The flu season that arrives each fall kills an average of 36,000 people in the United States alone. Far deadlier are worldwide outbreaks, called pandemics, that periodically sweep through human populations.

Over the past 300 years, there have been 10 influenza pandemics, including the so-called Spanish flu of 1918-19, which killed more than 500,000 people in the United States and more than 50 million worldwide.

Now, public health experts worry that an avian flu strain - called H5N1 - racing through animal populations in Southeast Asia could touch off the next pandemic. Since December 2003, the virus has killed 55 people and led to the slaughter of millions of infected chickens and other birds. Human cases have been reported in Thailand, Vietnam, Cambodia and, now, Indonesia, with reports last month of the first human infection there.

So far, the virus has shown an ability to jump from animals to humans. But it has limited ability to pass from person to person, with all but a few of the fatalities stemming from contact with poultry. Scientists, however, say a simple genetic change in the virus' outer coat could throw the necessary "switch" that would make it easily transmissible between people - triggering the pandemic that some fear.

Dr. Michael Osterholm, director of the University of Minnesota's Center for Infectious Disease Research and Policy and author of a recent article on "bird flu" in the New England Journal of Medicine, warns that avian flu is a gathering storm for which the world is unprepared. He says nations lack not only vaccines or anti-viral drugs, but also basic medical equipment such as masks, ventilators and hospital beds.

Last week in Baltimore, in an address to the Association for Professionals in Infection Control and Epidemiology, he spoke of his concerns. Afterward, he sat down with a reporter to share information that could lead to greater public understanding of the avian influenza virus and the possibility it will cause a pandemic.

Anyone over the age of 30 has lived through AIDS, SARS, ebola and the fear and reality of bioterrorism. Are you worried that there is a certain disease burnout that's going to numb people to the possibility you're warning about?

We today have unfortunately a very skewed view of what kills us versus what hurts us versus what worries us. Marburg virus in Angola makes for wonderful evening news and footage that really grips us. If a kid on a college campus dies of meningitis, we're all over that. I see how many times the media exploits situations where a child is suddenly missing. We're locked into that child, and she becomes the poster child. Now, I can't imagine any parent going through that, but why does the media pick one over the other? It's part of our inability to deal with too much information.

I fear desperately that one day this [pandemic] is going to happen and we're going to have a post-pandemic commission that's going to be like the post-9/11 commission. We'll go back and detail all the misses we had over the years to deal with that. That will be OK, but what a tragedy to have to get to that point. Why couldn't we do that now, when we see this thing coming?

Flu epidemics occur every year and a pandemic on average every 30 years, but pandemics really occur at odd intervals - 1918-1919, 1957-1958, 1968-1969. Are these random events or is there a particular logic to thinking that we're due for one, that the cycle is running its course?

It's a mix between random and potentially predictable. It's almost like hurricanes. You can't predict them from year to year, decade to decade, but if you average them over a long enough time, you're gong to see one.

You pointed out that the 1918 pandemic and potentially this one prey on people in the prime of life, between 20 and 40 years of age. Could you explain why?

First of all, it strikes everybody. But what you're asking is why does it do its severe damage in that age group. It uses your own immune system against you. People who are 20 to 40 years of age have on the whole the strongest immune systems. You spend the first 20 years of your life building it up. By the time you get to be 40, it starts to wane a little.

So what's happening here is a classic immunologic storm - what it does is turn on this inappropriate immune response. Basically, it's a cytokine storm. [Cytokines are proteins that recognize a foreign body, such as a virus, and alert the immune system to attack]. All these cytokines get produced and [that] calls in every immune cell possible to attack yourself. It's how people die so quickly. In 24 to 36 hours, their lungs just become bloody rags.

So the virus basically triggers an autoimmune response?

Exactly. With autoimmune disorders you tend to think about more of a long-term kind of thing. This is more acute, but it's in the same context. It particularly attacks the lungs and kidneys and liver, but the lungs are really where it goes. Again, you can't breathe if your lungs are blood-filled.

There's been just one confirmed report of human-to-human transmission. A girl in Thailand apparently caught the virus from chickens, and then passed it to her mother and aunt. But that's as far as it went. What would it take for H5N1 to spread more efficiently and suddenly trigger a pandemic?

I think it's coming down to almost a light-switch kind of issue. If we have a change in one or possibly two amino acids [on the surface of the flu virus], that's the difference between having a room key that fits in the lock but doesn't open the door and one that fits efficiently and opens efficiently. Now, you have that ability to infect humans at will.

Is that change a random mutation?

We're providing that virus every opportunity. I mean every day, every second, is an evolutionary experiment going on in Asia. You know, it's like a computer hacker that has a program that will figure out what a nine-digit security code is. If they have enough time and there's nothing to stop them, they can just run the program until all nine numbers work.

And the experiment is what?

It's everyday life. It's the virus being transmitted among billions of birds and other animals, and those animals exist because we need them for food today because the population has [risen] so much.

The virus really worries me because it really does act and feel like a 1918-like virus. And if you take the 1918 numbers and overlay them onto the modern world, you're talking about 180 to 360 million people [dying]. You say it will never happen because we live in a world of modern medical science.

But aren't we better able today than we were in 1918 to provide people supportive care such as intravenous fluids to keep people from dying?

Can you tell me how you come to that conclusion?

Well, I know that when my son gets sick and dehydrated, I can take him to the emergency room, and they'll hook him up to an IV, and he gets better.

That's right, but that makes two assumptions.

One is that IV fluids will make a difference. I have to tell you, I just came back from Southeast Asia, and you would be amazed at the level of ... care that exists there. Many of those patients get as good care as you are going to get at most medical centers in this country. But they still crash and burn - the point being, the cytokine storm even under the best of conditions is extremely difficult. I don't care if you're in the intensive care unit at Johns Hopkins or the Mayo Clinic or in Hanoi. It's a very difficult clinical condition to manage.

Second of all is the fact that those supplies you talked about for your son exist because your son is one of a limited number of people on a given day who need it. But we don't have a system of production or delivery today that would accommodate a burst in need. We're going to run out of many of those things overnight.

Age: 52

Education: B.A., Luther College, Decorah, Iowa; master's degree in environmental science and public health, University of Minnesota; Ph.D. in environmental science, University of Minnesota.

Current position: Professor and director, Center for Infectious Disease Research and Epidemiology, University of Minnesota; associate director for Department of Homeland Security's National Center for Food Protection and Defense. Also serves on Institute of Medicine's Committee on Infectious Disease. Frequent consultant to World Health Organization and various federal agencies.

Past positions: State epidemiologist and chief of the acute epidemiology section, Minnesota Department of Health, 1984-1999. Served as special adviser to HHS Secretary Tommy G. Thompson on bioterrorism and public health preparedness.

Expertise: Emerging infectious diseases, food safety, bioterrorism.

Influenza viruses are carried by birds and people, but there are differences in the makeup of the viruses that typically infect each species.

Both are among Type A flu viruses, but differ by subtype. The many subtypes are distinguished by certain proteins on the surface: hemagglutinin (HA) and neuraminidase (NA). There are 16 different HA subtypes and 9 different NA subtypes of flu A viruses. Many different combinations of HA and NA proteins are possible. Each combination is a different subtype.

All subtypes of flu A viruses can be found in birds. So-called "bird flu" viruses generally are those flu A subtypes that continue to occur mainly in birds and not in humans.

So-called "human flu viruses" are those subtypes that occur widely in people. There are only three known subtypes of human flu viruses (H1N1, H1N2, and H3N2); it is likely that some genetic parts came from birds originally. Flu A viruses are constantly changing.

The H5N1 virus is a flu A subtype that occurs mainly in birds. It was first isolated from terns in South Africa in 1961. Like all bird flu viruses, H5N1 virus circulates worldwide, is very contagious among birds, and can be deadly. In 1997, the first case of its spread from a bird to a human was seen during an outbreak of bird flu in poultry in Hong Kong. H5N1 is the virus that is currently causing human deaths in Asia.

Source: Centers for DIsease Control