"THE RIVER"

An exhaustive history of HIV and AIDS offers a bold new theory about its origins

Published October 6, 1999 4:00PM (EDT)

Frozen in time: 1959

Let us take a moment in time. Let us freeze it. Let us watch as the crystals form, as it becomes translucent. Let us mount it on a slide and lift it carefully to the microscope stand. Using strong light and mirrors, adjusting the focus, let us see what can be seen.

Truth, like beauty, resides in the eye in the beholder. Whatever the material on that glass slide -- be it a moment in history or a cluster of cells -- it is inevitable that what you see and what I see will be different. I may see colors, a myriad of dots, a divine impressionistic sweep of light and shade. You, the historian, may see a pattern, a grand design, the beginning of a chain of cause and effect. Now let us change the eyepiece, increase the magnification. This time I may see a meaningless smudge with specks of darkness within, while you, the biologist, may see a nucleus and mitochondria, the beauty of simplicity, the pulsating potential of a cell ready to divide.

How will we describe our truths, you and I, for the blind man, for the child without a microscope? And whose description will be more accurate? While I pack away the lenses, and you put the glass rectangle into its slot in the velvet-upholstered case, remember this. Empirically, the image that you see and that which I see are the same. What differs is our relative clarity of vision, level of understanding, power of analysis -- and the language we choose to describe what lies beneath the lens.

It is the February of 1959. It is a particular moment in the history of the world. The old order is breaking up; the barriers of time and space are tumbling. The first jet planes are taking off, heading for destinations -- Hong Kong, Nairobi, Sydney -- that once were days away, but are now just hours. There is a new type of global language too, as people talk of atom bombs, the cold war, of international power blocs, and the arms race. It is also a particular time in the history of Africa. The wind of change is blowing hard: in the last two years Ghana and Guinea have attained independence, and across the continent the clamor is rising. The old colonial powers -- the British, the French, the Belgians -- are, each in their own time, recognizing the inevitability of the process, acknowledging that these are the final days of the Raj; only the Portuguese are still defiantly opposed. Here, in the Belgian Congo, amidst the wide, gracious, tree-lined avenues of the capital, Leopoldville, the first round of riots has just ended, with more than fifteen hundred Africans arrested. The Belgians are bewildered. People returning to Brussels tell the man from the London Times that "something untoward is brewing at Stanleyville," the town a thousand miles upstream at the great bend in the river.

Meanwhile two doctors, one American and one Belgian, are traveling around the capital immersed in their own world, which is one of scientific inquiry. The American, funded by grants from the U.S. Public Health Service and the Rockefeller Foundation, arrived in Leopoldville just after the end of the unrest, and neither saw evidence of its impact nor, one suspects, would have had much appreciation of its significance had he done so. The Belgian, for his part, has just been appointed chair of microbiology at the newly built university of Lovanium, eight miles from the city center on the banks of the Congo River -- but for all that, he is happy for the chance to collaborate with such a rising star in the firmament of human genetics. These are impassioned men operating in an era that reveres their activities, in an era when science is the new religion, and the men in white coats its prophets and priests.

Over the next few weeks the American, Arno Motulsky, and the Belgian, Jean Vandepitte, with the help of other local doctors, start collecting blood samples from medical staff, hospital patients, and police recruits in Leopoldville, and from a large group of villagers living to the south, near the Angolan border. Motulsky is keen to investigate the relative incidence of two genetic traits in different ethnic groups in sub-Saharan Africa, and their possible relationship to malaria. Later, he visits several other regions of the Belgian Congo and the neighboring territory of Ruanda-Urundi, administered by the Belgians as a trusteeship since Germany was dispossessed of its African colonies after the First World War. At the end of three months, he and his Belgian colleagues have collected nearly eighteen hundred blood samples from eight different population groups, including pygmies from the Ituri Forest, hospital patients from Stanleyville, and schoolchildren from the two principal ethnic groups in Ruanda-Urundi, the Tutsi and the Hutu. Most of these samples are finger-prick specimens mounted on glass slides and examined in local laboratories the same day, but more than seven hundred are samples of whole blood, which are then refrigerated and flown back to Motulsky's department at the University of Washington in Seattle.

As Jean Vandepitte bids farewell to Arno Motulsky at the airport, neither man has any inkling of the additional significance which one of these 5-milliliter blood samples will assume just over a quarter of a century later.
Independence arrives, and the countries where Motulsky obtained his specimens subsequently become known as the Republic of the Congo, Rwanda, and Burundi. Over the next few years, all three experience tragic events, as ethnic tensions and the meddling of foreign powers combine to promote upheavals, violence, and bloodshed. Meanwhile, back at the University of Washington, various tests are conducted on the blood samples, and a series of papers published in journals of genetics.

Several years later, Moses Schanfield, a professor from Emory University, contacts Motulsky to ask if he can undertake further genetic studies on the Congo cohort, and the remaining 672 frozen plasmas are flown to Atlanta. Finally, in 1985, they change hands once more, and are given to another Emory professor, Andri Nahmias, who has an entirely different interest. He wants to test them for the presence of antibodies to a virus that has suddenly entered the medical limelight -- the virus that causes AIDS. He examines not only the Motulsky samples, but a further 500 plasmas originating from South Africa, Mozambique, and Congo-Brazzaville, and collected at various times between 1959 and 1982.

Over the next few months, the specimens are examined exhaustively, first at Emory and then at Harvard; the results are then confirmed at two other laboratories, by a total of four different testing procedures. Of all the plasma samples, just one comes out strongly positive on all the tests. Its code number is L70, and it comes from a group of 99 specimens taken in 1959, somewhere in or around Leopoldville.

In the mid-eighties, scientists are just awakening to the possibility that HIV (as it will soon become known) may have been present in sub-Saharan Africa for some years before the recognized start of the AIDS epidemic in North America and Europe in 1981, and the Nahmias investigation provides the first really dramatic evidence in support of this hypothesis. No further details appear to be available, however, about the source of the L70 sample. In the 1986 letter to The Lancet in which he reports the results of his investigations, Nahmias comments simply: "The identity of the donor is no longer known."

Nearly four decades have passed since his trip to Africa, but Arno Motulsky, now professor emeritus, still lives in Seattle and is still a man of spiky brilliance. And his papers do reveal a little more about the identity of the L70 donor. They record that the blood was taken from a Bantu male, one of 78 men in the group of 99 designated as "Leo." Unfortunately, of all the 12 groups tested by Motulsky, there is less documentation about the "Leo" series than any of the others. Motulsky says that most of them were normal members of the population, and that around 20 percent were hospital patients. The identity of the hospital is not recorded, although Jean Vandepitte, now professor emeritus at the University of Leuven and the Institute of Tropical Medicine in Antwerp, believes that it was probably that at Lovanium, the great campus the Belgians constructed on the outskirts of Leopoldville, and which many consider to have been their parting gift to the country they ruled for 75 years.

Whatever, it appears that this tiny amount of blood, taken in 1959 from an unknown man living in the city now known as Kinshasa, the bustling capital of the Congo, represents the oldest specimen of the human immunodeficiency virus in existence. We shall return to it later in the story.
As with the early course of a river, where water may seep unnoticed through sphagnum bogs, or plunge underground through limestone, so with the early course of a new disease. It is, of course, entirely possible that the first traces of an unusual and hitherto unseen condition (especially a disease syndrome with a diverse range of presentations and a long latency period, like AIDS) will pass by unremarked. There again, perhaps because of serendipity, or an especially conscientious team of doctors, it can also happen that the crucial clues are noticed and recorded for posterity.

On January 31, 1959, just as Arno Motulsky was leaving for Africa, a 25-year-old man from Reddish, a working-class suburb adjoining Manchester, was getting engaged. At the same time (though he could not have known it) he was becoming involved in a chain of events that would end up with his becoming public property, part of global folklore. For this man, David Carr, was about to become inextricably entwined with the early history of the AIDS epidemic.

By that year, Reddish was a place in decline. Cotton manufacturing was moving overseas to new nations where wages were lower, and the town's huge mill finally closed its doors at the end of 1958. Many were reemployed at the breweries and railway repair yards, but the soul of Reddish seemed to have departed, together with much of its disposable income. There was only a light scattering of TV aerials on the long terraced roofs around the mill. For the fortunate few in the black-and-white flicker below, Harold Macmillan was meeting with General Eisenhower, issuing joint communiquis from Chequers, reminding Britons that -- with a nuclear deterrent of their own -- they were one of "The Big Three," telling them they had never had it so good. Not all believed him.

The country that had, until recently, viewed itself as lying at the fulcrum of global activity was now in reality a leviathan, grown loose-eyed and sleepy, still touched by memories of wartime sacrifice and ration books. Its grandiose dreams were fading, as one by one the countries of Africa and Asia were granted freedom; the sun was setting on an empire over which, it was once boasted, the sun never set.

Dave Carr was a former seaman, a local Reddish lad with crinkly eyes and wavy brown hair. "Elsie," his fianci, was from northern Manchester; she had a strikingly trim figure and bright red hair, worn in a perm. They worked within yards of each other in the city center -- he as a printer on the Manchester Evening Chronicle; she as a mantle machinist, making ladies' gowns and raincoats. Each had a good sense of humor, but whereas Dave was easygoing, Elsie was strong-willed and known for speaking her mind. Their friends thought them a perfect match. To save money, they had bought the engagement ring from a pawnbrokers' shop -- a pledge made but broken, never redeemed.

Whether or not Dave and Elsie were planning an early wedding is a moot point, for since the end of the previous year, Dave's health had suddenly collapsed. Throughout 1958 he had suffered from small but persistent ailments -- chronic gingivitis, and a funny measles-like rash on his back and shoulders, for which he attended a local skin clinic on a monthly basis, receiving steroid creams and two courses of radiotherapy. In November, he had to have part of his lower gum removed in a gingivectomy, but for some reason, the wounds never healed properly. Then, toward Christmas, he developed a nagging cough and began having serious problems with his breathing. He had only to walk a few hundred yards or climb a flight of steps to end up gasping, panting, propped up against wall or lamppost. He was losing weight as well -- a lot of it.

In the weeks that followed the engagement, Dave Carr got substantially worse. In February the hemorrhoids and pruritis ani from which he had suffered intermittently for years suddenly became more inflamed, and he developed a painful sore around the anus. The weight loss, night sweats, and fevers also became more pronounced, and now his chronic cough began bringing up mucus which was flecked with blood. He began to take more and more time off work at the Chronicle, and after work, over a pint, his mates would talk in undertones about leukemia, or about his picking up some strange bug while swimming in the local canal or during his National Service in the navy.

In March, Dave began seeing a private consultant, Dr. Charles Don. On the morning of his second appointment, in early April, a telegram was delivered, requesting a postponement, but Dave's parents told him to turn up anyway. It was as well that he did. Dr. Don took one look at his patient's anal fissure, now three inches long, and arranged for him to be admitted to the Manchester Royal Infirmary. Ward M4 (male) at the MRI was to become Dave's home for the next five months.

The physicians in charge of the ward, notably the senior registrar, John Leonard, and the senior house officer, Trevor Stretton, were baffled by David Carr's various maladies -- the weight loss, persistent cough, breathing difficulties, the sore on his bottom, and the small "blind boil" that had appeared at the tip of his left nostril. All they knew was that here was a man just a few years younger than themselves, who until recently had appeared quite healthy, and who was now wasting away before their eyes, strafed by a series of apparently untreatable infections.

Their first response was to suspect miliary TB, an unusual form of tuberculosis, but when Dave failed to respond to the appropriate drugs, they wondered about sarcoidosis, and the collagen diseases (nowadays known as autoimmune disorders). They had already checked all the known cancers and lymphomas, but now they began to wonder about the possibility of an unknown malignancy.

Of course, they asked him questions about his past, about his time in the navy -- and noted that he did not recall having any tropical diseases. They tested for syphilis and found him negative, but they did not question him about his sexuality, for such matters were less frequently and openly discussed in 1959 and, in any case, did not seem relevant to the case. They tried further radiotherapy, together with chemotherapy, steroids, and an even wider range of drugs. Once or twice he picked up briefly, for a week or two, but the remission never lasted.

By June, Dave's fevers were becoming more frequent, and his breathing steadily worse. The spot in his nostril became an ulcer, which started eating away at his nasal cartilage and upper lip; shaving became impossible, so he grew a mustache, but it did little to hide the spreading open wound from view. The anal lesion also grew, until it became an excavated sore the size of a small football, covering most of his buttocks. A cradle was placed over him to keep the weight of the blankets from his body. But most dramatic of all was the emaciation. One year before, David Carr had been a strapping lad of 185 pounds, broad-shouldered and somewhat overweight for his five foot seven inch frame. Now, however, his face was drawn and his bones clearly visible through the skin. Elsie and his parents called at the hospital every day, but Dave began to discourage visits from friends.

Just a few days before Dave and Elsie's engagement, an unusual death occurred in Canada, at Toronto General Hospital. The deceased was a 36-year-old Japanese-Canadian man, who had been admitted six weeks earlier with severe breathing difficulties. Eventually he suffocated to death. At autopsy, Dr. John Barrie, a British imigri pathologist, found a honeycomb of cyst-like cavities throughout the man's lungs, which he ascribed to Pneumocystis carinii, a rare pathogen that takes advantage of a state of lowered resistance in the human host.

However, in the case of this patient, George Y., there were no clear indications as to what might have caused his resistance to be diminished, and for this reason Dr. Barrie wrote a paper about the case, which was published the following year. "We are not aware of any reports of deaths in adults which have been caused primarily by infection with Pneumocystis," wrote Barrie, in the introduction. He reported that the patient had been well until March 1958, when he had experienced a five-day fever with chills, headache, and nonproductive cough, an episode that was repeated several times in the following months. In late October, he began to experience sharp pains in his chest, drenching night sweats, and pronounced weight loss. By December 1958, when he was admitted to hospital, he was losing weight dramatically, had chest pains, and would become breathless after the slightest exertion. The physicians administered a range of drugs in a bid to save his life -- culminating in 100 milligrams (a very heavy dose) of a steroid, prednisone, every day for the final fortnight. At the autopsy, the only contributory factor noted was a mild cirrhosis of the liver, presumably from drinking.

In 1991, I located Dr. Barrie, by then in his late eighties, and he managed to procure a copy of his original autopsy report. This revealed that George had worked as a sawmill operator during the forties and then, for ten years from 1948, as a carpenter in Edmonton, Alberta. In 1958, however, he abandoned his steady job and migrated north to work in the Northwest Territories. It was when he arrived there in March that he suffered his first illness, followed by another in May, when "he developed ... a virus infection common in the camp in which he was working at that time." Something, it seems, had caused George Y. to become immunocompromised at some point during the final year or so of his life, leading to his demise from PCP in January 1959.

A few months later, in June of that year, Pneumocystis carinii pneumonia was responsible for another most unusual adult death at the Kings County Hospital in Brooklyn, New York. The patient, Ardouin A., had been born in Jamaica of Jamaican parents, but the family had moved to Haiti when he was seven, and he emigrated from there to the United States ten years later, marrying a Haitian imigri soon afterward. Ardouin was an attractive man, with slicked-back hair, a thin mustache, and sharp dress sense -- and he apparently had several girlfriends on the side. He also had several jobs, but after the Second World War began working as a shipping clerk for a dress manufacturer on Seventh Avenue in Manhattan -- a post he was to keep for the rest of his life.

Ardouin had never been seriously ill in his 49 years, but in March 1959 his smoker's cough became more severe and productive of large amounts of sputum, and he began losing weight. By June, his chest pains and wheezing had gotten so serious that he was admitted to hospital, where he was quickly placed on a respirator and treated with steroids. His doctors asked many questions and wanted to know whether he had ever been to Nevada, which suggests they thought he might have been present at an atom bomb test; he had not. They also tested his blood, bone marrow, and urine (including a check for beryllium content, since he had apparently broken a fluorescent lamp some while earlier), but found nothing untoward. Ardouin, meanwhile, became weaker, and told his family that he wanted to be buried in his blue suit. His prognosis was correct, for on June 28 he had to have a hole cut in his windpipe to assist his breathing, and he died later the same day.

His widow was terrified, fearing that voodoo was involved -- while the pathologist, Gordon Hennigar, was mystified as to why he could find no underlying disease that might explain why the Pneumocystis infection had taken hold and proved so remorseless. The case was sufficiently unusual to be written up in two medical journals, and although one of the papers pointed out that the white blood cell count had sometimes been high (which might suggest a leukemoid reaction), its conclusion was that Ardouin represented "the first reported instance of unassociated [Pneumocystis carinii] disease in an adult." Dr. Hennigar, meanwhile, decided to pickle Ardouin's lungs for posterity.

While Gordon Hennigar filled his bell jar with formalin, back in the Manchester Royal Infirmary, David Carr's symptoms were progressing inexorably. By July, the latest theory of his doctors was that he was suffering from Wegener's granulomatosis, a fatal disorder of the connective tissue that often involves the respiratory tract. Altogether, just 56 cases of Wegener's had been recorded in the medical literature.

Dave kept cheerful to the end, but by August he and Elsie and his parents all knew that he was dying. At this stage, pustular ulcers were appearing on his stomach, inner thighs, and fingers, over both his lips, and inside his mouth. He developed spiking fevers and found it more and more difficult to breathe. He had what appeared to be an untreatable pneumonia, and sometimes he became cyanotic, with his extremities turning blue from lack of oxygen and his fingers swelling at the tips. In the final week of his life, he was put in a separate room and treated with Euphoricus, a sedative cocktail of morphine, cocaine, and gin. At three o'clock on the afternoon of August 31, as he was being lifted on to the commode, he died.

It was only when the tissues taken at autopsy were examined microscopically by pathologist George Williams that two unexpected conditions were identified. One was disseminated "cytomegalic inclusion disease," a condition caused by a virus that, the following year, would be renamed cytomegalovirus, or CMV. The other was Pneumocystis carinii pneumonia, PCP.

Thus, in the first eight months of 1959, three apparently healthy men from different parts of the world died primarily as a result of PCP, a disease previously unrecognized in healthy adults. During the next twenty-five years, the doctors who had been involved with these three patients, either alive or dead, continued to be intrigued by their illnesses, and by the continuing mystery of underlying cause. At times they would review their papers, and wonder about this possibility or that -- exposure to some toxic agent, an undiagnosed cancer or leukemia, a congenital immunodeficiency that they had failed to spot. But none of these tentative explanations was entirely convincing. It was only in the eighties, after the recognition of the AIDS epidemic, that a solution to the mystery seemed to have emerged -- for between 1983 and 1987, several researchers proposed that these three deaths might represent pre-epidemic cases of AIDS.

Were they right? Was David Carr in Reddish an antecedent of the coming epidemic? Were George in Toronto and Ardouin in New York? Were these men the harbingers of a new disease beginning its global spread, the earliest, unfortunate infectees with some new pathogen that was already -- in 1959 -- becoming widely dispersed, albeit extremely thinly? This is one of the hypotheses that we will be investigating in some detail in the course of this book. As the condition of David in Manchester deteriorated ever faster, and as Ardouin in Brooklyn entered the final week of his life, a very different event was taking place in Washington, D.C. Whereas the savage disease processes affecting these two men were graphic reminders of how, even in the best-equipped medical systems in the world, nature could still get the better of doctors, this latter event was essentially a celebration of the triumph of modern medicine over disease.

Poliomyelitis, until then the most dreaded of illnesses, the one that caused authorities to close down schools and swimming pools, and that persuaded people across America to donate their small change to the March of Dimes, was about to be vanquished, and the world's pre-eminent virologists and physicians had gathered in the national capital to witness the coup de grace.
The event was called the First International Conference on Live Poliovirus Vaccines, and among the 70 attendees from the ranks of the great and the good were two doctors -- Albert Sabin and Hilary Koprowski -- who had probably done more than any others to bring about this hugely popular scientific achievement, this metaphorical lunar landing of the fifties. Both of them had developed their own sets of oral polio vaccines (OPVs), and all the indications were that the United States was about to adopt either Sabin's or Koprowski's strains. In fact the stakes were even higher, for it was apparent that whichever vaccine set was approved in America would -- in all probability -- be adopted by the rest of the world also.

The principle of vaccination is that a tiny amount of a virus (either a weakened live virus, or else a virus that has been killed by chemicals like formalin) is introduced to the vaccinee, whose immune system responds by producing the appropriate antibodies. The subject will then be protected against exposure to the "wild" form of the virus found in nature, which might otherwise cause serious disease. In the case of poliomyelitis, the first vaccine to be adopted for general use in America -- in 1955 -- was the killed vaccine developed by Jonas Salk. Referred to by scientists as an inactivated polio vaccine, or IPV, this preparation had already, by 1959, been given to millions of children around the world. It was, however, gradually falling out of favor by the end of the decade -- and not just because sugar lumps are more popular with kids than shots in the arm. More crucially, there were demonstrable problems with its safety and effectiveness. In one infamous episode, the "Cutter incident," hundreds of vaccinees and their close contacts contracted polio because a batch of vaccine had been improperly inactivated. Furthermore, by the end of the decade, an increasing number of vaccinees were becoming paralyzed even after receiving the full course of three shots, showing that not all batches of the vaccine were protective.

By 1959, many virologists were persuaded that the more easily administered oral vaccines of Sabin and Koprowski were also capable of giving longer-lasting protection. On the question of safety, opinions were more divided. The live poliovirus in OPVs has first been weakened, or attenuated, by a series of passages through animals (such as rodents and monkeys) or through tissue cultures (layers of cells -- typically from chicken embryos or the kidneys of monkeys -- that are kept alive under laboratory conditions). However, the theoretical side of attenuation (relating to what causes the poliovirus to become innocuous for humans, and what keeps it that way) was still shrouded in mystery. For this reason there was considerable interest when, in a discussion session on the fourth day of the conference, Professor Albert Sabin made a dramatic accusation.

He repeated a claim that he had first made three months earlier, in an article in the British Medical Journal, that at least one batch of his rival Koprowski's CHAT vaccine, which had been fed to hundreds of thousands of vaccinees in the Belgian Congo, had been contaminated with an unidentified simian virus, one that had nothing to do with polio -- but which, like polio, was cytopathic (it killed cells when introduced into monkey kidney tissue culture). The unspoken inference was clear -- that such a virus might also do damage when introduced into human beings.

A renowned Swedish virologist, Dr. Sven Gard, who had been on several months' sabbatical at Koprowski's research center, the Wistar Institute, spoke up in his defense. Gard said that he had tested the same lot of vaccine for the presence of extraneous virus, both in Sweden and the United States, and had found nothing.

And there, apparently, the matter rested. Certainly there is no further reference to the affair in the published record of the conference. But by voicing his concern, Albert Sabin had invoked a specter that was hovering over the proceedings -- the fear that OPVs, even while they were bringing the most feared viral disease of the era under control, might also be introducing new and perhaps more sinister viral agents into mankind, ones that proliferated during the process of vaccine manufacture.

This was a fear that was to become very much more substantial over the years that followed, as virologists began to learn a lot more about tissue cultures, especially monkey kidney tissue cultures, and the many ways in which they could become contaminated. Naturally, new procedures were introduced to ensure the safety of vaccines. But many of these men, when they looked back years later with the benefit of hindsight, would shiver at the risks which they had inadvertently taken in those days of blissful ignorance, those days of hope and courage, in the fifties.

Put the slide back in the case. Pick another. Here, try this one, from the nineties. Let us see whether it provides a different perspective -- one that benefits from the accumulation of scientific wisdom. Perhaps try another lens, too. Some, of course, may have the corrective properties of hindsight.

It is March of 1993. The intervening years have seen further great victories for vaccination programs and the public health system, with the conquest of smallpox, and the suppression of malaria, measles, and cholera. But they have also witnessed significant reverses, such as the emergence of AIDS and the re-emergence of tuberculosis. And now, almost thirty-four years after that first international conference on live poliovirus vaccines, Albert Bruce Sabin has died peacefully at his home in Washington, D.C., at the age of 86. Despite his many achievements during more than six decades of scientific toil, he was always best known for his development of the OPVs, which would later be adopted in almost every country in the world. In 1993, the World Health Organization is promoting a campaign of global poliomyelitis eradication by the year 2000. Even if this may be optimistic, polio is likely to become only the second viral disease to be conquered by human intervention, a state of affairs that owes much to the success of Albert Sabin's slightly dirty-looking sugar lumps.

One of Sabin's many other achievements was to identify a herpes virus of monkeys (B virus, or herpes B), which is harmless to its natural host but almost invariably fatal when transferred into humans, as evidenced by the deaths of some two dozen monkey handlers and laboratory workers since the thirties. Sabin's discovery of herpes B virus identified what then seemed the most formidable danger inherent in handling monkeys and their organs, and facilitated the adoption of minced monkey kidneys as a tissue culture for in vitro research and for the cultivation of viruses. This in turn paved the way for the golden age of virology in the fifties, and the production of polio vaccines on a commercial scale.

During his final years, Albert Sabin became increasingly concerned by the problem of AIDS, and wrote articles and letters about the problems inherent in developing an effective vaccine against the syndrome. The last of these was published in Nature a fortnight after his death. Like its predecessors, it predicted that attempts to vaccinate against HIV would prove unsuccessful, and ended with the words "In my judgment, it would be disastrous to continue the current inadequate methods of study of HIV and SIV vaccines, and to carry out large scale tests in humans of vaccines without adequate evidence that such vaccines can protect against natural infection." From such an eminence grise, these were powerful final words of warning.

Five weeks after Sabin's death, an obituary was published in Nature. It opened with a reference to "the heroic age of poliomyelitis research" and an acknowledgment that Sabin had been "one of the heroes," before moving on to review Sabin's life and works. By this stage of the obituary, the observant reader might have begun to suspect that writer and subject had not always been in agreement.

This was frankly admitted in the final paragraph, which read: "At one time, Sabin and I became adversaries over the selection of polio virus strains to be used as oral vaccines. This did not affect our long-lasting friendship and mutual respect. In a letter to me written just a year ago, reviewing a paper speculating that AIDS started with polio vaccination in the Belgian Congo, Sabin expressed his opinion that this was 'a most irresponsible and uncritical communication.' Courageous and wise. This is how I see him. I will miss him sorely."

The obituary was signed Hilary Koprowski, from the Wistar Institute in Philadelphia. Several of the scientists who knew the two men from the time of their great rivalry in the fifties and early sixties were intrigued by the obituary. They too had vivid recollections of the period, though their memories were rather different from Koprowski's. They spoke of two Jewish imigris from Eastern Europe, both possessed of keen intellects and quick tempers -- coupled, however, with great powers of persuasion (and, in Koprowski's case, of charm). They spoke of two men cast from the same mold, men who shared many of the same tendencies and personality traits -- but who had somehow evolved into polar opposites.

Few of them recalled any tangible friendship (let alone one that was long-lasting) between Sabin and Koprowski, or remembered demonstrations of mutual respect. Instead, they spoke of a bitter enmity that had been barely -- if at all -- concealed in their respective articles in the medical literature and papers delivered at the great virology conferences of the day. They remembered the occasions when the great men had posed together, smiling, for the photographers, and then each had swiftly turned on his heel the moment the cameras were packed away. This rivalry, some of them hinted, had perhaps stemmed from the fact that Koprowski had been the first to feed an oral polio vaccine to humans in 1950, fully three years before Sabin had entered the field -- and yet it was Sabin's vaccines that had been licensed, Sabin who had won the lasting acclaim. "Koprowski and Sabin hated each other," one contemporary told me. "Salk, Sabin, Koprowski, Cox -- I would have loved to see them tag-team wrestling," said another, referring to the four great polio vaccine-makers. "They were fighting like dogs over a bone -- about who would make the vaccine of choice," said a third.

Given this history, many scientists were dubious about Koprowski's motivation for praising Sabin's wisdom -- particularly as, in the same breath, he noted Sabin's rejection of a theory that suggested that one of his (Koprowski's) vaccines had given birth to AIDS. Perhaps in 1993 few scientists would have recalled that, back in 1959, it was Sabin who had introduced the first slither of doubt about the safety of this very vaccine.


By Edward Hooper

Edward Hooper has been a United Nations official and BBC correspondent in Africa. He is the author of "Slim," an account of the AIDS epidemic in East Africa.

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