There has been a relationship between the human species and even the animal species and the microbial world, and it's a fascinating interaction.

There's a lot of mutual dependency.

I mean, if you look at the recent delving into the human microbiome in which there's Maur d N.

A.

From microbes in your body in your gut and your genital track and your skin in your mucosal surfaces, nose and mouth, then they're all your normal cells.

DNA it.

It's sort of a kn interesting, jolting feeling, but you live together with the microbes every once in a while.

Those microbes could attack you there called pathogens.

You have pretty good defenses against many of them.

But every once in a while, a path of general breakthrough the defense, particularly if it's a new pathogen from the outside that you've never been exposed to, like an influenza that you've never been exposed to, or some other type of respiratory virus or even certain bacteria.

So it's it's an extraordinary world.

It's kind of the microbes in our environment will never, ever, completely destroy the human species normal, the human species ever or even want to get rid of all of the microbes.

So it's kind of a stand off, some mutual benefit and occasional incursion on your health that you tend to fight back with things that are natural, like your immune system, or that you make like antibiotics or anti virals.

It's a fascinating world.

No, I don't I don't I mean, as an infectious disease person in a public health person I'm constantly aware of and have to respond to outbreaks.

I mean, we know I look at it, the infectious disease world as the established infections, which means you can generally predict from year to year what the morbidity and mortality will be.

So if you look globally and you look a respiratory infections and diarrheal diseases, which are the big killers from an infectious disease standpoint, particularly of young Children and older people, people who have infirmities who have underlying diseases, then you have things like malaria and tuberculosis and hepatitis and things where at any given year you kind of know there'll be two million deaths due to respiratory diseases and one and 1/2 to 2 million deaths due to diarrheal diseases.

Those air the established infections with ones that are equally, if not more challenging, off the emerging infections where all of a sudden you get a new infection that you've never seen before.

In 1918 we had the pandemic flu that killed 1,005,200 people.

In 1981 we first recognized H I V, which has now had over 75 million infections and 38 million deaths.

50 years ago, there was no HIV to our knowledge, and it wasn't a public health threat.

Then, every once in a while you get a public health threat that's a blip and then goes away spontaneously, like SARS.

The severe acute respiratory syndrome years ago came and went before we had a chance to do a vaccine.

Before we had a chance to develop anti virals.

Some infections reappear in a different geographic location.

We've gone for centuries with West Nile virus in Africa and in the Middle East.

Then all of a sudden, West Nile comes to the United States, probably because of the ability to fly people, birds and mosquitoes from one continent to another over the Atlantic Ocean because we know that the West Nile very likely came from Israel.

If you look up the genetic typing of it yet it landed in Long Island, so those are convene threatening to some people and in some respects it is a threat.

But in some situations that could be very exciting because it gives you a really feel of this microbial world.

And as physicians and scientists, we tend to try and protect ourselves from the incursions of the microbial world without necessarily feeling we have to eliminate the microbial world because that will never happen.

And that would probably be detrimental to us as opposed to being healthy.

For us, it's it's it's I think it's the extend than the degree of impact that you can have when you're serving the public.

The public is a pretty big constituency, so if you're really a public servant and a public servant interested in global health, I kind of think of my constituency as the 6 to 7 billion people in the world that could be vulnerable to some of the infections that I study and that I hopefully help to make countermeasures for do you work?

But there's another very important part of what I do, and that's cool programmatic initiatives when you need to move the field when it isn't yet moving in a direction that you know it needs to move.

Let me give you a classic example of that in the summer of 1981 when I recognized that HIV AIDS and it wasn't even HIV yet because we didn't discover HIV until 1983 84 that I knew intuitively that this was going to be a major global health problem and I even wrote about it back then in 1981 82.

So in the early eighties, I became director in 1984.

In the early eighties, I had a push the field in the sense of saying, We're gonna put this amount of money aside and I want people to start working on this new disease.

So you give me a good idea and I'll fund it.

I didn't wait back and say, Okay, I'll wait till somebody comes in with a new die.

Say, Wait a minute.

We have to work on this disease.

It's a very, very important problem.

I did the same thing with the Ebola outbreak.

Well, as soon as we started seeing the outbreak of cases, I said, We have to rush the research to get a vaccine.

When we started to see drug resistant tuberculosis and drug resistant malaria, I said, We've got to start getting younger people, people with new ideas, people with different ideas to get into the field.

So it's a really balance of waiting for the ideas to come in and kind of stimulating the field to come in with these new ideas.

For me, it's infectious disease, microbial diseases, an auto immune diseases.

An immunological disease is.

However, the one profound difference between all the other institutes and my institute is that any given day, I could wake up and all of a sudden there's emergency that I have to respond to tomorrow.

So I tell my my my colleagues and I used to joke around with Dr Collins when he was the director of the genome.

It's the two days to say Francis, you go to bed at night.

There's no chance in the world that you will wake up to a genomic emergency the next day I go to bed at night, and I look at The Washington Post in The New York Times and I say, Oh my God, we have an outbreak of such and such in wherever and immediately you've got to turn on a dime and respond to it.

So it adds a little extra bit of challenge, excitement and tension that infectious diseases just pop up.

You know, they called emerging infectious diseases.

Although genetic makeup impacts to a greater or lesser degree virtually every disease, it's much less so in the situation of an infection coming in and infecting you.

What the genes might do with determine how well you'll respond to a particular infection, for example, and this is ah, it's an unusual example, but it's an example.

1% of the Caucasian population has a genetic defect of the cells that combined to HIV, the receptor for the AIDS virus, the Cory cept There's two receptors for the AIDS virus and their quote co receptors.

There's 1% of the Caucasian population that has a defect in one of that receptor, which means they cannot get infected with most strains of HIV.

There are some strange that could still affect them.

But most strains of HIV, no matter what they do, they won't get infected well.

But that's an unusual situation.

Most of us would you have a virulent infection.

Doesn't matter what your genetic makeup is.

You're going to get exposed, and you likely will get infected so the genetic makeup impacts to a greater or lesser degree.

So an example.

If you have a certain gene for breast or ovarian cancer, the chances of your getting in a very, very, very high.

Where is if you look a TTE?

Other diseases.

It's a what we call multi genic phenomenon, so you may have a genetic predisposition to diabetes.

But if you exercise, do not gain a lot of weight and you're not obese.

You eat well.

You don't eat, have a lot of show that you can likely avoid getting diabetes.

But if you have the propensity to diabetes and you just don't care for your diet, you don't exercise you overweight.

You have a much greater chance with infectious diseases that ability to control, except for exposure.

I mean, obviously, if you decide you're gonna go and drink dirty water, you're gonna get a diarrheal disease, but just in the environment, it's much more of something you don't have control over.

You know, the broad umbrella of control is leading a healthy life.

You get good sleep, eat well.

Exercise your immune system is in pretty good shape.

That doesn't mean you'll never get infected, but it means you have less of a chance of getting seriously ill if you get infected.

If you're really a very fundamentally healthy person, that's the reason why if you look at something like influenza, if you look at the mortality of influenza, it's heavily weighted towards elderly people and people who have underlying diseases.

Because their constitution is not able to mount the proper immune response to clear the virus.

Where is a young, strapping, healthy person?

They may get infected with influenza or another microbe, but their body is strong enough to be able to fight it very well.

That's the reason why there's less of a chance that a very healthy person will have one of the serious complications of these infections.

The immune system evolved evolutionarily in response toe early creatures and ultimately later creatures like mankind to respond to and defend themselves against the microbial world.

That's a pathogen.

So the immune system is a direct response of evolution to microbes.

So the reason the Infectious Disease Institute is also that the Institute for Immunology and Allergy is that that immune system, as it has evolved over the millions of years of evolution, is at the one hand, the Defense Department of the body.

But on the other hand, since it's so finely tuned, it can occasionally go awry and by going awry.

It's a finely regulated system, and when it gets dis regulated, it can attack the body itself.

And you get auto immunity, such as rheumatoid arthritis, Lupus and other diseases.

And it can also inappropriately respond two things like environmental anti Jin's like pollen and grass and weeds and tree pollen and things like that.

So people who have allergies, their immune system is inappropriately responding to an environmental factor that if a person didn't have the allergy, it wouldn't bother them at all.

For me personally, science is never every day, the eureka moment.

That's nonsense.

That never happens.

Science is a incremental increase of knowledge that a pasion aly eventuate ce into a eureka moment.

But most of the the science is slugging it out, getting incremental increases until you say, Ah, now we know where we are With that it was the same way with take HIV.

I mean, it's a very good example.

So HIV we find out there's AIDS.

In 1981 the virus is discovered in 1983 1984.

As soon as we discovered the virus, we started trying to both screen drugs to see if they could suppress virus and target the development of drugs against certain vulnerable points in the viruses replication cycle.

And it went.

The first drug in 1986 was a Z T.

It was approved in 1987.

It took three of four years for the second drug and then the third drug and then the fourth drug.

And then we realized that a single drug alone was not good enough.

Sooner related, the virus became resistant, so he had put two drugs together.

And then we found that we had to put three drugs together.

And then we found that that one of those drugs had a really be a powerful one, like the Proteus inhibit.

And then, in 1996 was the eureka moment when now the right combination of three drugs completely suppressed the virus to the point where all of a sudden it was not detectable, so people could then go on to develop and and essentially live normal life span.

So it started off with the discovery in 1984 83 the first drug in 87.

In the nine years later, in 1996 we had the combination referred to as the cocktail that completely suppressed the virus.

So that's incremental.

And that's the way science works, right?

Yeah, what a thrill it is to discover something that's not been discovered before.

And when that discovery is made, it's gonna help.

A lot of people see there's discoveries that people do that.

Our inventions, that all great, it really helps mankind.

But when you're dealing in the arena of science, particularly in the biological sciences, this the thrill of learning something that's never been known before.

There's nothing like that, and all you have to do is to get people to get a taste of that, and it becomes very addictive.

Very addictive.

Science, in its purest form, is discovery, and discovery is essentially infinite.

You don't get all the answers ever.

So you never get that feeling that, okay, I've done it.

Next, you've done it.

But then there's, as you say, another question that comes up or another permutation of what you've done.

Ah, there's never an end to the game.

It's what I referred to us kind of a perpetual challenge.

When you're a scientist looking for solutions and me, it's medicine.

That's why ultimately came.

So it's physical sciences, biological sciences, mathematical sciences.

There a little bit different.

I happen to be in the field of biological sciences, but you never have all the answers and biological sciences, particularly in the fields that I'm in infectious diseases.

So there's something both gratifying at it that you get answers but also challenging and a little bit unnerve ing.

I call it that productive tension that you get E.

I used to joke with my and I still do with my fellows and say, when you're when you're working in in science, it's never really Miller time.

When you say okay, I'm done.

I've just solved everything.

Now I'll go to something else.

There's always that tension that you have more to learn more to do war area's toe, pursue and discover it is.

It's tough, but it's the same aspect of it that's tough.

That makes you feel that that bit of uncertainty is also very stimulated.

I I I joke with people a little bit tongue in cheek, saying that when you realize that you'll never, ever know as much as you should know, Um, you got to get over that feeling of inadequacy.

Otherwise you'll always walk around like you're an attic.

It so some people say.

And I think that's interesting that some scientists, I hope not me walk around like they're really smart and know everything.

I walk around with a with a constant sense of inadequacy that I don't know enough or I haven't done enough.