Controversial research modifying A(H5N1) influenza viruses in the laboratory – Formal report of WHO technical consultationArchived

Formal note of a technical consultation undertaken by WHOWorld Health Organization Headquarters, Geneva, Switzerland – 16th-17th February 2012

As a consequence of controversy over the publication of two recent research studies concerning laboratory induced changes in the host range of avian influenza  A(H5N1) viruses the World Health Organization (WHO) recently convened a technical consultation on 16 and 17 February 2012. Following an initial rapid communication on the consensus points WHO has now issued a more formal record of the meeting.

The participants at this meeting were from a broad range of countries and bodies including all the global Influenza Collaborating Centres, the countries where the viruses were originally isolated, the funding body for the research (the US National Institutes of Health) and the journals which had accepted the articles following satisfying the peer review present. Also present were the two principle investigators, the chairs of the US Board that had been asked to consider the publication and the WHO Advisory Board for implementation of the Pandemic Influenza Preparedness (PIP) Framework as well as independent experts in ethics and public health from a number of countries.

Several issues relating to publication were considered:

• If the research were to be published in redacted form (obscuring some of the scientific information), would genetic sequence data and/or the research methods remain completely restricted, or should the information be made available to a limited audience, after a public health justification for use of the information
• If the latter, what workable mechanism would allow selective access to this information by laboratories involved in public health surveillance and legitimate research
• What criteria would be required for access, and which organization would exercise governance over access
• How could dissemination to those permitted access be performed securely
• Could the confidentiality of the information be maintained

In addition several questions were explored with regard to the laboratory-modified viruses:

• After the current moratorium on this research expires, should the viruses be destroyed
• Should the samples be kept at their current locations
• Is it necessary to transfer them to locations of increased laboratory biosecurity
• What biosafety and laboratory biosecurity considerations and standards should be required for any subsequent work
• If the viruses are not to be destroyed, how could the findings of research be applied towards the development of vaccine-candidate viruses or other countermeasures
• What further research would be acceptable or desirable, especially in light of the PIP Framework

The meeting, which was chaired by WHO achieved agreement on a series of points in relation to the above:

• The two studies in question have shown that these viruses at least have the potential to become more transmissible among mammals.
• Hence A(H5N1) viruses remain an important risk for causing a future pandemic and research on them, including on their transmissibility and pathogenicity, remains critical and should continue.
• The PIP Framework  (adopted by all Member States in 2011 at the World Health Assembly) provides a global framework both for the sharing of influenza viruses with human pandemic potential and the sharing of benefits arising from such sharing.
• Implementation of this Framework is integral to global pandemic preparedness and response. Future research projects like the two in question should continue to involve countries from which source material were obtained as is stated in the agreed Framework.
• The redaction option is not viable to deal with the two papers under discussion in view of the urgency of the above mentioned public health needs, although there may be a need for such a mechanism in the future.
• The papers should be published but critical issues needing to be addressed before publication are:
  • a focused communications plan to increase public awareness and understanding of the significance of these studies and the rationale for their publication,
  • a review of the essential biosafety and biosecurity aspects of the newly developed knowledge.
• The studies have also raised important concerns about whether they increase risks to the safety of humans, the potential misuse of the results or methods, and potential breaches in biosafety and biosecurity related to pathogens. Although such safeguards already exist, continued emphasis should be placed on assuring and reinforcing safety and security.
• The laboratory-modified influenza A(H5N1) viruses are stored in well-established research facilities with high security and high safety at what is known as BSL3+ levels. There have  been no safety breaches at these facilities.
• The current moratorium on research to enhance the transmissibility of influenza A(H5N1) viruses and further research on the laboratory-modified viruses should continue at least until the conditions under which such research can take place safely have been determined.
• Research on naturally occurring influenza viruses including A(H5N1) viruses, notably that concerning assessment of the risks they pose, should continue.

The next steps will be:

1. To define the essential biosafety and laboratory biosecurity standards and practices to be observed in future work with these laboratory-modified viruses (currently there is no agreed definition for BSL3+ and as a consequence the facilities doing this work use somewhat different practices, though all are of a high security level);
2. To increase awareness of the nature and objectives of this research and to place the results in the context of the current assessment of the threat posed by wildtypeH5N1 viruses.
3. To hold further discussions on the scientific and societal issues raised by this kind of research. Specific topics to be addressed include how to strengthen public safety and security while ensuring that critical scientific research continues, as well as mechanisms to assess and manage sensitive research.

ECDC Comment (26 March 2012)

On February 29th ECDC issued a Risk Assessment describing and commenting on a number of the complex and interlocking issues that have arisen. That made it clear that ECDC’s view is that the papers should be published. One reason for that is that there is now considerable confusion on the pathogenicity and transmissibility of the viruses that have been created and insufficient information to undertake a proper scientific risk assessment. While in ECDC’s view the data available suggest that the type of work that led to the creation of the viruses inherently requires high levels of biosafety the specific viruses produced seem not to be very transmissible or pathogenic, at least in ferrets.

As far we can see it from the data neither the Rotterdam nor Madison viruses will kill a ferret unless they are introduced in high does into the lungs. If allowed to transmit naturally they spread poorly among ferrets and at worse causes them to experience the equivalent of an upper respiratory tract infection. Such impressions are based on limited research (1), a short report (2) and an oral presentation.(3,4) This makes a strong case for full publication and the eventual lifting of the moratorium.