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Surprising Finding |
Blumberg thought he might have detected an inherited blood-protein polymorphism that affected people's susceptibility to leukemia , but he knew that other possibilities (including an infectious agent like a virus) might explain the link between Aa and leukemia. To clarify that link, he began searching for Aa in the blood of children with Down syndrome, who run a particularly high risk of developing leukemia. Almost one-third of these children had Aa. Blumberg then tested Down patients of various ages who were housed in various settings. Newborn patients tested negative for Aa, but the bigger the institution in which the patient resided, the more likely that he or she tested positive. This suggested that Aa might be linked to an infection of some sort.
Usually, the children who tested negative for Aa remained negative when retested and those who tested positive remained positive, as expected for a blood-protein polymorphism. But in 1966, Blumberg, W. Thomas London, and Alton Sutnick discovered that a 12-year-old boy with Down syndrome who had no trace of Aa in his serum when he was first tested showed presence of the antigen in his blood a few months later. Significantly, this boy not only displayed Aa by the agar gel diffusion test but he also had hepatitis. The coincidence suggested that, rather than being associated with an inherited blood-protein polymorphism, Aa was linked to hepatitis. Immediately researchers began exploring this hypothesis. In testing patients with and without hepatitis, they found that those with hepatitis tested positive for Aa more often than those without the disease. The hypothesis was dramatically bolstered when Blumberg's laboratory technician began to feel ill. Aware of the link between Aa and hepatitis, she tested her own serum for the presence of Aa--and found it positive. She later developed hepatitis and became one of the first people whose viral hepatitis was diagnosed with the Aa test.
Hearing of Blumberg's findings, virologist Alfred Prince of the New York Blood Center started an experiment in the mid-1960s that would eventually confirm the link between Aa and hepatitis. Knowing that at least one in 10 patients who received multiple blood transfusions would come down with hepatitis, Prince wanted to determine whether Aa appeared in the blood during the incubation period of the disease, before any symptoms of illness, as would occur if Aa were part of the virus that caused the hepatitis. Prince began taking blood samples from certain patients at the New York Blood Center at regular intervals and storing them in a freezer. Finally, in 1968, he heard that a patient whose blood he had collected had developed clear symptoms of hepatitis. When he tested the man's blood samples, he found no evidence of Aa in the early batches but clear evidence of it in blood taken a few weeks before onset of the illness. Such seemingly direct evidence strongly suggested that Aa was indeed involved in the development of hepatitis B.
At about the same time, University of Tokyo's Kazuo Okochi showed that blood that tested positive for Aa was much more likely to transmit hepatitis to transfused patients than blood that tested negative. Albert Vierrucci, of the University of Sienna, Italy, independently confirmed Prince's and Okochi's reports in the same year, 1968. Further strengthening the link between Aa and hepatitis were discoveries made with an electron microscope in 1970 by D. S. Dane and colleagues at Middlesex Hospital in London and K. E. Anderson and colleagues in New York of what looked like virus particles in the sera of people who tested positive for Aa. They also found particles in the liver cells of patients with hepatitis.
By the end of 1970, mounting evidence led nearly everyone in the field to the same conclusion: Aa was part of the virus that causes hepatitis B. (At this point nomenclature for Aa was changed to HAA, or hepatitis-associated antigen; it is now officially called HBsAg, for hepatitis B surface antigen.) The leukemia and hemophilia patients whose blood showed a high incidence of HBsAg all had needed frequent transfusions and therefore were more likely to have received blood contaminated with hepatitis B virus.
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 | | | All About Blood - From the American Association of Blood Banks. This site has information about blood, blood banking, and blood screening--and a page on the highlights of transfusion history. |  | | Hepatitis B - More information on Hepatitis B from the American Liver Foundation. | | | Understanding the Immune System - A detailed introduction to the immune system, including a section on antibodies. | | | Yellow Fever and the Reed Commission - An interesting historical article on yellow fever and the Spanish-American War. |  |
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