by Piot, Peter
This was not good news. Already we were dealing with HIV-1 and HIV-2: two viruses that created the same pathology but that were genetically quite distinct. We already knew that people could be infected with both different families of HIV viruses at the same time. If, in addition, strains within each of these families diverged to this degree, we were in trouble; it would tremendously complicate the development of a vaccine against HIV infection.
Per molecular clock calculations, Group O seemed to be the oldest virus strain yet identified. It may be even older than SIVcpz, a virus closely related to HIV-1 that Belgian microbiologist Martine Peeters had also found in a pet chimpanzee named Amandine in Gabon. (SIV denotes a simian, or monkey, virus and cpz is for chimpanzee.) That discovery came more or less by chance, when Martine and her French husband, Eric Delaporte, were screening monkeys and apes for HTLV human T-lymphotropic virus (a virus that can cause T-cell leukemia and myelopathy/tropical spastic paraparesis in humans). They were working in Franceville at a medical research center funded by the French petroleum company ELF-Aquitaine, and we maintained close contact with them from Antwerp (they sent us samples of gonococcal stains). All of us were stunned when an apparently healthy chimpanzee was found to have a virus almost identical to human HIV. In fact the chimpanzee virus so closely resembled HIV-1 that initially Martine’s publication was refused: there was disbelief that this was possible; the viruses were so similar that reviewers assumed it must be due to a lab contaminant. When Martine was back in Antwerp working in our team, she found a second SIVcpz in a chimpamzee named Noah, living in the zoo in Antwerp. He was healthy as was Amandine and is now living in a chimpanzee hotel in the Netherlands.
Many viruses have species-jumped at some point, and these are the viruses that overwhelm their new target group with epidemics, because no immunity has yet developed against them. So this research contributed to exploring the complexity and diversity of HIV, and to showing that its greatest diversity is in west Central Africa, specifically Cameroon and Gabon. I don’t like the term “Ground Zero,” which suggests a single, explosive event: the transition from ape virus to human virus was more like a kind of seepage. But this place is probably where it first happened.
In addition we found an extremely rapid rate of gene mutation, faster even than the flu virus. We did a lot of work on characterizing virus isolates, and following particular strains as they grew in various populations. For example, in Thailand there seemed to be several, fairly separate HIV epidemics under way, in gay men, heterosexual prostitutes, and injection drug users.
Could we find any kind of antibodies that would neutralize every possible strain of HIV? Some antigen, some piece of envelope protein, that could be a clue to help develop a vaccine? We began working on it in the late 1980s. It was painstaking work—monks’ work. And it came up with no practical results. (It was not until 2010 that researchers found any such antibodies.) The reality is that a lot of scientific research goes nowhere. Medical researchers have a saying: if you want quick results, become a surgeon.
In other areas at least, we were getting results. Studies in Rwanda by Philippe Vandeperre, and in Nairobi by Pratibha Datta, Joan Kreiss, and Joanne Embree, told us that children who were breast fed by HIV-positive mothers had a higher rate of infection than children who were not, particularly for women who were newly infected during their pregnancy. This confirmed our suspicion that recent infection led to a high viremia and far higher probability of transmission, but it also indicated that HIV was transmitted through breast milk more often than we had previously thought.
Frank Plummer in Nairobi made another fascinating observation. Some of the prostitutes who had been attending our clinic in Nairobi for years—women who were well known to us, who had literally had thousands of sex partners, and indeed several bouts of sexually transmitted disease—did not become infected with HIV. It was almost a Sherlock Holmes–type of observation—the dog that didn’t bark—but once he started thinking about it, it popped up again and again.
We came up with about two dozen women who appeared to be immune to HIV. Despite counseling, they didn’t always use condoms. But either their immune system was better equipped to recognize HIV-infected cells and remove them, or they had fewer target cells for HIV to infect in the first place. The good news was, the women’s constant exposure to the HIV virus reinforced their ability to fight the infection. The bad news was, if their exposure was stopped, even for a matter of weeks—if they took a break from sex work and returned to their villages—they lost their immunity. Frank and his team are still working on this immunological exception, and one day it may bring a clue to the development of a vaccine.
Other sex workers, the so-called elite controllers in research jargon, were infected with HIV, but they were somehow generating the ability to hold the viral load in check. Only with such a huge cohort of people, following them closely through time, could these observations have been made. Research still hasn’t figured out how to reproduce this ability, but disentangling this other immunological puzzle could open the door for how to develop a real cure, meaning that HIV can be eliminated from the body, or kept under control without permanent antiretroviral treatment.
The Nairobi team was also the first to make a seminal observation that would revolutionize HIV prevention over 15 years later: we found that HIV-positive men were far more often not circumcised as compared to HIV-negative men (in Kenya some men, such as the Kikuyu, traditionally are circumcised, whereas others, such as the Luo ethnic group, are not). Because male circumcision is intimately connected with religion, culture, and ethnic origin, the subsequent multiple observational studies could not exclude that the association was a confounding one. Also, the majority of European and Asian men are not circumcised, and yet there was not this major HIV epidemic as in Africa. We had to wait for three controlled trials in South Africa, Kenya, and Uganda to prove beyond doubt that male circumcision protects men from acquisition of HIV.
These were the years of relentless scientific progress in AIDS, but I felt time standing still and running out at the same time—in particular in southern Africa, where we needed every possible prevention intervention to reduce the continuing horrific spread of HIV.
CHAPTER 14
Changing of the Guard
IN MARCH 1990, Jonathan Mann sent a brief fax to a few dozen of his key allies in the fight against AIDS. He was quitting WHO. The news shook the AIDS community like a blast of icy air. Jonathan was our moral leader; for some he had acquired the status almost of a savior. But he couldn’t take Dr. Nakajima’s interference any longer. The new director-general of WHO, and therefore Mann’s boss, was now controlling Jonathan’s travel, public statements, high-level contacts, and budget. In a way some of this could be perceived as normal practice: the Global Programme on AIDS (GPA) had become like a state within a state at WHO. Moreover, Mann was the the public spokesman of AIDS, in fact, to some degree the public spokesman for world health in general. But Mann’s AIDS program had to be independent, because that was the only way to jump start HIV prevention programs in as many countries as possible, especially when many of them did not perceive the urgency. A number of donor governments withdrew backing from Mann and started to set up their own bilateral programs, after becoming critical of internal management in GPA and Jonathan’s human rights rhetoric. I guess that Jonathan felt backed up against a wall so he choose to leave rather than to try to change the system from within.
A few weeks later Michael Merson was appointed as director of the Global Programme on AIDS. Merson had been at WHO for over a decade, running the program on diarrheal diseases and respiratory tract infections—two of the major killers in the world. He was highly respected in public health circles and was a solid manager, but he had little knowledge of AIDS at that time or of any of the constituencies and activists who were such important actors in the AIDS community. The first thing he set out to do was “normalize” the GPA in WHO’s structure, and introduce proper accountability. Since
GPA was set up in a minimum of time as a new type of global emergency response, it had all the strengths and weaknesses of a start-up, with the culture of a small nongovernmental organization. This was obviously not sustainable and corresponded less to the needs of the AIDS response after a few years. He faced a working environment that was incredibly hostile: GPA staff rallied against him because they thought he was Nakajima’s man, and I admit that initially I felt the same way.
Soon after Merson was appointed I went to Geneva, as chairman of the Steering Committee on Epidemiology, to ask what his plans were and whether we should continue. And I found that unlike some people in the AIDS world, I immediately liked him. He was from Brooklyn, and he had a very different outlook on life from Mann, the Boston intellectual. Merson definitely did not have Mann’s charisma, but he was dogged. I found him very connected to reality. Jonathan gave thoughtful and important speeches on human rights, but he hadn’t been very engaged with program delivery, and Mike was all about finding the most effective way to impact people on the ground. He was more like an engineer than a philosopher, and to me it was obvious that we needed both.
IN MAY 1990 riots broke out at the university in Lubumbashi. I wasn’t there; I hadn’t been back for months. But I grasped the situation: President Mobutu used the copper mines of Shaba as his personal treasury, and he was not popular in Lubumbashi. Mobutu’s Civil Guard had shot dead several dozen students during demonstrations. According to the Belgian daily Le Soir, more than 50 people were killed. Belgium reacted by suspending all funding for Zaire except humanitarian aid, and demanded that an international commission of inquiry be set up. Tit for tat, Zaire expelled several hundred Belgians and cut off diplomatic relations. The EU cut off funds. We had to pull out of Lubumbashi.
We left money for salaries so the local staff could keep working, but we never managed to get the project back off the ground. It had lasted barely two years. We had clearly saved some lives, because now they were screening blood, and there was a functional lab, although that was plundered during the riots. Still, I knew we hadn’t worked there anything like long enough for the system to become self-sustaining.
International development programs are highly dependent on a safe, peaceful environment, as well as on the whims of the donor. And although in this case I agreed, politically, with the opinion of the EU to withdraw funds from Mobutu’s regime, I also saw that the result was that six months later, blood was no longer being screened for HIV in Lubumbashi. I had tried to send as many tests as possible, being creative with my research budget in Antwerp, but there was a limit to what I could do about the salaries.
A FEW MONTHS after his appointment, Merson asked me to help him develop some strategy ideas for the GPA. At the time we were working a lot in Nairobi on sexually transmitted infections and their role as a portal for transmission of HIV. We had lengthy discussions about the fact that WHO had two completely separate departments for sexually transmitted diseases and for AIDS; they did not collaborate. The sexually transmitted disease department was headed by André Meheus, my old friend from Antwerp with whom I had gone to Swaziland. I tried to get him and Mike together, but although André had a staff of three and GPA had hundreds, André felt that as the nominal head of the world’s efforts to fight sexually transmitted disease, he should have been in charge of AIDS too. Just as he had when Mann was in charge, he constantly challenged Mike Merson’s authority with donors and with WHO’s executive board At the same time, AIDS professionals ignored the wealth of experience in preventing classic sexually transmitted diseases, rather arrogantly claiming that AIDS is totally unique and that everything had to be reinvented. I proposed that WHO merge the programs, and I brokered an agreement that GPA’s board approved. André’s department was made a division of GPA and this made him answerable to Merson. Ultimately the two men came to a decent working relationship. I did not realize it at the time, but I was becoming a kind of health diplomat.
I was named to committees at the European Union, the US National Institutes of Health, to councils at WHO and in Belgium and France, and in Florence in 1991 I was elected president of the International AIDS Society, the association of AIDS professionals. I was laying out agendas for research, evaluating other people’s work. I was becoming part of the global AIDS establishment. I think I was quite hard on people working with me—what is the question we are trying to answer?—pushing our discussions until the question was staring stark at us. In science, asking the right question is key to finding a relevant answer, just as in life it is the path to wisdom. Sometimes research is like creating a flint: you have to tap it the right way until you find the sharp cutting tool inside the rock.
I reviewed the work of my juniors every six months. Had we maintained quality work? In the very messy world of field studies, had we done the job the way we’d intended? When the time came to break the code and correlate results, or analyze the data and find any kind of statistical associations or their absence, you had to maintain a sure hand. Some people underdo it; they do important work then fail to draw the interesting conclusions. Others go for drama, and that is even worse.
Money came in; work went out. But my administrative skills were definitely at their limit. I had over 100 people working for me in Antwerp alone, and budgets for all kinds of different programs to manage, often with several donors, each with their own rules and conditions. At one point I received a monetary award for my research, and instead of putting it into Nairobi or Kinshasa as I would usually have done, I invested in a much-needed three-week executive course in management at Harvard (everybody else was from private corporations). Like many academics, I was very disciplined with research but a terrible manager of people; my style was very ad hoc and impulsive, pushing problems away until the last possible minute, creating (though I had never seen it that way) stress and chaos. At Harvard I learned to be much more systematic, seeing my staff and collaborators regularly, asking for their feedback, giving positive reinforcement. It was an excellent course, which has helped me a great deal to this day.
IN THE LATE eighties a group of African scientists organized a Society for AIDS in Africa. They asked me to be part of the founding group, which I took as an honor. There had already been three conferences on AIDS in Africa in Europe—the first one organized by Nathan Clumeck in Brussels in 1985, and only one in Africa, in Arusha. The African society was now keen, and I fully supported them to organize these conferences on the African continent to allow scientists from the region to exchange experiences and foster collaboration, as they had far less opportunity to do so at international conferences. Dr. Bila Kapita badly wanted it to happen in Kinshasa. I felt we owed him an enormous, unrepayable debt. Although Kinshasa’s conference facilities were not great, to say the least—and despite the mounting political trouble in Zaire—I agreed to organize an international conference on AIDS and sexually transmitted disease in Africa in October 1990, which would be the second to actually take place in Africa.
We raised enough money to rent the Palais du Peuple, a convention hall graciously donated to Zaire by China and where Mobutu’s party held its meetings. But we didn’t have much money left over, and particularly needed some to host African participants. So for the first time I had dealings with the market in foreign exchange. I went to the diamond district in Antwerp—tiny shops that are the center of the world diamond trade—where Zaireans had more or less obscure dealings with diamond traders. I had over a hundred and fifty thousand Belgian francs (then about $50,000) with me in cash; it came from the nonprofit foundation of the department.
I had been given the name of a man. I gave him the money. He told me to come back the next day and he would give me the sum back in zaires (the Zairean currency). I was flummoxed and asked for a receipt. Of course he laughed at me: there are no receipts in this kind of market. Still, the next day he handed me the zaires: a small bag full of bank notes. This procedure multiplied by about three the budget I would have had if I had converted it at the official excha
nge rate.
So I flew to Kinshasa with money packed inside my underwear and socks. Normally every article was meticulously picked through by customs people looking for bribes, but I used my special Order of the Leopard card, and got through customs without a problem.
When I got to Kapita’s place he told me the budget that he had been promised from the government hadn’t arrived yet. The whole thing was looking like a disaster. But a couple of days later a man from the National Bank arrived, with no warning, at Kapita’s house with a suitcase full of freshly printed zaires. So this was our budget for our international conference: a bag and a suitcase of cash. Ultimately we had a surplus as far more participants showed up than we had planned, meaning higher income. We used all the benefits to refurbish some of the hospital wards at Mama Yemo Hospital in Kinshasa, construct a clinic in Kapita’s home village in Bas-Congo, and to support further education of young Zairean doctors.
I asked the prostitutes from Matonge to prepare food for the conference; I figured it would be a nice income-generating project, and an alternative to sex work. We budgeted enough food for 1000 people; this was how many we were expecting to attend. (In fact, 1500 showed up.) And we decided to have a big party with one of the hundreds of local live bands. But logistics were a nightmare. We had block-booked the Hotel Intercontinental, but it turned out the manager was new, fresh in from Florida, and had no idea of how to operate in Kinshasa. The day before the conference opened people who had reserved rooms were being made to double-up and some were turned away, because the desk clerks were accepting bribes from people who had no reservations. So I made a deal with the manager: I gave him a bottle of whisky and a carton of cigarettes and he gave me the codes of the computer reservation system. I sent the desk clerks home with pay and put Jan Vielfont, my creative and unflappable assistant in charge.