Infectious Disease · 1965
Discovery of the hepatitis B virus (Australia antigen)
In the early 1960s, the cause of serum hepatitis, the form transmitted by blood and needles, was unknown. No virus had been isolated, no reliable test existed, and blood banks had no way to screen donors. Post-transfusion hepatitis was a common and often serious complication of cardiac surgery, blood transfusions, and any procedure requiring multiple units. Baruch Blumberg, a physician and geneticist at the National Institutes of Health, was not looking for a hepatitis virus. He was cataloguing inherited variation in human serum proteins by testing sera from different populations against a panel of samples from multiply transfused patients.
In 1965, while testing serum from an Australian Aboriginal donor, Blumberg found a precipitin reaction against a sample from a hemophiliac patient who had received many transfusions. The reactive substance was a novel antigen he called the Australia antigen. Over the following two years, working with colleagues including Harvey Alter at NIH, Blumberg established that the antigen was present almost exclusively in patients with hepatitis B infection. What had started as a population genetics experiment had identified the surface protein of a pathogen responsible for millions of deaths annually worldwide.
The practical application came quickly. Diagnostic tests for the Australia antigen, later renamed hepatitis B surface antigen (HBsAg), were developed and blood banks began screening donated units in the early 1970s. Before screening, post-transfusion hepatitis was a frequent complication in patients who received multiple blood units during major surgery. Routine HBsAg testing substantially reduced those cases within a few years of its introduction.
Blumberg shared the 1976 Nobel Prize in Physiology or Medicine with Daniel Carleton Gajdusek. His identification of HBsAg also provided the molecular target for vaccine development. The first hepatitis B vaccine, based on purified surface antigen derived from the plasma of chronic carriers, was licensed in 1981. A recombinant version followed in 1986, produced in yeast cells by inserting the gene for HBsAg.
Universal infant hepatitis B vaccination, now part of most national immunization schedules, has sharply reduced the incidence of chronic HBV infection in vaccinated birth cohorts. Studies from Taiwan, where universal infant vaccination began in 1984, showed that hepatocellular carcinoma rates among vaccinated children fell by more than 70 percent compared with unvaccinated cohorts. That finding gave hepatitis B vaccination one of the most documented cancer-prevention track records of any vaccine program.
Key People
- Baruch Blumberg — Physician-geneticist who identified HBsAg; Nobel laureate 1976
- Harvey Alter — NIH researcher who extended blood screening work on hepatitis B and C
- Irving Millman — Blumberg collaborator who co-developed the first HBV vaccine
JAMA, 1965
Related landmarks
- 1960 · Sabin Oral Live-Attenuated Polio Vaccine (Infectious Disease)
- 1955 · Salk Inactivated Polio Vaccine Field Trial (Francis Report) (Infectious Disease)
- 1981 · First report of AIDS (Pneumocystis pneumonia cluster) (Infectious Disease)
- 1984 · Marshall & Warren: Helicobacter pylori causes peptic ulcer disease (Infectious Disease)