Julius Youngner

Julius S. Youngner (24 October 1920 – 27 April 2017)[1] was an American Distinguished Service Professor in the School of Medicine and Department of Microbiology & Molecular Genetics at University of Pittsburgh responsible for advances necessary for development of a vaccine for poliomyelitis[2] and the first intranasal equine influenza vaccine.[3]

Julius Youngner
Born
Julius S. Youngner

24 October 1920
New York, New York
DiedApril 27, 2017(2017-04-27) (aged 96)
Pittsburgh, Pennsylvania
Alma materNew York University
University of Michigan
Known forFirst polio vaccine, equine influenza vaccine
SpouseRina Youngner
Scientific career
FieldsMicrobiology
Virology
InstitutionsUnited States Army(-1946)
U.S. Public Health Service, National Institutes of Health, United States Navy
University of Pittsburgh School of Medicine and Department of Microbiology & Molecular Genetics (1949-2000)

Youngner survived many infections as a young child which left him with a lifelong interest in infectious disease. After completing an undergraduate degree in English, he was trained in Biology at University of Michigan before being drafted into the Army. After the war, he joined the U.S. Public Health Service, National Institutes of Health Cancer Institute before joining the Salk team responsible for polio vaccine.[4]

As a member of the Jonas Salk research team, Youngner contributed in the development of polio vaccine, including techniques for large scale production of poliovirus and the rapid color test measurement of polio virus in living tissue. He is considered "one of the seminal figures in contemporary virology and it's been that way for more than 50 years" by Arthur S. Levine, senior vice chancellor for the health sciences at University of Pittsburgh.[5] Research by Youngner and colleague Samuel Salvin was also responsible for the discovery of gamma interferon.[2]

Youngner was an important early pioneer in vaccine development, testing, and government licensing of drugs before allowing them to market. He was critical of Cutter Laboratories virus manufacturing prior to deaths resulting from Cutter inactivated vaccine.[4][6][7] He continued to promote research integrity and actions on misconduct until the end of his career.[8][9][10]

Early life

Younger was born in 1920 in Manhattan, New York, where his father was a businessman.[11] When he was seven-years-old Youngner was nearly killed by lobar pneumonia.[11]

Education and Manhattan Project

Youngner graduated Evander Childs High School, when he was 15 years old, and received a B.A. in English from New York University in 1939.[11] After completing a Sc.D. degree in microbiology at the University of Michigan, Youngner stayed on as a faculty member, and left in 1947 to join the National Cancer Institute (NCI) in Bethesda.[12] Youngner was drafted into basic U.S. Army infantry training. Upon completion he screened at Oak Ridge, Tennessee and assigned to classified research at University of Rochester School of Medicine on uranium salts.[13] The effects of inhaled uranium salts on human tissue was important to the war effort, related to purification of uranium for nuclear research and weapons. Youngner never knew the research was related to weapons until the end of the war. He thought nuclear energy would be used for planes or submarines for transportation.[4]: 20:15 

Career

In 1949, Youngner moved to the University of Pittsburgh to pursue virology at and, subsequently, to the University of Pittsburgh School of Medicine for the rest of his career. In 1960 he was appointed professor of microbiology. Between 1985 and 1989, he was chairman of the Department of Microbiology, Biochemistry and Molecular Biology.[12] Working on polio prevention, he was responsible for three key advancements in poliomyelitis vaccine development. 1. He proved a method for separation of monkey kidney cells, which led to techniques for large scale production. 2. He developed a process to prevent infection while retaining ability to vaccinate, and 3. safety testing for batches of vaccine and anti-polio antibodies in test subjects.[14] or in the words of his colleague: "“Juli figured out how to grow the virus, how to inactivate it, and then he figured how to test the immune response to see if it worked.”[12]

Trypsinization
Poliovirus particles in cell culture.

Youngner demonstrated the separation of monkey kidney cells using the pancreatic enzyme trypsin, a technique previously proven by the Rockefeller Institute[15] could be applied to high titer virus stocks.[16] Applying this method to a single kidney "could produce enough raw material for 6000 shots of polio vaccine."[6] This advance in production of virus raw material directly led to vaccine viability.

Titration

The measurement developed by Youngner for safely and quickly testing batches of vaccine and also antibodies to the virus after application were important advancements necessary for vaccine success. Youngner identified that a difference in pH, as indicated by metabolic activity by other researchers,[17] could be used to identify cell cultures infected with virus and also cultures with antibodies to virus. This pH could be easily indicated by phenol red in a tissue-culture system.[18]

Inactivated poliovirus

The Salk vaccine is based upon formalin inactivated wild type virus. The key to effective inactivation depended upon a color test developed by Youngner, which allowed formalin induced viral protein degradation to be accurately plotted. From Youngner's work, formalin application for six days was projected to produce only "one live virus particle in 100 million doses of vaccine."[19] By 1954, the first virus trials had immunized 800,000 children against polio.

Temperature-sensitive virus

Youngner studied the role of in-apparent infections in an effort to link a selection of wild type virus to chronic and persistent infections.[20] His team studied the mechanisms of these infections,[21] and also infections of vesicular stomatitis virus,[22][23] sendai virus,[24] and persistent newcastle disease virus.[25][26][27]

First intranasal equine influenza vaccine

Youngner is responsible for the first equine influenza vaccine, based upon cold-adapted influenza virus. Previous methods of vaccination required treatment up to six times per year without adequate protection. In collaboration with Flu Avert I.N., approval was granted for the use of cold-adapted virus that only replicates at temperatures in the respiratory tract, offering "unprecedented level of protection in the prevention of equine flu" and offering protection for up to twelve months.[3][28][29][30]

Patents

Youngner has contributed patents on Lipid purification and concentration of viruses and vaccines, an important contribution to the reduction of egg protein and associated vaccine induced complications,[31] antitumor processes of Brucella,[32] and numerous contributions to cold adapted influenza virus.[33]

Personal life

Youngner met and married his first wife, Tula Liakakis, in Michigan, in 1943. They had a son, Stuart, and a daughter, Lisa. Tula died of Hodgkin's Disease in 1963. He married Rina Balter in 1964. They had no children together but were active in the Jewish community in Pittsburgh, PA. He died there after a brief illness.[34]

See also

References
  1. Obituary: Julius Youngner | Last surviving member of Salk vaccine team
  2. "University of Pittsburgh Department of Microbiology & Molecular Genetics". University of Pittsburgh School of Medicine. Archived from the original on 28 March 2017. Retrieved 26 January 2016.
  3. "University of Pittsburgh Researchers Develop Virus for First Intranasal Equine Influenza Vaccine". www.upmc.com. Retrieved 2016-01-28.
  4. Racaniello, Vincent. "TWiV 373: The distinguished virology career of Julius S. Youngner". www.microbeworld.org. Archived from the original on 2017-06-02. Retrieved 2016-01-26.
  5. "Youngner proud to be a part of history, still angered by Salks slight". TribLIVE.com. Retrieved 2016-01-26.
  6. Austin, David M. Oshinsky George Littlefield Professor of History University of Texas at (2005-03-11). Polio : An American Story: An American Story. Oxford University Press, USA. ISBN 9780199726592.
  7. Offit, Paul A. (2007-09-01). The Cutter Incident: How America's First Polio Vaccine Led to the Growing Vaccine Crisis. Yale University Press. ISBN 978-0300126051.
  8. Youngner, J. S. (1998-01-07). "The scientific misconduct process: a scientist's view from the inside". JAMA. 279 (1): 62–64. doi:10.1001/jama.279.1.62. ISSN 0098-7484. PMID 9424047.
  9. Youngner, Julius S. (2003-04-01). "Promoting research integrity at the American Society for Microbiology". Science and Engineering Ethics. 9 (2): 215–220. doi:10.1007/s11948-003-0009-x. ISSN 1353-3452. PMID 12774654. S2CID 36123237.
  10. "Noted Finding of Science Fraud Is Overturned by a Federal Panel". www.nytimes.com. Retrieved 2016-01-27.
  11. Roberts, Sam (7 May 2017). "Julius Youngner, Polio Vaccine Pioneer, Dies at 96". The New York Times. p. A27. Retrieved 15 May 2017.
  12. Geoff Watts Julius Stuart Youngner Lancet, Volume 389, No. 10087, p2370,17 June 2017, DOI: 10.1016/S0140-6736(17)31574-X
  13. "Pitt Chronicle: Pitt Professor Julius S. Youngner Recalls Working on Manhattan Project". chronicle2.pitt.edu. Archived from the original on 2016-02-06. Retrieved 2016-01-28.
  14. "Youngner, Fisher, and Starzl Honored with Chancellor's Medals". Pitt Chronicle. May 19, 2014. Retrieved January 28, 2016.
  15. Rous, Peyton; Jones, F. S. (1916-04-01). "A Method for Obtaining Suspensions of Living Cells from the Fixed Tissues, and for the Plating Out of Individual Cells". The Journal of Experimental Medicine. 23 (4): 549–555. doi:10.1084/jem.23.4.549. ISSN 0022-1007. PMC 2125431. PMID 19868005.
  16. Dulbecco, R.; Vogt, M. (1954-02-01). "Plaque formation and isolation of pure lines with poliomyelitis viruses". The Journal of Experimental Medicine. 99 (2): 167–182. doi:10.1084/jem.99.2.167. ISSN 0022-1007. PMC 2180341. PMID 13130792.
  17. "The Nobel Prize in Physiology or Medicine 1954". www.nobelprize.org. Retrieved 2016-01-28.
  18. Salk, Jonas E.; Youngner, J. S.; Ward, Elsie N. (1954-09-01). "Use of Color Change of Phenol Red as the Indicator in Titrating Poliomyelitis Virus or Its Antibody in a Tissue–Culture System". American Journal of Epidemiology. 60 (2): 214–230. doi:10.1093/oxfordjournals.aje.a119714. ISSN 0002-9262. PMID 13197372.
  19. Williams, Gareth (2013-06-27). Paralysed with Fear: The Story of Polio. Palgrave Macmillan. ISBN 9781137299772.
  20. Meulen, V. ter; Katz, M. (2013-11-11). Slow Virus Infections of the Central Nervous System: Investigational Approaches to Etiology and Pathogenesis of These Diseases. Springer Science & Business Media. ISBN 9781461298830.
  21. Preble, Olivia T.; Youngner, Julius S. (1975-04-01). "Temperature-Sensitive Viruses and the Etiology of Chronic and Inapparent Infections". Journal of Infectious Diseases. 131 (4): 467–473. doi:10.1093/infdis/131.4.467. ISSN 0022-1899. PMID 163873.
  22. Youngner, J. S.; Dubovi, E. J.; Quagliana, D. O.; Kelly, M.; Preble, O. T. (1976-07-01). "Role of temperature-sensitive mutants in persistent infections initiated with vesicular stomatitis virus". Journal of Virology. 19 (1): 90–101. doi:10.1128/JVI.19.1.90-101.1976. ISSN 0022-538X. PMC 354835. PMID 181599.
  23. Youngner, J. S.; Quagliana, D. O. (1976-07-01). "Temperature-sensitive mutants of vesicular stomatitis virus are conditionally defective particles that interfere with and are rescued by wild-type virus". Journal of Virology. 19 (1): 102–107. doi:10.1128/JVI.19.1.102-107.1976. ISSN 0022-538X. PMC 354836. PMID 181590.
  24. Yoshida, Tetsuya; Hamaguchi, Michinari; Naruse, Hiroshi; Nagai, Yoshiyuki (1982-07-30). "Persistent infection by a temperature-sensitive mutant isolated from a Sendai virus (HVJ) carrier culture: Its initiation and maintenance without aid of defective interfering particles". Virology. 120 (2): 329–339. doi:10.1016/0042-6822(82)90034-4. PMID 6285606.
  25. Preble, Olivia T.; Youngner, Julius S. (1973-09-01). "Temperature-Sensitive Defect of Mutants Isolated from L Cells Persistently Infected with Newcastle Disease Virus". Journal of Virology. 12 (3): 472–480. doi:10.1128/JVI.12.3.472-480.1973. ISSN 0022-538X. PMC 356653. PMID 4795830.
  26. Preble, Olivia T.; Youngner, Julius S. (1972-02-01). "Temperature-Sensitive Mutants Isolated from L Cells Persistently Infected with Newcastle Disease Virus". Journal of Virology. 9 (2): 200–206. doi:10.1128/JVI.9.2.200-206.1972. ISSN 0022-538X. PMC 356283. PMID 5062677.
  27. Preble, Olivia T.; Youngner, Julius S. (1973-09-01). "Selection of Temperature-Sensitive Mutants During Persistent Infection: Role in Maintenance of Persistent Newcastle Disease Virus Infections of L Cells". Journal of Virology. 12 (3): 481–491. doi:10.1128/JVI.12.3.481-491.1973. ISSN 0022-538X. PMC 356654. PMID 4795831.
  28. "Equine Influenza". www.aaep.org. Archived from the original on 2016-03-10. Retrieved 2016-01-28.
  29. "Vaccination Update". TheHorse.com. April 2000. Retrieved 2016-01-28.
  30. Chambers, T. M.; Holland, R. E.; Tudor, L. R.; Townsend, H. G.; Cook, A.; Bogdan, J.; Lunn, D. P.; Hussey, S.; Whitaker-Dowling, P. (2001-11-01). "A new modified live equine influenza virus vaccine: phenotypic stability, restricted spread and efficacy against heterologous virus challenge". Equine Veterinary Journal. 33 (7): 630–636. doi:10.2746/042516401776249291. ISSN 0425-1644. PMID 11770982.
  31. Hans, Noll; Youngner, Julius S. (Apr 25, 1961), Lipid purification and concentration of viruses and vaccines therefrom, retrieved 2016-01-26
  32. Youngner, Julius S.; Feingold, David S.; Keleti, Georg (Jun 27, 1989), Antitumor process using a Brucella abortus preparation, retrieved 2016-01-26
  33. Selected Patents
  34. Mark Roth, "Obituary: Julius Youngner, Last surviving member of Salk vaccine team," Pittsburgh Post-Gazette (28 April 2017), http://www.post-gazette.com/news/obituaries/2017/04/28/Julius-Youngner-Salk-vaccine/stories/201704280215
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