It’s Baaack! The Biosecurity Controversy Over “Gain-of-Function” Research on Influenza Viruses Returns

On August 7th, a group of influenza scientists published online a letter in Nature in and Science in which they proposed conducting “gain-of-function” (GOF) research on the avian influenza A (H7N9) virus. GOF research is sometimes discussed as “dual use research of concern,” or DURC. I have posted on Arms Control Law, and published elsewhere, on developments in the biosecurity and public health controversy over GOF research on the highly pathogenic avian influenza A (H5N1) virus by Dutch researchers, led by Ron Fouchier from the Erasmus Medical Center, and American scientists, led by Yoshihiro Kawaoka from the University of Wisconsin-Madison. The announcement of the proposed GOF experiments on the H7N9 virus has brought the controversy back into the spotlight.

To recap, “gain-of-function” research involves scientific experiments that alter pathogens in ways that give them features or functions not presently found in the wild. In the H5N1 GOF research that sparked the worldwide controversy from late 2011 until early 2013, researchers manipulated the H5N1 virus so that it achieved transmissibility between mammals–a capability the virus had not readily demonstrated in nature. Generally speaking, an objective of GOF research on influenza viruses is to provide an earlier understanding of how the viruses might mutate in the wild and cause human pandemics, potentially giving scientists and public health experts more time to develop potential responses, such as alerting surveillance systems and preparing vaccine strategies.

Critics of the H5N1 GOF research worried about a number of problems, including whether (1) biosafety conditions in laboratories would be adequate to prevent accidents that could cause outbreaks, and (2) such experiments could threaten biosecurity by providing states, terrorists, or criminals with “blueprints” for making biological weapons. The controversy led to delayed publication of the H5N1 GOF research results, a voluntary moratorium on GOF research, and the development by the U.S. government of new, stricter rules and oversight processes for GOF research it funds.

Similar to the GOF H5N1 experiments, the proposed H7N9 GOF research includes, among other things, experiments “[t]o assess the pandemic potential of circulating [H7N9] strains and perform transmission studies to identify mutations and gene combinations that confer enhanced transmissibility in mammalian models (such as ferrets and guinea pigs).” Global health concerns about the H7N9 virus arose in spring 2013 when a worrying number of cases of humans infected by contact with birds occurred in China. As of early July, the mortality rate among humans infected with H7N9 was approximately 33%, making the virus a killer pathogen. To date, the H7N9 virus has not demonstrated serious human-to-human transmission, but the fear is that it might mutate and spread more readily in human populations. The proposed GOF experiments on the H7N9 virus are intended to give scientists and public health officials possible insights into how the virus might change into something more fearsome–and, thus, give them more time to prepare.

Critical reactions to the proposed H7N9 GOF research indicated that the biosecurity and public health controversy over GOF experiments has not subsided. A flavor of the criticism can be found in this story from Science:

“The scientific justification presented for doing this work is very flimsy, to put it mildly, and the claims that it will lead to anything useful are lightweight,” says Adel A. F. Mahmoud, an infectious disease specialist at Princeton University and the former president of Merck Vaccines. And the security precautions are “insufficient and amazingly lame,” says molecular biologist Richard Ebright of Rutgers University in Piscataway, New Jersey.

And from this story in The Scientist:

Simon Wain-Hobson, a virologist from the Pasteur Institute in France, was critical of the move. “Since when do scientists try to get manifestos into Nature and Science?” he asked. “If they were going to do the human genome or go after the Higgs boson, I could understand that, but this is extraordinarily focused. They are ramming gain-of-function experiments down our throats against debate, and it’s not scientific.”
. . .
Michael Osterholm, director of the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota and a vocal critic of last year’s decision to publish the H5N1 research, added that the flu community still has not rigorously weighed the risks and benefits of gain-of-function studies. “I support doing them for basic research purposes, and I have always maintained that Yoshi [Kawaoka] and Ron [Fouchier] could do this work safely,” he said. “But my concern is that publishing their data would allow labs around the world, which won’t adhere to the same safety requirements, to do the same.”

Osterholm added that the signatories of today’s letter have overstated the benefits of gain-of-function research, including the potential for developing better vaccines and antiviral drugs, or improving surveillance measures. “We still do H5N1 surveillance in the same way a year later,” he said.

In terms of arms control and non-proliferation, the GOF controversy includes arguments about the BWC’s (ir)relevance to the challenge of balancing public health and biosecurity in scientific research. The BWC review conference in December 2011 occurred when the H5N1 GOF controversy was in full swing, but the BWC states parties did not address it in any serious way , despite much rhetoric about the BWC being a central forum for discussing biosecurity issues beyond the traditional focus on non-proliferation of biological weapons by states. The reticence of BWC states parties to address this controversy connected to a larger governance problem that emerged from the H5N1 GOF research episode–the inadequacy, or lack of, adequate national and international rules and processes to deal effectively with the pros and cons of GOF research.

The scientists proposing the H7N9 GOF research are seeking U.S. government funding, so the proposal will be subject to the heightened U.S. rules and procedures adopted after the H5N1 controversy. The H7N9 GOF experiments, if approved and funded by the U.S. government, will go forward under these rules. How the U.S. government handles these proposals under its new approach will be closely watched by the biosecurity, public health, and scientific communities around the world.