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.

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

).

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.

Myriad's Lawyers Want to Patent the Periodic Table

Interesting arguments today before a Federal Appeals Court concerning the "BRCA 1/2" patents.  Recall first that the U.S. Government has filed an amicus brief supporting the trial judge's ruling that naturally-occurring genes cannot be patented (see "Big Gene Patent (Busting) News???" and "Surprise Outbreak of Common Sense in Washington DC").

The Appellate Court is going to decide whether two genes (BRCA 1 and 2), in which mutations are correlated with breast cancer, can be patented.  Myriad Genetics and its lawyers say yes, the ACLU and several groups representing patients, scientists, and clinicians say no.  So did the trial judge.  The basic argument is about whether a naturally-occurring gene sequence that is used in a diagnostic test can be considered an invention.

Nature's The Great Beyond blog has a bit of reporting from yesterday's proceedings.  There is a passage from the blog post I think is worth exploring a bit further for the way the litigants and the judges are talking about the nature of DNA and the nature of elements such as lithium:

Both the lawyers and the judges repeatedly compared the case to efforts to extract a valuable mineral from the ground.

"Why isn't the ingenuity [that justifies patentability] the process of extracting [the mineral]" rather than in the mineral itself, [Judge Kimberly Moore] asked [defendent's attorney Greg] Castanias. "God made it. Man didn't make it."

Castanias retorted: "What we have here are new tools [that are] the products of molecular biologists. They are not the products of nature. They are not the products of God."

If that's the case, [Judge William Bryson] pushed Castanias, are you saying that isolation of pure lithium is properly an invention?

"Yes," the lawyer replied.

That is extraordinary.  Castanias' assertion is contrary to more than a century of U.S. case law and administrative rulings by the USPTO.  Products of nature are explicitly excluded in laws, rulings, and administrative decisions from coverage by patents.  Castanias wants the Appellate Court to rule that the elements in the periodic table, along with any other naturally-occurring substance, are in fact patentable.

The mind boggles.  Following Castanias' reasoning pure oxygen, pure water, and pure gold could all be patented because some process was employed for purification.  If this sort of argument held sway, you could even patent the moon because you require a human invention to go visit and nab a piece of it.  Yes, yes, I know that other inconvenient case law would get in the way of patenting a celestial body, which really doesn't make any sense anyway.  But that is the point.  The trial judge in this case was actually the first to issue a ruling that patents on naturally-occurring genetic sequences are prohibited by law (see "Big Gene Patent (Busting) News???").

This argument revolves in part around the nature of DNA.  Here is another excerpt from the Nature blog post:

Chris Hansen, a staff attorney with the ACLU, told the judges: "Myriad's entire business is built on the proposal that isolated DNA and [naturally occurring] DNA are identical." They don't write to patients with their test results, saying: "You've got a mutation in your isolated DNA but I have no idea what's going on in your body," he said.

Judge William Bryson countered that the act of isolating DNA involves breaking covalent bonds, thus creating a product that does not exist in nature.

"With respect, your honor, I think not," Hansen replied. "DNA is DNA."

But Greg Castanias, a lawyer with the Jones Day firm in Washington DC who represented the defendants, begged to differ. "Isolated DNA does not exist in nature," and wouldn't exist at all without human ingenuity, he said. The entire biotechnology industry, he added, is built on interpreting existing law to say that DNA isolation is sufficient to show the human invention that is required for a patent.

I found the language quoted to be quite interesting.  The notion that "isolated DNA does not exist in nature" is based on the defendants' definition of "isolated DNA".  Judge Sweet spent three pages of his original decision dealing with Myriad's assertions about "isolated DNA", but it is hard to know from the Nature blog post whether this was part of yesterday's conversation.  Here is Judge Sweet's definition (p. 92 of his decision): "Isolated DNA is therefore construed to refer to a segment of DNA nucleotides existing separate from other cellular components normally associated with native DNA, including proteins and other DNA sequences comprising the remainder of the genome, and includes both DNA originating from a cell as well as DNA synthesized through chemical or heterologous biological means".

This is quite close to Myriad's definition of "isolated DNA", but Judge Sweet still found that because the isolated DNA is the same sequence, and therefore conveys the same information, as the sequence in vivo, it cannot be patented because it is a product of nature.

Incidentally, the definition of isolated DNA given above appears to include DNA that is free in the environment.  Free DNA is found in marine and terrestrial environments.  That DNA can be taken up by other organisms via horizontal gene transfer, which means that free DNA is perfectly funtional.  Here, for example, is an interesting little study looking at the uptake of free DNA by aquatic bacteria.

The point being that humans did not invent DNA that is "separate from other cellular components".  Humans may have invented processes to concentrate and purify DNA, or to extract DNA from complex structures, but that does not mean that isolated DNA is itself a human invention.

Video from "Preserving National Security: The Growing Role of the Life Sciences"

A couple of weeks ago I spoke at an event run by the UPMC Center for Biosecurity, Preserving National Security: The Growing Role of the Life Sciences.  Here is the video of my presentation, followed by Roger Breeze, with an introduction by Gigi Gronvall.  There is a short panel discussion at the end of the clip.  Video of the rest of the meeting is also online, along with a conference report (PDF).

Ice Loss Acceleration in Antarctica and Greenland

This month's Geophysical Research Letters brings more ice sheet melting data to be concerned about.  A paper by Eric Rignot and colleagues at JPL, Caltech, UC Irvine, and Utrecht University demonstrates the "Acceleration of the contribution of the Greenland and Antarctic ice sheets to sea level rise".  Here is a nice summary at ScienceDaily that goes into some broader implications for sea level rise.  In addition to putting a bunch of nice data and analysis on the table, Rignot et al will contribute substantially to a broader understanding of the overall ice/water system near the poles.

The paper describes work integrating a variety of methods to build up a two decade-long picture of ice mass loss in Antarctica and Greenland.  The numbers by themselves are pretty impressive: the ice sheet loss rate was ~478 Gigatons/year in 2006, with an acceleration of ~36 Gigatons/year^2.  Note that this means the acceleration is 7.5% of the rate -- in other words, ice sheet mass loss is speeding up at a remarkable clip for a process that is ongoing at continental length-scales.  Notably, the authors report a very small uncertainty in the acceleration (about 5%), which means that we can be quite certain there is a large non-linear contribution that is reducing ice sheet mass (one that is proportional to time^2).

Here are a few tidbits that are not in the paper or associated press stories.  I wrote to Dr. Rignot to satisfy my curiosity about a couple of points, and he graciously responded and gave me permission to quote the emails here.

First, after staring at the ice loss rate and acceleration data for a little while, I got to wondering why the authors extracted a linear change in the rate of ice loss, which results in a constant acceleration.  Given the data, you might wonder whether the acceleration was actually increasing rather than being a constant.  In our brief email exchange, Dr. Rignot said that while the linear fit was the simplest fit, it appears that, in fact, the acceleration is increasing in Antarctica (no word from Dr. Rignot about Greenland).  The team is going to wait for a few more years worth of data -- to increase their certainty and better constrain the statistical significance -- before they talk more about it.

This is pretty important.  We are talking about adding a highly non-linear term to models of the total ice sheet mass, one that is proportional to (time^3).  Depending on the size of the change in acceleration, this could radically change estimates of sea level rise from melting.

The present paper already demonstrates that ice sheet loss will account for substantially more sea level rise than is included in the IPCC models.  In addition, the authors observe that increased mass loss is likely to lead to a substantial increase in the speed at which glaciers deliver ice to nearby water, something that is not adequately addressed (or is simply not included, if you are following that story) in IPCC forecasts.

Perhaps it is time to revisit investing in water wings.

"Garage Innovation" in The Scientist

My column in this month's The Scientist is now available online.  "Garage Innovation" was written based on my presentation to the Presidential Commission on for the Study of Bioethical Issues and my experience over the last few years navigating discussions on regulating biological technologies.

I had to write the piece without having access to the Commission's recommendations, and relying instead on press reports of what Commission members said about the draft.  Now that I have perused the report (BIG PDF), I mostly like what I see.  Here is the relevant press release.  I'll have something more on the report after I have a chance to sit down and fully digest it.

Fly On the Wall: 2010 Meeting of States Parties to the Biological Weapons Convention

Last week I made it through the snow in Europe to attend meetings in Paris and Geneva.  In Paris I spoke at a joint meeting of the OECD and the ESRC Genomics Network, Delivering Global Promise Through the Life Sciences.  (I'll post a link to the slides when the conference puts it online.)  Then I hopped a TGV to speak at the UN at the 2010 Meeting of States Parties to the Biological Weapons Convention.

After giving my talk in Geneva, (here is my slide deck, "Engineering a More Secure Future") I sat in the back row of the official Meeting of States Parties.  I spent some time listening to the simultaneous translation of the public session on building national capacity for public health, watching the diplomatic sausage get made.

Among the interesting things I heard: the Russian representative emphasized their position on the need for a standing body for national inspection and enforcement of the Convention.  This from a country that, even after signing the BWC, maintained an extensive offensive biological weapons program until relatively recently.

Also, Iran asserted that it is having difficulty obtaining standard infectious disease strains due to various international restrictions and sanctions.  Noted that trust is a basis of all relationships.  Indeed.  Elsewhere in the building, Iran was simultaneously stating there would be no discussion of its uranium enrichment program in upcoming talks.

Finally, a minor tiff as Armenia made mention of the disputed region of Nagorno-Karabakh (NK), whereupon Azerbajan, within whose borders that region is presently located, then exclaimed that discussing NK has no place at the BWC Conference.  Armenia returns with, approximately, 'Regardless of who owns land, all people deserve care.'  Can't argue with that.

Okay, then.  That's more than enough sausage for one day.

Dipping My Toes in International Diplomacy, or Simulating Combat Flying in a British Taxi

In late September I spoke at a warm-up meeting for the 2011 Review Conference of the Biological Weapons Convention (BWC).  The BWC, as I understand it, is administered by the UN but is a direct agreement between the signatories, otherwise known as "States Parties".  The Review Conferences take place every five years.  The meeting was held at Wilton Park, an independent, academic branch of the British Foreign Office.  The venue was founded by Winston Churchill in 1946 as a "a forum for democracy building, post-conflict reconciliation and international dialogue".  Wilton Park is now housed at Wiston House, the initial construction of which dates back to the sixteenth century, and the style of the place certainly gives a unique air to proceedings there.  Here is a BBC story from a few years ago that provides more history.

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The meeting was attended by a very interesting collection of ambassadors, diplomats, scholars, and foreign-office types from around the world.  Definitely not my usual drinking buddies.  But more on that later.  Before continuing, to be clear: I was there in a personal capacity, invited by the organizers and meeting sponsors (Wilton Park and the British and Dutch Foreign Offices), and I was in no way representing the US government.

I gave the opening talk, during which I focused on how biological technologies have advanced in the last five years, who is investing and how revenues are apportioned worldwide, and what we may see in the bioeconomy over the next five years.  Much of what I said was evidently new to the assembled crowd, which led to some interesting conversation.  Time for another pause: According to the Wilton Park Protocol, under which the meeting was held, "participants are free to use the information and views discussed in the conference, but no individual speaker or participant should be quoted", so I will do my best to tread carefully.

There are, in fact, only a couple of things I think are worth passing on in this post because they may have some impact on public policy discussions more broadly.  My personal predilection is to measure what I can about the world and then figure out where to go once I have established an understanding of where we are.  In particular, I have been trying to understand the global bioeconomy because many countries around the world are investing heavily in biological technologies in order to be dominant players in the 21st century.  Most of those technologies and related skills are explicitly dual use; that is, they can be used to create good or cause harm.  It simply makes sense to me to figure out what those countries are up to and what the consequences are before taking any action, political or otherwise.

Not everyone thinks that this procedure is the way to make public policy.  After I presented data on how various countries are investing, and on how fast their domestic skilled biotech labor pools and domestic biotech revenues are growing, this was waved away by one group with (very approximately) 'Do not tell me about revenues and economic activity: we should decide on how we want the world to be and then implement it!'  This left me somewhat at a loss for words.  I was surprised at the notion that any one of the States Parties might feel, in today's geopolitical and economic climate, that it could dictate terms to any other Party.  Particularly in a technological area that is deemed crucial for economic competitiveness and success.  More generally, I am confused by the notion that a qualitative goal in an area of policy can be set before an effort is made to understand, and to quantify if possible, the size and shape of that area.  What if proposed qualitative goals are already irrelevant, or even misguided, given the current state of the world?

Somewhat later in the meeting, I observed that the National Strategy for Countering Biological Threats -- written by the National Security Council and signed by the President -- states that garage biology is good and necessary for the political and economic security of the United States.  I then made my usual observation that garages are the source of most of the innovative technologies in the global economy.  The response to this from one group was also interesting (again, very approximately): 'This garage or DIYBio is only a problem in the US.  In our country it is illegal to do such things.'  I managed to bite my tongue at this juncture -- recalling the setting, and aided by the fact that the session chair forgot to give me a chance to respond (for which he apologized later, though I silently thanked him at the time). But what I really wanted to observe aloud was that it must be very nice to live in a country where nothing bad happens because all bad things are illegal; I will try to remember that next time I get off an airplane or train there to be greeted by paramilitary troops with their fingers on the triggers of sub-machine guns.  Fortunately for me, at this point the conversation wandered off into a very apt discussion about intent and misuse, as opposed to dual use, a characteristic that biology shares with many other technologies.

Which brings me to my second confusion, which is that while it is all very well and good to define areas of misuse, perhaps by making it 'illegal', and to define potential responses to that misuse, simply defining that misuse does little to prevent it.  That is, with biological technologies already spreading around the world at a rapid clip, and with innovation in those technologies taking place in countries that may care little about any given definition of misuse, those definitions amount to security theater of the worst kind.  I have yet to hear any proposal for biosecurity that recognizes the futility of physical prohibition or containment of using biological technologies.  Preventing access to technologies by the wrong sort of chap sounds great, but in this context it is unlikely to work, and therefore only makes it sound like we are safer rather than actually making us safer.

Perhaps admitting the above in print here means my future as a diplomat is limited.  Oh well.  And with that I must curtail any further description of the discussions. 

While I can comment on only a small fraction of what was said at the meeting, I can relate a few other anecdotes from the trip.  The Wilton Park experience lives up to one's expectations: formal dinners, preceded by cocktails; a formal group photo in which you might find yourself standing next to an ambassador; nightly excursions to the bar, during which discussions continue amidst libations.  I have never been much of a scotch drinker, but one must, after all, be adaptable.  Particularly when, upon learning of this educational deficiency, an Ambassador takes you aside and does the buying.  "Young man, you should really give this a try."  I could be a convert.

The most memorable bit of the trip, however, was what happened the next afternoon, upon the close of the meeting.  Just after a rather large English lunch (can you say, "foreshadowing"?),  the American delegation shanghaied me for the ride back to London.  This ride took place in one of those tall, European passenger vans.  The ones that look somewhat unstable and that one might expect to sway considerably going around corners.  There were seven seats in the van.  One up front with the driver, three in the back facing forward, and three more facing backward.  I believe everyone in the van ate approximately the same, large English lunch.

Facing forward were three officials from the US State Department (hereafter State 1, State 2, and State 3).  Facing backward were myself, (following the naming convention) White House 1, and Defense 1, who is a PhD who spent an earlier life jumping out of helicopters with bullets flying.

The trip began slightly ominously, because I was originally seated facing forward, and State 1, who was last into the van and thus got a seat facing backward, politely asked to switch with me because she was prone to motion-sickness.  How could I refuse?  I had been motion-sick exactly once in my life, and never at sea, and that one time only because my lovely wife was sitting next to me on the airplane and led the way.  But I digress.

The taxi set off, and I was surprised to be included in conversations about potential diplomatic breakthroughs with various attendees at the meeting.  We had a jolly good time as the taxi driver wound his way through the English countryside, eschewing the nearby straight-as-an-arrow motorway for as many narrow, winding country lanes as possible.  This being England, the driving is on the left side of the country lane.  This being England, those country lanes intersect at roundabouts, wherein a taxi making a right turn involves first throwing passengers through a hard left to get into the roundabout, slamming the wheel over and accelerating hard to the right for 270 degrees around the circumference, followed by a short hard left to get onto the next country lane.  And repeat.  This particular driver evidently set about finding as many roundabouts as he could.  And then seemed to traverse some of them several times.  Just for kicks.  To my inner ear.

Where was I?

Ah, yes; diplomatic breakthroughs, discussions of how much various countries are investing in biotech, and what the medium- to long-term consequences are for the physical and economic security of the US.

And then another roundabout.  Whereupon State 1 suddenly -- for reasons I simply cannot fathom -- changes the subject and the following conversation ensues:

State 1: "Are you fellows feeling alright?

Myself, White House 1, and Defense 1: "Oh, fine."

State 1: "You are all looking a bit green."  Pause.  "Smint?  They help settle the stomach."

Me: "Nah, I'm fine."

White House 1 and Defense 1 (hereafter to be thought of as "The Sensible Ones"): "Sure."

<intervening roundabout>

State 1: "Smint?"

Me: "Uh, sure."

State 2: To the driver: "Can we get some windows open, please?"

White House 1: "I have a bag, just in case."

Me: <breathe in, breathe out> <breathe in, breathe out>  Out loud: "Um, no thanks."

Me, out loud, in a half-hearted attempt at humor: "It's a giant shopping bag: You prepared for this?"  To myself: Put the fucking bag away White House -- are you nuts?!?  Six people, confined space, big lunch: If one of us goes, we all go.  Don't even give anyone the option!

State 1: "So about country X..."  Pause.  "Are you sure you guys are alright?"

Defense 1: Enthusiastically: "This is just like flying in the back of a helicopter!"  With even more gusto: "I'm ready to go into combat!"

White House 1: Remember his own days in uniform: "Um, I was just thinking that."

Me: <breathe in, breath out>

State 1: "Smint?"

Somehow, just about then, or quite possibly many hours later, we arrived in central London.  At least some of us talked about business for at least part of that taxi ride.  The bag remained empty.

I'm headed to Geneva for the next BWC event, the Meeting of States Parties from 6-10 December.  There I will be speaking along with Andrew Hessel and Drew Endy in a session on "Synthetic Biology: Building a Secure Future".  I don't know if there will be any more late night scotch on this trip, but I certainly hope to avoid more taxi rides that simulate riding a helicopter into combat.

Surprise Outbreak of Common Sense in Washington DC

News today that the Justice Department has filed an amicus brief outlining a new position that naturally occurring genes should not be patentable.  The New York Times is reporting that "while the government took the plaintiffs' side on the issue of isolated DNA, it sided with Myriad on patentability of manipulated DNA."  The change in position was evidently prompted by the decision of a federal judge this past spring that certain claims in what are known as the BRCA 1/2 patents should be overturned because those genes are preexisting in nature.  Perhaps Jon Stewart has more influence in DC than we all thought.

I am largely on board with the line taken by the Justice Department.  It is pretty close to my own analysis, as described in my post from last spring: "Big Gene Patent (Busting) News???"  There are, however, a few bits that I am still chewing on, which I will get to later.

First, in broad strokes, the government's brief supports the decision of District Judge Robert Sweet that naturally occurring gene sequences are not patentable, but weighed in against Judge Sweet's analysis that DNA coding for natural genes is not patentable if it has been restructured in an artificial construct but is still the same sequence as occurs in nature.  The most obvious example of the latter is a coding sequence with all introns removed and packed in a plasmid as a cDNA.

Here is the Justice Department's language (the text of the brief is available via the NYT page):

The district court erroneously cast doubt on the patent-eligibility of a broad range of man-made compositions of matter whose value derives from the information-encoding capacity of DNA. Such compositions -- e.g., cDNAs, vectors, recombinant plasmids, and chimeric proteins, as well as countless industrial products, such as vaccines and genetically modified crops, created with the aid of such molecules -- are in every meaningful sense the fruits of human ingenuity and thus qualify as "'human-made inventions'" eligible for patent protection under section 101. (p.9)

...The district court correctly held, however, that genomic DNA that has merely been isolated from the human body, without further alteration or manipulation, is not patent-eligible. (p.10)

...Indeed, the relationship between a naturally occurring nucleotide sequence and the molecule it expresses in a human cell -- that is, the relationship between genotype and phenotype -- is simply a law of nature. (p.10)

Here is the meat:

The chemical structure of native human genes is a product of nature, and it is no less a product of nature when that structure is "isolated" from its natural environment than are cotton fibers that have been separated from cotton seeds or coal that has been extracted from the earth.

The scope of Section 101 is purposefully wide and its threshold is not difficult to cross.  See Bilski, 130 S.Ct. at 3225.  New and useful methods of identifying, isolating, extracting, or using genes and genetic information may be patented (subject to the prohibition against patenting abstract ideas), as may nearly any man-made transformation or manipulation of the raw materials of the genome, such as cDNAs. Thus, the patent laws embrace gene replacement therapies, engineered biologic drugs, methods of modifying the properties of plants or generating biofuels, and similar advanced applications of biotechnology. Crossing the threshold of section 101, however, requires something more than identifying and isolating what has always existed in nature, no matter how difficult or useful that discovery may be. (p.11)

It might seem that the Justice Department gives back a lot of power to those who hold patents on natural genes by including cDNAs (with introns removed) as patentable material.  This would seem to give patent holders a lock on the human proteins those genes encode, because the most common way to make a protein is to use a cDNA (or similar) to express a protein in a host like E. coli or yeast.  So unless people come up with a good way to cause overexpression of human proteins from native genes via mechanisms that chop out the introns -- and some methods like that do exist -- the patent seems to block use of the protein.

But I am not sure that this brief gives any succor to those hoping for patent protection of a genetic diagnostic.  Those diagnostics generally work by using a short sequence of the gene in question as a PCR primer to find (or exclude) particular sequences of clinical interest in a patient's genome.  Those primers generally can be found in regions of DNA not interrupted by an intron, or can include the intron in the primer sequence, which means that the primer can consist of sequences that were preexisting in nature.  Only if the primer has to be composed of a sequence that -- in nature -- is interrupted by an intron but is only found in somebody's edited cDNA library without that intron would a patent protect the diagnostic assay.

A penultimate thought on the brief: I am still pondering whether the Justice Department lawyers, in their extended discussion of DNA as information carrying medium, got their analysis right.  I will have to read the brief again.  And perhaps again after that.

Finally, the brief leaves most of my previous conclusions intact, namely that the biggest impact of Judge Sweet's ruling that natural sequences cannot be patented may be for work in organisms other than humans.  From my post last May:

...the rest of the biotech industry shouldn't be concerned about thisruling, frankly.  They might even celebrate the fact that they now have access, potentially, to a whole bunch more genes that are naturally occurring.  Not just in humans, mind you, but any organism.  This opens up a rather substantial toolbox for anybody interested in using biological technologies derived from viruses, bacteria, plants, etc.  If it holds up over the long run, Judge Sweet's decision should accelerate innovation.  That is definitely a good thing.

Now we wait for what the appellate court has to say.