H5N1 Research: Greater risk in publishing or withholding data?

In an unprecedented move, a U.S. biosecurity review board has asked the authors of two studies creating dangerous airborne strains of the H5N1 avian flu virus—possibly transmissible among humans—not to publish the details of their experiments.  Even among scientists, the decision has sparked a great deal of disagreement over the best action to take, now and going forward.

In an unprecedented move, a U.S. biosecurity review board has asked the authors of two studies creating dangerous airborne strains of the H5N1 avian flu virus—possibly transmissible among humans—not to publish the details of their experiments.  Even among scientists, the decision has sparked a great deal of disagreement over the best action to take, now and going forward.



Photo by Stephen Ausmus
avian flu

In a lab in the Netherlands and one in the United States, there exists a virus, a highly pathogenic strain of avian flu, that experts fear could pass easily between humans, if ever it escaped.  This virus, a strain of H5N1, did not evolve naturally, but was created by influenza researchers, whose work was approved and followed by the relevant authorities—including the U.S. National Institutes of Health, who funded the studies.  Nevertheless, the results of their work have raised grave concerns about the risk of accident or misuse, and the scientific community has struggled to decide both how to respond, and where to go from here.

The strains of highly pathogenic avian influenza (HPAI H5N1) currently found in nature do not infect people easily, but, when they do, they are vicious.  Since 1997, when the first person was known to be infected, HPAI H5N1 has caused 577 officially confirmed cases of human infection; 340, or almost 60%, were fatal.  (The actual death rate may be lower, as it is impossible to know how many infections may have occurred without causing serious symptoms.  Still, everyone agrees the virus is dangerous.)  Given its ability to kill, if H5N1 ever mutated to a form that passed easily within the human population, a pandemic of unimaginable proportions could result.

In the interest of public health and biomedical preparedness, two separate research programs were developed to examine what it would take for H5N1 to become transmissible between mammals, via the air alone.  At the Erasmus Medical Center in Rotterdam, the Netherlands, a team led by Ron Fouchier performed experiments to see which mutations would be necessary for this to happen.  Yoshihiro Kawaoka, of the University of Wisconsin-Madison and the University of Tokyo, led a similar project.  The scary thing is that they succeeded, and more easily than anyone expected.  Their research has provoked a storm of questions surrounding the chances of accidental escape, the potential for bioterrorism, and what on earth to do now with the knowledge gained.

When both teams sought to publish their findings, in the journals Science and Nature, respectively, the articles were sent for review by the American National Science Advisory Board for Biosecurity (NSABB).  This federal committee provides advice and guidance to government agencies regarding “dual-use research”—life sciences research that could be used for important public health purposes, but potentially for deadly bioterrorism, as well.

In the face of great uncertainty surrounding the risks for misuse of the H5N1 research, the NSAAB recommended in November that the two studies’ authors remove from their manuscripts details pertaining to their methods and to the exact mutations that led to the creation of the dangerous, airborne strain.   This decision is unprecedented and has the worlds of research and biosecurity divided.  Is this a responsible reaction to sensitive information, or scientific censorship?

Plenty of other dangerous pathogens are under study around the world—SARS, Ebola, anthrax—but what makes avian influenza research different, explains Aziza Kamel of the National Research Centre in Cairo, Egypt, and a 2012 Fellow of the L’Oréal-UNESCO For Women in Science program, is that H5N1 changes quickly, showing great genetic variability.  “The genome of the virus is segmented, which facilitates exchanges between strands of the genetic material, RNA.  This leads to the appearance of new strains every year.”  The fear is that the virus will naturally evolve into a form that is highly contagious between people.

The molecules of interest in the emergence of new strains are the cell surface proteins hemagglutinin (H) and neuraminidase (N).  These determine the way the virus interacts with cells and the mechanism it uses to infect them, Dr. Kamel explains.  “Every year there is new variation [in the H and N viral proteins], and we can’t know which mechanism the virus is using, or how it will react to our vaccines.”  Imagine if a killer version of the virus suddenly appeared in the human population; how long would it take to characterize the new strain and develop effective treatments and a vaccine?

In her work in Egypt, a country that suffered greatly during the swine flu (H1N1) outbreaks in 2009, and is currently experiencing cases of H5N1 infection in humans, Aziza Kamel follows the genetic changes taking place in the avian flu virus.  She watches how each new strain operates to attach to its target cells, compares avian versus human strains, and certifies vaccines accordingly.  Clearly, the recent work of Ron Fouchier and Yoshihiro Kawaoka is different: they have intentionally created—albeit under strict conditions of biosecurity—a lethal strain of H5N1 that may be transmissible among humans.  Nevertheless, the guiding principle behind Kamel and Fouchier’s work is the same: to stay one step ahead of serious outbreaks by studying newly emergent or potential new forms of the virus.

By asking the authors of these recent studies not to publish significant details of their experiments, opponents say the NSABB is depriving influenza researchers of vital information needed for understanding this virus, controlling it, and finding effective defenses, before a deadly outbreak.  According to Peter Palese, a virologist who was involved in research to resurrect the H1N1 virus responsible for the 1918 pandemic of “Spanish flu”, forewarned is forearmed.  Writing in Nature, he explains that “knowing which mutations render the virus more dangerous could help on a public-health level — if an outbreak of bird flu occurs in Taiwan, for instance, and researchers sequence the virus and see those mutations, we would know to ramp up the production of appropriate vaccines and antiviral drugs.”

Others, though, say the risks far outweigh any potential public health benefit.  D.A. Henderson, of the Center for Biosecurity at the University of Pittsburgh Medical Center, feels strongly that instructions for creating such a dangerous virus should not be released to the public.  “The H5N1 influenza strain poses a potential biological hazard far more serious than any we have ever known.  It is a virus that is capable of killing half its victims, a proportion greater than that for any other epidemic disease. Were that coupled with the transmissibility of a pandemic flu virus, it would have characteristics of an ultimate biological weapon unknown even in science fiction.”

In the end, the authors of both H5N1 studies have agreed to remove key details from their manuscripts, even if they believe this is neither the most responsible reaction to their research, nor the most effective.  Regarding the feared security threat if details of their study are published, Ron Fouchier emphasizes that they did not develop any new methods for this work, and that the logic used was obvious enough that any virologist motivated to create a biological weapon from H5N1 would be able to do so, even if their methods are not disclosed.  “Bioterrorists can't make this virus, it's too complex, you need a lot of expertise. And rogue nations that do have the capacity to do this don't need our information.”

For Ron Fouchier, it is a moral obligation of infectious disease specialists to carry out this type of dual-use research.  He does, however, recognize that international discussion is badly needed on how best to proceed.  On January 20th, a group of 39 influenza researchers, including Fouchier, announced a voluntary 60-day moratorium on “any research involving highly pathogenic avian influenza H5N1 viruses leading to the generation of viruses that are more transmissible in mammals."  A meeting is due to be held by the World Health Organization in late February, where the scientific community will be able to discuss the best way to proceed, striking a balance between important opportunities and the gravest of risks.