The National Bioeconomy Blueprint

Last week the White House Office of Science and Technology Policy (OSTP) closed a Request for Information for the National Bioeconomy Blueprint.  I previously submitted the Biodesic 2011 Bioeconomy Update as background information, and I then extended my comments with a proposal aimed at "Fostering Economic and Physical Security Through Public-PrivatePartnerships and a National Network of Community Labs" (PDF).  In short, I proposed that the U.S. government facilitate the founding and operation of community biotech labs as a means to improve the pace of innovation and reduce the attendant level of risk.

Garages are a critical component of technological innovation and job creation in the United States.  Over the last few years the Kauffman Foundation has published analyses of Census data that show start-ups under a year old are responsible for 100% of the net job creation in the U.S.; firms of all other ages are net job destroyers.  Moreover, as I made clear in my testimony before the Presidential Commission for the Study of Bioethical Issues, garages played a crucial role in developing many of the technologies we use on a daily basis.  Thus if we want to maintain a healthy pace of innovation in biological technologies, it makes sense that we will need to foster a profusion of garage biotech labs.

A biotech lab in every garage will make many a policy wonk uneasy.  What about safety and security?  I suggest that the emerging model of community labs (Genspace, Biocurious, etc.) is a good foundation to build on.  The FBI already has a program in place to engage these labs.  And as it turns out, the President has already signed a document that states garage biology is good and necessary for the future physical and economic security of the United States.  The USG could offer grants (financial, equipment, etc) to labs that sign on to follow educational and operational guidelines.  The existence of such labs would facilitate access to infrastructure for innovators and would also facilitate communication with those innovators by the USG.

I will admit that in my early conversations with the founders of Genspace and Biocurious that I was skeptical the model would work.  More than a decade ago I put serious effort into figuring out if a commercial bio-incubator model could work, and I concluded that numbers were nowhere near workable.  I also think it is too early to take real lessons away from the for-profit hackerspaces that are cropping up all over, because there isn't enough of a track record of success.  Anyway, and fortunately, the folks at Genspace and Biocurious ignored me.  And I am glad they did, because I was stuck thinking about the wrong kind of model.  Not for profit and community engagement is definitely the way to go.  I think most medium to large U.S. cities could support at least one community biotech lab.

Where should we put these labs?  I suggest that, following the recent model of installing Fab Labs and Hackspaces in public libraries, the USG should encourage the inclusion within libraries and other underused public spaces of community biotech labs.  There are endless benefits to be had from following this strategy.

I could go on, but there's more in my submission the OSTP: "Fostering Economic and Physical Security Through Public-Private Partnerships and a National Network of Community Labs" (

PDF

).

Diffusion of New Technologies

A Tweet and blog post from Christina Cacioppo about technological diffusion led me to dig out a relevant slide and text from my book.  Ms. Cacioppo, reflecting on a talk she just saw, asks "Are we really to believe there was no "new" technology diffusion between 1950 and 1990? I thought this was the US's Golden Age of Growth. (Should we include penicillin, nuclear power, or desktop computers on this chart?)".  There is such data out there, but it can be obscure.

As it happens, thanks to my work with bio-era, I am familiar with a 1997 Forbes piece by Peter Brimlow that explores what he called "The Silent Boom".  Have a look at the text (the accompanying chart is not available online), but basically the idea is that keeping track of the cost of a technology is less informative than tracking actual market penetration, which is sometimes called "technological diffusion".  The time between the introduction of a technology and widespread adoption is a "diffusion lag".  The interesting thing for me is that there appears to be a wide distribution of diffusion lags; that is, some technologies hit the market fast (which can still mean decades) while others can take many more decades.  There really isn't enough data to say anything concrete about how diffusion lags are changing over time, but I am willing to speculate that not only are the lags getting shorter (more rapid market adoption), but that the pace of adoption is getting faster (steeper slope).  Here is the version of the chart I use in my talks, followed by a snippet of related text from my book (I am sure there is a better data set out there, but I have not yet stumbled over it):

And from pg 60 of Biology is Technology:

Diffusion lags in acceptance appear frequently in the adoption of new technologies over the last several centuries. After the demonstration of electric motors, it took nearly two decades for penetration in U.S. manufacturing to reach 5% and another two decades to reach 50%. The time scale for market penetration is often decades[6] (see Figure 5.6). There is, however, anecdotal evidence that adoption of technologies may be speeding up; "Prices for electricity and motor vehicles fell tenfold over approximately seven decades following their introduction. Prices for computers have fallen nearly twice as rapidly, declining ten-fold over 35 years."[4]

Regardless of the time scale, technologies that offer fundamentally new ways of providing services or goods tend to crop up within contexts set by preceding revolutions. The interactions between the new and old can create unexpected dynamics, a topic I will return to in the final chapter. More directly relevant here is that looking at any given technology may not give sufficient clues as to the likely rate of market penetration. For example, while the VCR was invented in 1952, adoption remained minimal for several decades. Then, in the late 1970's the percentage of ownership soared. The key underlying change was not that consumers suddenly decided to spend more time in front of the television, but rather that a key component of VCRs, integrated circuits, themselves only a few decades old at the time, started falling spectacularly in price. That same price dynamic has helped push the role of integrated circuits into the background of our perception, and the technology now serves as a foundation for other "independent" technologies ranging from mobile phones, to computers, to media devices.

iGEM 2011: First Thoughts

Congratulations to the 2011 University of Washington iGEM team for being the first US team ever to win the Grand Prize.  The team also shared top honors for Best Poster (with Imperial College London) and for Best Food/Energy Project (with Yale).  The team also had (in my opinion) the clearest, and perhaps best overall, wiki describing the project that I have seen in 5 years as an iGEM judge.  I only have a few minutes in the airport to post this, but I will get back to it later in the week.

The UW team had an embarrassment of riches this year.  One of the team's projects demonstrated production of both odd and even chain alkanes in E. coli directly from sugar.  The odd-chain work reproduces the efforts of a Science paper published by LS9 last year, but the team also added an enzyme from B. subtilis to the pathway that builds alkanes starting from a 3-carbon seed rather than the normal 2-carbon seed in coli.  This latter step allowed them to make even-chain alkanes via a synthetic biological pathway, which has not been reported elsewhere.  So they wound up directly making diesel fuel from sugar.  The yields aren't all there yet to roll out this sort of thing more widely, but its not so bad for a summer project.

And that's not all.

The other main project was an effort to produce an enzyme to digest gluten.  There is one such enzyme in clinical trials at the moment, intended for use as a therapeutic for gluten intolerance, which afflicts about 1% of the population.  However, that enzyme is not thermostable and has an optimum pH of 7.

The UW team found an enzyme in the literature that was not known to digest gluten, but which works at pH 4 (close to the human stomach) and is from a thermophilic organism.  They used Foldit to redesign the enzyme to process gluten, and then built a library of about 100 variants of that design.  One of those variants wound up working ~800 times better than the enzyme that is currently in clinical trials.  And the team thinks they can do even better by combining some of the mutants from the library.

Nice work.

I could go on and on about the competition this year.  The teams are all clearly working at a new level.  I recall that a couple of years ago at iGEM Drew Endy asked me, somewhat out of frustration, "Is this it?  Is this all there is?"  The answer: No.  There is a hell of a lot more.  And the students are just getting started.

Plenty of other teams deserve attention in this space, in particular Imperial College London, the runner up.  They built a system (called Auxin) in E. coli to encourage plant root growth, with the aim of stopping desertification.  And their project was an extremely good example of design, from the technical side through to conversations with customers (industry) and other stakeholders (Greenpeace) about what deployment would really be like.

More here later in the week.  Gotta run for the plane.

Biodesic 2011 Bioeconomy Update: U.S. Revenues from Genetically Modified Systems Now $300 Billion, or Greater than 2% of GDP.

Biodesic has released a short Technical Report on the size of U.S. Bioeconomy.  The Biodesic 2011 Bioeconomy Update (PDF) walks the reader through changes in revenues from GM crops, biologics, and industrial biotech.  The Technical Report updates the figures and analysis published in, Biology is Technology: The Promise, Peril, and New Business of Engineering Life.

I continue to be surprised by the misreporting in major publications of revenues from GM crops.  Based on USDA statistics and average crop prices, the three main GM crops in the U.S. (corn, soy, and cotton) brought in farm scale revenues of $100 billion in 2010.  As I noted in 2009 in Nature Biotechnology, many news outlets continue to report the $5.5 billion in revenues from U.S. GM seed sales as total sector revenues.

With U.S. biologics revenues of $75 billion, and industrial biotech revenues of $115 billion, total U.S. 2010 revenues from genetically modified systems were $300 billion, or the equivalent of more than 2% of GDP. 

Globally, biotech investment continues to accelerate, as do revenues (see table below).  China and India have made domestic biotech a priority for producing jobs and economic growth and as an independent source of fuels, food, and materials.  Malaysia has recently reported biotech constituted 2.5% of its 2010 GDP, up from zero in 2005.  Pakistan's biotech economy presently consists entirely of GM cotton, which the USDA estimates to now be 100% of the annual drop, and which until 2010 was entirely illegal.

Read more in the Biodesic 2011 Bioeconomy Update.

Country	2010 Biotech Revenues	2010 Est. Growth	2020 Target Biotech Revenues
Malaysia	2.5%	25%	10%
China	2.5%	20%	5-8%
United States	>2%	10-15%	NA
India	0.24-0.40%	20%	1.6% (2015)
Pakistan	1.6%	<5%	NA
Europe	<1.0%	5%	NA

Table 1.

Biotech Revenues as Share of GDP. Source: Biodesic 2011 Bioeconomy Update.

Staying Sober about Science

The latest issue of The Hastings Center Report carries an essay of mine, "Staying Sober about Science" (free access after registration), about my thoughts on New Directions: The Ethics of Synthetic Biology and Emerging Technologies (PDF) from The Presidential Commission for the Study of Bioethical Issues.

Here is the first paragraph:

Biology, we are frequently told, is the science of the twenty-first century. Authority informs us that moving genes from one organism to another will provide new drugs, extend both the quantity and quality of life, and feed and fuel the world while reducing water consumption and greenhouse gas emissions. Authority also informs that novel genes will escape from genetically modified crops, thereby leading to herbicide-resistant weeds; that genetically modified crops are an evil privatization of the gene pool that will with certainty lead to the economic ruin of small farmers around the world; and that economic growth derived from biological technologies will cause more harm than good. In other words, we are told that biological technologies will provide benefits and will come with costs--with tales of both costs and benefits occasionally inflated--like every other technology humans have developed and deployed over all of recorded history.

And here are a couple of other selected bits:

Overall, in my opinion, the report is well considered. One must commend President Obama for showing leadership in so rapidly addressing what is seen in some quarters as a highly contentious issue. However, as noted by the commission itself, much of the hubbub is due to hype by both the press and certain parties interested in amplifying the importance of the Venter Institute's accomplishments. Certain scientists want to drive a stake into the heart of vitalism, and perhaps to undermine religious positions concerning the origin of life, while "civil society" groups stoke fears about Frankenstein and want a moratorium on research in synthetic biology. Notably, even when invited to comment by the commission, religious groups had little to say on the matter.

The commission avoided the trap of proscribing from on high the future course of a technology still emerging from the muck. Yet I cannot help the feeling that the report implicitly assumes that the technology can be guided or somehow controlled, as does most of the public discourse on synthetic biology. The broader history of technology, and of its regulation or restriction, suggests that directing its development would be no easy task.8 Often technologies that are encouraged and supported are also stunted, while technologies that face restriction or prohibition become widespread and indispensable.

...The commission's stance favors continued research in synthetic biology precisely because the threats of enormous societal and economic costs are vague and unsubstantiated. Moreover, there are practical implications of continued research that are critical to preparing for future challenges. The commission notes that "undue restriction may not only inhibit the distribution of new benefits, but it may also be counterproductive to security and safety by preventing researchers from developing effective safeguards."12 Continued pursuit of knowledge and capability is critical to our physical and economic security, an argument I have been attempting to inject into the conversation in Washington, D.C., for a decade. The commission firmly embraced a concept woven into the founding fabric of the United States. In the inaugural State of the Union Address in 1790, George Washington told Congress "there is nothing which can better deserve your patronage than the promotion of science and literature. Knowledge is in every country the surest basis of publick happiness."13

The pursuit of knowledge is every bit as important a foundation of the republic as explicit acknowledgment of the unalienable rights of life, liberty, and the pursuit of happiness. Science, literature, art, and technology have played obvious roles in the cultural, economic, and political development of the United States. More broadly, science and engineering are inextricably linked with human progress from a history of living in dirt, disease, and hunger to . . . today. One must of course acknowledge that today's world is imperfect; dirt, disease, and hunger remain part of the human experience. But these ills will always be part of the human experience. Overall, the pursuit of knowledge has vastly improved the human condition. Without scientific inquiry, technological development, and the economic incentive to refine innovations into useful and desirable products, we would still be scrabbling in the dirt, beset by countless diseases, often hungry, slowly losing our teeth.

There's more here.

References:

8. R. Carlson, Biology Is Technology: The Promise, Peril, and New Business of Engineering Life (Cambridge, Mass.: Harvard University Press, 2010).

12. Presidential Commission for the Study of Bioethical Issues, New Directions, 5.

13. G. Washington, "The First State of the Union Address," January 8, 1790, http://ahp.gatech.edu/first_state_union_1790.html.

It is the End of the World as We Know it, and I feel Strangely Ambivalent: Synthetic Biology 5.0

Synthetic Biology 5.0 has come and gone.  I expected, as in previous years, to be busy liveblogging amid the excitement.  I tweeted some during the proceedings (here is Eric Ma's summary of #synbio5 tweets), but this is my first post about the meeting, and probably the last one.  I mostly just listened, took a few notes, and was delighted to see the progress being made.  I was not nearly as amped up about the proceedings as in previous years, and I am still trying to figure out why. 

Here are a couple of reasons I have sorted out so far.  It was the end of the beginning of synthetic biology.  The meeting was full of science and engineering.  And that's about all.  There were a few VC's and other investors sniffing around, but not nearly so many as in previous years; those who did show up kept a lower profile.  There were also fewer obvious government officials, no obvious spooks, no obvious law enforcement officers, nor any self-identified Weapons of Mass Destruction Coordinators.  And I only encountered a couple of reporters, though there must have been more.  I skipped 3.0 in Zurich, but at 1.0 at MIT, 2.0 at Berkeley (parts 1, 2, 3, 4, 5), and 4.0 in Hong Kong (part 1), there was much more buzz.  Synthetic Biology 5.0 was much shorter on hype than prior gatherings. 

There was substantially more data this year than previously.  And there was substantially less modeling.  All in all, Synthetic Biology is substantially more ... substantial.  It was like a normal scientific meeting.  About science.  No stunts from "civil society" groups looking for their next fear bullet point for fundraising.  No government officials proclaiming SB as the economic future of their city/state/country.  Just science.

What a relief.

And that science was nothing to sneeze at.  There were great talks for 3 days.  Here are a couple of things that caught my eye.

Jef Boeke from Johns Hopkins presented his plans to build synthetic yeast chromosomes.  I first heard this idea more than ten years ago from Ron Davis at Stanford, so it isn't brand new.  I did notice, however, that Boeke having all his synthetic chromosomes made in China.  Over the longer term this means China is getting a boost in building out future biomanufacturing platforms.  If the project works, that is.

As tweeted, Jack Newman from Amyris gave an update on commercialization of artemisinin; it should be on the market by the end of the year, which should be in time to help avert an expected shortfall in production from wormwood.  Fantastic.

Pam Silver and her various students and post-docs showed off a variety of interesting results.  First, Faisal Aldaye showed in vivo DNA scaffolds used to channel metabolic reactions, resulting in substantial increases in yield.  Second, Pam Silver showed the use of those scaffolds to generate twice as much sucrose from hacked cyanobacteria per unit of biomass as from sugar cane.  If that result holds up, and if the various issues related to the cost of bioreactors used to culture photosynthetic organisms are worked out, then Pam's lab has just made an enormous step forward in bringing about distributed biological manufacturing.

This is the sort of advance that makes me feel more sanguine about the future of MIcrobrewing the Bioeconomy.  It will take some years before the volume of Amyris' Biofene, or Gevo's bio-PET, or Blue Marble's bio-butyric acid begins to impact the oil industry.  But it is clear to me now as never before that the petroleum industry is vulnerable from the top of the barrel -- the high value, low volume compounds that are used to build the world around us in the form of petrochemicals.  Biology can now be used to make all those compounds, too, directly from sugar, cellulose, and sunlight, without the tens of billions of dollars in capital required to run an oil company (see The New Biofactories). 

So SB 5.0 was the end of the world as we know it.  Synthetic biology is now just another field of human endeavor, thankfully producing results and also thankfully suffering reduced hype.  I can see how the pieces are starting to fit together to provide for sustainable manufacturing and energy production, though it will be some years before biological technologies are used this way at scale.  Perhaps this is less in-your-face exciting for the attendees, the press, and the public, and that may be part of the reason for my ambivalence.  I fell asleep several times during the proceedings, which has never happened to me at SB X.0, even when overseas and jetlagged.  I have never before thought of achieving boredom as constituting progress.

New Cost Curves

Sitting here at Synthetic Biology 5.0, it's time to update the DNA synthesis and sequencing cost curves. (Here is some prior commentary on why these curves are slow, are fast, and have the shape they do.) Here you go:

Piracy, Food Security, and Global Supply Lines

I've just landed in Washington DC for a biosecurity meeting -- a chat about how not to get caught with our pants down.  Catching up on the news in my hotel room, I notice that over at Danger Room Adam Rawnsley is reporting that the Chinese are talking tough about "crashing" the land bases of pirates in Africa.

With regards to biosecurity, and its extension into other security matters -- food security, in this case -- I've been expecting China to get more aggressive on pirates.  And this is just the beginning.  China's food demand is skyrocketing as incomes rise, and much of that food is going to come from overseas (see my previous post "More on China's Economy, Food Production, and Food Demand").  The Economist recently estimated that of the approximately 80 million hectares of land deals in developing countries in the last decade -- "more than the area of farmland of Britain, France, Germany and Italy combined" -- two-thirds were by Chinese companies.  A very good guess is that a substantial fraction of the other one-third were made by countries or companies who hope to sell to the Chinese.

The motivation for this land rush is simple: despite plans by the Chinese government, it is highly unlikely that the country will be able to maintain "food independence" -- the ability to feed its population with domestic supplies.  So China's critical supply lines for food and other raw materials are going global, and those shipping lines often pass through waters off eastern Africa -- prime pirate waters.  Chinese shipping is also at threat in the Straight of Malacca.

It is thus no surprise that China is getting serious about piracy.  The U.S. should expect the Chinese Navy to be more active around the world, and we should expect more investment by the Chinese government in the ability to protect global supply lines.  We should also not overreact to this situation.  We know that it is coming, and everyone should be paying attention, in part so that there are no misunderstandings.  The U.S. Navy, among others, should get its ducks (and, admirals, and carriers, etc) in a row now in the form of real engagement with the Chinese Navy.  This is an opportunity for more cooperation.

Increasing demand for food will create more situations like this in coming years.  The security of all countries depends on getting this right, and not getting caught with our pants down.

Headed out for a little cruise...

The NOAAS Rainier, just outside my office window, headed out to sea:

Osama bin Laden and PCR

By now everybody has heard that bin Laden is dead.  R.I.H.

When I heard President Obama say last night that bin Laden's identity had been confirmed by DNA analysis (here's a post from Scientific American about how this might be done), I started mulling over what you might put in place to pull off this analysis quickly.

First, you need DNA.  US forces had OBL's, and everyone is reporting they compared his DNA to his sisters.  How?  If I really wanted to be certain, I would sequence some of her DNA and then prepare PCR primers based on that information.

Second, you need to check the suspect sequence.  There is certainly at least one of Idaho Technology's JBAIDS real-time PCR systems in theater.  Could be on the ground in Afghanistan, could be on an aircraft carrier or assault ship.  I doubt they flew one in and did the test in the air, but that is certainly possible.  (Side note, if you click through to the JBAIDS site, the photo totally makes the instrument look smaller than it is.  The box in real life is waaay bigger than a laptop.  "Man-portable RT-PCR" they say.  I say not by me.)

It probably took longer to fly the body out and get a sample to the PCR machine than it did to actually process the DNA and certify identity by RT-PCR.

So I have only one question: Who got the contract for high purity bin Laden-specific DNA primers?