Winning the fight against liver disease

Hepatitis B: The Hunt for a Killer Virus

Princeton University Press: 2002. 272 pp. $27.95, £19.95
Looking back: Baruch Blumberg's research on hepatitis B drew on earlier fieldwork in Suriname.

Hepatitis B is a common viral infection of the liver and a major global public-health problem. More than 2 billion people alive today — over a third of the world's population — have been infected with the hepatitis B virus, and of these about 350 million will become carriers of the virus. Some 20–25% of carriers will progress to serious liver disease, including chronic active hepatitis, cirrhosis and primary liver cancer. Primary liver cancer is the seventh most common cancer in males and the ninth most common in females, and the hepatitis B virus is second only to tobacco among the known human carcinogens. Although the precise molecular mechanisms by which the virus induces malignancy remain largely unknown, it is the cause of 80% of the world's primary liver cancer, which is one of the three most common causes of cancer deaths in males in east and Southeast Asia, the Pacific Basin and sub-Saharan Africa.

The discovery by Baruch Blumberg of the Australia antigen, a specific viral marker of the hepatitis B virus, was one of the most important advances in medical knowledge during the past 50 years and had huge implications for preventive medicine. This inspiring book is an intensely personal and interesting account of the work of Blumberg and his close associates who, after discovering the Australia antigen, continued to work on hepatitis B and devised the first-generation vaccine for this infection.

Because of this personal focus, there is relatively little mention of the contributions made by many researchers across the world and the crucial role of the World Health Organization in the unfolding story of the five different types of viral hepatitis and the implementation of universal immunization against hepatitis B in over 100 countries. Rates of liver cancer have fallen significantly in regions that have immunization programmes, such as Taiwan. If immunization is introduced universally, the hepatitis B virus could be eradicated within 20–50 years.

Blumberg was born in Brooklyn, New York, and attended a yeshiva, the intellectual powerhouse of traditional Jewish education. He continued his education at Far Rockaway School in New York, a public high school that counts three Nobel laureates, including Blumberg, among its alumni. He read medicine at Columbia University College of Physicians and Surgeons before leaving New York to read biochemistry at Balliol College, Oxford, UK.

The discovery of the Australia antigen was based on Blumberg's interest in genetic variation and specific susceptibility to disease, and his use of the Ouchterlony double-gel diffusion test to detect antigen–antibody interactions by the formation of precipitin lines in a gel. Blumberg did not set out to find a marker for hepatitis B — his interest was in inherited polymorphic traits. He conducted a systematic search of sera from multiply transfused patients to find antisera that could detect new antigenic polymorphisms among low-density lipoproteins and other proteins. He also used sera obtained from Australian Aborigines as part of a collaborative study.

The antibody used to find the antigen was serum obtained from New York patients with haemophilia, who had received many transfusions (and thus almost inevitably contracted hepatitis B). The rest, of course, is history, and is narrated in an eloquent and engaging style. The paper on the association between the Australia antigen and hepatitis was initially rejected by the Annals of Internal Medicine in 1967 because the reviewer was reluctant to risk another false claim for the identification of the elusive hepatitis virus(es). But it was published in the end, and Blumberg received the Nobel prize in Physiology or Medicine in 1976.

The book is a gem, though it is a pity about the title, which was borrowed from an overworked newspaper headline. It is essential reading for all aspiring scientists, the faceless bureaucrats who control the budgets for medical research, and devotees of the Research Assessment Exercise (it is doubtful if Blumberg's work would have attained a significant score). And it should be read by the thousands of people who work on the control and eradication of the hepatitis B virus.

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Zuckerman, A. Winning the fight against liver disease. Nature 417, 900 (2002). https://doi.org/10.1038/417900a

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