Biodefense Net Assessment: Causes and Consequences of Bioeconomic Proliferation

Revenues from biotechnology continue to grow rapidly around the world.  For several years I have been trying to assess these revenues, in part as a proxy metric for technological capabilities.  A couple of years ago, I received a commission from the U.S. government to explore this topic for the 2012 Biodefense Net Assessment (BNA).  I recently received approval to release the resulting report, which carries the title "Causes and Consequences of Bioeconomic Proliferation: Implications for U.S. Physical and Economic Security" (PDF).  As far as I am aware, this is the first publicly-released document from the BNA. 

There is a relatively small amount of information available about the BNA available on the web. The BNA is a quadrennial review required under Homeland Security Presidential Directive 10 (HSPD-10): "These assessments are meant to provide senior level decision makers with fresh, non-consensus, perspectives on key issues underlying the Nation's biodefense."  The first few pages of the report provide more information about the origin and use of the BNA.

My own motivation for doing this work is to better understand what is going on in the world.  When it comes to developing policy to improve security and safety, I unapologetically insist that data drive policy.  There are far too many people who develop policy in spite of data rather than in light of data.  That leads to messy thinking and demonstrably makes us less safe and less secure.  All that said, one conclusion from my work on this report is that nobody is doing a very good job of gathering and publishing the data necessary to understand the rapid technical and economic development of biotechnology around the world.

One final thought about the report: this particular document was funded by the U.S. government, and I was given a particular set of charges in the task (see pg iii-iv); the report is therefore tilted toward U.S. security concerns.  However, the basic analyses and conclusions are relevant to developing policy in any country, and for that matter to developing strategy for many private companies and other organizations.  I will continue work on this story, and look forward to engaging people around the globe in better understanding how our world is changing.

Here is the "Background" section of the report.  Please note that the report is now a few years old, and the bioeconomy has continued to grow rapidly around the world.

Biotechnology is becoming increasingly de-skilled and less expensive, leading to a proliferation of localized innovation around the world. In addition to major investments by growing economic powerhouses India and China, other developing countries such as Indonesia, Pakistan, and Brazil are equally intent on developing domestic biotech research and development capabilities. All of these countries are interested initially in producing drugs for diseases that predominantly affect their citizens, a project that requires a particular infrastructure and set of skills. Yet those same skills can be used to develop other applications, from fuels and materials to weapons, all of which can serve as a lever to increase power and presence on the world stage, thereby enabling developing countries to become rivals to the US both regionally and globally.

Economic demand will serve as a driver for ever greater proliferation of biotechnology. Today, in the US, revenues from genetically modified systems contribute the equivalent of almost 2% of GDP, and are growing in the range of 15 to 20% per year. China, among other countries, is not far behind and is following explicit government policy to substantially increase its independent, domestic development of new biological technologies to address such diverse concerns as healthcare, biomass production, and biomanufacturing. As is already the case in many other industries, trade between developing nations in biotech may soon exceed trade with the US. Therefore, among the challenges the US is likely to face in this environment is that the flow of technology, ideas, and skills may bypass US soil. Moreover, because skills and instrumentation are widely available, biotechnological development is possible in unconventional settings outside of universities and corporate laboratories. The resulting profusion of localized and distributed innovation is likely to provide a wide variety of challenges to US security, from economic competition, to intelligence gathering, to the production of new bio-threats.

Censoring Science is Detrimental to Security

Restricting access toscience and technology in the name of security is historically a losing proposition.  Censorship of information that is known to exist incentivizes innovation and rediscovery. 

As most readers of this blog know, there has been quite a furor over new results demonstrating mutations in H5N1 influenza strains that are both deadly and highly contagious in mammals.  Two groups, led by Ron Fouchier in the The Netherlands and Yoshihiro Kawaoka at The University of Wisconsin, have submitted papers to Nature and Science describing the results.  The National Science Advisory Board for Biosecurity (NSABB) has requested that some details, such as sequence information, be omitted from publication.  According to Nature, both journals are "reserving judgement about whether to censor the papers until the US government provides details of how it will allow genuine researchers to obtain redacted information".

For those looking to find more details about what happened, I suggest starting with Dorveen Caraval's interview with Fouchier in the New York Times, "Security in Flu Study Was Paramount, Scientist Says"; Kathleen Harmon's firsthand account of what actually happened when the study was announced; and Heidi Ledford's post at Nature News about the NSABB's concerns.

If you want to go further, there is more good commentary, especially the conversation in the comments (including from a member of the NSABB), in "A bad day for science" by Vincent Racaniello.  See also Michael Eisen's post "Stop the presses! H5N1 Frankenflu is going to kill us all!", keeping in mind that Eisen used to work on the flu.

Writing at Foreign Policy, Laurie Garrett has done some nice reporting on these events in two posts, "The Bioterrorist Next Door" and "Flu Season".  She suggests that attempts to censor the results would be futile: "The genie is out of the bottle: Eager graduate students in virology departments from Boston to Bangkok have convened journal-review debates reckoning exactly how these viral Frankenstein efforts were carried out."

There is much I agree with in Ms. Garrett's posts.  However, I must object to her assertion that the work done by Fouchier and Kawaoka can be repeated easily using the tools of synthetic biology.  She writes "The Fouchier episode laid bare the emptiness of biological-weapons prevention programs on the global, national, and local levels.  Along with several older studies that are now garnering fresh attention, it has revealed that the political world is completely unprepared for the synthetic-biology revolution."   As I have already written a book that discusses this confusion (here is an excerpt about synthetic biology and the influenza virus), it is not actually what I want to write about today.  But I have to get this issue out of the way first.

As far as I understand from reading the press accounts, both groups used various means to create mutations in the flu genome and then selected viruses with properties they wanted to study.  To clarify, from what I have been able to glean from the sparse accounts thus far, DNA synthesis was not used in the work.  And as far as I understand from reading the literature and talking to people who build viruses for a living, it is still very hard to assemble a functioning, infectious influenza virus from scratch.   

If it were easy to write pathogen genomes -- particularly flu genomes -- from scratch, we would quite frankly be in deep shit. But, for the time being, it is hard.  And that is important.  Labs who do use synthetic biology to build influenza viruses, as with those who reconstructed the 1918 H1N1 influenza virus, fail most of the time despite great skill and funding.  Synthesizing flu viruses is simply not a garage activity.  And with that, I'll move on.

Regardless of how the results might be reproduced, many have suggested that the particular experiments described by Fouchier and Kawaoka should not have been allowed.  Fouchier himself acknowledges that selecting for airborne viruses was not the wisest experiment he could have done; it was, he says, "really, really stupid".  But the work is done, and people do know about it.  So the question of whether this work should have been done in the first place is beside the point.  If, as suggested by Michael Eisen, that "any decent molecular biologist" could repeat the work, then it was too late to censor the details as soon as the initial report came out. 

I am more interested in the consequences of trying to contain the results while somehow allowing access to vetted individuals.  Containing the results is as much about information security as it is biological security.  Once such information is created, the challenge is to protect it, to secure it.  Unfortunately, the proposal to allow secure access only by particular individuals is at least a decade (if not three decades) out of date.

Any attempt to secure the data would have to start with an assessment of how widely it is already distributed.  I have yet to meet an academic who regularly encrypts email, and my suspicion is that few avail themselves of the built-in encryption on their laptops.  So, in addition to the university computers and email servers where the science originated, the information is sitting in the computers of reviewers, on servers at Nature and Science, at the NSABB, and, depending on how the papers were distributed and discussed by members of the NSABB, possibly on their various email servers and individual computers as well.  And let's not forget the various unencrypted phones and tablets all of those reviewers now carry around.

But never mind that for a moment.  Let's assume that all these repositories of the relevant data are actually secure.  The next step is to arrange access for selected researchers.  That access would inevitably be electronic, requiring secure networks, passwords, etc.  In the last few days the news has brought word that computer security firms Stratfor and Symantec have evidently been hacked recently.  Such attacks are not uncommon.  Think back over the last couple of years: hacks at Google, various government agencies, universities.  Credit card numbers, identities, and supposedly secret DoD documents are all for sale on the web.  To that valuable information we can now add a certain list of influenza mutations.  If those mutations are truly a critical biosecurity risk -- as asserted publicly by various members of the NSABB -- then that data has value far beyond its utility in virology and vaccinology.

The behavior of various hackers (governments, individuals, other) over the last few years make clear that what the discussion thus far has done is to stick a giant "HACK HERE" sign on the data.  Moreover, if Ms. Garrett is correct that students across the planet are busy reverse engineering the experiments because they don't have access to the original methods and data, then censorship is creating a perverse incentive for innovation.  Given today's widespread communication, restriction of access to data is an invitation, not a proscription.

This same fate awaits any concentration of valuable data.  It obviously isn't a problem limited to collections of sensitive genetic sequences or laboratory methods.  And there is certainly a case to be made for attempting to maintain confidential or secret caches of data, whether in the public or private interest.  In such instances, compartmentalization and encryption must be implemented at the earliest stages of communication in order to have any hope of maintaining security. 

However, in this case, if it true that reverse engineering the results is straightforward, then restriction of access serves only to slow down the general process of science.  Moreover, censorship will slow the development of countermeasures.  It is unlikely that any collection of scientists identified by the NSABB or the government will be sufficient to develop all the technology we need to respond to natural pathogens, let alone any artificial ones.

As with most other examples of prohibition, these restrictions are doomed before they are even implemented.  Censorship of information that is known to exist incentivizes innovation and rediscovery.  As I explored in my book, prohibition in the name of security is historically a losing proposition.  Moreover, science is inherently a networked human activity that is fundamentally incompatible with constraints on communication, particularly of results that are already disclosed.  Any endeavor that relies upon science is, therefore, also fundamentally incompatible with constraints on communication.  Namely developing technologies to defend against natural and artificial pathogens.  Censorship threatens not just science but also our security.

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.

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.

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?

Hey look -- I have an Idea!

On my head, that is.  Not in, alas, but on.  That's the way it goes, some days.  But at least I am pressing forward.  Or the idea on my head is.  That is what the sign says, anyway. 

carlson.jpgWeek before last, I spent an enjoyable couple of days at The Economist's Ideas Economy: Human Potential 2010.  I'll post the video when it is available.

Among the most interesting things I heard: Richard Florida says that the "creative sector" has never been above 5% unemployment, and that sector now constitutes 30% of the US workforce.  Here is his presentation:

I also had the chance to meet Vivek Wadhwa (very smart fellow), whose recent fascinating blog post on whether job creation comes from big companies or startups I have been pondering for weeks.  Here is a snippet from the post: "Startups aren't just an important contributor to job growth: they're the only thing. Without startups, there would be no net job growth in the U.S. economy. From 1977 to 2005, existing companies were net job destroyers, losing 1 million net jobs per year. In contrast, new businesses in their first year added an average of 3 million jobs annually."

The differing impacts of startups and established companies on the economy and on innovation are much on my mind these last few months.  Unconventional innovation tends to come from startups, and often from garages, and as I examine in my book that is precisely where we should be looking for new biological technologies.  I've been pondering what it takes for a small company developing a biological technology to succeed in industries dominated by Goliaths.  Microbrewing provides a great existence proof of the potential.  Garage biology is here.  Hang on to your hats.