After prolonged controversy, Science magazine has published in its current issue the second of the bird flu papers detailing how a human-transmissible virus could spontaneously arise in nature. This one, by a team lead by Ron Fouchier in Rotterdam (see photo), identified five mutations in the H5N1 virus itself that could render it transmissible through the air from one mammal to another. The previous paper, done by a Wisconsin team and published earlier this year in Nature, showed how a human transmissible virus could arise from a recombination of genetic material between the bird flu and swine flu viruses.
How easily might the transmuted human-transmissible virus arise in nature, and how virulent might it be? In a press conference accompanying publication of the second paper, Fouchier said that two of the five mutations have been found widely in H5N1 viruses, one just once, and the other two in other pandemics but never in H5N1. Asked why we haven’t already seen all five mutations in H5N1, Fouchier said there is no way to estimate how easy or hard it would be for the five to arise spontaneously. If the virus were to appear, it might turn out to be considerably less lethal than the predominant H5N1 virus we see today. This is because the engineered virus attached in the upper airways, not the lower, so that the risk of pneumonia would like be much smaller.
Asked by the New York Times about the danger of a “rogue scientist” using the bird flu papers as a recipe for a bio-weapons, Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said that the potential benefits from publishing the papers far exceeded the doomsday scenario. He said publication enhanced the probability of “good guys” bringing expertise, knowledge and insight to bear on study of the virus much more than it aggravates the likelihood of a mad scientist making nefarious use of charted mutations.
Though this topic takes me well out of my technical comfort zone, I cannot altogether rid myself of the sense that security concerns still are getting somewhat short shrift in this discussion and that the possible benefits from publication may be getting overstated. As I suggested in an earlier post, what if the world puts an enormous effort into watching for the specific mutations identified in the two papers, only to see a human transmissible virus arise from a different combination of mutations? And what if, meanwhile, some team of apocalyptically minded terrorists sets to work on replicating and releasing a version of the Wisconsin-Rotterdam viruses?
Fouchier seemed to say during the press conference last week that there was a lot of overlap between the potentially lethal mutations that the Wisconsin and Rotterdam teams identified, despite differences in approach. (“When we look at the hemagglutinin gene, there are more similarities than differences,” the real-time transcript of his remarks has him saying. “There was a different approach to identify the viruses that are commonly airborne. The mutations that we find are largely similar.”) That would seem to suggest that the mutations identified by the two teams do very likely represent the way in which a human transmissible virus would appear.
But a “policy forum” commentary accompanying the Fouchier paper seems to cast doubt, at least implicitly, on whether that necessarily is the case. The authors of that paper argue, for example, that studies of drug resistance have widely found a high degree of unpredictability in the way viruses evolve. “By emphasizing the limits of predictability, we do not mean to suggest that molecular studies of influenza transmissibility and virulence, or surveillance of animal virus populations, lack value…But because we cannot predict how these strains will behave in humans or critically, how they will evolve, such studies…are particularly risky and deserve special treatment.”
The authors of that commentary, from Harvard, the University of Pennsylvania and George Washington University, suggest that a single inter-agency committee should assess the risks and benefits of every proposed virus study of the kind discussed here and regulate how the research is conducted.
