Bernice Eddy

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Bernice Eddy
Bernice Eddy cropped.png
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

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]

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 bacteriology 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, where 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] Most notably, Eddy was responsible for testing different Polio vaccines from 5 different companies while working in the Biologics Control Division.[5]

NIH flu virus vaccine testing[]

The Influenza pandemic of 1918 was one of the deadliest pandemics of the 20th century, killing more than 20 million people around the world. One reason early flu vaccines were not effective was due to the fact that their potency could not be easily checked.[6] This resulted in batched with variable consistency. When World War II started Eddy was made responsible for checking the quality of influenza vaccines used by the United States Army. As part of the Division of Biological Control, Eddy and her team created the first reliable potency test for flu vaccines so that the quality and effectiveness could be consitent throughout manufacturing.[7] Eddy checked army flu vaccines for 16 years and was promoted to chief of flu virus vaccine testing in 1944.[8]

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.[9]

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.[10] Eddy's job was to test the vaccines from five different companies.[11] 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.[12] 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[13] and therefore contained live polio virus pointed to a flawed vaccine manufacturing process at Cutter Laboratories.[14]

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.[15] 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.[16] 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.[17] 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.[18] On the 6 of 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.[19] Between 1955 and 1963, over 98 million Americans were exposed to the deadly Polio virus.[20] Soon after The Cutter incident occurred, federal researchers discovered and disclosed to the public that the vaccine did not cause cancerous tumors in humans.[20] The Cutter incident was one of the worst pharmaceutical disasters in US history, and exposed several thousand children to live polio virus on vaccination.[16] 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.[21]

Testing of common cold vaccines[]

The NIH took Eddy off polio research and asked her to test a common cold vaccine.[22]

Polyomavirus research[]

While testing common cold vaccines, Eddy and her NIH colleague Sarah Elizabeth Stewart began research on a virus that Stewart had discovered.[23] Building on earlier work by Ludwig Gross, Stewart and Bernice E. Eddy were the first to describe a polyomavirus.[24] They did so by injecting the mice with ground organs of other mice that were known to contain leukemia, and observing cancerous tumor growth that was unrelated to leukemia.[25] They satisfied Koch's postulates to demonstrate that polyomavirus can cause cancer to be transmitted from animal to animal. Stewart and Eddy continued to test the theory that viral components are able to induce tumors. They tested tumor extracts from both monkey and mouse embryos, and found that the mouse embryos contained a higher quantity of cancer causing viral agents, thus leading them to reason that viruses can be causative agents of cancer.[26] They also concluded that the polyomavirus was able to cause 20 different types of mouse tumors.[27] Some of the tumors observed were angiomatous sarcomas in Syrian hamsters, sarcomas in rats, and mesenchymal nodules in rabbits.[28] The virus was named the Stewart-Eddy or SE polyoma virus, after their respective surnames.[1] Their collaborative efforts earned them recognition by Time magazine in 1959, featuring a cover story on newly discovered viral agents that cause cancer.[29]

SV40 virus research[]

At the time, common cold vaccines and polio vaccines were both manufactured using viruses grown in monkey kidney cells.[30] 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.[31] Specifically, 109 of 154 mice injected with RMKC extracts showed signs of tumor growth.[32] The extracts of these neoplasms were transplanted into a new group of mice where similar tumor growth was observed. Tumor extract transplants occurred for 5 generations of mice, where the last group all showed tumor growth.[32] 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][33] 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.[34] 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.[35]

Notable studies[]

Since before joining the NIH in 1930, Bernice Eddy was actively studying and publishing her own findings on different diseases such as leprosy, tuberculosis, and diphtheria.

Leprosy Research[]

In 1937, Eddy and her colleagues studied multiple aspects of Mycobacterium leprae, the bacteria that causes leprosy, to gain valuable information for future diagnostic purposes. One study conducted by Eddy included finding new mediums to culture Mycobacterium leprae on in labs.[36]Another notable study done by Eddy includes the research on certain behaviors of leprosy bacteria in the presence of leukocytes.[37]

Published studies[]

Eddy, Bernice E. (1944). "A Simplified Procedure for Detecting Cross Reactions in Diagnostic Antipneumococcic Serum". Public Health Reports (1896-1970). 59 (32): 1041–1045. doi:10.2307/4584990. ISSN 0094-6214. JSTOR 4584990.

Eddy, Bernice E. (1944). "Cross Reactions between the Several Pneumococcic Types and Their Significance in the Preparation of Polyvalent Antiserum". Public Health Reports (1896-1970). 59 (15): 485–499. doi:10.2307/4584847. ISSN 0094-6214. JSTOR 4584847.

Eddy, Bernice E. (1940). "A Study of Pneumococcus Typing Serums for the Purpose of Standardizing a Test for Potency". Public Health Reports (1896-1970). 55 (9): 347–361. doi:10.2307/4583194. ISSN 0094-6214. JSTOR 4583194.

Eddy, B. E. (1933-03-01). "Hemoglobinophilic Bacilli from Infantile Meningitis". Journal of Infectious Diseases. 52 (2): 242–245. doi:10.1093/infdis/52.2.242. ISSN 0022-1899.

Eddy, B. E. (1928-05-01). "Search for Protective, Bacteriophagic and Enzymatic Agents in Pneumonic Sputums". Journal of Infectious Diseases. 42 (5): 449–460. doi:10.1093/infdis/42.5.449. ISSN 0022-1899.

Eddy, Bernice E. (1944). "A Study of Cross Reactions among the Pneumococcic Types and Their Application to the Identification of Types". Public Health Reports (1896-1970). 59 (14): 451–468. doi:10.2307/4584838. ISSN 0094-6214. JSTOR 4584838.

Chinn, Alice L.; Eddy, Bernice E. (1941). "Report of a New Type of Pneumococcus Which Crosses with Types X, XI, XX, XXIX, and XXXI Antipneumococcic Serums". Public Health Reports (1896-1970). 56 (2): 62. doi:10.2307/4583579. ISSN 0094-6214. JSTOR 4583579.

Eddy, Bernice (December 1960). "Neoplasms in Guinea Pigs Infected with Se Polyoma Virus". The Journal of Infectious Diseases. 107 (3): 361–368. doi:10.1093/infdis/107.3.361. JSTOR 30101899. PMID 13725645 – via JSTOR.

Ward, T. G.; Eddy, B. E. (1950-10-27). "An Antigenically Distinct Subtype of Influenza Virus A Which is Virulent for Mice in Primary Passage of Allantoic Fluid". Science. 112 (2913): 501–503. doi:10.1126/science.112.2913.501. ISSN 0036-8075. PMID 14787447.

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 May 24, 1989 die to cardiopulmonary arrest.[38]

References[]

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  2. ^ Jump up to: a b c d e f 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.
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