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Transcript of PBS Video - Ending AIDS

Foundations of Global Health

>>Is it an impossible mission? Or will their efforts pay off in the greatest medical miracle of our times? >>I can't think of a bigger biomedical research problem today than finding an AIDS . >>It's hard to know what's the most important thing we don't know. Ignorance is not bliss on this one. >>As long as the society does not value , industry will not make vaccines and there will be no trials and there will never be an AIDS vaccine.

Ending AIDS, The Search For a Vaccine. Next on PBS. Funding for this program has been provided by the Alfred P. Sloan Foundation to enhance public understanding of the role of technology in society and to portray the lives of men and women engaged in scientific and technological pursuit. Additional support was provided by the John D. And Catherine T. MacArthur Foundation.

>>In Kampala Uganda, AIDS workers are recruiting volunteers for a trial of an AIDS vaccine. The words are simple, "Imagine if there was a vaccine to prevent AIDS." But imagining a vaccine is imagining a world without AIDS. A world without 15,000 people infected each day, with tens of millions more dying. For science, the rapidly mutating AIDS virus has proven to be one of the most defiant biological enemies humanity has ever had to face. And the battle against it has been raging for a quarter of a century. >>I need the patient's name, age, sex, and weight and they underlying reason for the immunosuppression. >>The year was 1981. >>There's no underlying reason for the immunosuppression? >>A mysterious disease was spreading like wildfire in places like , , and New York. Here, men were dying from diseases like pneumonia that shouldn't have killed them. Clearly, their immune systems were not doing their job, but no one knew why. >>Mysteries are frightening. When it comes to public health, a mystery is the scariest thing in the world. If you don't know the enemy, you can't make a weapon. >>Doctors would name the mysterious disease Acquired Immune Deficiency Syndrome, AIDS. >>Doctors say the epidemic which first surfaced here in New York is now more lethal than Legionaire's disease or toxic shock syndrome. Experts emphasize the number of victims have doubled 2 every six months since 1978 when the first case -- >>A mysterious new disease is -- >>There were as many theories as there are people in the early days about what caused AIDS. >>There was worry that mosquitos could have caused the disease. That a fungus could have caused it. That a bacteria could have caused it. >>All over the states the search is on for some organism that could transmit a -- >>Everyone came out of the woodworks with a theory. >>Fungal spores take the green stain -- here, they're looking at diseased lymph nodes. >>Improving cognation's just a tough thing to do. It's really hard to prove that something causes something else. >>There has been a new and important discovery in the search for the cause of AIDS. Scientists think they have identified a virus. >>At the in Paris researchers had discovered a virus now known as HIV. And in the , scientists of the National Cancer Institute had proven that this was the virus that caused AIDS. The discovery was the gunshot that launched the race for an AIDS vaccine. >>In this country, the Federal government is predicting that a vaccine against AIDS may be developed within three years. >>We hope to have such a vaccine ready for testing in approximately two years. >>We're probably two years before we could begin clinical testing on a vaccine. >>Do you think the two-year guess is a realistic one? I've heard a lot of people say that -- >>The mysterious virus was a killer. >>The progress that's been made so far is good cause for optimism. Although I -- >>And the government rushed to reassure the public that a vaccine was on the horizon. >>Once the virus was identified, there was an understandable but misplaced euphoria that, "Ah, now that we have the virus at hand, a vaccine is around the corner." >>As the biotechnology leader, our immunology researchers investigate components of the immune -- >>The fledgling Biotech Industry had just had a startling success, a success that fuel the optimism surrounding the search for an AIDS vaccine. >>Is one of the few companies that pursues the discovery of vaccines. >>The Biotech startup, Chiron, had used genetic engineering to build an effective vaccine against another lethal virus, . >>The Hepatitis B vaccine had just come out with a genetically engineered version that was really clever. All it did was it 3 took a piece of the virus from its surface and made that the vaccine. Threw it into people, they made the Hepatitis antibody, no Hepatitis B. It worked beautifully. >>The influence that Hepatitis B had on HIV was immense. Now, with recombinant technology, we can say well, this is the virus. I want to make these pieces of it. You just cut out the genetic material then you manufacture those pieces. And if they're perfect imitations of nature, they should stimulate an immune response. >>The genetic engineering techniques that made possible a vaccine for Hepatitis B seemed capable of solving medical problems that had plagued mankind for ages. Biotech companies, including Chiron's Bay Area rival, Genentech, plunged into the AIDS vaccine race. >>I was probably as naive as everyone else at that time that once you have a virus, you should be able to make a vaccine. >>But Don Francis had another reason to be optimistic. He had been a government epidemiologist with the CDC, the Centers for Disease Control. In the 1970s he had battled one of the deadliest bugs known to man, the smallpox virus. >>The CDC chases epidemics all around the world. >>He headed up the CDC's smallpox eradication campaign in , India, and . >>I have got to see the real affect of a vaccine. There, it's a horrible scourge that infects mostly kids with a God-awful disease and kills 30, 40 percent of those that it infects. And, literally, you go in and vaccinate everyone around that individual and a month later there's no more disease. And you go on to the next outbreak and the next country and the next state and, ultimately, you can just drive the disease into the ground. >>In country after country, Francis watched the smallpox vaccine wipe the disease off the face of the earth. >>We know that vaccines can do unbelievable, unbelievable things to human health. Nothing changes human health more dramatically than vaccinating a population. >>But finding a way to apply the lessons of smallpox and Hepatitis B to this new epidemic was becoming increasingly difficult. Public spending on AIDS research was now a major front in the culture wars. >>Too much emphasis has been put on finding a cure and not enough on preventing the spread of the disease from the gay community to heterosexual. >>They actually go and -- and involve themselves in the most base of -- of perverted activities. >>Mr. Farwell says AIDS is God's way of spanking of us. >>Everything went down to the dollar level. There was no new money. >>The folks in Washington just did not want to hear that more resources were needed. This was primarily a gay disease in the United States or heterosexual disease in Africa, neither one of 4 which they cared about. They could let those populations die as far as I could tell. >>But the virus had contaminated the nation's blood supply. And in 1985, America would meet the new face of AIDS. Brian White, a teenage hemophiliac would become infected through tainted blood. >>People would get up and leave so they will not have to sit near me. Even at church people will not shake my hand. >>The AIDS crisis could no longer be labeled a gay plague. >>Scientists from around the world are getting together in Paris this week to talk about the war against AIDS. >>The 2,000 AIDS experts meeting here tomorrow arrive with stacks of reports and new information on the alarming spread of the disease. The latest figures -- >>At the 1986 International AIDS Conference, the rapid spread of the unchecked viral epidemic became perfectly clear. >>The Director General of the World Health Organization announced that as many as 100,000 people in 92 countries have AIDS, and that that five to ten million more are infected by and capable of transmitting the virus. >>But in the hallways outside the auditorium reporters were buzzing with excitement around two scientists from Genentech. >>Genentech has developed a prototype AIDS vaccine. >>At the AIDS conference in Paris today, two groups announced successful experiments with genetically engineered products. >>It's the very first stab towards a potential vaccine. >>Genentech researchers -- >>The researchers had made critical headway with a feature on the surface of the virus. A protein called gp120. Using the same approach that works with Hepatitis B, they genetically engineered a prototype vaccine from this surface protein. >>Genentech says we've made this protein from HIV and put it into animals and we got antibodies that in a test tube they work against the virus. >>In lab experiments, the gp120 protein had successfully induced the production of HIV antibodies. >>Antibodies are really simple. Everybody understands the basic concept. You've got a bug, it comes into your body. An antibody can jump on it and stop it from infecting a cell. >>Genentech says we've kicked open a door here. A little bit of hard work, we can put this into humans and get the same thing and it'll work and we can all go home and goodbye AIDS. >>The Food and Drug Administration has announced approval for the first testing on humans of an experimental AIDS vaccine that could be -- >>The race for a genetically engineered vaccine was heating up. >>-- an immune response in someone, which means when we inject the material -- >>One year after the Genentech news, Anthony Fauci of the 5

National Institutes Health went on National Television and announced that researchers at another biotech company, Microgenesis, would be allowed to test the safety of a recombinant AIDS vaccine by injecting it directly into human subjects. >>Because once we show it's safe and induces an immune response, the next stage which is stage two -- >>But for those most affected by HIV/AIDS, a small safety trial of a vaccine was not enough. Drugs for those already infected by the virus were under-funded, and in the eyes of activists, a much higher priority. >>We die! They do nothing! We die! They do nothing! >>The gay community did not organize itself around the vaccine search. What they did with the drug search was revolutionary and they changed the pharmaceutical industry. They shut down the National Institutes of Health. They shut down the Food and Drug Administration with their demonstrations. All about get us better drugs, but never once about move faster, do more to make a vaccine. >>You never had that powerful voice that you saw for therapeutics or even some behavioral preventions for a vaccine. >>One of my best friends who's HIV positive said, "I don't want to see an AIDS vaccine." And I said, "Why"? And he said, "I don't mean I don't want to see an AIDS vaccine. I mean I'm scared. I'm scared if there's an AIDS vaccine, what does that mean for me? What does that mean in terms of drugs? Are they going to still -- are they going to still work on trying to get drugs for people who need them, or are they just going to forget about us"? >>By 1991, 10 years after the first reported case of AIDS, the disease had exploded into a massive pandemic. Globally, millions were dying. The first treatment drugs were only slowly beginning to appear on the market, tied up in red tape at the FDA. In Africa, the situation was spiraling out of control. Hospitals crammed with victims and no treatment available. Infection rates had soared off the charts. Ten thousand people a day were falling ill. Each case a death sentence. >>AIDS is a family disease. It's not a disease of homosexuals. It's not a disease of heterosexuals. It's a family disease. Kids with no parents. Kids losing their siblings. And the burden that it puts on the grandparents when they die they're orphans and the societal impact that that has. And that -- (sigh) -- that hit home to me. >>As Deputy Director for AIDS at the NIH, Margaret Johnston was in a position to have an impact on government policy. >>I kind of got the vaccine bug in a big way, and I -- I kind of realized that if we were going to actually stop this epidemic, not just treat people, not just give them long productive lives, but actually stop the epidemic, that really the best way to do that was going to be finding a safe and 6 effective vaccine. >>Well, who makes vaccines? Well, it isn't the government. I was a career government person, but the government just didn't do it. The only places it really was done is industry. They had the power. They had the knowledge. They -- they knew what to do. >>As government scientists, Margaret Johnston and Don Francis both believe the public and private sectors had to work together. But while Johnston would stay inside the government urging the NIH to partner on vaccine development with biotech companies, Don Francis would quit his government job and join them. >>I was going to work in vaccines for HIV and the hottest place to make an HIV vaccine was at Genentech. >>At Genentech, the gp120 vaccine had proven safe in early human trials, but it would soon become apparent that when it comes to making an AIDS vaccine, nothing would be easy. >>The Genentech vaccine is in humans, and they are preparing for a massive real world test. Their vaccines look safe and they're stimulating antibodies and these antibodies are working in the test tube against HIV. >>We had come to the end of the high-tech recombinant technology hotshot laboratory work that we could do and all the data looked very good. >>For Genentech and its chief competitor, Chiron, the finish line was in sight. >>The first ever large scale trials to test for efficacy seemed like a possibility, but in 1993, experiments were conducted that would raise serious questions about both company's gp120 vaccines. >>And lo' and behold, we got an answer no one expected that we'd get. >>The researchers take blood from people who have received the vaccine, and when they mixed those antibodies with HIV that they grew up in the laboratory, just like 1986, works great. Terrific. But then when they take a real strain of the virus that's never been grown in the laboratory, they just pull it out of somebody who's infected, mix it with those antibodies, nothing. Zilch. >>The serum didn't neutralize any of these viruses. Any of these recently isolated viruses in fresh cells. >>Everything we learned was not good for the vaccine. There was absolutely no evidence of selection pressure, there was anything meaningful, that it was antibody responses introduced to the vaccine did nothing against the virus. >>So we sat scratching our heads, what does this mean? Is it that the antibodies aren't any good? They don't do anything? Or is there something peculiar about this assay that doesn't reflect what happens in people? >>Some people said don't do these trials. This doesn't make sense. But another group of people said was those are test tube 7 experiments, we're not going to know whether this works until it goes into humans and in a real world setting. >>So how do you resolve that? The shakiness of the science, the commitment that was given years ago with the reality of where we are right now? >>The big decision needed to be made to move this vaccine to phase three studies. >>And on June 17th that decision would be made. The fate of the gp120 vaccines would be decided at a meeting of the NIH's AIDS research advisory committee. >>It looked like a normal meeting except for the fact that there was elevated tiers in the back for the press and the cameras. >>My sense of it going in that day was it was a hell of a wild ride. I didn't know where it was going to end up. >>You are here today on a most important task. >>I characterized the mood as similar to what one would see in a courtroom, you know, where the verdict is going to be expected to come down and there's testimony given and arguments for and against. >>We at Genentech think we've developed a vaccine like -- >>When we presented at the meeting, we made arguments that it's safe, that everyone who receives the vaccine gets a strong immune response and that that immune response was the same as the Chimpanzees that were protected. >>We've had tremendous increase in our knowledge base through basic research. >>Now, there was a lot of questions. Is it effective? Will it work? We don't know, but that's why you do the experiment. >>If we could get the -- the modified phase one, it would cost us -- >>I've never been to an advisory committee like that in my life. The advisory committee had a chance to speak and ask questions and talk about the issues in public. >>It was like watching a finals basketball game, you know. It's up! It's down! One team's one point ahead, then the other team's two point ahead, you know. And it just went back and forth. >>But it was not a game. The outcome of the discussion would be a matter of life and death for the gp120 vaccine. If the government would not be a partner in the expensive phase three trial, the companies might scuttle their AIDS vaccine programs. >>There was considerable concern that companies would bow out. That if they couldn't get the U.S. government support to take their products through to an efficacy stage, that the U.S. government wasn't then a trustworthy partner. >>Dealing with -- with the cost of this vaccine trial that we're purposing is trivial -- >>As the day wore on, the mood grew darker. >>I thought we could turn it around because it was a naive 8 group of people who couldn't really make a decision. And it was Tony Fauci who made the decision. >>The meeting adjourned and people started leaving and he went directly to the press -- >>Here's Dr. Fauci. >>-- and said, "I've decided" you know "That we are not going to support another trial, a large trial of this candidate in the United States." >>It wasn't an easy decision. I decided not to go ahead, but I didn't do that necessarily with total confidence because I didn't know definitively that it would fail, but I nonetheless decided not to go ahead with it because the weight of the evidence; namely, the lack of even the rudimentary type of responses that you needed weighed to push it on the side of deciding not to go. >>After spending 50 million dollars on a gp120 vaccine that the NIH would no longer support, Genentech abandoned AIDS vaccine research. The apparent impotence of gp120 against HIV made one thing perfectly clear, the virus was a more impressive enemy than anyone had predicted. >>Its target, diabolically, is the very immune system that you need to fight against viruses. Polio comes in, attacks cells of the nervous system. The immune system is perfectly intact to come in and suppress polio. Not so with HIV. It can come in and destroy very early on the exact soldiers of the immune system that the body utilizes to protect itself against viruses. >>It comes in and there's a sugar cloud around the surface protein, hiding pieces of it, so that the immune system can't even see it. In addition, it can mutate and change and invade the immune system. That mutation may not have any relevance, it may just be a mutation that has nothing to do with function, but when you mutate enough, every once in a while you change enough to evade the body's immune system. >>Antibodies are very specific. They only work against a protein that looks exactly like the one that they're made from. Well, some HIV's might have a protein that look like this, some might look like this, some might look like that. It's all the same protein. But it's just a little bit different. And those little nuances will make that antibody worthless. So on multiple different levels, this is a very defiant virus. >>People really go back to the drawing boards and really start asking the hard questions. Okay. If this simple antibody idea is not going to work, what are we going to do? What's next? >>The world is waiting for a breakthrough, a vaccine against AIDS. It's not here yet, but tonight, tonight there is a major development, what is being called a scientific landmark in AIDS research. And a Harvard scientist who described this research -- >>In 1992, the national media had focused its lenses on a researcher at Harvard's Medical School, Dr. Ron Desrosiers. >>Today in a Scientific Journal, we describe the -- 9

>>Desrosiers had stunned the scientific community by successfully vaccinating research monkeys. >>-- the vaccine approach that we've used in monkeys? It's protected them against infection and against disease, against the AIDS positive virus. We had an outbreak of disease in our monkey colony here at Harvard Medical School in the late 1970s. The first report of AIDS in humans appeared in the "New England Journal of Medicine" in 1981. And I remember our director, Ron Hunt, at the time walking around the hall carrying the journal article saying, "Look it, this looks like what our monkeys have." >>Like AIDS, it turned out to be a disease caused by a virus, a virus that would become known as SIV, Simian Immunodeficiency Virus. >>When we discovered this monkey virus in 1984 and found that it was closely related to the human virus, we knew we were on to something important. We began to think, okay, what can we use this for? Or what is this important for? And it became clear to us right from the beginning that there were really important uses of this monkey equivalent of the human AIDS virus. >>Desrosiers decided that the monkey virus provided an opportunity to try something too risky to test in humans. Rather than isolating a small part of the virus to use as a vaccine, he would use a live but crippled version of the virus itself as the vaccine. >>It is an adage among immunologists that the best induction of immunity is infection with the microbe itself. >>But HIV's so nasty that you don't want a weakened version of HIV in your body because who can trust it? It might cause AIDS down the road. It might cause cancer because of the weird way it inserts itself in the human chromosomes. There are all these theoretical problems with it that are very serious. >>It being the early 1990s, we had better tools available to us and so the approach that we took was to delete genes. >>Using genetic engineering to remove genes from the virus, Desrosiers hoped he could keep the virus alive but make it safe. >>To make it weaker, he's pulled out genes. So imagine taking a human and cutting off the arms and legs? It's still a human, but it can't hit you. >>In 1992, monkeys were given Desrosiers' vaccine and then hit with a blast of full strength SIV. The results were remarkable. The vaccine protected the monkeys. >>The importance of the results grew on me in that no, this -- this really works! The other approaches we tried didn't work. This approach works great. >>After Desrosiers' study comes out, there are humans who say let's put this into humans. There are physicians who gathered together and say we are willing to test this in our bodies. There are people who come up with all sorts of schemes to safely, quote, unquote, test it. 10

>>AIDS researchers who have volunteered to become human guinea pigs, they injected a live virus vaccine could begin soon. They say the vaccine has already shown positive results in tests on monkeys. >>In the fall of 1997, the controversy over a live virus AIDS vaccine would be brought to a head. >>It is time to go to human trials. There are going to be risks and there may some causalities. >>Whether people are going to be safe with -- >>On September 26th, Dr. Charles Farthing announced that he was recruiting volunteers to be injected with a human version of Desrosiers live attenuated monkey vaccine. >>But there's controversy over the long-term effects of the vaccine which at this point are unknown. >>Giving it to a handful or more people now is not going to address that long-range safety issue. There needs to be the design of experiments in animals and other models to be able to get as much knowledge as we can about that safety issue. >>Sometimes it happens in a scientist's life that what you project, what you think, what you postulate, is not what turns out in actual results. >>In Boston at the Dana-Farber Cancer Institute, Dr. Ruth Ruprecht shared Desrosiers initial excitement and decided to build on his experiment. >>She does experiments where she takes the vaccine virus that Desrosiers has shown worked so well and puts it into newborn monkeys. >>What we saw when we just gave the vaccine strain with these three deletions to newborn Rhesus monkeys, was that those animals progressed to AIDS. We never challenged them with -- you know, the full length virus. We just gave them the vaccine strain and nothing but the vaccine strain. And yet, they progressed to AIDS. >>An infant immune system is much different than an adult immune system. It's not as developed. It can't handle it. The virus gets the upper hand. >>Death in a vaccine study is a pretty serious side effect, and I basically felt that since all of the newborn Rhesus monkeys progressed to AIDS, not some of them but all of them, that this should be taken very seriously. In order for a vaccine to be acceptable, it has to be safe and it has to be efficacious. >>Ruprecht's test results would prove a death mill for Farthing's vaccine trial. >>He was probably ahead of his time. He probably needed to wait 20 years and step -- step to the fore. I think we probably need to go though 3, 4, 5, 6 more phase three efficacy failures before anyone's willing to put live attenuated on table as an -- an option to consider. >>So much attention went toward that idea of these human 11 experiments that I think the field as a whole took its eyes off the ball, which was answering the question of why did the vaccine work in monkeys? >>The live weakened vaccine to this day is one of the best examples of the immune system learning to defeat the virus. This might hold the secret. It's proof or principal. Scientists can make a vaccine that can beat this bug. >>For scientists in search of a path to an effective AIDS vaccine, Desrosiers' success with monkeys was a light in the darkness. But in an unlikely place, scientists were making a startling discovery about the human body's own capacity to resist the defiant virus. In Marjanka, a crowded slum of Nairobi Kenya, public health researchers were working at a clinic frequented by local prostitutes. >>That clinic was set up in 1986 mainly to look at sexually transmitted diseases because they were a lot at that time and, naturally, we were encouraging women who practice commercial sex to actually come to the clinic. >>Anybody can afford to come and have sex in this slum area. When business is bad, the commercial sex worker might take 75 cents from a client if she's been out the whole day and has not had anybody, she might be forced to now have sex without condoms. >>We have seen a lot of sexually transmitted diseases. So what we really wanted to understand is that is HIV also in the sex workers that we were looking at. If you're getting exposed to other sexually transmitted diseases, chances are they're also getting exposed to HIV. >>Almost 20 years ago as a young woman with little means of support Howa Chandahot began making her living as a prostitute. She was one of Dr. Anzala's first patients at the Marjanka clinic. >>Howa's been coming to the clinic since 1985. She's been treated for gonorrhea. I do not remember how many times, but her case I remember once, and she had -- there's a time she had a boyfriend that she has had kids with who died of HIV. >>In 1987 the clinic tested her for HIV for the first time. [Speaking foreign language]. >>To her great relief, Chandahot tested negative. [Speaking foreign language]. >>But Howa Chandahot was not alone. Despite impossible odds, she and dozens of other commercial sex workers in Marjanka would continue to test negative for HIV. >>These women had special immune systems that were doing something right. That somehow it figured out a way to keep the virus at bay. >>The scientific community world wide did not believe us. All right? And I remember, I think, it was an AIDS/HIV conference in Berlin, you know, everybody thought that we had mixed up samples. We were not doing the right thing. Because I think the 12 initial belief was that if you get exposed, you get infected. Then they also observed the same phenomena among gay men in the United States, that's where now people believed, uh-uh, this phenomena is -- is there and it's -- it's a fact. >>In a field filled with disappointment, in a field filled with let-down after let-down, clues like this are what make people get up excited the next day. >>So the only natural process now is to try and understand is there a mechanism, and if there is, what is the mechanism. >>If researchers could figure out the mechanism that was protecting women like Chandahot from HIV, it might unlock the secret to a vaccine. >>There are maybe two or three hypotheses. One, that maybe the women are just lucky. The people they have sex with might have gonorrhea or syphilis but not HIV which we discounted. For sex workers in Marjanka who see seven clients on average per day and remain HIV negative for a period of three years, I don't think that there's any mathematical model that could fit to show that they were lucky. >>The next thought was that the women had genetic protection. To test the theory Anzala removed cells from their bodies and exposed them to HIV, but he found that they were not protected. >>If you took the cells from these women and exposed them to HIV, the cells can be infected outside of the body so that we are only left with one thing, the are actually mounting an immune response. >>In order to learn from these women and develop a vaccine, scientists would have to study exactly how they were dodging the virus. To find the answer, they began analyzing the women's blood. A Kenyan team collaborated with a group of researchers at Oxford University in England who had observed the same unexpected phenomenon in Gambian sex workers. >>Scientists have made a major breakthrough in the search for an AIDS vaccine. >>At Oxford, Sarah Rowland-Jones unlocked the mystery hidden in the blood of the African women. >>A group of African prostitutes has produced evidence that the body can fight HIV on its own. >>I will add in my sensitive message, we can't find a virus in them now, so we believe they may actually have staved the virus. >>The collaboration between the team at Oxford and Anzala's lab in Nairobi had netted surprising results. >>There's something unique about the women. They're actually mounting an immune response and that immune response is not antibodies as it is cellular. >>What researchers found were cells called killer T-cells. While antibodies prevent invaders from infecting cells, a killer cell response destroys cells once they're infected clearing the virus from the body. >>The implication is that if our -- our guess is right and 13 that it's the T-cell immunity that has protected these women, then this is the kind of immunity that we should be trying to make with a vaccine. So I think it changes the direction of vaccine research toward the T-cell vaccine away from the previous vaccine strategies which has not been so far very successful. >>But what was unknown was how to create a vaccine that would elicit killer cell response? >>All of the conventional vaccines that have been designed have actually been designed with the aim of using antibodies. The challenge was now to figure out how do we actually design this vaccine. >>The killer cells recognize pieces of the HIV virus. So what they did was they characterized from these small number of women all of the pieces of HIV that their cells recognized. >>They're selecting the very small little pieces of information from HIV that they think the body needs to learn how to defend itself against the virus. >>They said okay. This person has these killer cells that recognizes this piece or pieces and they're not infected. This person recognizes this piece or pieces and they're not infected. So let's make a vaccine and put all those pieces together and see if we can induce in people the same types of killer T-cells that these women had. >>Anzala and the team in Kenya believe that they now had a working hypothesis that could lead to a vaccine, a vaccine that might one day relieve Africa of the terrible burden of AIDS. >>I think Europe and North America because of the fact that people have access and we provide our drugs, less and less people are seeing HIV as a prolem in North American and Europe. I don't think that that is ever going to be true for Africa. Africa is a continent that is most affected and we cannot sit back and wait for somebody else somewhere else will actually do this work for us. We have to be able to do it here in Africa. >>Those countries in the developing world are the ones that are most affected by HIV. They're the ones that need the vaccine the most. The challenge is to make them full partners in the development of the vaccine. If they are part of the solution, if they're part of the clinical trials, they will also then be in a position to get those vaccines as soon as they're proven efficacious as soon as possible. >>But in countries where money can't even be found for treatment drugs, finding money to run trials of an uncertain vaccine candidate is difficult. >>Industry doesn't exist as a philanthropy, why would industry devote enormous resources to this sub-Saharan Africa? There's a great market. That's how pharmaceuticals look at it. Pharmaceuticals don't want sub-Saharan Africa as a market. They want the United States, Europe, Australia, Japan. They want people with deep pockets. 14

>>The vaccine effort, especially for the developing world was going to be non-existent. >>It is an embarrassment, the lack of effort that's gone into vaccine development for HIV. You can't expect industry to do it, you have to find another model. >>Here. Here is where the gap is. Is there a need for new organization? And if so what that -- what is that -- might that new organization be? >>The vision of what this was going to be was very clear. The biggest problem was the skepticism that a small NGO could make a difference, could really try to change the way things were done. >>We wanted to have a new organization that would really help fill that gap in taking ideas and turning them into products and get them into human trial. >>But despite the skepticism, the institution they had imagined became a reality. The AIDS vaccine effort had a new champion, the International AIDS Vaccine Initiative, IAVI was created. One of IAVI's first beneficiaries was the Kenya AIDS vaccine initiative at the University of Nairobi. On June 3rd, 2001, 9 years after the Kenya team first noticed the unexplained resistance to HIV in the Nairobi prostitutes, Dr. Pamela Mandala became the first volunteer in Africa to receive the vaccine derived from that discovery. The phase one study proved that the vaccine was safe. >>So we know that this vaccine cannot cause what? AIDS, all right? So for some of you, we like you to come forward -- >>With continued support from IAVI, Dr. Anzala began recruiting volunteers for the next phase of testing to see if and how their immune systems would respond to the vaccine. But finding out if any such immune response would actually protect the body against the virus would require something bigger, a final third phase of testing with thousands of volunteers costing millions more. Despite the fact that many questions surrounding the Nairobi vaccine remain unanswered, IAVI and its partners in neighboring Uganda are already laying the groundwork for such a trial. >>If we do not have a well-prepared population that will accept the HIV vaccines, it will be very difficult to conduct the study. >>In January 2004, Sissy Kericho and the team from Marjanka began taking down medical histories of the nearly 10,000 employees of the Kakira Sugar Plantation on the shores of Lake Victoria. >>Kakira Sugar Works is one of the largest employers in the country. I think the vaccine trial is something that I think everybody would love -- love to see. I think it's just very important for Uganda and Africa and the whole world. >>And so they wait here for a promising vaccine candidate to be ready for a massive trial. The one researcher was convinced he had a vaccine candidate that was ready. In 1994, despite 15 serious doubts from the rest of the scientific community, Don Francis was convinced that Genentech's gp120 vaccine was ready for a massive trial. >>If there's no product to try, there will be no vaccine trials even though there's lots of people willing to do trials, and there will never be an AIDS vaccine. >>I remember stating it, you know, look these vaccines would not work. Don Francis responded by saying he -- did I expect him to -- to leave the vaccine in the freezer for the next several years? Basically responded no, I think it's time to turn the freezer off. I think it's time to give up on this approach and to move on to something that would be more likely work. >>You don't say I don't think it's going to work therefore I'm not going to do the experiment. You wouldn't do that in the laboratory in the test tube. So it's really no different when you get out to efficacy trials except that they cost more money. >>But with the NIH's refusal to fund those trials in 1994, Don Francis was now on his own. To help raise the money, Francis turned to Biotech finance wizard, Robert Nowinski. >>The way I talk to investors is I point out how many people are at risk, even in the most modest means, what does this mean financially if we were to develop a vaccine? And when you look at the size of the market, it's absolutely enormous. >>Together the team of Francis and Nowinski raised $89 million and licensed the gp120 vaccine owned by Genentech. Phillip Berman who had helped develop it came on board too. They called their company Vaxgen. For the company's founders, for its investors and for an anxious world awaiting good news on AIDS, success or failure would only be decided through the first ever phase three trial of an AIDS vaccine. But it would mean recruiting over 5,000 volunteers in North America and Europe, something which had never been done for an AIDS vaccine. >>A San Francisco based company believes it has a potential vaccine for AIDS and is looking for volunteers for an efficacy trial to start later this year. The volunteers are lining up. >>Wow, to me -- I mean the more that I think about it, the -- the more exciting it is to be a part of this. I'm -- I'm grateful to have the opportunity. >>It was an experiment that began with great fanfare. The goal of vaccine to protect against infection with the virus that causes AIDS. >>On June 24th, 1998, Vaxgen began a massive phase 3 test, the same test that the NIH had refused to fund four years earlier. >>You take 5,000 people, ask them to volunteer for a trial. Bring them in to a trial. Have them give informed consent so they understand what it is. Have their blood taken. Inject them with vaccine. Have them come back every 5 and-a-half months to have blood taken again and that's a very complicated endeavor. >>The worse case scenario would be to arrive at the end of a study like this and say we don't know what the results mean. 16

That's not what happened. They arrived at the end and the results couldn't have been more clear. >>Years and years ago in 1994, I made the decision that we should not go ahead. Others differed. The company differed with that so they went ahead. It proved that in fact it didn't work. I'm sorry that it didn't work. I would have liked to have been wrong on that, but it didn't work. >>Vaxgen's failure to demonstrate that gp120 could protect people from HIV, revealed a widening rift in the AIDS community. >>If we continue to -- to fail so publically, eventually my fear is that the public, the taxpayer, the press, will simply say we've heard that before, let's -- let's pull the plug and that will be a catastrophe. So I think sometimes when -- when failure is -- is very predictable, it may be best not to stick the head in the oven. >>In January 2004, "Science Magazine" published an open letter from some of the top names in AIDS vaccine research including John Moore and Ron Desrosiers. The letter argued that the push for phrase three efficacy trials had come too soon before enough was know about HIV to develop realistic vaccine candidates. With limited resources the scientists said, the U.S. government should not be supporting expensive phase three trials until more of the fundamental questions have been answered. >>We don't know what the body is doing or why it's doing something wrong. We need to find that out. >>What are the immune responses that lead to protection, what are they? Is it a special antibody? Is it a special killer cell? Is a combination of killer cells and antibodies? Is it a primitive innate immune system? Is it a combination of the primitive innate immune system with antibodies and killer cells? Who knows. >>You cannot over-emphasize the impact of that gap in our knowledge and to get the answer or to fill in that gap is not very easy because this is such an extraordinarily, illusive and different virus than what we've been dealing with before. >>The flip side of that equation is do you have to know the answer to make a working vaccine? No. You don't. You can prove that a vaccine works with no understanding whatsoever of why it worked. Edward Jenner in the late 1700s made the smallpox vaccine that eradicated smallpox virus form the earth with no knowledge of viruses, no knowledge of an immune system. He didn't need to know anything. >>We will never understand totally why a vaccine works and why it doesn't. I'd love it if we did. >>Now, I've given the talk of the difficulties of not knowing all these things. I've had the same slides myself. But does that mean you don't progress onwards? Of course you have to continue to put money into the basic science. But you also have to test the products as you move forward. Unless you actually put the effort together and take the social commitment to take risks, 17 spend the money, then you're not going to have an AIDS vaccine. Our phase three trials were the first time anyone's ever done an AIDS vaccine trial and so it was unknown territory then. It's not now. >>That trial is not quote, a failure, because it's helped to push the agenda forward. >>There's no failing here. It is just adding on to the knowledge which will eventually add up to that vaccine. For us, failure is not an option. That word is a no-no. If you begin to have that thought that we nay-say, then chances are if we nay-say, then why do it? >>In August 2004 Dr. Anzala learned that the preliminary results of the Kenya trial were extremely discouraging. In the absence of more promising data, IVAI does not intend to develop this vaccine any further. But for Omu Anzala, the question of whether or not to push on is not an academic argument. It's much more personal. >>My brother was infected. I was still in Canada completing my Ph.D. work, but he never let anybody know. Eventually, he told me what was happening. Then to me the big question was why didn't you phone me? Why didn't you write a letter to me and tell me what was going on. And his response was that "Oh, we didn't want to disturb you, you were busy studying. Eventually within six months of my coming home he passed away. That added to my thoughts that we must do something, and maybe the only thing that we could do to alleviate this problem is to do more research and more so research that will lead to the discovery of a vaccine. >>Today more than 80 trials have been conducted of some 30 different vaccine candidates yet an effective HIV/AIDS vaccine continues to remain illusive. Unchecked by a vaccine, the HIV/AIDS pandemic is rapidly spreading in India, China and the former Soviet Union where within a decade another 50 million lives could fall to the viruses' unrelenting advance. >>I can't think of a bigger biomedical research problem today than finding an AIDS vaccine or one that's more important or one that will have bigger impact on the world when we are successful. >>In the face of adversity there is hope. Scientists are reorganizing their efforts. A coordinated International Enterprise promises to pour millions of new dollars into research and development targeting some of the most vexing questions in the field. How did Desrosiers' vaccine protect monkeys from infection? Why is that some Nairobi sex workers remain uninfected? Can recent insights about HIV lead to the holy grail an effective antibody, or will combining different vaccines turn on parts of the immune system yet unknown? >>It might not happen in the next two years, it might not happen in the next five years, but it will happen. >>I liken it to the workers that used to go to cathedrals in 18 the old days. Building a cathedral was a task that took generations. What was honored about the profession was you could contribute to a piece of that cathedral and build a piece and you knew that it wasn't going to be finished in your lifetime or even your children's lifetime, but just knowing that you were contributing to something magnificent and great that was going to have an impact on the world and stand as a success of mankind's efforts, that's what I feel like. I feel like we're making a piece of the cathedral and yeah, I might not see the end of it, and I can't tell the kids of today that if you go into this profession, you'll see the end of it. All I can say is if you make a contribution and everybody will make a contribution in their -- their own little way in some way, you will have contributed to one of the biggest things that's ever been accomplished in biomedical research. And for me, I couldn't think of a better way to spend my life.

"Ending AIDS The Search For a Vaccine" is available on DVD. The companion book to the program is also available. To order, call PBS Home video at 1-800-playpbs.

(Transcription by www.HRICART.com) 19