H5N1 Transmissable Research: Key Documents at 1 Jan 2012

[Editor’s Note: We present three key statements involving the continuing debate around publication of recent H5N1 research on transmissible strains and related biosecurity concerns: The NSABB statement, a WHO statement of concern, and a Washington Post editorial]

Press Statement: National Science Advisory Board for Biosecurity (NSABB) Review of H5N1 Research
The U.S. government remains concerned about the threat of influenza, for the risks it poses seasonally, as well as its potential to cause a pandemic. Our domestic and global influenza surveillance efforts have become increasingly capable, along with expanded vaccine manufacturing capacity and assistance to other countries in their efforts to detect and respond to a pandemic. To enhance the detection of and response to influenza outbreaks, the U.S. government supports a broad range of domestic and global preparedness and response efforts that include research on better diagnostics, vaccines, and therapeutics.

Currently, H5N1 avian influenza virus — the strain commonly referred to as “bird flu” — rarely infects humans and does not spread easily from person to person. However, many scientists and public health officials are concerned that the virus could evolve in nature into a form that is transmissible among humans — an event that could potentially make this deadly virus an extremely serious global public health threat. Thus research on factors that can affect the transmissibility of the H5N1 virus is critically important to international efforts to prepare and prevent threats to public health.

While the public health benefits of such research can be important, certain information obtained through such studies has the potential to be misused for harmful purposes. The National Science Advisory Board for Biosecurity (NSABB) — an independent expert committee that advises the Department of Health and Human Services (HHS) and other Federal departments and agencies on matters of biosecurity — completed a review of two unpublished manuscripts describing NIH-funded research on the transmissibility of H5N1. These manuscripts — which describe laboratory experiments that resulted in viruses with enhanced transmissibility in mammals – concluded that the H5N1 virus has greater potential than previously believed to gain a dangerous capacity to be transmitted among mammals, including perhaps humans, and describe some of the genetic changes that appear to correlate with this potential.

Following its review, the NSABB decided to recommend that HHS ask the authors of the reports and the editors of the journals that were considering publishing the reports to make changes in the manuscripts. Due to the importance of the findings to the public health and research communities, the NSABB recommended that the general conclusions highlighting the novel outcome be published, but that the manuscripts not include the methodological and other details that could enable replication of the experiments by those who would seek to do harm.

The NSABB also recommended that language be added to the manuscripts to explain better the goals and potential public health benefits of the research, and to detail the extensive safety and security measures taken to protect laboratory workers and the public.

HHS agreed with this assessment and provided these non-binding recommendations to the authors and journal editors.

Recognizing the significant potential benefit of the information about the experimental details to the global influenza surveillance and research communities, the U.S. government is working to establish a mechanism to allow secure access to the information to those with a legitimate need in order to achieve important public health goals. The U.S. government is also developing a proposed oversight policy that would augment existing approaches to evaluating research that has the potential to be misused for harmful purposes.

The NSABB supports the overall goals of the National Institutes of Health, in conducting safe, ethical and informative research to enhance health, lengthen life, and reduce the burdens of illness and disability. http://www.nih.gov/news/health/dec2011/od-20.htm

Statement: WHO concerned that new H5N1 influenza research could undermine the 2011 Pandemic Influenza Preparedness Framework
30 December 2011
The World Health Organization (WHO) takes note that studies undertaken by several institutions on whether changes in the H5N1 influenza virus can make it more transmissible between humans have raised concern about the possible risks and misuses associated with this research. WHO is also deeply concerned about the potential negative consequences. However, WHO also notes that studies conducted under appropriate conditions must continue to take place so that critical scientific knowledge needed to reduce the risks posed by the H5N1 virus continues to increase.

H5N1 influenza viruses are a significant health risk to people for several reasons.  Although this type of influenza does not infect humans often, when it does, approximately 60% of those infected die. In addition, because these viruses can cause such severe illness in people, scientists are especially concerned that this type of influenza could one day mutate so it spreads easily between people and causes a very serious influenza pandemic.

Research which can improve the understanding of these viruses and can reduce the public health risk is a scientific and public health imperative. In order to enable those public health gains, countries where these viruses occur should share their influenza viruses for public health purposes while countries and organizations receiving these viruses should share benefits resulting from the virus sharing. Both types of sharing are on equal footing and equally important parts of the collective global actions needed to protect public health.

While it is clear that conducting research to gain such knowledge must continue, it is also clear that certain research, and especially that which can generate more dangerous forms of the virus than those which already exist, has risks. Therefore such research should be done only after all important public health risks and benefits have been identified and reviewed, and it is certain that the necessary protections to minimize the potential for negative consequences are in place.

In May 2011, the new Pandemic Influenza Preparedness (PIP) Framework came into effect. This Framework was adopted by all WHO Member States as a guide to the sharing of influenza viruses with pandemic potential and the resulting benefits. One specific requirement of this Framework, which pertains to influenza viruses of pandemic potential, and is in keeping with best scientific practice, is for laboratories receiving them through WHO’s Global Influenza Surveillance and Response System (GISRS) to collaborate with, and appropriately acknowledge, scientists in countries where the virus originated when initiating research.

WHO recognizes that the scientists who led the work of the new studies received their virus samples from the WHO Global Influenza Surveillance Network (GISN), which preceded GISRS, and before negotiations on the new PIP Framework began. However, now that the Framework has been adopted by all WHO Member States, WHO considers it critically important that scientists who undertake research with influenza viruses with pandemic potential samples fully abide by the new requirements.

Since the PIP Framework represents a major step forward and was agreed upon only after several years of difficult negotiations, WHO stresses that this H5N1 research must not undermine this major public health achievement. WHO will work with Member States and other key parties to ensure scientists understand the new requirements that have been agreed to with the Framework.


Editorial: A flu virus risk worth taking
Washington Post
30 Dec 2011
By Anthony S. Fauci, Gary J. Nabel and Francis S. Collins
Anthony Fauci is director of the National Institute of Allergy and Infectious Diseases (NIAID), Gary Nabel works in the virology laboratory at the NIAID and Francis Collins is director of the National Institutes of Health.

A deadly influenza virus has circulated widely in birds in recent years, decimating flocks but rarely spreading to humans. Nonetheless, because of its persistence in bird flocks, this highly pathogenic virus has loomed as a major public health threat. Seasonal influenza kills less than 1 percent of the people it infects. In contrast, human infections with the H5N1 virus, though exceedingly rare, are fatal in most cases. Should this virus mutate in a way that allows it to be transmitted as efficiently among people as seasonal influenza viruses are, it could take an unprecedented toll on human life.

A number of important scientific and public health questions regarding this virus remain unanswered, including the likelihood of such mutations arising and the mechanisms by which they may occur. Two recent studies co-funded by the National Institutes of Health have shed light on how this potentially grave human health threat could become a reality. Working carefully with influenza viruses they have engineered in isolated laboratories, scientists in Europe and the United States have identified several mechanisms by which the virus might evolve to transmit efficiently in the ferret, the best animal model for human influenza infection. This research has allowed identification of genetic pathways by which such a virus could be better adapted to transmission among people. This laboratory virus does not exist in nature. There is, however, considerable concern that such a virus could evolve naturally. We cannot predict whether it or something similar will arise naturally, nor when or where it might appear.

Despite these uncertainties, much good can come from generating a potentially dangerous virus in the laboratory. We have to consider the unpredictable and explosive nature of influenza epidemics.

While the World Health Organization and the Centers for Disease Control and Prevention (CDC) provide excellent public health surveillance for novel influenza strains, influenza outbreaks still occur suddenly and in unexpected places. The recent H1N1 pandemic exemplifies the problem: In 2009, a new influenza virus emerged. It was shown to have originated from an animal reservoir, and it spread so rapidly that it strained the pharmaceutical industry’s capacity to prepare vaccines fast enough to blunt its spread.

Moreover, we do not fully understand the underlying factors that allow influenza viruses to be transmitted efficiently in humans after they emerge from different species.  The ferret transmission studies were intended in part to fill these important gaps in knowledge.

Understanding the biology of influenza virus transmission has implications for outbreak prediction, prevention and treatment. In defining the mutations required for mammalian transmission, public health officials are provided with genetic signatures that, like fingerprints, could help scientists more readily identify newly emergent, potentially harmful viruses, track their spread and detect threatening outbreaks. The ability to identify such viruses even a few months faster than by conventional surveillance provides critical time to slow or stop an outbreak. The CDC provides this health security by implementing public health protective measures, preparing vaccines and stockpiling antiviral drugs. Identifying threatening viruses can also facilitate the early stages of manufacturing vaccines that protect against such a virus in advance of an outbreak.

In addition, determining the molecular Achilles’ heel of these viruses can allow scientists to identify novel antiviral-drug targets that could be used to prevent infection in those at risk or to better treat those who become infected. Decades of experience tell us that disseminating information gained through biomedical research to legitimate scientists and health officials provides a critical foundation for generating appropriate countermeasures and, ultimately, protecting public health.

The underlying question, of course, is whether the benefits of such research outweigh the risks. The answer is not simple. A highly pathogenic avian influenza virus transmissible in humans could arise in ways not predicted by laboratory studies. And it is not clear whether the laboratory virus would behave in humans as it does in ferrets. Nonetheless, new data can provide valuable insights that would inform influenza preparedness and help delineate the principles of influenza virus transmission between species.

Along with support for this research comes a responsibility to ensure that the information is used for good. Safeguarding against the potential accidental release or deliberate misuse of laboratory pathogens is imperative. The engineered viruses developed in the ferret experiments are maintained in high-security laboratories. The scientists, journal editors and funding agencies involved are working together to ensure that access to specific information that could be used to create dangerous pathogens will be limited to those with an established and legitimate need to know.