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.
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