The Sky May Not Be Falling: An Eminent Scientist's Cautious View on Bird Flu Anxiety

Edwin Dennis Kilbourne has spent his professional lifetime in the study of infectious diseases, with particular reference to virus infections. His early studies of coxsackieviruses and herpes simplex preceded intensive study of influenza in all of its manifestations. His primary contributions have been to the understanding of influenza virus structure and genetics and the practical application of these studies to the development of influenza vaccines and to the understanding of the molecular epidemiology and pathogenesis of influenza. His studies of influenza virus genetics resulted in the first genetically engineered vaccine of any kind for the prevention of human disease.

He has held a variety of academic positions, including founding chair of the Department of Microbiology at Mount Sinai School of Medicine, at which he was awarded the rank of Distinguished Service Professor. His most recent academic position was as Emeritus Professor at New York Medical College.

As an avocation, Kilbourne has published light verse and essays and articles for the general public on various aspects of biological science, collected and published most recently in a book, Strategies of Sex.

Multinational Monitor: Is it inevitable or virtually inevitable that H5N1 avian flu virus will become transmissible among humans?

Dr. Kilbourne: No. I don't know where people get these crystal balls from.

Certainly every pandemic has been different, slightly different at least.

The more it circulates in birds, the better adapted it becomes to birds and probably the less potential it has to adapt to man. As it better adapts to birds, it more or less becomes fixed in its genetic state.

MM: So the longer the virus goes on not being transmissible among humans, the less likely it is to become so?

Kilbourne: It is a double-edged sword. There is a greater chance for genetic re-assortment with a human strain the longer we get occasional cases in humans. But the other part of it is that the thing becomes so intensely adapted to the avian system that it is difficult for it to make the transition, to become a virus transmissible among humans.

MM: Is there any way to estimate a probability of this?

Kilbourne: No, there's not. And I've seen these papers about 50 percent mortality and a 50 percent chance that it is going to happen, and I just don't know where some of my friends get these figures. This is not based on a lot of people having a lot of knowledge about avian influenza and pandemics.

MM: If it becomes transmissible, would it likely spread quickly?

Kilbourne: Once it becomes transmissible for several generations in man, then the greater is the risk that it will become pandemic, yes.

I am not saying that I'm not concerned about this avian epizootic. I'm just saying I don't know any way to assess the likelihood except on the basis of what I've just said.

There is another factor which is rarely mentioned these days, which is that the human population has antibodies against the N1 component of at least human H1N1 viruses. I see the possibility that there may be a kind of immune barrier that will damp any possibility of H5N1 [the current virus in birds] really zooming into humans.

I'm no longer running a laboratory so I can't do it myself, but I think the question that needs to be answered very badly is of the relationship of the N1 in H5N1 and the N1 in the H1N1 virus which has infected humans for years. Now, the basis of designating something as N1 is an antigenic relationship, so almost by definition it implies that there are going to be some antibodies in humans to that component, even though it is a minor component of the H5N1 virus.

MM: In the cases where the H5N1 virus has taken hold in humans, it has had a very high reported mortality rate. You have suggested that if it were to become transmissible that might change?

Kilbourne: There is another issue before we accept the fact that it has a high mortality rate. I don't think we have any idea what that mortality rate is because we don't have any idea of the denominator - how many people have been infected.

We know that influenza can cause asymptomatic infection - that is an infection without disease - in maybe as high as 20 to 30 percent of people.

A survey done in rural, southern China in 1992 allows one to project the possibility that millions of Chinese have antibodies to the H5 component of the virus. That study is regularly ignored too.

So when we start talking about percentages, we don't have a denominator - we don't know how many people have been asymptomatically infected, or infected with mild symptoms.

Let me just say that a virus of any kind that has a mortality rate of 50 percent is killing itself, because it will have nowhere to go if it wipes out all the hosts. So it is not in the virus's interest to kill many people.

MM: So for these reasons and perhaps others, a 50 percent mortality rate or anything like that is very unlikely if it were to become transmissible?

Kilbourne: Certainly.

MM: Apart from this existing avian flu virus, there are a lot of predictions along the lines of: If it's not this one, there is going to be a pandemic in the future.

Kilbourne: We don't know that. Why do people say that?

If you look back over the history of pandemics, they come at irregular intervals.

The environmental conditions on the globe are changing with warming trends.

I think one of the after-effects of this avian influenza will be more attention paid to animal husbandry and more care taken as to how these flocks are treated and handled and sequestered. So I'm not sure there will be another pandemic.

MM: Was the 1918 pandemic a unique event in history, something we should not worry about happening again?

Kilbourne: Each pandemic is unique. No pandemic has been the same as others.

It's not just the virus, which is probably very similar to the swine virus that we have now. It is the environment at the time, the ecosystem. In 1918, it was wartime; boys that came in from the countryside were crowded into the army camps, and crowding facilitates the spread of virus. None of what I'm saying is negating the present efforts to plan and prepare. But I'm talking about what I consider to be likelihood or not.

Let me say a bit more about 1918. Many of the deaths of 1918 were caused by secondary bacterial infection. We now have antibiotics that were not available at that time, so at least to some extent, there could be mitigation that way.

We also now have the capability to quickly capture an influenza virus and make it into a vaccine; we didn't have that in 1918.

So in that sense, I think the likelihood is probably less.

In 1976, I wrote an op-ed piece published in the New York Times predicting the possibility of a pandemic because we were then apparently on an every-decade cycle of 1947, 1957 and 1968, and we were approaching the end of the seventies. I did admit in the op-ed piece that this was a short series of observations, and this was the first time in history that there seemed to be a chance to stop an incipient pandemic. Never to our knowledge had a major new antigenic variant appeared without a subsequent pandemic.

I don't make predictions after that experience because the swine flu never extended beyond Fort Dix, New Jersey. That was a much more severe threat, in my view, than the present avian flu, because it went seven or eight generations of transmission among soldiers right from the beginning. And then there was the double threat of it being similar to what we know about the 1918 virus on the basis of antibody studies of older people. So now I am very reluctant to make predictions.

MM: What does it mean when you talk about a generation of transmission?

Kilbourne: We're talking about serial transmission. In other words, man to man, that virus spreading to the next series of people and so on.

MM: In 1918, lots of people were coming from rural areas and living in high-density areas. Aren't there similar conditions now in the very densely populated slums in the Third World? Does that suggest a greater likelihood of a pandemic erupting?

Kilbourne: I would have concerns about that, sure - once it gets started.

MM: But again, there remains the issue of the initial trigger.

Kilbourne: Yes.

MM: What are the kinds of things that the United States ought to be doing to prepare for the possibility of a new, serious influenza outbreak?

Kilbourne: Well, you know, they've been discussed endlessly.

I'll tell you some things I don't believe will be useful. Quarantine will not be useful because of the fact that we have the silent cases that will not be recognized. So, who are you going to quarantine?

I think that face masks will not be useful, because most of the ordinary gauze masks can be traversed by an aerosol virus with a cough and sneeze. And, as the mask becomes moist and wet, it becomes less useful. Besides, I don't think people in the United States will wear them. If they do, it will be in limited numbers. I know the compliance rate in Japan is pretty high.

We also hear all sorts of things about hand washing. Hand washing may prevent the common cold because the virus there is very stable and lingers on the hands. It won't prevent influenza, because the virus is very unstable and is not transmitted by hand-to-hand contact.

These are what the public health people love to talk about because they are things they can do.

The only answer is an effective vaccine in large supply. That is the only chance of making an impact on influenza pandemics.

I'm sorry if that sounds dogmatic, but this comes from over 50 years of working with the virus and seeing a lot of things come and go.

MM: Are you able to talk about the national or global capacity to develop a vaccine quickly?

Kilbourne: I can tell you a limited amount, because only a limited amount is known. The majors producers of course are in the West, with the exception of Japan and very little going on in Asia.

The manufacturers here are having difficulty just producing ordinary flu vaccine. It is not an easy product to produce.

There are hopes of getting away from the chick embryo [as an incubator for the vaccine, a time-consuming process]. But it is going to take at least five years and possibly 10 before the tissue culture systems are sufficiently worked out to produce large quantities of virus. So I think that with all of the advances in molecular biology and genetic manipulation, we're not going to see the fruits of those very soon.

The other problem is that it is very hard to sustain interest in influenza because its pandemics are irregular in occurrence. We haven't had one now since 1968. It's alright to go around and get the public all annoyed and worried - you've got to - but you can't cry wolf too often. That's part of the problem.

I think that the efforts that are being made by Health and Human Services Secretary Leavitt, in terms of getting preparedness at the local level, are good ones. But again, I think the efficiency of those will slack off just like terrorism preparation has in the absence of a continuing threat.

The focus should really be on the only things that we can do to influence the pandemic: better surveillance - and our surveillance is now pretty good, but it could be expanded in the Southern hemisphere particularly; and get that vaccine.