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The American Association of Immunologists

Wendell Meredith Stanley, Ph.D.

Wendell Meredith Stanley, Ph.D. (1904–1971)

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Nobel Prize in Chemistry

1946, one-half of the prize was awarded jointly with John Howard Northrop “for for their preparation of enzymes and virus proteins in a pure form," and the other half was awarded to James Batcheller Sumner "for his discovery that enzymes can be crystallized.”

AAI

Joined: 1957

Scientific Accomplishments

Wendell M. Stanley, Ph.D., AAI '57, was awarded the 1946 Nobel Prize in Chemistry with John Howard Northrop and James Batcheller Sumner. One-half of the prize was awarded to Sumner for "his discovery that enzymes can be crystallized," and the other half was awarded jointly to Northrop and Stanley for "their preparation of enzymes and virus proteins in a pure form."1 By isolating and crystallizing tobacco mosaic virus (TMV), Stanley demonstrated that viruses blurred the lines between the living organisms studied by biologists and the nonliving molecules studied by chemists.2

When Stanley began working with TMV in 1932, this entity had been confounding biologists for 40 years. In 1892, Russian biologist Dmitri Ivanovsky3 observed that the causal agent of tobacco mosaic disease in plants passed through every available filter known to retain other infectious agents, including bacteria. Dutch microbiologist Martinus Beijerinck repeated this experiment six years later, confirming Ivanovsky's findings and suggesting that the filterable agent was not a bacterium but rather, a new type of microorganism, soon referred to as "filterable viruses."4 In the three decades that passed between Beijerinck's work and Stanley's research, scientists had identified hundreds of diseases in plants and animals caused by viruses. Yet, as the techniques used to isolate and culture bacteria proved ineffective in the study of viruses, the most basic questions regarding the nature of viruses remained unanswered.5

Trained as a chemist, Stanley approached TMV from a different perspective than that of the microbiologists. He brought a new set of biochemical techniques for crystallization, recently developed by Sumner and modified by Northrop, to the field of virology. Stanley and Northrop were colleagues at the Department of Plant and Animal Pathology, an extension of the Rockefeller Institute for Medical Research in Princeton. With Northrop's encouragement and support, Stanley modeled his TMV work on Northrop's studies of enzymes. Having crystallized the enzyme pepsin in 1929, Northrop demonstrated the following year that it was a pure protein.6 Five years later, Stanley crystallized TMV and suggested that it, too, was a pure protein.7 By 1937, however, he recognized that TMV crystals were actually nucleoproteins.8 Furthermore, Stanley demonstrated that these nucleoproteins, apparently lifeless in crystallized form, sprang back to life and multiplied when dissolved and reintroduced into tobacco. This was a revolutionary discovery, for it challenged the widely held belief that diseases were transmitted only by living organisms.

Stanley continued to study virology and served as a spokesman for the field for the remainder of his career. During the Second World War, he experimented with various techniques for purifying influenza virus9 and devised a method for preparing the influenza vaccine by centrifugation.10 Under his guidance, the Virology Laboratory at the University of California (UC), Berkeley, became one of the leading virology centers in the world. Among the many breakthroughs made by scientists at the UC Virology Laboratory were the crystallization of polio virus, the identification of TMV's subcomponents and descriptions of how they are arranged in virus particles, and the determination that viral RNA was the molecular component responsible for TMV replication.11 Later in his career, Stanley turned his attention to the study of cancer, declaring in 1956, "I believe the time has come when we should assume that viruses are responsible for most, if not all, kinds of cancer."12 He worked tirelessly in the 1950s and 1960s to promote cancer awareness and raise funds for further research, arguing that further virological investigations might hold the key to a cure.

Stanley's fundamental contributions to the study of virology were recognized by his fellow scientists as well as the general press. "Stanley's findings, which have been confirmed, are extremely important because they have induced a number of investigators in the field of infectious diseases to forsake old ruts and seek new roads to adventure," declared Thomas M. Rivers (AAI '21, president 1933–34), director of the Rockefeller Institute, in 1941. "As much as many bacteriologists hate to admit it, Stanley's proof that tobacco mosaic virus is a chemical agent instead of a microorganism is certainly very impressive. . . . The results of Stanley's work had the effect of demolishing bombshells on the fortress which Koch and his followers so carefully built to protect the idea that all infectious maladies are caused by living microorganisms or their toxins."13 The popular press, too, praised Stanley for his discovery, frequently comparing him with Louis Pasteur.14

Biography

Stanley was born on August 16, 1904, in Ridgeville, Indiana, where his parents published the two local newspapers. He attended nearby Earlham College, majoring in chemistry and mathematics and playing varsity football. Captain of the Earlham team and an Indiana all-state selection during his senior year, Stanley intended to become an athletic coach after receiving his B.S. in 1926. A meeting with Roger Adams, head of the Chemistry Department at the University of Illinois, Champaign-Urbana, changed his mind, however, and Stanley began graduate work in organic chemistry under Adams, earning his M.S. in 1927 and his Ph.D. in 1929. He stayed at the University of Illinois as Adams's postdoctoral research assistant for one year before working with chemist Heinrich Wieland at the University of Munich as a National Research Council Fellow from 1930 to 1931.

After his fellowship, Stanley returned to the United States and became an assistant at the Rockefeller Institute for Medical Research in New York. At the invitation of the director of the institute, Simon Flexner (AAI '20), and plant pathologist Louis O. Kunkel, Stanley transferred to the Department of Plant and Animal Pathology to work on TMV in 1932, marking his introduction to the field of virology. With the success of his early research on TMV, he quickly rose through the ranks of the Rockefeller Institute, becoming an associate member (1937) and a member (1940). When it was announced that the Rockefeller Institute would close its Princeton campus in 1948, Stanley moved to UC Berkeley to launch and direct the Virology Laboratory. He remained at UC Berkeley for two decades, founding and chairing both the Department of Biochemistry (1948–53) and the Department of Virology (1958–64) before retiring from his position as the director of the Virology Laboratory in 1969.15

Throughout his career, Stanley worked to promote public health, serving as a member of the National Advisory Cancer Council of the United States Public Health Service as well as the Expert Advisory Panel on Virus Diseases of the World Health Organization. For many years, he served as director-at-large of the American Cancer Society.16

Stanley died of a heart attack on June 15, 1971, while traveling in Salamanca, Spain, days after presenting a paper at a scientific conference in Barcelona. He was 66.17

Awards and Honors

Stanley was a member of the American Philosophical Society (1940), the National Academy of Science (1941), and the American Academy of Arts and Sciences (1949).

In addition to the Nobel Prize, his awards and honors include the American Association for the Advancement of Science Prize (1937), the Isaac Adler Prize (1938), the Rosenberger Medal (1938), the John Scott Award (1938), the Gold Medal of the American Institute (1941), a Copernican Citation (1943), the Franklin Medal (1948), the Presidential Certificate of Merit (1948), the Modern Medicine Award (1958), the American Cancer Society Medal for Distinguished Service in Cancer Control (1963), and the American Medical Association Scientific Achievement Award (1966).18



Notes:

1 "The Nobel Prize in Chemistry 1946—Summary," Nobelprize.org, http://www.nobelprize.org/nobel_prizes/chemistry/laureates/1946.

2 Lily E. Kay, "W. M. Stanley's Crystallization of the Tobacco Mosaic Virus, 1930–1940," Isis 77, no. 3 (1986): 450.

3 Alternative transliterations include Iwanowski and Ivanovski.

4 Although he did not coin the term virus, which had been used as a broad label for disease-causing agents since the eighteenth century, Thomas M. Rivers suggested in 1927 that the pathogens in question be consistently referred to as "filterable viruses," primarily because the name was already widely used. T. M. Rivers, "Filterable Viruses: A Critical Review," Journal of Bacteriology 14, no. 4 (1927): 217.

5 Wendell M. Stanley, "The Isolation and Properties of Crystalline Tobacco Mosaic Virus," Nobel Lecture, 12 December 1946, Nobel Lectures, Chemistry, 1942–1962 (Amsterdam: Elsevier, 1964), 137–38, http://www.nobelprize.org/nobel_prizes/chemistry/laureates/1946/stanley-lecture.pdf; Thomas M. Rivers, "The Infinitely Small in Biology," Science 93, no. 2407 (1941): 143–45.

6 J. H. Northrop, "Crystalline Pepsin," Science 69, no. 1796 (1929): 580; J. H. Northrop, "Crystalline Pepsin, I. Isolation and Tests of Purity," Journal of General Pathology 13, no. 6 (1930): 739–66.

7 W. M. Stanley, "Isolation of a Crystalline Protein Possessing the Properties of Tobacco-Mosaic Virus," Science 81, no. 2113 (1935): 644–45; Kay, "W. M. Stanley's Crystallization of the Tobacco Mosaic Virus," 450–72.

8 A team of British scientists, led by biochemist Norman W. Pirie and plant pathologist Frederick Bawden, first suggested that TMV was a nucleoprotein. Believing that the nucleic acid these scientists had detected was nonessential and that the TMV crystal would remain active even if the nucleic acid were removed, Stanley initially rejected this assertion. Stanley, "The Isolation and Properties of Crystalline Tobacco Mosaic Virus," Nobel Lectures, 147–48.

9 W. M. Stanley, "An Evaluation of Methods for the Concentration and Purification of Influenza Virus," Journal of Experimental Medicine 79, no. 3 (1944): 255–66.

10 W. M. Stanley, "The Preparation and Properties of Influenza Virus Vaccines Concentrated and Purified by Differential Centrifugation," Journal of Experimental Medicine 81, no. 2 (1945): 193–218.

11 Seymour S. Cohen, "Stanley, Wendell Meredith," American National Biography Online, Oxford University Press, February 2000, http://www.anb.org/articles/12/12-01666.html; "Wendell Meredith Stanley," World of Microbiology and Immunology, ed. Brenda Wilmoth Lerner and K. Lee Lerner (Detroit: Gale, 2006).

12 "Viruses Studied as Cancer Link," New York Times, 12 August 1956, 52.

13 Rivers, "The Infinitely Small in Biology," 144.

14 "Dr. Wendell M. Stanley Dead; Virologist Won '46 Nobel Prize," New York Times, 16 June 1971, 48; Kay, "W. M. Stanley's Crystallization of the Tobacco Mosaic Virus," 450.

15 "Guide to the Wendell M. Stanley Papers, 1926–1972," Bancroft Library, University of California, Berkeley, http://oac.cdlib.org/data/13030/vc/tf3p3003vc/files/tf3p3003vc.pdf; Cohen, "Stanley, Wendell Meredith," American National Biography; Kay, "W. M. Stanley's Crystallization of the Tobacco Mosaic Virus," 450–72; "Dr. Wendell M. Stanley Dead," New York Times.

16 "Wendell M. Stanley—Biography," Nobelprize.org, http://www.nobelprize.org/nobel_prizes/chemistry/laureates/1946/stanley.html; "Guide to the Wendell M. Stanley Papers," Bancroft Library.

17 Victor Lieberman, "Wendell M. Stanley, Virologist, Dies," Washington Post, 16 June 1971, C8.

18 Wendell M. Stanley—Biography," Nobelprize.org; "Guide to the Wendell M. Stanley Papers," Bancroft Library.

 


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