From 1989 until 1994 Blumberg was Master of Balliol College, Oxford, after which he embarked on a second scientific career as an astrobiologist with Nasa, investigating the possibility of life on other planets.
In the 1950s Blumberg began compiling and analysing data from blood samples from remote populations from Africa to the Arctic in the hope of discovering why different ethnic groups have different levels of resistance to various diseases. Among the mysteries he hoped to solve were why some Africans carry a higher susceptibility to sickle-cell disease and why many women among the Basques of Spain have blood types that often clash with their unborn children, leading to higher rates of infertility and miscarriage.
He came cross the hepatitis B virus entirely by chance. In 1963, while examining thousands of blood samples, Blumberg found a mysterious substance in the blood of an Australian aborigine that provoked an immune response in the sample of an American haemophilia patient.
Three years later a Down's Syndrome patient who had previously tested negative for the same immune system-triggering substance (or antigen) suddenly tested positive, and soon developed hepatitis. This sequence of events was then observed in another patient. It turned out that the antigen was found frequently in the blood serum of those suffering from hepatitis B, and was, in fact, the surface antigen of the virus. Exposed to numerous blood transfusions, the haemophiliacs had developed antibodies against the virus which had reacted against the antigen.
Blumberg's discovery of what became known as the "Australian antigen" made it possible for him and his colleagues to develop diagnostic tests that reduced the spread of hepatitis B (which is also a leading cause of liver cancer) through donated blood. Crucially, it also led to the development of a vaccine, from the serum of those with the antigen, that has since spared countless lives.
Yet as a "mere" biochemist Blumberg at first had difficulty in convincing virologists to take him seriously. In 1967, the Annals of Internal Medicine rejected his first attempt to publish his findings: "We were outsiders not known to the main body of hepatitis investigators, some of whom had been pursuing their field of interest for decades," Blumberg recalled; "we were surprised by the hostility engendered among our new colleagues." But he took it all in his stride, knowing that "if such rejections are taken too seriously, they can lead to an attitude of martyrdom". As it turned out, other groups soon corroborated Blumberg's findings.
One of three children of a lawyer, Baruch Samuel Blumberg was born on July 28 1925 in Brooklyn, New York, and educated at Far Rockaway High School in Queens, where he won a science prize after making a working refrigerator from junk parts. After leaving school he enlisted in the US Navy, serving on landing ships during the Second World War. Afterwards he took a degree in Physics at Union College, Schenectady, then embarked on graduate work in Mathematics at Columbia University, soon switching to Medicine.
Before his final year he spent several months at Moengo, an isolated mining town in the rainforest of Surinam (then Dutch Guiana), populated by a hotchpotch of different races. He became fascinated by their very different responses to the many infectious agents in the environment. His observation that miners of African origin were more likely to be infected by Wuchereria bancroftia (the mosquito-borne parasite which causes elephantiasis) than miners of Indonesian or Chinese heritage led to his first published paper and set the scene for his lifetime's work.
After a clinical fellowship at Columbia Presbyterian Medical Center, Blumberg went to Balliol College, Oxford, where he did a PhD under Alexander Ogston on the physical and biochemical characteristics of hyaluronic acid – one of the major constituents of connective tissue and the vitreous humour of the eyes. In 1957 he made a trip to Nigeria where he collected blood samples from several population groups in order to study polymorphisms (inherited traits from different forms of the same gene) of the serum proteins of milk and of haemoglobin.
He returned to the United States the same year to join the National Institutes of Health, heading its Geographic Medicine and Genetics Section until 1964, when he became associate director for clinical research at the Fox Chase Cancer Center in Philadelphia. There he continued to research the biology and ecology of the hepatitis B virus and the relationship between the virus and liver cancer. From 1986 he was the centre's vice-president for population oncology and in 1989 he became the first Fox Chase Distinguished Scientist. From 1977 he also held chairs in Medicine and Anthropology at the University of Pennsylvania.
In 1983-84, Blumberg spent a year as a visiting professor at Balliol and four years later, in 1988, he was elected to succeed Anthony Kenny as its Master, becoming the first American and the first scientist (bar an alchemist in the 14th century) to occupy the post. During his five years in the Master's Lodge, Balliol became one of the first Oxbridge colleges to introduce a "development" programme to raise funds from alumni, foundations, companies, and other donors. Blumberg sought to bring the old members back into the orbit of the college by holding seminars on topics of broad interest to which they were invited, and travelled extensively to meet them.
From 1999 to 2002 Blumberg worked as director of the Astrobiology Institute at Nasa's Ames Research Center in California with a brief to wrestle with such cosmic questions as whether life exists elsewhere in the universe and whether humans can survive on other planets, and to oversee research on the origins of life on Earth. In 2003 he was a castaway on Desert Island Discs. From 2005 he was president of the American Philosophical Society, the oldest learned society in the United States.
A keen film fan whose hobbies included carpentry and photography, Blumberg enjoyed running, mountain walking, cycling and canoeing, and was a regular squash player. With several friends he owned a beef farm in western Maryland, claiming that shovelling manure was "an excellent counterbalance to intellectual work". In 2002 he published Hepatitis B: The Hunt for a Killer Virus, an account of the discovery for which he won the Nobel Prize.
In 1954 he married Jean Liebesman, an artist who survives him with their two sons and two daughters. His younger daughter, Jane, is married to Mark Thompson, the director general of the BBC.