The Hunt for the AIDS vaccine - transcript

NARRATOR (AMANDA BURTON): Take six scientists who have spent nearly twenty years, for most their entire working lives trying to design a vaccine to stop the most deadly disease known to man.

DR RON DESROSIERS (Harvard Medical School): The virus is impervious to almost everything you throw at it, throw at it, (echo).

NARRATOR: They are fighting a bug that makes ten billion copies of itself everyday, each one of them a little different. But destroys the very cells the body uses to protect itself.

DR RON DESROSIERS: It’s like the virus is there laughing at you, laughing at you, (echo).

NARRATOR: This is a virus that is transmitted by sex. This is in effect the perfect killing machine. And every day these scientists lose this battle and fail to find a vaccine another eight thousand people will die from Aids.

DR DON FRANCIS (GENENTECH 1993-1995): This is the Castro district of San Francisco, clearly the major dynamic neighbourhood of the gay community.

NARRATOR: Twenty years ago, the Castro was a gleeful celebration of gay pride and sexual freedom. Until an unknown disease started to rip the community apart. A handful of deaths turned in to hundreds, at an astonishing rate. Don Francis was a government scientist who rang the warning bells loudest.

DR DON FRANCIS: Looking back the Castro lost about close to half its population because of HIV, so the population you see now is kind of either old or young and nothing between. But there was a time when you just see these walking skeletons going up and down the street. I never want to see another person die of Aids in my life, it’s er, it’s just God-awful.

NARRATOR: Back in the early nineteen eighties no one knew anything about this new disease. But everyone realised they had to come up with the solution to stop the growing devastation. The first break came twenty years ago when the eminent scientist Robert Gallo made his mark in history.

VIDEO OF PRESS CONFERENCE 20 YEARS PREVIOUSLY: And I’d like to ask Dr Gallo to come forward to make a brief statement.

NARRATOR: In May 1984 the United States Health Secretary announced at this press conference that Gallo had identified a virus as the probable cause of Aids.

VIDEO OF PRESS CONFERENCE 20 YEARS PREVIOUSLY: Good afternoon Ladies and Gentlemen, there is of course important news. A probable cause of Aids has been found.

NARRATOR: The discovery meant that a cure for this deadly disease seemed to be, just around the corner.

VIDEO OF PRESS CONFERENCE 20 YEARS PREVIOUSLY: A new process will enable us to develop a vaccine to prevent Aids in the future. We hope to have such a vaccine ready for testing in approximately two years, approximately two years (echo).

DR ROBERT GALLO (Institute of Human Virology, Baltimore): The press conference in 1984 there was one memorable scientific, shall I say a mistake or misjudgement?

VIDEO OF PRESS CONFERENCE 20 YEARS PREVIOUSLY – DR GALLO: What’s going to be available in two years as best as a scientist can calculate, we can't predict anything a hundred percent, but you’ve got to give some answers.

DR ROBERT GALLO: I never had any experience working on a vaccine or in public health before. And when asked well when will you have a vaccine, I, I was, I should have expected the question, I was a little stunned. And I thought to myself well when, let’s give some estimate, we can grow the virus for ever in culture, that means we can produce tremendous amounts of virus particles, gee that means in a few years we should have a vaccine.

NARRATOR: The optimism was so great because after all Gallo and others had already done the hard part. They knew how the virus worked.

DR ROBERT GALLO: Let’s look at this schematically, let us say this is a cell in the blood. That’s the membrane of the cell, let’s call that the nucleus and these some of the chromosomes.

NARRATOR: The cells HIV targets are those that control our body’s defences, the cells of the immune system. Gallo learned that to get in to these cells the virus has to latch on to receptors on the surface of the cell, called CD4.

DR ROBERT GALLO: HIV needs the CD4 receptors to enter the cell, so let’s look at it, this will be HIV.

NARRATOR: Gallo’s lab had even identified how the virus latched on to the CD4 receptors, by using these spikes.

DR ROBERT GALLO: The infectious process begins when that spike interacts with CD4. So when these membranes come together and fuse the goodies inside the virus are emptied in to the cytoplasm of the cell. This really now starts the process of gaining control of that cell. It also means that when the cell divides to become daughter cells the DNA will be transmitted of the virus in to each daughter cell. That means not only is this cell the target cell infected forever, but very likely the individual.

NARRATOR: This was the challenge that scientists faced in 1984. Find a vaccine to stop the bug entering and multiplying in the immune system cells. By the time the cause of Aids was discovered in 1984 just one thousand two hundred and ninety two people had died from the disease in the USA. At the same time in 1984, just as Robert Gallo was discovering how HIV worked, the virologist Ron Desrosiers had made a dramatic breakthrough of his own. Desrosiers had found a very similar virus causing Aids in monkeys. Now they understood the virus and they had an animal to test their theories on. Even this scientific sceptic was feeling optimistic about the prospects for a vaccine.

DR RON DESROSIERS (Harvard Medical School): The viral diseases that have been controlled or even eliminated because of vaccination is indeed quite impressive. Smallpox has been eradicated from the face of the earth, polio, measles, yellow fever.

IMMUNISATION ADVERT: It’s up to you to protect your child by immunisation.

IMMUNISATION ADVERT: Take them to your family doctor now.

IMMUNISATION ADVERT: And your child should be immunised.

NARRATOR: Vaccines have been one of the great success stories of modern medicine.

IMMUNISATION ADVERT: Polio, polio, smallpox, smallpox. These diseases can kill.

NARRATOR: Smallpox, scourge of Europe in the Middle Ages had been eradicated. Polio was close to following it.

IMMUNISATION ADVERT: Start this protection now with the first of three lumps of sugar.

NARRATOR: And the list was constantly growing. The most recent triumph had been Hepatitis B. And one of those who had played a key role in testing it was Don Francis. By 1993 he thought he had found a way to defeat Aids. He joined a private company Genentech that was making a vaccine based on the same principle as that for Hepatitis B. The ideas was straightforward, they would target the spikes on the outside of the virus called GP120.

DR DON FRANCIS: This is a cartoon of HIV which is actually a spear. These purple projections are the GP120 that cover the surface of the ball much like you’d see the fuzz of a tennis ball. Now what this virus is going to do is actually going to invade the cell which has specific receptors on the surface for that GP120. In the blood of the individual are these antibodies.

NARRATOR: Francis and Genentech thought they had worked out a perfect way to trick the virus and stop any infection at all from happening. They would make a vaccine that encouraged the immune system to produce antibodies in the blood.

DR DON FRANCIS: Antibodies will be produced against the GP120, so the next time that this individual becomes exposed to HIV then these little antibodies come in and glue directly on to the GP120, lock on to it and they’re obviously with those covering the total fuzz of this tennis ball, this virus is unable to buy in to the cell.

NARRATOR: It sounded so simple, generate antibodies and stop the infection.

DR ROBERT GALLO: Do you make antibodies that will block the attachment and thus block entry of the virus into the cell? The answer is yes, so the field, almost everyone that worked on vaccine between 1985, let us say, in 1988, ’89, maybe ’90, focussed virtually solely on the envelope GP120.

NARRATOR: In 1989 there was more good news, Genentech’s antibody vaccine was tested and it worked, in chimps.

DR DON FRANCIS: It was a hundred percent effective in all the vaccinated animals. This was the first time in history that any one had shown that an HIV vaccine could really work. So now you have the, the ultimate question. The vaccine will protect chimpanzees, immune response in humans is as good as those chimpanzees. Now the question is will it actually work in humans.

NARRATOR: But Genentech’s vaccine had only been tested on lab strains of the virus. Before the government would commit to large scale human trials they had to assess how the vaccine worked against real strains of the virus prevalent in the population. Streetwise strains that had tricks of their own. The tricks that HIV can play are well known to Steve Wolinsky. He has access to the biggest HIV database in America, thousands of samples amassed over twenty years. He has spent his working life analysing how HIV has changed and spread around the world.

Prof STEVEN WOLINSKY (Northwestern University Medical School): In the tree that we see here the shapes gives us an indication of the evolutionary history. The branches are the genetic distances that one sees within the virus. And as we can see here these changes that exist over time are constantly expanding.

NARRATOR: All viruses changes, but when Wolinsky and others compared HIV to flu they were astonished. The flu showed this amount of genetic variation around the world in 1997. Then he looked at how many variations of HIV existed in one individual whose blood was tested the same year. In a year HIV changes more in one person than all the changes in flu around the world. And again in 1997 this is how many different strains of HIV had evolved from a single strain in the democratic republic of Congo alone. The flu virus changes a tiny amount every year, yet every year we need a new vaccine to protect us against it. But HIV is in a whole different league.

Prof STEVEN WOLINSKY: HIV variation is quite spectacular. Every time the virus makes a copy of itself it makes a mistake. So it creates a vast swarm of mutant viruses that exist in every one person.

NARRATOR: HIV replicates and mutates incredibly fast, as many as ten billion copies in one person in one day. Against this kind of diversity the antibody vaccine makers would struggle to keep up. Dennis Burton is a football playing Brit. He works at the Scripps Research Institute, yards from the Pacific Ocean. In nearly twenty years studying HIV antibodies he has found out a great deal about the structure of GP120, the target for Genentech’s antibody vaccine.

Dr DENNIS BURTON (Scripps Research Institute): Here’s a GP120 on the virus and here’s CD4 on a human T cell. They form this handshake and the virus is now linked and infection can begin.

NARRATOR: Antibodies can stop this happening but only if they know exactly what to target.

Dr DENNIS BURTON: A single change in the amino acids that make up the whole of the GP120 molecule, can completely eliminate the binding of one particular antibody.

NARRATOR: Genentech’s problem was that they had thought that there GP120 antibodies would work against many different strains of HIV. But in fact while they worked on their vaccine GP120 was changing beyond their reach. For it turns out that GP120 is the most variable part of the fastest changing virus in the world. In the time that it took to have this man’s blood tested GP120 may have changed to move beyond the reach of an antibody. Genentech’s vaccine may have worked in chimps but many believed it would not make effective antibodies to real viruses.

Prof STEVEN WOLINSKY: Well the vaccine that Genentech is using is based on a viral strain that existed somewhere back there towards the beginning of the HIV starburst, and what we have right now are all these different strains that exist on the periphery of the starburst.

DR DENNIS BURTON: Worldwide it’s a matter of hundreds of thousands of strains, and that is a problem because if you're going to vaccinate people you don’t know which virus they’re going to be exposed to. You have to cover them against all the world’s viruses for a really effective vaccine.

NARRATOR: Don Francis didn’t get funding for human trials from the government, they just didn’t think his vaccine would work. He sees it as a terrible missed opportunity.

DR DON FRANCIS: It’s an uphill battle to convince either the private sector or the public sector to pay for. And finally when they come round to saying it’s important is going to be just that much later. And thousands and thousands of people will die.

NARRATOR: But Don Francis didn’t give up. In 1995, cap in hand, he went to Wall Street and tried to raise the money there.

VIDEO OF PRESS CONFERENCE 20 YEARS PREVIOUSLY: We hope to have such a vaccine waiting for testing in approximately two years. In approximately two years (echo).

NARRATOR: Ten years after that famous press conference five million people had died from Aids around the world. And there was still no vaccine. Professor Roy Anderson is an expert in how epidemics spread. He knows that compared with other diseases this one is digging in for the long haul.

DR ROY ANDERSON (Imperial College London): Now if you think about SARS the incubation period, time for infection, to when the clinical symptoms appeared was about four to six days. And then a few days to a few weeks recovery. If you think about HIV and Aids, from the point of infection to when Aids is diagnosed in the absence of treatment is ten years. So just compare four to six days with ten years. SARS epidemic over in six months, generation time of four to six days. Aids incubation period ten years, epidemic overall at its equilibrium, hundreds of years. Hundreds of years.

NARRATOR: For fourteen years Andrew McMichael has driven from a pretty Oxfordshire village to the John Radcliff hospital in Oxford to work on Aids vaccines.

PROF ANDREW McMICHAEL (Oxford University): When we visit Africa you don’t see anything particular and then you meet people and then you realise that everybody you meet has been affected by this disease. So they have relatives or friends who died or they’re looking after orphaned children. It does bring it home to us how big, big the problem is and how there is such a need for a vaccine.

NARRATOR: Concerns about the first antibody vaccines had made all these scientists pessimistic about the future. But then in 1992 McMichael’s lab came across some extraordinary people that seemed to offer new hope.

PROF ANDREW McMICHAEL: Came across a report from Kenya, from Nairobi, that there were some very highly exposed sex workers who were apparently resisting infection.

NARRATOR: These prostitutes were infected with HIV but remain completely healthy. But a bigger surprise came when their blood was tested. There was no sign of antibodies stopping the infection of cells, instead it seemed the prostitutes were staying healthy because the infected cells were being rapidly destroyed, by another powerful weapon in the immune system’s armoury, killer T cells. This discovery opened up an entirely new frontier in the race to build a vaccine against Aids. Norman Letvin is a clarinet-playing immunologist at Harvard Medical School. As a young researcher in the early 90’s he too saw the opportunity of using killer cells to build an Aids vaccine.

PROF NORMAN LETVIN ( Harvard Medical School): When a cell is infected with the Aids virus, or any virus, that virus begins to multiply inside of a cell. The proteins of the virus get chopped up inside the cell in to very small fragments. These small fragments move to a protein that sits on the surface of cells that we refer to as HLA. This infected cell is then recognised as being infected by a white blood cell referred to as simply as killer T cells. The infected cell is seen by the killer T cell and eliminated from the body.

NARRATOR: For the first time these scientists believed that where antibody vaccines had failed the body’s immune system could be boosted with killer cells. If you couldn’t keep the virus out then destroy it once it had got in.

PROF NORMAN LETVIN: Our hope therefore is to create vaccines that induce large populations of killer T cells. When an infection occurs the Aids virus replicating in the infected individual should be held in check and replicate at a much, much lower level than we ordinarily would see in the absence of that vaccine.

DR ROBERT GALLO: Perhaps we can have a vaccine that will greatly lower the amount of virus so the person may get infected but they never get disease.

NARRATOR: The mantra now became, if we can't prevent infection can we prevent disease? One famous experiment suggested they could. Four years ago Norman Letvin gave eight monkeys a vaccine based on bits of the virus he thought would produce lots of killer cells. They were then infected with SIV, the monkey version of HIV. The results were astonishing.

PROF NORMAN LETVIN: When those monkeys were then infected with the Aids virus what we saw was quite extraordinary. While the monkeys universally became infected with the Aids virus, the level of viral replication in those infected individuals was held to extraordinarily long levels. In fact those monkeys that held the virus in check lived much longer than unvaccinated monkeys and were quite healthy for prolonged periods of time.

NARRATOR: A vaccine based on killer cells worked in monkeys. Now it had to be tested on humans. This is McMichael’s killer cell vaccine being injected in to a volunteer. McMichael’s and more than twenty other groups have pushed ahead with human trials, hundreds of millions of pounds have been invested. For the last ten years a killer cell vaccine has been seen as the best hope of eradicating Aids. But recently it has dawned on these scientists that the killer cell approach might not work. Because they’re not just fighting a clever virus that changes fast, they are up against the most powerful force in nature. These leopard sharks have changed over millions of years in to the perfect hunter killers of the ocean, thanks to one of nature’s most fundamental principles, evolution.

Dr DENNIS BURTON: Evolution is a principle of life based essentially upon two forces, mutation and selection. The first of those mutation produces lots and lots of different variations on the theme. And the second is selection, whereby the fittest, the ones that’s most suited to the environment survives and propagates its offspring.

NARRATOR: HIV too is fighting for its survival. It is locked in a deadly evolutionary battle with our immune system. Which ever adapts the fastest will survive. And HIV adapts very fast indeed.

Dr DENNIS BURTON: Viruses that are able to avoid the immune system are going to leap ahead of those that, that can not deal with the immune system at any given time. HIV can mutate and evolve at enormous speeds. Rather than millions of years we are talking literally of days and weeks.

NARRATOR: Laird Peterson is a perfect example of this evolutionary battleground between our immune system and HIV. For twenty years he has been contributing to Steve Wolinsky's study. And in that time, like all infected people, the virus has been struggling to evade the killer cells that aim to destroy it. HIV strategy is focussed here on these tiny viral particles which appear on the surface of an infected cell, and make it a target for killer cells. By changing this target the virus can ensure its own survival, because the killer cells won’t recognise it.

Prof STEVEN WOLINSKY: So the virus comes along and says, well if I mutate I can avoid being presented to the killer T cells and hence evade the host’s immune responsive.

NARRATOR: It takes only a tiny mutation, a change in just one amino acid, the smallest building block of these bits of the virus, to outwit and defeat the killer cells.

Prof STEVEN WOLINSKY: And as we look down here you can see you could see that there are certain areas where the Y changes to an F, or a T changes to a V.

NARRATOR: This is SL9, an absolutely minute nine amino acid sequence of the virus. It is one of the targets for the killer cells. Within three to five years of the virus infecting someone, two of these amino acids will change. With two amino acids changed SL9 becomes invisible to the killer cells. Without an effective killer cell response The immune system gives up and the virus spreads unchecked. Then infected people like Laird Peterson have to rely on drugs to combat the disease.

Prof STEVEN WOLINSKY: So there really seems to be some strong evidence that escape from a cellular immune response, escape from a killer T cell, actually gives the person the point for the virus to proceed unimpeded and cause disease.

NARRATOR: The consequence of this discovery for killer cell vaccines was potentially devastating. Two years ago Norman Letvin found out just how devastating.

PROF NORMAN LETVIN: We saw this situation play out in a very dramatic fashion in a monkey, a monkey we call Monkey 798.

NARRATOR: 798 was no ordinary monkey, this was a monkey whose immune system had been boosted with a killer cell vaccine. A monkey which had successfully held the virus at bay for a year.

PROF NORMAN LETVIN: When we first saw the amino acid change, the mutation in the virus, then eventually we saw the loss of that killer T cell response. Then we could predict that the virus replication in that monkey would rise and it did. Finally we could predict that in fact the monkey would eventually die of immunodeficiency, and the monkey did. We saw that no matter how potent a killer T cell response we generate with a vaccine the virus can eventually escape from control.

NARRATOR: Andrew McMichael and his colleagues have invested fifteen years of their lives in the dream of a killer cell vaccine, and they’re pressing ahead with trials anyway. But the evidence from SL9 and Monkey 798 is a threat to all of their work.

PROF ANDREW McMICHAEL: What I’m saying is not that it’s impossible but that it is perhaps harder than many people realise and that we have to be able to deal with the virus variability. But it is the major problem I think, it, it could be the reason why this approach proves to be extremely difficult.

DR ROBERT GALLO: The worry of the whole field including Andrew and others, would be that maybe you hold the virus down for a while, but two, five, ten years later it takes off.

NARRATOR: A young man in Botswana today has an eighty percent chance of getting Aids in his lifetime. This is the graduation ceremony at a teacher training college in South Africa. In the past five years more teachers have died of Aids in this region than have been trained. And yet a vaccine still seems years away. Bruce Walker is a Boston Doctor who has been working in South Africa’s Natal province, one of the worst affected parts of the world. Eight years ago in America he met an extraordinary man called Bob Massey, a man that may offer another new hope in the search for a vaccine, but who has also revealed our ignorance.

DR BRUCE WALKER (Massachusetts General Hospital): The incredible excitement around Bob Massey when he came in was here was a person that seemed to be keeping the virus in check.

NARRATOR: Massey was infected with HIV from a blood transfusion in 1978. But when Walker met him seventeen years later he only had a tiny amount of the virus in his blood, and he’d never taken drugs to control it.

DR BRUCE WALKER: So the basic question that Bob Massey was asking is why am I feeling well right now and how long will I continue to feel well. And if we could just understand how he was able to achieve that we might be able to reproduce that in people who weren’t able to control the virus. If one could turn people in South Africa and other places in to Bob Massey’s I would call that success.

NARRATOR: But Bob Massey has turned out to be a mystery. At first they thought he might have a genetic advantage that could explain his good fortune.

DR BRUCE WALKER: We are all genetically slightly different and the way that we deal with viruses that come in to our bodies are slightly different. But in Bob Massey we haven’t identified a genetic component in him that’s responsible for this.

NARRATOR: Nor did Massey have vast numbers of antibodies to fight off the disease.

DR BRUCE WALKER: If you look at neutralising antibodies in Bob the neutralising antibody levels are actually quite marginal.

NARRATOR: Then they discovered Massey did have a huge killer cell count. But people with large numbers of killer cells can still get sick. After eight years there is still no real explanation for Bob Massey’s good health. What is and isn’t understood about Bob Massey sums up the spectrum of frustrations and hopes of the vaccine makers. Andrew McMichael and Norman Letvin still believe that the answer will like in a killer cell vaccine, if they can find a way to keep up with the rapidly evolving virus.

PROF NORMAN LETVIN: I have always been optimistic that this will be a solved problem, it’s a difficult problem but certainly not an insoluble one.

NARRATOR: Dennis Burton continues his long search to find antibodies that combine to a wide selection of viruses.

Dr DENNIS BURTON: The honest answer to the question of, of whether or not we will have an HIV vaccine is I don't know. We are going to work on it as hard as we possibly can. And that’s all we can do.

NARRATOR: But Ron Desrosiers sees little chance of success until we find out much more about how the virus works.

DR RON DESROSIERS: Our real problem is the virus. The virus is just impervious to almost everything you throw at it. We’ve got results that, that have just astounded me and, and I tell my science friends about it and they go my God the virus is amazing.

NARRATOR: And every day these scientists try to solve these problems fifteen thousand people get infected with HIV, and eight thousand die of Aids. The situation is now desperate. As a result even though we don’t really know what will and will not work vaccines are being tested on humans on a vast scale.

DR RON DESROSIERS: The vaccine products that are going forward in to clinical testing I view as analogues to sending blind batters to the plate in a baseball game. The hope is that if we send enough blind batters up to the plate maybe one of them will get lucky and hit a home run. Well I don't think we’re going to have a blind batter hitting a home run in the All Star game. I would argue that practically we’re no closer to a vaccine today than we were twenty years ago when the virus was first discovered.

NARRATOR: And all the while the virus has been spreading. But the terrible irony is there may have been a protective vaccine around, for years. Seven years ago this man volunteered to take part in an extraordinary experiment. One which for many was absurdly dangerous.

DR ANDREW PAVLOTOS: I really wanted to do this, it was a very spontaneous thing, I read this and it clicked and I said yes I want to be involved.

NARRATOR: the experiment was to be a trail of another and very special kind of vaccine. Doctor Andrew Pavlotos and others were to be injected with live HIV. This live attenuated vaccine was very different to antibody and killer cell vaccines. By injecting someone with real live HIV the idea was to stimulate all of the immune system defences against the virus. There have been spectacular successes, live attenuated vaccines have helped make polio a memory in most places in the world. They protect against yellow fever, measles and mumps. But would it work with HIV? Back in 1993 Desrosiers removed a gene in SIV, the monkey variant of HIV. By removing this gene he hoped he could keep the virus live but make it safe. This was his vaccine. Monkeys were given the vaccine and then a full blast with SIV. The results were remarkable.

DR RON DESROSIERS: As the data came in and kept looking better and better and better for protection that, that we were very excited.

NARRATOR: Ron Desrosiers’ live virus vaccine was working.

DR RON DESROSIERS: I think a case can be made for starting trial, safety trials in limited numbers of people soon. In people soon.

NARRATOR: But just as Desrosiers was making his claims there were dire warnings. Warnings that this approach would lead to trouble, that the virus would yet again play its trump card. It would evolve and reconstitute itself as a killer. At some time in the future this live attenuated vaccine could mutate to give you Aids. Because of these safety fears no human trial was ever carried out, no one was vaccinated with a live attenuated virus.

DR RON DESROSIERS: The dangers associated with such a vaccine approach are so enormous that it, it makes it sort of this piece of cake or candy that you can't reach, can't use, can't take.

NARRATOR: Desrosiers’ vaccine remains the most effective vaccine to protect against Aids in animals. And yet even so it is considered by many too dangerous to use in humans. But so was the live attenuated polio vaccine. Until scenes like this became unbearable. Desrosiers is beginning to wonder how many more years of failed vaccines and how many more millions of deaths from Aids before someone takes the chance. The statistics are almost incomprehensible.

DR ROY ANDERSON: There are as far as we understand forty two to forty five million people with HIV or Aids at the moment. Most of those are in poor regions of the world, in the absence of good treatment they sadly will die in the longer term. Now that number is the beginning to mid phase of the global epidemic, so undoubtedly it could at least double, mortalities could at least double if we’re talking about a high, a time scale of a hundred years or more. My own guess is that if nothing is done, is you're not talking about tens of millions you're talking about hundreds of millions.

VIDEO OF PRESS CONFERENCE 20 YEARS PREVIOUSLY: The new process will enable us to develop a vaccine to prevent Aids in the future. We hope to have. We hope to have such a vaccine ready for testing in approximately two years.

DR ROBERT GALLO: Did I ever dream that we would have this degree of difficulty, no of course not. We thought it would be straightforward to begin trials, it was far, far more difficult than straightforward.

DR RON DESROSIERS: That’s what it’s like, it’s like the virus is there laughing at you. Somehow the virus eventually gets where it needs to go through a natural process of accelerated evolution, and is really difficult to defeat.

DR ROBERT GALLO: All of us who worked on this problem have a sense of deep frustration. Each month that goes by that we don’t solve the problem we know the time ticks for the death of other people, and suffering of other people in the millions.

NARRATOR: In the twenty years since that press conference twenty five million people have died of Aids. This makes it the deadliest epidemic since the black death. 1994 wasn’t the end of Don Francis’s vaccine after all. He set up a spin off company Vax Gen, and raised millions of dollars of private capital. Ten years later and the world held its breath as Vax Gen analysed the results from trials of its Aids vaccine on thousands of people in the US and Thailand. And the vaccine failed. That is nearly twenty years to find out that one kind of vaccine didn’t work.

VOICE OVER: Next week Horizon celebrates the hundredth anniversary of the first ever flight. With the amazing story of Percy Pilcher. We rebuild his long lost aeroplane and discover if he could have claimed the glory and been the first ever person to fly.