Four papers published today in the online, open access journal mBio offer wide-ranging perspectives about the biocontainment facilities that researchers should use to work with bird flu viruses that can transmit in mammals.
The controversy centers on two lab-made versions of H5N1 influenza that for the first time can transmit in mammals. The studies, done with ferrets, led the U.S. government's National Science Advisory Board for Biosecurity (NSABB) to recommend in December that papers describing the experiments redact details to prevent the information from aiding bioterrorists. NSABB's review also triggered intense debates about whether work with these viruses should take place in biosafety level 3 (BSL-3) labs, as was done by the two groups that made the viruses, or in still more secure BSL-4 labs.
An opening overview, co-authored by an NSABB member and mBio editor Arturo Casadevall, notes that raising the containment level has a stark tradeoff: The extra steps to protect society could make it more vulnerable because "critical experimental work will not be done simply because BSL-4 facilities are few in number and already engaged in research with numerous other pathogens."
This perspective contends that at "the heart of the controversy" is the presumed case-fatality rate of H5N1. According to the World Health Organization, nearly 60% of the 600 or so confirmed cases of H5N1 have resulted in death. But many researchers have noted that this likely overestimates the true case fatality as many subclinical cases go undetected. In a separate article, Lisa Murillo of the Theoretical Biology and Biophysics Group at Los Alamos National Laboratory in New Mexico argues that because of the confusion about the case fatality rate "it would be beneficial to err on the side of caution."
A separate article co-authored by NSABB member Michael Imperiale of the University of Michigan Medical School in Ann Arbor similarly urges following the precautionary principle and using BSL-4, given that there are many unknowns, including the reliability of the ferret model. This perspective notes that the biocontainment level can change if more information comes in later that suggests these viruses are not as dangerous as feared. "It is almost hard to believe today that the cloning of the herpes simplex virus thymidine kinase gene in 1979 was carried out at BSL4 (or P4, as it was then known) containment," the article notes, referring to a time when recombinant DNA experiments first emerged and stoked similar safety concerns. "This experiment was originally judged to be high risk, but over time we came to understand that it is not: today, the same work would be performed at BSL1 containment."
The final article by Adolfo García-Sastre of the Mount Sinai School of Medicine in New York City contends that BSL-3 provides enough safety. García-Sastre argues that H5N1 viruses are susceptible to both antivirals and existing vaccines, which would protect any lab workers who were accidentally exposed. "The use of BSL4 containment would not decrease the risk of virus release any more than enhanced BSL3 containment, but it would result in an unnecessary burden that would restrict research on H5N1 inﬂuenza transmission to a few facilities and considerably decrease the speed of research on this important pathogen," he writes.