The Invisible Cure Why We Are Losing the Fight Against AIDS in Africa

A New York Times Notable Book of 2007 The Invisible Cure is an account of Africa's AIDS epidemic from the inside--a revelatory dispatch from the intersection of village life, government intervention, and international aid. Helen Epstein left her job in the US in 1993 to move to Uganda, where she began work on a test vaccine for HIV. Once there, she met patients, doctors, politicians, and aid workers, and began exploring the problem of AIDS in Africa through the lenses of medicine, politics, economics, and sociology. Amid the catastrophic failure to reverse the epidemic, she discovered a village-based solution that could prove more effective than any network of government intervention and international aid, an intuitive response that calls into question many of the fundamental assumptions about the AIDS in Africa. Written with conviction, knowledge, and insight, The Invisible Cure will change how we think about the worst health crisis of the past century--and indeed about every issue of global public health.

Chapter One
The Outsiders
APRIL 1993 About two weeks before I was supposed to leave for Uganda, I packed up the materials I would need for the experiment I planned to do there and called Dr. Arthur Murray, whom I would be working with, to confirm the shipping address. “Maybe you shouldn’t send the stuff just yet,” he said. “There’s a problem?” “There may be a problem.” “Is it a bad problem?” “It could be.” “Is it a political problem?” “Well, not the whole country.” “Just the project?” “Yeah, just the project.” A few days later he called and said that everything was OK; the problem had had to do with a truck. “A truck?” “Yeah, a truck.” I knew there had to be more to it than this. I arrived at Entebbe airport in a small propeller-driven plane from Nairobi and walked across the tarmac to a two-story building that had been almost completely gutted. The only light came through the doorway; fragments of electrical wiring and old plumbing fixtures, black with tar and dirt, dangled from the walls and ceiling. A man lounged on an elevated platform; a sign above his head said health. This was the man who checked your immunization papers. Before I left, I had been told that to be allowed past him you needed to show that you’d had injections for yellow fever, cholera, and typhoid. Malaria pills and injections for hepatitis A and B and rabies were recommended. Arthur was there to meet me. During the drive to Kampala, we talked about my materials, which still hadn’t arrived. I’d called the shippers before I left, and they’d told me they thought a project called CHIPS was closing and, thinking that my project was part of CHIPS, they hadn’t sent anything out for me. I told the shippers to send my parcels anyway, but what was CHIPS? When I asked Arthur, he became tense. “Just don’t talk about that,” he said. So I didn’t. It was midday. I had been up all night on the airplane, and my first view of Africa out of the car window seemed like part of a waking dream. Soldiers in baggy green uniforms carrying heavy machine guns shambled by on the road. We drove along the shore of Lake Victoria, which sparkled in the sun. A bright yellow bird ?ew up out of a marsh, and vines cascaded from the crabbed and twisted branches of giant trees. I made myself a promise, which I would soon break, to learn the name of every plant and animal I saw. Within a few miles of the airport, the road gave way to threadbare patches of tarmac and our progress slowed considerably. The air was heavy with diesel fumes, wood smoke, and fine ochre dust. We passed through towns: the road became an open-air market, with kiosks selling furniture, chicken coops, spare parts for cars, machine tools, jerry-built appliances of all kinds. Pale green trucks stood in the middle of the street wheezing black vapors. Their flimsy metal frames were piled high with bananas, foam-rubber mattresses, and chickens crammed in their cages, their feathers raining everywhere. Along the roadside, there were old men in baggy suits; dusty, barefoot workers; children dressed in rags; stray goats; and stout women in colorful wraps selling green bananas and charcoal from lean-tos constructed from stripped tree branches roped together with banana leaves. Everything seemed handmade, makeshift, rough-hewn. Small, colonial-style cement bungalows, their roofs dented and askew, ranged untidily over the hillsides. Without a sterilizing winter, their foundations were riddled with cracks from the intrusions of tree roots, creeping molds, burning sun, and driving rain. Over the coming months and years, I too would have to contend with the forces of nature. There would be power cuts and water shortages and broken toilets and stuck doors and cars that started only when you kicked them. Most of the time, someone would find a way of rigging things to avert disaster. ARTHUR DROPPED ME OFF at the house of his colleague, Dr. Celeste Quinn, on the campus of Makerere University, where I wouldbe staying. Celeste was a gynecologist working with the urban poor in Kampala. She was also the director of CHIPS, the U.S.Agency for International Development–funded project that I was not supposed to talk about. Like most expatriate residences in Kampala at the time, Celeste’s house was a space pod of Western comfort. There were guards, servants, a telephone, a television. Celeste was a large, slightly intimidating woman, with a physician’s scrubbed white hands. When we were introduced, she extended an ivory arm and gave me a brief smile. She was seeing off some friends at the door and seemed distracted, so I sat in a wicker chair on the back porch and played with her cat, which emerged from its cardboard box and slunk over to me. I would be working in a lab at the Uganda Cancer Institute, a compound of weathered one-story concrete buildings on the grounds of Mulago Hospital, the only state-run hospital in Kampala at the time. The lab was next to the dental clinic, and the screams of the children being treated there could be heard all day long.The Cancer Institute had two barn-like open wards that were so dark and overcrowded that most of the patients and their families lounged on the verandahs and gravel yards outside. They bathed their children under an outdoor spigot and prepared maize meal and mashed bananas on open wood fires. On the Cancer Institute grounds I saw people with growths on their necks the size of pineapples, and people without arms or legs. I saw a man without a nose. My lab was a short distance uphill from the Cancer Institute. Arthur took me there the day after I arrived. We walked through the main lab, which was crowded with equipment and Ugandan technicians, and entered a much smaller room, which had no light and was full of empty cardboard boxes and rusty machine parts. When he pushed the door open, plumes of red African dust rose and swirled around us. “We were thinking of putting you here,” Arthur said. It was clear that some other place would have to be found for the boxes and machine parts. A plasterer and painter would have to be hired, and we would have to install a refrigerator, a light, and a table. Some time would pass before I could begin my experiment.A few days later, a contractor was hired, but he quarreled with the institute’s accountant over how much the job would cost. The two men negotiated within five dollars of each other before the contractor lost his temper and left. It took two days to get him to come back and accept his own terms. I grew accustomed to such delays. The materials I had shipped from California were still missing in any case. The American shipping company assured me the boxes had been sent and should have arrived. The airline said the boxes were with customs, customs said they were with the clearing agent, and the clearing agent said they were at the Cancer Institute, where, according to Celeste, who kept track of the shipments that came in, they could not be found. I had come to Kampala to carry out an experiment that I hoped would contribute to the development of a vaccine to protect Ugandans against HIV, the virus that causes AIDS. I became interested in the problem when I was doing postdoctoral work in California. I had been studying the sexual organs of a tiny insect the size of the letter I in ELIZABETH on an English penny, when I realized I was finding it increasingly difficult to concentrate. I had recently heard a lecture given by a scientist named Kathelyn Steimer about the HIV vaccine that her lab at Chiron, a bio technology company near San Francisco, was working on. It had been injected into about two hundred volunteers so far, and the results were encouraging. After the lecture, my mind never seriously returned to the insect world. My research had been bothering me for some time. In my university biology department, and others like it, “frontiers” were the thing. It was unfashionable to study anything for a practical reason. We thought of ourselves as the astronauts of the cell, exploring the logic left behind by evolution’s intricate digressions. Our heroes were the men and women who described the structure of the gene, saw the first microtubule, and found out how ribosomes worked. We were not in the business of developing cures or vaccines. My academic outpost near San Francisco was some distance from the frontier. In the 1920s, a German scientist discovered that if you stained the nucleus of certain insect cells and looked at them under a light microscope, you saw a black dot. He wrote a series of long, detailed articles on the subject suggesting that the black dot was a chromosome, and left it to posterity to figure out what it was for. My boss believed that the black dot was extremely important. He theorized that it determined sex, that it contained a genetic memory bank, that it was some sort of death clock. We spent hours discussing it. The aphid-like bug I was studying was tiny and round and had six legs, each consisting of three segments. It had a pair of short antennae with seven segments and a tiny mandible. Its little body was covered with pores from which it secreted a white goo in which it hid. I asked my boss whether we all shouldn’t be out helping the poor and the sick, rather than studying the molecules inside the sex organs of a bug that was almost too small to see. “The poor and the sick will always be with us,” he said, “but we will change the way people think about the world.” Although my boss didn’t say it, I knew that he considered work like Steimer’s pedestrian. He had a point, I suppose, but when I looked around at all the people in the lab muttering recondite gene-speak, it all began to seem very strange. I longed for a biological problem that had meaning outside the world of academic conferences and biochemical journals. I had known several people who had died of AIDS. Most were young; all suffered horribly. Although scientists had spent billions of dollars trying to understand how the virus worked, they had as yet found no way to stop its spread. AIDS had devastated the gay enclaves of New York, San Francisco, and Los Angeles, and the news from the developing world was even worse. Millions of people in East Africa, Thailand, and India were already infected. Steimer’s vaccine consisted of a harmless suspension of molecules called gp120, and doctors had injected it into two hundred HIV-negative volunteers so far. Steimer hoped that the gp120 molecules would train their immune systems to fight off HIV if they were ever exposed to it. Many of the volunteers were homosexual men who had watched their friends die of AIDS. Some of these men were sexually active themselves, and thus they were also at risk of HIV infection. Although they had been advised to avoid risky sex and use condoms, not all of them complied with this advice. Soon Steimer would know whether her vaccine protected these men or not. She was hopeful because Chiron had developed a similar vaccine for hepatitis B that had saved many lives and earned the company billions of dollars. So far the results with the HIV vaccine looked promising too. A few weeks after Steimer’s lecture, I asked a doctor I knew who had worked on AIDS in East Africa if he thought a molecular biologist might be useful there. He suggested I write to a professor in San Francisco who was conducting a study of sexually transmitted diseases (STDs) in Uganda. Perhaps he would be able to give me some advice. I had read about the AIDS epidemic in Uganda. One-third of adults in the capital city, Kampala, were HIV positive, and the virus was spreading along trade routes into the countryside. Thousands of children had been orphaned by the disease, their farms left idle because their parents were dead or too sick to work. I wrote to the professor and phoned his secretary some time in August. She said he was very busy but had time to see me at eleven-thirty on October 23, 1992, for about fifteen minutes. Professor Cornelius was about fifty, a small, round man with a tennis-ball fuzz of hair around his cheery face. “So, you want to go to Africa!” he boomed. He talked about the poignant beauty of Kampala—the crowded, dirty city; the skeletal remains of the stone buildings, gutted by war; the surrounding hills and the vast slums in the folds of land between them—and about Makerere University and Mulago Hospital, once the most distinguished in East Africa, destroyed by Idi Amin, Milton Obote, and twenty-five years of murder, corruption, and neglect. In the mid-1980s, when health officials first recognized the magnitude of the AIDS crisis in Africa, they feared that this great plague affecting heterosexual people would spread north, to Europe, the United States, and other developed regions. There were predictions that it was only a matter of time before large numbers of ordinary non-gay, non-drug- using Americans—college students, Wall Street executives, housewives—would find they were HIV positive. So the U.S. government, through the National Institutes of Health and the U.S. Agency for International Development, poured money into research. Professor Cornelius was one of those trying to find out why so many heterosexual people in Africa were infected with HIV. At the time, there were many theories about it, but Professor Cornelius and others believed that it had something to do with the prevalence of STDs there. HIV-infected cells and virus particles do not penetrate unbroken skin, and they don’t survive long outside the body. In order to pass from one person to another, they must encounter mucous membranes, the slimy surfaces of the body’s internal cavities, such as the vagina and rectum, and even then, it is not a certainty that infection will occur. STDs—syphilis, gonorrhea, herpes, and so on—cause genital sores and ulcers that Professor Cornelius and others thought created direct channels to the bloodstream through which HIV could pass very easily. STDs were common in Uganda. Although most cases could be cured with cheap antibiotics, two decades of civil war and economic demise had left half the population without any medical care at all, and the situation wasn’t much better in other impoverished African countries. Professor Cornelius was overseeing several projects related to AIDS in Uganda, one of which, CHIPS, the project I was discouraged from talking about, was being run in Kampala by his young colleagues Celeste Quinn and Arthur Murray. In the course of their work they had collected blood samples from thousands of patients at a public STD clinic in Kampala, which were now stored in a freezer. About half the patients were HIV positive. No one had yet studied these samples. Perhaps this was something I would like to work on? We discussed possible experiments. During the meeting, Professor Cornelius was interrupted by an urgent phone call, and his secretary appeared at the door making frantic gestures that I was not supposed to understand. I HAD BEEN IN KAMPALA for three weeks. The plasterer had fixed up my little lab, which now had a light and a table, but I still needed a refrigerator.The Cancer Institute’s accountant authorized the money to pay for it, and Vicki, the large, beautiful Ugandan woman who ran the institute storeroom, said she would help me buy one. She warned that Ugandan dealers would double the price of anything a white person bought, and recommended we go to an Asian shop.Traders from the Far and Middle East have been coming to East Africa for centuries. Until the 1970s, South Asians ran most of Uganda’s businesses, factories, and sugar and cotton mills; they built many of the towns, taught in the university, and owned a great deal of property. Then, in 1972, Idi Amin threw them all out and gave their property to black Ugandans. Chaos ensued. The new African entrepreneurs were totally inexperienced and the economy fell into ruin. Amin spent what little foreign exchange remained in the country on whiskey and transistor radios to placate the army, and soldiers and other government henchmen looted at will.1 Yoweri Museveni, president since 1986, in a bid to both redress past injustice and restore the economy, offered the Asians the chance to return and reclaim their houses, shops, and factories, and many did. The Asian shop Vicki took me to was small and crowded, but the man behind the counter seemed to know her, so we didn’t have to wait long. He showed us a refrigerator called a Sno-Cap. “How much?” Vicki asked. “Twelve hundred thousand shillings.” “Eight.” “No.” Silence. “OK, eleven hundred and fifty.” “Nine.” “No.” “Come on, nine hundred.” “Eleven hundred and that’s as low as I can go.” Vicki looked at me and I shrugged. “OK,” she said. The refrigerator that arrived at the lab a few days later was half the size of the one we thought we had purchased. My boxes were still missing. I consulted Celeste, but all she could do was sympathize. In the two years she had been working in Africa, she had seen this happen a thousand times. Sometimes things just vanished. Uganda was a developing country after all, and life here was chaotic. Celeste had something to confide in me too. The project she was running was also in trouble. CHIPS—the Community Health Initiative to Prevent Sexually Transmitted Diseases—was a $1.5 million project funded by the U.S. Agency for International Development (USAID). Celeste was the director and had written the original request for funding and had hired the 132-person Ugandan staff. CHIPS had been running for about a year and was located in a Kampala slum called Kisenyi, which means “swamp” in Swahili. It lies between two hills, where two of Kampala’s many cathedrals stand. Catholic and Protestant missionaries brought Christianity to Uganda in the 1870s, but within a decade the converts were at war. Thousands were killed and peace would not return for another twelve years. Religious tensions persist in Uganda to this day; Kampala’s Catholic and Protestant cathedrals now face each other from adjacent hills, and Kisenyi lies in the depression between them. When it rains, garbage and silt run down the hills and collect in Kisenyi. The air smells of rotting banana peels, children gather food from garbage heaps, and rivulets of sludge course through the narrow passageways that serve as streets. Kisenyi is where people displaced by war or poverty end up when they come to Kampala. Everyone is poor and unemployed, and yet everyone appears to be doing something. The men fix bicycles, make things out of wood, or steal. The women sell things: roasted bananas, cigarettes, sweets, themselves. The prevalence of both STDs and HIV infection was very high. CHIPS was established to see what effect a neighborhood STD clinic and HIV testing center would have on the spread of HIV. At the time of my visit, the only treatment available to people with STDs was the clinic at Mulago Hospital, which was overcrowded, faraway from where most poor people lived, and frequently out of medicine. Like many AIDS projects in Africa, CHIPS was an uneasy collaboration among three parties with different interests: USAID, which provided the money; Celeste, who was responsible for spending it; and the people of Kisenyi, on whom the money would be spent. USAID’s goal, determined by the US government, was to reduce cure the spread of HIV and other STDs and to promote family planning in developing countries. Its officials hoped that the CHIPS clinic would serve as a model for programs throughout Africa that would achieve both aims at the same time. USAID had a lot of money to spend—some twenty million dollars in Uganda alone at the time—and therefore it also had considerable power. It gave jobs to scores of American experts in public health, waste management, education, and so on, who in turn hired hundreds of local people. The interests of the people of Kisenyi were different. Free condoms and treatment for STDs were fine, but the CHIPS clinic was the largest, most modern building in the area. When they saw the walls going up, they must have wondered what it was all about. They must have hoped it would provide treatment to save the countless children in Kisenyi who die of malaria, diarrhea, and pneumonia every year, or the scores of women who die in childbirth. Perhaps it would even offer treatment for AIDS. Some people may have hoped to get jobs there. Moreover, Celeste was a scientist. She wanted to know which STDs were most common in Kisenyi, and the best and cheapest ways of treating them. She also wanted to know exactly how many people living in the area contracted HIV each year, and how many cases of infection could be prevented by the services offered at the clinic. Such a project might seem simple, but she must have encountered many frustrations along the way. I can only imagine all the things that could have gone wrong. AT MULAGO HOSPITAL, down the hill from the lab at the Cancer Institute, an American doctor was trying to determine how best to treat cryptococcal meningitis, which often affects people dying of AIDS. The doctor was ordinarily a mild man, but when I asked him if I could accompany him on his rounds, he agreed only reluctantly and seemed irritated. I asked if anything was wrong. “You’ll see,” he said. Cryptococcal meningitis is caused by a fungus that infects the fluid bathing the brain and spinal column. Everyone is exposed to the germ that causes the disease; its spores can be found on the leaves of certain trees or in the air. But the only people who get sick are those whose immune systems are in such disrepair, because of AIDS, cancer, or some other cause, that they can’t fight it off. The symptoms are nausea, vomiting, disorientation, and headaches so severe that when a child dies of AIDS in Uganda, it is often said that he died of headache. At the time, the powerful antiretroviral drug cocktails that can vastly improve the lives of AIDS patients had not been developed and would not become widely available in Uganda for another decade. The only treatment for cryptococcal meningitis available in Uganda at the time was amphotericin, a highly toxic medicine that, even in moderate doses, caused permanent kidney damage. The doctor was being paid to study a relatively new drug called fluconazole, which was not as toxic, but was very expensive. It was provided free to all AIDS patients willing to participate in the doctor’s study, but without antiretroviral drug cocktails, most of these patients would die within a few months anyway. Following the doctor on his rounds, I was not surprised by the chipped paint and grimy windows, the torn, dirty sheets, and the few items of rusty furniture. But I didn’t expect to see someone lying in a pool of blood, or meet a man who had spent the previous night having a seizure. A nurse, had there been one, would have known how to stop it, but the man stopped it himself, by lapsing into a coma. There were so few nurses at Mulago that patient care—feeding, washing, and alerting the doctors in emergencies—was virtually all done by family members. Mulago was a public hospital, and basic drugs and supplies should have been provided free, but they were rarely available. When a patient needed a drip line or an aspirin, a relative went to a market nearby. Some nurses and doctors also sold drugs and equipment—some of it stolen from the hospital stores—and they tended to overcharge. In the early 1990s, doctors at Mulago earned about $150 a month; nurses, fifty dollars. It was not surprising that some of them were so alienated that they made what extra money they could from their patients. Some, having taken other jobs, did not show up for work at all. The doctor went from bed to bed. There was another man in a coma, and another so weak he seemed able to move only his eyes. One patient had a private room. The place was tidy and sunny and clean. He must have been rich. Someone had brought two straw shopping bags full of provisions: cups and saucers, a Thermos flask, books, a soap dish. The patient looked all right to my untrained eye, not thin, with no obvious rashes or sores, breathing quietly—although he was moaning and writhing and holding his head. The doctor said he would give the man co deine, but the only way to make him comfortable would be to knock him out completely. He died the next day anyway. “Sometimes I don’t know what I am doing here,” the American doctor told me. But I did, and so did this doctor’s employers. Conducting this trial in the United States would have been far more expensive because the American patients would have required far better care. But ethical standards required that the pharmaceutical company needed only to ensure that the Ugandan patients received the standard of care in Uganda, which was very low indeed. At least the patients were getting something as a result of the trial, I thought. There was no placebo group, so everyone was treated. Nevertheless, the doctor knew that after the trial ended, he and the company would leave Uganda. No further patients at Mulago would receive free fluconazole until 2002, nine years later, when Pfizer, the company that makes it, under pressure from AIDS activists and manufacturers of generic drugs in Thailand and India, offered the drug free to African hospitals. Pfizer’s donation program, though generous, has been slow to get off the ground, and even today, cryptoccocal meningitis remains a common cause of AIDS-related death throughout Africa. Medical research in Uganda can be profoundly frustrating for the doctors involved. They are caught between the demands of their employers for convincing survival curves and those of their patients for help of any kind. A high proportion give up and leave. But for some, Mulago is a rewarding place, recalling a time when doctors were closer to their patients than they are now. Medicine in the West relies on expensive diagnostic techniques unavailable here, but some doctors I met in Uganda admitted that they had learned a great deal from being forced to rely only on a stethoscope. As one of them told me, “I never realized there was so much you could learn just from listening to someone’s heart.” I withdrew after a while to sit on a bench beside a thin old man who was staring straight ahead and wheezing. Between patients, the doctor came over to me. “Are you all right?” he asked. A funny question, I thought, to ask someone visiting such a place. “I’m not sure I can take this,” I said. “I can understand that.” If only my materials would turn up so I could start my experiment, I might not feel so useless, I thought. I tried to think of ways around it, of what local substitutions I could make, of what I could borrow from other scientists around Kampala. But what I was trying to do—design an HIV vaccine for Uganda—was way out on the high-tech edge. Many of the materials I was expecting came from highly specialized labs in the United States, and existed in small quantities. They were made nowhere else. Some of the materials had been donated to me by scientists who cared about the AIDS epidemic in Africa and wanted to contribute in some way to my project. I had been in Uganda for only a month, and already, I was disappointing them. WHEN HIV was first identified in 1983, many researchers thought it would be easy to develop a vaccine to protect people against it. But by the time I arrived in Uganda a decade later, this optimism was beginning to fade. To understand why it has been so difficult to make an AIDS vaccine, it helps to know what happens when a person first becomes infected with HIV. HIV is a spherical virus whose surface is covered with tiny stalks. There is a ball at the end of each stalk that consists of a clump of molecules called gp120. The gp120 molecules function like a key, enabling HIV to break into particular white blood cells—called CD4 cells—that help protect the body from disease. Once inside the CD4 cells, the virus takes over the DNA copying machinery and forces the cells to churn out millions of new viruses, until the cells eventually burst open and disintegrate or clump together and die. In the bloodstream of HIV-positive people, a billion CD4 cells are hijacked and killed each day, and 100 billion new HIV viruses are produced. 2 Right after infection with HIV, people feel nothing, but after a few weeks or months, some people become feverish, and the lymph nodes in their necks and armpits swell as the first immune response against HIV is being made. Lymphocytes and antibodies—Y-shaped molecules with mitten-like protrusions that latch onto and kill infected cells and microbes—clear most of the virus particles, but some viruses escape by mutat ing: they change slightly, infect new cells, and continue to reproduce. The body must make new lymphocytes and new antibodies to fight the mutants, but the mutants mutate again, necessitating a new immune response. The human immune system is able to fight off most viruses and clear them from the body, but not HIV. By the time the immune system begins making cells and antibodies it is too late. The virus has embedded itself in so many CD4 cells that it is impossible for the immune system to clear it without destroying itself in the process. As the CD4 cells die off, the body loses its ability to respond to a range of other infections. The patient is slowly consumed by diseases that are harmless to other people and dies. When I first heard Dr. Steimer’s lecture, I learned that it might be possible for a vaccine to prevent the virus from taking hold in people who were exposed to it. This is what had encouraged me to abandon the tedious complexities of the insect gonads that I was studying. The vaccines that protect people against infections are usually made from harmless versions or fragments of the microbe that causes the infection itself. When the vaccine is injected into the body, the immune system reacts as though it were the real thing. The bone marrow and lymph nodes generate cells and antibodies that specifically kill that particular microbe. These cells and antibodies constitute what biologists call “immunological memory.” They remain in the blood for years. If the real microbe enters the body, they are able to destroy it in hours rather than weeks or months, and clear it before it seizes control of vast numbers of CD4 cells. Back in California, I had learned that there were about thirty HIV vaccines under development, but many researchers were already losing hope that any of them would work because of the vast number of mutants. By all accounts, the most promising vaccine at the time was the one designed in Steimer’s lab at Chiron Corporation. Shortly after Professor Cornelius suggested that I might work with the bank of serum samples in Uganda, I contacted Dr. Steimer and she invited me to visit her lab. Chiron was founded in 1981 by a group of molecular biologists from the University of California, San Francisco, who had been among the first to isolate a human gene and clone copies of it in a test tube. Cloning provided an entirely new mechanism for making drugs and vaccines, and it soon inspired visions of corporate empires in biology similar to the rapidly growing software empires that had been established a decade before. Biologists who had once scrounged through forests, swamps, and sewers to find natural molecules that might be effective in treating diseases could now engineer them in bright, clean laboratories, or so it was hoped. Chiron occupies a ten-acre lakeside compound near San Francisco, and employs two thousand people, largely paid for by its multibillion-dollar sales of a vaccine for hepatitis B, the first vaccine to be created by cloning. I recognized Dr. Steimer immediately. She was tall, slim, and blond, and had the same efficient but melancholy and distracted manner I had noticed when she was giving her lecture. She showed me around the lab. We passed through the two main rooms, where work with uninfected specimens took place, and the isolation room, where technicians wearing blue bodysuits, booties, shower caps, rubber gloves, and face masks were working with live HIV virus. Was the virus really so dangerous to work with? I wondered. Dr. Steimer explained that although HIV mutates, she and her colleagues had a strategy that might contain it. Her vaccine consisted of gp120 molecules that her technicians had cloned in her lab. Because gp120 was the “key” that allowed the virus to break into cells, part of it was “conserved”—meaning it could not mutate without destroying the function of the key. Steimer hoped her vaccine would stimulate the production of antibodies that would grab onto this special conserved part of gp120. Like a piece of gum on a door key, the antibodies would prevent the virus from unlocking the cells and infecting them. Steimer hoped that her vaccine would give the immune system a head start, so that it could make such antibodies early and kill HIV in hours, before it began flooding the body with mutants. Because the vaccine was made artificially by cloning, it contained none of the virus’s genetic material and posed no risk of infection. At the time, the DNA of the HIV mutants from about five hundred different patients around the world had been analyzed. No two of them were identical, but they seemed to fall into some ten distinct categories known as subtypes, which tended to circulate in different populations around the world. Most people in the United States were infected with the subtype known as B, and Dr. Steimer’s vaccine was made from the gp120 of a subtype B virus that had been isolated from a patient in San Francisco. Dr. Steimer hoped that it would protect people from infection with subtype B, but she knew it would be unlikely to protect people from infection with other subtypes circulating in other parts of the world. Nevertheless, a vaccine for subtype B would be an enormous breakthrough. A test of any vaccine involves three phases. First it is administered to a small number of volunteers to ensure that it does not make them sick. Next it is given to a larger group of volunteers, to see if it induces the production of the right kinds of antibodies and cells. Blood is drawn from these volunteers and added to the virus in a test tube. If the volunteers are making good antibodies, the blood will kill the virus. Phase III is a massive, fantastically expensive venture involving thousands of healthy volunteers, who receive either the vaccine or a placebo. After several years, the rates of infection in the vaccinated group and the placebo group are compared, and the statistics indicate whether the vaccine protects people or not. If the vaccine fails completely, equal numbers of people in the vaccinated group and the placebo group will become infected. If the vaccine is perfect, no one in the vaccinated group will become infected. If the vaccine is only partly effective, some members of the vaccinated group will become infected, but far fewer than in the placebo group. While the volunteers in a Phase III trial are healthy, they are chosen because they have a high risk of becoming infected. In the case of HIV, they might be young gay men or intravenous drug users. They must be told that the vaccine is experimental and might not work and that in any case, they might receive only the placebo. They are warned to take every measure to protect themselves. The success of the trial depends on the fact that a significant number of these people—for whatever reason— will be exposed to the virus anyway, despite these warnings. Dr. Steimer’s vaccine was in the second stage of testing. It had been deemed safe, and the antibodies produced by healthy volunteers killed various laboratory mutants of subtype B. These lab strains contained pure stocks of virus that had been propagated in an incubator for years. Viruses taken from patients were far more diverse and complex, having adapted to survival in the body, in the presence of an active immune system, rather than in a plastic flask. Dr. Steimer and her colleagues were preparing to determine whether the antibodies her volunteers made would kill these “wild-type” HIV strains, taken from real people with real infections. If that worked, they would proceed to Phase III. Chiron could not finance a Phase III trial of the vaccine itself, but the U.S. Congress, on the advice of the National Institutes of Health, was considering pitching in with $20 million. Their decision would depend on additional lab data, and was expected sometime the following year. My thoughts were these: The World Health Organization (WHO), sensitive to the fact that the poorest nations might be overlooked in the high-tech scramble for an AIDS vaccine, had designated four developing countries as potential sites for AIDS vaccine trials—Thailand, Brazil, Uganda, and Rwanda. Dr. Steimer’s vaccine was designed only to work against subtype B infections, prevalent in the United States. Nevertheless, if it worked, and if information could be obtained about the subtypes circulating in Uganda, the company might consider making a vaccine that could be tested there in the future. Although Ugandans would never be able to afford to buy such a vaccine, perhaps the United Nations or some other institution would pay for it. My contribution would be to determine which subtypes of HIV were prevalent in Uganda. Some information about this was already available, but Chiron scientists had developed a new test that could identify HIV subtypes from blood samples very rapidly. Once the experiment was up and running, it would be possible to test hundreds of samples in a few weeks. This would enable me to find out just how common the different subtypes in Uganda were, and what kind of gp120 vaccine might work there. I could begin by testing some of the thousands of samples from the STD clinic that had been stored in the freezer at the Cancer Institute in Kampala. Routine HIV tests, such as those offered in hospitals and clinics around the world, are designed to detect not the virus itself, but antibodies that react with HIV. Such tests, known as enzyme-linked immunosorbent assays, or ELISAs, were first developed in the 1970s. The ELISA forms the basis for home pregnancy tests, as well as tests carried out in doctors’ offices for hormone deficiencies, infections, and other medical conditions. One of Dr. Steimer’s colleagues had designed an ELISA that could distinguish antibodies against different HIV subtypes. It could tell if someone was infected with A, B, C, or some other subtype. Dr. Steimer suggested I use this technique to investigate the antibodies in the Kampala serum samples. I worked in Dr. Steimer’s lab on the vaccine project for a couple of months to earn money and learn the new ELISA technique. Meanwhile, I planned the trip to Uganda carefully. Not knowing what to expect, I packed as though I were setting up an ELISA on the moon. I packed scissors, pencils, tape, pipettes, chemicals, plastic ELISA dishes. These were among the materials that were lost on the way to Kampala. Dr. Steimer was prepared to pay for the materials I would need to do the experiment, but not for me. In Uganda, I would have to support myself. The doctors in Kampala were prepared to let me use the stored blood samples in their freezers and give me space in a lab, but they would not pay me either. Nevertheless, I was happy about the arrangement. The project was very small, and although it would turn out that others were thinking along the same lines and would also publish surveys of HIV subtypes in Uganda, I felt like a pioneer. 3 Such feelings are rare in biology these days. The hour of the lone scientist following his or her imagination into the unlit corners of nature is passing. These were the days of the Human Genome Project, the biotech revolution, and the five-million-dollar grant. Whatever you might have wanted to do, others had thought of it already, and they had more money, more technicians, more pipettes, more frogs, more of whatever it takes than you did. So you joined their lab and you did what they said, or forget it. But here in Kampala, I was on my own. I WAS STILL WAITING for my materials to arrive when Arthur offered to show me the blood samples stored in the freezer at the Cancer Institute. They had been collected over the preceding four years, subjected to a routine HIV test, and labeled with numbers but no names. Arthur carefully opened the upright freezer where they were stored. There must have been a hundred plastic sandwich bags filled with vials in there. He put out his hand to make sure they didn’t fall on the floor. “They’re kind of a mess,” he said. The vials were stored randomly, without regard to the age of the patients, or where they came from, or any detail of their medical history. Arthur left me to sort through the bags. It took an hour to go through the first one, from which I retrieved four samples that I thought I could use. The next bag went more quickly, but it contained only three usable samples. By the end of the week, exhausted from boredom, I had 193. I decided to test these first and if my results were ambiguous, I would somehow find the strength to return to the freezer for more. But in order to proceed, I needed my materials from California, which still could not be found. One day, while I was still waiting for my boxes to arrive, I took a taxi across town to visit a friend. The driver asked me what I was doing in Uganda. When I told him, he bristled. “How can you make a vaccine when the virus mutates so much? As soon as you make your vaccine, the virus turns into something else, and your old vaccine is useless.” I explained that we hoped to get around that problem and told him about the neutralization experiments, the T-cell binding sites that we thought might make good targets for vaccine-generated antibodies, and so on. He seemed to accept this, but then he asked, “Why bother looking at this V3 loop?” “Well, we think that’s important too,” I said. I had similar conversations with a construction worker, a group of high school students, a hairdresser, and the man who mopped the floor of the lab. I had to confront questions about mutation rates, opportunistic infections, and why some people didn’t get infected even though they seemed to be having a great many sexual relationships. Nowhere else had I found people so inquisitive and well informed about AIDS. In Kampala, everyone talked about AIDS. There were AIDS clubs, meetings, conferences, marches, candlelight vigils, benefit breakfasts, lunches, and dinners; there were AIDS T-shirts, hats, banners, books, and cartoons; there were movies, plays, songs, poems, and dances about AIDS.When I told the cab driver that I was impressed with how much people in Uganda seemed to know about HIV, he said, “Everyone is affected by it. Everyone has a friend, a sister, someone who is sick or dead because of AIDS.” Excerpted from The Invisible Cure by Helen EpsteinCopyright © 2007 by Helen EpsteinPublished in 2007 by Farrar, Straus and GirouxAll rights reserved. This work is protected under copyright laws and reproduction is strictly prohibited. Permission to reproduce the material in any manner or medium must be secured from the Publisher.