The Million Dollar Genome

This week's Science carries a short news piece by Eliot Marshall on "Project Jim", the effort to sequence James Watson's genome by 454 Life Sciences.  Eliot writes that:

When the project began, 454's equipment wasn't up to the task...But improved technology made it possible to sequence 10 billion bases in multiple overlapping fragments of Watson's DNA "in a space of a few weeks."...The project cost is "about $1 million."

That puts it a bit ahead of my original estimates of exponential pace decreases described, for example, here.  I dropped by Bob Waterston's office a few weeks ago, and he put a rough estimate on a human genome at a few million dollars, which more or less corroborates 454's number.

Where Should We Look For Biofuels?

The Press is full of reports describing the investment boom in biofuels.  So much hoopla.  The problem is that not all biofuels are the same, and some of them will apparently do more harm than good. 

Bio Economic Research Associates has studied the alternatives quite intensely, and now that "Genome Synthesis and Design Futures" is published we are examining more closely where Synthetic Biology fits into the biofuels picture.  More broadly, we are now exploring not just the technological angles, but also the economic and social costs built into choices about what crops to use for biofuels, where and how to grow those plants, and what happens to carbon emissions under the various options.

Vinod Khosla laid out his views in Wired last fall with "My Big Biofuels Bet", describing a plan to reduce carbon emissions and reduce reliance on imported oil, with all the best of intentions.  And here is a story from the AP (via Wired) "Betting on a Green Future", that appeared "way back" in April, 2006.  It's easy to find articles on biofuels in every major (and minor) news outlet, in big and small scientific journals, and of course in blogs.  Money is chasing opportunities in ethanol fermented from corn and straw, biodiesel from soy and palm, various liquid fuels produced from animal and plant biomass via Fischer-Tropsch or similar processes, methane from manure and garbage heaps, all the way through genetically modified plants that either directly produce fuels or are easier to process into fuels, to direct production of liquid biofuels using microbes modified with the tools of Synthetic Biology.  Venture Capitalists were as prominent as biologists and engineers at Synthetic Biology 2.0 last year in Berkeley.

Very interesting and promising stuff indeed.  But perhaps not so well thought through as it needs to be.  For example, the last couple of days have seen a profusion of articles on carbon release from land in Indonesia and Malaysia cleared for growing oil palms destined for use as biodiesel.  Here is an excellent story from the AP, via the IHT, that carries the title, "Energy companies rethink palm oil as biofuel":

A report late last year by a Netherlands-based research group claimed some plantations produce far more carbon dioxide than they save. Seeded on drained peat swamps, they unleash a warehouse of carbon from decomposed plants and animals that had been locked in the bogs for hundreds of million years, which one biologist described as "buried sunshine."

"As a biofuel, it's a failure," said Marcel Silvius, a climate change expert for Wetlands International, the institute that led the research team.

The story does note that, "Wetlands' figures could not be independently verified by the U.N. Climate Change Secretariat in Bonn, Germany, by the World Resources Institute in Washington, D.C., nor by academic experts. But all said the research appeared credible."

Companies that produce and consume palm oil are hoping that a trusted trading scheme can be set up to ensure oil comes from sustainable sources:

With concerns mounting over sourcing, plantation owners joined forces with processors, investors and environmentalists three years ago to form the Roundtable on Sustainable Palm Oil with the aim of monitoring the industry and drawing up criteria for socially responsible trade. But the RSPO has yet to create a foolproof system to verify the supply chain.

I have serious doubts about whether any such system is possible.  Given the fungibility of the palm oil, just as with petroleum, I wonder whether it will be possible to keep track of sources, particularly if the oil is consolidated or mixed during harvesting, processing, and shipping.  It only gets worse once the raw palm oil is converted into higher value diesel fuel

The size of the potential carbon release from peat and rain forest cleared for growing biofuels is so large that biodiesel use could easily run afoul of carbon caps being considered in Europe, Japan, Canada, and perhaps eventually the U.S.  Given how lucrative the plant oil market is becoming, there will be plenty of incentives for cheating on the supply side, as is now happening with sugar cane production in Brazil.  I don't see an easy technological fix for tracking sugar, ethanol, palm oil, or biodiesel, so I don't understand where any sort of lever will be useful for suppressing the emergence of a black market as plants become fuel.  It seems to me that there could be significant costs associated with verification, tracking, and perhaps certification, of sources, and I suspect this will have a big effect on plans for importing and processing oil.  Not only are the direct economic costs something to consider, but the social and public relations impacts could be substantial.  Indeed, the latter are affecting decision making already.  From the IHT:

"We spent more than a year investigating the sustainability issues with palm oil," said Leon Flexman, of RWE npower, Britain's largest electricity supplier. The company decided against palm oil because it could not verify all its supplies would be free of the taint of destroyed rain forest or peat bogs, he said.

Beyond the effects on carbon emissions, converting crops into biofuels fundamentally impacts food supplies.  Not to mention all the water that will be required to irrigate crops grown using modern farming methods.  George Monbiot, writing at The Guardian, makes a surprisingly good (for The Guardian) argument for a moratorium on governmental targets and incentives for biofuel use.  Monbiot cites all sorts of gloomy facts and figures regarding the climate effects and market impacts of using food crops as fuel, and of clearing rain forest to grow sugar cane or oil palms.

An altogether different set of problems arises when you start examining the prospects for biofuels produced from genetically modified versions of food crops.  While leakage of genes from GM crops into their un-modified cousins is still a hypothetical danger, there is a very real and immediate possibility of governmental regulations that limit planting.  Here, for example, is an interesting collection of stories about GM crops, leakage, and policy from gepolicyalliance.com.  With recent examples of pharmaceutically-modified rice and corn finding their way into the food supply, some farm state congressmen are wondering aloud about legislation to limit the planting of such crops.

So it makes sense to think ahead about the effects on biofuels.  In a long and detailed letter published last month in Nature Biotechnology under the title, "Biofuels and biocontainment", C. Neal Foster at the University of Tennessee, writes:

It is difficult to imagine that transgenic technologies will not be pivotal in transforming the process of going from grass to gas, in particular enhancing the production of lignocellulosic-based plant feedstock and its conversion into ethanol or biodiesel. Although biotech has an opportunity to increase yields and efficiency of bioenergy crop production as well as aid the conversion of complex carbohydrates and plant oils to fuels, unless modifications are performed with an eye to meet future regulatory and consumer issues, these potential benefits might never be realized.

...On the regulatory side, history has shown that it is nearly impossible to prevent industrial or pharmaceutical crops from entering the human food chain or feed when grown in proximity to one another. Low levels of adventitious presence of agronomic traits have been tolerated to some degree, but there is less tolerance for pharmaceutical and industrial transgene adventitious presence in the food chain.

...Because large tracts of land will likely be planted in bioenergy crops, there are important ecological considerations for sustainability. We need to prepare now to detour obvious roadblocks on the road to biofuels sustainability. One enduring lesson from agricultural biotech is that it is a huge mistake to underestimate biosafety concerns. A corollary is that Nature will always find a way; Murphy's law implies that no matter how unlikely it seems that genes will flow, they eventually will.

Foster explores the various options for GM food crops and non-food crops, and the rest of the letter is well worth reading.  Given the recent decision by a federal judge that the USDA was negligent in approving GM alfalfa without greater study (here is the press release from the Center for Food Safety), it is clear that open planting of GM crops may not be as easy in the future.  But there are other possibilities for high-yield biofuel production from plants.

One potentially less controversial source of biofuels, at least for North America, is to use non-GM, native grasses as the raw material.  David Tilman and his colleagues published a paper last December in Science arguing that restored native grasslands could be used as a source of biomass for producing liquid fuels.  More significantly, using existing technology, it appears that the resulting fuel production infrastructure would be carbon negative, that is, storing more carbon than emitted during harvesting, processing, and use as fuel.  Tilman, an ecologist at the University of Minnesota and a member of the NAS, lays out his plan with research associate Jason Hill in an essay on checkbiotech.org,  originally carried in The Washington Post on 25 March.  Tilman and Hill summarize the paper in Science as follows:

In a 10-year experiment reported in Science magazine in December, we explored how much bioenergy could be produced by 18 different native prairie plant species grown on highly degraded and infertile soil. We planted 172 plots in central Minnesota with various combinations of these species, randomly chosen. We found, on this highly degraded land, that the plots planted with mixtures of many native prairie perennial species yielded 238 percent more bioenergy than those planted with single species. High plant diversity led to high productivity, and little fertilizer or chemical weed or pest killers was required.

The prairie "hay" harvested from these plots can be used to create high-value energy sources. For instance, it can be mixed with coal and burned for electricity generation. It can be "gasified," then chemically combined to make ethanol or synthetic gasoline. Or it can be burned in a turbine engine to make electricity. A technique that is undergoing rapid development involves bioengineering enzymes that digest parts of plants (the cellulose) into sugars that are then fermented into ethanol.

Whether converted into electricity, ethanol or synthetic gasoline, the high-diversity hay from infertile land produced as much or more new usable energy per acre as corn for ethanol on fertile land. And it could be harvested year after year.

Even more surprising were the greenhouse gas benefits. When high-diversity mixtures of native plants are grown on degraded soils, they remove carbon dioxide from the air. Much of this carbon ends up stored in the soil. In essence, mixtures of native plants gradually restore the carbon levels that degraded soils had before being cleared and farmed. This benefit lasts for about a century.

Across the full process of growing high-diversity prairie hay, converting it into an energy source and using that energy, we found a net removal and storage of about a ton and a half of atmospheric carbon dioxide per acre. The net effect is that ethanol or synthetic gasoline produced from this grass on degraded land can provide energy that actually reduces atmospheric levels of carbon dioxide.

All in all, an exceptionally interesting proposal.  Tilman was a co-author on a Science paper earlier in 2006 that showed high diversity grasslands produce considerably more biomass per acre than monocultures of either grass or corn.  And that healthy prairie full of perennial grasses serves as habitat for all kinds of other wildlife, suggesting this approach could be a big win in many different ways.

But you still have to turn the raw biomass into fuel, and that is where Synthetic Biology will probably play a role.  Not in open fields, but in contained vats where microbes, first with modified enzymes, then later with altogether new pathways, will eat the harvested grasses and turn it into fuels.  This is an explicit focus of the new biofuels institute at UC Berkeley/LBL and the University of Minnesota, funded to the tune of $500 million by BP (story in Nature, from BP, and UCB).  And start ups like LS9 and Amyris are pouring effort into building microbes that directly produce fuels from simple feedstocks.

While this seems like a relatively straightforward path to producing significant amounts of ethanol, biodiesel, and eventually butanol, it will probably take 5-10 years before anything hits the market.  Then again, much of this is more a matter of money and organization than science.  We could get significant supplies of biofuels soon depending on our choices.

Chip Fab Now Costs US$2.5 Billion

Chip fabs just keep getting more expensive.  The AP, via Wired, reports that Intel is investing US$2.5 billion in a new factory in China.  The facility will churn out chips only for the Chinese market, evidently, and using old technology.  U.S. export rules require that Intel restrict the fab to using 90-nm processing, whereas chips made and sold in the U.S. will soon use a 45-nm process.

And biology just keeps getting cheaper.

Update on Public Access to "Genome Synthesis and Design Futures"

Due to confusion about access to "Genome Synthesis and Design Futures", I would like to make a clarification.  The original order page was not as clear as it could have been.  The report is publicly available, and is available as a free PDF or via a print-on-demand service for $95.  There are no restrictions to obtaining a copy, unless you are shy or are obviously misrepresenting yourself.  While the report does not contain sensitive material, Bio-era is requiring registration to receive a copy in an effort to both track interest and be a responsible public citizen.  I think it is rather ironic that the decision to require registration has been the target of public criticism by people who have made a business of making noise about restricting access to, and progress in, biological technologies.

Here is the new, clearer, web page.

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.

Stewart Brand -- “Where are the green biotech hackers?”

Tomorrow's New York Times has a great article on Stewart Brand.  In it, he asks the question, “Where are the green biotech hackers?”  We're coming, Stewart.  It's just that we're still on the slow part of the curves.

It's an interesting question, actually -- when do we get to the fast part?  When does biology start to go really fast?  And what does fast mean?

One answer to the question is the speed and the cost at which we can presently sequence or synthesize an interesting genetic circuit or organism.  Costs for reading genes are halving every 18 months or so, and if the rumors are true, we will hit the Thousand Dollar Genome sooner than my original estimate.  Sequencing is pretty easy at this point, as long as you already have a map to work with, which is the case for an increasing number of organisms.  And if you build the organism yourself, or pay someone else to do it, then you already know both the basic structure of the genome (the map) and the specific sequence.

At the moment, synthesis of a long gene takes about four weeks at a commercial DNA foundry, with a bacterial genome still requiring many months at best, though the longest reported contiguous synthesis job to date is still less than 50 kilobases.  And at a buck a base, hacking any kind of interesting new circuit is still expensive.  As I reported from SB 2.0, the synthesis companies are evidently now using my cost estimates as planning devices, even though that's not why made those estimates in the first place.  They project costs to continue falling by a factor of 2 approximately every year, which means that it will be another 5 years before synthesizing something the size of E. coli from scratch will cost less than US$ 1000, or 1 kilobuck.

The bigger problem, though, is the turnaround time.  No engineer or hacker wants to wait four weeks to see if a program works.  Hit compile, wait for four weeks, no "Hello World."  Start trying to debug the bug, with no debugging tools.  No thanks.  (I've actually had discussions with geneticists/molecular biologists who think even waiting a few days for a synthesis job isn't a big deal.  But what can you say -- biology just hasn't been a hacker culture.  And we are the poorer for it.)

So, Mr. Brand, it will be a few years before green hackers, at least those who aren't supported by Vinod Khosla or Kleiner Perkins, really start to have an impact.  The hackers who are lucky enough to have that kind of support, such as the blokes at Amyris Biotechnologies if their past accomplishments are anything to go by, will probably have something to show for themselves pretty soon.

The article ends with a couple of great paragraphs, which, along with "Science is the only news", are all you need to live by:

“I get bored easily — on purpose,” he said, recalling advice from the co-discoverer of DNA’s double helix. “Jim Watson said he looks for young scientists with low thresholds of boredom, because otherwise you get researchers who just keep on gilding their own lilies. You have to keep on trying new things.”

That’s a good strategy, whether you’re trying to build a sustainable career or a sustainable civilization. Ultimately, there’s no safety in clinging to a romanticized past or trying to plan a risk-free future. You have to keep looking for better tools and learning from mistakes. You have to keep on hacking.

"Genome Synthesis and Design Futures: Implications for the U.S. Economy"

After many, many months of work, Bio Economic Research Associates (Bio-era) today released "Genome Synthesis and Design Futures: Implications for the U.S. Economy".  Sponsored largely by Bio-era and the U.S. Department of Energy, with assistance from Dupont and the Berkeley Nanosciences and Nanoengineering Initiative, the report examines the present state of biological technologies, their applications to genome design, and potential impacts on the biomanufacturing of biofuels, vaccines, and chemicals.  The report also employs scenario planning to develop four initial scenarios exploring the effects of technological development and governmental policy.   Here is a link to the press release; over on the right side of the page are links to a short Podcast with myself and Jim Newcomb describing some of the findings.

It is a giant topic, and even at 180 pages we have really just barely scratched the surface.  The changes we've already witnessed will pale in comparison to what's coming down the pike.  The report deals mostly with science, technology, economics, markets, and policy, and only starts to explore the social and ethical aspects of forthcoming decisions.  Future work will refine the technological and economic analyses, will flesh out the security aspects of the ferment in biological technologies, and will delve into what all this means for our society.  In the preface, Jim Newcomb and Steve Aldrich note:

In presenting this analysis, we are mindful of the limitations of its scope. The arrival of new technologies for engineering biological systems for human purposes raises complex questions that lie at the intersection of many different disciplines. As the historian Arthur M. Schlesinger has written, “science and technology revolutionize our lives, but memory, tradition and myth frame our response.” Because this report is focused on potential economic implications of genome engineering and design technologies for the U.S. economy, there are many important questions that are not addressed here. In particular, we have not attempted to address questions of safety and biosecurity; the likelihood or possible impact of unintended consequences, such as environmental damage from the use of these technologies; or the ethical, legal, and social questions that arise. The need for thoughtful answers to these and related questions is urgent, but beyond the scope of this work. We hope to have the opportunity to investigate these questions in subsequent research.

We had a lot of help along the way, and for my part I would like to thank Drew Endy, Brian Arthur, George Church, Tom Kalil, Craig Venter, Gerald Epstein, Jay Keasling, Brad Smith, Erdogan Gulari, John Beadle, Roger Brent, John Mulligan, Michele Garfinkel, Ralph Baric, and Stephen Johnston, and Todd Harrington. 

Here is web page to buy a hard copy and/or download the PDF.  Just fill out the form (we're trying to track interest), and you will be sent a link to the PDF.

A Few Thoughts on Rapid Genome Sequencing and The Archon Prize

The December, 2006 issue of The Scientist has an interesting article on new sequencing technologies.  "The Human Genome Project +5", by Victor McElheny, contains a few choice quotes.  Phil Sharp, from MIT, says he, "would bet on it without a questionthat we will be at a $1,000 genome in a five-year window."  Presently we are at about US$10 million per genome, so we have a ways to go. It's interesting to see just how much technology has to change before we get there. 

The Archon X-Prize for Genomics specifies sequencing 100 duplex genomes in 10 days, at a cost of no more than US$10,000 per genome.  In other words, that is roughly 600 billion bases at a cost of microdollars per base.  Looking at it yet another way, winning requires 6000 person-days at present productivity numbers for commercially available instruments, whereas 10 days only provides 30 person-days of round-the-clock productivity.

I tried to find a breakdown of genome sequencing costs on the web, and all I could come up with is an estimate for the maize genome published in 2001.  I'll use that as a cost model for state of the art sequencing of eukaryotes (using Sanger sequencing on capillary based instruments).  Bennetzen, et al., recount the "National Science Foundation-Sponsored Workshop Report: Maize Genome Sequencing Project" in the journal Plant Physiology, and report:

The participants concurred that the goal of sequencing all of the genes in the maize genome and placing these on the integrated physical and genetic map could be pursued by a combination of technologies that would cost about $52 million. The breakdown of estimated costs would be:

  • Library construction and evaluation, $3 million
  • BAC-end sequencing, $4 million
  • 10-Fold redundant sequencing of the gene-rich and low-copy-number regions, $34 million
  • Locating all of the genes on an integrated physical-genetic map, $8 million
  • Establishing a comprehensive database system, $3 million.

From the text, it seems that decreases in costs are built into the estimate.  If we chuck out the database system, since this is already built for humans and other species, we are down to direct costs of something like $49 million for approximately 2.5 megabases(MB).  The Archon prize doesn't specify whether competitors can use existing chromosomal maps to assemble sequence data, so presumably all the information is fair game.  That lets us toss out another $8 million in cost.  The 10-fold redundant sequencing is probably overkill at this point, but I will keep all those costs because the Archon prize requires an error rate of no more than 1 in 100,000 bases; you have to beat down the error regardless of the sequencing method.  Rounding down to $40 million for charity's sake, it looks like the labor and processing associated with producing the short overlapping sequences necessary for Sanger sequencing account for about 17.5 percent of the total.  These costs are probably fixed for approaches that employ shotgun sequencing.

Again using the Archon prize as a simple comparison, that's US$1.75 million just to spend on labor for getting ready to do the actual sequencing.  In 1998, the FTE (full time equivalent) for sequencing labor was US$135,000.  If you assume the dominant cost for preparing the library and verifying the BACs is labor, you can hire about 15 people.  This looks like a lot of work for 15 people, and, given the amount of time required to do all the cloning and wait for bacteria to grow, not something they can accomplish even within the 10 days alloted for the whole project.

The other 82.5 percent of the $10 million you can spend on the actual sequencing.  The prize guidelines say you don't have to include the price of the instruments in the cost, but just for the sake of argument I'll do that here.  And I'll mix and match the cost estimates from the maize project for Sanger sequencing with other technologies.  The most promising commercial instrument appears to be the 454 pyrosequencer, at $500,000 a pop, looking at its combination of read length and throughput, even if they don't yet have the read length quite high enough yet.  If you buy 16 of those beasties, it appears you can sequence about 1.6 GB a day, about a factor of 40 below what's required to win the Archon prize.  Let's say 454 gets the read length up to 500 bases, then they are still an order of magnitude shy just on the sequencing rate, forgetting the sample prep.

Alternatively, you could simply buy 600 of the 454 instruments, and then you'd be set, at least for throughput.  Might blow your budget, though, with the $300 million retail cost.  But you could take solace in how happy you'd make all the investors in 454.

Microsoft Supports Biobricks

Last weekend at the 2006 International Genetically Engineered Machines Competition (iGEM 2006), Microsoft announced a Request For Proposals related to Synthetic Biology.  According to the RFP page:

Microsoft invites proposals to identify and address computational challenges in two areas of synthetic biology. The first relates to the re-engineering of natural biological pathways to produce interoperable, composable, standard biological parts. Examples of research topics include, but are not limited to, the specification, simulation, construction, and dissemination of biological components or systems of interacting components. The second area for proposals focuses on tools and information repositories relating to the use of DNA in the fabrication of nanostructures and nanodevices. In both cases, proposals combining computational methods with biological experimentation are seen as particularly valuable.

The total amount to be awarded is $500,000. 

"Smallpox Law Needs Fix"

ScienceNOW Daily News is carrying a short piece on the recommendation by the National Science Advisory Board on Biosecurity (NSABB) to repeal a law that criminalizes synthesis of genomes 85% similar to smallpox.

The original law, which surprised everyone I have ever talked to about this topic, was passed in late 2004 and wasn't written about by the scientific press until March of '05:

The new provision, part of the Intelligence Reform and Terrorism Prevention Act that President George W. Bush signed into law on 17 December 2004, had gone unnoticed even by many bioweapons experts. "It's a fascinating development," says smallpox expert Jonathan Tucker of the Monterey Institute's Center for Nonproliferation Studies in Washington, D.C.

...Virologists zooming in on the bill's small print, meanwhile, cannot agree on what exactly it outlaws. The text defines variola as "a virus that can cause human smallpox or any derivative of the variola major virus that contains more than 85 percent of the gene sequence" of variola major or minor, the two types of smallpox virus. Many poxviruses, including a vaccine strain called vaccinia, have genomes more than 85% identical to variola major, notes Peter Jahrling, who worked with variola at the U.S. Army Medical Research Institute of Infectious Diseases in Fort Detrick, Maryland; an overzealous interpretation "would put a lot of poxvirologists in jail," he says.

According to the news report at ScienceNOW:

Stanford biologist David Relman, who heads NSABB's working group on synthetic genomics, told the board that "the language of the [amendment] allows for multiple interpretations of what is actually covered" and that the 85% sequence stipulation is "arbitrary." Therefore, he said, "we recommend repealing" the amendment.

Relman's group also recommended that the government revamp its select agents list in light of advances in synthetic genomics. These advances make it possible to engineer biological agents that are functionally lethal but genomically different from pathogens on the list. The group's recommendations, which were approved unanimously by the board, are among several that the board will pass on to the U.S. government to help develop policies for the conduct and oversight of biological research that could potentially be misused by terrorists.