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DR. ROBERT WEBSTER
Dr. Robert Webster
Director, U.S. Collaborating Center (WHO)
Rose Marie Thomas Chair
Department of Infectious Diseases, St. Jude Children’s Research Hospital
Memphis, Tennessee
Dr. Robert Webster is a world-renowned virologist, an expert in the structure and function of influenza virus proteins and the development of new vaccines and antivirals. He has spent more than 50 years studying influenza, and was the first to isolate and identify the strain of avian influenza that killed thousands of chickens in Hong Kong in 1997 (when it moved into humans, the virus killed a third of the people it infected).
Dr. Webster has traced the history of pandemics back through time, analyzing the descriptions of illness in the ancient medical records held at the Royal Society in the United Kingdom.
Dr. Webster’s laboratory contains more than 12,000 samples of avian influenza – a collection like no other in the world. There, he tracks new and emerging flu viruses and guides the development of vaccines to stop them.
He calls H5N1 the “scariest thing†he’s ever seen, and is currently working to pinpoint the threat of influenza transfer among migratory birds – something he thinks would be a primary source of the influenza’s spread.
The following is an edited excerpt from and interview with Dr. Robert Webster, conducted in late 2005...
Why should we be worried about influenza?
Many people in the world think it’s a big deal. Influenza is like taxes – it comes around every year whether we want it or not. And it is necessary to have vaccines for it. The truth of the matter is that influenza is much more serious than we realize.
The cost of influenza to the community runs into billions of dollars and occasionally, once or twice a century, we can have a pandemic that appears. And it’s the pandemics that we really worry about.
Tell me more about the pandemic of 1918.
The pandemic of 1918 is the worst pandemic in recent history. 1918 appeared at the end of WWI. In fact, it was the virus that finished WWI. Unwittingly, the Americans used biological warfare to finish WWI. They took the highly pathogenic, so-called “Spanish flu†with them to France. The virus blew across to the Germans. (It was called Spanish flu because neither the Allies nor the Germans wanted to acknowledge this virus was there, so they blamed it on the Spanish.)
This virus decimated the troops on the both sides and eventually the soldiers at the end of WWI brought the virus to the rest of the world: to the United States, Canada, New Zealand, everywhere in the world it was spread and it was absolutely devastating in its pathogenicity.
The 1918 flu was so pathogenic that people really didn’t believe that it was classical influenza. We can think about the very serious viral diseases that we know about. Ebola is one that everyone knows about. 1918, I can best describe it as ‘respiratory transmitted Ebola.’ The virus had the capacity to infect young soldiers in the morning, who died in the afternoon. They turned from white to black because there was no oxygenation of their blood.
This was a terribly disastrous virus. The total genome sequence of the 1918 virus has been established by Jeffrey Taubenberger, based on samples obtained from Alaska. In the beginning of October 1918, Alaska was under total quarantine. A mail ship arrived in Nome and there was no apparent influenza aboard on this ship. So they off-loaded the mail gave it to the dog sled.
The postman who carried the mail got very sick and it was apparent now that he had 1918 influenza. Unfortunately his dog team dragged him home to Brevig Mission. And the following week, 72 or 80 people of Brevig Mission died. That’s how severe this virus was.
How many people were killed worldwide by the 1918 pandemic?
The overall global death rate for 1918 was probably much closer to 100 million than 20 million. We really don’t know. The truth of the matter is we have no idea. If we go back to New Zealand, where I come from, whole villages simply disappeared. These figures never entered the tallies. So probably 100 million is a low figure.
How likely do you think it is that something like the influenza virus could mutate into something like 1918 ever again?
Whether or not we could have another 1918-like outbreak? The answer is absolutely yes. The H5N1 virus that’s currently causing problems in Asia could easily mutate to produce a 1918-like pandemic. 1918 caused something like 2.5 per cent mortality globally. Lets look at what the H5N1 is doing in Asia at the moment. More than 50 per cent of people being affected are dying. Imagine what would happen if that was transferred to a global situation.
The only thing that this virus hasn’t learned yet is how to transmit between humans. If that happens, we are in great trouble in the world. 1918 would seem like a duck walk. This would be much, much more severe.
There are meteorites that have a 1 in 80,000 chance of hitting the Earth – where does this fit on that scale?
One of the questions that I’m frequently asked is how likely is this to happen. I spent my whole life working with influenza and I have never seen such a pathogenic virus.
Here in Memphis we sit on the Madrid fault, an earthquake fault line. The last major earthquake in Memphis made the Mississippi River flow backwards for a week and created a huge lake. When we plan for influenza we have to think about the planning for rare events like earthquakes.
The hospital at St. Jude’s Children's Research Hospital is built to stand a class 10 earthquake. And so we should be globally thinking about what would happen if this virus spreads. In other words, we need to think about the possibility that this virus will really happen.
Shouldn’t we plan the design of a hospital to withstand a force 10 earthquake? Of course we should. And of course we should prepare for this virus. We have to realize that influenza has been in the world forever, almost. It goes back to the time of the ancient Greeks.
This virus has always occurred. And it’s inevitable that there will be a pandemic. The most likely one at the moment is H5N1 and I tell you, you should prepare for it. It is probably the biggest threat to mankind at the moment.
How good of a job have we been doing with preparations so far?
Are we prepared for this event? Hell no! We are not prepared. We’ve given a bit of lip service to having a pandemic plan. We have plans that sit on shelves and we are implementing the plan. This is the key issue at the moment. How much implementation of this plan have we done?
I think Canada is probably better prepared than most countries in the world. They have shown great wisdom in vaccine plans for influenza and antiviral planning. The rest of the world is way behind Canada. And so there are many things that can be done.
People are inclined to say ‘Webster, you are always calling wolf.’ But this time I really have to take the gloves off. It’s going to happen guys. But I hope I’m wrong.
What specific things should the world be doing right now?
We should be preparing vaccines that are suitable for H5N1. There is disagreements in the scientific community as to which will be the virus that transmits human to human. I would argue that any H5N1 vaccine is better than no H5N1 vaccine.
None of the people in the world have immunity to H5. We are totally susceptible. So if we make the vaccine against the current strain that we know about and stockpile it, we could use that as an interim vaccine until we make the perfect one. We know that it takes six months from the moment we decide that this virus that is going human to human.
But let me explain the difference between a vaccine that’s not a good match and one that is a perfect match. The vaccine that is currently available, and there is a vaccine that’s currently available for H5N1, this vaccine could protect you from death. If you’re vaccinated it would likely protect you from death. You may get sick. You may get deadly sick. But it will likely protect you from death. Such a vaccine is what I argue the world should be stockpiling.
Where are we at right now in terms of vaccine production capabilities?
A vaccine has been produced; the new technology of reverse genetics permitted the preparation of this vaccine in about two weeks. And this vaccine has been growing and is in clinical trials in United States.
I have not heard the results of the vaccine – but on the other hand I have not heard any complaints about the vaccine. So the vaccine trial is clearly going on and we will get the answer within months of whether that vaccine is efficacious.
If you got a notice tomorrow that there was human-to-human transmission in several sites across Asia, can you describe how that six-month process would work?
My suggestion would be to immediately crank the handle for every vaccine company in the world to start making the currently available vaccine that’s been tested in humans in maximum amounts.
We know that there are not enough vaccine companies in the world to achieve this. But at least we should do our best to make the current vaccine – and at the same time develop the perfect match vaccine through the laboratories. Until the perfect one is ready, produce the vaccine that is currently available.
What can I do personally to protect myself right now?
The supplies that you would put in your house for an earthquake should be put into people’s houses for the event of this H5N1. Because if it is catastrophic or super catastrophic, all of the services as we know them are likely to collapse. Each household will be dependent on its self for water for food and so on.
I might be painting a black picture but I think we have to think in those terms.
H5N1 is not considered a pandemic virus at this time. There have been no human cases of H5N1 reported in Canada as of January 11, 2006.
What might be the progress of a pandemic H5N1 virus – how might spread around the world?
If we know where the index cases are occurring say in Vietnam, the World Health Organization has a contingency to use antivirals to slow the spread of the virus. And so that is a useful strategy to think about. If we are unlucky and we don’t know where this virus occurs – there are many areas in there where this could occur and we would not know. And so this virus could break out in an area where we don’t have good surveillance.
We have to look back at what happened with SARS and the initial cases with SARS and the spread from China to Hong Kong and from Hong Kong to Canada to many areas including Singapore, Vietnam and elsewhere. And that happened very rapidly with international transport on airplanes.
One of the things that one would think about would be stopping air travel. But if the virus is already transmitted, what is the point? But people will think about stopping international travel by air.
When this virus does transmit to Western countries and to the rest of the world, I think we have to look back at what happened in 1918. It would be a similar pattern to what happened in United States, Canada, New Zealand. The chances are we are not going to have enough facilities to bury the dead. That’s what we’re faced with.
Initially, this virus is going to go through a burst of causing enormously high pathogenesis – let’s hope it’s not 50 per cent lethal. Even down to 1918 levels, we know what 2 per cent mortality did in 1918. Humanity isn’t prepared for such an event. It’s almost as if we can’t be prepared for such an even.
People are going to survive of course. There is no doubt that society will survive. But it’s likely to be a catastrophic event. And then the finger pointing will begin. We saw this happen with SARS. In Hong Kong, the finger pointing of why we weren’t better prepared.
It’s human nature to have such an investigation. And so we should do what we can. The science is in place right now to make vaccines, to make antivirals and stockpile all these antivirals to limit the catastrophe. So lets do it, it’s the best we could do.
You argue we could stop a pandemic at its source – what do you mean by that?
I wrote an article in ‘Nature’ about that, about ducks in particular. I still think that it’s possible to stop this virus before it learns to go human-to-human. If we look at what’s being done in Asia, what countries were successful, Thailand is one of those countries. In 2004, there were deaths going on in humans in Thailand. Are there deaths now? No. There are no more deaths in Thailand.
Thailand has understood the problem, and the problem is the domestic duck. This virus, the H5N1 virus came from the wild. From the migrating bird, it got into domestic ducks, then into chickens, and learned to be a killer.
In the past year, this virus has changed and evolved again in the duck so that it is no longer killing the duck - yet the duck is carrying this virus that is lethal for chickens and humans. The duck is the Trojan horse of influenza in Asia. The duck is the Trojan horse for H5N1. The duck looks perfectly healthy. It’s pooping out lethal virus in the poultry markets in Vietnam and it’s transmitted back to the wild migrating birds.
This is the real danger. It’s not the dead chickens. We know when the chickens are dead. There is a problem when ducks look perfectly healthy and are pooping out virus at levels that will transmit to humans and chickens. That’s the danger.
We have to do what the Thais have done, to understand that in every village where we have free reign ducks in Asia, that they are a risk. And we have to go and do surveillance. In Thailand, they sent 70,000 people to the villages. Every village was tested. We can do the same thing in Vietnam. Put in the infrastructure for the rest of the world and maybe we can still stop this thing.
If the virus is now in multiple countries, Indonesia – South Russia, China – does it really matter what Thailand or Vietnam does?
It’s still not too late. China has been controlling this virus at least in part by using vaccine in poultry. Indonesia has been doing the same by using vaccine in poultry. And so the whole region can use poultry vaccines, better quality vaccines to control this virus at the domestic poultry level.
To get back to humans the virus has got to go through the domestic duck, back to the chicken, or the pig, to humans. We are still in a position to stop that. The first step is bio-security: keeping those wild birds out of the chicken houses and simple washing of the hands can prevent the transmission of most viruses to humans. And it’s still possible to do that.
How do you personally feel about the pandemic?
H5N1, I think, is the most dangerous, the most highly lethal virus that I have ever encountered. When you inoculate a chicken in the afternoon, and the next day, the chicken is dead – the virus has gone through this business of attachment, penetration, replication, and kills overnight – that’s an extremely lethal virus.
This is the hottest one I’ve ever seen. It terrifies me that the virus, if it ever learns to transmit from human-to-human, we are in terrible trouble. I know what this virus does in the chicken and in the ferret, and in the animal models, so don’t blame me if I am concerned about what is going to happen to you and me if it learns to transmit. I think we need to put every possible resource in place, to put our defenses in order, to do what we can to ahead of time, before this virus does learn to transmit in humans.
If you speak to the influenza community in the rest of the world, they may not be as scared as me, but there is general agreement that this is a virus that we have to take extremely seriously. There is not one scientist, influenza virologist, in the world who would dismiss this as something that we don’t need to be concerned about.