The New York Times
April 21, 2013 Sunday
It was a brew to rival any in ”Macbeth.” The main ingredients were rat brain and a fearsome, carefully cultivated virus.
In his laboratory in Pearl River, N.Y., 20 miles north of Manhattan, Dr. Hilary Koprowski macerated the ingredients in an ordinary kitchen blender one January day in 1948. He poured the result — thick, cold, gray and greasy — into a beaker, lifted it to his lips and drank. It tasted, he later said, like cod liver oil.
With that sip, Dr. Koprowski, a virologist who died on April 11 at 96, inoculated himself against polio, years before the vaccines of Jonas Salk and Albert Sabin.
Dr. Koprowski was one of the world’s foremost biomedical researchers, helping usher in a spate of innovations, including a safer, less painful and more effective rabies vaccine that remains widely used.
But his most noteworthy innovation — developing the first viable vaccine against polio and testing it successfully on humans — is far less well known. It has long been eclipsed in public memory by the triumphs of Salk, whose injectable vaccine was introduced in 1955, and Sabin, whose oral vaccine was introduced in stages in the early 1960s.
”Koprowski’s was the first serious scientific attempt at a live-virus polio vaccine,” said the historian David M. Oshinsky, whose 2005 book, ”Polio: An American Story,” chronicles the race to pre-empt the disease. ”Jonas Salk is a god in America, Albert Sabin’s got a ton of publicity, and Hilary Koprowski, who really should be part of that trinity, is the forgotten man.”
From the beginning, a live-virus vaccine like Dr. Koprowski’s was the most coveted weapon in the war on polio. Such vaccines can be administered orally and are far cheaper than injections. And because they involve live viruses, which can spread within a community, they can also confer immunity on others. (The Salk vaccine, made from killed viruses, cannot.)
But there was a grave catch: for a live polio vaccine to be safe, the viruses would have to be sufficiently weakened — attenuated, in medical parlance — so they would produce antibodies without inducing polio’s neurological effects.
On the evidence, the Koprowski vaccine did precisely this. But though it was given to patients overseas with good results, it was never approved for use in the United States.
Dr. Koprowski was the last of the three great virologists who stalked polio at midcentury; Sabin died in 1993, Salk in 1995. His death raises a large retrospective question: Why, in an era when a polio vaccine was the most urgently sought grail in American public health, did his go unused?
The answer, gleaned from period news accounts, histories of the war on polio and interviews with Dr. Koprowski’s associates, illuminates the delicate balance of risk and reward — and the uneasy confluence of science, politics and personality — that can inform the development of a drug.
Dr. Koprowski, who spent more than 30 years as the director of the Wistar Institute, a biomedical research center in Philadelphia, was widely described as a titanic, sometimes polarizing figure: a refugee from Nazi-occupied Poland, he was a trained concert pianist, a fluent speaker of seven languages, a connoisseur of food and wine, and a collector of old master paintings.
”He was the single most forceful, dominant, charismatic person I have ever met in my life,” said Dr. Paul A. Offit, the chief of infectious diseases at Children’s Hospital of Philadelphia, who worked under Dr. Koprowski at Wistar in the 1980s.
That outsize personality, combined with Dr. Koprowski’s outsider status — he spent part of his career in industry at a time when academia had far more prestige — may have played a role in the fate of his vaccine, his biographer, Roger Vaughan, and Professor Oshinsky said in interviews.
Others, including Dr. Offit, say the outcome was based on science alone. But all agree that Dr. Koprowski, by demonstrating that a live-virus polio vaccine could be safe and effective, paved the way for the Sabin vaccine.
And it was Sabin’s vaccine, even more than Salk’s, that brought about the near-eradication of polio worldwide.
”Sometimes,” Dr. Koprowski says tellingly in Mr. Vaughan’s biography, ”Listen to the Music: The Life of Hilary Koprowski” (2000), ”I introduce myself as the developer of the Sabin poliomyelitis vaccine.”
Hilary Koprowski was born in Warsaw on Dec. 5, 1916. He attended the Warsaw Conservatory and Warsaw University simultaneously, earning a medical degree from the university in 1939.
Late that year, after the German invasion of Poland, Dr. Koprowski, who was partly of Jewish extraction, left the country with his family. He studied music in Rome before moving to Rio de Janeiro, where he worked for the Rockefeller Foundation’s Yellow Fever Research Service.
In 1944, Dr. Koprowski arrived in the United States and joined Lederle Laboratories, a pharmaceutical concern in Pearl River. It was there, in the late 1940s, that he began his work on polio.
By the mid-20th century, the United States was reporting 20,000 to 60,000 new cases of polio a year, most affecting children. In 1938, President Franklin D. Roosevelt, who had contracted polio as an adult, established what became the March of Dimes, which would finance the Salk and Sabin vaccines.
”What you have to understand about Koprowski was that he was the leading polio researcher from private industry,” Professor Oshinsky said. ”Had he come out of the university and had he been funded by the March of Dimes, I think he would have been a favorite of the virology community.”
But he seemed, at least at times, to roil that community, already skittish about polio.
In the 1930s, researchers had tested two vaccines made from killed polio viruses, in principle safer than live ones. But as it transpired, the viruses had not been killed entirely, and the vaccines paralyzed some children.
As a result, the idea of testing a polio vaccine — much less a live one — on humans was almost beyond contemplation by midcentury.
The first successful live-virus vaccine of any kind was for yellow fever, developed in the late 1930s by the virologist Max Theiler; for his work, he received the 1951 Nobel Prize in Physiology or Medicine.
The method Theiler devised for attenuating the virus involved injecting it into a series of nonhuman embryo cells, including those of mice and chickens. In the late ’40s, Dr. Koprowski wondered whether a similar method could be used to attenuate polio.
Because the cotton rat, a genus found in the Americas, was susceptible to polio, Dr. Koprowski injected the virus into cotton rat brains.
”The thinking is this,” Dr. Offit explained: ”As the virus gets better and better at growing in, in this case, a rodent, it would become less and less capable of growing or reproducing itself in people.”
The result was the grim gray cocktail Dr. Koprowski drank in the lab that day in 1948. He suffered no ill effects.
Two years later, Dr. Koprowski received a call from Letchworth Village, a home for mentally disabled children in Rockland County, N.Y. Fearing an outbreak of polio, the home asked him to vaccinate its children.
In February 1950, in the first human trial of a live polio vaccine, Dr. Koprowski vaccinated 20 children there. At the time, approval from the federal government was required to market drugs but not to test them.
Seventeen of the children developed antibodies against polio. (The other three turned out to have the antibodies already.) None of the children experienced complications.
Describing his trial at a scientific meeting the next year, Dr. Koprowski met with astonished displeasure. In an exchange recounted in Professor Oshinsky’s book, Sabin, who was present, accosted him, saying: ”Why did you do it? Why? Why?”
Sabin’s objection was not to Dr. Koprowski’s testing the vaccine on cognitively disabled children — that was common practice then. It was to his having tested a live polio vaccine on any human being at all.
”Koprowski replied that someone had to take the next step,” Professor Oshinsky wrote, ”so it might as well be him.”
In 1958, Dr. Koprowski administered his vaccine to nearly a quarter million patients in the Belgian Congo. ”It appears to have been completely safe, almost 100 percent effective,” Time magazine reported.
(His work in the Congo came to renewed attention in the 1990s after two publications — Rolling Stone magazine and ”The River,” a book by the British writer Edward Hooper — asserted that Dr. Koprowski had unwittingly spread H.I.V., the virus that causes AIDS, by injecting patients there with contaminated polio vaccines. The assertions have since been discredited.)
In 1960, after several live attenuated polio vaccines, including Sabin’s and Dr. Koprowski’s, had been studied, the United States surgeon general, Leroy E. Burney, announced the approval of Sabin’s. Tests on monkeys had shown it to be somewhat more attenuated, and therefore somewhat safer, than Dr. Koprowski’s.
”He believed they exaggerated the deficiencies and the dangers of his vaccine,” Professor Oshinsky said of Dr. Koprowski. ”Hilary Koprowski’s rebuttal to Sabin would have been, ‘If you had started your vaccine when I started, in the late 1940s, there would be tens of thousands of kids who are not paralyzed now.’ ”
At Wistar, which he led from 1957 to 1991, Dr. Koprowski is credited with transforming the place from a moribund Victorian institution into a first-class research facility. Several important vaccines were created there under his stewardship, including one for rubella, developed in the 1960s by Stanley Plotkin.
Besides his own work on the improved rabies vaccine, which he helped develop in the ’60s, Dr. Koprowski was known for significant early work on the therapeutic use of monoclonal antibodies.
Occurring naturally in the body, these antibodies help the immune system attack particular kinds of cells. Made in quantity in the laboratory, they can be used to combat a range of infectious diseases, as well as certain cancers.
Dr. Koprowski, who held faculty positions at the University of Pennsylvania, with which Wistar is associated, was later affiliated with Thomas Jefferson University in Philadelphia.
Dr. Koprowski’s wife, the former Irena Grasberg, whom he married in 1938, died last year. He is survived by two sons, both of whom received his vaccine as children without complications — Christopher, who confirmed his father’s death, at his home in Wynnewood, Pa., and Claude — and by five grandchildren and three great-grandchildren.
Asked publicly about the lack of recognition for his polio vaccine, Dr. Koprowski was courtly, saying the corresponding lack of hoopla freed him to focus on pure research.
His private feelings differed.
”I think that there was a great deal of hurt and jealousy on his part that he never got credit for what he discovered, and for the path that he blazed for others to follow,” Professor Oshinsky said. ”He pretty much told me that when I interviewed him.”
Dr. Koprowski received many laurels, including the French Legion of Honor. In 2007, his work was recognized with a signal honor, presented annually for distinguished contributions to vaccinology.
The award is known as the Albert B. Sabin Gold Medal.