Bernice Eddy

Bernice Eddy (1903–1989) was an American virologist and epidemiologist. She and Sarah Elizabeth Stewart are known for their discoveries related to polyomavirus[1] and SV40 in particular, a cancer-causing monkey virus that millions of people were exposed to through contaminated polio vaccines.[2]

Bernice Eddy
Bernice Eddy as a staff member of the Laboratory of Biologics Control, 1938
Born
Bernice E. Eddy

(1903-09-30)September 30, 1903
Glen Dale, West Virginia
DiedMay 29, 1989(1989-05-29) (aged 85)
NationalityAmerican
Alma materMarietta College
University of Cincinnati
Known forfirst describing the polyomavirus, work on the polio vaccine
Spouse(s)Dr. Jerald Wooley
Scientific career
FieldsMedical research,
virology and epidemiology
InstitutionsUnited States Public Health Service, National Institutes of Health, American Public Health Association

Education

Eddy was born in 1903 to the physician Nathan E. Eddy and Clara C. Eddy (née Griffith) in Glen Dale, West Virginia. The family lived in Auburn. After her father's death, Eddy's mother moved to Marietta, Ohio. Eddy graduated at Marietta College in 1924. She went on to study at University of Cincinnati, earning a Master's degree in 1925 and a Ph.D. in 1927.[3]

National Institutes of Health (NIH) career

In 1930 Eddy joined the United States Public Health Service (USPHS). In 1935 Eddy transferred to the National Institutes of Health (NIH) in Bethesda, Maryland, were she joined the Biologics Control Division, the department of the NIH responsible for checking the quality of vaccines distributed by the Federal government of the United States.[4]

NIH flu virus vaccine testing

When World War II started Eddy was made responsible for checking the quality of influenza vaccines used by the United States Army. Eddy checked army flu vaccines for 16 years and was promoted to chief of flu virus vaccine testing in 1944.[5]

Research on polio vaccines

In parallel to her job as chief of flu virus vaccine testing Eddy began research on polio vaccines at NIH in 1952. In 1953 she was awarded the NIH Superior Accomplishment Award for the research on polio vaccines.[6]

Cutter incident

In 1954 the NIH asked Eddy to perform safety tests for a batch of inactivated vaccine developed by Jonas Salk for Cutter Laboratories. Salk's inactivated polio vaccine was a killed-virus vaccine that was to be used in a massive national vaccination program.[7] Eddy's job was to test the vaccines from five different companies.[8] Testing the vaccines on 18 monkeys, she and her team discovered that the inactivated vaccine manufactured by Cutter Laboratories contained residual live poliovirus, resulting in the monkeys showing polio-like symptoms and paralysis. Eddy reported her findings to William Workman, head of the Laboratory of Biologics Control, but her findings were never given to the vaccine licensing advisory committee.[9] Cutter Laboratories had submitted sample batches of their polio vaccine months before licenses were granted. Eddy's finding that three of the six batches paralyzed monkeys[10] and therefore contained live polio virus pointed to a flawed vaccine manufacturing process at Cutter Laboratories.[11]

The flawed vaccine manufacturing process produced 120,000 doses of polio vaccine that contained live polio virus. Of children who received the vaccine, 40,000 developed abortive poliomyelitis (a form of the disease that does not involve the central nervous system), 56 developed paralytic poliomyelitis—and of these, five children died from polio.[12] The exposures led to an epidemic of polio in the families and communities of the affected children, resulting in a further 113 people paralyzed and 5 deaths.[13] Two days after the first reports of paralysis the NIH started to examine Cutter's manufacturing process. On the 29 April 1955 the NIH director William Sebrell chaired a meeting to examine Cutter's manufacturing protocols. The one day meeting was also attended by Eddy and produced no conclusion on what Cutter should do differently in its manufacturing process.[14] The associate director of NIH Leonard A. Scheele, also the surgeon general of the Public Health Service, knew that the NIH could not force Cutter Laboratories to recall their polio vaccine, because the Biologics Control Act only provided the federal government with the power to license a vaccine.[15] On the 6 May 1955 Scheele announced to the press that the national polio vaccination program would be postponed until further notice. Vaccine manufacturers withheld 3.9 million doses of polio vaccine as a result and the polio vaccine program suspension in the United States was followed by a suspension of similar polio vaccination drives in Great Britain, Sweden, West Germany and South Africa.[16] The Cutter incident was one of the worst pharmaceutical disasters in US history, and exposed several thousand children to live polio virus on vaccination.[13] The director of the microbiology institute lost his job. Secretary of Health, Education, and Welfare Oveta Culp Hobby stepped down. Sebrell, the director of the NIH, resigned.[17]

Testing of common cold vaccines

The NIH took Eddy off polio research and asked her to test a common cold vaccine.[18]

Polyomavirus research

While testing common cold vaccines, Eddy and her NIH colleague Sarah Elizabeth Stewart began research on a virus that Stewart had discovered.[19] Building on earlier work by Ludwig Gross, Stewart and Bernice E. Eddy were the first to describe a polyomavirus.[20] They satisfied Koch's postulates to demonstrate that polyomavirus can cause cancer to be transmitted from animal to animal. The virus was named the Stewart-Eddy or SE polyoma virus, after their respective surnames.[1]

SV40 virus research

At the time, common cold vaccines and polio vaccines were both manufactured using viruses grown in monkey kidney cells.[21] In 1961, Eddy showed that an extract of rhesus monkey kidney cells (RMKC), notable because of its use as a growth medium in the creation of the polio vaccine, caused tumors in newborn hamsters.[22] In 1962 she presented evidence that the oncological agent present in the RMKC serum was capable of inducing histologically similar tumors under the same conditions as SV40, and that these tumors showed different properties than the SE polyoma virus, which was the only other biological material known to be capable of inducing tumors in almost all hamsters injected as newborns.[2] Similar to SV40, RMKC extracts remained infectious after passage through filters, and similar levels of exposure to diethyl ether, heat, and storage at -70 °C. Eddy also provided evidence that the RMKC extracts were inhibited (tumors would not develop) under conditions that also inhibited SV40 tumor development. This includes inhibition in animals that received RMKC extracts combined with anti-SV40 rabbit serum. Given the preponderance of evidence, this paper drew the conclusion that the oncological agent in the RMKC extracts were identical to the SV40 virus.[2]

This discovery was of both practical and theoretical importance. Practically speaking, the discovery explained the origins of the widespread contamination of a variety of stocks of seed viruses and live polio virus vaccine by SV40 that had been written about in a 1960 paper written by Ben Sweet and Maurice Hilleman.[2][23] Eddy suggested that this contamination could be avoided in the future by screening cultures of C. aethiops kidney cells for the characteristic cytopathic (cellular) changes that SV40 causes.[2] This discovery led to Merck to voluntarily withdraw its killed-virus polio vaccine.[24] Theoretically speaking, it added to a growing body of evidence that the monkey, like the mouse, could harbor oncogenic (cancer causing) viruses that could affect other animal species.[2]

In 1998, the National Cancer Institute undertook a large study, using cancer case information from the Institute's SEER database. The published findings from the study were considered of little value in a 2002 review that called for further investigation. Another large study in Sweden examined cancer rates of 700,000 individuals who had received potentially contaminated polio vaccine as late as 1957; the study again revealed no increased cancer incidence between persons who received polio vaccines containing SV40 and those who did not. The question of whether SV40 causes cancer in humans remains controversial, however, and the development of improved assays for detection of SV40 in human tissues will be needed to resolve the controversy.[25]

Retirement

Eddy retired from the NIH in 1973 aged 70. Upon retirement she received several awards, including a Special Citation from the secretary of the Department of Health, Education, and Welfare (HEW). In 1977 she was honored with the NIH Director's Award. Eddy died in 1989.[26]

References
  1. Fulghieri C, Bloom S (2014). "Sarah Elizabeth Stewart". Emerging Infectious Diseases. 20 (5): 893–5. doi:10.3201/eid2005.131876. PMC 4012821. PMID 24751102.
  2. Eddy BE, Borman GS, Grubbs GE, Young RD (May 1962). "Identification of the oncogenic substance in rhesus monkey kidney cell culture as simian virus 40". Virology. 17 (1): 65–75. doi:10.1016/0042-6822(62)90082-x. PMID 13889129.
  3. Yount, Lisa (2007). A to Z of Women in Science and Math. Infobase Publishing. p. 78. ISBN 9781438107950.
  4. Yount, Lisa (2007). A to Z of Women in Science and Math. Infobase Publishing. p. 78. ISBN 9781438107950.
  5. Yount, Lisa (2007). A to Z of Women in Science and Math. Infobase Publishing. pp. 78–79. ISBN 9781438107950.
  6. Yount, Lisa (2007). A to Z of Women in Science and Math. Infobase Publishing. p. 79. ISBN 9781438107950.
  7. Yount, Lisa (2007). A to Z of Women in Science and Math. Infobase Publishing. p. 79. ISBN 9781438107950.
  8. "Archived copy". Archived from the original on 2013-03-10. Retrieved 2013-06-05.CS1 maint: archived copy as title (link)
  9. Offit, Paul A. (2005). The Cutter Incident: How America's First Polio Vaccine Led to the Growing Vaccine Crisis. Yale University Press. p. 62-63. ISBN 978-0-300-10864-4.
  10. Offit, Paul A. (2007). The Cutter Incident: How America's First Polio Vaccine Led to the Growing Vaccine Crisis. Yale University Press. p. 62. ISBN 9780300126051.
  11. Offit, Paul A. (2007). The Cutter Incident: How America's First Polio Vaccine Led to the Growing Vaccine Crisis. Yale University Press. p. 63. ISBN 9780300126051.
  12. Nathanson N.; Langmuir A. D. (1963). "The Cutter incident. poliomyelitis following formaldehyde-inactivated poliovirus vaccination in the United States during the spring of 1955. II. Relationship of poliomyelitis to Cutter vaccine". Am. J. Hyg. 78: 29–60. PMID 14043545.
  13. Offit, Paul A. (2005). "The Cutter incident, 50 years later". N. Engl. J. Med. 352 (14): 1411–1412. doi:10.1056/NEJMp048180. PMID 15814877.
  14. Offit, Paul A. (2007). The Cutter Incident: How America's First Polio Vaccine Led to the Growing Vaccine Crisis. Yale University Press. p. 96. ISBN 9780300126051.
  15. Offit, Paul A. (2007). The Cutter Incident: How America's First Polio Vaccine Led to the Growing Vaccine Crisis. Yale University Press. p. 71. ISBN 9780300126051.
  16. Offit, Paul A. (2007). The Cutter Incident: How America's First Polio Vaccine Led to the Growing Vaccine Crisis. Yale University Press. p. 98. ISBN 9780300126051.
  17. Edward Shorter, The Health Century, Doubleday, New York, 1987, pp 68–70 ISBN 0-385-24236-0
  18. Yount, Lisa (2007). A to Z of Women in Science and Math. Infobase Publishing. p. 79. ISBN 9781438107950.
  19. Yount, Lisa (2007). A to Z of Women in Science and Math. Infobase Publishing. p. 79. ISBN 9781438107950.
  20. Eddy BE, Stewart SE (November 1959). "Characteristics of the SE Polyoma Virus". Am J Public Health Nations Health. 49 (11): 1486–1492. doi:10.2105/ajph.49.11.1486. PMC 1373056. PMID 13819251.
  21. Yount, Lisa (2007). A to Z of Women in Science and Math. Infobase Publishing. p. 79. ISBN 9781438107950.
  22. Eddy BE, Borman GS, Berkely WH, Young RD (May 1961). "Tumors induced in hamsters by injection of rhesus monkey cell extracts". Proc. Soc. Exp. Biol. Med. 107 (1): 191–197. doi:10.3181/00379727-107-26576. PMID 13725644.
  23. Sweet BH, Hilleman MR (November 1960). "The vacuolating virus, S.V. 40". Proc. Soc. Exp. Biol. Med. 105 (2): 420–427. doi:10.3181/00379727-105-26128. PMID 13774265.
  24. Levine, A.J. The Origins of Small DNA Tumor Viruses In: Foundations in Cancer Research, Academic Press, 1994 pp. 152-153.
  25. Institute of Medicine (US) Immunization Safety Review Committee; Stratton K, Almario DA, McCormick MC, editors. Immunization Safety Review: SV40 Contamination of Polio Vaccine and Cancer. Washington (DC): National Academies Press (US); 2002.
  26. Yount, Lisa (2007). A to Z of Women in Science and Math. Infobase Publishing. p. 79. ISBN 9781438107950.
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