In focus. Proposed experiments that could make the H7N9 avian influenza more dangerous are provoking discussion.

Centers for Disease Control and Prevention/Cynthia S. Goldsmith and Thomas Rowe

Roundup: Researchers React to Controversial H7N9 Research Proposal

Reporters around the world are getting mixed reactions to today’s publication, by Science and Nature, of a letter from 22 flu researchers that makes the case for launching potentially risky experiments with the H7N9 avian influenza virus.

You can read the letter and Science's coverage here. There is also a letter from officials at the U.S. Department of Health and Human Services, in which they announce plans to give extra scrutiny to any proposals for experiments that would give H7N9 enhanced transmissibility.

In other coverage, Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases (NIAID), which funds the laboratories where the signers of the letter work, told Bloomberg Businessweek that:

"There are strong arguments to do the science," but it has to be done properly or not at all. … “It's not a rubber stamp," Fauci said. "If the risk is felt to be too high by this outside review, they will recommend it won't be done and we won't fund it."

Marc Lipsitch, a professor of epidemiology at the Harvard School of Public Health in Boston, told by e-mail that:

“The benefits are sketchy and uncertain for doing this kind of research, while the risk of creating a highly virulent, highly transmissible strain of flu are significant; the probability of an accidental or deliberate risk is small, but the consequences would be potentially staggering. … The fact that the global population is being put at risk by such experiments, to an appreciable but unknown degree, without being informed, much less consenting, is an ethical problem that has not been faced squarely.”

Wendy Barclay of Imperial College London was more supportive in comments distributed by the United Kingdom’s Science Media Centre and reported by MedPage Today:

"The gain-of-function experiments are a natural extension of the work that has already shown limited transmissibility of the wild type virus. … It would be ludicrous not to do them and they will be performed under appropriate containment."

"This type of work is like fitting glasses for someone who can't see well. …  Without the glasses the vision is blurred and uncertain, with them you can focus on the world and deal with it a lot more easily."

JSOnline in Milwaukee, Wisconsin, is reporting that the University of Wisconsin’s biosafety committee has already looked at a proposal for work with H7N9 by one of the letter’s lead authors, virologist Yoshihiro Kawaoka:

UW-Madison's institutional biosafety committee supports the new research on the H7N9 virus and resuming transmissibility research for the H5N1 virus, according to a UW-Madison official.

"We have H5N1. And our institutional biosafety committee has reviewed the proposed H7N9 work," said William Mellon, associate dean for research policy and a professor of pharmacy, who oversees UW's program for pathogens and toxins that require special oversight and have been highly regulated by the government since Sept. 11, 2001.

"There may be one experimental protocol still being discussed, but the university wishes to move forward," Mellon said Wednesday.

Virologist Michael Imperiale of the University of Michigan, Ann Arbor, has doubts about the proposed research, and the strategy behind the letter, reports Science News.

Unfortunately, the tone of the letter doesn’t invite debate, says Michael Imperiale, a virologist at the University of Michigan. “They’re hoping this is going to make the work appear more transparent,” he says, but beyond influenza researchers, he says, the scientific community has not engaged in adequate discussions about whether such experiments should be done in the first place.

And Imperiale raises another concern shared by many in the public but largely dismissed by infectious disease researchers:  the fear that a lab-created pandemic virus could escape containment. “If this type of work proliferates, eventually there is going to be a lab accident,” he says. “It becomes a matter of statistics. I’m not saying these guys aren’t being incredibly careful. We know from past experience that lab accidents happen.”

The United Kingdom’s The Independent also quotes Imperiale, saying that:

"The authors state that the H5N1 studies have 'contributed to...the development of vaccines and therapeutics, and improved surveillance'. I would like to see the evidence that supports this claim."

Michael Osterholm, director of the University of Minnesota's Center for Infectious Disease Research and Policy, is part of the NIAID-funded network of influenza centers that employ those who signed the letter. Although he is not opposed to gain-of-function research in principal, he declined to sign for several reasons, he told ScienceInsider earlier this week. One is that he a member of a U.S. government advisory board, the National Science Advisory Board for Biosecurity, which could end up reviewing some of the proposed H7N9 studies, posing a potential conflict of interest. Another is that governments have not yet pursued a thorough risk-benefit analysis of such work, and researchers and journals have not yet figured out how to selectively withhold results that might be useful to evil-doers, or promote copycat work in the laboratories without adequate safety and security precautions. As the Canadian Press's Helen Branswell reports in a story reprinted by The Province:

Osterholm remains concerned about the possibility of an accidental release of a mutated bird flu virus.

"I continue to support gain-of-function work from a basic research standpoint. But ... I sit in the middle here where I think there still are major questions about the risks-benefits of this work that need to be addressed," he said.

The Scientist also quotes Osterholm on the 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.”

In an editorial, Nature notes that:

A sense of perspective is crucial here. The long-term benefits of such work are clear — as long as it is done to the highest biosafety standards. It will shed light on, for example, the mechanisms of virus transmissibility and pathogenicity. But the immediate benefits to public health and our short-term ability to counter the threat of H7N9 are less clear-cut. Scientists cannot predict pandemics, so to assess the pandemic potential of viruses — and to decide which strains warrant the manufacture of trial vaccines — comes down to judgements of relative risk.