by Piot, Peter
CHAPTER 11
Projet SIDA
SO THAT WAS it: a second trip to Zaire that changed my life. The Ebola epidemic had transformed me when I was in my twenties; and now, seven years later, with this trip to Mama Yemo Hospital in Kinshasa, I was transformed again.
I sat on the bed in the room we were sharing at the Fométro that night and wrote down the thoughts that came to me as I faced the prospect of devoting a huge portion of my professional life to pursuing another lethal epidemic in Central Africa:
PROS:
INTERESTING AND NEW
• Huge problem
• Making a difference for people
• Prestigious
• Exciting research
• Lot of publications and possibility of developing
a long-standing program in Zaire
CONS:
• Several trips a year to Zaire, in addition to Nairobi
• A lot of administrative fights in
Zaire, Belgium, with the Americans
• Mediating permanent conflicts
• Constant reports to the NIH
I tried to dissect things down to bullet points, to very simple questions. But these are often not that useful in decision making, as was the case here. I didn’t need the list; I already knew the answer in my gut. It was one of those very rare moments in life when you can almost physically feel the trajectory of your life shift. I had met something unknown, enormously powerful, that I, with my experience in Africa, and as a microbiologist, was in many ways equipped to hunt down. I knew I was going to pursue this thing as far as I could.
Still, the list that I came up with was clear. This was going to be a passionately exciting adventure—an opportunity to influence the course of history—but it would also mess up my professional and personal life with way too much travel and create enormous political and bureaucratic tangles.
Indeed, the next page in my notebook contains observations about a meeting we had the next day at the University of Kinshasa with Professor Jean-Jacques Muyembe, now the dean of the medical school. He was a good man and a very able scientist, but the university was in dire straits professionally and financially, dependent on rapacious officials in the Ministries of Health and of Higher Education. I knew him from Ebola days, as he had led the first team that went to Yambuku before the internationals arrived. He asked us for subsidies, scholarships, a budget to help set up a group on AIDS work, reagents, and also a commitment to produce two publications, so that the staff from the University of Kinshasa would also get scientific recognition. So the complications of working in a country struggling with poverty and failed governance came up right away. This meeting also exacerbated my own feelings of impotence: I knew that Muyembe’s requests for help were all legitimate and yet I was unable to do much to assist him.
We needed to start collecting and examining blood samples. We set up a small lab at the Cliniques Universitaires with Sheila Mitchell from the CDC doing cell counts by hand. There was still no accepted laboratory test for the cause of AIDS. A team headed by Professor Luc Montagnier of the Pasteur Institute in Paris had identified the virus causing AIDS—he called it lymphadenopathy associated virus (LAV)—from a gay man who had traveled in the United States. But there was still no serological test for “LAV” available, and there was dispute about whether it was the cause of AIDS: Robert Gallo from the US National Institutes of Health claimed to have independently discovered the virus causing AIDS, calling it HTLV3. (Later it became clear that his virus was the same as Montagnier’s.) Still other people theorized that the cause of AIDS was not a virus but some combination of various toxins.
Thus, initially the best marker for the virus was the ratio of T lymphocyte “suppressor” cells and “killer” cells, and all of them had to be counted manually. A little later an energetic young French researcher, David Klatzmann, showed that the human immunodeficiency virus, as the cause of AIDS would be called, selectively killed T lymphocytes with CD4 receptors, which are like the traffic cops of the immune system. Following Klatzmann’s discovery, we no longer had to measure T helpers, just CD4s. And later still, we had the antibody test. But in 1983 it was still all far more complex and indirect.
We stayed in Kinshasa for five weeks, taking samples and working out a clinical case definition, because we knew that people would tell us, “This thing you’ve found in Africa—it’s not AIDS, it’s immune deficiency, maybe it’s something to do with malnutrition or parasitic infections.” We were working in an area of obvious diagnostic uncertainty, and we wanted our data to be unchallengeable, rock solid so that what we called a case of AIDS was, beyond dispute, a case of AIDS.
By November 2 we had about a hundred cases from Mama Yemo Hospital and the University Hospital that we felt were probably AIDS, but we were certain about 38 of them: 20 males and 18 females. Ten of them died during the study period, and 8 more died before the end of 1983, giving a 47 percent fatality rate within three months. They had striking clinical features: profound weight loss, with punishing, intractable diarrhea of unknown origin that seemed completely resistant to treatment: you don’t often see that kind of diarrhea in adults. They were also plagued by persistent fever; headache; cough; difficulty in swallowing; oral thrush; swollen lymph nodes; dramatic itching with goosebump-type skin lesions; cryptococcal meningitis; herpes; oral candidiasis; and bilateral pneumonia. Sixteen percent had disseminated Kaposi’s sarcoma. Twenty-five percent showed past or present syphilis. Men reported a lifetime average of seven sex partners, while the women (who were younger than the men, and almost all divorced) averaged three. The chronology suggested female-to-male transmission as well as male to female, and though this wasn’t hard evidence, it was the first suggestion of female-to-male transmission. We could find no suggestion of homosexuality of drug use.
We also did a rapid overview of the hospital records, using cryptococcal meningitis as a marker, as the ubiquitous and normally innocuous fungus Cryptococcus neoformans only causes severe infections such as meningitis in people with severe immunodeficiency. And we found a few cases dating back to 1975, though it was impossible to confirm that they were AIDS. There was about one case per year until 1979 in each of the hospitals—University Hospital, about 40 minutes’ drive from downtown, the Clinique Ngaliema, the Clinique Kinoise, and Kitambo Hospital, as well as the massive Mama Yemo, which was the only one that offered free medical care. But since 1980 each hospital showed more than 30 cases per year, which suggested the real boom in AIDS infections in Kinshasa might be roughly simultaneous with the one that appeared to be underway in the United States.
One day I did a very stupid thing: something I had warned I don’t know how many hundreds of students never to do. I recapped the syringe that I had used to draw blood. I tried to put the plastic cap back on the needle before throwing it away. Such a pointless gesture. (It must be something to do with the Flemish obsession for neatness.) And I missed. I stuck the needle into my finger. I watched the blood pool up from the tiny puncture wound and hastily pressed it as hard as I could, hoping to squeeze out every drop of blood. There was nothing else I could do except disinfect it and move on. There was every reason to suppose the man whose blood I had just drawn had AIDS: he was in a terrible state. But there was no way then to know whether he was infected or I had been infected.
On my way home I flew to Johannesburg to speak at an Infectious Disease conference at the University of Witwatersrand. I could talk of nothing but AIDS and the epidemic we had just seen in Kinshasa. There was just one AIDS case in South Africa back then: a gay white man who had probably become infected while traveling in the United States. These were well-trained physicians I was talking to, eager to learn about AIDS, fascinated by what I was telling them about the outbreak in Zaire. But no, they kept telling me, no: they were certain, there was absolutely no unusual immune deficiency in South Africa at all. (Today we know that they were correct. Although later South Africa was swamped by the world’s biggest AIDS epidem
ic, in 1983 the virus had not yet hit the country.)
When I got back to Belgium I spoke to Tom Quinn, who had left Kinshasa earlier, to attend a World Health Organization meeting in Copenhagen. He said the whole conference was about AIDS in Europe and North America. Africa didn’t figure at all in the picture, and there was no discussion of AIDS among heterosexuals who didn’t use drugs.
Early 1984 I sent the blood sera we had gathered to Montagnier and Françoise Brun-Vézinet in Paris, so that they could take a look at the antibodies, checking them against the so-called LAV virus that they had identified. Even though Tom and Joe were American, there was no dispute about sending our samples to Paris when I suggested it following a brief encounter with Montagnier at an EC meeting on my return to Europe.
One of the blood samples we sent to Montagnier’s team was from the man whose blood briefly mixed with mine when I made the stupid error with the needle-stick. And I also sent them my blood. I was really scared.
I sent the sera under code, and I was the only one who had the code. Montagnier’s lab had no way of knowing which samples were from suspected AIDS patients and which ones were healthy controls, so in some sense this was just as much a test of the validity of his research as it was of ours. When he phoned me with the results, in February 1984, he seemed as nervous as I was. He went down the list—sample number 2, positive; sample number 3, negative—and I checked them against the code. Oh my God! That was it! He had a test! Montagnier’s positives included just about all the people with clearly manifested clinical signs of AIDS: 97 percent. And although some of the people who had no symptoms were also positive, that result was not necessarily false: they might be asymptomatic carriers of the virus.
It was a very important and thrilling moment. And to me, equally thrilling was that my blood came out negative. The man whose blood briefly mingled with mine was antibody positive but I was clear. The relief was almost too much to take. It was a real life lesson for me and, ever since, I make sure that every HIV test performed by any team of mine involves the least possible waiting time before the result is given to the patient. This is not a routine procedure where you can tell people, “Come back in two weeks.” The anxiety is simply unbearable.
Coincidentally, it was about this time that I read Shadow on the Land, a great book by Thomas Parran, a US surgeon general in the 1930s. He brought syphilis out of the closet; back then you couldn’t even say the word “syphilis” in polite conversation, not to mention discuss its transmission. He estimated that well over 1 percent of the US population was infected, and it was Parran’s drive for public awareness about syphilis, just as much as the discovery that penicillin could cure it, that drove the shadow from the land. (By the end of World War II, the US Public Health Service estimated that 1 in 10 Americans would acquire syphilis in their life time.) The book was an eye-opener for me. I had no clue that the Western world had so recently had such a huge syphilis problem, and I had never really thought deeply about the nature of bigotry about the disease, and the lethal effects such denial could have. (In 1998 I was awarded the Thomas Parran Award by the American Sexually Transmitted Diseases Association; this moved me greatly.)
Some people in Europe often clearly looked on AIDS as God’s way of saying you shouldn’t be a homosexual. The discrimination against AIDS patients was horrible. To me it recalled my childhood afternoons at the Father Damien museum, mulling over the hideous and medically unjustifiable stigma against leprosy.
I went on a live TV show with a colleague general practitioner from Antwerp, Dirk Avonts. We had painted a piece of broomstick in pink—it was pretty big, like a foot and a half tall, so it would show clearly on camera—and without giving any advance warning to the TV crew, Dirk showed how to put a condom on. That created quite a scandal and a flurry of letters to newspapers: how could we be permitted to broadcast such obscenity? My point was we needed to take this kind of shame out of the equation.
It wasn’t until July 1984 that our paper with the Kinshasa results appeared in The Lancet. Initially it was rejected as being “of local interest only.” (For another, later paper I submitted to the New England Journal of Medicine, an early referee wrote as sole comment: “it is a well-known fact that AIDS cannot be transmitted from women to men.”) People had already developed the mindset that this was “just” a gay disease. I never understood why a virus would care about the sexual preference of its human host, because I applied what Stanley Falkow had told me when I was working in his labs: put yourself inside the pathogen. From the perspective of a virus, what is sex between human beings but contact between mucosal surfaces? It may not sound very romantic, but that’s the contact that makes the virus jump from one cell to another to perpetuate its own life. I don’t think the virus cares whether the sex is good, or about the color or gender of the person who inhabits that mucosal surface. Granted, some types of intercourse may be more efficient than others but none was exclusive. So I was always puzzled by this dogmatic insistence on AIDS as a homosexual disease.
Meanwhile, I wrote up a $600,000 grant proposal for the NIH that was about 70 pages long, laying out a whole research plan for a three-year project to study what was happening in Zaire. We were all very excited about it. Six hundred thousand dollars—total—for a three-year program seems like so little today, but I was just an associate professor in those days, and I made $1000 a month at the exchange rate of the time. The major point was that our brief experience in Kinshasa already made clear that AIDS was, at least in certain conditions, a heterosexual problem. That meant that there was really an enormous potential for harm across the population as a whole.
We needed to clarify that, and look at risk factors in a very systematic, in-depth way. Also, we could already see there was probably at least some mother-to-child transmission, and this was completely new to us. A third point, perhaps more controversial, was the span of the problem we’d seen, which suggested that the disease could have been around in Central Africa for longer than in the West, even though it didn’t look that way at first. Fourth, we needed to understand the course of the disease in Africa. Was it the same as in the West? For example, it already seemed from our experience with AIDS in Belgium that Africans had less Pneumocystis carinii pneumonia and Kaposi’s sarcoma, and more cryptococcal meningitis, than their European counterparts, but our sample was relatively small, and we did not know whether these findings were representative of what was going on in Africa.
We planned to establish a lab at Mama Yemo Hospital, with facilities for hematology, microbiology, and immunology tests including analysis of lymphocytes. We would do a full immunologic profile of patients who looked like they had AIDS and compare them with healthy controls, surgical patients, and people with TB, and various parasitic illnesses, so we could develop a solid case definition of AIDS in Africa. We would study potential risk factors—sexual activity, blood transfusions, needle exposure—basically, an epidemiological study just like we’d done with Ebola. And we would do a prospective study with family contacts and sexual contacts of the patients, to look at their clinical and immunologic status over time, and whether HIV could spread through casual contact in households in an environment where people live very close to each other in overcrowded houses and are constantly exposed to bites of all kinds of insects. Finally, we planned a major study of AIDS in children.
The proposal sailed through various committees and everything looked fine until suddenly, toward the end of January 1984, there was silence from the side of the NIH. The CDC had decided to start their own program in Kinshasa and had recruited the state epidemiologist of New Mexico—a doctor named Jonathan Mann—to do the job.
The first I heard about this was a phone call one afternoon in early March from Jonathan Mann. He said he was on his way to Kinshasa to set up a CDC project on AIDS. I wanted to say, “WHAT?” but didn’t. But he asked if he could stop by my office in Antwerp on his way there, and of course I agreed. So I picked him up at airport in Brussels, and although I was ver
y tense initially, he turned out to be a very charming man, rather diffident, physically something between Albert Einstein and Groucho Marx, with an intense, interested manner, almost like a psychoanalyst. He told me right away that he’d never been to Africa and he was clearly nervous about it. His French was very good; he was then married to a Frenchwoman. So we hit it off reasonably well, and we agreed that we would have no problem working together.
I joined him in Kinshasa at the end of March. I introduced him to various people, and I gave him a copy of the proposal that I had written up with the help of Tom Quinn and Joe McCormick. Going around the hospitals, it was clear there were new cases of AIDS: Bila Kapita, at Mama Yemo told us he suspected about another 100 since we had left less than four months before, with two new patients with cryptococcal meningitis turning up every week.
In April I received news from the NIH that my grant was not accepted. Later I found out that Jonathan blocked it for reasons that I can understand now since he was going to head up what would rapidly become the largest biomedical research project in Africa. Happily it took several years before I learned this, and by then I had developed enormous respect for him. He was a very complex personality—as an individual, rather insular and a control freak—but he had an incredible mind in terms of linking things that had not been linked before, like human rights and health. He had studied at the famous Sciences Po school in Paris, and combined political analysis with the public health aspects of AIDS; he strove extremely hard to move the field toward justice for the downtrodden in a way that was completely unique. He became an extremely skilled diplomat with a long-term vision, and on the other hand he had no tolerance for all the bureaucratic nonsense and inaction that is so characteristic of international agencies.
But at the time, the salient information was that the NIH had decided to drop me completely. They would partner directly with the CDC, and they selected Skip Francis, an African American immunologist who worked for Tom Quinn, to go to Zaire and work with Jonathan. So now I had no money for the work that I so badly wanted to do. However, Jonathan agreed that the Institute of Tropical Medicine could become a partner in Projet SIDA (SIDA is the French acronym for AIDS). We would be in charge of clinical studies, an area that he wasn’t much interested in. The proviso was that I had to come up with the money to fund our work.