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).

"Saltwater Crops May Be Key To Solving Earth's Land Crunch"

Wired News is carrying a story by Alexis Madrigal on saltwater agriculture, focusing on a new Perspectives piece in Science by Jelte Rozema and Timothy Flowers.  Here is the opening paragraph from the Science piece, which contains some good numbers:

Currently, humans use about half of the fresh water readily available to them to support a growing world population [expected to be 9.3 billion by 2050]. Agriculture has to compete with domestic and industrial uses for this fresh water. Good-quality water is rapidly becoming a limited and expensive resource. However, although only about 1% of the water on Earth is fresh, there is an equivalent supply of brackish water (1%) and a vast quantity of seawater (98%). It is time to explore the agronomic use of these resources.

The authors go on to explore the many advantages, including 1) local agriculture (near coastal populations), 2) irrigation using seawater (yummy micronutrients as fertilizer), and 3) the utility of combined aquaculture practices.  The usual caveats about land use, local property rights, and environmental effects all apply.  But the numbers, at the depth presented, are impressive.

Here is a nice bit from Madrigal's story:

After taking into account environmental protections and other factors, [Robert] Glenn's report estimates that 480,000 square miles of unused land around the world could be used to grow a special set of salt-tolerant plants -- halophytes. Glenn's team calculated that this could produce 1.5 billion barrels of oil equivalent per year. That's 35 percent of the United States' liquid fuel needs.

Why aren't we already employing salt-tolerant plants to produce food and fuel?  Back to Rozema and Flowers:

...Although between 1996 and 2006 there were more than 30 reports of transformation of rice with different genes aimed at increasing salt tolerance, transgenic salt-tolerant rice is not close to release. The likely explanation is that salt tolerance is a complex trait determined by many different genes, so that transformation of multiple genes into a plant is required.

Wandering down this road a bit led me to Pamela Ronald's blog "Tomorrow's Table", one entry of which is up at the Nature Network and mentions local research in Bangladesh to create GM, salt-tolerant rice.  On a visit to Dhaka university, she explains the local imperative:

...Salinity is a problem for rice farmers here. Not only is the sea water rising, but fresh water supplies are under pressure partly because farmers are pumping more every year and also because Bangladesh is downstream from India, who gets first dibs on the fresh water through a network of dams. The result is that every year the saline lands encroach north, hurting rice yields, a serious problem here where the average Bengali receives 2/3 of their diet from rice.

The local research effort is proceeding both via breeding and genetic engineering.  Ronald writes of seeing "...Newly developed transgenic lines thriving under high salt concentrations that kill the conventional variety".  This is interesting both because the Bangladeshi team may be making progress and because a local team has taken on the task -- the country isn't going to be on any conventional list of biotech leaders.  So kudos to the local team.

What could we do to make this all go faster?  The story on salt-tolerance appears to be that it isn't yet a very well understood trait.  This means anyone interested in hacking plants to that end needs to have all the relevant genes and also a good way to get them into any given plant.

My guess is that this is going to start going a lot faster in systems where minichromosomes are up and running in plants of interest.  This will dramatically facilitate the insertion of genes into plants, without worrying about disrupting the endogenous genetic structure. I mentioned this in my post on SB 4.0, and just as a pointer here is the PLoS Genetics describing the creation of stably inheritable minichromosomes in Maize: "Meiotic Transmission of an In Vitro-Assembled Autonomous Maize Minichromosome".  Chromatin appears to have this technology working pretty well.  Recapitulating the work in rice and other crops will take time, of course, but my scrawled notes from Daphne Preuss' talk in Hong Kong suggest it went pretty fast in Maize once they figured out what they were doing.  I'll have more on this when I understand it better.

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 Colbert ReportMon - Thurs 11:30pm / 10:30c

Pakistani Threat - Bob Graham

Colbert at Christmas
Colbert Christmas DVD

Green Screen
Bill O'Reilly Interview

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.

"Tracking the spread of biological technologies"

I have an editorial in the Bulletin of the Atomic Scientists dated 21 November, 2008 (Open Access).

Regular readers will recall that I do not see that history provides useful examples of effective regulation of distributed technologies.  Here are the final 'graphs from the editorial:

The counterargument typically relies on inspiring fear and encouraging proactivity. We cannot wait for perfect policy to implement security measures, the thinking goes. Yet this argument obscures the investigation and debate that must come first: Is it at all possible to slow down the actions of potential aggressors? Will regulation increase knowledge of threats or further obscure them? Finally, will these efforts, whether successful or not, also retard crucial research required to produce countermeasures for both natural and artificial threats?

Most proponents of regulation have not addressed these questions. Greater knowledge of potential threats is clearly desirable. Reducing the threat from bioerror and bioterror is an even more important goal. Formulating effective policy requires acknowledging the pace and proliferation of biological technologies as well as carefully weighing any potential negative impacts of action.

Judith Miller on Bioterrorism Preparedness

Judith Miller has a piece in the recent edition of City Journal carrying the title, "Bioterrorism's Deadly Math".  Her perspective is that after many years and billions of dollars, the U.S. remains quite vulnerable to attack.

Here is one interesting bit that stands out as good news about the Department of Homeland Security's National Biodefense Analysis and Countermeasures Center (NBACC): 

The agency's original plan was to operate the NBACC mostly in secret by classifying the entire center as a Sensitive Compartmented Information Facility (SCIF, pronounced "skiff")--a place where top-secret information and materials could be stored and discussed. But the NBACC's new director, J. Patrick Fitch, says that he intends to operate the lab with the greatest possible transparency. "Eighty percent of our projects and their results will be unclassified, and we will encourage our scientists to publish," he says. While his facility would be "SCIFable" in an emergency, he intends to encourage as much interaction as possible between NBACC scientists and their American and foreign counterparts. "In such a fast-moving area," he explains, "it's self-defeating to isolate yourself."

This is a welcome change.  There is also an independent advisory board looking over the NBACC's shoulder, but the idea of classified work on pathogens still makes me uneasy.

It is interesting to see Miller back on the biodefense beat.  Even if some of her prior work is now frowned on, she seems to have a knack for putting pieces together.

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."

Gene Synthesis Cost Update

While at iGEM this past weekend, I learned that GeneArt is now charging $.55 per base for ~1 kB synthesis jobs, with delivery within 10 days.

Here is an interesting tidbit: They only charged iGEM teams $.20 per base.  Anybody have any idea whether this represents their internal cost, and how much margin this might include?

Here is an updated plot for synthesis and sequencing cost.  No new data, just a new rendering.

(Update: 12 November, 2008.  There is a news piece in last week's Nature that claims Illumina's Genome Analyzer (GA1) was just used to sequence a whole genome in 8 weeks for $250K.  However, the paper describing that sequencing efforts says:

We generated 135 Gb of sequence (4 billion paired 35-base reads) over a period of 8 weeks (December 2007 to January 2008) on six GA1 instruments averaging 3.3 Gb per production run. The approximate consumables cost (based on full list price of reagents) was $250,000.

Thus the price does not include labor, and is not a true commercial cost (labor is only truly free for professors).

I am therefore not sure if/how this price can be compared to the prices in the figure below.

Update 2: I fixed the significant figure issue with the cost axis.  Alas, Open Office does not give great control over the appearance of the digits.)

Amyris Opens Biodiesel Pilot Plant

Amyris appears to be making good progress towards meeting their goal of getting biofuels to market by 2010.  They just opened their first pilot plant in California, with the aim of importing fuel into the US from Brazil within two years.  The output of the pilot plant will be used to gain EPA certification.  The announcement pretty well tracks with my previous posts about biofuels.

Here are a few graphs from the press release:

Amyris' diesel is characterized as a No Compromise™ fuel because it is designed to be a scalable, low‐cost renewable fuel with performance attributes that equal or exceed those of petroleum‐sourced fuels and currently available biofuels. Other attributes include:

• Superior environmental performance: Preliminary analyses show that Amyris diesel fuel has virtually no sulfur and significantly reduced NOx, particulate, carbon monoxide and hydrocarbon exhaust emissions relative to petroleum‐sourced diesel fuel.
• High blending rates: Because Amyris renewable diesel contains many of the properties of petroleum diesel, Amyris can blend the fuel at high levels ‐‐ up to 50  pecent ‐‐ compared with 10‐20 percent for conventional biodiesel and ethanol.
• Compatibility with  existing infrastructure: Unlike many commercially available biofuels, Amyris expects to distribute its renewable diesel through the existing fuel distribution and storage infrastructure, thus speeding time to market while minimizing costs.
• Adaptive: Amyris can produce its fuels from a broad range of feedstock including sugarcane and cellulosic biomass. It is starting with Brazilian sugar cane because it provides the most environmentally sound, economical, and scalable source of energy available today.

"This new diesel fuel has all the characteristics to make an important contribution toward solving our global transportation energy and climate crisis," said John Melo, chief executive officer of Amyris. "The opening of our pilot plant is a significant business marker for us, taking us one step closer to bringing our diesel fuel to market."

Craig Rubens at earth2tech provides interesting coverage, and his story notes:

Melo described the company's business model as "a capital-light model to scale up fast." The company plans to partner with existing ethanol plants and convert a portion of those partners' production capacity to make diesel and other chemicals using Amyris IP. The startup will then buy the products back from the refiner and take them to market, Melo said. The startup has already formed a joint venture with Santelisa Vale, Brazil's second largest sugar grower, called Crystalsev, which aims to produce 200 million gallons of fuel a year by 2011 at several of its existing ethanol plants at a price of less than $2 a gallon.

The Brazilian partnership, Melo explained, gives Amyris access to ports and ships to export the fuel. Amyris plans to import it to the U.S. and sell its to large customers, like Wal-Mart and the U.S. government. Foreign ethanol is hit with a 54-cent-per-gallon tariff as it comes into the U.S., but Amyris would be importing hydrocarbons, not ethanol, and therefore avoid the tariff. Amyris is already marketing other companies' biofuels in the Southeast to make sure its distribution channels will work.

To date, Amyris' strategy hasn't seamed particularly "capital light." The company has raised more than $120 million in capital (see previous coverage here and here) from heavy-hitting cleantech and biotech investors, including Kleiner Perkins, Khosla Ventures, TPG Biotech and DAG Ventures.

I understand the present need for scale, both physical and financial, and earth2tech's skepticism seems a bit naive.  Amyris is facing enormous competition, both from established petroleum companies and from other start-ups.  As I would not expect any of these companies to have a firm lock on IP surrounding biological production of fuels, Amyris must establish itself and its brand quickly and rely on first-mover advantage. (I wonder how thoroughly they are scrubbing the waste stream?  Dumpster diving for competitive intelligence takes on a new meaning here.)  Shell is dropping seven billion on upgrading a single refinery in Texas.  Amyris seems pretty light in comparison.

Writing at Cleantech, Emma Ritch provides an excellent tidbit: "The company has shelved its plans for a bio-gasoline".  "We're focused on the products with the highest value," Melo said. "We're not investing our resources in developing a bio-gasoline because we see the U.S. as the last gasoline-based economy."  That is particularly fascinating, as Melo is the former President of BP Fuels.  It is also a change since I heard Zach Serber speak at SB 4.0 last month in Hong Kong.  The fluctuating price of oil may be important here.

Unfortunately, Ritch mischaracterises the competitive landscape a bit: "Amyris plans to use the cheapest nonfood feedstock available, which for now means sugarcane... The company could also use algae for its biodiesel--much like Solazyme, LiveFuels, GreenFuel Technologies and many others."  In contrast to Amyris, the latter three companies are directly producting fuel in algae, with Solazyme feeding sugar to bugs in the dark and completely skipping photosynthesis. (Hmm...I wonder what sort of selection pressure that is putting on their algae strains?)  If Amyris does use algae -- sorry, when Amyris starts using algae -- the company will almost certainly be using it as a feedstock fed to microbes that then produce fuels.  This would require building a front-end process onto their yeast production system, but I don't see that as taking very long to happen.  See my earlier post on Blue Marble Energy.

Things are moving forward.  I would note that I see a lot of stainless steel in the photos of Aymris' pilot plant.  I am no fermentation jock, but it seems that they could probably use solvent resistent plastic as their culture vessels.  Here is one home-brew kit that basically just consists of plastic buckets.  Maybe that is a step for later.

Congratulations to everyone at Amyris.  Keep up the good work.

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?):

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

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

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.

Heading to MIT and iGEM

I'm off to give a talk at MIT on Friday and be a judge for iGEM again this weekend.

Here are talk coordinates (I've no idea how big the room is):

"Engineering (and) the Bio-economy"
Rob Carlson

7 November, 2008
12 to 2 PM
MIT
E38, 6th floor conference room.
292 main street, directly above the MIT press book store.

Can't wait to see what the students have come up with this year.