P&S Journal: Winter 1996, Vol.16, No.1
Profile: Baruch Blumberg'51
By Peter Wortsman
Curiosity-driven science may not kill the cat, but critics claim it drains the kitty, a "Capitol" crime in the current climate of fiscal austerity and managed care. If future funding for basic biomedical research is on trial, few can make a more convincing case in its favor than Baruch Blumberg'51.
The story of the discovery of the hepatitis B virus and development of a test to detect it and a vaccine to harness its virulent effects (for which he shared the 1976 Nobel Prize in Physiology or Medicine) is formidable proof of the viability and cost-effectiveness of fundamental scientific inquiry. The fact is that he and his eclectic team of researchers at the Philadelphia-based Fox Chase Cancer Center (a private cancer care and research facility that profited handsomely from its investment in the vaccine patent) did not originally have hepatitis on their minds. They were, Dr. Blumberg insists, merely pursuing a compelling line of scientific questioning with "the faith that if you study basic problems you'll find clinical applications." In so doing, they stumbled on the resolution of a medical puzzle that had eluded generations of immunologists and virologists.
In a chapter of "Immunology: The Making of a Modern Science" (edited by Gallagher, Gilder, Nossal, and Salvatore, Academic Press, 1995), Dr. Blumberg describes the studies that "started as an esoteric exercise to identify human biochemical variation in relation to susceptibility to disease." Our approach, he says, "was that of amateurs adventuring in a field which we found to be intriguing and mysterious, but not totally familiar." Yet surely his sense of the scientific "amateur" calls into question the very notion of "professional."
Have Mind, Will Travel
Who was and is this captain courageous, intellectual ringleader of a hand-picked band of brilliant scientific adventurers (comprising clinicians, basic scientists, immunologists, epidemiologists, statisticians, and computer scientists) whose research took them hundreds of thousands of miles afield, from Philadelphia to the Australian outback and throughout much of Southeast Asia, testing serum samples in a portable laboratory?
Baruch Blumberg eschews easy labels and traditional categories of learning. At 70, he is still very much the maverick thinker, ever setting out in new directions. (Agile of foot as he is of mind, he recently began rock climbing and took up botany a few years back.) His impish smile belies a childlike curiosity. He rejects the compartmentalization of knowledge. "The world is all put together," he says. "There aren't any holes or lines! To climb the academic ladder, people feel compelled to declare loyalty to a particular discipline. So now we know more and more about less and less, until we'll soon know everything about nothing!"
Once asked by a journalist to define his approach, Blumberg replied: "The virologists say I'm not really a virologist. The geneticists say I'm not really a geneticist. Actually, I think of myself as a clinical researcher." Yet even his sense of clinical research stands outside the norm, based not on therapeutic trials but on a broader notion of population studies.
An undergraduate physics major at Union College in Schenectady, N.Y., he earned an M.A. in physics and mathematics at Columbia and captained a ship in the U.S. Navy before applying to medical school. While still ostensibly studying physics (a discipline he found too impersonal), he took a job as an orderly in the operating room at Presbyterian Hospital, where he was inspired and encouraged by the legendary Virginia Apgar'33 to apply to P&S.
In the personal statement of his student application to P&S, he explained, "The practice of medicine had often appealed to me as possessing these qualities to which I felt best suited: a scientific sub-ject combined with constant contact with people."
Blumberg relished the intellectual ferment of P&S, the scientific rigor and clinical expertise of Robert Loeb, and the pioneering biochemistry of scientists like Karl Meyer. He found the human element he'd been looking for in a fourth year class in parasitology taught by Harold Brown. For firsthand knowledge of the subject, Brown sent his students to the tropics, where, as Blumberg would later put it in his Nobel lecture, "nature operates in a bold and dramatic manner ... and biological effects are profound and tragic." The experience of treating and studying a native population afflicted with filariasis (elephantiasis), among countless other ailments, in a remote corner of Surinam was to mark him for life. "There was sickness all over the place and many people who had never seen a doctor," he recalls. "I was struck by the fact that with relatively minor input you could have an enormous effect on health!"
What he also found in Surinam was a population-based approach to research and a scientific focus on inherited susceptibilities to disease.
Dr. Blumberg pursued his residency under Nobel laureate Dickinson W. Richards'23 at Bellevue's First (Columbia) Division and trained in medicine with Robert Loeb at Presbyterian, subspecializing in rheumatology under Charles Ragan.
From Polymorphisms to Hepatitis B
Eager to expand the scientific base of his knowledge, he subsequently earned a Ph.D. in biochemistry from Oxford. It was there, while completing his doctoral work, that he was first introduced to the notion of "inherited polymorphic systems," as propounded by the Oxford lepidopterist E.B. Ford. That is, as Blumberg explains, "the existence in the same region of two or more inherited forms of a trait in such numbers that the form in lowest frequency could not have been maintained by recurrent mutation."
Returning to the States in 1957 to head up the Geographic Medicine and Genetics Section at the National Institutes of Health, he teamed up with A.C. Allison, whom he'd met at Oxford, and together they designed a new method to discover immunological inherited or acquired variation. "We were looking for common inherited traits and their distribution in populations with the hope that we could identify inherited susceptibility to disease."
Dr. Blumberg later moved to Philadelphia where he was named professor of human genetics at the University of Pennsylvania (a title to which he would later add professor of anthropology) and senior member of the Fox Chase Cancer Center.
Working with Allison and later with microbiologist Irving Millman and fellow clinical researchers W. Thomas London, Alton Slutnick, and others,
Dr. Blumberg and his team studied blood sera from transfused individuals in search of inherited immunological variations.
"We reasoned," he explains, "that if people inherit different proteins, some of those proteins may be antigenic in the sense that, if exposed by a transfusion to a serum protein from another peson, they will develop an antibody against it."
"In 1966," he writes in the chapter in "Immunology: The Making of a Modern Science," "we identified an antigen-antibody system ... The antiserum was found in the blood of a haemophilia patient from New York and the antigen in an Australian aborigine ... [and] by 1967 we had evidence that the antigen was on the surface of one of the hypothesized hepatitis viruses and that the antibody had developed in the transfused patient as a consequence of exposure to the virus ... Later, it was concluded that 'Australia antigen' identified HBV [Hepatitis B virus] was characterized by bloodborne transmission."
Blumberg insists that they didn't start out looking for the hepatitis B virus. They were interested in a normal variation, "with the faith that if you kept the search, you'd eventually find some disease connection." Find it they did.
They went on to develop a vaccine prepared from the purified blood of carriers of the disease, the first vaccine ever made from human blood. Marketed by Merck & Co., and subsequently reproduced by recombinant method, the vaccine is now used in some 40 countries.
Dr. Blumberg and his team also developed an effective diagnostic technique for detecting HBV, which became the first required blood test for a virus and has led to a dramatic drop in posttransfusion hepatitis around the world.
A Scientific Problem Solver
Yet the introduction and general acceptance of this simple and relatively inexpensive detection test created a bioethical problem by turning hepatitis B virus carriers (estimated at 1 million in the United States and 100 million the world over) into a virtual new class of stigmatized persons.
Sensitive to bioethical issues, Dr. Blumberg has questioned in numerous papers the extent to which biological knowledge should be allowed to influence and control the workings of society. "Experience has shown," he wrote in his Nobel lecture, "that these bioethical considerations cannot be separated from 'science,' that answers cannot be provided on a 'purely scientific' basis, and that our technical knowledge is inseparably intertwined with bioethical concerns."
Science, as he sees it, is a dynamic process. "One of the greatest problems that scientists and technologists who apply science have to get across to the public," Dr. Blumberg points out, "is that there are no perfect solutions. And there's always this danger that a striving for perfection, the perfect, drives out the good. Yet if you're satisfied with less than perfect, you won't try to make things as good as you can."
In a paper co-authored with the medical sociologist RenŽe Fox, titled "The Daedalus Effect," (Annals of Internal Medicine, 1985), Blumberg taps Greek mythology for the prototype of the ultimate problem solver and curiosity-based scientific thinker.
"Daedalus, you remember, first created the Labyrinth and then created wings to escape it. Every time he solved a problem he created another one," Blumberg reflects. "And then he'd solve that problem and that would create another and another. You get the sense that he was almost more interested in the problems than in the solutions."
Recognition in the form of the Nobel Prize and countless other encomia (including the P&S Alumni Gold Medal in 1979 and honorary degrees from 23 institutions of higher learning at last count) have enabled Dr. Blumberg to influence the course of international health care on a wide scale. His input has been particularly important in China, where hepatitis B is more prevalent than anywhere else in the world. He also has helped start vaccination programs in New Zealand, Saudi Arabia, Jordan, and Brazil.
Dr. Blumberg has not shied away from using his influence as a member of the Human Rights Committee of the National Academy of Sciences. As part of a delegation to Chile during the Pinochet regime, he helped identify and free imprisoned scientists.
In 1989 he was named Master of Balliol College at Oxford University, a post from which he recently retired.
He has of late embarked on a new study, analyzing the blood sera he collected over the past three decades and stored in deep freeze, searching for the presence of two viruses, AIDS and the HTLV1 (human T-cell leukemia virus 1), microbes that had not yet been identified at the time the blood was drawn.
Co-owner of a cattle farm in western Maryland, hiker, rock climber, botanist, broadcaster (he hosted a PBS special on "Plagues, A Selective Look at the Mysteries of Epidemics"), Baruch Blumberg is as complex and multifaceted as the science he loves. "Nature is dynamic, it keeps changing," he points out. So, it seems, does Dr. Blumberg.