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Unacknowledged contributions of Pavlov and Barcroft to Cannon's theory of homeostasis
Appetite 51 (2008) 428–432
Contents lists available at ScienceDirect
Appetite journal homepage: www.elsevier.com/locate/appet
Research review
Unacknowledged contributions of Pavlov and Barcroft to Cannon’s theory of homeostasis Gerard P. Smith Department of Psychiatry, Weill Cornell Medical College, Payne Whitney Westchester, New York Presbyterian Hospital, White Plains, NY 10605, USA
A R T I C L E I N F O
A B S T R A C T
Article history: Received 30 June 2008
Cannon’s theory of homeostasis is the first, major, American contribution to physiological thought. Although it is clear that Cannon’s account of homeostasis is personal and based primarily on the work of his laboratory, Cannon made it easy for readers to mistake his 1929 paper and 1932 book for a comprehensive review of the literature relevant to homeostasis. This is unfortunate because Cannon never acknowledged the important contributions of two of his contemporaries, Ivan Pavlov and Joseph Barcroft. Since he did not mention them, their contributions are rarely discussed. This paper attempts to correct this historical problem in two ways. First, I describe the unacknowledged contributions of Pavlov and Barcroft. Then I consider the possible reasons why Cannon ignored them. ß 2008 Elsevier Ltd. All rights reserved.
Accepted 4 July 2008 Keywords: Barcroft Cannon Bernard Pavlov Homeostasis Conditioned reflexes Foetal physiology Literature citations Sympathetic nervous system
Contents
Cannon’s theory of homeostasis . . . . . . . . . . . . . . Ivan Pavlov . . . . . . . . . . . . . . . . . . . . . . . . . . . . Joseph Barcroft. . . . . . . . . . . . . . . . . . . . . . . . . . Why were Pavlov and Barcroft not acknowledged?. Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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Cannon’s theory of homeostasis The self-maintenance of animals and people was first recognized as a problem by the Greeks (Adolph, 1961). What Cannon brought to the problem in the late 1920s was a name, homeostasis, six postulates of defining properties that provided a framework for research, and a specific mechanism, the sympathetic nervous system, particularly its stimulation of adrenomedullary secretion (Cannon, 1925, 1926, 1929a,b). As Cooper notes in the lead paper of this Special Section, Cannon’s 1929 article in Physiological Reviews entitled ‘‘Organization for Physiological Homeostasis’’ is a landmark
E-mail address: [email protected]. 0195-6663/$ – see front matter ß 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.appet.2008.07.003
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in physiological theory (Cannon, 1929a). The article commanded attention because of Cannon’s personal prestige as an experienced, productive, and thoughtful physiologist, as the Chairman of arguably the best Department of Physiology in America, and his high-minded civility and interest in the international issues of war and peace that grew out of his military experience in the first World War. The article, clearly written and closely argued, is the first major American contribution to physiological theory. Rereading that article and the three that led up to it, it is clear that Cannon based his ideas of homeostasis on Claude Bernard’s fluid matrix that constituted the internal environment of all cells. Bernard argued that the constancy of the fluid matrix was necessary for the free life and was achieved by many unidentified mechanisms mediated by the brain.
G.P. Smith / Appetite 51 (2008) 428–432
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contributions are rarely discussed. For example, the useful collection of papers concerning homeostasis by Langley (1973), the recent review by Woods and Ramsay (2007), and the accompanying papers by Cooper (2008) and Booth (2008) do not mention them.2 This paper attempts to correct this historical problem in two ways. First, I describe the unacknowledged contributions of Pavlov and Barcroft. Then I consider the possible reasons why Cannon ignored them.
Ivan Pavlov
Fig. 1. Cannon used this figure as a summary for his discussion of the homeostasis of blood sugar in his classic article in Physiological Reviews. His commentary on the figure was: ‘‘The general scheme which has been presented above is represented diagrammatically in Fig. 1. As Hansen (1923) has pointed out, there are normal oscillations in blood sugar occurring within a relatively narrow range. Possibly these ups and downs result from action of the opposing factors, depressing or elevating the glycemic level. If known elevating agencies (normally and primarily the sympathico-adrenal apparatus) are unable to bring forth sugar from storage in the liver, the glycemic level falls from about 70 to about 45 mg per cent, whereupon serious symptoms (convulsions and coma) may supervene. The range between 70 and 45 mg per cent may be regarded as the margin of safety. On the other hand, if the depressing agency (the insular or vago-insular apparatus) is ineffective, the glycemic level rises to about 180 mg per cent and then sugar begins to be lost through the kidneys. The range from 100 or 120 to 180 mg per cent may be regarded as the margin of economy—beyond that, homeostasis is dependent on wasting the energy contained in the sugar and the energy possibly employed by the body to bring it as glucose into the blood’’ (Cannon, 1929a, pp. 409–410).
It was Cannon’s investigation of the numerous effects of the sympathetic nervous system, particularly its stimulation of the adrenomedullary secretion of adrenaline,1 that provided the experimental basis for Cannon’s theory. It led him to envision the constancy as a variation within limits achieved by the dynamic interaction of opposing humoral and neural mechanisms. The opposing effects of insulin and adrenaline on blood sugar that he and his colleagues demonstrated is a clear example of Cannon’s thinking (Fig. 1). Cannon did not claim too much. He emphasized that many of the mechanisms he discussed were provisional; their relative importance depended on further experiments. As Cooper notes, Cannon reinforced the impact of his ideas in a book in 1932, The Wisdom of the Body (Cannon, 1932). It was less technical than his journal articles and accessible to interested readers, lay and professional, as well as working physiologists. As a result it was widely influential and remains a classic statement of Cannon’s idea of homeostasis. Although it is clear that Cannon’s account of homeostasis is personal and based primarily on the work of his laboratory, Cannon made it easy for readers to mistake his 1929 paper and 1932 book for a comprehensive review of the literature relevant to homeostasis. This is unfortunate because Cannon never acknowledged the important contributions of two of his contemporaries, Ivan Pavlov and Joseph Barcroft. Since he did not mention them, their
Pavlov, the Russian master and first physiologist to win the Nobel Prize, made two major contributions to homeostasis. First, he discovered that the volume and enzymic concentration of pancreatic secretion changed as a function of the nutrient stimuli in the small intestine (Pavlov, 1910, p. 43). For example, when a diet changed from flesh to milk and bread, the enzymic content of pancreatic juice changed over days to produce more digestive action on starch and less on proteins. This adaptive change is a homeostatic response inside the small intestine. This was new. Bernard and Cannon had discussed two environments of the body, the internal and external. They never mentioned the third, the intestinal, that is in the body and separated from the internal environment by the mucosal barrier of the small intestine. Pavlov’s second contribution to homeostasis was more important. This was his discovery of conditioned reflexes, first in salivary and gastric secretion, then on many motor systems. Pavlov recognized their importance for homeostasis immediately and discussed them in his Nobel Prize lecture in 1904 (Pavlov, 1928). The claim was explicit: ‘‘. . . the signalizing properties of the objects (at a distance) represent the physiological basis of the finest reactivity of the living substance, the most delicate adaptation of the animal organisms, to the outer world (p. 80) . . .. Thus in the psychical experiment the connection of the objects exciting the salivary glands becomes more and more distant and delicate. Undoubtedly we have before us here an extreme degree of adaptation’’ (p. 52). For Pavlov the conditioned reflexes were how prior experience with environmental stimuli could contribute to homeostasis by direct effects on the internal environment through cephalic reflexes to salivary and gastric glands or by indirect effects, such as behaviors that minimized changes in body temperature or increased the probability of finding food. These homeostatic effects of conditioned reflexes pervade modern homeostatic theory (Booth, 2008; Woods & Ramsay, 2007). Despite writing the Introduction and assisting in the editing of Gantt’s translation of Pavlov’s Lectures on Conditioned Reflexes in 1928, Cannon cited Pavlov only once. That was in the second edition of The Wisdom of the Body in 1939 where Cannon discussed the salivary secretory response Pavlov had observed when an injurious stimulus, such as acid, was put in the mouth (Cannon, 1939, pp. 217–218). This response, however, was unconditioned, i.e., not influenced by prior experience. About Pavlov’s conditioned responses and adaptive changes in the intestinal environment, Cannon was silent.
1 Cannon called the active substance of the adrenomedullary secretion detected by the biosassay of the denervated heart adrenin in most of his early papers. 2 Woods and Ramsay (2007) and Booth (2008) discuss the importance of Pavlovian conditioning in homeostasis of food and water intake in the literature beginning in the 1960s, but neither discusses Pavlov’s work before 1910 which is explicit about the homeostatic function of conditional reflexes.
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Joseph Barcroft Barcroft was a very distinguished physiologist, becoming a Fellow of the Royal Society in 1910 at the age of 38. The successor of Langley as the Professor of Physiology at Cambridge he was knighted in 1935, and nominated for the Nobel Prize in 1933 and 1936 (Franklin, 1953). He first discussed Bernard’s fixity of the internal environment in the Dunham Lectures at Harvard in October 1929. This was only 3 months after Cannon’s article appeared in Physiological Reviews. Barcroft was in Boston from August when he came over to attend the 13th International Congress of Physiology. No record exists of discussions between Cannon and Barcroft during this time. It is very unlikely, however, that Barcroft did not seek out Cannon to learn his ideas about homeostasis because Barcroft preferred to obtain scientific information by personal discussions with other physiologists rather than relying entirely on what he gleaned from the literature (Franklin, 1953). Holmes, who published the most comprehensive and thoughtful article about Barcroft’s work on Bernard’s insight (Holmes, 1961), concluded that Barcroft made two important theoretical contributions in the critical review he published in 1932 (Barcroft, 1932). First, by comparing lower animals with higher animals, he showed that higher animals maintain their internal environment by correcting disturbances, while lower animals evade the disturbing event or stimulus. Second, he offered a new view of Bernard’s ‘‘free life.’’ Noting that the recent discussion of the constancy of the internal environment by Haldane, Henderson, and Cannon focused on the means by which the internal environment was fixed, he raised the question of what the ‘‘free life’’ was for. He argued that the end was more important than the means. Citing the results of his own work at high altitude and reviewing the animal data presented in Cannon’s 1929 review, Barcroft showed that the most sensitive symptoms and signs of disturbance of the internal environment were correlated with disturbance of higher neural function (Table 1). ‘‘Thus, the fixity of the internal environment is the condition of mental activity’’ (Barcroft, 1932, p.86).
Table 1 Symptoms and signs when heat and various substances in the internal environment are deficient or excessive Environment
Deficient
Excessive
Temperature Oxygen cH
Inertia Unconsciousness Headache
Delirium – Coma
Glucose
Nervousness Feeling of ‘‘goneness’’ Hunger
–
Water
Weakness, Asher
Headache Nausea Dizziness Asthenia Incoordination
Sodium
Fever
Reflex irritability Weakness Paresis
Calcium
Nervous twitchings Convulsions
Apathy Drowsiness verging on coma General atonia
Barcroft expanded his discussion and tightened his argument in 1934 in a brilliant book, Features in the Architecture of Physiological Function (Barcroft, 1934). This is one of the great expositions of physiological thinking. Broader, deeper, and more demanding than The Wisdom of the Body, it is a classic waiting to be rediscovered. The book made it clear that, although Bernard and subsequent physiologists down to Cannon had held that the central nervous system mediated many of the efferent mechanisms necessary for the fixity of the internal environment, Barcroft was the first to say that higher brain function required the most stable internal environment. Thus, homeostasis was not only organized by the brain—homeostasis served the brain. To Barcroft this meant that a fine control of the internal environment was the prerequisite for the intellectual ascendancy of man. I believe that Barcroft made a third contribution. In 1933 when he was nearly 60 years old, Barcroft began to investigate foetal physiology. His interest was triggered by an observation during his work on the spleen’s reservoir function. He noted that the spleen of a pregnant dog was shriveled (Barcroft & Stevens, 1928). Barcroft surmised that the blood had gone to the placenta. Over the next 13 years, he pursued an intense research program in foetal physiology. This was hands-on research. In fact, he took a sabbatical leave during the Lent term of 1935 so that he could operate on 100 ewes. During that sabbatical he hung this sign on his office door: ‘‘Professor Barcroft is away from Cambridge for all purposes except research’’ (Franklin, 1953). The program was immensely productive. In 1935 he gave the Croonian Lecture on ‘‘Foetal Respiration’’ (Barcroft, 1935b) and two lectures in Dublin, one of which was entitled ‘‘Chemical Conditions of Mental Development’’ (Barcroft, 1935a). Two years later, he delivered the Terry Lectures at Yale. Their theme was the internal environment and the actions of the developing brain and they were published in 1938 as The Brain and its Environment (Barcroft, 1938). He thought that his foetal research (for details see Barcroft, 1938; Franklin, 1953; Holmes, 1961) provided new and strong support for his insight, arguing that Cannon, Henderson, and Haldane were ‘‘not particularly interested in the nature of the effects but merely in the size of the chemical or physical changes which produced them . . . [I believe] the effects are all mental or at least involve the brain’’ (p. 87). He made a strong inference in this soaring conclusion: ‘‘We have therefore arrived at the point where we can say not only that the form of life – man – which has developed an intellectual power far beyond any other, is that in which the constitution of the fluids that bathe his cells is most exactly regulated; but also that the most immediate effect of interference with chemical or physical properties of the blood is impairment of the higher qualities of the brain’’ (p. 109). Why were Pavlov and Barcroft not acknowledged?
Note: ‘‘The signs and symptoms in man if the higher or lower limits of the fixity of the internal environment are passed over . . .. The fixity of internal environment, then, is controlled by the upper part of the central nervous system which suffers if the environment alters beyond physiological limits. The fixity of the internal environment is in short the condition of mental activity’’ (Barcroft, 1934).
The failure of Cannon to acknowledge the important contributions of Pavlov and Barcroft was not due to the fact that they were unknown to him or that they had published in obscure journals. Cannon had cited Pavlov’s first book in 1911 in The Mechanics of Digestion (Cannon, 1911), and wrote the Introduction and polished the English translation of Pavlov’s later book, Lectures on Conditioned Reflexes, in 1928 that contained his Nobel lecture (Pavlov, 1928). In addition, Cannon was concerned about Pavlov’s situation during and after the Bolshevik Revolution (Cannon, 1921) and was Pavlov’s host for the International Physiological Congress in 1929 (Cannon, 1945). In Barcroft’s case, Cannon regularly cited Barcroft’s work on the spleen as a reservoir of blood and its contraction by sympathetic stimulation. They certainly met during Barcroft’s visit to Harvard in 1929 and Cannon probably attended Barcroft’s Dunham lectures.
G.P. Smith / Appetite 51 (2008) 428–432
They spent time together in 1930 when Cannon visited Cambridge to give the Linacre Lecture (Cannon, 1930). As leaders in physiology, they must have rubbed together frequently at international meetings. I believe that Cannon failed to acknowledge Pavlov and Barcroft for different reasons. Cannon failed to acknowledge Pavlov’s conditioned reflexes in which the stimuli from the external environment could enhance the constancy of the internal environment (see above) because Cannon believed that behavioral responses to stimuli in the external environment always disturbed the internal environment. Such disturbances then had to be returned to their normal values by the sympathetic nervous system and other internal homeostatic mechanisms. Furthermore, Cannon’s homeostatic responses were all automatic and unlearned. Thus, I believe Cannon’s exclusion of learning from homeostasis accounts for his failure to acknowledge Pavlov’s contribution. This ban on learning from homeostatic mechanisms was reinforced by Richter in his influential experiments on the behavioral responses to internal deficits that had homeostatic effects (Smith, 2007). The ban was not lifted until the 1960s when the ideas and techniques of Pavlov, Skinner and Miller seeped into the investigation of visceral and behavioral homeostatic responses (Dworkin, 1993). The failure to acknowledge Barcroft in the 1929 Physiological Reviews is easily explained—Barcroft’s review did not appear until 1932. Yet this does not explain why Barcroft’s work is not discussed in the The Wisdom of the Body in 1932 except for this passing comment. ‘‘Repeatedly in foregoing chapters I have called attention to the fact that insofar as our internal environment is kept constant we are freed from the limitations imposed by both internal and external agencies or conditions that could be disturbing. The pertinent question has been asked by Barcroft, freedom for what?’’ (Cannon, 1932, p. 284). Cannon does not give Barcroft’s answer (the brain) nor describe any of his extensive evidence. Instead Cannon asserts, ‘‘It is chiefly freedom for the activity of the higher levels of the nervous system and the muscles which they govern.’’ Thus, Barcroft’s 1932 review is cited for his question, but not for his answer. In 1939, the second edition of The Wisdom of the Body appeared (Cannon, 1939). Cannon repeated what he wrote in the first edition and did not mention Barcroft’s extended, synthetic discussion of the problem in Features in the Architecture of Physiological Function (Barcroft, 1934). There is more. Cannon wrote a new chapter on ‘‘The Aging of Homeostatic Mechanisms’’ for this second edition. It opens with three sentences on the foetus. Barcroft’s extensive and novel results in the ovine foetus were not mentioned. Cannon’s exclusion of Barcroft suggests that he saw Barcroft’s work on the mechanisms that maintained the fixity of the internal environment and the fact that homeostasis served the brain as significant competition for his own ideas. Certainly Barcroft, not Cannon, had shown that the requirements for that fixity were more rigorous for the brain than for any other organ. From that Barcroft had drawn the important evolutionary conclusion that the fixity was the precondition for the ascendancy of humans beyond other animals. Cannon is such an important and likeable figure in American Physiology (Alvarez, 1932; Lusk, 1932) during the period between World Wars I and II, that he has received little, if any, negative criticism such as I raise here based on my interpretation of his citation practices. Though their meaning can be ambiguous, I believe the persistent failure to cite the work of Pavlov and Barcroft for a decade is significant and is evidence that Cannon, like other scientists, was protective of his scientific ideas. One of the ways to
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maintain a claim for originality is to ignore, perhaps unconsciously, the relevant contributions of other investigators. His failure to incorporate Pavlov’s learning mechanisms into homeostasis had a persistent and limiting effect on the investigation of autonomic mechanisms and ingestive behavior within a homeostatic framework. It was not until the 1960s that Pavlov’s ideas and techniques began to supplement the internal, automatic, and unlearned homeostatic mechanisms of Cannon in American physiology and physiological psychology.3 I know it is a long way from citation practices to intellectual limitations on later research. In this case, however, the path seems clear. Acknowledgements I thank Marcia Miller for great bibliographic assistance, James Gibbs and David Booth for constructive criticism of the penultimate version of this paper, and my Chairman, Jack Barchas, for encouragement and support. I also want to note that the late Steve Cooper’s scholarship and historical sense stimulated me to write this paper. References Adam, G. (1967). Interoception and behaviour; an experimental study. Budapest: Akademiai Kiado. Adolph, E. F. (1961). Early concepts of physiological regulations. Physiological Reviews, 41, 737–770. Alvarez, W. C. (1932). The influence of Doctor Cannon’s work upon medical thought and progress. In Walter Bradford Cannon, exercises celebrating twenty-five years as George Higginson professor of physiology (pp. 10–25). Cambridge: Harvard University Press. Bykov, K. M. (1957). The cerebral cortex and the internal organs. New York: Chemical Publishing Company. Barcroft, J. (1932). La fixite du milieu interieur est la condition de la vie libre (Claude Bernard). Biological Reviews and Biological Proceedings of the Cambridge Philosophical Society, 7, 24–87. Barcroft, J. (1934). Features in the architecture of physiological function. Cambridge: Cambridge University Press. Barcroft, J. (1935a). Chemical conditions of mental development. Irish Journal of Medical Science, 7S, 302–313. Barcroft, J. (1935b). The Croonian Lecture: Foetal respiration. Proceedings of the Royal Society, Series B, Biological Sciences, 118, 242–263. Barcroft, J. (1938). The Brain and Its Environment. New Haven: Yale University Press. Barcroft, J., & Stevens, JG. (1928). The effect of pregnancy and menstruation on the size of the spleen. Journal of Physiology (London), 66, 32–36. Booth, D. A. (2008). Physiological regulation through learnt control of appetites by contingencies among signals from external and internal environments. Appetite. Cannon, W. B. (1911). The mechanical factors of digestion. New York: Longmans Green & Co. Cannon, W. B. (1921). Pawlow is still alive. Journal of the American Medical Association, 77, 1040. Cannon, W. B. (1925). Some general features of endocrine influence on metabolism. Transactions of the Congress of American Physicians & Surgeons, XIII, 31–53. Cannon, W. B. (1926). Physiological regulation of normal states: Some tentative postulates concerning biological homeostatics. In A. Pettit (Ed.), A Charles Richet: ses amis, ses collegues, ses eleves (pp. 91–93)Paris: Les Editions Medicales. Cannon, W. B. (1929a). Organization for physiological homeostasis. Physiological Reviews, IX, 399–431. Cannon, W. B. (1929b). The sympathetic division of the autonomic system in relation to homeostasis. Archives of Neurology & Psychiatry, 22, 282–294. Cannon, W. B. (1930). The autonomic nervous system: An interpretation. Lancet, I, 1109–1115. Cannon, W. B. (1932). The wisdom of the body. New York: Norton. Cannon, W. B. (1939). The wisdom of the body (2nd ed.). New York: Norton. Cannon, W. B. (1945). The way of an investigator. New York: Hafner Publishing Company. Chernigovsky, V. N. (1967). Interoceptors. Washington: American Psychological Association. Cooper, S. J. (2008). From Claude Bernard to Walter Cannon: Emergence of the concept of homeostasis. Appetite. Dworkin, B. R. (1993). Learning and physiological regulation. Chicago: University of Chicago Press. 3 Where Cannon’s ban did not reach, visceral and autonomic conditioning flourished, e.g. in Russia (Bykov, 1957; Chernigovsky, 1967) and Hungary (A´da´m, 1967).
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Franklin, K. J. (1953). Joseph Barcroft. Oxford: Blackwell Scientific Publications. Hansen, K.M. (1923). Acta Medica Scandinavia lviii, Supplement iv. Holmes, F. L. (1961). Joseph Barcroft and the fixity of the internal environment. Journal of the History of Biology, 2, 88–122. Langley, L. L. (Ed.). (1973). Homeostasis. Stroudsburg: Dowden, Hutchinson & Ross, Inc. Lusk, G. (1932). The life of a professor. In Walter Bradford Cannon, exercises celebrating twenty-five years as George Higginson professor of physiology (pp. 45–54). Cambridge: Harvard University Press.
Pavlov, I. P. (1910). The work of the digestive glands (2nd ed.). London: Charles Griffin & Company, Limited. Pavlov, I. P. (1928). Lectures on conditioned reflexes. New York: Liveright Publishing Corporation. Smith, G. P. (2007). Introduction to four papers on Curt Richter and analysis of his scientific practice. Appetite, 49, 347–352. Woods, S. C., & Ramsay, D. S. (2007). Homeostasis: Beyond Curt Richter. Appetite, 49, 388–398.
Contents lists available at ScienceDirect
Appetite journal homepage: www.elsevier.com/locate/appet
Research review
Unacknowledged contributions of Pavlov and Barcroft to Cannon’s theory of homeostasis Gerard P. Smith Department of Psychiatry, Weill Cornell Medical College, Payne Whitney Westchester, New York Presbyterian Hospital, White Plains, NY 10605, USA
A R T I C L E I N F O
A B S T R A C T
Article history: Received 30 June 2008
Cannon’s theory of homeostasis is the first, major, American contribution to physiological thought. Although it is clear that Cannon’s account of homeostasis is personal and based primarily on the work of his laboratory, Cannon made it easy for readers to mistake his 1929 paper and 1932 book for a comprehensive review of the literature relevant to homeostasis. This is unfortunate because Cannon never acknowledged the important contributions of two of his contemporaries, Ivan Pavlov and Joseph Barcroft. Since he did not mention them, their contributions are rarely discussed. This paper attempts to correct this historical problem in two ways. First, I describe the unacknowledged contributions of Pavlov and Barcroft. Then I consider the possible reasons why Cannon ignored them. ß 2008 Elsevier Ltd. All rights reserved.
Accepted 4 July 2008 Keywords: Barcroft Cannon Bernard Pavlov Homeostasis Conditioned reflexes Foetal physiology Literature citations Sympathetic nervous system
Contents
Cannon’s theory of homeostasis . . . . . . . . . . . . . . Ivan Pavlov . . . . . . . . . . . . . . . . . . . . . . . . . . . . Joseph Barcroft. . . . . . . . . . . . . . . . . . . . . . . . . . Why were Pavlov and Barcroft not acknowledged?. Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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. . . . . .
. . . . . .
. . . . . .
. . . . . .
Cannon’s theory of homeostasis The self-maintenance of animals and people was first recognized as a problem by the Greeks (Adolph, 1961). What Cannon brought to the problem in the late 1920s was a name, homeostasis, six postulates of defining properties that provided a framework for research, and a specific mechanism, the sympathetic nervous system, particularly its stimulation of adrenomedullary secretion (Cannon, 1925, 1926, 1929a,b). As Cooper notes in the lead paper of this Special Section, Cannon’s 1929 article in Physiological Reviews entitled ‘‘Organization for Physiological Homeostasis’’ is a landmark
E-mail address: [email protected]. 0195-6663/$ – see front matter ß 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.appet.2008.07.003
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in physiological theory (Cannon, 1929a). The article commanded attention because of Cannon’s personal prestige as an experienced, productive, and thoughtful physiologist, as the Chairman of arguably the best Department of Physiology in America, and his high-minded civility and interest in the international issues of war and peace that grew out of his military experience in the first World War. The article, clearly written and closely argued, is the first major American contribution to physiological theory. Rereading that article and the three that led up to it, it is clear that Cannon based his ideas of homeostasis on Claude Bernard’s fluid matrix that constituted the internal environment of all cells. Bernard argued that the constancy of the fluid matrix was necessary for the free life and was achieved by many unidentified mechanisms mediated by the brain.
G.P. Smith / Appetite 51 (2008) 428–432
429
contributions are rarely discussed. For example, the useful collection of papers concerning homeostasis by Langley (1973), the recent review by Woods and Ramsay (2007), and the accompanying papers by Cooper (2008) and Booth (2008) do not mention them.2 This paper attempts to correct this historical problem in two ways. First, I describe the unacknowledged contributions of Pavlov and Barcroft. Then I consider the possible reasons why Cannon ignored them.
Ivan Pavlov
Fig. 1. Cannon used this figure as a summary for his discussion of the homeostasis of blood sugar in his classic article in Physiological Reviews. His commentary on the figure was: ‘‘The general scheme which has been presented above is represented diagrammatically in Fig. 1. As Hansen (1923) has pointed out, there are normal oscillations in blood sugar occurring within a relatively narrow range. Possibly these ups and downs result from action of the opposing factors, depressing or elevating the glycemic level. If known elevating agencies (normally and primarily the sympathico-adrenal apparatus) are unable to bring forth sugar from storage in the liver, the glycemic level falls from about 70 to about 45 mg per cent, whereupon serious symptoms (convulsions and coma) may supervene. The range between 70 and 45 mg per cent may be regarded as the margin of safety. On the other hand, if the depressing agency (the insular or vago-insular apparatus) is ineffective, the glycemic level rises to about 180 mg per cent and then sugar begins to be lost through the kidneys. The range from 100 or 120 to 180 mg per cent may be regarded as the margin of economy—beyond that, homeostasis is dependent on wasting the energy contained in the sugar and the energy possibly employed by the body to bring it as glucose into the blood’’ (Cannon, 1929a, pp. 409–410).
It was Cannon’s investigation of the numerous effects of the sympathetic nervous system, particularly its stimulation of the adrenomedullary secretion of adrenaline,1 that provided the experimental basis for Cannon’s theory. It led him to envision the constancy as a variation within limits achieved by the dynamic interaction of opposing humoral and neural mechanisms. The opposing effects of insulin and adrenaline on blood sugar that he and his colleagues demonstrated is a clear example of Cannon’s thinking (Fig. 1). Cannon did not claim too much. He emphasized that many of the mechanisms he discussed were provisional; their relative importance depended on further experiments. As Cooper notes, Cannon reinforced the impact of his ideas in a book in 1932, The Wisdom of the Body (Cannon, 1932). It was less technical than his journal articles and accessible to interested readers, lay and professional, as well as working physiologists. As a result it was widely influential and remains a classic statement of Cannon’s idea of homeostasis. Although it is clear that Cannon’s account of homeostasis is personal and based primarily on the work of his laboratory, Cannon made it easy for readers to mistake his 1929 paper and 1932 book for a comprehensive review of the literature relevant to homeostasis. This is unfortunate because Cannon never acknowledged the important contributions of two of his contemporaries, Ivan Pavlov and Joseph Barcroft. Since he did not mention them, their
Pavlov, the Russian master and first physiologist to win the Nobel Prize, made two major contributions to homeostasis. First, he discovered that the volume and enzymic concentration of pancreatic secretion changed as a function of the nutrient stimuli in the small intestine (Pavlov, 1910, p. 43). For example, when a diet changed from flesh to milk and bread, the enzymic content of pancreatic juice changed over days to produce more digestive action on starch and less on proteins. This adaptive change is a homeostatic response inside the small intestine. This was new. Bernard and Cannon had discussed two environments of the body, the internal and external. They never mentioned the third, the intestinal, that is in the body and separated from the internal environment by the mucosal barrier of the small intestine. Pavlov’s second contribution to homeostasis was more important. This was his discovery of conditioned reflexes, first in salivary and gastric secretion, then on many motor systems. Pavlov recognized their importance for homeostasis immediately and discussed them in his Nobel Prize lecture in 1904 (Pavlov, 1928). The claim was explicit: ‘‘. . . the signalizing properties of the objects (at a distance) represent the physiological basis of the finest reactivity of the living substance, the most delicate adaptation of the animal organisms, to the outer world (p. 80) . . .. Thus in the psychical experiment the connection of the objects exciting the salivary glands becomes more and more distant and delicate. Undoubtedly we have before us here an extreme degree of adaptation’’ (p. 52). For Pavlov the conditioned reflexes were how prior experience with environmental stimuli could contribute to homeostasis by direct effects on the internal environment through cephalic reflexes to salivary and gastric glands or by indirect effects, such as behaviors that minimized changes in body temperature or increased the probability of finding food. These homeostatic effects of conditioned reflexes pervade modern homeostatic theory (Booth, 2008; Woods & Ramsay, 2007). Despite writing the Introduction and assisting in the editing of Gantt’s translation of Pavlov’s Lectures on Conditioned Reflexes in 1928, Cannon cited Pavlov only once. That was in the second edition of The Wisdom of the Body in 1939 where Cannon discussed the salivary secretory response Pavlov had observed when an injurious stimulus, such as acid, was put in the mouth (Cannon, 1939, pp. 217–218). This response, however, was unconditioned, i.e., not influenced by prior experience. About Pavlov’s conditioned responses and adaptive changes in the intestinal environment, Cannon was silent.
1 Cannon called the active substance of the adrenomedullary secretion detected by the biosassay of the denervated heart adrenin in most of his early papers. 2 Woods and Ramsay (2007) and Booth (2008) discuss the importance of Pavlovian conditioning in homeostasis of food and water intake in the literature beginning in the 1960s, but neither discusses Pavlov’s work before 1910 which is explicit about the homeostatic function of conditional reflexes.
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Joseph Barcroft Barcroft was a very distinguished physiologist, becoming a Fellow of the Royal Society in 1910 at the age of 38. The successor of Langley as the Professor of Physiology at Cambridge he was knighted in 1935, and nominated for the Nobel Prize in 1933 and 1936 (Franklin, 1953). He first discussed Bernard’s fixity of the internal environment in the Dunham Lectures at Harvard in October 1929. This was only 3 months after Cannon’s article appeared in Physiological Reviews. Barcroft was in Boston from August when he came over to attend the 13th International Congress of Physiology. No record exists of discussions between Cannon and Barcroft during this time. It is very unlikely, however, that Barcroft did not seek out Cannon to learn his ideas about homeostasis because Barcroft preferred to obtain scientific information by personal discussions with other physiologists rather than relying entirely on what he gleaned from the literature (Franklin, 1953). Holmes, who published the most comprehensive and thoughtful article about Barcroft’s work on Bernard’s insight (Holmes, 1961), concluded that Barcroft made two important theoretical contributions in the critical review he published in 1932 (Barcroft, 1932). First, by comparing lower animals with higher animals, he showed that higher animals maintain their internal environment by correcting disturbances, while lower animals evade the disturbing event or stimulus. Second, he offered a new view of Bernard’s ‘‘free life.’’ Noting that the recent discussion of the constancy of the internal environment by Haldane, Henderson, and Cannon focused on the means by which the internal environment was fixed, he raised the question of what the ‘‘free life’’ was for. He argued that the end was more important than the means. Citing the results of his own work at high altitude and reviewing the animal data presented in Cannon’s 1929 review, Barcroft showed that the most sensitive symptoms and signs of disturbance of the internal environment were correlated with disturbance of higher neural function (Table 1). ‘‘Thus, the fixity of the internal environment is the condition of mental activity’’ (Barcroft, 1932, p.86).
Table 1 Symptoms and signs when heat and various substances in the internal environment are deficient or excessive Environment
Deficient
Excessive
Temperature Oxygen cH
Inertia Unconsciousness Headache
Delirium – Coma
Glucose
Nervousness Feeling of ‘‘goneness’’ Hunger
–
Water
Weakness, Asher
Headache Nausea Dizziness Asthenia Incoordination
Sodium
Fever
Reflex irritability Weakness Paresis
Calcium
Nervous twitchings Convulsions
Apathy Drowsiness verging on coma General atonia
Barcroft expanded his discussion and tightened his argument in 1934 in a brilliant book, Features in the Architecture of Physiological Function (Barcroft, 1934). This is one of the great expositions of physiological thinking. Broader, deeper, and more demanding than The Wisdom of the Body, it is a classic waiting to be rediscovered. The book made it clear that, although Bernard and subsequent physiologists down to Cannon had held that the central nervous system mediated many of the efferent mechanisms necessary for the fixity of the internal environment, Barcroft was the first to say that higher brain function required the most stable internal environment. Thus, homeostasis was not only organized by the brain—homeostasis served the brain. To Barcroft this meant that a fine control of the internal environment was the prerequisite for the intellectual ascendancy of man. I believe that Barcroft made a third contribution. In 1933 when he was nearly 60 years old, Barcroft began to investigate foetal physiology. His interest was triggered by an observation during his work on the spleen’s reservoir function. He noted that the spleen of a pregnant dog was shriveled (Barcroft & Stevens, 1928). Barcroft surmised that the blood had gone to the placenta. Over the next 13 years, he pursued an intense research program in foetal physiology. This was hands-on research. In fact, he took a sabbatical leave during the Lent term of 1935 so that he could operate on 100 ewes. During that sabbatical he hung this sign on his office door: ‘‘Professor Barcroft is away from Cambridge for all purposes except research’’ (Franklin, 1953). The program was immensely productive. In 1935 he gave the Croonian Lecture on ‘‘Foetal Respiration’’ (Barcroft, 1935b) and two lectures in Dublin, one of which was entitled ‘‘Chemical Conditions of Mental Development’’ (Barcroft, 1935a). Two years later, he delivered the Terry Lectures at Yale. Their theme was the internal environment and the actions of the developing brain and they were published in 1938 as The Brain and its Environment (Barcroft, 1938). He thought that his foetal research (for details see Barcroft, 1938; Franklin, 1953; Holmes, 1961) provided new and strong support for his insight, arguing that Cannon, Henderson, and Haldane were ‘‘not particularly interested in the nature of the effects but merely in the size of the chemical or physical changes which produced them . . . [I believe] the effects are all mental or at least involve the brain’’ (p. 87). He made a strong inference in this soaring conclusion: ‘‘We have therefore arrived at the point where we can say not only that the form of life – man – which has developed an intellectual power far beyond any other, is that in which the constitution of the fluids that bathe his cells is most exactly regulated; but also that the most immediate effect of interference with chemical or physical properties of the blood is impairment of the higher qualities of the brain’’ (p. 109). Why were Pavlov and Barcroft not acknowledged?
Note: ‘‘The signs and symptoms in man if the higher or lower limits of the fixity of the internal environment are passed over . . .. The fixity of internal environment, then, is controlled by the upper part of the central nervous system which suffers if the environment alters beyond physiological limits. The fixity of the internal environment is in short the condition of mental activity’’ (Barcroft, 1934).
The failure of Cannon to acknowledge the important contributions of Pavlov and Barcroft was not due to the fact that they were unknown to him or that they had published in obscure journals. Cannon had cited Pavlov’s first book in 1911 in The Mechanics of Digestion (Cannon, 1911), and wrote the Introduction and polished the English translation of Pavlov’s later book, Lectures on Conditioned Reflexes, in 1928 that contained his Nobel lecture (Pavlov, 1928). In addition, Cannon was concerned about Pavlov’s situation during and after the Bolshevik Revolution (Cannon, 1921) and was Pavlov’s host for the International Physiological Congress in 1929 (Cannon, 1945). In Barcroft’s case, Cannon regularly cited Barcroft’s work on the spleen as a reservoir of blood and its contraction by sympathetic stimulation. They certainly met during Barcroft’s visit to Harvard in 1929 and Cannon probably attended Barcroft’s Dunham lectures.
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They spent time together in 1930 when Cannon visited Cambridge to give the Linacre Lecture (Cannon, 1930). As leaders in physiology, they must have rubbed together frequently at international meetings. I believe that Cannon failed to acknowledge Pavlov and Barcroft for different reasons. Cannon failed to acknowledge Pavlov’s conditioned reflexes in which the stimuli from the external environment could enhance the constancy of the internal environment (see above) because Cannon believed that behavioral responses to stimuli in the external environment always disturbed the internal environment. Such disturbances then had to be returned to their normal values by the sympathetic nervous system and other internal homeostatic mechanisms. Furthermore, Cannon’s homeostatic responses were all automatic and unlearned. Thus, I believe Cannon’s exclusion of learning from homeostasis accounts for his failure to acknowledge Pavlov’s contribution. This ban on learning from homeostatic mechanisms was reinforced by Richter in his influential experiments on the behavioral responses to internal deficits that had homeostatic effects (Smith, 2007). The ban was not lifted until the 1960s when the ideas and techniques of Pavlov, Skinner and Miller seeped into the investigation of visceral and behavioral homeostatic responses (Dworkin, 1993). The failure to acknowledge Barcroft in the 1929 Physiological Reviews is easily explained—Barcroft’s review did not appear until 1932. Yet this does not explain why Barcroft’s work is not discussed in the The Wisdom of the Body in 1932 except for this passing comment. ‘‘Repeatedly in foregoing chapters I have called attention to the fact that insofar as our internal environment is kept constant we are freed from the limitations imposed by both internal and external agencies or conditions that could be disturbing. The pertinent question has been asked by Barcroft, freedom for what?’’ (Cannon, 1932, p. 284). Cannon does not give Barcroft’s answer (the brain) nor describe any of his extensive evidence. Instead Cannon asserts, ‘‘It is chiefly freedom for the activity of the higher levels of the nervous system and the muscles which they govern.’’ Thus, Barcroft’s 1932 review is cited for his question, but not for his answer. In 1939, the second edition of The Wisdom of the Body appeared (Cannon, 1939). Cannon repeated what he wrote in the first edition and did not mention Barcroft’s extended, synthetic discussion of the problem in Features in the Architecture of Physiological Function (Barcroft, 1934). There is more. Cannon wrote a new chapter on ‘‘The Aging of Homeostatic Mechanisms’’ for this second edition. It opens with three sentences on the foetus. Barcroft’s extensive and novel results in the ovine foetus were not mentioned. Cannon’s exclusion of Barcroft suggests that he saw Barcroft’s work on the mechanisms that maintained the fixity of the internal environment and the fact that homeostasis served the brain as significant competition for his own ideas. Certainly Barcroft, not Cannon, had shown that the requirements for that fixity were more rigorous for the brain than for any other organ. From that Barcroft had drawn the important evolutionary conclusion that the fixity was the precondition for the ascendancy of humans beyond other animals. Cannon is such an important and likeable figure in American Physiology (Alvarez, 1932; Lusk, 1932) during the period between World Wars I and II, that he has received little, if any, negative criticism such as I raise here based on my interpretation of his citation practices. Though their meaning can be ambiguous, I believe the persistent failure to cite the work of Pavlov and Barcroft for a decade is significant and is evidence that Cannon, like other scientists, was protective of his scientific ideas. One of the ways to
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maintain a claim for originality is to ignore, perhaps unconsciously, the relevant contributions of other investigators. His failure to incorporate Pavlov’s learning mechanisms into homeostasis had a persistent and limiting effect on the investigation of autonomic mechanisms and ingestive behavior within a homeostatic framework. It was not until the 1960s that Pavlov’s ideas and techniques began to supplement the internal, automatic, and unlearned homeostatic mechanisms of Cannon in American physiology and physiological psychology.3 I know it is a long way from citation practices to intellectual limitations on later research. In this case, however, the path seems clear. Acknowledgements I thank Marcia Miller for great bibliographic assistance, James Gibbs and David Booth for constructive criticism of the penultimate version of this paper, and my Chairman, Jack Barchas, for encouragement and support. I also want to note that the late Steve Cooper’s scholarship and historical sense stimulated me to write this paper. References Adam, G. (1967). Interoception and behaviour; an experimental study. Budapest: Akademiai Kiado. Adolph, E. F. (1961). Early concepts of physiological regulations. Physiological Reviews, 41, 737–770. Alvarez, W. C. (1932). The influence of Doctor Cannon’s work upon medical thought and progress. In Walter Bradford Cannon, exercises celebrating twenty-five years as George Higginson professor of physiology (pp. 10–25). Cambridge: Harvard University Press. Bykov, K. M. (1957). The cerebral cortex and the internal organs. New York: Chemical Publishing Company. Barcroft, J. (1932). La fixite du milieu interieur est la condition de la vie libre (Claude Bernard). Biological Reviews and Biological Proceedings of the Cambridge Philosophical Society, 7, 24–87. Barcroft, J. (1934). Features in the architecture of physiological function. Cambridge: Cambridge University Press. Barcroft, J. (1935a). Chemical conditions of mental development. Irish Journal of Medical Science, 7S, 302–313. Barcroft, J. (1935b). The Croonian Lecture: Foetal respiration. Proceedings of the Royal Society, Series B, Biological Sciences, 118, 242–263. Barcroft, J. (1938). The Brain and Its Environment. New Haven: Yale University Press. Barcroft, J., & Stevens, JG. (1928). The effect of pregnancy and menstruation on the size of the spleen. Journal of Physiology (London), 66, 32–36. Booth, D. A. (2008). Physiological regulation through learnt control of appetites by contingencies among signals from external and internal environments. Appetite. Cannon, W. B. (1911). The mechanical factors of digestion. New York: Longmans Green & Co. Cannon, W. B. (1921). Pawlow is still alive. Journal of the American Medical Association, 77, 1040. Cannon, W. B. (1925). Some general features of endocrine influence on metabolism. Transactions of the Congress of American Physicians & Surgeons, XIII, 31–53. Cannon, W. B. (1926). Physiological regulation of normal states: Some tentative postulates concerning biological homeostatics. In A. Pettit (Ed.), A Charles Richet: ses amis, ses collegues, ses eleves (pp. 91–93)Paris: Les Editions Medicales. Cannon, W. B. (1929a). Organization for physiological homeostasis. Physiological Reviews, IX, 399–431. Cannon, W. B. (1929b). The sympathetic division of the autonomic system in relation to homeostasis. Archives of Neurology & Psychiatry, 22, 282–294. Cannon, W. B. (1930). The autonomic nervous system: An interpretation. Lancet, I, 1109–1115. Cannon, W. B. (1932). The wisdom of the body. New York: Norton. Cannon, W. B. (1939). The wisdom of the body (2nd ed.). New York: Norton. Cannon, W. B. (1945). The way of an investigator. New York: Hafner Publishing Company. Chernigovsky, V. N. (1967). Interoceptors. Washington: American Psychological Association. Cooper, S. J. (2008). From Claude Bernard to Walter Cannon: Emergence of the concept of homeostasis. Appetite. Dworkin, B. R. (1993). Learning and physiological regulation. Chicago: University of Chicago Press. 3 Where Cannon’s ban did not reach, visceral and autonomic conditioning flourished, e.g. in Russia (Bykov, 1957; Chernigovsky, 1967) and Hungary (A´da´m, 1967).
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Franklin, K. J. (1953). Joseph Barcroft. Oxford: Blackwell Scientific Publications. Hansen, K.M. (1923). Acta Medica Scandinavia lviii, Supplement iv. Holmes, F. L. (1961). Joseph Barcroft and the fixity of the internal environment. Journal of the History of Biology, 2, 88–122. Langley, L. L. (Ed.). (1973). Homeostasis. Stroudsburg: Dowden, Hutchinson & Ross, Inc. Lusk, G. (1932). The life of a professor. In Walter Bradford Cannon, exercises celebrating twenty-five years as George Higginson professor of physiology (pp. 45–54). Cambridge: Harvard University Press.
Pavlov, I. P. (1910). The work of the digestive glands (2nd ed.). London: Charles Griffin & Company, Limited. Pavlov, I. P. (1928). Lectures on conditioned reflexes. New York: Liveright Publishing Corporation. Smith, G. P. (2007). Introduction to four papers on Curt Richter and analysis of his scientific practice. Appetite, 49, 347–352. Woods, S. C., & Ramsay, D. S. (2007). Homeostasis: Beyond Curt Richter. Appetite, 49, 388–398.