Nearly 50 years ago, in a South American rain forest, Baruch Blumberg was struck by the pattern of parasitic disease among workers in a mining town.
The workers came from immigrant families who had been in the area for generations. All lived in the same company-owned housing. All had contact with the mosquitoes that carried the parasite.
Despite their similar lifestyles, the miners of African origin were much more likely than those of Indonesian or Chinese heritage to be infected.
Blumberg, then a medical student at Columbia University, was intrigued. Could it be, he wondered, that genetic differences made some people but not others susceptible to infectious disease, even though all faced the same exposure risk?
It was a question that set Blumberg on a quest.
In 1967, at Fox Chase Cancer Center in Philadelphia, that quest led to an unexpected find: discovery of the virus that causes hepatitis B, a liver disease that each year kills more people worldwide than AIDS. Blumberg and his colleagues at Fox Chase soon developed a blood test for the hepatitis B virus and later a vaccine to prevent infection.
Blumberg’s work won medicine’s highest honor: the 1976 Nobel Prize in medicine. But the real payoff is just becoming evident.
Not only has the incidence of hepatitis B declined but there is new evidence that a deadly form of liver cancer stemming from chronic infection with hepatitis B also is on the wane.
In Taiwan, there has been a fourfold decline in the incidence of liver cancer among children 6 to 9 since hepatitis B vaccination began in 1984. The gains, reported in June by Chinese scientists in the New England Journal of Medicine, are the first to document the impact of hepatitis B vaccination on liver cancer, which typically leads to death less than a year after diagnosis.
With 85 countries conducting national immunization programs against hepatitis B, the worldwide impact on liver cancer could be enormous. In some parts of Asia, hepatitis B-associated liver cancer is the leading cancer, killing tens of thousands of people each year.
“If the results are sustained, it will mark the first major international program against a preventable cancer,” said Blumberg, 72, now senior scientific adviser at Fox Chase, a federally designated comprehensive cancer center.
To Blumberg, the serendipitous discovery of hepatitis B underscores the importance of basic scientific research–broad inquiry into seemingly esoteric questions that have no immediate payoff but can lead to significant advances.
It was just such a question that Blumberg asked in the South American rain forest when he began to wonder whether inherited traits could make different groups of people more or less susceptible to the same infectious disease.
In the early 1950s, Blumberg and his colleagues decided to look for genetic differences first and then explore whether these differences were associated with disease.
As it turned out, that tack would be key to the discovery of hepatitis B.
The scientists trekked the globe, collecting blood samples from a wide variety of populations. The goal was to look for “polymorphisms”–inherited traits stemming from different forms of the same gene.
Blumberg was interested in the polymorphisms found in serum, the liquid part of blood, because it is home to dozens of proteins, including those that fight infectious disease.
The scientists hypothesized that people in different parts of the world would have different forms of the same blood proteins. These differences might be explained by classic Darwinian theory–survival of the fittest.
People who lived in the tropics, for instance, might have higher frequencies of protein types that conferred resistance to certain tropical diseases. Such a trait would have been maintained from one generation to the next because it offered a survival advantage.
Working before the revolution in molecular biology, Blumberg had no way to study inherited susceptibility to disease at the genetic level, so he developed an indirect way.
He reasoned that people such as hemophiliacs, who had received numerous blood transfusions, would have been exposed to blood serum proteins that they themselves had not inherited but that had been inherited by their donors.
The immune systems of the transfused people would perceive these transfused blood proteins as foreign invaders and would produce antibodies to combat them.
Because antibodies are perfectly designed to lock onto one and only one antigen, or foreign invader, the antibodies in the hemophiliacs could then be used to test blood the scientists had collected from around the world.
Using a laboratory technique that allowed them to match antibodies to antigens, the scientists identified a match between an antibody from a New York hemophiliac and an antigen found in the serum of an Australian aborigine.
The antigen turned out to be rare in Western countries but common among the Australian aborigines, Micronesians, Vietnamese and Taiwanese. Curiously, it also was common in leukemia patients in the U.S.
The scientists named the unknown substance “Australia antigen”–or Au–because it originally was taken from the aborigine’s blood.
The researchers had no idea why Au was found in leukemia patients, but they developed several hypotheses, including the possibility that people with Au were more susceptible to leukemia and that susceptibility was inherited.
Because children with Down syndrome are at much greater risk of developing leukemia than other children, Blumberg and his colleagues reasoned that Down syndrome children also might have a higher probability of having Au.
To study that, they turned to the New Lisbon State School, an institution for the mentally impaired in New Lisbon, N.J. Blood samples taken from Down syndrome patients found that 30 percent had Au. By contrast, only 5 percent of the other mentally impaired people at the school had Au.
This seemed to support the hypothesis that the susceptibility to leukemia was inherited.
Then the unexpected happened. A Down syndrome patient, James Bair, a teenager who had previously tested negative for Au, suddenly turned positive. At the same time, he developed hepatitis.
On June 28, 1966, Blumberg’s colleague at Fox Chase, Alton Sutnick, wrote a dramatic note in Bair’s chart: “SGOT (a liver enzyme) slightly elevated! Prothrombin time (an indicator of liver disease) low! We may have an indication of his conversion to Au+.”
As it turned out, Au was a protein on the outer coat of an exceedingly small virus, one that would come to be called hepatitis B.
The leukemia patients had gotten Au from blood transfusions. The Down syndrome patients had acquired it from close contact with infected people in crowded institutions.
