, with increasing publication via the Public Library of Science and similar efforts.  The second point, embodied in patent reform, will probably take forever and will be hobbled by vested interests.  The third may not produce useful results for many years.

So here we sit, needing much fast innovation in biological technologies in order to produce carbon neutral fuels, improve human health, and deal with emerging threats such as SARS and pandemic influenza.  Open Biology is part of that, somehow, but I still don't see a clear path to implementing the ideas within the context of the real economic system we live in every day.

The Costs of Complying with Open Source

The International Herald Tribune has a story by Kevin O'Brien on the costs associated with open source software, "In open source, an unexpected trap".  The future of Open Source Biology will include similar costs.

The article relates several episodes in which companies have included open source code in products without then publishing the resulting code appropriately as dictated by the relevant license.  These infractions have resulted in efforts by coders to push for compliance, and also spawned a new market segment for services that screen for open source code in commercial products.  Palamida, for example, provides code due diligence for a fee.

This is another example of the interesting legal and practical landscapes created by open innovation.  The main message of the O'Brien article for me is that open source continues to be a way for companies to reduce development costs.  And this requires figuring out ways to use open source code effectively, intelligently, and legally.  If code created by the masses is close enough to a solution required by Cisco, Intel, or IBM, it seems the Fortune 500 has no difficulty justifying the use of technology that results from open innovation.  Open source doesn't seem to be killing off traditional companies, as claimed by some large organizations; instead, it's helping the companies that adapt to thrive.  The use of the open source code to reduce costs, and the existence of Palamida, suggest the market is providing the solutions to make open source work.

And if the strategy works for electrons, why not for molecules?  If it works for hardware, why not wetware?  Most relevant to the IHT article, I wonder about verifying compliance with biological versions of open source licenses.  There will obviously be companies spun up to analyze the contents of molecular systems -- genomes, proteomes, in vitro enzymatic cocktails -- just as compliance has become an issue for software companies.

This gets one thinking a bit deeper about the challenges of ensuring compliance.  I suspect open source wetware is like open source hardware, in that compliance probably requires a suite of physical tools that enable one to pick apart the molecular contents of a system unambiguously.  I wrote a few days ago about Intel's Sun's release of the Verilog code for the UltraSPARC T1 chip under and open source license; how are they going to police all the chips out there to make sure some of their code isn't used by a competitor?  Or even in a chip that is used for something else entirely?  If the code for the offending chip isn't published, you would have to subject the chip to all sorts of tests, from running test vectors on the chip to sticking the thing under an electron microscope to directly examine the architecture.

Similarly, looking under the hood of a synthetic biological system to check for open source license compliance will require identifying physical objects and proving their use either is consistent or conflicts with the terms of the license.  Another motivation for better biological test and measurement gear.

If Palamida exists primarily because big corporations don't want to get sued, then I wonder if a biological version -- a service company, say -- can assemble the appropriate tools based on funding from big corporations that want to ensure they are complying with Open Source Biology licenses.  Plus user fees from inventors and developers trying to ensure they get paid?  Interesting.