THE VAXGEN EXPERIMENT
The Sunday Times Magazine (London) October 3 1999
By Brian Deer
(part 1)
Once a month, at around 3pm, Dr Donald Francis, president of the VaxGen corporation, boards a 747 at San Francisco airport for an 18-hour flight to Bangkok. The route is unpopular - with maddening stops in Seoul, Hong Kong or Taipei - and he insulates himself in a business class window seat with earplugs, eye-mask and face-cream. The tedium drives him crazy, but he doesn't sleep much. His adrenaline levels stay high. Speculations loop like a tape through his head: "What if I do? Supposing I don't?"
He's 57, but looks ten years younger, with blue eyes and an animated style that makes people think that he's gay. When they grasp that he's not (married twice, two sons) the next thing they guess is that he works in show business; say, music or motion pictures. Boyish, fit, articulate, charismatic; he's a person you'd choose to sit next to. But he's a doctor and scientist in the gruesome field of Aids, so demons lurk behind the mask.
I couldn't wait to meet him. We've something in common: we've followed the epidemic since the start. I reported on the first known death in Britain, in December 1981. He was the first to alert America's blood banks, arguing that a virus was to blame. In Randy Shilts's 1987 Aids history, And The Band Played On, Francis storms across 76 pages, warning, demanding, lambasting. In the movie of the book, starring Richard Gere and Anjelica Huston, he's played by Full Metal Jacket's Matthew Modine. He's ER meets JFK.
A man with his record might have taken it easy, sure he'd done enough. In the 1960s, as a young MD with the American government's epidemiology service, the Centers for Disease Control (CDC), based in Atlanta, he was dispatched to India to help eradicate smallpox: a triumph against infectious illness. In the 1970s, while studying virology at Harvard, he was rushed to Sudan by the World Health Organisation - the WHO - to investigate the first outbreak of ebola. In the 1980s, he led trials in Phoenix of a successful vaccine against another killer, hepatitis B.
But for him these achievements merely judder like turbulence; they remind him of what's still to be done. When he slips into Bangkok the following morning, his destination is Taksin Hospital, by the Chao Phraya river, a corroded-concrete and grimy-glass hulk full of poor people patiently waiting. He goes to the second floor and through a pair of glass doors, where the atmosphere transforms. There are maroon carpets, soft furnishings and secretaries in beautiful dresses. A sign inside says: "Bangkok Aids Vaccine Evaluation Group". The VaxGen experiment.
People laughed when he declared - seven years ago - that he would be first with a shot against Aids. After 20 years as a fireman with the CDC, everybody said that he couldn't focus on such an intricate project. Although he'd set-up an Aids lab back in 1983, ten minutes at a bench would have him yawning and twitching. He preferred khaki shorts to white coats.
Since the human immune deficiency virus was discovered in 1984, moreover, it has been the definitive white coat challenge - and quite different from his previous foes. Unlike smallpox - an easy target- HIV kills some of the very cells (so-called T-helper cells) which are fundamental to our immune system defences. Unlike ebola, a rare disease, HIV has slayed 14m people and infected another 35m. And unlike hepatitis B virus, which is quite stable, HIV is a so-called "retrovirus", with its genes coded in ribonucleic acid (RNA), and changes so much with each replication that it breeds an infinity of strains.
When Francis was at medical school in the 1960s, a virus was a virus, with maybe three strains, like polio. Vaccines were easy. But such is HIV's frenetic shape-shifting that each infected person harbours an astonishing swarm of strains, totalling about 1 billion, all slightly-different, virions. Scientists lump them into two types (HIV-1 and HIV-2), three groups and ten subtypes. Thousands of strains are studied. At med school he learnt that parasites evolve to live in harmony with their hosts. But HIV is so new and unstable in humans that it may evolve to become a quicker killer, or be more infectious. The truth is, nobody knows.
Cleverer doctors and scientists than him have got lost in this terrain. So far, some three dozen would-be vaccines have been tested in labs, animals or a few individuals, but none has done any good. Vaccines work by priming our immune systems - including antibodies and T-cells - so that they will be ready for action if a bug comes along. But so far every attempt to accomplish this with HIV has either proven dangerous or to have no effect. Some experts say that nothing will work.
Francis crosses the Pacific with an approach to the problem that sounds beguilingly simple. The VaxGen experiment is with a product - brand-named AidsVax - that mimics part of the viruses skin, or envelope. By inoculating healthy people with a manufactured clone of this part - a sugary "glycoprotein" called "gp120" - antibodies are supposed to be primed to protect in the event that sex, blood or drug misuse causes the virus to later intrude.
At Taksin Hospital he fine-tunes the experiment - a "placebo-controlled double-blind trial" - so far the only full-scale Aids vaccine trial ever. On 24 March, the first of 1,250 HIV-negative Thai volunteers started on a course of seven six-monthly shots. Another 1,250 are getting an inactive placebo. Who is getting what is concealed in codes, and any difference in the numbers who later become HIV-positive should reveal if the product works.
Francis meets with Dr Kachit Choopanya, his principal investigator. In silk suits and gold-rimmed glasses, Kachit, 65, controls 17 Bangkok drug dependency clinics, chosen to take part by Francis's old friends at the CDC and WHO. Heroin misusers are top of the HIV risk-list, due to poverty-driven needle-sharing. If they can be protected, the agencies reason, then you, I, or anyone can. "If the VaxGen vaccine can create immunity in humans, then we can solve the whole problem," Kachit declared on the day of the first jab. A 27-year-old heroin addict was equally upbeat. He said: "I believe the trial could bring great benefit to mankind."
There's a similar impression at a high level in America that history may be about to be made. The US government's National Institutes of Health and its Food and Drug Administration, both in Maryland, are backing the experiment. So are officials of the World Bank in Washington and United Nations agencies. And so is the principle lobby group: the International Aids Vaccine Initiative. "The group's president, Dr Seth Berkley, said. "We applaud VaxGen."
Francis basks in these endorsements. He settles on the thought that he'll do it. VaxGen is one quarter owned by Genentech Inc, a medical biotechnology leader. Genentech is a subsidiary of Hoffman-La Roche, the Swiss pharmaceutical colossus. All are poised for full-scale production. When shares in the company were launched on the New York Nasdaq market at the end of July, they jumped from $13 to $26. He banks on a license for a crash programme of inoculations like the world has never seen.
But when he flies in from San Francisco, he can never quite quell his anxieties. In his files are papers which suggest that AidsVax can't really work. And he's familiar with scientists who warn of possible hazards on a globally catastrophic scale. His vaccine may make it into millions of people. The profits could buy Bangkok. But the momentum behind the experiment could turn out to be one of medicine's greatest mistakes.
*****
At first glance, Thailand is a strange location to carry out medical trials. The CIA rates the country as merely an "emergent democracy"; the last military coup was only eight years ago; and there were Bangkok riots in 1992, when 91 died or went "missing". Corruption is de rigeueur, while police are accused by Amnesty International of "extra-judicial killings". Much of its profile relies on sex: first with young women and later with children.
Since the coup, however, quick cheap, experiments on the Thai population have been added to the country's attractions. Dozens of projects are currently in progress, run by foreign pharmaceutical companies and sponsored by the CDC and WHO. With an estimated 800,000 Thais infected with HIV, Aids is the big one, with tests of drugs, immune-system stimulants, and top of the list Francis's AidsVax trial.
It makes sense to test products where the risk of Aids is greatest, but my attention was drawn to potential problems during a conference in a Bangkok hotel. The topic was Aids vaccines. Francis spoke. And a doctor pointed out that some volunteers in an AZT trial were mothers from remote hill tribes. "They come across the border from Burma." he said. "They don't speak Thai, so there is the question of whether they can understand enough to give informed consent."
The question was brushed aside ("They keep coming back.") and might not have meant much if I hadn't also met an activist from the northern town of Chiang Mai. Despite grilling 11 people who swallowed tablets daily, he complained that he couldn't discover even the name of the product or the pharmaceutical company involved. This man was a former heroin user, so I asked him where VaxGen was recruiting. "Go to Khlong Toei," he said. "By Port Authority Building. That's where they'll get people for the trial."
Khlong Toei is a slum; a sewage-stinking wasteland; a cauldron of disease and drug use. The better-off live in concrete hutches, with wire-fenced windows and balconies. Next down in the social scale are wooden-shack coops on plots of flood-prone ground. Then there are kennels: festering shantytown alleys of plank, sheet-iron and debris sheds. The "streets" are dim corridors, with boardwalk floors, cluttered with children and dogs. At night frail figures shuffle around, suffering from Aids, tuberculosis or both.
Thailand was once praised for anti-HIV efforts in disease hot zones such as this. But evidence suggests that since the 1992 coup priorities have changed. In 1992, a health minister complained that talk about the virus had "seriously affected tourism". And now, official figures show that Aids prevention has been slashed by one third against comparable public health programmes.
The biggest cuts have been in initiatives aimed specifically at drug misusers. "There used to be a project for clean needles in the early 90s, but now it's gone" a spokeswoman for a Khlong Toei charity, the Duang Prateep Foundation, told me. A health department official said the same thing. His time-frame: "about seven years ago". Targeted education, known to be most effective, has also been axed, he said.
Nobody could explain the thinking, but the effect on the junkies can be measured. Blood tests reveal that HIV prevalence peaked among female prostitutes in 1993 - when 30% were positive - and has since fallen back to 21%. Among rent boys, prevalence peaked in the following year at 18%, and is now half that figure. But prevalence among heroin-injectors has leapt from 31% in 1994 to a staggering 47% now.
Were these changes evidence that the government were allowing the junkies to be put at greater risk to make them useful for experiments? (Health department officials told me that if AidsVax is marketed, they expect a billion-dollar manufacturing plant.) I couldn't find out. People wouldn't talk when I raised such contentious concerns. Even Bangkok's Medicines Sans Frontieres staff went silent when asked about the trial.
Francis is convinced that nothing is amiss, and his collaborators voice no worries. "All have assured me that this has been done ethically," he told me, when eventually we met. "We are going out of our way not to increase the vulnerability of an already vulnerable population." The trial was conducted in Thailand, he said, for scientific reasons. Different parts of the world are linked with different HIV subtypes, with their myriad subsidiary strains. B subtype strains, for instance, are most common in North America, Europe and Australasia; A, C and D in Africa. In Thailand, there's a mix of B and E strains and, for technical reasons to do with E strains, the company argues that success is more likely there "than anywhere else in the world."
But there are aspects of the project which suggest that the junkies may be involved in an unusual way. A parallel trial among gay men at American clinics is having problems finding and keeping volunteers, due to scepticism towards the venture. But at Kachit's clinics the programme has features which may help to avoid these snags. The junkies get methadone, an oral heroin substitute, plus $10 expenses for each of up to 17 visits. The risk is the appearance of offering drugs and money as inducements to this desperate group.
There's also a feature of the experiment's design that seems self-contradictory. If the methadone liquid got people off injecting heroin, the volunteers' risk of infection would slump and they would be of little use to the vaccine trial. In fact, documents drawn up with the CDC and WHO show that that 7% of clinic users are expected to become HIV-infected each year. So, despite the oral methadone, they keep injecting heroin. They may even buy it with VaxGen's money and have an increased risk of getting Aids.
The logic of the trial creates a dilemma for Francis. The moral uncertainties about using junkies as guinea pigs might be offset by humanity's greater needs. But there would need to be plausible scientific grounds to think that AidsVax might work. And on that the VaxGen experiment is open to even greater doubts. |
