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Oswald Avery

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Oswald Avery JR.
FRS[2]
Oswald Avery Jr. in 1937
Born(1877-10-21)October 21, 1877
Halifax, Nova Scotia, Canada[3]
DiedFebruary 20, 1955(1955-02-20) (aged 77)
Nashville, Tennessee, US[3]
NationalityCanadian-American
Alma materColumbia University
Known for
Awards
Scientific career
FieldsMolecular biology[1]
InstitutionsRockefeller University Hospital

Oswald Theodore Avery Jr. (October 21, 1877 – February 20, 1955) was a Canadian-American physician and medical researcher. The major part of his career was spent at the Rockefeller Hospital in New York City. Avery was one of the first molecular biologists and a pioneer in immunochemistry, but he is best known for the experiment (published in 1944 with his co-workers Colin MacLeod and Maclyn McCarty) that isolated DNA as the material of which genes and chromosomes are made.[4][5][6]

The Nobel laureate Arne Tiselius said that Avery was the most deserving scientist not to receive the Nobel Prize for his work,[7] though he was nominated for the award throughout the 1930s, 1940s, and 1950s.[8][9]

The lunar crater Avery was named in his honor.

Early life and education

Oswald Avery was born in Halifax, Nova Scotia in 1877 to Francis Joseph Avery, a Baptist minister, and his wife Elizabeth Crowdy. The couple had immigrated from Britain in 1873. Oswald Avery was born and grew up in a small wooden row house on Moran Street in the North End of Halifax, now a designated heritage building.[10] When Avery was 10, his family moved to the Lower East Side of New York City. Oswald Avery began participating in church activities at a young age.[11] He and his older brother Ernest learned how to play the cornet from a German musician who played at church.[11] Soon, both were playing at church themselves.[11] The brothers played on the steps of Mariners’ Temple to attract worshippers.[12] Both earned a scholarship to the National Conservatory of Music.[11] Ernest became sick and did not continue, but Oswald pushed onward.[13] He became talented enough to play with the National Academy of Music in Antonin Dvorak’s Symphony No. 5, From the New World, under direction of Walter Damrosch.[13]

Oswald Avery began at Colgate University in 1896.[13] Even though Colgate was a Baptist school, there were signs of rebellion against orthodoxy during Avery's time at the university.[13] In Avery's senior year, he and a few of his classmates asked their philosophy professor to create a metaphysics class that would allow them to explore the credibility of the Christian faith.[14] Avery’s senior year was entirely electives, but he did not choose to take a single science elective, even though many were offered.[15] Avery made exceptional grades throughout his years at Colgate.[15] He received 8.5 out of 10 or above in all courses his freshman year and 9 out of 10 or above his sophomore through senior year.[15] Avery’s top grades were in his public speaking courses, in which he never received lower than a 9.5.[15] He even tied for first with his friend Emerson in an oratorical contest.[15] Avery earned his undergraduate degree in humanities at Colgate University and was a member of the Class of 1900.[16][15]

Oswald Avery began medical studies at The College of Physicians and Surgeons at Columbia University in New York later in the year of 1900.[15] At the college, he made good grades in all of his courses, except bacteriology and pathology. [17] He graduated with a medical degree in 1904, and then he began to practice general medicine.[18] Avery did not like dealing with patients who have chronic diseases that he was unable to fix.[18] He practiced medicine until 1907 when he began working as an associate director to Benjamin White in Hoagland Laboratory.[19]

Hoagland Laboratory

At Hoagland Laboratory, he began by studying the bacteriology of yogurt and other fermented milk products and their effects on gut bacteria.[20] He recorded his findings in “Observations on Certain Lactic Acid Bacteria of the Bulgaricus Type”. [21] During the years 1909 through 1913, he performed medical research with bacteriological, immunological, and chemical approaches.[21]

For a period of time, White came down with tuberculosis.[21] Avery went with him to Trudea Sanatorium for a cure.[21] Afterwards, Avery went back to take vacations at the sanatorium.[21] He became interested in tuberculosis and began doing research in the Trudea Laboratory, where he looked at the clinical and experimental aspects of tuberculosis.[21] Here he carried out 100 consecutive blood cultures of tuberculosis patients in the active phase of the disease.[21] He never found evidence of secondary infection.[21] His careful clinical investigation caught the eye of Dr. Rufus Cole at Rockefeller Institute.[21]

At Hoagland, Avery performed a chemical and toxicological study of a product derived from tubercle bacilli.[22] With White as a colleague, he extracted the product with alkaline ethanol.[22] The research was published in 1912.[22] This further showed his systematic effort to observe and analyze bacterial activity using their chemical structure.[22] In 1911, Avery instructed staff of H. K. Mulford Company in bacteriological techniques, and they taught him the industrial methods for production of antitoxins and vaccines.[22]

Throughout his time at Hoagland, Avery published nine papers, one of which was a chapter on “Opsonins and Vaccine Therapy”.[22] He collaborated with Dr. N. B. Potter for this chapter, which was put in Hare’s Modern Treatment - a popular medical magazine at the time.[22] Avery also taught a course to student nurses at Hoagland.[22] During the course, he conveyed the dangers of pathogens spread through sneezing.[22] During his teaching, he was given the nicknames “The Professor” and “Fess”.[22] While working at Hoagland, Avery was mailed two written offers from Rockefeller Institute, and he denied them both.[23] Avery did not accept the offer until Rufus Cole from Rockefeller came to offer the position to him in person.[23]

Rockefeller Institute

In 1913, Rufus Cole, who had noticed some of Avery's publications, offered him a position at the recently opened Rockefeller Hospital, a facility for clinical research and part of the Rockefeller Institute. Avery accepted. At the institute, Cole, Avery and Alphonse Dochez developed the first effective immune serum against a strain of pneumococcus, a bacterium causing pneumonia. The serum was produced from the blood of infected horses.[24]

Debate over the pathogen in the 1918 influenza epidemic

At the height of the 1918 influenza epidemic, the dominant hypothesis was that the causative agent in the disease was a bacterium — specifically, Haemophilus influenzae (then called 'Pfeiffer's bacillus' or Bacillus influenzae), a microbe first isolated by German bacteriologist Richard Pfeiffer, which he had identified in nasal samples of patients infected by seasonal influenza decades earlier and which was also found in many but not all samples taken from patients in the 1918 epidemic.[25] The failure to isolate B. influenzae in some patients was generally attributed to the difficulty of culturing the bacterium.[25]

Peter Olitsky and Frederick Gates at the Rockefeller Institute found that nasal secretions from infected patients could still cause disease in the lungs of rabbits after having been filtered through a bacterium-excluding Berkefeld filter, but other researchers were unable to reproduce their results. Avery initially doubted Olitsky's and Gates's data, and set out to prove the B. influenzae hypothesis. For that purpose, he developed improved culture media for B. influenzae, which were widely adopted and reduced the possibility of false negatives.[25] However, B. influenzae could still not be found in all influenza patients. The true cause of influenza, a virus, would not be discovered until the 1930s.[26]

DNA as the basis for genes

Double helix
Main article: Avery–MacLeod–McCarty experiment

After the influenza epidemic, Avery returned to his work on pneumococcus. He identified R and S strains of the bacterium; the latter caused disease and had a polysaccharide capsule, while the former lacked the capsule and was harmless. Griffith's experiment of 1928 showed that the ability to produce a capsule could be transferred from S to R strain bacteria, even if the S strain bacteria were killed first.

For many years, genetic information was thought to be contained in cell protein. Continuing the research done by Frederick Griffith, Avery worked with Colin MacLeod and Maclyn McCarty on the mystery of inheritance. He had received emeritus status from the Rockefeller Institute in 1943, but continued working for five years, though by that time he was in his late sixties. Oswald Avery, along with Colin MacLeod and Maclyn McCarty, isolated S-strain bacteria from dead mice and killed the bacteria with heat. They used available techniques to remove various macromolecules - proteins, RNA, and DNA - from the bacteria.[27] S-bacteria first had the large cellular structures removed. Then they were treated with protease enzymes, which removed the proteins from the cells before the remainder was placed with R strain bacteria. The R strain bacteria transformed, meaning that proteins did not carry the genes causing disease. Afterwards, the S strain bacteria were treated with ribonucleases to degrade their RNA. [27]The R strain still transformed, suggesting that RNA was not the transforming substance. [27]Then the remnants of the S strain bacteria were treated with a deoxyribonuclease enzyme which removed the DNA. After this treatment, the R strain bacteria no longer transformed. This showed that DNA was the substance that transformed R strain into S strain bacteria and indicated that it was the carrier of genes in cells.[28][29]

Avery's conclusion, that "The evidence presented supports the belief that a nucleic acid of the desoxyribose type is the fundamental unit of the transforming principle of Pneumococcus Type II" greatly influenced Erwin Chargaff, who upon reading those words dedicated his work to identify a "chemistry of heredity" which he later elucidated in Chargaff's rules. Chargaff would later comment that "As this transformation represents a permanently inheritable alteration of a cell, the chemical nature of the substance responsible for this alteration had been elucidated for the first time. Seldom has more been said in so few words."[30]

Alfred Hershey and Martha Chase furthered Avery's research in 1952 with the Hershey–Chase experiment. These experiments paved the way for Watson and Crick's discovery of the helical structure of DNA, and thus the birth of modern genetics and molecular biology. Of this event, Avery wrote in a letter to his youngest brother Roy, a bacteriologist at the Vanderbilt School of Medicine: "It's lots of fun to blow bubbles but it's wiser to prick them yourself before someone else tries to."[31]

Nobel laureate Joshua Lederberg stated that Avery and his laboratory provided "the historical platform of modern DNA research" and "betokened the molecular revolution in genetics and biomedical science generally".

Retirement and Later Years

While working at Rockefeller Institute, Avery contracted Grave’s disease, which caused him to experienced mood swings of depression and irritability.[32] After undergoing a thyroidectomy, Avery once again became more lively and began sailing, where he fell in love with the sport.[32] Shortly after, he retired in Nashville, Tennessee, where he lived close to his brother and his brother’s family, where he was regarded not as a scientist, but as a pleasant family man and a kind country gentleman.[33] While in the southern United States, Avery took a particular interest in the local flora and would act as a gardener would, learning about and appreciating the flowers and trees.[33]

Avery's enthusiasm toward researching nucleic acids continued into his retirement, and he would continue his work with Dr. Hugh Morgan, chairman of the department of medicine at Vanderbilt Medical School.[33] Dr. Morgan was given a research grant from the Department of Defense to study immunity to streptococcal infection, and he convinced Avery to help him in his research.[33] Avery worked on this research with Dr. Bertram E. Sprofkin.[33] The two wrote a joint report on “Studies on the bacteriolytic property of Streptomyces albus and its action on hemolytic streptococci”.[33]

During his later years, Avery became terminally ill with extensive hepatoma, or liver cancer.[33] He died at age 77 on February 20, 1955 and was buried in Mount Olivet cemetery in Nashville.[33]

Bibliography

The collected papers of Avery are stored at the Tennessee State Library and Archives and at the Rockefeller Archive. Many of his papers, poems, and hand written lab-notes are available at the National Library of Medicine in the Oswald T. Avery Collection, the first of their Profiles in Science series.[34]

References

  1. ^ Barciszewski, J. (1995). "Pioneers in molecular biology: Emil Fischer, Erwin Schrodinger and Oswald T. Avery". Postepy Biochemii. 41 (1): 4–6. PMID 7777433.
  2. ^ Dubos, R. J. (1956). "Oswald Theodore Avery 1877–1955". Biographical Memoirs of Fellows of the Royal Society. 2: 35–48. doi:10.1098/rsbm.1956.0003. JSTOR 769474.
  3. ^ a b "The Oswald T. Avery Collection. Biographical Information". Profiles in Science. US National Library of Medicine (NIH). Retrieved 18 May 2018.
  4. ^ Hotchkiss, R. D. (1965). "Oswald T. Avery: 1877–1955". Genetics. 51: 1–10. PMID 14258070.
  5. ^ "Oswald Theodore Avery, 1877–1955". Journal of General Microbiology. 17 (3): 539–549. 1957. doi:10.1099/00221287-17-3-539. PMID 13491790.
  6. ^ Dochez, A. R. (1955). "Oswald Theodore Avery, 1877–1955". Transactions of the Association of American Physicians. 68: 7–8. PMID 13299298.
  7. ^ Judson, Horace (2003-10-20). "No Nobel Prize for Whining". The New York Times. Retrieved 2020-11-22.
  8. ^ Erica Westly (October 6, 2008). "No Nobel for You: Top 10 Nobel Snubs". Scientific American.
  9. ^ Reichard, P. (2002). "Osvald T. Avery and the Nobel Prize in Medicine" (PDF). Journal of Biological Chemistry. 277 (16): 13355–13362. doi:10.1074/jbc.R200002200. PMID 11872756. S2CID 29494719.
  10. ^ "Avery House", Canada's Historic Places
  11. ^ a b c d Dubos, René J. (1976). The Professor, the Institute, and DNA. New York: Rockefeller University Press. p. 54. ISBN 0874700221.
  12. ^ Dubos, René J. (1976). The Professor, the Institute, and DNA. New York: Rockefeller University Press. pp. 54–55. ISBN 0874700221.
  13. ^ a b c d Dubos, René J. (1976). The Professor, the Institute, and DNA. New York: Rockefeller University Press. p. 55. ISBN 0874700221.
  14. ^ Dubos, René J. (1976). The Professor, the Institute, and DNA. New York: Rockefeller University Press. pp. 55–56. ISBN 0874700221.
  15. ^ a b c d e f g Dubos, René J. (1976). The Professor, the Institute, and DNA. New York: Rockefeller University Press. p. 57. ISBN 0874700221.
  16. ^ "Gene Idol | Colgate Magazine". 2020-01-31. Retrieved 2020-06-29.
  17. ^ Dubos, René J. (1976). The Professor, the Institute, and DNA. New York: Rockefeller University Press. p. 58. ISBN 0874700221.
  18. ^ a b Dubos, René J. (1976). The Professor, the Institute, and DNA. New York: Rockefeller University Press. p. 59. ISBN 0874700221.
  19. ^ Dubos, René J. (1976). The Professor, the Institute, and DNA. New York: Rockefeller University Press. pp. 59–60. ISBN 0874700221.
  20. ^ Dubos, René J. (1976). The Professor, the Institute, and DNA. New York: Rockefeller University Press. pp. 60–61. ISBN 0874700221.
  21. ^ a b c d e f g h i Dubos, René J. (1976). The Professor, the Institute, and DNA. New York: Rockefeller University Press. p. 61. ISBN 0874700221.
  22. ^ a b c d e f g h i j Dubos, René J. (1976). The Professor, the Institute, and DNA. New York: Rockefeller University Press. p. 62. ISBN 0874700221.
  23. ^ a b Dubos, René J. (1976). The Professor, the Institute, and DNA. New York: Rockefeller University Press. p. 63. ISBN 0874700221.
  24. ^ Barry, John M. (2005). The Great Influenza: The Epic Story of the Deadliest Plague in History. Penguin. pp. 181–189. ISBN 978-0-14-303649-4.
  25. ^ a b c Van Epps, HL (April 17, 2006). "Influenza: exposing the true killer". Journal of Experimental Medicine. 203 (4): 803. doi:10.1084/jem.2034fta. PMC 2118275. PMID 16685764. Retrieved 7 May 2020.
  26. ^ Taubenberger JK, Hultin JV, Morens DM (2007). "Discovery and characterization of the 1918 pandemic influenza virus in historical context". Antiviral Therapy. 12 (4 Pt B): 581–591. doi:10.1177/135965350701200S02.1. PMC 2391305. PMID 17944266.
  27. ^ a b c Parker, Nina; Schneegurt, Mark; Thi Tu, Anh-Hue; Forster, Brian M.; Lister, Philip (2018). Microbiology. Rice University: Openstax. ISBN 978-1-50669-811-3.
  28. ^ Avery, Oswald T.; MacLeod, Colin M.; McCarty, Maclyn (February 1, 1944). "Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types - Induction of Transformation by a Desoxyribonucleic Acid Fraction Isolated from Pneumococcus Type III". Journal of Experimental Medicine. 79 (2): 137–158. doi:10.1084/jem.79.2.137. PMC 2135445. PMID 19871359.
  29. ^ McCarty, Maclyn (2003). "Discovering genes are made of DNA". Nature. 421 (6921): 406. Bibcode:2003Natur.421..406M. doi:10.1038/nature01398. PMID 12540908. S2CID 4335285.
  30. ^ Weintraub, Bob (September 2006). "Erwin Chargaff and Chargaff's Rules". Chemistry in Israel - Bulletin of the Israel Chemical Society (22): 29–31.
  31. ^ Davies, Kevin (2001). Cracking the Genome: Inside the Race to Unlock Human DNA. The Free Press.
  32. ^ a b Dubos, René J. (1976). The Professor, the Institute, and DNA. New York: Rockefeller University Press. pp. 63–67. ISBN 0874700221.
  33. ^ a b c d e f g h Dubos, René J. (1976). The Professor, the Institute, and DNA. New York: Rockefeller University Press. pp. 67–68. ISBN 0874700221.
  34. ^ "The Oswald T. Avery Collection". National Library of Medicine. Retrieved April 28, 2011.

Further reading

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