A bon vivant, Koprowski obtained a state alcohol permit that made the Wistar an island of merriment on the dry University of Pennsylvania campus and his office a hub of happy hours where he mixed Bloody Marys using Gdansk vodka—a liqueur speckled with flakes of twenty-two-karat gold.6 “The Wistar operated in Philadelphia like a small independent European municipality. I think Hilary saw himself as Cosimo de’ Medici,” recalled Peter Doherty, a Nobel Prize–winning immunologist whom Koprowski recruited to the institute in 1975.7
If he recognized his faults, Koprowski had a hard time owning them. Once, when a young Wistar scientist named Michael Katz failed to win NIH funding for a grant, Koprowski, who wanted Katz doing other work, celebrated the failure to the young man’s face: “Congratulations! Now you can devote yourself to real science.” Stung, Katz told Koprowski to go do something that was anatomically impossible. He was summoned to Koprowski’s office at 5:00 p.m. that same day. The young man walked in fully expecting to be fired. Koprowski was sitting behind his desk with a twinkle in his eye and a pitcher of ice-cold martinis in front of him. “Olive or lemon peel?” he inquired.8
Koprowski could be imperious, domineering, and brutal in his dealings with those he perceived to have been disloyal. “He could run over them with a bulldozer,” his son Christopher recalled.9
“Hilary had a penchant for roughing up people,” Edwin Lennette, a mentor of the young Koprowski, told Koprowski’s biographer, Roger Vaughan.10
He could also be generous. The virologist Robert Gallo recalls Koprowski quietly upgrading Gallo’s airline ticket so that the younger man could join him in first class as the two men flew to meetings in Europe and Asia.11
Koprowski disliked confrontation, and often sent his loyal lieutenant, a genteel, chain-smoking New Englander named Tom Norton, to send packing whatever scientist had fallen out of his good graces at the Wistar. Stormy partings with his former acolytes occurred regularly. “When you decided to leave Wistar, Koprowski considered it betrayal no matter how you did it. When I told him I was leaving, he tried to trap me, personally and emotionally,” the cancer scientist Vittorio Defendi recalled.12
Koprowski’s enemies—and there were many—were driven to distraction by his irrepressibility, his manipulativeness, and his happy refusal to acknowledge, never mind attend to, their criticisms.
“There can be no doubt that he is a splendid scientist,” I. S. Ravdin, the powerful surgeon in chief at the Hospital of the University of Pennsylvania and a member of the Wistar’s board of managers, wrote to the outgoing university provost Jonathan Rhoads in 1960, slightly more than two years after Koprowski’s arrival at the Wistar. “But there is also no doubt that he can cause more trouble than any man with whom I have ever been associated.”13
Ravdin and other top University of Pennsylvania officials soon failed in an attempt to oust Koprowski, who blithely ignored their demands for itemized expense reports, wouldn’t disclose whether he was consulting on the side, and was being accused by his former bosses at the drug company Lederle Laboratories of having stolen the polio vaccine that he developed at the company, bringing it to the Wistar.14 Koprowski outmaneuvered them, helped by a revolt by loyal Wistar scientists.15 The institute would remain his domain for another thirty-one years.
Koprowski was born in 1916 in Warsaw. His mother was a dentist and his father a textile manufacturer. Hilary Koprowski fled Nazi-occupied Poland in 1940 with his dominating mother and his young, very-pregnant wife, Irena Koprowska.16
The family eventually landed in Brazil, after a hair-raising flight during which Koprowska, separated from her husband, defied Nazi orders to continue working as a physician and fled France with her newborn baby in her arms; and Koprowski escaped from Italy on the very day that Mussolini closed the borders to men capable of bearing arms. In Rio de Janeiro Koprowski was forced to earn a living by teaching piano to ungrateful students while his wife worked as a pathologist conducting autopsies in the green marble morgue of the city’s biggest hospital.
Several months later, through a chance meeting with an old high school friend on a Rio sidewalk, Koprowski was hired by the Rockefeller Foundation, which maintained a lab in the city. There the New York City–based research powerhouse was busy refining the young yellow fever vaccine. Koprowski spent three years doing work with yellow fever and several other viruses before the family received a U.S. visa that Koprowski had applied for years earlier.
En route to the United States in 1944, the aging merchant marine vessel that the Koprowskis were aboard laid over in Trinidad. With typical enterprise, Koprowski sought out a leading Trinidadian scientist, J. L. Pawan, who had made the groundbreaking discovery that rabies was transmitted by bats and that humans could be infected by vampire-bat bites. Koprowski was already fascinated by vampire literature. And he had read widely on rabies after he observed a rabid vampire bat—its brain was later dissected to look for the microscopic hallmarks of rabies—when he was working for the Rockefeller Foundation in Rio. He turned up unannounced at the door of Pawan’s lab. The senior scientist spoke with Koprowski at length about rabies. Koprowski’s resulting, keen interest in the disease and in making an improved vaccine against it would last his whole life.17
In the United States, Koprowski presented himself, without a job, at the Rockefeller Institute for Medical Research and succeeded in impressing the senior virologist, Peter Olitsky—the same man who had worked with the young virologist Albert Sabin to grow polio in brain tissue from human fetuses a decade earlier. Through Olitsky’s influence, in January 1945 Koprowski landed a research job in the virology department of Lederle Laboratories in Pearl River, New York, twenty-six miles northwest of Manhattan.18
Lederle, the pharmaceutical arm of the chemical giant American Cyanamid, was a superbly outfitted research complex, thanks to the backing of Cyanamid’s science-loving chief executive, William Graham Bell. While there, Koprowski became locked in an all-out race with the man who became his archrival, Albert Sabin. Sabin was ten years older than Koprowski. Driven and extremely bright, he was a refugee from pogroms in eastern Poland who had landed with his family on U.S. shores at the age of fifteen, speaking no English. By 1931 he had worked his way through medical school at New York University, and by the time Koprowski arrived at Lederle, Sabin had established himself as a top polio expert, first at the Rockefeller Institute and then at the University of Cincinnati.19
Both Koprowski and Sabin were bent on inventing the first live polio vaccine. A live vaccine consists of a naturally occurring virus that has been weakened so as to produce a low-grade infection that generates antibodies in a vaccinee without making that person sick. By contrast, a killed vaccine uses viruses that have been killed by chemical or physical processes to prompt an immune response.
However, Jonas Salk, a New York City native who was the son of unschooled Russian immigrants, would beat both Koprowski and Sabin to the glory of inventing the first polio vaccine. Salk’s vaccine contained naturally occurring polio virus that had been killed by the chemical formaldehyde. The injected vaccine tricked the immune system into recognizing and responding as if the virus were alive, generating antibodies in the blood. Salk’s vaccine was licensed by U.S. regulators in 1955, turning him into an instant public hero.
But Koprowski, Sabin, and many other virologists were convinced from the beginning that a vaccine that contained live, weakened virus would be more effective than a killed vaccine. Salk’s vaccine required several injections and later booster shots, and even these did not seem to prevent immunity from declining with time. What was more, Salk’s vaccine, which was injected into muscle, would not generate robust levels of antibodies in the throat or the walls of the digestive tract, which are the body’s main ports of entry for the polio virus.
Naturally occurring polio virus enters the body through the mouth via infected water or food. It then multiplies in the digestive tract and is excreted in the feces. In most peo
ple this infection is mild, and many, many people were infected without even being aware of it in the prevaccine era. It is when polio invades the blood from the digestive tract and travels to the spinal cord and brain that it causes paralysis and even death. Sabin, Koprowski, and many other immunologists believed that a live vaccine, given in a drink or on a sugar cube, would mimic the natural route of human infection and in so doing would confer lifelong immunity, producing robust levels of antibodies both in the walls of the digestive tract and in the blood. An oral vaccine would also be cheaper and easier to administer; it wouldn’t require injections or highly trained health personnel. And it would be shed in recipients’ feces and, in environments with poor sanitation and unclean water, passed on to other, unvaccinated people, provoking a protective immune response in some of them too—so-called passive immunization. The corresponding danger was that a live vaccine virus, shed in the feces, could mutate over time, reverting to an infective form and spreading the disease, rather than protecting people.
Making a live vaccine meant striking a delicate balance. A scientist needed to weaken the virus enough to stop it from causing disease, but not so much that it failed to cause a mild infection that provoked a protective immune response. Koprowski spared no effort to win the race to develop the first, and best, live vaccine. On a wintry evening in 1948, he swallowed his own experimental polio vaccine: a gray, fatty, viscous glop of cotton-rat brain and spinal cord that he had pulverized in a Waring blender.20 It was infected with a naturally occurring polio virus that he had weakened—he hoped.
He had done so by injecting blood serum and cerebrospinal fluid, which bathes the brain and spinal cord, from a twenty-nine-year-old man with polio directly into the brains of mice. When a mouse came down with polio, he injected that mouse’s ground-up brain and spinal cord into a new group of mice, and so on through many groups of mice. Then he took the virus from the mice and sequentially injected the brains of several groups of cotton rats, furry rodents that resemble mice and were common lab animals at the time, again using the infected brains and spinal cords of sickened animals to inject each new group.21 The idea behind these “passages” of the virus through multiple rodent generations is that, as the virus adapts to causing disease in a different species, it becomes less good at causing it in human beings; this weakening process was fundamental to the development of a live vaccine.
Koprowski next fed his live vaccine to chimpanzees. They developed antibodies against polio and did not get sick when they were exposed to naturally occurring virus.22, 23 But this wasn’t proof of safety: chimpanzees did not contract polio naturally, as human beings did.
While it was a time-honored tradition among scientists to be the first to receive their own vaccines, swallowing the cotton-rat vaccine from the Waring blender didn’t put Koprowski at risk for polio; like so many people at the midpoint of the twentieth century, he already had antibodies to the virus from being exposed to polio in the course of daily living.24 To know if his vaccine worked, Koprowski needed human “volunteers” who, unlike himself, weren’t already immune.
In 1950 Koprowski tested his vaccine on intellectually disabled children at Letchworth Village in Thiells, New York, an institution where “naked residents, unkempt and dirty, huddled in sterile dayrooms.”25 His use of people with mental disorders was not without precedent. During the war, under the sponsorship of the U.S. government, leading researchers had infected psychotic residents at an Illinois state hospital with malaria to test the effectiveness of experimental drugs.26 They had also tested trial influenza vaccines by requiring intellectually disabled people to breathe in influenza virus through aviation masks or to inhale a nebulized spray into their nostrils for four minutes; both vaccinated people and unvaccinated controls were forced to breathe in the virus.27 One of the leaders of these experiments was the young Jonas Salk.28
Koprowski told the story of the Letchworth Village trial in a lecture three decades later. He said that George Jervis, a friend and colleague who was the laboratory director at Letchworth Village, sought him out in the late 1940s and asked him to test the children living there to see if they had protective polio antibodies circulating in their blood. Jervis, Koprowski said, feared a polio epidemic: hand-to-mouth transmission by polio-infected feces was a special concern among the mentally ill children living at Letchworth. Koprowski drew blood from the children and found no antipolio antibodies in about 60 percent of them. Jervis then asked him to test his experimental vaccine at Letchworth, according to Koprowski. “I realized we would never get official permission from the state of New York. Therefore, we asked permission from the parents of these children.”29
Over the course of thirteen months beginning in February 1950, Koprowski fed the vaccine—the same gray glop that he himself had ingested but now disguised in chocolate milk or corn syrup—to twenty children at Letchworth Village. Aside from Koprowski and his lab manager, Tom Norton, the children were the first experimental recipients of live polio vaccine anywhere. Two of the children, including the first child fed the vaccine, were so disabled that they had to receive it through feeding tubes inserted into their stomachs.30
The earlier wartime experiments notwithstanding, Koprowski infuriated his peers when he presented the results of his Letchworth Village trial at a meeting of polio-vaccine scientists in 1951. It was no longer wartime, and polio was a dangerous, sometimes lethal virus. Sabin demanded to know how Koprowski had dared put a live poliovirus vaccine in children.31 Joseph Stokes, the esteemed physician in chief at the Children’s Hospital of Philadelphia, asked if he had thought about the fact that the Society for the Prevention of Cruelty to Children could sue him.32 Others simply sat in stony silence.33 The scientists couldn’t argue with Koprowski’s results, however: all of the intellectually disabled “volunteer” children—that is how Koprowski described them in the resulting paper—who lacked antipolio antibodies before they consumed the vaccine promptly developed them. None showed any signs of illness.34
It wasn’t the last time that Koprowski would give his polio vaccine to institutionalized children. They were easily controlled and readily accessible, and they couldn’t talk back. They were certainly no match for Koprowski, who, when he wanted something, used every tool in his considerable arsenal of charm, persuasive power, and underhandedness to make sure that he got it.
• • •
The southern spring was in full flush as Leonard and Ruth Hayflick drove the 1,600 miles from Galveston to Philadelphia early in 1958. Their family was twice the size it had been when they left Philadelphia. Joel was now a toddler, and Deborah, aged five months, rode hanging in a drawer suspended from the dashboard of the family’s four-door sedan. Soon the Hayflick clan would be still larger: another child was on the way, due that November. Also looming into view ahead was a job that, even if it wasn’t a plum research position, was planting him on the ground floor of what sounded like an exciting new phase in the life of the Wistar Institute.
In 1956 Norman Topping, the energetic vice president of medical affairs at the University of Pennsylvania and a new, active member of the Wistar’s board of managers, took matters in hand at the decrepit, dying Wistar. It presented “a particular problem,” with its ancient whale skeleton and equally ancient labs. The Napoleonic acting director, Farris, with his not quite licit infertility clinic, was also on Topping’s radar screen, and not in a good way. “His reputation was not of the best,” Topping recalled in his memoir. Topping initiated a search for a permanent director. He knew of Koprowski and his polio work because of his own connections at Lederle. Topping had met the man and was impressed.35
Koprowski himself was on the lookout for a new position when he heard from Topping. At Lederle management had changed multiple times, and the situation for scientists had deteriorated badly from the company’s heyday in the 1940s. So Koprowski was all ears when Topping offered him the Wistar’s directorship, along with space for his research on the third fl
oor of the institute.36
The forty-year-old Koprowski saw opportunity where others might have seen a quick route to obscurity. He told Topping that the third floor wasn’t enough. He wanted the whole institute, with its 68,000 square feet of floor space. He also wanted—demanded—two full professorships at the University of Pennsylvania in the School of Arts and Sciences and in Research Medicine.37
Topping, eager to shed his Wistar worries, agreed, and in late January 1957 Koprowski accepted the Wistar job. It came with a $17,000 annual salary ($145,000 in 2016 dollars), a $2,400 expense account, and a start date of May 1, 1957. It also came with the written promise, in the letter offering the job, that his salary would be reviewed every year “so as to be commensurate to that of the best-paid professor of the University of Pennsylvania.” He would also have “the same rights and privileges as to tenure” as a full Penn professor.38
“I liked [the Wistar] because it was dead,” Koprowski told his biographer, Vaughan.39 It was an empty shell that he, Hilary Koprowski, was going to remake as a mecca of unconstrained, imagination-fired biological research.
The Vaccine Race Page 5