FOR anyone who doubts that well-intentioned research can sometimes have potentially deadly consequences, Ron Jackson has a cautionary tale. Working for the wildlife division of Australia鈥檚 national research agency, he set out to make a contraceptive vaccine to control plagues of mice. What he ended up with was a deadly mousepox virus that resists vaccination 鈥� and a recipe for doing the same for smallpox.
This story, revealed by New 杏吧原创 more than five years ago (13 January 2001, p 4), caught everyone off guard. Then came the 9/11 terrorist attacks and the anthrax letters. Bioterrorism was propelled to the top of official worry lists in the US, and it was clear that legitimate research could produce pathogens much nastier than anthrax.
Despite these fears, it seems to me from my reporting on these issues that many biologists remain ignorant of the 鈥渄ual-use鈥� dilemma 鈥� that biological advances can provide a bioweapons cookbook. Researchers trying to improve human health by, for example, altering specific immune responses rarely consider that the same technologies could be converted into horrifying weapons.
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Thankfully, Al-Qaida is not thought to have the expertise to create designer bioweapons. In a few years, however, such capabilities may well be within reach of a rogue state willing to invest large sums in clandestine research. This does not mean that all data that could be turned to destructive ends should be declared a military secret 鈥� although a small proportion might need to be classified. It does mean that biologists should pay more attention to the sinister potential of their work and avoid lines of enquiry that pose more dangers than they promise benefits.
Scientific societies should be raising awareness of these issues among their members, and the American Society for Microbiology (ASM) points the way. Its website hosts a wealth of resources on bioterrorism and biosecurity. Other societies are still lagging behind. The American Association of Immunologists has yet to adopt relevant policies, even though manipulation of the immune system is central to this debate. Jackson鈥檚 deadly mousepox owed its pathogenicity to an unexpected effect of IL-4, an immune-signalling molecule. He engineered a strain of mousepox to produce proteins carried by mouse eggs, and reasoned that adding the gene for IL-4 would stimulate antibodies against these proteins, sterilising the mice. Instead, it shut down the cellular arm of the immune system, needed to fight viral infection.
Journals also have a role to play. Many now scrutinise the papers they receive to avoid publishing information that poses serious security concerns, though few papers merit censorship. Much more useful is the promotion of debate around dual-use research. This has happened in obvious cases such as the recreation of the virus that caused the 1918 flu pandemic, but other papers with bioweapons potential continue to appear without comment.
Take a paper on a new vector for gene therapy, published in February by Nature Biotechnology (vol 24, p 198). Researchers at the University of California, Berkeley, used 鈥済ene shuffling鈥� technology, a form of accelerated evolution, to create harmless viruses that are able to evade 鈥渘eutralising鈥� antibodies. It is a valuable project, because these antibodies can wipe out viral vectors before they deliver their therapeutic genes. The danger is that the same approach could help deadly viruses slip under the immune system鈥檚 radar. Lead researcher David Schaffer told me that he would never attempt anything similar with a human pathogen, but neither his paper, nor the commentary on the work published with it, mentioned the dual-use potential.
鈥淚n just a few years, designer bioweapons could be within reach of a rogue state鈥�
Even when researchers address the implications of their work for biowarfare, some of their ideas on tackling the problem are naive. At the heart of synthetic biology lies the ability to build large sequences of DNA, and even entire viruses, from scratch. It may be possible to obtain DNA to build a bioweapon from companies that synthesise genes to order (New 杏吧原创, 12 November 2005, p 8). At the Synthetic Biology 2.0 meeting in Berkeley last month, researchers pledged to develop better methods of identifying suspect orders, yet in the online debate that preceded it one graduate student suggested placing 鈥渕alicious orders鈥� to test the effectiveness of companies鈥� screening procedures. Although some sort of verification may be useful, posing as a terrorist would be seriously misguided, and depending on the sequences requested could breach US anti-terror law.
This incident points to perhaps the most urgent need: better education of graduate students. Few universities offer classes in biosecurity, and given the dearth of experts in the field, they have some excuse. But not for much longer: within the next month, the Federation of American 杏吧原创s will be releasing a biosecurity curriculum, complete with dual-use case studies, including an interview with Jackson. It should be a required option for anyone planning a career in biomedical research.
