Virologists plan influenza H7N9 gain of function experiments

A group of virologists lead by Yoshihiro Kawaoka and Ron Fouchier have sent a letter to Nature and Science outlining the experiments they propose to carry out with influenza H7N9 virus.

Avian influenza H7N9 virus has caused over 130 human infections in China with 43 fatalities. The source of the virus is not known but is suspected to be wet market poultry. No human to human transmission have been detected, and the outbreak seems to be under control. According to the authors of the letter, the virus could re-emerge this winter, and therefore additional work is needed to assess the risk of human infection.

The research that the virologists propose involve gain-of-function experiments which provide the H7N9 virus with new properties. The isolation of avian influenza H5N1 viruses that can transmit by aerosol among ferrets is an example of a gain-of-function experiment.

The proposed gain-of-function experiments fall into five general categories:

Determine whether viruses with altered virulence, host range, or transmissibility have changes in antigenicity, or the ability of the virus to react with antibodies. The results of these studies would suggest whether, for example, acquisition of human to human transmissibility would have an impact on protection conferred by a vaccine produced with the current H7N9 virus strain.

Determine if the H7N9 virus could be adapted to mammals and whether it could produce reassortants with other influenza viruses. The results of this work would provide information on how likely it is that the H7N9 virus would become better adapted to infect humans.

Isolate mutants of H7N9 virus that are resistant to antiviral drugs. The purpose of these experiments is to identify how drug resistance arises (the mutations can then be monitored in clinical isolates), determine the stability of drug resistant mutants, and whether they confer other properties to the virus.

Determine the genetic changes that accompany selection of H7N9 viruses that can transmit by aerosol among mammals such as guinea pigs and ferrets. As I have written before, the point of these experiments, in my view, is not to simply identify specific changes that lead to aerosol transmission. Such work provides information on the mechanisms by which viruses can become adapted to aerosol transmission, still an elusive goal.

Identify changes in H7N9 virus that allow it to become more pathogenic. The results of these experiments provide information on the mechanism of increased pathogenicity and whether it is accompanied by other changes in properties of the virus.

I believe that the proposed gain-of-function experiments are all worth doing. I do not share the concerns of others about the potential dangers associated with gain-of-function experiments: for example the possibility that a virus selected for higher virulence could escape the laboratory and cause a lethal pandemic. Gain-of-function is almost always accompanied by a loss-of-function. For example, the H5N1 viruses that gained the ability to transmit by aerosol among ferrets lost their virulence by this route of infection. When these experiments are done under the proper containment, the likelihood that accidents will happen is extremely small.

All the proposed experiments that would use US funds will have to be reviewed and approved by the Department of Health and Human Services:

The HHS review will consider the acceptability of these experiments in light of potential scientific and public-health benefits as well as biosafety and biosecurity risks, and will identify any additional risk-mitigation measures needed.

While I understand that the authors wish to promote a dialogue on laboratory safety and dual-use research, I question the ultimate value of the communication. Because the letter has been published in two scientific journals, I assume that the target audience of the letter is the scientific community. However, the letter will clearly have coverage in the popular press and I am certain that it will be misunderstood by the general public. I can see the headlines now: “Scientists inform the public that they will continue to make deadly flu viruses”. The controversy about the H5N1 influenza virus transmission studies in ferrets all began with a discussion of the results before the scientific papers had been published. I wonder if the publication of these letters will spark another controversy about gain-of-function research.

In my view, science is best served by the traditional process known to be highly productive: a grant is written to secure funding for proposes experiments, the grant proposal is subject to scientific review by peers, and based on the review the work may or may not be supported. The experiments are done and the results are published. I do not understand why it is necessary to trigger outrage and debate by announcing the intent to do certain types of experiments.

I am curious to know what the many readers of virology blog – scientists and non-scientists – feel about the publication of this letter. Please use the comment field below to express your views on this topic.