Timeline of key events related to hepatitis B

Blumberg and his team found the antigen to common in 1 in 10 leukaemia patients. By contrast it was rare in healthy individuals (1 in 1,000). BS Blumberg, HJ Alter, S Visnich, A new antigen in leukemia sera, JAMA, 191 (1965), 541-6.1965-01-01T00:00:00+0000The patient was James Blair, a twelve year old. Six months before he tested negative for the disease1966-07-20T00:00:00+0000She made a full recovery1967-04-01T00:00:00+0000Carried out with more than 700 mentally disabled children, the experiments were later criticised for being unethical. The research, however, revealed hepatitis was made up of A & B strains, that HBsAG could provide means for a hepatitis B vaccine and gamma globulin antibodies from hepatitis patients' blood could help treat hepatitis B. The experiment had both an an experimental and a control group. Those in experimental group were children already housed at Willowbrook. They were injected with protective antibodies. The control group involved newly admitted children. This group had a subset of children deliberately infected with hepatitis A obtained from sick children with remainder being given nothing. S Krugman, JP Giles, J, Hammond, 'Infectious hepatitis. Evidence of two distinct clinical, epidemiological and immunological types of infection', JAMA, 200 (1967), 365–73.1967-05-01T00:00:00+0000AM Prince, 'An antigen detected in the blood during the incubation period of serum hepatitis', Proc. Natl Acad. Sci. USA, 60 (1968), 814–21.1968-01-01T00:00:00+0000This was done using an agar gel diffusion assay Prince developed. 1968-01-01T00:00:00+00001968-01-01T00:00:00+0000Hilleman launched the work based on sample HBsAg supplied to him by Alfred Prince1968-01-01T00:00:00+0000JB Smith, BS Blumberg, 'Viral hepatitis, postnecrotic cirrhosis, and hepatocellular carcinoma', Lancet, 2/7627 (1969), 953; AI. Sutnick, et al, 'The role of Australia antigen in viral hepatitis and other diseases', Annual Review Medicine, 23 (1972), 161-76.1969-01-01T00:00:00+0000Four members of staff and seven patients died. The outbreak prompted Kenneth Murray to launch project to genetically engineer vaccine against hepatits B. 1969-01-01T00:00:00+0000Baruch Blumberg and Irving Millman appled for the patent following pressure from the Federal government to show applications from basic research. BS Blumberg, I Millman 'Vaccine against viral hepatitis and process', US patent 3636191A1969-10-08T00:00:00+00001970-01-01T00:00:00+00001970-01-01T00:00:00+0000DS Dane, CH Cameron, M Briggs, 'Virus-like particles in serum of patients with Australia-antigen-associated hepatitis', Lancet, 1 (1970), 695–8.1970-04-04T00:00:00+00001971-01-01T00:00:00+0000Hilleman achieved this on the basis of collecting blood from homosexual men and drug users, mainly living in flophouses, stairwells and fire escapes in the Bowery neighbourhood of New York. 1971-01-01T00:00:00+0000Known as the solid-phase sandwich radioimmunosassay, the test combined the specificity of the biological antigen-antibody interaction with the high sensitivity of modern physicochemical analytical method. It used lablelled antigens or antibodies with radioactive substances such as iodine-15. CM Ling, LR Overby, 'Prevalence of hepatitis B virus antigen as revealed by direct radioimmune assay with 125 I-antibody', Journal Immunology, 20 (1972), 834–41.1972-01-01T00:00:00+00001972-01-01T00:00:00+0000BS Blumberg, I Millman 'Vaccine against viral hepatitis and process', US patent 3636191A1972-01-18T00:00:00+0000JE Maynard, et al., 'Experimental infection of chimpanzees with the virus of hepatitis B', Nature, 237/5357 (1972), 514-15; LF Barker, et al., 'Transmission of type B viral hepatitis to chimpanzees', Journal Infectious Diseases, 127/6 (1973), 648-62.1972-06-01T00:00:00+0000
Date Event People Places Sciences
1965Blumberg called newly found protein 'Austalian antigen' and saw it as genetic marker for leukaemiaBlumberg, Alter, VischFox Chase Cancer Center 
20 Jul 1966Boy with Down Syndrome found to have chronic hepatitis whose blood 6 months before tested positive for Australian antigenBlumbergFox Chase Cancer Center 
April 1967Barbara G Werner, technician working in Blumberg's laboratory developed hepatitis after working with Australian antigenWerner, BlumbergFox Chase Cancer Center 
1 May 1967Willowbrook State School experiments offered new understandings about hepatitis, its treatment and preventionKrugman, Giles, HammondNew York University, Willbrook State SchoolInfectious diseases
1968Alfred Prince, virologist, showed Australian antigen part of hepatitis B virusPrinceNew York Blood Center 
1968Prince set up scheme to test donor's blood for hepatitis B at New York Blood CenterPrinceNew York Blood Center 
January 1968Collaboration set up between Blumberg's team and Philadelphia General Hospital to test donor's blood for Australian antigenBlumbergPhiladelphia General Hospital, Fox Chase Cancer Center 
1968Maurice Hilleman began investigating use of HBsAg to develop hepatitis B vaccine HillemanMerckVaccines, Infectious diseases
1969 - 1972Chronic hepatitis B linked to the development of liver cancerSmith, Blumberg, Sutnick, Millman, LondonFox Chase Cancer Center 
1969 - 1971Severe outbreak of hepatitis B in dialysis unit at Edinburgh Royal Infirmary  Infectious diseases
8 Oct 1969Blumberg and Millman applied for patent to use HBsAg to produce hepatitis B vaccineBlumberg, MillmanFox Chase Cancer CenterVaccines
1970US blood banks started using screening test for hepatitis B carriers   
1970WHO Bulletin recommended the detection and exclusion of blood donors carrying the Australian antigen   
4 Apr 1970David Dane and colleagues showed Australian antigen is a surface particle - rename it Hepatitis B surface antigen (HBsAg)Dane, Cameron, BriggsCentral Middlesex Hospital 
1971New York State passed legislation requiring testing for hepatitis B for all blood donors   
1971HBsAG purified for first timeHillemanMerck 
1 Jan 1972Scientists at Abbott Laboratories published a new highly sensitive test, Austria 125, for detecting hepatitis BLing, OverbyAbbott LaboratoriesDiagnostics
1972Abbott marketed the first adequate hepatitis B diagnostic test Abbott LaboratoriesDiagnostics
18 Jan 1972Patent granted to Blumberg and Millman for making hepatitis B vaccineBlumberg, Millman Vaccines
1972 - 1973Hepatitis B found to be transmitted to chimpanzeesBarker, MaynardFDA, Hazleton Laboratories, Hammersmith Hospital, Scripps Clinic and Research Foundation, University North Carolina, Pohenix Laboratories, National Institute of Health 

1965

Blumberg called newly found protein 'Austalian antigen' and saw it as genetic marker for leukaemia

20 Jul 1966

Boy with Down Syndrome found to have chronic hepatitis whose blood 6 months before tested positive for Australian antigen

Apr 1967

Barbara G Werner, technician working in Blumberg's laboratory developed hepatitis after working with Australian antigen

1 May 1967

Willowbrook State School experiments offered new understandings about hepatitis, its treatment and prevention

1968

Alfred Prince, virologist, showed Australian antigen part of hepatitis B virus

1968

Prince set up scheme to test donor's blood for hepatitis B at New York Blood Center

Jan 1968

Collaboration set up between Blumberg's team and Philadelphia General Hospital to test donor's blood for Australian antigen

1968

Maurice Hilleman began investigating use of HBsAg to develop hepatitis B vaccine

1969 - 1972

Chronic hepatitis B linked to the development of liver cancer

1969 - 1971

Severe outbreak of hepatitis B in dialysis unit at Edinburgh Royal Infirmary

8 Oct 1969

Blumberg and Millman applied for patent to use HBsAg to produce hepatitis B vaccine

1970

US blood banks started using screening test for hepatitis B carriers

1970

WHO Bulletin recommended the detection and exclusion of blood donors carrying the Australian antigen

4 Apr 1970

David Dane and colleagues showed Australian antigen is a surface particle - rename it Hepatitis B surface antigen (HBsAg)

1971

New York State passed legislation requiring testing for hepatitis B for all blood donors

1971

HBsAG purified for first time

1 Jan 1972

Scientists at Abbott Laboratories published a new highly sensitive test, Austria 125, for detecting hepatitis B

1972

Abbott marketed the first adequate hepatitis B diagnostic test

18 Jan 1972

Patent granted to Blumberg and Millman for making hepatitis B vaccine

1972 - 1973

Hepatitis B found to be transmitted to chimpanzees

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