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NOBEL PRIZEMEN
897
Annotations NOBEL PRIZEMEN
Prof. Peyton Rous, of the Rockefeller Institute in New York, and Prof. Charles B. Huggins, of Chicago, have been awarded this year’s Nobel prize in medicine. Workers in many branches of medical research have cause to pay tribute to Peyton Rous. His discoveries of tumour-inducing viruses-for which he is now honoured - concern only one of several areas of research in which he has made substantial contributions. The first to demonstrate the existence of an oncogenic virus were Ellerman and Bang in 1908, but there were doubts whether the leukosis to which their virus gave rise was truly neoplastic. The discovery in 1910 of the Rous sarcoma virus was not open to the same doubt : nevertheless, it started a controversy about the role of viruses in the aaiology of cancer which, far from being resolved, is still raging today. In 1918 Dr. 0. H. Robertson organised the world’s first blood-bank on the basis of a method for preserving whole blood developed by Rous with the assistance of Dr. J. T. Turner. Rous was also a pioneer in the use of trypsin for the separation of cells from tissues; and his demonstration, with Dr. P. D. McMaster, that bile is concentrated in the gall-bladder by absorption of water led to the development of diagnostic cholecystography. He was responsible for a technique which enabled experiments to be conducted on the peripheral lymphatic system in mammals, and he made important observations on the flow and turn-over of lymph. The work by Rous and various colleagues on the induction of tumours by combinations of agents such as coal tar, other chemicals, and wound healing led to the two-stage theory of carcinogenesis; and parallel experiments on the complementary action of Shope papilloma virus and chemical agents provided evidence for the theory that the apparent induction of cancer by chemical agents may be the result of the "lighting up" of a latent oncogenic virus. Rous was one of the first to recognise the high sensitivity of newly born animals to carcinogenic stimuli. He correctly attributed the "spontaneous" appearance of skin tumours in a batch of mice to the fact that they had been born and reared during early life in creosote-preserved wooden boxes. In the late 1950s a young research-worker asked Rous his opinion of a curious result in an experiment involving the induction of tumours in rabbit skin, a subject on which Rous had previously written several long and detailed
papers. The
inquirer’s
letter
ran to
4 pages of
single-
spaced quarto; Rous’s reply consisted of a single sentence to the effect that one of the most valuable attributes of a research scientist is the knowledge when to stop investigations in a particular field. Perhaps this is one of the secrets of Rous’s greatness and the reason why he has been able to contribute to so many areas of research. Professor Huggins is a surgical scientist of the first order who has himself put his findings into practice-to the great benefit of thousands of patients. His fundamental work on the treatment of neoplasms by hormonal methods has had a profound effect not only on the theoretical basis of cancer therapy but also on the practical results of treatment in man. The contributions which have won him
world renown started in 1939 with his experimental studies on hormones and the prostate in animals, and they were followed in 1941 by his advocacy of castration and oestrogens for prostatic cancer in man. The astonishing success of this treatment encouraged early hopes that here was a cure, but time showed that it was only a long and useful period of control. Not until cortisone became available was Huggins able fully to test his theories that adrenal ablation should also affect prostatic cancer. Though it proved disappointing in this role, he applied it with much greater success to carcinoma of the breast, and he supported his views not only with clinical evidence but also with a mass of experimental work. The Huggins technique for the rapid induction of mammary tumours in rats, by the oral administration of massive doses of a carcinogenic polycyclic hydrocarbon, could have been discovered twenty years ago. Most researchers interested in mechanisms of carcinogenesis,
however, were content to use established techniques, or thought they would be more likely to gain new information by the use of even smaller doses of carcinogens. Huggins’ aim, on the other hand, was to develop a convenient laboratory model for the study of the effect of hormones and endocrine ablation on mammary cancer. His technique, by which mammary tumours can be induced in rats in a few weeks, has been adopted for this purpose in laboratories all over the world. During the past year he has evolved a technique for the rapid induction of leukaemia in rats by the administration of massive doses of a chemical carcinogen. Of special interest in both these techniques is the fact that regression from the neoplastic state is not infrequent: thus, some of the mammary tumours regress spontaneously and some of the leukaemias are in reality no more than leukaemoid states from which the animals recover.
AN INSULIN HAZARD?
STRUCTURAL differences in the insulin molecule from species to species have been described since the classical work of Sanger and his colleagues on the aminoacid 2 sequence of the bovine hormone.’ Species variation, lately summarised by L. F. Smith of Cambridge,3has been of great interest to the biochemist, to the molecular biologist, and to the immunologist. The paper by Dr. J. G. Devlin and his colleagues on p. 883 and a letter from the medical advisory committee of the British Diabetic Association on p. 910 suggest that insulin species differences may also have importance for the clinician. In Britain, 95% of the insulin used therapeutically is supplied by British companies which prepare it largely from beef pancreas, though up to 10% of the final product may come from pig pancreas. In certain of the shorter-acting insulins prepared overseas, the proportion of beef and pig insulin in the final product is approximately reversed and some contain no appreciable quantity of beef insulin. Injected into the human, beef insulin seems to be a much more potent antigenic stimulus than pork; furthermore, the antibody produced, though it partially neutralises the biological effect of injected bovine insulin, shows little affinity for pork insulin.4 There is therefore a theoretical 1. 2. 3. 4.
Sanger, F., Tuppy, H. Biochem. J. 1951, 49, 481. Sanger, F., Thompson, E. O. P. ibid. 1953, 53, 353, 366. Smith, L. F. Am. J. Med. 1966, 40, 662. Berson, S. A., Yalow, R. S. ibid. p. 676.
Annotations NOBEL PRIZEMEN
Prof. Peyton Rous, of the Rockefeller Institute in New York, and Prof. Charles B. Huggins, of Chicago, have been awarded this year’s Nobel prize in medicine. Workers in many branches of medical research have cause to pay tribute to Peyton Rous. His discoveries of tumour-inducing viruses-for which he is now honoured - concern only one of several areas of research in which he has made substantial contributions. The first to demonstrate the existence of an oncogenic virus were Ellerman and Bang in 1908, but there were doubts whether the leukosis to which their virus gave rise was truly neoplastic. The discovery in 1910 of the Rous sarcoma virus was not open to the same doubt : nevertheless, it started a controversy about the role of viruses in the aaiology of cancer which, far from being resolved, is still raging today. In 1918 Dr. 0. H. Robertson organised the world’s first blood-bank on the basis of a method for preserving whole blood developed by Rous with the assistance of Dr. J. T. Turner. Rous was also a pioneer in the use of trypsin for the separation of cells from tissues; and his demonstration, with Dr. P. D. McMaster, that bile is concentrated in the gall-bladder by absorption of water led to the development of diagnostic cholecystography. He was responsible for a technique which enabled experiments to be conducted on the peripheral lymphatic system in mammals, and he made important observations on the flow and turn-over of lymph. The work by Rous and various colleagues on the induction of tumours by combinations of agents such as coal tar, other chemicals, and wound healing led to the two-stage theory of carcinogenesis; and parallel experiments on the complementary action of Shope papilloma virus and chemical agents provided evidence for the theory that the apparent induction of cancer by chemical agents may be the result of the "lighting up" of a latent oncogenic virus. Rous was one of the first to recognise the high sensitivity of newly born animals to carcinogenic stimuli. He correctly attributed the "spontaneous" appearance of skin tumours in a batch of mice to the fact that they had been born and reared during early life in creosote-preserved wooden boxes. In the late 1950s a young research-worker asked Rous his opinion of a curious result in an experiment involving the induction of tumours in rabbit skin, a subject on which Rous had previously written several long and detailed
papers. The
inquirer’s
letter
ran to
4 pages of
single-
spaced quarto; Rous’s reply consisted of a single sentence to the effect that one of the most valuable attributes of a research scientist is the knowledge when to stop investigations in a particular field. Perhaps this is one of the secrets of Rous’s greatness and the reason why he has been able to contribute to so many areas of research. Professor Huggins is a surgical scientist of the first order who has himself put his findings into practice-to the great benefit of thousands of patients. His fundamental work on the treatment of neoplasms by hormonal methods has had a profound effect not only on the theoretical basis of cancer therapy but also on the practical results of treatment in man. The contributions which have won him
world renown started in 1939 with his experimental studies on hormones and the prostate in animals, and they were followed in 1941 by his advocacy of castration and oestrogens for prostatic cancer in man. The astonishing success of this treatment encouraged early hopes that here was a cure, but time showed that it was only a long and useful period of control. Not until cortisone became available was Huggins able fully to test his theories that adrenal ablation should also affect prostatic cancer. Though it proved disappointing in this role, he applied it with much greater success to carcinoma of the breast, and he supported his views not only with clinical evidence but also with a mass of experimental work. The Huggins technique for the rapid induction of mammary tumours in rats, by the oral administration of massive doses of a carcinogenic polycyclic hydrocarbon, could have been discovered twenty years ago. Most researchers interested in mechanisms of carcinogenesis,
however, were content to use established techniques, or thought they would be more likely to gain new information by the use of even smaller doses of carcinogens. Huggins’ aim, on the other hand, was to develop a convenient laboratory model for the study of the effect of hormones and endocrine ablation on mammary cancer. His technique, by which mammary tumours can be induced in rats in a few weeks, has been adopted for this purpose in laboratories all over the world. During the past year he has evolved a technique for the rapid induction of leukaemia in rats by the administration of massive doses of a chemical carcinogen. Of special interest in both these techniques is the fact that regression from the neoplastic state is not infrequent: thus, some of the mammary tumours regress spontaneously and some of the leukaemias are in reality no more than leukaemoid states from which the animals recover.
AN INSULIN HAZARD?
STRUCTURAL differences in the insulin molecule from species to species have been described since the classical work of Sanger and his colleagues on the aminoacid 2 sequence of the bovine hormone.’ Species variation, lately summarised by L. F. Smith of Cambridge,3has been of great interest to the biochemist, to the molecular biologist, and to the immunologist. The paper by Dr. J. G. Devlin and his colleagues on p. 883 and a letter from the medical advisory committee of the British Diabetic Association on p. 910 suggest that insulin species differences may also have importance for the clinician. In Britain, 95% of the insulin used therapeutically is supplied by British companies which prepare it largely from beef pancreas, though up to 10% of the final product may come from pig pancreas. In certain of the shorter-acting insulins prepared overseas, the proportion of beef and pig insulin in the final product is approximately reversed and some contain no appreciable quantity of beef insulin. Injected into the human, beef insulin seems to be a much more potent antigenic stimulus than pork; furthermore, the antibody produced, though it partially neutralises the biological effect of injected bovine insulin, shows little affinity for pork insulin.4 There is therefore a theoretical 1. 2. 3. 4.
Sanger, F., Tuppy, H. Biochem. J. 1951, 49, 481. Sanger, F., Thompson, E. O. P. ibid. 1953, 53, 353, 366. Smith, L. F. Am. J. Med. 1966, 40, 662. Berson, S. A., Yalow, R. S. ibid. p. 676.