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Debate Persists Over Publishing Bird Flu Studies

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IRA FLATOW, HOST:

This is SCIENCE FRIDAY. I'm Ira Flatow. Our next story is about ferrets, those furry little animals that some people keep as pets but which some scientists use as guinea pigs, and that's the story that interests us because experiments using ferrets to study how the bird flu spreads has caused quite a commotion in the world of science.

Two labs, one in the Netherlands and the other in Wisconsin, say they have developed a deadly strain of bird flu virus that can be transmitted through the air from ferret to ferret, something that couldn't happen easily before. A federal advisory board has urged the journals Science and Nature not to publish the details, all the details of the research.

Members of the advisory board and some biosecurity experts are concerned that the research could fall into the wrong hands. Other researchers disagree, and they call the studies too valuable not to share with the scientific community.

So we're going to talk about that this hour, our number 1-800-989-8255, sort of have a debate between two sides of the issue, and let me introduce my guests. Dr. D.A. Henderson is professor of public health and medicine at the University of Pittsburgh. He's also a distinguished scholar at the Center for Biosecurity at the University of Pittsburgh Medical Center. He led the successful worldwide effort to eradicate smallpox in the '70s and directed the U.S. Office of Public Health Emergency Preparedness after the deadly anthrax letter attacks. He joins us from WYPR in Baltimore. Welcome to SCIENCE FRIDAY, Dr. Henderson.

DR. D.A. HENDERSON: Very happy to be with you.

FLATOW: Thank you. Dr. Vincent Racaniello is a professor of microbiology and immunology at Columbia, and he is here in our New York bureau. Welcome to SCIENCE FRIDAY.

DR. VINCENT RACANIELLO: Thank you for pronouncing the name right.

FLATOW: Well, we try. I pronounce them so badly so many times that even my own name gets wrong. Let me begin with you, Dr. Racaniello. What do we know about this virus developed by the two labs?

RACANIELLO: So we know little because it hasn't been published. That's important to point out at the outset. What we know is what we've heard through stories, and that is that the scientists in the Netherlands took avian H5N1 influenza virus strain, which is lethal in ferrets but is not transmitted, and they passed it from ferret to ferret until they obtained an isolate that could then be transported through the air from one ferret to another, from a ferret in one cage to an uninfected ferret in another.

And then they identified the genetic changes that occur to accompany that process.

FLATOW: And you say that we don't know that much about it because stuff has been held back.

RACANIELLO: That's right.

FLATOW: What has been held back?

RACANIELLO: So the methods, how exactly they passed the virus from ferret to ferret, what types of ferret, how many ferrets, how much virus they put in and most importantly the genetic changes that occurred when the virus was able to pass from one ferret to the other.

FLATOW: And why would you need to know those things?

RACANIELLO: So we don't understand why the H5N1 viruses do not transmit among people, and this kind of experiment gets at that, why the virus is not able to be transmitted. We can't do that experiment in people, obviously, so we use an animal model, which is the ferret.

FLATOW: Dr. Henderson, you believe it was the correct call to hold back that data.

HENDERSON: I do believe it was, no question about it.

FLATOW: Tell us why.

HENDERSON: I think we're dealing here with a very serious organism, which if indeed it did spread well among people and killed as many people as it has to date, occurring as individual cases or small groups of cases, and that is a death rate of more than 50 percent, we would have a real disaster on our hands.

So how this organism spreads is important, but once it is - the information is made widely available, I think the fear is that this will be a point of experiment for a number of people, and we have to worry about an accident in a laboratory, release, escape by some means.

FLATOW: Dr. Racaniello?

RACANIELLO: So this is a common misconception about H5N1 avian influenza, that it's highly lethal. The number of 50 percent lethality is quoted widely. What that means is half of the 600 people who have been admitted to hospitals die. But we don't know how many people have been infected, and there is some good evidence that many more people have been infected without being sick.

And so that would make the virus much less scary than everyone thinks it is.

FLATOW: Dr. Henderson?

HENDERSON: Well, wait.

FLATOW: Go ahead, respond. I'm giving you a chance, go ahead.

HENDERSON: OK, with all deference to Dr. Racaniello, there is one study that was done in Thailand, just recently reported, in which it appeared that nine percent of the population did carry antibody against the H5N1. However, since back in 2003, there have been many studies done of patients and the individuals in their family, in their village, contacts in hospitals and so forth. The transmission rate is extremely low.

We're looking at one or two cases, and thus we're seeing - counting the cases that way, and these are more than 20 studies. You would see that the death rate was right around 50 percent, and that seems to hold up from the small outbreak to small outbreak.

The study in Thailand is a distinct exception to anything that's been seen.

RACANIELLO: There have been about 17 or 18 such studies done, starting in the late 1990s, when these viruses first infected people up to the present, and there are a handful that show seropositivity in certain populations. I think we need to go into rural Asian populations that have contact with poultry and really get at this. Before we do that, we can't say that this virus is 50 percent lethal.

FLATOW: Dr. Henderson, if there is so much concern on your part and the part of others about the outcome of this research, why was this study given the go-ahead to begin with if it might have turned out this way?

HENDERSON: Well, I think decisions with regard to research are usually in the hands of investigators and their institutions. Very rarely is there any imposition on the part of government with regard to what one does or doesn't do with the viruses.

However, I think it's important to point out that there is precedent for a group of scientists to get together and, working with government, impose restrictions on the use of a virus, which was highly lethal and would have an enormous effect if it was - got into the population.

And that pertains to smallpox virus, which carries a case fatality rate, death rate of about 30 percent. Most of the population of the world now, roughly 75 percent, are fully susceptible to it. We don't really have enough vaccine to control it, and the concern was that if it got out, began to spread, we'd have a hard job controlling it.

It was felt to be serious enough that it was decided that only two laboratories would be allowed to work with the virus. And those two laboratories, one in Moscow, one in Atlanta, two laboratories with a history of working with it, and secondly that any protocols that they wished to implement, studies, would have to pass muster with an international group of scientists in regard to the need for doing it and risk and so forth. Both are working in high-security laboratories. Now, that provision has been in place more - really more than 10 years, and it is still being adhered to today.

Now this is not to suggest that H5N1 would be handled in the same way, there are different conditions here, but what has been established is a precedent where there are a group of scientists and governments who decide that this is too serious a virus or organism to be circulating, and we should keep this under the closest of supervision.

FLATOW: Dr. Racaniello?

RACANIELLO: It's clear in this post-9/11, post-anthrax situation that we need to regulate in some way experiments that are perceived as dangerous. You have to always balance the danger imposed by an experiment versus restricting publication. Science works best when information is freely exchanged.

In my view, the science in this case does not support the view that this is a dangerous experiment to release information about. It's not the one to set the precedent going forward.

FLATOW: I recall back in 1974 when genetic engineering was in its infancy, and the tools were being developed, there was the Asilomar Conference. I'm sure - you're shaking your head, you remember.

RACANIELLO: Correct.

FLATOW: And scientists got together to discuss whether this brave new world of genetic engineering would creep out of the laboratory uncontrollably, and they voluntarily stopped their research while they had this discussion. Would something like that be workable in this situation?

RACANIELLO: So I started my work with recombinant DNA just at that time. I remember it well. And many scientists got together and said wait, this may be dangerous, let's talk about it, far more scientists than are on the NSABB, for example, the board that is intervening in the H5N1 studies.

So I think this would be a great idea to talk about science, to get a very wide community of scientists together and talk about what are the dangers, what kinds of experiments do we have to restrict, and which do we have to restrict publication of. I don't think this is the example to set the precedent for that.

FLATOW: No. Dr. Henderson?

HENDERSON: I would be supportive of this with one exception. I don't see this, at this point, being a time to look at the possibility of working with any virus and under any circumstances. I think the smallpox virus situation is what we call an outlier, an extreme situation. In the case of the H5N1, as they say, I think we have a difference of opinion on what the case fatality rate is, but it certainly looks to me from the 20 or so studies been done that it's about 50 percent. It is now been demonstrated to be able to be transmitted from ferret to ferret.

There's a belief that that may have application in humans that it could be transmitted from human to human by aerosol. If we had a release of this mutant virus into the air and it was able to be transmitted, as appears it can be transmitted at least to some degree, we, I think, are taking a real risk. Were it to escape, I don't see anyway by which you can control it. We could control smallpox. If a smallpox escaped from a laboratory, we have the vaccine. We could control it. So it poses less of a threat in terms of transmission and less of a case fatality rate than does H5N1.

But H5N1 is in the outer limits of the spectrum, and the question is: Are we willing to go through experiments to make the virus, a mutant virus available to a number of different laboratories, to risk the possible escape from the laboratory of that virus, or are we going to control it much more severely and hold the data and maybe have the discussion? But keep the discussion focused on an agent which potentially is now, I think, many agree, potentially a catastrophic virus.

RACANIELLO: I think there is no reason to assume that this virus will transmit among humans based on the ferret experiments. Ferrets have been shown to be wrong over and over. The 2009 swine-origin virus, when it first emerged, was put into ferrets. It was highly lethal and deadly. Everyone warned that this would be a bad virus. It turned out to be milder than we think. So I think that that's not a good argument to use if we are really worried about H5N1 spreading. And I think it's been around a long enough time, it's infected enough people to be able to acquire that capability. If we're really worried, we should stockpile antivirals, which are known to inhibit viral replication and perhaps even a vaccine.

FLATOW: I'm Ira Flatow. This is SCIENCE FRIDAY from NPR. Talking - and the debate about whether some research with ferrets and the spread of bird flu among them should be totally released in two journals, Science and Nature. My guests are Dr. D.A. Henderson, Dr. Vincent Racaniello. Our number, 1-800-989-8255. Some questions coming in on Twitter. You can also tweet us @scifri, @-S-C-I-F-R-I. Thebrownword(ph) wants to know how much of this info has already been sort of WikiLeaked, published on the Internet? How much could a scientist guess about what has happened?

RACANIELLO: Well, we know that if you pass the virus in ferrets, you can make a transmissible form, and that's a relatively easy experiment to do. So that's out. And the next step to knowing the sequence is really easily obtained.

FLATOW: So that - you're saying that hiding the details really doesn't matter.

RACANIELLO: That's right. I don't think it's of any effect at all.

FLATOW: Dr. Henderson?

HENDERSON: Well, I think the virus that has been involved here with the transmission experiments, we do not know what the genetic character of it is. We can suppose that we have not some knowledge of it, but we don't know this for sure. I'm sure this will be in the paper. I think there are other factors on this that I would think we would do better, at this time, to say stop and let's talk about it and let's not plunge on. Meanwhile, what I think we ought to be doing is developing a much larger capacity to produce influenza vaccine than we now have, which we need anyway, for - in - with other pandemics, which we know we can expect.

And that we look to advances - the science and the vaccine technology so that we have a vaccine that is more broadly protective and for a longer period of time. And we could put a good deal of money into that and a good deal of scientific work and, I think, have something which would be a value irrespective of whether it is needed for H5N1, it is needed generally for other vaccine strains.

FLATOW: You know, we are in our 21st year of SCIENCE FRIDAY. Every single year, I could take Dr. Henderson, I could take your statement and play it going back 20 years.

(SOUNDBITE OF LAUGHTER)

FLATOW: We need to develop an alternative method of making vaccines, yada yada yada, and we should do something and, you know, something every - it's always 30 years away, like nuclear fusion or something. It's developing a new way to make these vaccines. Dr. Racaniello?

RACANIELLO: Well, it's being worked on. There are very promising alternative vaccines, for example, made in plants.

FLATOW: Right.

RACANIELLO: And within five years, the clinical trials with those will be done, and they can be made very rapidly within weeks of a new virus emerging. So I think it's going to be less than 20 or 30 years.

FLATOW: You agree, Dr. Henderson?

HENDERSON: I do indeed, and I would say, even now, we're producing influenza vaccine and tissue cell culture rather than in eggs. We see ways by which it could be - the antigenicity can be broadened. And I think we can get a much better vaccine. We're already on the way, but we have not addressed this as a serious matter, that is to really move ahead on it. And I can say that with some feeling because it was 2006 that we made a strong pitch to put more money into vaccine production. $200 million was made available to some four different laboratories. That was later raised to $2 billion to speed the process along, plus the product has not been outstanding - could be a lot more done. And I think we need to press on.

FLATOW: All right. We're going to take a break, come back and continue the debate, your discussions. Your questions are welcomed. Our number is 1-800-989-8255. You can tweet us, @scifri, also go to our Facebook page at SCIFRI and our website at sciencefriday.com. Talking with Dr. Vincent Racaniello and Dr. D.A. Henderson. Stay with us. We'll be right back after this break.

(SOUNDBITE OF MUSIC)

FLATOW: I'm Ira Flatow. This is SCIENCE FRIDAY from NPR.

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FLATOW: You're listening to SCIENCE FRIDAY. I'm Ira Flatow. We're talking this hour about two bird flu studies that may not be published in the fall due to security concerns. Talking with Dr. Vincent Racaniello, professor of microbiology and immunology at Columbia University, and Dr. D.A. Henderson, professor of public health and medicine at the University of Pittsburgh. Our number is 1-800-989-8255. Lots of - what was the - let me just get - bring us up to date. What is the status of those studies? Are they being just held up, the details?

RACANIELLO: Well, my understanding is that journals are negotiating with the NSABB to determine exactly how the papers will be phrased.

FLATOW: Let's go to Raul(ph) in Columbia, South Carolina. Hi, Raul.

RAUL: Hi. I had a question regarding the leaking the details of the study. So science says that it wants this information to be open and that perhaps specific details of the study should be distributed within a particular group of approved scientists. But how exactly do you create those (technical difficulty) for – who is an approved scientist? How do you evaluate who's trustworthy? Does someone coming from an academic institution, such as Duke or Harvard, does that just immediately make them eligible to receive information? Is there some sort of test that we have to give to ensure that the people who receive this information are trustworthy? How do you create those guidelines and evaluate who can receive this information?

FLATOW: Dr. Henderson, you want to tackle that?

RAUL: Sorry, what?

HENDERSON: Well, I think that is a real problem, and I think the more that this information is disseminated even to - even a small whatever arbitrarily limited group is there, there's going to be - it's a challenge, and more people are going to be involved in experimenting. And I think there's no question about it. Scientists are curious people, and this is set out as a real challenge. I think what is needed is for the science community to be fully educated as to what the real risk is here.

If the real risk is, as I perceived it and I know a number of my colleagues do, this is a virus that we shouldn't really be experimenting with, even - except under the most rigid circumstances of safety. So one mistake in one laboratory and one escape with the pace that influenza normally spreads, you don't have a chance of stopping it. And we've looked at this again and again. I've been involved with the most recent epidemic, 207 – 2007 back in 1957, we tried to stop or contain outbreaks of influenza, and it was just impossible. It was beyond you before you could really do anything about it.

FLATOW: Dr. Racaniello?

RACANIELLO: I fully appreciate the need for virologists to be educated about biosecurity, and I also would like the biosecurity specialists to be educated about the science underpinning our views on this. And again, the science says that this is not a large threat, the use of ferrets, the natural course of the disease, not being transmissible, the wrong case fatality ratio, all of this is something you need to consider beyond just worrying about someone nefarious getting hold of this information.

FLATOW: So here, you're saying there's a dispute between microbiologists who actually work with the viruses and epidemiologists who study the spreads of diseases. Is there a disconnect you're saying?

RACANIELLO: So I have talked with many influenza virologists about it, and they are, to the number, all in favor of releasing this information. The caution is being raised by epidemiologists and biosecurity experts, which is, of course, their job to do so. So there - yes, there is some kind of disconnect, and they have to get together and talk about this.

FLATOW: Dr. Henderson, do you think you could modify your views a bit if you spoke more with them or are you pretty set in the way you believe?

HENDERSON: Well, I - it sounds to me like maybe Dr. Racaniello is pretty set on the way things he believes in this case. And I think we're looking at it, yes, in different ways, but I think there are a number of virologists who are fully in accord with what I've been talking about. And there a number of virologists who have been very supportive of the restrictions that have been imposed on smallpox. At the same time, I think there is a concern here and the public health concern ultimately, that is our concern, the health of the public.

And what is worrisome is not necessarily that you have somebody with malicious intent, but that you have an experiment done and in which in all good faith proper measures are taken and an escape occurs. This has happened before. It will happen again. And so that at this point in time, I think Doctor Racaniello was right. I think what we do is stop where we are, right now. And we had that dialogue, or we had that discussion about the - among the people concerned as to where we go from here. But meanwhile, I would say, I don't think it would be wise to publish it. And I would say, let's have the discussion as he suggests.

FLATOW: How quickly could - if you've now just decoded the virus, how quickly can you make a vaccine for it in advance of any other research that you might?

RACANIELLO: Well, if you make an egg-based vaccine, it takes you six months minimum to that. If we make a - but the other vaccines which would be quicker to plant, based ones, as I mentioned, they're faster, but they're still experimental. So it's still a long time, and we're always behind the curve when a pandemic emerges. We're always very late in hitting that first outbreak with vaccine.

FLATOW: How long did it take for this vaccine to mutate itself - the virus to mutate between the ferrets, going back and forth?

RACANIELLO: Well, according to what we've read in science, it took 10 ferret-to-ferret passes. So you pass it - you infect the ferret. You harvest what the ferret makes. You infect another ferret. You do that 10 times.

FLATOW: So you manually have to do the infection. And by the 10th time, they were infecting each other?

RACANIELLO: By the 10th time, the virus that you got from that 10th ferret, if you then infected a ferret in one cage, that ferret would infect an uninfected animal in a separate cage.

FLATOW: Mm-hmm. And ferrets have generally been used as models for human?

RACANIELLO: Yes. For influenza, they are very good models because they do a lot of the things that we do when we get flu. They sneeze and cough and get a fever and so forth.

FLATOW: So then, what is wrong with Doctor Henderson's reading here? If they can - if ferrets can pass it easily between them - the two of them, and they're good models for humans, why are they not good models for human-to-human transmission?

RACANIELLO: Well, the key there is the word model. It doesn't tell you everything that you want to know about human infection. As I referred to earlier, there are many occasions where a virus that does X in people, doesn't do the same thing in ferrets. Plus, we have this long experience with human infection with H5N1, and it simply has not transmitted, except it infects people that have contact with sick birds, for example. So I think all of that information argues against that virus being able to transmit in people.

FLATOW: On the other hand, do you think you microbiologists might stop, as Doctor Henderson says he might think about, and have a conversation first about...

RACANIELLO: He - this is a good idea. I think, instead of publishing a watered down version of this paper, just stop. Don't publish anything and have this discussion. That would be fine. I think it's a travesty to publish a paper which doesn't allow anyone else to reproduce the results.

FLATOW: Mm-hmm. And you'd go for that, too, Dr. Henderson?

HENDERSON: Well, I think, yes. I think this makes sense. But I think it's a little more than passage from ferret to ferret. If I understand the studies that were done, there was one set of passages which had became more transmissible. There was another passage which was not successful. One would - might assume that there are differences between the two viruses that emerged. And the differences between the virus that we're looking at with regard to the virus that caused the transmission and the - its beginning parent, these are studies that - and information's needed. I think it's not quite so simple as just passing it from ferret to ferret. And anybody is likely to do it. I think that there are some other problems here. And I think we need to have a hard look. And I think a varied - you got to have some sort of group has to look at it. If you can't make a huge group looking at it and handling it, what you're looking at is a small group making some decisions. But I think the penalty we pay if we make a mistake could be very high, indeed. And maybe we're...

FLATOW: But you - but then, again, you have no concrete suggestion of how to choose that group of people.

HENDERSON: It's going to have to be arbitrarily selected. There's never doubt about it. There's no other way to do it.

FLATOW: Yeah. All right. We're going to have to leave. This is quite interesting. I want to thank both of you for taking time to be with us. Maybe we found some common ground here. And maybe there will be something - somewhere in between where you folks will get together and come up with a solution. DA Henderson is professor of public health and medicine at the University of Pittsburgh, also a distinguished scholar at the Center for Biosecurity at the University of Pittsburgh Medical Center. And Doctor Vincent Racaniello is professor of microbiology and immunology at Columbia University here in New York. Thank you, gentlemen.

RACANIELLO: Thank you.

FLATOW: Thank you for taking time to be with us.

HENDERSON: Thank you.

FLATOW: And have a happy New Year. Transcript provided by NPR, Copyright NPR.

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