The ‘security threat' posed by H5NI mutations is already out there. What is needed is collaborative research based on the sharing of scientific literature.
The United States National Science Advisory Board for Biosecurity (NSABB) decision to “recommend” that Science and Nature journals publish only redacted versions of bird flu research results is nothing but an exaggerated and over-zealous reaction that is bound to fail in its prime objective. Most of the information the United States government intends to censor is already available in scientific literature. If anything, its decision will only seriously impact legitimate flu researchers.
The core of the issue is the advisability of sharing publicly through journals the results of a man-made H5N1 mutant that has all the characteristics of a virus capable of creating a global pandemic — a lethal strain that spreads through air and maintains its virulence after killing its infected hosts.
The problem arises as researchers and the government agency look at the results with totally different priorities. The NSABB sees it from a narrow national security point of view — the perceived threat of someone using the sensitive information to engage in bio-terrorism. But researchers are driven by public health concerns.
The controversy started when Science, in accordance with the Dutch Code of Conduct for Biosecurity and the U.S. regulations on “dual use” research, sought the NSABB's advice on a paper submitted to it for publication. The research was carried out by a team led by Ron A.M. Fouchier of the Rotterdam-based Erasmus Medical Center.
Virologist Yoshihiro Kawaoka of the University of Wisconsin, Madison and his team also studied the same problem and submitted their paper to Nature. This paper too was reviewed by the agency.
In an unparalleled move, the NSABB took exception to both the studies, approved and funded by the U.S. National Institutes of Science (NIH), and “recommended” that both journals publish only a redacted version. The censored papers, bereft of sensitive details of H5N1 transmissibility, will prevent misuse, the agency believes.
But the editors of both journals have stood firm and have expressed concerns about “withholding potentially important public-health information from responsible influenza researchers.” What course the journals finally take rests primarily on how the government institutes a mechanism that identifies legitimate researchers and quickly provides full access to the censored papers on a need-to-know basis.
Meanwhile, a letter signed by 39 influenza researchers around the world, and jointly published in both the journals on January 20, has called for a 60-day voluntary moratorium on any research connected to the transmission of H5N1 highly pathogenic avian influenza. This period will be used for “informed global discussions” regarding the “regulation and subsequent publication” of dual-use flu research.
The research details have been in the eye of the storm ever since Dr. Fouchier presented the broad details of his team's study at the annual conference of the European Scientific Working Group on Influenza in Malta in September 2011.
The prevailing notion is that the highly virulent influenza strains can turn pandemic only through airborne transmission. Avian influenza, H5N1 in particular, has so far not attained this capability, and is generally considered incapable of attaining such ability.
For instance, there has not been sustained human-to-human transmission of the bird-flu virus since its outbreak in April 1997. Nearly all of the 577 laboratory-confirmed human cases, which killed 340, were contracted only through direct contact with animals.
Yet, the eventuality of H5N1 mutating into a transmittable, virulent form cannot be completely ruled out. Influenza researchers, hence, wish to stay a step ahead of the virus. This can be achieved only by knowing in advance the kind of mutations required for pandemic-causing viruses to emerge and the conditions under which they can emerge. This prompted the two teams to carry out their experiments.
Contrary to our current understanding, the virulent strains produced by the teams were capable of airborne transmission. The team led by Dr. Fouchier started off by introducing three mutations to the virus. This was sufficient to kill ferrets (considered the best animal models for influenza research as they closely mimic human responses to flu), but lacked the ability to spread through aerosols.
The researchers then turned to the time-tested method of passing the virus from one infected ferret to another many times. After the 10th transmission, the virus had many more mutations, two of which acted in unison with the three already introduced to make the virus easily transmissible by air.
The virus created by Dr. Kawaoka, though transmissible by air, lacked the virulence to kill the ferrets. Currently available vaccines were effective against the strain.
Reaction of scientists
Despite these findings, the concerned authors and other scientists insist the perceived security threats cannot be allowed to override genuine public health concerns.
For instance, Dr. Kawaoka has made a strong case to make the full paper freely available to all scientists across the field. Getting researchers from other areas involved has become absolutely necessary as “new ideas are needed to answer some of the urgent questions,” he wrote in a comment piece in the January 26 issue of Nature. The specific mutations that his team identified suggest that “influenza transmission is more complex than anticipated.”
“We did not develop novel methods and we only used information and methods that are available freely from the scientific literature,” writes Dr. Fouchier in an opinion piece in Science (January 19, 2012). All three mutations introduced by his team are already present in nature. Similarly, the two that the virus developed are also seen in nature. What made the virus transmissible through aerosols was the lethal combination of these five mutations. It is, therefore, naive to assume that such a combination would never occur on its own.
The futility of censoring the results has also been driven home by Daniel R. Perez of the University of Maryland in his opinion piece in the same issue of Science. “[... These] two and other research groups [that] have already published similar studies in the past make it almost impossible to prevent access to details on the methodology,” he emphasises.
Assumptions proved wrong
Apart from disproving the impossibility of airborne transmission, the mutant strain has proven wrong three other important assumptions of H5N1 virus — only virus subtypes H1, H2 and H3 can cause pandemics; flu viruses cannot cause pandemics without genetic mixing (reassortment) of human and animal viruses; and the inevitability of pigs as an intermediate host to yield pandemic viruses.
There is another issue that has unfortunately not attracted sufficient attention. Researchers across specialisations in Southeast Asian countries, where H5N1 is endemic in poultry, have a right to know the full details of the study. Apart from being the worst affected, these countries have a right to have free access to the results as they fulfil their obligation of supplying H5N1 virus samples to WHO collaborating laboratories. In turn, they have a right to access the benefits of research and vaccines arising from research using their data. Indonesia, a hotbed of bird flu outbreaks, brought the spotlight on the inequity of the current sharing mechanism when it stopped sharing its samples with WHO in 2007.
Dr. Fouchier warns that the WHO-coordinated Pandemic Influenza Preparedness (PIP) Framework that went into effect last year is based on the principle of mutual sharing of samples for access to vaccines and other benefits by these countries.
“Withholding information” from countries that share samples will be a “major step backward in the field of global infectious disease surveillance and research,” he says.