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The discovery of the poliovirus
Brain Research Bulletin, Vol. 50, Nos. 5/6, p. 461, 1999 Copyright © 1999 Elsevier Science Inc. Printed in the USA. All rights reserved 0361-9230/99/$–see front matter
PII S0361-9230(99)00134-3
The discovery of the poliovirus Krister Kristensson* Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden [Received 28 April 1999; Accepted 8 May 1999] BACKGROUND
SIGNIFICANCE
Poliomyelitis is a nervous system disease typical of the twentieth century: sizable epidemics appeared at the turn of the century and the disease will be eradicated during the first year of the next. In the field of neurovirology, it is therefore hard to point out a more important discovery in our century than that of the poliovirus made by Karl Landsteiner in 1909. Before the discovery of the infectious nature of the disease, the paralytic aspect was considered to be its characteristic feature, as documented by the denomination “infantile paralysis”. Although long hypothesized, the infectious nature of polio was first clearly shown by Wickman [6] after a large epidemic in Sweden 1905.
The discovery of the virus causing poliomyelitis was immediately accepted and a group led by S. Flexner at the Rockefeller Institute took almost instantly over the research, leaving little room for Landsteiner to continue. In monkey experiments, Flexner made the observation that polio could be an air-born infection, spreading to the nervous system along the olfactory route. This observation is considered to be one of the most unfortunate in medicine and led to neglecting epidemiological studies claiming that the human disease was transmitted as a gastrointestinal infection. Thus, the focus on monkey experiments may have delayed polio prophylaxis by several decades [4]. It has now been shown that the human poliovirus receptor may determine targeting of the virus to the gastrointestinal tract and motoneurons [5], whereas differences in tissue expression of the monkey homologues of this receptor may explain the different route of virus spread in monkeys. The chemical formula for poliovirus is known and it may become the first virus to be synthesized in the test tube—just in time for its eradication from the earth. The discovery of polio and its successful eradication with the vaccine show that a severe human nervous system disease can be eliminated; however, the polio story also tells how leading groups of investigators can direct research into misleading routes.
THE DISCOVERY Landsteiner and his assistant E. Popper at the WilhelminenSpitals in Vienna injected intraperitoneally suspensions from the spinal cord of a 9-year-old boy (died from rapidly progressive infantile paralysis) into rabbits, guinea pigs, mice and monkeys (two animals of each species). Only the monkeys, which were left over from an experiment with syphilis, showed signs of disease: one of them (Cynocephalus hamadryas) died 8 d post infection (p.i.), whereas the other (Macca rhesus) showed paresis 17 d p.i. and was sacrificed 2 days later. Both monkeys displayed severe degeneration of motoneurons and inflammatory cell infiltration in the spinal cord. No bacteria were found, and the nervous system changes resembled those of rabies, so that a viral etiology of the disease was suggested [3]. Since no more monkeys were available for experiments in Vienna, Landsteiner sent fragments of spinal cord from a 13month-old child afflicted with poliomyelitis to the Pasteur Institute in Paris. In collaboration with C. Levaditi the infectious agent was shown to be a filterable virus that could spread along nerves and be transferred between monkeys [1,2]. After the first World War, Landsteiner was appointed as pathologist in The Hague. A few years later he became member of the Rockefeller Institute for Medical Research in New York to continue his studies on the human blood groups, which he had discovered during the same period of time as poliovirus, and for which he was awarded the Nobel Prize in 1930.
REFERENCES 1. Landsteiner, K.; Levaditi, C. La paralysie infantile expe´rimentale. Compt. Rend. Soc. Biol. 67:787–789; 1909a. 2. Landsteiner, K.; Levaditi, C. La transmission de la paralysie infantile aux singes. Compt. Rend. Soc. Biol. 67:592–594; 1909b. ¨ bertragung der Poliomyelitis acuta auf 3. Landsteiner, K.; Popper, E. U Affen. Zeitschr. Immunita¨tsforsch. Orig. 2:377–390; 1909. 4. Paul, J. R. A history of poliomyelitis. New Haven and London: Yale University Press; 1971. 5. Solecki, D.; Gromeier, M.; Harber, J.; Bernhardt, G.; Wimmer, E. Poliovirus and its cellular receptor: A molecular genetic dissection of a virus/receptor affinity interaction. J. Mol. Recognit. 11:2–9; 1998. 6. Wickman, I. Beitra¨ge zur Kenntnis der Heine-Medinschen Krankheit (Poliomyelitis acuta und verwandter Erkrankungen). Berlin: Karger; 1907.
* Address for correspondence: Prof. Krister Kristensson, Dept. of Neuroscience, Karolinska Institutet, S-171 77 Stockholm, Sweden. Fax: ⫹46-8-32 5325; E-mail: [email protected]
461
PII S0361-9230(99)00134-3
The discovery of the poliovirus Krister Kristensson* Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden [Received 28 April 1999; Accepted 8 May 1999] BACKGROUND
SIGNIFICANCE
Poliomyelitis is a nervous system disease typical of the twentieth century: sizable epidemics appeared at the turn of the century and the disease will be eradicated during the first year of the next. In the field of neurovirology, it is therefore hard to point out a more important discovery in our century than that of the poliovirus made by Karl Landsteiner in 1909. Before the discovery of the infectious nature of the disease, the paralytic aspect was considered to be its characteristic feature, as documented by the denomination “infantile paralysis”. Although long hypothesized, the infectious nature of polio was first clearly shown by Wickman [6] after a large epidemic in Sweden 1905.
The discovery of the virus causing poliomyelitis was immediately accepted and a group led by S. Flexner at the Rockefeller Institute took almost instantly over the research, leaving little room for Landsteiner to continue. In monkey experiments, Flexner made the observation that polio could be an air-born infection, spreading to the nervous system along the olfactory route. This observation is considered to be one of the most unfortunate in medicine and led to neglecting epidemiological studies claiming that the human disease was transmitted as a gastrointestinal infection. Thus, the focus on monkey experiments may have delayed polio prophylaxis by several decades [4]. It has now been shown that the human poliovirus receptor may determine targeting of the virus to the gastrointestinal tract and motoneurons [5], whereas differences in tissue expression of the monkey homologues of this receptor may explain the different route of virus spread in monkeys. The chemical formula for poliovirus is known and it may become the first virus to be synthesized in the test tube—just in time for its eradication from the earth. The discovery of polio and its successful eradication with the vaccine show that a severe human nervous system disease can be eliminated; however, the polio story also tells how leading groups of investigators can direct research into misleading routes.
THE DISCOVERY Landsteiner and his assistant E. Popper at the WilhelminenSpitals in Vienna injected intraperitoneally suspensions from the spinal cord of a 9-year-old boy (died from rapidly progressive infantile paralysis) into rabbits, guinea pigs, mice and monkeys (two animals of each species). Only the monkeys, which were left over from an experiment with syphilis, showed signs of disease: one of them (Cynocephalus hamadryas) died 8 d post infection (p.i.), whereas the other (Macca rhesus) showed paresis 17 d p.i. and was sacrificed 2 days later. Both monkeys displayed severe degeneration of motoneurons and inflammatory cell infiltration in the spinal cord. No bacteria were found, and the nervous system changes resembled those of rabies, so that a viral etiology of the disease was suggested [3]. Since no more monkeys were available for experiments in Vienna, Landsteiner sent fragments of spinal cord from a 13month-old child afflicted with poliomyelitis to the Pasteur Institute in Paris. In collaboration with C. Levaditi the infectious agent was shown to be a filterable virus that could spread along nerves and be transferred between monkeys [1,2]. After the first World War, Landsteiner was appointed as pathologist in The Hague. A few years later he became member of the Rockefeller Institute for Medical Research in New York to continue his studies on the human blood groups, which he had discovered during the same period of time as poliovirus, and for which he was awarded the Nobel Prize in 1930.
REFERENCES 1. Landsteiner, K.; Levaditi, C. La paralysie infantile expe´rimentale. Compt. Rend. Soc. Biol. 67:787–789; 1909a. 2. Landsteiner, K.; Levaditi, C. La transmission de la paralysie infantile aux singes. Compt. Rend. Soc. Biol. 67:592–594; 1909b. ¨ bertragung der Poliomyelitis acuta auf 3. Landsteiner, K.; Popper, E. U Affen. Zeitschr. Immunita¨tsforsch. Orig. 2:377–390; 1909. 4. Paul, J. R. A history of poliomyelitis. New Haven and London: Yale University Press; 1971. 5. Solecki, D.; Gromeier, M.; Harber, J.; Bernhardt, G.; Wimmer, E. Poliovirus and its cellular receptor: A molecular genetic dissection of a virus/receptor affinity interaction. J. Mol. Recognit. 11:2–9; 1998. 6. Wickman, I. Beitra¨ge zur Kenntnis der Heine-Medinschen Krankheit (Poliomyelitis acuta und verwandter Erkrankungen). Berlin: Karger; 1907.
* Address for correspondence: Prof. Krister Kristensson, Dept. of Neuroscience, Karolinska Institutet, S-171 77 Stockholm, Sweden. Fax: ⫹46-8-32 5325; E-mail: [email protected]
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