Isolation of Poliovirus — John Enders and the Nobel Prize
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《新英格兰医药杂志》
When John Enders was informed, 50 years ago this month, that he was the sole recipient of the Nobel Prize in Medicine or Physiology for 1954, he declined the honor. He wrote to the Swedish authorities that he would accept the prize only if it could be shared with "those who did the work." It was agreed that Thomas Weller and Frederick Robbins would be corecipients with Enders. This act, one of the most gracious in the history of the Nobel Prize, reveals the profound decency and modesty of John Enders.
John Franklin Enders was a Connecticut Yankee, born into a large family of prosperous bankers and insurance executives. He was educated at the St. Paul's School and Yale with the expectation that he would join the other Enders men in the banking and insurance world. But his interests lay in Celtic and early English literature, and he went to Harvard to pursue a thesis on the use of gender in Middle English.
As fate would have it, he shared living quarters with another graduate student, Hugh K. Ward, who had come from Australia to study with Hans Zinsser in the Department of Microbiology at Harvard Medical School. Enders frequently accompanied Ward to the laboratory in the evenings, and a long-latent interest in biology was roused in him. When he finally received his Ph.D. from Harvard in 1930, his thesis was about the purification of an anaphylactogenic carbohydrate from Mycobacterium tuberculosis that was separate and distinct from the protein that caused delayed-type hypersensitivity. Enders's subsequent work with Ward resulted in a classic paper in the Journal of Experimental Medicine in 1933. Until then, the cause of the opsonic activity of serum had been unknown. Using type II pneumococci, Enders and Ward showed that this activity was due to type-specific antibody and complement.1
Enders continued working in the Department of Microbiology, where his interest in virology was stimulated by a lethal and devastating epizootic in 1937 affecting cats that were kept in the animal quarters at the medical school. He wrote what must be an outstanding classic in the clinical literature on cats, in which he described in clear and concise detail the course of feline distemper, the pathology of the disease, and its cause.2
Enders was next confronted with the problem of propagating viruses in vitro. He achieved success with the introduction of tissue culture in roller tubes, in 1940, in the cultivation first of vaccinia virus and then of influenzavirus.3 These promising leads were interrupted by the world political situation in 1941 and the impending outbreak of war. Zinsser had died in 1940, and Enders became acting chairman of the department. The Secretary of War also tapped him as a consultant on infectious diseases, and he joined the plasma-fractionation effort in E.J. Cohn's laboratory. There, he anticipated the discovery of immunoglobulins when he showed that antibodies to a variety of antigens did not separate from other plasma proteins as a uniform group.4
At war's end, when Howard Mueller was appointed chairman of microbiology, Enders accepted the invitation of Charles Janeway and Sidney Farber to move to Children's Hospital, Boston. He was certain that he would find a more amiable environment at Children's — his tweedy, cultured lifestyle had put him at odds with Mueller. Once in his new post, Enders resumed his work on mumps virus. He was joined in the laboratory by two former Harvard medical students, Tom Weller and Fred Robbins, who had just completed pediatric residencies at Children's.
Owing to a lack of funds, the team could not set up roller-tube cultures, but Weller managed to grow the Lansing strain of poliovirus on fetal tissue in Erlenmeyer flasks. Robbins found that he could easily detect viral growth by putting a pH-indicator dye in the tissue-culture fluid. Normal cells made excess acid and the dye yellowed, whereas poliovirus-infected cells died and the color of the culture fluid did not change.
In 1949, the group reported in Science, in terse and understated language, the sensational finding that they had successfully propagated poliovirus in tissue cultures of cells of nonneurogenic origin. As a matter of fact, they reported an increase by a factor of 1015 in the amount of infective virus as assayed with the use of intracerebral inoculation in mice.5 Soon thereafter, they were able to simplify the assay of virus, thanks to their observation of a cytopathic effect in human-foreskin fibroblasts in culture. The groundwork was laid for the development of a vaccine that would alleviate untold amounts of human suffering.
(Figure)
Nurses Tending Young Patients with Poliomyelitis in an Iron Lung, 1938.
Photograph by Hansel Mieth, Time Life Pictures, Getty Images.
After John Enders came to a satisfactory agreement about sharing the Nobel Prize with Weller and Robbins, he telephoned his father, then the chairman of the Federal Reserve District of New York. He announced that he was to receive the Nobel Prize, and his father replied: "John, I never heard of such a thing as getting a prize for doing your job!" Perhaps Enders found more sympathetic father figures in Edward Jenner and Louis Pasteur, whose pictures prominently adorned the walls of his office. He clearly — and correctly — believed that such discoverers were his true intellectual ancestors.
Source Information
From the Center for Blood Research, Children's Hospital and Harvard Medical School, Boston.
References
Ward HK, Enders JF. An analysis of the opsonic and tropic action of normal and immune sera based on experiments with the pneumococcus. J Exp Med 1933;57:527-547.
Hammon WD, Enders JF. A virus disease of cats, principally characterized by aleucocytosis, enteric lesions and the presence of intranuclear inclusion bodies. J Exp Med 1939;69:327-351.
Fellers AE, Enders JF, Weller TH. The prolonged co-existence of vaccinia virus in high titre and living cells in roller tube cultures of chick embryonic tissues. J Exp Med 1940;72:367-388.
Enders JF. Chemical, clinical, and immunological studies on the products of human plasma fractionation. X. The concentrations of certain antibodies in globulin fractions derived from human blood plasma. J Clin Invest 1944;23:510-530.
Enders JF, Weller TH, Robbins FC. Cultivation of the Lansing strain of poliomyelitis virus in cultures of various human embryonic tissues. Science 1949;109:85-87.(Fred S. Rosen, M.D.)
John Franklin Enders was a Connecticut Yankee, born into a large family of prosperous bankers and insurance executives. He was educated at the St. Paul's School and Yale with the expectation that he would join the other Enders men in the banking and insurance world. But his interests lay in Celtic and early English literature, and he went to Harvard to pursue a thesis on the use of gender in Middle English.
As fate would have it, he shared living quarters with another graduate student, Hugh K. Ward, who had come from Australia to study with Hans Zinsser in the Department of Microbiology at Harvard Medical School. Enders frequently accompanied Ward to the laboratory in the evenings, and a long-latent interest in biology was roused in him. When he finally received his Ph.D. from Harvard in 1930, his thesis was about the purification of an anaphylactogenic carbohydrate from Mycobacterium tuberculosis that was separate and distinct from the protein that caused delayed-type hypersensitivity. Enders's subsequent work with Ward resulted in a classic paper in the Journal of Experimental Medicine in 1933. Until then, the cause of the opsonic activity of serum had been unknown. Using type II pneumococci, Enders and Ward showed that this activity was due to type-specific antibody and complement.1
Enders continued working in the Department of Microbiology, where his interest in virology was stimulated by a lethal and devastating epizootic in 1937 affecting cats that were kept in the animal quarters at the medical school. He wrote what must be an outstanding classic in the clinical literature on cats, in which he described in clear and concise detail the course of feline distemper, the pathology of the disease, and its cause.2
Enders was next confronted with the problem of propagating viruses in vitro. He achieved success with the introduction of tissue culture in roller tubes, in 1940, in the cultivation first of vaccinia virus and then of influenzavirus.3 These promising leads were interrupted by the world political situation in 1941 and the impending outbreak of war. Zinsser had died in 1940, and Enders became acting chairman of the department. The Secretary of War also tapped him as a consultant on infectious diseases, and he joined the plasma-fractionation effort in E.J. Cohn's laboratory. There, he anticipated the discovery of immunoglobulins when he showed that antibodies to a variety of antigens did not separate from other plasma proteins as a uniform group.4
At war's end, when Howard Mueller was appointed chairman of microbiology, Enders accepted the invitation of Charles Janeway and Sidney Farber to move to Children's Hospital, Boston. He was certain that he would find a more amiable environment at Children's — his tweedy, cultured lifestyle had put him at odds with Mueller. Once in his new post, Enders resumed his work on mumps virus. He was joined in the laboratory by two former Harvard medical students, Tom Weller and Fred Robbins, who had just completed pediatric residencies at Children's.
Owing to a lack of funds, the team could not set up roller-tube cultures, but Weller managed to grow the Lansing strain of poliovirus on fetal tissue in Erlenmeyer flasks. Robbins found that he could easily detect viral growth by putting a pH-indicator dye in the tissue-culture fluid. Normal cells made excess acid and the dye yellowed, whereas poliovirus-infected cells died and the color of the culture fluid did not change.
In 1949, the group reported in Science, in terse and understated language, the sensational finding that they had successfully propagated poliovirus in tissue cultures of cells of nonneurogenic origin. As a matter of fact, they reported an increase by a factor of 1015 in the amount of infective virus as assayed with the use of intracerebral inoculation in mice.5 Soon thereafter, they were able to simplify the assay of virus, thanks to their observation of a cytopathic effect in human-foreskin fibroblasts in culture. The groundwork was laid for the development of a vaccine that would alleviate untold amounts of human suffering.
(Figure)
Nurses Tending Young Patients with Poliomyelitis in an Iron Lung, 1938.
Photograph by Hansel Mieth, Time Life Pictures, Getty Images.
After John Enders came to a satisfactory agreement about sharing the Nobel Prize with Weller and Robbins, he telephoned his father, then the chairman of the Federal Reserve District of New York. He announced that he was to receive the Nobel Prize, and his father replied: "John, I never heard of such a thing as getting a prize for doing your job!" Perhaps Enders found more sympathetic father figures in Edward Jenner and Louis Pasteur, whose pictures prominently adorned the walls of his office. He clearly — and correctly — believed that such discoverers were his true intellectual ancestors.
Source Information
From the Center for Blood Research, Children's Hospital and Harvard Medical School, Boston.
References
Ward HK, Enders JF. An analysis of the opsonic and tropic action of normal and immune sera based on experiments with the pneumococcus. J Exp Med 1933;57:527-547.
Hammon WD, Enders JF. A virus disease of cats, principally characterized by aleucocytosis, enteric lesions and the presence of intranuclear inclusion bodies. J Exp Med 1939;69:327-351.
Fellers AE, Enders JF, Weller TH. The prolonged co-existence of vaccinia virus in high titre and living cells in roller tube cultures of chick embryonic tissues. J Exp Med 1940;72:367-388.
Enders JF. Chemical, clinical, and immunological studies on the products of human plasma fractionation. X. The concentrations of certain antibodies in globulin fractions derived from human blood plasma. J Clin Invest 1944;23:510-530.
Enders JF, Weller TH, Robbins FC. Cultivation of the Lansing strain of poliomyelitis virus in cultures of various human embryonic tissues. Science 1949;109:85-87.(Fred S. Rosen, M.D.)