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).

Ah, technology...

I just finished addressing a meeting in Islamabad, Pakistan -- Synthetic Biology and its Dual Use.  I was scheduled to give my talk via two-way video teleconference that turned out to be ... one-way.  So rather than being able to interact with my audience, I had to simply page through my presentation on my end and hope they were still listening.  I was basically practicing my talk, except there was a live video connection to the other side of the world.  Very strange.

Garage Innovation and Recreational Drugs

(12 July, 2012: Updated with a few comments on recent US efforts to ban synthetic drugs.)

When a carpenter turns to chemistry to pay the rent, you can be certain innovation has been democratized.  As told by Jeanne Whalen in The Wall Street Journal, chemo-entrepreneur David Llewellyn found it an easy transition to begin making recreational drugs when his construction business tanked.  Llewellyn specializes in making "legal high" drugs for sale in Europe, always ready to move onto the next compound when authorities ban whatever he has been selling.  And he intends to keep operating that way: "Everything we sell is legal. I don't want to go to jail for 14 years."  This story has interesting implications for anyone interested in the future of synthetic biology, and in particular those who feel that regulating access to tools, skills, and materials will lead to a safer world.  But I will get to that later.

Welcome to the real world, Neo.  And to the spotlight.

Mr. Llewellyn looks to academic literature for inspiration for the next drug, and the WSJ named Purdue chemist David Nichols' papers as the source of several such drugs.  The WSJ article led Nichols to pen an essay for the 6 January issue of Nature entitled "Legal highs: the dark side of medicinal chemistry".  He writes: "Although some of my results have been, shall we say, abused, one cannot know where research ultimately will lead. I strive to find positive things, and when my research is used for negative ends it upsets me."  The essay constitutes a bit of soul searching, with an unspoken conclusion that he is doing the best he can to try to make the world a better place.  Here is NPR's version of a subsequent AP story on Professor Nichols.

Underlying the Professor's discomfort is that simple fact that science, as a method and as information, is value neutral.  By this I mean that regardless of what prompted a particular line of research (which might, in fact, be motivated by particular values), the resulting information is neither good nor bad.  It is just information.  That said, obviously that information will be used by humans for both good and bad ends.  This is about as close as I can get to a statement of fundamental human nature.  Humans will do good things and they will do bad things -- just as we always have -- with "good" and "bad" of course being highly contingent definitions.

The world we live in is dirty, full of disease and despair, and some people have no problem contributing to the mess.  It is very easy to sometimes forget this when working within a university.  But Science (with a capital "S", please) is just another human institution, inhabiting that same dirty world.  Anyone who does anything that hurts another person in today's world is likely using some bit of science or technology invented by somebody who was attempting to improve the world.  Pointing a finger at Professor Nichols as the source of information used to manufacture drugs that cause harm is like pointing a finger at whomever invented the screwdriver as the source of suicide bombers, or like pointing a finger at Isaac Newton as the source of ballistic missiles.  Academic publishing makes it easy to trace Professor Nichols by his research, and thus to point a finger at him, but that completely misses the point and is a distraction.

Laboratory-Adept Entrepreneurs: Just Trying to Pay the Rent

For his own part in this story, David Llewellyn is self-cast as a bit of a underdog trying to make an interesting living while keeping just this side of today's definition of "good".  From Ms. Whalen's WSJ article:

Mr. Llewellyn is part of a wave of laboratory-adept European entrepreneurs who see gold in the gray zone between legal and illegal drugs. They pose a stiff challenge for European law-enforcement, which is struggling to keep up with all the new concoctions. Last year, 24 new "psychoactive substances" were identified in Europe, almost double the number reported in 2008, according to the Lisbon-based European Monitoring Centre for Drugs and Drug Addiction, or EMCDDA.

As he scurries to stay ahead of the law, authorities have put speed bumps, not roadblocks, in his path. Mr. Llewellyn says Belgian customs officials recently raided one of his storehouses and seized his chemicals, threatening to use environmental laws to shut him down. And he says he may have to move one of his production labs from the Netherlands because authorities there are planning to outlaw the use of certain lab equipment without a professional license.

...Other than that, however, Mr. Llewellyn's business is cruising along largely unimpeded. He and eight employees make drugs in a pair of "underground" labs--one in Holland and a new, $190,000 lab in Scotland.

If you are inclined to believe that it should be easy to solve problems through regulation or licensing, the very existence of Mr. Llewellyn's operation might give you pause.  If the Belgian authorities threaten to shut him down with environmental laws, it isn't going to be that hard to get them to go away because so many other "legitimate" businesses somehow manage to comply with those same environmental laws even while using the same raw materials -- and the "legitimate" companies are probably managing this with much lower profit margins.  Or perhaps governments could attempt to impose license restrictions on anyone using a particular material or laboratory instrument, but then of course they would be imposing those costs on all such users, "legitimate" or otherwise.  Finally, you might hope to directly stop Mr. Llewellyn from making or selling his wares.  And then you would fail outright, because there are so many potential compounds of interest that the regulations would have to restrict making anything that might someday be found to possibly cause harm to humans.  And that would shut down the entire chemical industry, and thus the entire economy.

(Update: Wired is reporting that a ban on certain synthetic drugs signed into law by President Obama in June of 2012 has already been made obsolete -- within a few weeks -- by new compounds not covered by the law.  Senator Charles Schummer called the law "the final nail in the coffin for the legal sale of bath salts."  Not so much, I guess.)

Trouble for a Nose

Mr. Llewellyn describes Nopaine, a chemical derivative of Ritalin, as "every bit as good as cocaine. You can freebase it. You can snort it like crack."

Whatever one thinks of Mr. Llewellyn's product guarantees, or of his marketing copy, he might be right.  Nopaine might be as "good" as cocaine.  Or it might, as is the concern of Professor Nichols, cause death, liver cancer, or other long-term damage.  But Mr. Llewellyn can make it to market with a synthetic compound created in his "underground lab" without having to find out whether it is good or bad.

Whether you like it or not, innovation of this sort is here to stay.  It may be hard these days to buy a chemistry set for your kid that is in any way interesting, but it is demonstrably easy to incorporate and get one's mitts on enough information and raw materials to synthesize compounds new to science.  And even if this becomes hard in any particular country, the general problem of widely accessible information and infrastructure is here to stay.       

Many of the "legal highs" evidently come from China, as must some of the raw materials used by Mr. Llewellyn and his ilk.  Ms. Whalen's earlier article "Designer Drugs Baffle Europe", from July of 2010, notes that in China "lax control of chemicals makes it easier for manufacturers to obtain the raw ingredients."  Her later article suggests that China is attempting to control the manufacture and sale of some new compounds, but I am not sure I have much confidence in that effort.  If it becomes too annoying (and it will never be more than annoying for those interested in making and selling drugs) to operate in China, or somewhere in Eastern Europe, they will pick up and move elsewhere.  And they will still have access to international markets wherever they go.  Our policy may be to fight them, to chase them away, but we will never fully prevail.

Which brings us back to definitions of "good" and "bad".  "Bad" Mr. Llewellyn isn't acting alone; he has "bad" customers.  Their aggregate demand supports the market.  (Oh, and wait a moment -- what Mr. Llewellyn is doing is actually legal, so therefore it is "good"?)  Unless governments somehow come up with a way to keep people from imbibing "bad" substances, defined as "bad" on any given day, the demand for those substances isn't going away.

Chemistry Today, Biology Tomorrow

There was a time when synthetic chemistry was not so easy.  And then some time passed, and now today we can order novel psychoactive drugs over the Internet.  Or make them ourselves.

Today it is hard to build a genetic circuit that does exactly what you want.  Synthetic biology is in its infancy.  Yet it is already possible to outfit a lab in your garage (at least in the US) that is sufficient to do all kinds of interesting things.  And if you don't have room in your garage, then you can stroll down to the corner DNA hackspace.  (Update: Genspace's Dan Grushkin wrote in to observe that I have unintentionally juxtaposed drug production and Genspace in an unfortunate way, which was of course not my intent at all.  Note that I did this to myself, too, as one of the former examples was my own garage lab.)  Access to tools doesn't make molecular biology easy, but it does give you the opportunity to learn, and perhaps to innovate.

And thus people will innovate with biological tools and information just as they have with everything else.  That innovation will be "good", and it will be "bad".  Regulation will not be a panacea for biological technologies, and will not necessarily make the world a safer place, just as regulation fails in the case of chemistry.  As I argued last month in Garage Innovation in The Scientist, restriction of access will always produce perverse incentives when there is an "attempt to control tools and skills in the context of a market in which consumers are willing to pay prices that support use of those tools and skills".

I am reminded of my experience last year at a warm-up meeting for the 2011 Review Conference for the Biological Weapons Convention.  At one point in the discussion, one delegate asserted that "garage or DIYBio is only a problem in the US.  In our country it is illegal to do such things."

I wonder if this delegate knows whether or not a chemo-entrepreneur has an "underground lab" next door?

The Economist debate on the most significant technological development of the 20th century

The Economist has just posted my invited comments on their current debate: "This house believes the development of computing was the most significant technological advance of the 20th century."

As with the last time I was invited to be a "guest speaker" (just one of the oddities of horning an Oxford-style debate into an online shoe), I have difficulty coloring between the lines.  Here are the first couple of graphs of today's contribution:

The development of computing--broadly construed--was indeed the most significant technological advance of the 20th century. New technologies, however, never crop up by themselves, but are instead part of the woven web of human endeavour. There is always more to a given technology than meets the eye.

We often oversimplify "computing" and think only of software or algorithms used to manipulate information. That information comes in units of bits, and our ability to store and crunch those bits has certainly changed our economies and societies over the past century. But those bits reside on a disk, or in a memory circuit, and the crunching of bits is done by silicon chips. Those disks, circuits and chips had to improve so that computing could advance.

Progress in building computers during the mid-20th century required first an understanding of materials and how they interact; from this knowledge, which initially lived on paper and in the minds of scientists and engineers, were built the first computer chips. As those chips increased in complexity, so did the computational power they conferred on computer designers. That computational power was used to design more powerful chips, creating a feedback loop. By the end of the century, new chips and software packages could only be designed using computers, and their complex behaviour could only be understood with the aid of computers.

The development of computing, therefore, required not just development of software but also of the ability to build the physical infrastructure that runs software and stores information. In other words, our improving ability to control atoms in the service of building computers was crucial to advancing the technology we call "computing". Advances in controlling atoms have naturally been extended to other areas of human enterprise. Computer-aided design and manufacturing have radically changed our ability to transform ideas into objects. Our manufactured world--which includes cars, aircraft, medicines, food, music, phones and even shoes--now arrives at our doorsteps as a consequence of this increase in computational power.

I go on to observe that computation is already having an effect on food through increased corn yields courtesy of gene sequencing and expression analysis.

Like so:

Biodesic_US_corn_yield.pngClick through to read the rest.

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.

DIYBio and Making at the BBC

This morning's biosecurity update from the Partnership for Global Security carried a mess of links I hadn't seen, including a story at the BBC entitled "Tech Know: Life hacking with 3D printing and DIY DNA kits".  The embedded video has an interesting clip on a printed stainless steel Mobius strip with freely moving rings that can run around the perimeter -- interlinked complex shapes.  Neat.  (Not a new thing in plastics, but I hadn't seen it in metal before.)

Cambridge's James Brown gets the honor of introducing the Beeb's audience to synthetic biology, biobricks, and engineering methods for biological systems.  The 3D-printed DremelFuge gets a photo and a significant mention.  I explicitly pointed to this sort of application of 3D printing in my book, though it is happening even faster than I had imagined.  Shapeways is now printing all sorts of interesting materials, though the resolution of most 3D printers and processes still doesn't make them useful for the sorts of objects I want to print.  That said, there is clear improvement over time.

It will be interesting to see how long it takes before you can print mixed media functional objects, say something like a zero-dead volume, positive displacement membrane pump.  Or better yet an entire pump block.  (Which is usually milled from a piece of stainless steel -- see where this is going?)  That gets you the most annoying bit of kit needed for a DNA synthesizer.  At which point you can forget any regulations limiting access to DNA of any sequence. 

"National Strategy for Countering Biological Threats"

I recently had cause to re-read the National Strategy for Countering Biological Threats (Full PDF), released last fall by the National Security Council and signed by the President. I think there is a lot to like, and it demonstrates a welcome change in the mindset I encounter in Washington DC.

When the document came out, there was just a little bit of coverage in the press. Notably, Wired's Threat Level, which usually does a commendable job on security issues, gave the document a haphazard swipe, asserting that "Obama's Biodefense Strategy is a Lot Like Bush's".  As described in that post, various commentators were unhappy with the language that Under Secretary of State Ellen Tauscher used when announcing the Strategy at a BWC meeting in Geneva. According to Threat Level, "Sources tell this reporter that the National Security Council had some Bush administration holdovers in charge of editing the National Strategy and preparing Ms. Tauscher's script, and these individuals basically bulldozed the final draft through Defense and State officials with very little interagency input and with a very short suspense." Threat Level also asserts that "Most are disappointed in the language, which doesn't appear to be significantly different than the previous administration." It is unclear who "Most" are.

In contrast to all of this, in my view the Strategy is a clear departure from the muddled thinking that dominated earlier discussions. By muddled, I mean security discussions and policy that, paraphrasing just a little, went like this: "Biology Bad! Hacking Bad! Must Contain!" 

The new National Strategy document takes a very different line. Sources tell this reporter, if you will, that the document resulted from a careful review that involved multiple agencies, over many months, with an aim to develop the future biosecurity strategy of the United States in a realistic context of rapidly spreading infectious diseases and international technological proliferation driven by economic and technical needs. To wit, here are the first two paragraphs from the first page (emphasis added, of course):

We are experiencing an unparalleled period of advancement and innovation in the life sciences globally that continues to transform our way of life. Whether augmenting our ability to provide health care and protect the environment, or expanding our capacity for energy and agricultural production towards global sustainability, continued research and development in the life sciences is essential to a brighter future for all people.

The beneficial nature of life science research is reflected in the widespread manner in which it occurs. From cutting-edge academic institutes, to industrial research centers, to private laboratories in base­ments and garages, progress is increasingly driven by innovation and open access to the insights and materials needed to advance individual initiatives.

Recall that this document carries the signature of the President of the United States.  I'll pause to let that sink in for a moment.

And now to drive home the point: the new Strategy for Countering Biological Threats explicitly points to garage biotech innovation and open access as crucial components of our physical and economic security. I will note that this is a definite change in perspective, and one that has not fully permeated all levels of the Federal bureaucracy and contractor-aucracy. Recently, during a conversation about locked doors, buddy systems, security cameras, and armed guards, I found myself reminding a room full of biosecurity professionals of the phrase emphasized above. I also found myself reminding them -- with sincere apologies to all who might take offense -- that not all the brains, not all the money, and not all the ideas in the United States are found within Beltway. Fortunately, the assembled great minds took this as intended and some laughter ensued, because they realized this was the point of including garage labs in the National Strategy, even if not everyone is comfortable with it. And there are definitely very influential people who are not comfortable with it. But, hey, the President signed it (forgive me, did I mention that part already?), so everyone is on board, right?

Anyway, I think the new National Strategy is a big step forward in that it also acknowledges that improving public health infrastructure and countering infectious diseases are explicitly part of countering artificial threats. Additionally, the Strategy is clear on the need to establish networks that both promulgate behavioral norms and that help disseminate information. And the new document clearly recognizes that these are international challenges (p.3):

Our Strategy is targeted to reduce biological threats by: (1) improving global access to the life sciences to combat infectious disease regardless of its cause; (2) establishing and reinforcing norms against the misuse of the life sciences; and (3) instituting a suite of coordinated activities that collectively will help influence, identify, inhibit, and/or interdict those who seek to misuse the life sciences.

...This Strategy reflects the fact that the challenges presented by biological threats cannot be addressed by the Federal Government alone, and that planning and participation must include the full range of domestic and international partners.

Norms, open biology, better technology, better public health infrastructure, and better intelligence: all are themes I have been pushing for a decade now. So, 'nuff said on those points, I suppose.

Implementation is, of course, another matter entirely. The Strategy leaves much up to federal, state, and local agencies, not all of whom have the funding, expertise, or inclination to follow along. I don't have much to say about that part of the Strategy, for now. But I am definitely not disappointed with the rest of it. It is, you might say, the least bad thing I have read out of DC in a long time.