Interview: David Ho
AIDS Research Pioneer

Dr. Ho, you were born in Taiwan. Perhaps you could tell us a little about your childhood. What was life like in your home town?

David Ho: Tai Chung at that time was a pretty small city. We lived at the edge of the city, sort of bordering on the rice fields. I remember that my father had left Taiwan to come to the United States and pursue graduate studies in engineering. And so, my brother and I were left in my mother's care, in essence grew up in Taiwan without my father being present. But, he was pursuing something that we all viewed as very important, very scholarly type of work.

In Taiwan you had to take these entrance examinations for junior high school, and everybody wanted to go to the best school. So as little kids we were already subjected to a fair amount of pressure. I remember having to study a lot. Because of what my father did, there was a great deal of emphasis on scholarly endeavors.

It must have been difficult without your father there, even though you knew he was still part of the family. What effect do you think it had on you as a child?

David Ho: In many ways served as a role model from a distance. It was rare for people to get this unique opportunity, pursuing a new life in this land of opportunities. Since others around me emphasized that as important and valuable, I came to appreciate the fact that what he was doing was important. Obviously, one misses out on a lot of the interactions with the father. I'm not sure what would have happened if he had stayed and we had stayed there.

It must have been a great sacrifice for him.

David Ho: It was a sacrifice for all involved. To have my mother in Taiwan away from my father, that had to be very difficult, coming here all by himself to pursue a new education, and working on the side to make enough money to cover the expenses and send some pocket change back.

Did he already speak English?

David Ho: He knew some English prior to coming, but a new culture and a new environment must be extremely difficult. We experienced some of that upon coming to the States some years later, although it's easier for a child.

Were you ever afraid that he would just find a new life in America and never come back for you?

David Ho: It was never a consideration. Even though he was thousands of miles away, we got a letter every week and we wrote a letter back every week. My brother and I had to report what happened over the preceding week on a regular basis like clockwork. Our conversation was always based on when we would be able to join him, so we never considered other options.

Do you remember how you felt when he was ready to have you come?

David Ho: Excitement, at the same time some level of concern. This is something that we had looked forward to for a long time, so it was great to know it was finally upon us. I was only 12 years old at the time, but I realized it was going to be dramatically different for me, my mother and my brother. We were going to a country that is completely different from Taiwan culturally, linguistically, and in many other aspects as well. There was this anxiety that brewed and brewed, and it certainly came true when we landed. It's an entirely different culture, and culture shock is a good description of the initial phase. I had done fairly well in school in Taiwan. I came here and all of a sudden I couldn't communicate. It was a devastating period.

School was nearly impossible even though I went every day, not being able to comprehend what the teacher and the classmates are saying and not being able to express any thoughts because at that stage we hadn't even learned the ABC's. And so, it was very, very difficult for a period of about three months.

Is it true that your father didn't want you to learn English until you got to America?

David Ho: He wanted to be sure that we learned English appropriately. Of course, the English taught in Taiwan would be accented, but it might also be not completely correct, and he didn't see much point to it. One would be learning extremely slowly and it might make a difference of a week or two, but I think in the end he was correct. We were immersed in this new world, and you had to pick it up. As a child, one is flexible enough to do that quickly. It went fast, and by the end of the first six months or so, both my brother and I were picking up enough to get along in school.

Did the school system make any extra effort to teach you English?

David Ho: We had extra English classes to attend in addition to some of the regular classes, but there was no bilingual program at the time.

Where did you live when you first came to America? What was it like?

David Ho: This was in 1965 in Los Angeles. Well, for a few months when I first came, I hadn't finished elementary school education, and my father was just in the starting a new job and finishing his studies at USC. So we lived near USC in what is today a predominantly black neighborhood. Whether it was white or black, it was all culture shock to me. We were there for a few months, and then moved nearer to the Los Feliz neighborhood some months later. I went to King Junior High and Marshall High School near Los Feliz.

When you first arrived in Los Angeles and couldn't speak English, the kids probably were not very sympathetic. How did they treat you?

David Ho: I encountered an array of receptions from the kids. As you might expect, some kids are cruel and if you can't say anything, they make fun of you. They call you stupid or other names. But, there are also a lot of kids who are quite reasonable, who try to help. I certainly remember a lot of them. Sure, when other kids are being cruel, it's very, very tough and then you have nothing to come back with simply because you can't express yourself.

But I must emphasize that was only a short period of time.

What was your ambition growing up?

David Ho: I was always interested in pursuing science, not because of any particular role model, but because I was curious. I wanted to learn about things, ask questions. As I came to the U.S., I naturally gravitated in that direction, not so much in medical science at first, but in physics and related topics. I went to Cal Tech to study physics, although during the later years I developed an interest in the new molecular biology, and that was what led me to into medical research.

Didn't you also spend some time at MIT?

David Ho: As an undergraduate I spent one year at MIT and three years at Cal Tech. I got into both schools, and I had a great deal of ambivalence about where to go. People were kind enough to allow me to set up a hybrid program and I got to experience both institutions. Obviously, I had to devote more time at one than the other, and I was attracted to Cal Tech because of figures like Richard Feynman and Murray Gell-Mann, giants of physics.

When books were extremely important to you when you were growing up?

David Ho: I was reading a fair amount of science fiction as well as science written for the general public. Although some of it was certainly way over my head, I still remember reading books by Isaac Asimov, science fiction stories, and also books by physicists, talking about things that normal people can't readily conceive of, like anti-matter. It was just interesting to try to think in that way, even though I wasn't understanding everything.

I was curious about all these things I couldn't understand and I tried to learn more by reading more. Gradually a little bit would sink in. Looking back, I must admit my understanding was quite sketchy, but it was that kind of curiosity that drove me into science. I remember going to the library and trying to look at the Feynman lectures in physics. That's very fundamental physics, nothing too fancy, but presented in his unusual style. I hadn't taken all the requisite courses before reading it, I was just very interested by it.

How did your parents respond to your choice of physics and then molecular biology?

David Ho: My parents never tried to influence my decisions. They pretty much left it up to me. I wasn't a troubled child. I was doing well in school, so they said to do what you like, which is the same attitude I now have with my own kids: "Just do what you like. You have to pursue what you're interested in. Just do it well, whatever you pick."

Why did you switch from physics to molecular biology?

David Ho: In high school my biology was just trying to remember the names of various animal species, plant species, and it was not all that exciting. But in my sophomore and junior year of college, I realized that there was a lot of fascinating new biology coming along. The era of molecular biology using recombinant DNA techniques was also just emerging, and that was fascinating. That hit me the same way some of the questions in the physical sciences did.

I got very interested and could appreciate the fact that medical research based on the new biology could have immediate applications if one were to apply those techniques to specific illnesses. I was most interested in things like particle physics and astrophysics, but those things are much less tangible day to day. In trying to talk to your friends and relatives, it's very hard to convey what you're actually doing and why you're doing it. Through a long and slow period I finally decided that I was going to continue to pursue science in the form of medical research. I had already taken enough biology and other courses to meet the requirements for medical school, so I made the transition. I wanted to pursue science, because it's what I loved to do. But the fact that by pursing medical science you could also indirectly help people, made it even more a reason for doing that.

I understand also playing a little blackjack at that time?

David Ho: I would rather call it an exercise in probability and statistics. I read a little paperback book called Beat the Dealer, by a mathematician with a computer background who tried to calculate all the odds and concluded that even if you played perfectly, you can't beat the dealer except by varying your bet. By counting the cards, you could increase your bet if the situation is in your favor and when the situation is against you, you decrease your bet. In the end you could actually win. So I tested that on a very modest scale. I could count cards with reasonable efficiency to make sure that I don't lose, but I never did win much money. But you know, in casinos they don't like people to count cards, so if they spot you doing that they get you out. The dealer could very quickly tell whether you know how to play or not. If all the face cards have been played, the aces have been played, and only small cards are left, which is a situation in favor of the dealer you are decreasing your bet. On the other hand, when there are only huge cards left and you increase your bet, they get suspicious. Many of them are very good players themselves, that's why they're hired as dealers. I always learned a lot of games because it's one of those intellectual challenges, so I played chess rather seriously also. I don't have time for it these days.

How did medical school change you? Did it change your personality or your outlook?

David Ho: Medical school per se did not change my personality. It was difficult for me to adjust at the beginning. At Cal Tech where we had take-home exams, they were very difficult problems. You could open any book you want, you just have to solve problems. In medical school you had to memorize everything. That transition initially was difficult. In terms of personality, the biggest event in my life was coming to the States from Taiwan. From being a fairly outgoing child I retreated and became rather reserved for a number of years. It took the late high school years, college years and medical school years, to reemerge, having gained greater confidence.

Was there a teacher along the way who was especially important to you?

David Ho: There were teachers who put in a lot of effort to make sure I learned English. There were teachers in junior high school who appreciated the fact that even though my English wasn't up to par, I was particularly good in certain classes, and put me in with the more advanced students despite the language handicap. In high school, there were teachers who recognized my particular interest in chemistry and physics, and allowed me to do more than the usual students.

Who made the greatest impression on you growing up, as a mentor?

David Ho: My father is an engineer. He came over to study and he had a circle of friends, most of whom also came from Taiwan or China to pursue either engineering or science, and there were a lot of accomplished individuals that we saw on a regular basis. My uncle was a graduate student in chemistry at Cal Tech. These people were really quite accomplished. That immediate circle had a very positive influence on me.

From a distance, I was beginning to recognize some of the big role models in science. Even as a child, one of course hears about Einstein. I had known about Richard Feynman for a long time before he became more popular with the general public. There were two young scientists who got the Nobel Prize in their early '30s for working on particle physics. I think it was 1957. They worked in New York, on parity of charge and spin of subatomic particles. Their names are Yang and Lee, they were both from mainland China. From a distance they served as great role models.

You were quite young when you first encountered AIDS, but no one knew what AIDS was. Where were you when you first encountered it?

David Ho: I finished medical school at Harvard and went to train in internal medicine at UCLA. I was getting ready to pursue research on viruses. Then I was asked to stay on as a chief resident for an extra year. As a chief resident, you see a lot of patients. You hear about all the patients that are admitted. It was during that period that I heard from the interns and residents that the night before a man had come into the hospital with severe pneumonia. He couldn't breathe, and had to be put in the ICU. Pneumonia had wiped out both lungs, but at the same time he also had gastrointestinal problems and seizures, as if there was something else in the brain. This man died very quickly. His pneumonia was due to a parasite called pneumocystus craniae that only occurred in patients who were getting chemotherapy. There was another parasite in the brain, and a virus in the gastrointestinal tract, and this man some weeks before had been "perfectly healthy." in quotes. We couldn't explain the illness.

We knew what the complications were, but we couldn't explain the illness. We saw another one a few weeks later, and then another one and the common link was that these were all young gay men. Upon taking a closer history, we found that they were gay men with lots of sexual contacts. They didn't have exactly the same set of complications, but the conclusion was that something was wiping out their immune system, allowing them to be sick with all of these other things. We were very concerned that something was being transmitted which is capable of destroying the immune system. Without thinking too much, we already believed that this had to be something new, something that wasn't in the textbooks, and in fact that turned out to be the case.

I began with an interest in this medical curiosity, never realizing that this was going to be a big health problem for the public. But, the scientific aspect was extremely interesting in that here we were looking at something that was transmissible, capable of destroying the immune system. That was new and one way or another the science behind that would shed light on bugs and on the immune system. So, I was gung-ho from day one of the epidemic.

You were in the right place at the right time.

David Ho: Right, I was.

I was at the right place at the right time, having just finished the right type of training, getting ready to do the right type of training that would be relevant to this problem. Chance does play a very, very important role. The other thing I've been telling some of the students here is that serendipity plays an important role, but we have to be prepared to take advantage of the opportunities that are bubbled up by serendipity. And, I certainly, for this particular problem, once I grabbed onto it I did not let go, even though in the early years it was not a problem and people would say, "Well why are you interested in a problem that effects the gay men and drug users?" You know, it's a disease and one should not look upon it in that way. And so, I went full speed ahead on this particular problem.

When and why did you suspect a virus so early on?

David Ho: From the very beginning, after seeing the first five cases or so. The common link was that the sufferers were all gay men with lots of sexual contacts. We had seen a lot of gay men with infectious diseases like Hepatitis B and other sexually transmitted diseases. We always put a transmissible agent as the number one cause. There were people who proposed the idea that some of this problem was due to some drugs that were used by the gay community at the time, poppers and nitrates, but it just didn't seem that way to us.

Why do you think we're seeing these new microbes, these new viruses like HIV that we did not grow up with as children?

David Ho: Many have written about the demise of bugs with the development of antibiotics. I think that was overly optimistic, and now we're seeing the revenge of the bugs. Some of the bacteria that are treatable with antibiotics are becoming more resistant to the drugs that we have in our arsenal. At the same time, we're also realizing that there are a lot of bugs that were with us for a long time, but are just newly recognized, Lyme disease for example. We thought it was a new syndrome and the field collectively identified the bug only in the past decade or so. But, looking back in the textbook, that illness has been described for decades. Hunter virus I suspect has been with us periodically in minor epidemics for a long, long time, but now we have the technology to detect it and identify and characterize it.

But there are some other illnesses that truly appear to be new, and AIDS is clearly one of those. Ebola is probably another and related hemorrhagic viruses and that's probably because we have as a human population invaded a new territory. In central Africa, people are going into jungle areas, having contacts with certain bats which allowed the Ebola virus to jump species. It causes devastation and can go through a village very quickly, but it burns itself out very quickly because it's so deadly.

Based on the work that's been done over the past decade and a half, it's clear that HIV emerged about 60 or 70 years ago, and the virus jumped species from an African monkey or ape species into the human. This jump probably was not completely new. It may have occurred hundreds of years ago or thousands of years ago, but it burned itself out, and didn't spread. But societies were changing. Population density was increasing, transportation was getting better, people were able to move around, sexual behavior was changing. A lot of these socioeconomic factors permitted the initial introduction to be transmitted in waves. I think there's a very valuable lesson there for us when we look back upon how AIDS may have started.

We have to be mindful of the factors that allow epidemics to occur. We have to think critically about population density, what transportation actually can do. Today transportation is global, and diseases do not obey any national boundaries. These are lessons we should bear in mind.

What were your first important discoveries about HIV and AIDS?

David Ho: I saw the first patient in 1981. By '82 I had moved to Boston to pursue research on viruses, and I continued to look for the cause. The cause was initially identified by scientists at the Pasteur Institute, and then confirmed by scientists at the NIH. I had a more substantial role beginning in 1984 when my colleagues and I showed that the virus is not just in people who are sick, but in people who are very healthy who belong in the same risk group. We were the first to show that there is a carrier state that can last for a long period of time.

You can be HIV positive, feel well, but still be carrying lots of virus?

David Ho: That's exactly right. Moving on, we showed that the virus, in addition to attacking the immune system, actually could attack the central nervous system. Particularly for late stage patients, there's a great deal of involvement of the brain, causing dementia in some severe cases. We also found an illness, associated with the initial phase of infection that looked like flu. It lasted for several weeks then disappeared. During that phase, the patient has an enormous amount of virus before the immune system begins to kick in to keep it in check. My research has focused on trying to understand how the replication of the virus results in the depletion of the immune system.

There had been an old dogma in the field that HIV comes in and after this acute phase that looks like flu, there's a prolonged dormancy. The virus wasn't doing much and the person is pretty well. And, we know that because we now know that period could be about ten years. And, somehow we realized that during this period the person's immune system is gradually dwindling and I didn't necessarily like the notion that -- we knew the patient is well -- but I didn't necessarily like the notion that the virus is dormant. And, for a long period of time my research effort is to measure the virus, to quantify the virus. I would say that's a decade long effort, having been one of the first to measure how much virus there is, and then very gradually demonstrating that the old notion is incorrect.

In fact, the virus comes in and grows and churns out lots of virus each day. It's destroying lots of immune cells each day, and the body has to pump out more of those cells to keep up. So we ultimately proved the old notion was incorrect. We're dealing with a highly dynamic virus and a highly dynamic process of replacing the lost cells.

I understand you attempted a very important experiment with CD4 molecules that didn't work out. Could you tell us about that?

David Ho: The CD4 molecule is necessary for HIV to bind to before it can enter the cell. We thought if we could make free soluble forms of this CD4, they would serve as decoys for the virus and help block the entry of the virus into the cell. It's a very logical thing to think of, and using molecular techniques several groups actually came up with such a strategy. We helped test it, and showed that it wasn't working. When we figured out why, we learned a very important lesson.

Up to that point in 1989, people had been studying HIV grown in the laboratory and had not concentrated on HIV as it exists in the body of infected individuals. It turns out they're not the same. HIV grown in the laboratory is very susceptible to this approach and the drugs were developed based on use of these laboratory viruses, and when soluble CD4 was applied to viruses that came directly from patients, it simply didn't work. There's a cloud of sugar around the virus cells to protect against antibodies, so the virus has a protective mechanism. It's one of the reasons we're having such trouble in coming up with a vaccine.

When an experiment doesn't work, you may learn a great deal anyway, but it must be crushing when you've spent a lot of time on it.

David Ho: It's crushing in some ways but it led to a new set of findings, and that's pretty exciting.

We went into the experiment expecting to see some positive effect of the approach, and it didn't come up and we thought, "Well, maybe it's only this case. Let's wait until one and many more," and repeatedly it failed and failed. We were more interested in finding out why because there has to be an answer there. And, that process was pretty exciting, to be the one showing that it doesn't work although we wanted the positive result rather than the negative result, but that's science. You get a negative result and now you have to figure out why because it works beautifully in the test tube. Why isn't it working in the patient? And that answer and that discovery process really taught us a lot about HIV. And, this is the joy of science because you go into it because you're curious and you figure things out and you say, "Wow."

Did you ever feel disheartened or want to quit and do something easier than this?

David Ho: I felt disheartened and beaten for a long time. Even though the science was coming out positively, we weren't making much progress for the patients. So, as scientists we could sit and celebrate each successful experiment, but we made very little difference to the lives of patients with HIV infection and that was very disheartening. And, seeing lots of patients go over that decade and almost a decade and a half is quite devastating, but I never said, "This is too disheartening. I'm going to quit." We were learning so much about the virus, one optimistically could expect some progress to come along. And, in fact, it did come along in 1994 when the protease inhibitors first went into human testing.

We had worked on such inhibitors in the laboratory in the late '80s and early '90s. No one paid any attention, and it was only through the clinical application and the results that the recognition came. We now had a powerful tool to fight HIV, and people were finding out that combining the older drugs was also powerful. We were strategically placed in 1994 to combine the protease inhibitors with several of the old drugs. We could knock the virus down so it's no longer measurable, and if the patient could tolerate the drugs we could keep it down for two to three years. That's where we are today. Even though it's not gone, we can control it. Not in everyone, but in many, many patients, and this result is reflected in the national statistics.

How have the statistics changed?

David Ho: If one looks at the inpatient census for AIDS patients, it's gone way down. These complicated infections that we call opportunistic infections have gone way down. Most importantly, AIDS mortality has gone down about 50 percent in each of the last two years. Lots of patients have turned around from a very sick state to a functional state where they are able to return to their jobs.

When did you realize you were onto something that could really help people?

David Ho: The first 20 patients we gave the protease inhibitors to showed us how potent these drugs were in the body, not just in the test tube. The virus fell ten fold, then a hundred fold, and in some cases a thousand fold in a matter of a few weeks. The patients put on weight, became functional. The sick ones resolved their problems. It was very dramatic.

We also knew that if you gave the drugs one at a time, the virus replicates so fast that you will create the mutations necessary to become resistant to the drugs. And, therefore, if the drugs were given individually, the virus would find a way to evade the drugs. And so, during that period, we did a lot of mathematics to calculate what it would take to control the virus with great potency and with great durability. And, for a period in 1994, it was truly an exciting phase in my professional career. One would go to bed thinking about it, waking up in the middle of the night thinking about what we're looking at, what this piece of evidence means and how do we take this and translate it into practical application.

A lot of what we're looking at is the result of that process from our lab as well as the laboratories of several groups around the world, basically realizing the kinetics of the virus, using that information to do calculations. And, this is where my physical science background really came in useful, having a strong background in mathematics and applying it to biology and then being able to go on with a hypothesis, saying that if we approach treatment in this fashion with these types of drugs in combination, these are the results we expect. And, most of that has come true over the last few years, and now we need to see how far we could go with this whole strategy.

How do the protease inhibitors work?

David Ho: The protease is an enzyme for the virus. This enzyme is a chemical scissor. HIV makes its proteins in big chunks, and this enzyme cuts them into six or seven small pieces. If the enzyme does not make the cuts, the proteins are inappropriate. They won't form the full mature progeny particle.

The protease structure had been studied for a long time. Particularly in the late '80s we realized what it looked like three dimensionally, and there's a cavity in the middle. And inside that cavity are the enzymatic sites, or the cutting sites. And so, the big proteins could come and sit in this groove and then be cut. Well it was easy to think that if you could fill that cavity with a small chemical so the proteins could not be cut. And so many, many groups started to try to fill that cavity with small chemicals, and there were rationally designed chemicals -- as well as chemicals that were done by a more empirical screening process -- that would fill this cavity. And so, what protease inhibitors are is simply something that would gum up the chemicals. So now HIV could not cut its proteins, and so it makes that progeny, and therefore it can't spread the infection. As long as the patient is taking the drug, it can't spread the infection. So it's now kept in control.

What is the role of the CCR5 molecule in the disease cycle?

David Ho: This is a very recent discovery made within our institute about two and a half years ago. A susceptible cell has the CD4 molecule on the surface. It turns out that by itself is not enough for HIV to bind to and enter. For a decade or more we knew there was a missing factor, but we didn't know its identity. About two and a half years, ago we realized that CCR5 was that molecule. It took a lot of fancy molecular biology to prove it. HIV has a dual docking system. It needs to bind to CD4, then bind to CCR5, and then it will fuse with the cell and get in. Now armed with this information, we can design inhibitors that will block CCR5. That should be tested in patients sometime next year. That would create a new class of drugs to use against HIV.

Interestingly, it turns out that not everyone's CCR5 is the same. Certain people of Caucasian background are missing more CCR5. If that molecule is not there it's very hard for HIV to infect those individuals. These are the lucky few. There's a lot of variation in CCR5. Certain forms allow the faster disease and other forms the slower disease. We're beginning to understand how genetics affect a disease that is caused by a virus.

That's fascinating. To a lay person, it looks like you've encountered a lot of professional jealousy, especially after the Time Magazine "Man of the Year" story. I'm sure some of this is sincere disagreement in the scientific community, but how do you respond to being criticized by your peers and colleagues?

David Ho: I think genuine scientific disagreement is healthy. That's how we move science forward. And, yes there are certain people who would disagree with me about how, say, the lymphocytes are specifically destroyed by HIV, so the mechanistic issues. It's a very controversial area. I have my views and others don't agree with those views, but each one of us are involved with experiments trying to prove our case or in fact sometimes disproving ourselves. So, that is good and that is what science should be.

I think there are other forms of criticisms that are not healthy where it becomes very personal.

I've gotten a lot of recognition, especially by Time magazine. I've never said that I am the representative for the AIDS community. It was Time that, in trying to recognize the achievements in the field, they typically do it through the story of one and I was the chosen one. I fully realize that it's symbolic for the progress made by the field. And, a lot of people deal with that very well and many colleagues have said very nice things to me about that and about how good that is for the field and for science in general. But, there are a lot of big egos in the field and if they're not the one, some of them can be vicious and have been vicious. But, I don't think you would find much in terms of a response from me about such type of criticism. I've said that I'm just going to continue to work and to do my science and advance the field. I don't want to be dragged into the mud into such an unnecessary debate which is harmful to the field, to science, and most importantly, what does that look like from a patient's perspective?

Do you still use AZT in the anti-AIDS cocktail, or has it been replaced?

David Ho: There are now many different cocktails. We have about twelve drugs against HIV in our armamentarium, and with that you can mix many different combinations. Typically they involve one or two of the protease inhibitors together with several of the older drugs, such as AZT, D14, 3TC. The whole field is trying to learn what the best combinations are. We don't have the final answer, but we know some good combinations.

What is the likelihood that we will see a cure or a vaccine for AIDS in the near future? Do you have any kind of time line in your mind?

David Ho: Those are our objectives. We want to push the therapy from controlling the virus to curing the virus. We are facing several major obstacles. We know now, having controlled the virus for three years, that in a lot of patients there's still a residual pool of virus, and we have to come up with strategies to flush that out. We have to tickle those viruses out of quiescence so they can be attacked by the drugs that we administer. That's going for the cure, but I can't give you any time line. A vaccine is another goal. These therapeutic advances of the past few years are great for American and European patients who can afford it.

How expensive is this treatment?

David Ho: The drugs cost about $15,000 a year. You add on all of the testing and the doctor's fee and the hospital and clinic fees, and it's an enormous cost, which is simply out of the question for the patients in other countries. And that's where the epidemic is, numerically speaking. Over 90 percent of AIDS cases occur in Africa, Asia and in developing countries. Were not going to make an impact on the global epidemic of HIV infection through these drugs, so we have to do it through prevention. Prevention can be tackled through education, but as scientists our responsibility is to develop a vaccine. That has been the most difficult task. If HIV were as easy as polio or Hepatitis B or measles, we would have had a vaccine sometime in the mid to late '80s, but it's a different virus. It changes very quickly. It has this shield which I talked about earlier, and the immune system doesn't see it very well. We need new strategies to come up with a vaccine, so there isn't one now. Even if there was one today, it would take several years to test it and apply it, so a vaccine is still years away. But everyone working in the field realizes in the field how important it is. It's center stage in AIDS research.

You entered a large controversy surrounding AIDS experiments in Africa. You resigned from the Board of the New England Journal of Medicine, didn't you?

David Ho: Right. There's an experiment being done in several developing countries, in Africa and Thailand for example, where pregnant infected women are given AZT or a placebo. In the US we've already shown that AZT is superior to a placebo in reducing the chance of infection being transmitted to the newborn. The AZT regimen that's used in the U.S. is extremely complicated, protracted and costly. It's almost completely out of the question for use in developing countries. The new studies in Africa compare shorter courses of AZT to a placebo. Many have said the use of a placebo is inappropriate, and that it's akin to the tragedy that occurred with the Tuskeegee experiment, where southern blacks were denied effective syphilis therapy.

Because they wanted to see how the disease would progress?

David Ho: Right. But this is an inappropriate comparison in my view. In Africa the standard of care is nothing. People are trying desperately to come up with measures that would be applicable in real life in Africa and other developing countries. These studies were done after extensive discussion among the scientists, the doctors, the clergyman, government officials from the U.S. and the respective countries, and with the population at risk. It's completely open. So the comparison with Tuskeegee is simply not appropriate. If you insist that Africans do what we do here, it won't be feasible.

If you insist on the infeasible, you'll get into a situation where nothing is done. And, the most important thing we could do now is to come up with strategies that would decrease mother-to-infant transmission of HIV. So I got involved with that controversy because the New England Journal took a very strong ethical position against any use of placebo and basically did not welcome my opposing view and I had to express my view in Time Magazine. And they didn't care for that, and therefore because of this disagreement, I said I had to go with my own beliefs and I don't think I could serve the Journal well by remaining on its editorial board.

It sounds like this an uncomfortable situation. You must have felt very strongly about this.

David Ho: You have to go with your beliefs. One can't be hypocritical about it. And, I think I wanted to send a strong message to the Journal that it's much more complicated than what we have discussed so far. I mean, if the Journal had a particular view, the best approach is to talk to the people involved, to have a dialogue with the U.S. scientists, with the African scientists and with the subjects that are enrolling and get a true understanding at the grass root level, rather than pontificate from the ivory tower of Harvard University or, you know, the New England Journal. I think that kind of approach is not appropriate.

How did your association with the Aaron Diamond Center begin?

David Ho: The Aaron Diamond AIDS Research Center was put together by people in New York. The philanthropist Irene Diamond provided the funds to get it going, and the institute is named for her husband. Some of the city officials as well as Irene Diamond's advisors came up with the idea of concentrating their money and effort on an institute that would be devoted to AIDS research. I agreed with the idea and was recruited to direct the Center. I really appreciate the fact that I was given that opportunity.

Do you believe you had opportunities in America that you would not have had somewhere else?

David Ho: I've lived the American dream so far.

Only in America would a 37 year-old be given that opportunity to become an institute director. I think the culture overall here is enlightened enough to be able to give responsibility to a young person without that much regard for age and with greater emphasis on merit, on potential, and such things. It's in many ways an amazing experience. I've done well. I was working hard. I had a certain vision of what I wanted to do and those things fitted well with the goals of the new institute. So, I was given the chance and I believe I've taken advantage of that golden opportunity.

I had the same conversation with John Shalikashvili. Only in America would a foreign born person be made Chairman of the Joint Chiefs of Staff as he was, or Secretary of State like Madeleine Albright, who's also foreign born. I think it's fantastic. This would not happen in China, Taiwan, Japan or many of the European countries. I'm truly grateful to be here, and to my father in particular for putting in that tremendous effort during those early, difficult years. This is a very enlightened country.

Just coming back to my own area, AIDS, it's now a problem largely of developing countries. A vaccine would probably have not made that much of a difference to the United States, but yet the vaccine research for AIDS is almost entirely funded by U.S. money. So it's taken the broader view, that this is a problem for the world and therefore we're going to solve it. And, this is not limited to AIDS. Malaria is not much of a problem, yet we're taking it on, same with tuberculosis and so on and so forth. The past few years, as I had more and more chance to reflect upon my career so far and my life so far, I've come to appreciate much more of what this country is.

When I speak to students now, I try to emphasize some of these points. This a very special place, and in my view, truly a land of opportunities.

Thank you so much.