Science: Confronting the Implications of Research on H5N1 Avian Influenza

Scientists working on the transmission of the H5N1 avian influenza strain have voluntarily agreed to halt research for 60 days to allow time for international discussion on its benefits and potential harms.

In a letter published today by Science and Nature, the researchers acknowledge that they and the rest of the scientific community need to clearly explain the benefits of this research and the measures taken to minimize its possible risks. They propose an international forum for the scientific community to discuss these issues.

“We realize that organizations and governments around the world need time to find the best solutions for opportunities and challenges that stem from the work,” they write. “To provide time for these discussions, we have agreed on a voluntary pause of 60 days on any research involving highly pathogenic avian influenza H5N1 viruses leading to the generation of viruses that are more transmissible in mammals.”

Since its first detection in 1997, the H5N1 avian influenza virus has devastated the poultry industries of numerous countries and caused over 300 human deaths. The virus does not spread easily between humans, but if it did—via aerosol transmission, for example—it could cause a deadly pandemic. But when two research teams described mutations in the H5N1 genome which allow the virus to spread via small droplets, or “aerosols,” among ferrets, they created a heated controversy.

The researchers were trying to understand how H5N1 works, and how it might mutate to become lethal to humans. But other scientists, including the U.S. government’s National Science Advisory Board on Biosecurity (NSABB), have been concerned that the research could be used for harmful purposes, or that the mutated virus might accidentally be released from the laboratory where it is contained.

In the letter, 39 scientists in the influenza research community have voluntarily agreed to a 60-day pause on all research involving the transmission of the H5N1 virus to other mammals. The letter is now available to the public, along with additional resources, at Science’s Public Health, Biosecurity, and H5N1 site.

This letter follows a recommendation in December 2011 by the NSABB that Science and Nature should limit the publication of this research substantially, omitting information that would make it possible for those with harmful intentions to replicate the work.

Science, published by the non-profit AAAS, is taking these recommendations seriously and is now considering its next steps. Science’s Editor-In-Chief Bruce Alberts has said that the journal’s response will be heavily dependent upon the further steps taken by the U.S. government to set forth a written, transparent plan to ensure that any information omitted from publication will be provided to responsible scientists who are engaged in legitimate efforts to improve public health and safety.

A special set of commentaries published in the 19 January issue of Science reveals the widely diverging views among scientists about how to proceed, with both this field of research and the publication of the two studies in particular.

The Study Authors Speak

The H5N1 virus has already destroyed many countries’ poultry industries and taken a toll on human life. Outbreaks in poultry are not always stamped out with a sense of urgency for human health, partly as a consequence of inconsistent scientific advice about the risk that this virus could cause a human pandemic, according to the commentary by Ron Fouchier and coauthors from the Erasmus Medical Center in Rotterdam, the Netherlands.

This is the situation that Fouchier and his colleagues aimed to address with their research on H5N1 virus transmission, which is one of the two studies that have caused the recent controversy.

If the virus could acquire the ability to spread among humans via aerosols, then measures for identifying and responding to a pandemic would need to be revised substantially. The more precisely researchers understand the changes responsible for the virus’ evolution into a transmissible form, Fouchier and colleagues argue, the better they will be able to detect harmful strains and to tailor diagnostic tests, antiviral drugs, and vaccines that will help keep humans safe.

From the planning stages onward, this research followed a process involving serious local, national, and international consultation, the researchers say. Regarding the recent recommendation of the NSABB to publish only the conclusions of the research but not the experimental details or mutation data that would enable replication of the experiments, Fouchier and colleagues write: “We do not agree with the NSABB recommendations. Nevertheless, we have respected their advice.”

An Argument for Full Publication

Information related to influenza transmissibility should be published in its entirety, according to Daniel Perez of the University of Maryland. In his commentary, Perez focuses on the serious threat that avian flu viruses pose as they continue to spread and evolve in domestic poultry.

If nations do not make a concerted effort to help countries eradicate H5N1 viruses from domestic poultry, Perez says, they will continue to face a potential H5N1 influenza pandemic. Further, it is likely that viruses with the mutations identified by Fouchier and others will occur in nature at some point.

Perez argues that the key elements that have made these viruses transmissible by respiratory droplets in the laboratory must be communicated properly in order to help public health officials make informed decisions if they are faced with similar viruses outside the lab. He also cautions against stopping this type of research out of fear for the potential misuse of it and reminds readers that many countries have improved their capacity for making vaccines since the 2009 H1N1 pandemic.

“It is not through fear that we will stop H5N1 from becoming pandemic,” he writes. “The pursuit of knowledge is what has made humans resilient, a species capable of overcoming our worst fears.”

An Argument Against Full Publication

Releasing the methods and results of the two studies would not do enough to protect the public from a future H5N1 pandemic, which would be one of the most virulent infectious outbreaks ever known, according to Michael Osterholm of the University of Minnesota and D.A. Henderson of the University of Pittsburgh.

Further, the specific mutational changes identified in this research should not be shared with anyone outside of a small, select group of established researchers already working within the World Health Organization Network. Every possible effort should be made to keep the details of these studies from falling “into the hands of those who might use it for nefarious purposes,” these researchers argue in their commentary, saying this should be the highest priority of agencies like the World Health Organization.

Although others have claimed that more specific information in the two studies would help surveillance organizations identify potential H5N1 pandemics quickly, experience has shown that detecting an emerging pandemic virus in animals before it occurs in human populations is unrealistic, according to Osterholm and Henderson. Even when H5N1 infections are detected in animals, there is rarely enough veterinary and laboratory support on-hand to sequence the genes of the virus and create a mutation map in a timely fashion.

The real focus now should be on licensing and manufacturing new influenza vaccines that could be readily available on a global scale and target multiple strains, the researchers argue. Accordingly, it is the duty of life scientists to minimize the risks of a pandemic, say Osterholm and Henderson, and to ensure that such a virus does not become the agent of a large-scale, unplanned human experiment.

What are the Limits to Government Regulation of Science?

In the final commentary, John Kraemer of Georgetown University School of Nursing and Health Studies and Georgetown University Law Center and Lawrence Gostin of Georgetown University Law Center turn to history, highlighting past publication restrictions and court cases involving federal research funding to offer perspective on the sometimes rocky relationship between the U.S. government and scientific freedom.

The first time the U.S. government requested that a journal not publish information occurred in 1979, when the Department of Energy secured an injunction against the magazine The Progressive to prevent publication of an article about building a hydrogen bomb (even though the information was in the public domain). While government requests to withhold information do not violate First Amendment rights, the researchers note that it is far less clear whether the government may suppress the publication of research conducted with federal funding, particularly when the results are categorized as “uncontrolled unclassified information,” as is the case with the H5N1 research.

The inconsistent classification practices among federal agencies add to the problem of government discretion. Kraemer and Gostin call for improvements to institutional oversight of high-risk research as a preferred alternative to government constraints on scientific information by force of law.

Kathy Wren, Brandon Bryn, and Nadia Ramlagan

20 January 2012