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Interview with Dr. David Ho, Interviewed by Judy Woodruff, CNN
MS. WOODRUFF: Dr. Ho, let me begin by asking you what does it mean to you to be considered for Time's Man of the Year?
DR. HO: It obviously is a great honor, and I'm quite overwhelmed by this honor. But I do want to emphasize that this honor should be shared with a lot of people in AIDS research: my colleagues, my collaborators, and many other researchers who laid the foundation for the success of the last couple of years. So I am honored, but I want to make sure that the credit is properly given to a lot of people. I'd also like to say that this honor, I think, reflects the new optimism in AIDS research, the new understanding, the better treatment, particularly in the form of combination of treatment, that is now available to some patients in our society. And obviously these patients are benefitting more than previously. But we also don't want to convey to everybody that the AIDS problem is over. In fact, the odyssey is far from over. A lot remains to be done. So I do want to emphasize those points while being honored in this way.
MS. WOODRUFF: This sort of recognition, what do you think it'll mean for research on AIDS?
DR. HO: Well, it's good in the sense that recognition of scientific accomplishments -- it's good for those of us who are involved in doing these sort of things. I think in our society scientists, engineers, people who build things, discover things, are not as often recognized compared to entertainers and sports stars. And so it is good in the sense that science and scientific accomplishments are singled out for recognition. I would like to, once again, say that I'm just overwhelmed by the selection of me as that one individual, when in reality it represents many, many scientists and patients.
MS. WOODRUFF: Do you think that this recognition will have an effect on your professionally?
DR. HO: Well, those who know me well will probably interact with me the same way, and I think from my perspective I don't think I will change all that much in how I operate within our institute and within the field. There may be a few more individuals who did not know me previously who would now recognize perhaps the name or the face. I'm not sure that would necessarily affect what I do on a day-to-day basis.
MS. WOODRUFF: What about you personally? How do you think this will affect you personally?
DR. HO: Well, for me, this is a great honor, but our work is in progress, and I've been focused on our mission in AIDS research. And our studies are still ongoing, and the questions remain to be answered. So we will be doing pretty much what we had planned to do anyway, to pursue the unanswered questions. I don't think it will change what I do day to day.
MS. WOODRUFF: What about in your own family?
DR. HO: I think my children, my family in general, keep me pretty humble. Dad is dad, for example. Whether he's on television or he's in a magazine probably doesn't change things very much.
MS. WOODRUFF: Let's go back to the beginning -- David Ho growing up as a young boy in Taiwan. When did you begin to get interested in science and biology?
MS. WOODRUFF: All I recall is, as a young child in elementary school, I was taught my parents that being scholarly was very important, studying and education are important things. And I know I developed a keen interest in science and mathematics fairly early on.
MS. WOODRUFF: How old were you, do you think, when you knew you were interested -- you said you were interested in science and math. When do you remember that?
DR. HO: Probably eight or nine. So it was pretty early, and I couldn't explain why I was particularly interested in science. I think perhaps having a father who's an engineer and an uncle who's a chemist and other family members who are doing either science or engineering had some influence. And the fact that scientists and doctors were generally well regarded in society in the society that I grew up in made a difference.
MS. WOODRUFF: Talk a little about your family and the decision to come to the United States and what effect that had on you. You were 12 years old when you came to the U.S. How much of a change was that for you growing up in Taiwan and then suddenly you're in California?
DR. HO: My father actually left Taiwan for the U.S. many years before we actually moved over. So he came to get an advanced degree to have a better future in the field of engineering. And so that was the kind of thing that I looked up to, because that kind of opportunity was rather rare for someone coming from Taiwan back in the late '50s. And so that provided an example. So when we had the opportunity to come after he got his degree and settled down and had a steady job, we came over, and myself, my brother and my mother regarded that as a very unique opportunity for us, because we could build our futures in this land of opportunity. And so I think I learned from that point on that this was an opportunity and one has to take advantage of it.
MS. WOODRUFF: We were talking about the change from Taiwan to the U.S. What was that transition like coming from T'ai-chung, a city in Taiwan, to the United States?
DR. HO: It was truly a culture shock. In the course of 48 hours I moved from Taiwan to Los Angeles, and every aspect of life became different. I couldn't speak English, and that immediately was a great difficulty. But from the home to other aspects of life, everything was different. The supermarket was different. Cars. We didn't have cars. We had bicycles. Television. We barely had a radio. So it was truly a shock, and I only remember that it was a difficult adjustment period. But I don't remember it as being very long. I think as a younger child one tends to be fairly flexible. And so the difficult period lasted only a few months, and after that period I think I knew enough English to get by and so I consider myself lucky to have come at that age, rather than, say, at a later age during high school or college when the communication problems would have been greater.
MS. WOODRUFF: And sports? Was that part of it, part of the transition?
DR. HO: Well, sports was something that did not rely on language skills as much, so it was a good way to make friends and just to have fun. So it was a nice relief from other aspects of life during that period.
MS. WOODRUFF: You were commenting about the various infectious diseases that were interesting and being identified in the late '70s.
DR. HO: Well, after finishing medical school, while training in internal medicine in Los Angeles, I gradually developed an interest in infections. In the early 1980s, while I was a chief medical resident, I began to see some patients who came into the hospital with a number of infectious complications simultaneously. Pneumonia, brain infection, gut infection and so on, and these were primarily homosexual men in Los Angeles. And we, obviously, did not know what was going on with them. We just knew by their clinical presentation that there had to be something wrong with their immune defenses in that they were coming down with infections that "normal" people do not get, people with an intact immune system. So in the beginning it was a curious case or two, but then gradually we saw more and more such patients. And, of course, in retrospect, we now know those were the initial cases of what we call AIDS. But it was a great puzzle, a great mystery during those early days. And those cases piqued my interest, even though it was a rare disease, we didn't know what was going on. It peaked my scientific interest. What was going on with these people that destroyed their immune system? They had previously been healthy, so it appeared to be acquired and not inherited. So that already appeared to be a new disease. And this new disease was occurring in men who had, by history, a lot of sexual contacts. And so there was a chance that we were dealing with a transmissible disease. An infectious disease that destroyed the immune system. And, right away, it doesn't take more than a medical student to recognize, that is not something written about in the textbooks. It appeared to be new and it was interesting in that it so severely affected the immune system. So my interest in AIDS developed from those days, from the clinical perspective.
MS. WOODRUFF: Why do you think that was interesting to you? I mean, there were other puzzles out there on the medical front, and even in the infectious disease area, I presume. Why was that puzzle particularly interesting, you know, kept you fascinated?
DR. HO: Well, it seemed like a fascinating medical problem, something that appeared to be transmissible that knocked out the immune system. Even if we were dealing with a rare case, that already presented a very interesting scientific and medical question. But, over the course of the ensuing few months, we realized that cases were coming in one after another. And so, it appeared to be growing, even in those early days. Obviously, I did not know that it was going to turn into a major epidemic world-wide. But it was a new syndrome, and cases were trickling in, and so -- and I had first-hand experience with these cases.
MS. WOODRUFF: Was there a point at which you made a choice when you had an opportunity to go in a different direction with infectious diseases, but you chose to stick with this yet undefined --
DR. HO: Right. Right. It became clear this was a growing epidemic affecting gay men, some drug users, and cases in blood transfusion recipients, and hemophiliacs, and kids were just appearing, but it was growing. And, therefore, it represented a -- a mystery that could be solved by research. And so, I had that growing interest, and my mentor at the time, Marty Hirsch at Mass General, had a growing interest in the same problem. And, therefore, when I was ready to enter the laboratory full-time to pursue a research topic.
MS. WOODRUFF: Did you ever project forward and think, maybe I can be involved in helping find an answer?
DR. HO: Well, the initial question was, what was the cause of this syndrome? It seemed like an infectious disease. So is it a bacterium, is it a fungus, is it a parasite, is it a virus? And so the whole, I think, research community interested in infections, there was a considerable focus on addressing that fundamental question. And the bacteriologists went at it looking for a new bacterium, and virologists went looking for viruses. And, of course, shortly thereafter, Luc Montagnier and his colleagues in Paris made the first identification of a retrovirus that was found in one patient, and shortly, thereafter, Dr. Gallo and his colleagues at the NIH made it clear that this new syndrome was due to a retrovirus by fully characterizing it and developing a test to show that some people -- all of these people with AIDS have antibodies to this new virus, which was later called HIV.
MS. WOODRUFF: And you were involved in those early stages?
DR. HO: Well, we were involved in doing some of the exactly same experiments, but I must say that others got there before we did and made these important contributions. But because we had done the work, we were very early in getting started on working on the virology of HIV, and so it was very easy for us then to enter this field and start to do experiments and make contributions in a number of areas.
DR. HO: I had my questions that I wanted to pursue. I wanted to ask a number of things. We were seeing, for example, many AIDS patients suffering from dementia and other neurological complications. So we logically asked whether HIV could be the cause of those problems in addition to the immune deficiency. And so we pursued some of that, and quite successfully showed that HIV is directly linked to a lot of the neurological complications. Many of our initial projects were very much based on questions presented by the patients. We also recognized early on that some patients were coming in with a flu-like illness, and we helped recognize that as the initial infection by HIV. And so that's how our research began at the interface of patient care and this new field, retrovirology. And by staying at that interface, we asked a lot of questions that are pertinent to the patients we were seeing at the time.
MS. WOODRUFF: Were you affected personally, do you think, by what happened to them?
DR. HO: I think everybody who's involved in patient care in the AIDS field has been personally affected in many different ways. We've seen too many tragedies, too many deaths, due to this virus. There's no question that myself and all of my colleagues who have cared for AIDS patients have been touched in a very deeply emotional way.
MS. WOODRUFF: Let me go back now to -- we were talking about the research and your own research. But let me just ask you, if you would, to describe in layman's terms what you think the main developments along the way since the early to mid 1980s have been with regard to HIV and AIDS.
DR. HO: Well, let me go even a little bit back and say that the people at the Centers for Disease Control, played a vital role in recognizing this new syndrome and then tracking it. And that has been absolutely crucial in dealing with this epidemic. Then, of course, following the initial identification of the virus and the subsequent characterization from the mid '80s on, there were a lot of things to be done. And I think credit goes to Dr. Gallo and his colleagues for growing the virus in mass quantities and developing a test to make the diagnosis of the HIV infection. This test was then very quickly utilized to protect the blood supply, and that's absolutely vital, and to protect any products that derive from blood, such as factor eight for the patients with hemophilia. So I think that has to be a major development. And then just the fundamental studies on the virus, characterizing all the genes, getting all of them sequenced, characterizing the proteins that are made from these genes, and begin to understand their structure and function. There's a lot of basic science to be done, and those things were quickly done or initiated in the mid '80s and in the subsequent few years. So there was tremendous progress during that period. A lot of things came out. And, of course, during the serious activity, research activities, AZT emerged as the first drug that showed activity, great activity against the virus in the test tube, and later, in rapid pace, was found to be partially efficacious in slowing down the disease; not a great deal, but it definitely had an impact. And then over the ensuing years, a few other drugs were developed that blocked one of the viral enzymes called reverse transcriptase. And so these inhibitors of reverse transcriptase gradually became our weapons in our arsenal against HIV. And I think those are important developments. And also during this period I think physicians and clinical researchers contributed a great deal by doing studies that showed us how to better care for the patients, to manage the patients, how to prevent certain infections from happening. And those type of findings directly impacted on the longevity of patients infected with HIV. So all of those things are crucial. And then the fundamental research on viral genes and proteins began to pay off, and let me just give you one example. It was quickly realized that, like other retroviruses, HIV has an enzyme called protease, and this protease is essential for cutting the viral proteins into the smaller components so an infectious viral particle could be made and, by blocking this protein, you could render the virus non-infectious. So the basic scientists went on to show all of these things and to make this protein in large quantities so the crystals of the protein could be generated and then the structure of the protein could be solved by x-ray crystallography and then the structure could be defined. And now other scientists could come into play. With the structure known, they could design small chemicals that would fit into the active side of this enzyme and block it, and these then resulted in the first generation of protease inhibitors, which were only licensed earlier this year. So it's a classical example of how fundamental research could then translate into practical differences for patients who are suffering from this disease.
MS. WOODRUFF: So then talk about how your own more recent research -- you were interested in measuring the amount of the virus, and what's interesting, I think, to some people, and you've commented on this yourself, is that that that -- typically that might have been done sooner. You might have expected -- one might have expected that it would be done sooner, but it hadn't been. How did all that come about, and what did you think needed to be done in that area?
DR. HO: I think that when HIV was discovered and began to be characterized, a lot of people went on to do a lot of experiments as I just outlined, but a lot of it involved new biology, go and characterize the genes and solve the structure of the proteins of this virus. Something that is rather fundamental to a classical virologist, such quantifying it in various specimens from patients, quantifying the virus in blood, in urine and in other bodily samples, is a common practice in virology. We do that for other viruses. But that wasn't done for HIV at the beginning and wasn't done for a few years. So in the late 1980s when my colleagues and I had the opportunity to conduct a trial involving a new therapeutic called soluble CD4, we wanted to come up with a test that would monitor the antiviral effect of that new drug. And so we asked the question, "Well, how do we do that and how come that wasn't done earlier?" So we, from that point on, began to do quantitation experiments, to look at the amount of virus in blood of infected individual. And what we found surprised us, and we did not believe in those initial results for a while. This would be late 1988, early 1989.
MS. WOODRUFF: Why didn't you believe them?
DR. HO: Because we were finding that in the blood of infected people there was quite a bit of virus. In fact, we could inoculate tiny amounts of plasma into a culture and still recover virus. That suggests there has to be a fair amount per cc of blood -- per cc of plasma, for example. And we didn't have to use too many cells from the patient to turn a culture positive. That implied there has to be a fair amount of virus per million cells from the blood, for example. We had questioned our initial findings because the notion from the mid '80s on was that we were dealing with an infection that was largely quiescent. And perhaps that impression was due to the fact that patients could be infected with HIV and be clinically latent for a while; that is, they don't have symptoms for periods of years and sometimes 10 years. And so that began to create a notion that this virus wasn't doing very much for a while. And our findings during the late '80s suggested that wasn't the case and, in fact, we're looking -- even though the patient may be asymptomatic, feeling great, and even when CD4 cell count could be reasonably high, there was a fair amount of virus. And I would still view the technologies that we used in 1988, '89 to be rather crude, but we were still picking up a fair amount of virus. So that began to -- for me -- to paint a different picture. Even in some of the early cases of HIV infection, we were finding a reasonable amount of virus, and that began to suggest maybe this virus is more active than we had previously thought. And so our research direction was altered quite a bit by those initial findings. And subsequently we've been pursuing these viral measurement studies in a very serious way. And so I would say we continued that research effort through the early '90s to show that more and more virus is associated with more and more advanced disease, and then the opportunity really came in 1994 when some of the better drugs became available and we actually had a tool to figure out how active the virus replication really is. And let me give you an analogy. We know that certain individuals have a certain amount of virus in their circulation, but if we ask, "Well, how much -- how many viral particles are produced each day?" you cannot get the information just by taking the level of the virus, because that level could be kept fairly constant because of high production and high clearance. And so you reach that equilibrium. Or very low production and very low clearance, and yet you could still maintain that same level. So you have to use something to perturb the system, and we used the new drugs that became available in 1994 to perturb this balance between the virus and the host. And by doing so, we could then throw in this drug and the virus falls. And by tracking it and in quantifying that and analyzing that, we could get at the kinetics of what's going on, and the subsequent realization after analyzing the result is that we're looking at an enormously active process. This virus is constantly churning, producing more progeny virus which go on to produce new infections. And this goes on relentlessly. So we came to this realization in mid 1994, and unbeknownst to us, another group had been pursuing the same, and that's the group of George Shaw and his colleagues at the University of Alabama, Birmingham. And they came to the same realization completely independently, and in casual conversations we actually came to know about the other's findings. And so we decided to publish our results back to back, which came out in 1995.
MS. WOODRUFF: And what implications did that have for a philosophy of treatment, then, of AIDS?
DR. HO: If one then utilized the information generated from these initial studies to understand how active the virus is, then -- and we know this virus is quite error prone when it tries to copy its genes, because this reverse transcriptase that HIV carries makes mistakes at a high frequency. So that, if you have virus replication and high frequency, then you could see that the virus is going to make a lot of mutant viruses. And some of those mutant viruses could escape from the drug one uses, from AZT for example. So the numerology here predicted that we would have a great deal of difficulty treating the virus with a single drug, and it essentially predicted the doom of mono therapy as was being administered to most patients at the time. And the numbers allow us to make certain predictions about combining drugs, cornering the virus simultaneously with multiple drugs, forcing the virus to mutate in many different positions at the same time. And that -- the numbers suggested it would be difficult -- not impossible, but more difficult -- for HIV to do so. And so that led us to the conclusion that, if we began now to treat much more aggressively with a combination of anti-HIV drugs, we should begin to see better results. And, fortunately, along with these new understandings of what's going on, came the better agents against -- to use against HIV. Drugs such as 3TC was developed as another reverse transcriptase inhibitor. And the new family of drugs that targeted a different side of the virus, and that is the protease side, were being developed, and several of them show great potency; in fact, much more potent than the prior drugs.
MS. WOODRUFF: Let's see, you brought us up to, I think, 1995, and then at that point you wanted to apply this information to real patients. What happened at that stage?
DR. HO: Well, with the new information and the advent of the new potent drugs, we wanted to test the principle for whether we could indeed control the virus well with combination therapy. So in 1995 we initiated several different programs to treat patients, some at the very early stage of HIV infection and some at later stages of HIV infection, and treated then with what we thought was the best combination therapy. So that involved two inhibitors of reverse transcriptase and an inhibitor of the protease. And by administering these, we were very happy to see that the virus indeed responded dramatically to the treatment by dropping precipitously in the first few weeks so one could measure, for example, a hundred-fold decrease in the amount of virus in the bloodstream of a person in the first few weeks, and then this continues to decrease, although much more slowly thereafter. And then it was quite common for most of the patients who could tolerate the regimen and be compliant with the regimen that the virus eventually, after eight, 10 weeks, would dip below detection. So we then went after better and better detection techniques in collaboration with some scientists in industry who are developing such assays to measure virus. We were able to show that, even with the better techniques, the amount of virus was not detectable in the bloodstream, and that is a outcome that we had not seen previously. And this was being achieved consistently in the patients. And concurrently as the virus went down, there is some immunological improvement so the CD4 T-cells typically went up by 100 or 150 cells per cubic millimeter, and this is a significant increase. And, most importantly, associated with these changes in the laboratory values, the patients felt better, and some dramatically better. We realize that this is just the first step. This is not a cure. We, basically, have, for the first time, staggered the virus, and the new optimism comes from the fact that we now realize maybe, just maybe, this virus is not as invincible as we have previously thought. So that's, in my view, the reason for the new optimism. But, as I said, at the outset, this is just a beginning of this battle, and I think we have taken the first step successfully.
MS. WOODRUFF: What was you reaction when you saw these results coming back from real, live people?
DR. HO: Pretty exciting.
There are periods where one cannot think about other things, other than these rather exciting results on patients that we see. And some of these patients we know extremely well, and it's obviously very gratifying. But it also, at the same time, posed a lot of interesting questions, scientific ones. What is going on as the virus drops off? Could we explain why it drops off in the way it does? And if we could understand why, we would get a lot more additional information. And then, why does it start to decrease much more slowly after a few weeks? And if we understand that better, would that tell us about how long we need to keep going with these type of treatments before the amount of virus would eventually decay to nothing. And so, they naturally pose to us a lot of logical extensions for us to pursue.
MS. WOODRUFF: Was there a moment or a day or an hour or something when the results were coming in when it became clear that you really had something very special here? I mean, I mean, that made you want to stay at work late at night, or that you couldn't stop -- you said you couldn't stop thinking about it when you went home. I mean, what --
DR. HO: Well, there are two periods where we were more than preoccupied with the experiment and the outcome. There's a period in 1994 when we realized that the protease inhibitors were very potent on their own, and that showed us how the virus decreased and allowed us to generate the information about the rates of virus replication, the magnitude of virus growth. And, that, as a scientific question, certainly took up most of my mental energy and those of my associates, particularly Dr. Markowitz, who was actually administering the drugs to the patients. So that was very exciting from a scientific point of view. Then, as we moved on later to the combination therapy and saw that the virus went down, but stayed down. In the past, using single drugs, we've seen the virus go down, but, typically, the virus would return after a few weeks or a few months, and that, certainly, was always very disappointing. But now we see it go down further and stay undetectable. And that, certainly, is very exciting, but we were always anxious that when would the breakthrough come, so the virus would reemerge and start to replicate again? And to this day, we're fortunate in that, as long as the patients are compliant and tolerant of the medications, the virus is controlled. And we have about 10 to 15 percent of our patients who, for one reason or another, develop side-effects of the medication and/or are noncomplying with the prescribed regimen. Then, in those subjects, we could see, clearly see, the virus coming back, as we would predict. But for those who are maintained on therapy, it is very, very gratifying, and a lot more gratifying to the patients, that the viral load would stay down.
MS. WOODRUFF: Did you ever -- do you ever allow yourself to get really excited about this?
DR. HO: I think we always look at this as a good first step or second step. But we do know our opponent pretty well here. It's beaten us again and again in the past, and the game is not over. So, being cautious scientists, we don't celebrate at this point. And this is why I'm so overwhelmed by this kind of recognition, because we haven't paused to celebrate. We are anxious about what might happen six months from now, a year from now. Would this continue? Is it possible that we could suppress it long enough so the virus and the cells that contain the virus burn itself out?
MS. WOODRUFF: What are the most important questions to be answered, because you've talked often about the questions that present themselves. What are the questions that you think most urgently need to be answered right now?
DR. HO: In these combination treatment studies, we have knocked the virus down when we're measuring the blood. So the next question is could we sustain this? And how long could we sustain this? So only time will answer that question for us. Another very logical follow-up is, well, if the virus is down in blood, is it also down in other compartments in the body, particularly in the lymphocytes in the lymphoid tissues? So lymph nodes, spleen and other tissues that contain a lot of lymphocytes. Have we controlled the virus in those places? We are doing those experiments by taking cells from either lymph nodes or other tissues that contain them --
MS. WOODRUFF: So you've come this far. What are the questions out there now that you think most urgently still need to be answered?
DR. HO: We have found that the virus is no longer detectable in the blood stream, so that another logical follow-up is, is the virus in tissues? Particularly those that contain a lot of lymphocytes. So that would be lymph nodes, spleen, liver and many other tissues. And so we are pursuing those experiments right now by taking lymph nodes, or sampling tissues that contain lymphocytes to test if we could find evidence of ongoing HIV replication or evidence of a lot of virus production in these sites. Obviously the best outcome would be that the virus is also suppressed in tissues, but those experiments are ongoing at this time.
MS. WOODRUFF: So this really is a hunt for a killer. I mean, I think most people think well, you test the blood and you know what's there. But you're saying it's not that simple.
DR. HO: It's not that simple. Testing the blood does tell us a great deal about what's going on, in that the blood equilibrates with many tissues and is a reasonable reflection of what goes on in lymphoid tissues when it comes to HIV. But we have to be much more careful that that. We have to ask questions about compartments that are hiding the virus, and compartments that are inadequately penetrated by the drugs. And so,there are a lot of logical follow-up experiments that must be done, and we're busy doing those. And, of course, we are using certain drug combinations. We could always ask whether we could use even more potent combinations. And with the development of more and more experimental drugs against HIV, we are now trying to come up with other cocktails of medications that perhaps will be even more potent than the ones that we have in progress at this time. So you can see that there are many, many unanswered questions. And then ultimately, if we find that the virus is not detectable in blood, not detectable in tissue, the ultimate experiment is to stop the medication and see if the virus would resurface. And we haven't gotten to that point yet. And so you can see that there are a lot of very interesting and, we think, important experiments to be done.
MS. WOODRUFF: Overall, what important research is yet to be done, that we can foresee at this point?
DR. HO: Well, there's a lot of work that remains. Most important, I think, is in the area of vaccine development. The therapies that we've been talking about affect only a small percentage of the infected population -- worldwide, the large community of infected individuals will not be affected by the therapies that we're talking about. And so the only effective way to contain this epidemic is to do it by preventive methods -- through education and through the development of a protective vaccine. And that area has been slow in going, in moving forward. But there's now a redoubling of effort to pursue the development of a vaccine. And we do know, from certain monkey experiments for example, with a related virus called SIV, that it is possible to achieve vaccine protection. But we need to come up with a way of doing it safely, because the vaccine will be administered to a lot of uninfected people. So it must be quite safe and must be quite effective. And so I think the global effort against HIV will be quite a bit more focussed on vaccine development, and there are a lot of fundamental questions that still need to be addressed and answered. In the past year in AIDS research, there's been tremendous boom in the area of chemokine and second receptor research, and they're linked. Long ago, Dr. Levy in San Francisco, and his colleague, showed that certain lymphocytes, called CD8 lymphocytes, in the body could release factors that suppress HIV, but the identity of these factors remained elusive until late last year when Doctor Gallo showed that three proteins, are these CD8 factors that are capable of suppressing virus replication. And that served as the foundation for subsequent work, which show that HIV, in order to enter a cell, requires two molecules: one we've known about for a long time, called CD4. But there was a second factor that was known since the mid '80s, but again remained elusive until this year, and Dr. Berger and his colleagues at the NIH showed one of the factors to be something that they call fusin (sp). And several of my colleagues here, as well as colleagues at Harvard, at Penn and elsewhere, went on to show that another factor is called CCR5. And what CCR5 is, is the receptor for those chemokines that I just mentioned. And so we now know that HIV, in order to enter the cell, requires a second receptor, and the chemokines block HIV entry by engaging the receptors so HIV can't penetrate. And so we brought two fields together. And then there was a new twist to it: colleagues here, Doctors Landau and Kalb and Paxton showed that there are some individuals who are repeatedly exposed to the virus, and yet escape infection. And a few of those individuals apparently have a genetic defect in this CCR5. So their CCR5 gene is abnormal; they don't make such a protein, and HIV is unable to find that receptor to penetrate. And they are actually, because of a defect, protected from HIV infection. So a lot of things came together in a very exciting way this past year concerning chemokines, second receptor and people who are exposed but remain uninfected. And so this is now a new area of AIDS research that is most exciting, and people are pursuing drugs that would block CCR5 so the virus cannot penetrate. And we know we could perhaps do it with some degree of impunity, because we know that molecule is not essential for the survival of the patient. So you could attack it a bit more than you would, for example, a CD4 molecule. So this is a -- this is a rather exciting turn of events.
MS. WOODRUFF: You've now been working with this fatal disease for, what, 15, 13-15 years. Do you ever get down about it, or What keeps you going?
DR. HO: Well, I think the first part was the most difficult part, the recognition of the syndrome and just sitting back with nothing that we could do to significantly impact on the disease and watching patients succumb to the infection very quickly. That was the hardest part. As we learn more, there are many scientific questions that need to be addressed, and they are a very important diversion from the clinical aspect, which remained bad for a while. But then, as better drugs became available, as better patient management became routine, we knew that we -- whatever we were doing, we were beginning to make an impact, although not dramatically. And then, of course, the more recent developments in the last couple of years have really made a lot more difference, and that's the return that begins to motivate me and my colleagues and collaborators a lot more.
MS. WOODRUFF: And yet, worldwide, millions of people have died, many more millions are or will die -- are dying or will die. Many of them will never even have a hope of having access to the kinds of combination therapies that you've been working on. So, I mean, the task is gargantuan, to put it mildly. How do you keep from being overwhelmed by that?
DR. HO: I think we could only work on one problem at a time, or a set of questions at one time. It would be impossible for one group or one institute to address all the questions out there. But hopefully the field, collectively, will cover the entire waterfront. We want to now continue our work on understanding the virus, on trying to control the virus, but we also have been doing work on the immune responses to the virus all along, and these are very relevant types of research for vaccine development, and we certainly want to make that effort grow over the coming years. It is frustrating for us to hear about what's going on in the developing countries with HIV, and it just makes our commitment to the vaccine area stronger. I mean, if I were a behavioral biologist, I would try to work on educational methods that would help prevent infection, but I'm a basic researcher, so my emphasis would logically have to focus on vaccine development. So our center, as was many groups in the field, are going to take a hard look at vaccine science.
MS. WOODRUFF: Let me ask you about some -- one aspect of the disease here in this country, and that is those people who say, well, you know, there are so many gay men who have this problem. It's their behavior, their lifestyle that has brought this upon them. They -- I mean, some have gone so far as to say, they deserve this, they are acting in a way that's unnatural. What do you say to that philosophy, that view that is out there? It's a minority, but it's out there.
DR. HO: I think that view is obviously wrong. Especially as scientists and as physicians, we're not here to make moral judgments. We're here to take care of a problem. We never say, I don't take care of patients with lung cancer because such patients are typically smokers. We don't behave that way. Why should we behave that way when it comes to HIV? So I simply think that is wrong. This is a very tragic disease, and we have to just work our hardest to find answers. I simply cannot accept that attitude.
MS. WOODRUFF: And in the course of working on this program, CNN talked to a number of people who -- patients, and among other things, they wanted to say to you how grateful they are for the work that's been done, but they want you to -- of course, they want you to keep at it. What would you say to them, to the patients out there waiting for an answer?
DR. HO: I think the field is moving very quickly in the therapy arena, not just our work, but the work of the entire scientific community, and we expect the progress to continue. We expect to be able to control the virus better and better, and hopefully, in the near future, we could begin to talk of glimmers of getting rid of this virus. But one should not think that this battle is over, but progress is being made, and particularly recently. I also should say that I'm impressed by the large number of very talented and dedicated scientists in the field all over the country, all over the world. And with these devoted and smart individuals working so hard to tackle these questions, I could only expect good results at some point. And I think many of the unfortunate infected individuals should take advantage of the therapies that are available to more effectively control HIV, and hang in there. It would be quite conceivable that a year or two down the line, we would have more than the ten drugs we have in our arsenal against HIV.
MS. WOODRUFF: But we're talking major expense, or at least -- and solid health insurance coverage, too.
DR. HO: Right. And I think these economical constraints would need to be addressed by our whole society. We have to find ways of supporting things, supporting the use of these medications. There are many other things we do that are awfully expensive -- bypass surgery, dialysis. But when indicated, these forms of treatment are administered without question, and they're equally expensive. So I think society will have -- if these therapies are shown to be very, very effective for the patients, then we have to collectively find a way to pay for them.