In a statement posted today on the Web sites of Nature and Science, a group of 39 influenza researchers announced a 2-month moratorium on studies that make the avian influenza strain H5N1 more transmissible between mammals. The moratorium is intended to allow time for an international debate about this type of research, which some people say has the potential to help bioterrorists.
ScienceInsider talked to Ron Fouchier of Erasmus MC in Rotterdam, the Netherlands, who carried out one of the two studies that triggered the international debate. (His paper is under review at Science.) Fouchier's answers have been translated from Dutch and edited for clarity and brevity.
Q: Who took the initiative for this announcement?
R.F.: The initiative came from Adolfo Sastre-García [an influenza researcher at Mount Sinai Medical Center in New York City who has a grant from the National Institute of Allergy and Infectious Diseases (NIAID) that funded Fouchier's study], Yoshihiro Kawaoka [whose H5N1 study, in press at Nature, has also been reviewed by the U.S. National Science Advisory Board for Biosecurity (NSABB)], and myself. We discussed it with a group of about 10 scientists who are doing similar studies themselves; then we asked another 30 or so influenza researchers who are not working on these studies but who could do them, if they wanted to sign. They all agreed wholeheartedly. So it's not a Fouchier show. It's an initiative that is supported very broadly.
Q: Why did you take this step now?
R.F.: We were advised by various organizations, and of course we've followed the press coverage and the political debates. We had the impression, based partly on advice from third parties, that it would be sensible to announce a moratorium.
Q: Which third parties?
R.F.: The organizations that fund our research, but also governments that we are talking to. So much is happening at the moment that it makes sense to take a break, to give the infectious diseases field time to think this over and talk about how to handle this kind of research in the future. This research offers opportunities and challenges, and governments and organizations need time to react.
Q: Are you doing this because if you don't, governments might move to halt the research?
R.F.: The debate is so controversial that we can't rule that out. We'd rather have everybody take a breather to reflect carefully on how to handle this.
Q: But have you received clear signals that there might be a ban of some sort?
R.F.: We don't have clear signals that something is about to happen, but you see the signals in the press, from experts and advisers, and those signals reach governments as well. We see articles from Michael Osterholm [director of the Center for Infectious Disease Research and Policy at the University of Minnesota, and an influenza expert], and from people like Laurie Garrett, the Pulitzer Prize winning author [and a Senior Fellow for Global Health at the Council on Foreign Relations]. And then there are the biosecurity experts at the University of Pittsburgh, like Thomas Inglesby. ... And [smallpox eradication leader] D. A. Henderson has been very vocal . All of these people can have quite an impact on the White House and elsewhere.
Q: How do you feel about the moratorium yourself?
R.F.: It's a pity that it has to come to this. I would have preferred if this hadn't caused so much controversy, but it has happened and we can't change that. So I think it's the right step to make. It's comparable to what happened in 1975 at the Asilomar conference. But I think that was driven more by the scientists themselves; this time it's mostly the public controversies that drive it.
Q: Do you have ideas about how the debate about these studies should be organized and who should participate?
R.F.: I think there has to be a whole series of debates. A couple are on the rails already. As we say in our statement, a meeting will be organized in the next couple of weeks, which I hope will include participation of the World Health Organization (WHO) and the U.S. government. The [American Society for Microbiology] has organized a plenary session at its biodefense meeting next month. The New York Academy of Sciences has a meeting as well. People need to talk, and infectious diseases specialists need to take the microphone and explain why this research is important and how you can do it safely.
Q: Has the scale of the controversy surprised you? Had you expected this when you first discussed the study at a meeting in Malta in September?
R.F.: When we presented this, of course we expected that there would be some commotion, and that we would have to explain to the public and the press why we're doing this and how you can do it safely.
I think we have done that very well in the Netherlands. We were very proactive; before we submitted the paper for publication we informed all the relevant authorities, so they knew what was happening and had the time to prepare, and when the story started making the rounds in the U.S. media, we spent 3 days talking to newspapers, TV, and radio. And that nipped the debate in the bud. In the U.S., this hasn't happened. And the people who are the most vocal in the press are the biosecurity experts. It's a pity that so few people from the flu field have jumped in front of the cameras, especially in the U.S.
Q: Did the NSABB recommendations take you by surprise?
R.F.: Absolutely. This was something that was unprecedented, and something I wasn't counting on at all.
NSABB has said that the risks outweigh the benefits, and now many people are saying: In that case, you shouldn't do this research at all. That's a very logical response. But the infectious disease community doesn't agree with NSABB on this. What NSABB should explain better is what the risks are exactly. How much bioterrorism have we seen in the past? What are the chances that bioterrorists will recreate these viruses? And is it really true that publication of this research would give bioterrorists or rogue nations an advantage? That's what I would like to hear from the NSABB.
Q: You think it doesn't give them an advantage?
R.F.: No. Because bioterrorists can't make this virus, it's too complex, you need a lot of expertise. And rogue nations that do have the capacity to do this don't need our information. So I don't think they will benefit from this information at all. Meanwhile, NSABB gives very little credit to the public health benefits, while the entire influenza community is crying just how important that is. For them the balance between risk and benefit is very different than for NSABB.
Q: But NSABB has several infectious disease researchers among its members, including Osterholm, who's an influenza expert himself. And they hired Robert Webster, a flu researcher at St. Jude Children's Research Hospital in Memphis, as a special adviser.
R.F.: The question is whether that was enough, or whether they should have asked more influenza experts. If they had asked somebody like Peter Palese of Mount Sinai School of Medicine, you would have had a very different answer. If you read his piece in Nature—I think he was totally right.
Osterholm, in his article [published yesterday with Henderson] in Science, has a very fatalistic attitude. He says countries in Asia, Africa, and the Middle East are unable to do surveillance, so they don't need the data from our paper. That's too fatalistic. It would be better to say: How can we help those countries set up a decent surveillance system? Osterholm also says that the data make no difference for vaccine development. That's really based on nothing. So if that is the influenza expert within NSABB, I'd like to see someone with a more positive attitude.
Q: How will the moratorium affect research at your own lab?
R.F.: We were of course working to find out exactly which mutations cause the virus to become transmissible by aerosol. That is going to stop now; we were almost done with that, but not quite. We were working to find out which biological properties of the virus are associated with the mutations that we have found. The biological properties of the virus are really more important than the mutations themselves.
Q: What biological properties are you referring to?
R.F.: In a paper in Current Opinion in Virology, we said we thought there were a number of things that might make an avian influenza virus transmissible between mammals. At the time, that was purely hypothetical. We said the virus probably has to do better in the upper respiratory tract than deep inside the lungs; it must bind to certain mammalian receptors; it has to reproduce in large amounts, to increase chances of transmission; it has to be stable in small droplets, and so on.
Now that we have these mutations, we can look at each of these steps to see if they occur. And you will see that for each step, there are multiple options, more possible mutations than just the ones we have found so far. So that's very important.
Something else that has to happen is evaluating existing vaccines and antiviral drugs. Until now, we only have looked in vitro whether these virus's characteristics match existing vaccine strains, and whether the virus is sensitive to antiviral drugs. We haven't tried it in our animal model yet.
Q: You also want to repeat the experiments with more H5N1 strains?
R.F.: Yes. We did this with one genetic lineage of the H5N1 virus. The question is whether all lineages can become aerosol-transmissible. If they can't, if it's just this lineage, perhaps you can focus on the region where it came from and try to stop H5N1 outbreaks there to prevent a pandemic. If it can happen everywhere, you've got to work everywhere.
Q: Would you also like to do similar studies in other avian influenza strains, such as H7N7?
R.F.: That is certainly something we'd like to do in the long run. But that has a much lower priority because we're not seeing H7N7 outbreaks at the moment, and we're definitely not going to do that anytime soon; I don't think that would be wise.
Q: Have you had requests from other labs to share the virus you have created?
R.F.: Not explicitly. Everybody understands that this is not the right time to ask.
Q: But if they did ask, what would you do?
R.F.: I have an agreement with our funder, the NIAID, that if such requests were made, I will discuss it with them. So I can't decide that on my own.
Q: Andrew Pekosz recently told Science that a moratorium would be especially harmful for the young scientists who do the actual lab work. Do you see that as a problem?
R.F.: I think that that is a small problem compared to the other issues. I have a postdoc here, Sander Herfst, who has worked on this extremely hard for 4 years and for whom a terrific breakthrough in his career is on hold. But those are individual cases. I think the repercussions of the NSABB recommendations for the life sciences are much more important. If we get very strict new guidelines for prescreening proposals, I think that could hobble the life sciences for years.
Q: In a policy forum you co-authored and which was published yesterday on Science's Web site, you suggest that you cannot promise to always keep the key details from your paper secret. Under what circumstances would you decide to reveal them?
R.F.: Well, Science and we have said that we're going to try to adhere to NSABB's recommendations. The U.S. government is now searching for a mechanism to share the key details with people who have a legitimate need to see them, but this is far from easy; there are all kinds of legal issues. So what that mechanism will look like and whom that information can be shared with is very unclear.
Meanwhile, WHO has said: This research is super-important, but it's just as important that the data are shared, or it could mean the end of the Pandemic Influenza Preparedness Framework. And rightly so, because that framework is very important for surveillance systems. Suppose it would collapse if for whatever reason the manuscript couldn't be shared with certain people. Then we'll have to talk to the U.S. government and WHO. That could happen. Again, you will have to weigh benefits and risks.
Also, as researchers, we work very closely with people in Indonesia. It would be very unwise for us not to share our results with our close collaborators.
Q: So if those researchers weren't approved to make use of the sharing mechanism ...
R.F.: I don't know who will be at the controls of that mechanism, and what the arguments would be for denying access to certain people. But if the result is that I can't share details with my collaborators, then I have a problem. That kind of situation can arise. So we're giving the American government and the NSABB the chance to set up a mechanism, and we are waiting what they come up with. But we cannot say now that we will never share that information.
Q: When do you think you will know more about that mechanism and the publication of your paper?
R.F.: The previous deadline was the end of January, but from what I have heard, the U.S. government has asked for a 4-week extension. So I think it will be late February.
Q: Are you in touch with Yoshihiro Kawaoka?
R.F.: On a daily basis.
Q: You have been all over the press while he has remained completely silent. Wouldn't you have preferred to make the case for these studies together?
R.F.: We both made a conscious choice to do what we did. I feel I have a responsibility to defend my point of view and to answer those media calls. And of course I made that decision when I decided to go to Malta. He hasn't talked about his work at a meeting, so what he has done is still under wraps in that paper at Nature. And I can understand his decision; he has two labs to run, one in Japan and one in the U.S. Frankly, the last 3 months I have done nothing but politics, press, and things like that. I don't have time for my science anymore.