The Challenges of International Regulatory Regimes for Biological Technologies

Arriving in my mailbox this morning was a story from the Washington Times Post (Thanks, Oliver), dated 18 June 05, "Bird Flu Drug Rendered Useless: Chinese Chickens Given Medication Made for Humans", by Alan Sipress.  Chinese farmers, encouraged by the government, have since the late 1990's been feeding the antiviral drug amantadine to chickens infected with H5N1.  (Update: Recent news stories in Science and Nature carry claims from the Chinese gov't that this usage was most certainly not officially sanctioned or  encouraged.)  The story notes that this usage is in violation of international agreements on the treatment of livestock with drugs, and that the resulting long term selective pressure is the reason amantadine is no longer effective in treating the influenza strain currently causing concerns about a pandemic.  This sets up China (and due to growing economic interdependence, the rest of the industrialized world) for serious woe, amplified by the fact that the most populous country on the planet is not prepared for a pandemic

In summary, an important tool in dealing with a potential pandemic outbreak in humans has been rendered useless despite an international agreement aimed specifically at preventing that sort of occurrence.  Writes Sipress;

The Chinese Agriculture Ministry approved the production and sale of the drug for use in chickens, according to officials from the Chinese pharmaceutical industry and the government, although such use is barred in the United States and many other countries. Local government veterinary stations instructed Chinese farmers on how to use the drug and at times supplied it, animal health experts said.

Amantadine is one of two types of medication for treating human influenza. But researchers determined last year that the H5N1 bird flu strain circulating in Vietnam and Thailand, the two countries hardest hit by the virus, had become resistant, leaving only an alternative drug that is difficult to produce in large amounts and much less affordable, especially for developing countries in Southeast Asia.

The scientific evidence that using antivirals in poultry is a bad idea has been around for quite some time, and international policies regarding veterinary application of the drugs is based on clear evidence: "In 1987, researchers at a U.S. Department of Agriculture laboratory demonstrated that bird flu viruses developed drug resistance within a matter of days when infected chickens received amantadine."

So we have a situation where scientific, technical, and policy components were all directed towards a particular regulatory goal, and all were ignored.  There is one more key piece to this story, and that is the number of years it has taken to confirm the information.  Sipress, again;

Health experts outside China previously said they suspected the virus's resistance to the medicine was linked to drug use at poultry farms but were unable to confirm the practice inside the country. Influenza researchers at the U.S. Centers for Disease Control and Prevention, in particular, have collected information about amantadine use from Chinese Web sites but have been frustrated in their efforts to learn more on the ground.

This is truly the crux of our challenge over the coming decades.  Despite efforts determine the extent of veterinary use of amantadine within China, even widespread government sanctioned (recommended, according to the story!) use that violated explicit international agreements continued unabated.  Even if the relevant intelligence had been confirmed, it isn't clear that the Chinese government would have changed its policies.  Regulation failed in this case, and because information was hard to come by our response to the problem is further impaired.  (Update:  Regardless of the involvement of the government, my point about the importance of good information stands.)

This is why I have been arguing so strenuously that open and distributed networks of people using and developing biological technologies are strongly preferable to closed ones. In my recent essay "Synthetic Biology 1.0", I discussed the effect of regulation on preparedness for natural and artificial biological threats, in part with conditions in China in mind.  Though many states and organizations will be pushing biological technologies in the coming years, China is front and center because of its growing economic might and educated population.  It is clear they are going their own way, developing and, more importantly, using technology as they see fit.

In the year 2000, Jiang Zhemin, the former President (Premier? I can never remember which) of China, said in no uncertain terms that in order to deal with their health care crisis they would use all tools at their disposal.  He specifically mentioned genetically engineering the population (this story is now finally on the record in Gerald Epstein's recent report from CSIS, "Global Evolution of Dual-Use Biotechnology").  Such efforts will explicitly require sophisticated biological technologies, in particular those related to DNA synthesis and sequencing.  Countries throughout Asia are already pushing the technology without much, if any, concern for what we decide to do here in the states.  Creating and enforcing regulatory regimes for this sort of thing would require an international effort that historically doesn't work so very well for just about anything else.  Witness the amantadine problem.

Then there is the problem that the technology and skills do not respect borders.  Synthetic genes can be ordered from companies in Seattle, San Francisco, throughout western Europe and Russia, Dalian, Tehran; the list goes on.  How do we monitor the flow of Epindorf tubes full of lyophilized DNA around the globe?  Used synthesis instruments are not only available worldwide, but the parts for a new 192 channel instrument (styled after ABI or Gene Machines) can be had for about $10,000.  The plans and process specs were published long ago.  Yes, it requires some skill to assemble the instrument, and yes, it requires some skill to write the software, but most people with undergraduate degrees in engineering or physics have this skill or can fumble their way to it in a relatively short period of time.  Reagents are available worldwide, and I don't understand how we can track those reagents any better than we do it now for industrial chemicals or drugs.  The grey and black markets for everything from drugs to fluorocarbon coolants are thriving around the world.  I don't understand how reagents, short oligos, genes, or even synthetic genomes can be controlled any better.

This raises two main issues.  The first is that I suspect regulation will only slow down scientific and technological progress here in the US.  Other countries (and organizations) are likely to explore the relevant fields a their own pace.  This resulting technology gap constitutes the second issue, which is that we will be unprepared for surprises.  Given the history of technology from the last century, I do not believe we can control the pace of development of biological technologies.  If we, here in the US, are not in the lead, somebody else is.  And we will thus experience surprise on a regular basis.  Our choices about developing biological technologies will determine whether we are willing to let potential adversaries be in the lead.

The above arguments are primarily directed at our physical security, but I am equally concerned about our economic security.  It is clear that China and India are pushing ahead with biological technology.  The sheer numbers of talented and smart students in these countries is to me mind boggling.  I am not sure that we can maintain our economic vitality even if we keep going at the current rate, but I am certain we will lose out if we decide to slow down.  We absolutely require increased government investment in technology and increased numbers of skilled people.  If you don't believe me, then the interviews Bio-ERA has been doing for our DOE-funded Synthetic Biology project clearly indicate that our global competitiveness is already at risk.  There is absolutely no reason European or Asian scientists and businesses should order synthetic genes from the US.  More specifically, my experience at a Global Business Network meeting a few weeks ago indicates that even though China is likely to experience some internal disruption over the coming decade or two, they are pushing hard not just to be competitive, but to take the lead.  In everything.

In summary, given my historical study of other technologies and my experience developing new biological technologies, I do not believe that regulation will result in improved security.  On the contrary, I believe it will impair our preparedness, reduce our security, and reduce our economic competitiveness.  Independently from these issues, I do not see how international regulatory regimes for biological technologies are workable, even if agreements are reached and are implemented -- by no means trivial efforts in themselves.

Finally, I would observe that no regulatory regime is perfect, and regulation is in actuality more a problem of managing barriers (to entry and use) that are inherently leaky.  Implementation of regulations always seeds resistance.  Given the power of biological technologies how many surprises can afford?