2000 BC First recorded references to hepatitis epidemics. 1947 F. O. MacCallum, using human volunteers, differentiates hepatitis A, which is spread by contaminated food and water, from hepatitis B, which is spread by blood. 1963 Baruch Blumberg and Harvey Alter discover Aa, the Australian antigen (later called HBsAg). 1967 Between 1967-1968, Blumberg, Kazuo Okochi, Alfred Prince, Alberto Vierrucci, and colleagues report that Aa is involved in the development of hepatitis B. 1969 Irving Millman and Blumberg devise a concept and through the Fox Chase Cancer Center receive a patent for using Aa to prepare a hepatitis B vaccine. 1970 D. S. Dane discovers whole hepatitis B virus particles in blood samples examined with the electron microscope. 1972 Laws are passed in the United States requiring testing of donor blood for HBsAg antigen. 1973 Between 1973-1974, Stephen Feinstone and colleagues and Maurice Hilleman and colleagues discover and describe hepatitis A virus. 1975 Wolf Szmuness and Hilleman and colleagues begin tests of the hepatitis B vaccine. 1977 Mario Rizzetto and John Gerin discover hepatitis D. 1980 Between 1980-1981, subunit hepatitis B virus vaccine derived from blood serum is developed by Hilleman and colleagues, proved effective, and licensed for general use. 1983 Mikhail Balayan describes the hepatitis E virus. 1983 Between 1983-1986, subunit hepatitis B virus vaccine derived from yeast is developed by William Rutter and colleagues and approved for use. 1989 Daniel Bradley provides Chiron with non A-non B hepatitis serum from chimpanzees; Michael Houghton and colleagues discover a single virus, publish the genetic sequence of the viral agent, and change the name to hepatitis C. 1990 Blood screening for hepatitis C begins. 1996 The first hepatitis A vaccine, made by Merck, is licensed for general use; another hepatitis A vaccine, developed by SmithKline Beecham, is proved to be effective.