On the Assembly of Things

“Crying wolf over bioterrorism” in the Los Angeles Times

The threat posed by synthetic bugs is microscopic. So why are U.S. officials making such a big deal?

By Wendy Orent
March 2, 2008

‘Mother Nature is the most dangerous terrorist,” says Michael Kurilla, the nation’s unofficial biodefense czar. “The microbial world is almost unlimited in its [terrorist] potential.”

But despite the emergence of such new diseases as SARS and the H5N1 avian flu, it isn’t Mother Nature only that worries Kurilla, the director of the Office of Biodefense Research Affairs of the National Institute of Allergy and Infectious Diseases. He’s also concerned about the threat from synthetic biology — the possibility that rogue scientists and bioterrorists could make diseases in the laboratory to be used for terrorism. As he puts it, “The threat and the reality of synthetic biology is becoming greater and greater every day.”

A recent report in Science magazine seems to add another arrow to the quiver of those who worry that synthetic biology could become a source of terrorist weapons. A group of scientists, among them J. Craig Venter, whose team decoded the human genome in 2000, has succeeded in synthesizing a bacterial genome entirely from scratch.

Venter’s feat, however, doesn’t mean that terrorists will be making new germs to kill us. And it shouldn’t mean that the government should spend billions of dollars trying to counter a chimerical threat by developing an equally chimerical antidote.

Synthesizing a bacterium from an existing genome changes nothing fundamental in our understanding of synthetic biology. Virologist Eckhard Wimmer synthesized poliovirus in 2002, and Venter’s team made a bacteria-eating virus in 2003. But Venter’s latest experiment was the first to synthesize so large a piece of DNA. He hasn’t gotten his germ to “boot up” yet — it still has to be put into a living cell and show that it can grow and multiply. Even so, scientists skeptical about the significance of his achievement think Venter will get his synthetic germ up and running in a matter of months.

Venter’s work makes the creation of murderous new life forms seem more believable. Indeed, the fear of dangerous synthetic germs has prompted the enormous, cumbersome apparatus that is the U.S. biodefense program to lurch in a new direction. If we don’t know what pathogens are coming, the reasoning goes, we had better develop new ways of countering them — not one at a time but all of them.

After the anthrax letter attacks of 2001, which began a week after 9/11 and killed five people, the biodefense establishment’s immediate response was to focus on the greatest and likeliest of bioterror threats — the unholy trinity of anthrax, smallpox and plague. In 2004, billions of dollars were set aside for Project Bioshield, which was jointly run by the departments of Homeland Security and Health and Human Services. The program aimed to produce new, safer vaccines and treatments for anthrax and smallpox, in particular.

Almost four years later, Project Bioshield has little to show for all the billions of dollars showered on it. The old “one-bug-one-drug” strategy — designed to develop vaccines and therapies for anthrax, smallpox and plague separately — has been abandoned in favor of “broad spectrum technology” — drugs and methods that will, at least in theory, kill many types of germs.

Rutgers microbiologist Richard Ebright believes that the broader approach is better. As the effectiveness of the antibiotics we already have wanes, it makes sense to search for new classes of these drugs, he believes. The same goes for antivirals. Very few effective ones exist, and viral strains can develop resistance to them too, as some influenza strains have already done with Tamiflu, the newest licensed drug for treating the flu.

But new antibiotics and antivirals represent only a small part of the National Institute of Allergy and Infectious Diseases’ current biodefense program, according to Ebright. The institute is assigning higher priority to radical new approaches. Chief among them is the modulation, or enhancement, of “innate immunity.”

Simply put, there are two components to human immunity: innate, or general, immunity and acquired, or specific, immunity. Innate immunity involves killer cells and chemicals the body launches to fight invading germs. While the germs are held at bay, so to speak, the body develops specific antibodies to mop up the infection. In theory, enhancing innate immunity means creating ways to intensify or strengthen these immune responses so the body can fend off all infections, whether newly evolved or artificial, as soon as they appear.

This sounds good. If you could treat any new disease before the germ is even identified, then artificial bioweapons, or such naturally emerging germs as SARS, would cease to be terrorist specters.

But things are never that simple. Innate immunity is an exquisitely fine-tuned system, honed by millions of years of natural selection.

“It’s not like a stereo system where you can just turn the volume up or down,” says evolutionary biologist Paul W. Ewald of the University of Louisville. He points out that ratcheting up innate immunity might turn the body against itself, producing such autoimmune diseases as lupus or multiple sclerosis. Besides, if innate immunity could really wipe out all infections, why hasn’t it already done so? Why did we evolve the second system of acquired, or specific, immunity at all if innate immunity could completely protect us from disease?

There’s lots of research into innate-immunity enhancement but precious little data supporting it. The scientist most prominently associated with the idea is Ken Alibek, a bioweapons designer who defected from the Soviet Union in 1992 and for years peddled an immunity-boosting nostrum on his commercial website. Harry Whelan, professor of neurology and pediatrics at the Medical College of Wisconsin and lead author of a 2005 article backing this approach in the Journal of Allergy and Clinical Immunology, cites Alibek as one of the “experts” consulted for the article. But though Whelan and his coauthors reviewed a host of research projects testing how various chemical compounds boosted innate immune activity, they reported no data on how well these compounds worked in preventing disease and death.

Charles Hackett of the National Institute of Allergy and Infectious Diseases offers some evidence that limited stimulation of innate immunity can provide some advantages. He points to various vaccine adjuvants, or boosters, that prompt innate immunity to turn on acquired immunity more quickly. But that, Hackett acknowledges, isn’t the same thing as enhancing general innate immunity. “Innate immunity is an area that’s evolved over millenniums and is very clever,” he told me. “If you want to [enhance] it, you really have to understand it better than we understand it now.”

Artificial germs remain an illusion. Venter, like scientists before him, has not made a new germ. He used a genome map to re-create an old one. Similarly, despite all the interest in enhanced innate immunity, no one has been able to show that the approach works. The wreckage of Project Bioshield shows that the one-bug-one-drug approach is a failure. But by banking on the possibility of boosting innate immunity, the U.S. biodefense leviathan could well be, once again, staggering in the wrong direction.

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Nano-Terra is receiving over 50 patents from Harvard University– according to the article, the largest transfer in Harvard history– from the lab of George Whitesides, chemist and nano-bio pioneer. It’s not clear what the transfer means, since NanoTerra was “founded in 2005 with the goal of creating a home for the Whitesides patents.” Is it news or just business as usual?

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A recent article in The New Atlantis by its editor, Adam Keiper comes as close as anyone has to publicly diagnosing the strange state of affairs around nanotechnology research in social science. The article makes a number of points that have been made in various places, though not quite all together: that “nanoethicists” can’t agree on what nanotechnology is (as if the scientists could!); that the “low-hanging fruit” of environmental health and safety has dominated all the research; that academics are self-obsessed and self pitying at the same time(?); and that nanoethicists can’t keep their facts and their values straight. All told, it’s a bit of strange article, in that it’s main point seems to be that academic nanoethics has no clue, and should learn something from academic bioethics before it can become a real *ethics. But by the same token, it seems to suffer from any real sense of what social scientists and human scientists are actually doing in this area, and why some of them might cringe at being lumped together under the label of *ethics. Indeed, it doesn’t appear that Keiper questions at all the need for a proper ethics of x,y or z– only that it be a proper ethics.

There is, however, something intellectually curious (interesting? worth researching perhaps?) in the contemporary demand that research in the social sciences and humanities should take the form (if not the content) of ethics. Certainly ethics in the way it is used here has very little of the connotation of philosophy, and much more the sense of responsibility. Social science and humanities work is thus expected to pass judgment on the responsible (or not) development of science and technology and not to contribute directly to what might be considered basic research in ethics. Of course, to the extent that social scientists and humanists are willing to subject themselves to this, to put themselves in the degraded position of the technician of the responsible, there may be little hope for something like a “basic” social science or humanities work on the subject of nanotechnology, and on this note, the Keiper article makes a very important point: do social scientists and humanists–even those who are proper ethicists–really know the facts of the matter in nanotechnology?

Keiper’s critique, which I am fully in agreement with, is that there is way too much leeway granted to the most far-out promises of nanotechnology: space elevators and nanobots and human enhancement and gray goo, when there are in fact plenty of good, current and troubling ethical issues hard at work in the trenches of current nanotechnology. The boondoggle of Drexlerian nanoscience is that it so easily allows people to stay at the level of college textbook science, rather than diving into the difficulties of real science–a problem and an insight I think science studies has been making for several decades now, but not all of its practitioners seem to remember.

This “are you really paying attention to the science” critique is one that could also be pointed at the bioethicists who spend their time debating the finer points of stem cells as if there had never been a human cell in culture before, and as if the promises of disease-curing and life-enhancement were simply true, just not yet. In the case of nanotechnology, it is all too easy to focus on the promises, because the realities are all too often ethically trivial: what ethical difference does it make that my washing machine claims to eliminate bacteria with tiny silver particles, or that my shirt repels water with NanoTex coating?

Of course, these same questions make it clear why all the action is in the area of safety–environmental and biological implications of nano. Sure these aren’t the only issues– but they are currently the most troubling, and the ones that scientists and engineers are most likely to spend their time thinking about. Ironically, in fact, it appears that these kinds of issues have in fact been successfully rendered scientific, even basic science (especially here at my home institution, with CBEN)–and not just “implications.” If that’s the case, does it mean that the social scientists and humanists should breath a sigh of relief and move on to the really ethical issues? I think not. The more routine the pursuit of safety and greenicity becomes in the day to day practice of nanoscience, the more ethically (and politically) fraught it becomes. The more detailed our knowledge is about the nature of toxicity and exposure, the more detailed our plans for treating water, soil, food and air with nano, the more complex our ecological future becomes. Is this the place for ethics? If not, why not? It seems to me that the same critique that we should be looking to the facts of nanotechnology, is the same reason why we should redouble the concern with understanding research and development in the area of safety and environmental consequence. I doubt very much that an issue like “social justice” will disappear the closer you get to these questions.

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No one, so far as my blogosphere radar is concerned, has quite picked up on this story yet– a paper in PNAS detailing the effects of nanoparticles on proteins, causing fibrillation of the form associated with Alzheimer’s, Creutzfeld-Jakobsen et. al. Because I am in the loop, I know that ICON has published a “backgrounder” that explains what this article means–with the advance intuition that this is going to be spun. I keep waiting… in a version of that old zen koan, since no one reads this blog, is it possible that I might affect my own observations of this event, even if no one is yet talking about it…

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A while back, DuPont and Environmental Defense released a proposed framework for best practices in handling nanotechnologies– part product development strategy, part risk analysis and unusual for being a cooperation between a corporation and an NGO (though not that unusual, Elise pointed out this collaboration on sustainable forestry as another example). Two weeks ago a coalition of various “civil society actors” as we like to say these days (ETC, AFL-CIO, Greenpeace, Friends of the Earth, United Steelworkers, etc) sent out an open letter decrying this voluntary “framework” as back-door, corporate-driven regulation. The protesting groups claim it is an attempt to usurp “broad public participation in government oversight of nanotech policy” and that (if successful) such a framework would be “a precedent of abdicating policy decisions to industry by those entrusted with protecting our people, communities, and land.”

There hasn’t been much discussion around this online, but here are two starting points (1,2).

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I’ve now seen two posts in rapid succession about how few posts there have been in the last couple of weeks, blogosphere-wide, that is, not just here, which has been totally silent. Not sure whether two data points makes for a trend, but in my case, it has been because I really haven’t had anything to say. April is sometimes like that. But recently, my attention has turned to the question of “responsibility” and in pertiular, “responsible nanotechnology.”

I have been thinking about the difference between the evaluation of costs vs. the evaluation of benefits: what is a responsible attitude towards one or the other? It seems to me that when most people within the world of nanotechnology speak about responsibility they are talking primarily about responsible responses to the potential costs of nanotechnology–i.e. risk understood as a negative outcome of some action. It isn’t clear to me, however, just how much people see responsible response as part of the benefits side of the equation: i.e. by what criteria does one make claims about the “risk” of a proposed benefit. Since all this stuff is in the future anyways, it seems only fair to suggest that benefits are just as uncertain as costs… so why should we believe the people at Responsible Nanotechnology or ForeSight or even the scientists when they make claims on what nanotech will deliver: molecular manufacturing, better materials, an end to global poverty, cleaner water, etc.

Take for example, this recent article (blogged at Responsible Nanotechnology), which contains an interview with “Jeff Wacker, a futurist with Plano-based Electronic Data Systems Corp” (I should probably stop here) in which the technique for weighing the liklihood of possible benefits appears to be distinguishing the three categories “mild, wild, and magical.” Now it is no secret that most newspapers, especially crap rags like the Dallas Morning News will readily substitute futurology for science reporting, but I still think it is worth taking Mr Wacker at face value. Presumably he is paid to be a futurist, even if out of his own venture capital, or wherever the money comes from, but presumably he has a system of some sort for distinguishing the likely from the unlikely benefits of nanotech. What is it? Is it polyhedral dice? Is it an “intuition” enhanced by nanobots? Is it a careful reading of science fiction? What makes it possible for this industry of benefit-weighers to agree that it is more likely that, for instance, we will be able to put trash into a microwave-sized device and retrieve a side of beef (Drexler’s example, thank you very much) rather than that we will be able build a fuel-cell to produce small amounts of pure water or a new kind of plastic? How do we weigh the benefits of nanotech today? Is responsibility the right (or duty) only of hand-wringers?

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And in other news:

This article was brought to my attention by a grad student in MIT’s Endy lab as a (cynically) “real-world application” of synthetic biology:
http://www.abc.net.au/science/news/stories/2007/1872191.htm

That’s right, scientists are coaxing bacteria into manufacturing beer dresses. N.B. the convergence of the bleeding-edge technical and the Primitive in the photo of haute couture swampthing…

Now, I don’t think this is synthetic biology. It isn’t using standardized biological parts, and it isn’t attempting to catalog those parts in order to separate design from fabrication. This is pretty much straight-up biotech. Nonetheless, it did inspire a brief meditation on the etymology of fabrication, which I have found to be a useful word with which to think about synthetic biology.

A fabrication is something manufactured from standardized parts, as well as a deception (think George Eliot’s “‘dear deceit’ of beauty,” in this case). Along with fabric, which is both fiber and structure, fabrication comes from the latin root that haunts homo faber, that problematic persona of the human imbued with a natural impetus to manufacture tools, and tools to make more tools…and more and more tools… (to which Huizinga contrasts homo ludens, but, of course, nanotech and synthetic biology are also forms of deep play, no?).

So this odd internet meme opens up for me a few questions about the nature of synthetic biology, which of course I will leave someone else to address: what is the relationship between nature and artifice as it pertains to fabricated biological materials? And, a question that pertains to both nanotech and synthetic biology, as disciplines concerned primarily with building new things rather than engaging in discovery science, what is the relation of design to fabrication? And what sorts of imaginaries are implied by the choice of applications and artifacts of synthetic biology and nanotechnology (the earlier mentioned bacterial clocks, nanoguitars, and now whimsical fermentation fashion)?

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In response to a question Chris asked earlier re: the convergences and divergences of synthetic biology and nanotechnology:

This is a question I’ve been puzzling over for a while. At first gloss, the most obvious overlap between the two fields is that they have generated a lot of hype in the last few years, and are extremely promissory in nature (think of the asymptotic prophesy of Moore’s law that proliferates–exponentially?–in both fields). And because both fields have gained momentum and press coverage primarily by generating a breathless imaginary of potential future technologies–robotic armor! organisms “made to order”!, discourse surrounding the fields has gravitated towards debates about risks, whether they be gray goo scenarios or synthetic organisms running amok. And the inevitable backlash from colleagues in less high-profile (read: sexy) fields, in this case materials science and bioengineering, is shared by nanotech and synthetic biology. This blog itself is symptomatic of the overlap (as well as, quite possibly, one of the fields’ only junctions) of synthetic biology and nanotechnology as much as it is a critical response to them.

So, the next question is what are the more concrete overlaps between the two fields–I’d be interested in hearing about any hybrid synbio-nanotech research being done, or people or institutions that are applying the methods of one field to the goals of another. So far I don’t know of any… And what is the disciplinary taxonomy of either field? SynBio is the syncretic offspring of synthetic chemistry, electrical engineering, and computer science. Someone working more closely on nanotech can map its origins better than I.

And a third convergence I would like to open up for discussion is that of scale–synthetic biology is about decoupling scales of manufacture, so that parts, devices, and systems can be seamlessly constructed while blackboxing previous levels of organization (ideally, one would not need to know what parts go into a device in order to plug it into a larger system), and DNA synthesis separates the process of DNA design from that of fabrication, which can be contracted out to synthesis companies. And scale is clearly integral to nanotech, which so far seems to primarily devote itself to building nanoversions of technical objects–nanocars and nanoguitars (it is interesting to note that one of the primary goals of synthetic biology is to build biological versions of archetypal machines (bacterial cameras and clocks, “computers” that operate in different species platforms using a standardized chassis, etc).

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After meeting today with the PI of the SynBERC project, of which our (i.e. Paul Rabinow, Gaymon Bennett, and Anthony Stavrianakis) work in Human Practices is a part, Paul Rabinow and I were reflecting on some of the challenges of making Human Practices an integral part of scientific collaboration. Here are some initial thoughts:

Existing models for formal interaction among biologists and anthropologists and ethicists, as well as existing organizational practices and research structures in biology position the human and philosophical sciences outside of biological research per se. This positioning, among other reasons, constitutes a core rationale for the development of new arrangements—hence our work in designing and implementing the Human Practices approach. The persistence of this external positioning means that any entrance of the human and philosophical sciences into the space of biological research requires justification. This justification is expected to be articulated in terms of the benefits the human and philosophical sciences can offer to existing challenges and goals within the bio-scientific space in its present form. That is to say, the human and philosophical sciences are put in the position of having to articulate justifications for their presence within collaborations that are merely instrumental relative to the existing bio-scientific objectives; we are allowed in if we help them do what they are already doing more effectively.

Why is this a problem? First, it reduces the human and philosophical sciences to the position of consultants at best, handmaidens at worst (technical experts in any case) and thereby inhibits equality in collaboration. Second, and more importantly, it forces an accommodation of the supposition that human, philosophical, and biological scientists are working in separate problem domains and thereby reinforces the very practices that a Human Practices approach seeks to disrupt and remediate. In order for Human Practices to work, biologists and their funders must be willing to change their habits and self understanding such that they conceive of their work as existing within a shared domain of problems, problems shared with anthropologists, ethicists, and the like. If this can happen, and what form this would take, remains to be seen.

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Among the many oddly non-reflexive forms of reasoning that puzzle me about the case of nanotechnology is the obsession with risk perception. That is, not the study of objective risk, which is I think, a fully well developed scientific field, in which it is possible for instance in the case of the environmental and health issues associated with nanotechology to distinguish clearly between exposure risks and toxcicity and to find clever experimental ways to measure these risks in absolute and relative terms. The other side is the study of subjective risk–an area that also has a long and august, if somewhat more philosophical tradition, stretching back at least to Pascal. But for the most part, the study of “risk perception” proceeds in the most naive forms: We (experts) know the objective risks, but (they) the public refuses to see them, and instead relies on irrational, non-logical processes, “affect” and “values” that are not in sync with objective risk assessment. So, for instance, this study titled “Affect, Values, and Nanotechnology Risk Perceptions: An Experimental Investigation” by members of the Cultural Cognition Project at Yale reveals that people’s understanding of facts are… wait for it… conditioned by their values! OMG! Stop the presses!

But seriously, it’s a very interesting article that explores “affect” and “value” as something which has, apparently, been absent from academic thinking on subjective risk perception. Fear, hope, disgust, anger, purity, danger? Indeed, Mary Douglas is paraded out here to make claims for “shared systems of cultural value.” The article makes a simple point that there are cognitive and cultural heuristics at work in the processing of information–Herbert Simon would be proud. But what’s ultimately frustrating is that 1) there is no sophistication to these models, they are simple cognitive processing models and 2) that they perforce treat the information being processed as neutral and unbiased, rather than the outcome of political contests, whose signs and signals are also apparent (i.e. when Nanotechnology is being done at Lawrence Livermore Labs, it’s not just another scientific field to most people, even very smart people in profound control of their affect). Would it make any difference to such a study if we actually gave the public credit for being more sophisticated observers of the political stakes not only of nanotechnology, but of nanotechnology information and facts about “risk” as well?

Then there is David Berube’s novel attempt to apply a similar heuristic to nanotoxicology (”intuitive toxicology”). I find this approach creative, but ultimately puzzling. It’s not clear what the goals of these kinds of analyses are: to make subjective risk perception coincide with objective risk perception? To find better ways to manipulate culture and affect in order to secure public assent? To make humans more rational? To defend the nanogravytrain from attacks by emotionally driven do-gooders taking time out from GM foods and Nuclear power? To understand “cultural cognition”?

Perhaps the point is a simple one: I think the fact that the goals of this kind of work are not clear is actually emblematic of the “risk perception” problem. The fact that no one really knows the interests of academics, especially those heavily funded by industry as well as government, contributes to the affect and “values” that shape public perception. Facts simply aren’t neutral, at least, not without a great deal of effort in making them so. But risk perception research seems to proceed as if there are no questions about facts, that they emerge clean and clear from laboratories that and neutral and untainted by the political sphere. The trick is not to make science more neutral, but to make it more clearly open, to reveal the “coarse signs” of its political claims to make the world (or humans) better (to recall Lippmann). But risk perception research so far seems to me to be little more than a replay of Edward Bernays “Engineering of Consent”– with considerably more sophisticated tools.

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