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Selected Papers of Charles H. Best

Selected Papers of Charles H. Best

Series: Heritage
Copyright Date: 1963
Pages: 724
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  • Book Info
    Selected Papers of Charles H. Best
    Book Description:

    This volume records the achievements of forty years of medical research, giving direct and easy access to over sixty of Dr. Best's original important research papers in the fields particularly of insulin, heparin, and choline.

    eISBN: 978-1-4426-5691-8
    Subjects: Health Sciences

Table of Contents

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  1. Front Matter
    (pp. i-vi)
  2. Foreword
    (pp. vii-x)

    I am glad to respond to the request from the University of Toronto Press, for a word of introduction from me to this collection of original scientific publications by Professor Charles Best. It will be seen that, for a large proportion of these, he has shared the responsibility of authorship with various colleagues and collaborators. Such collaboration has long been common, of course, in scientific researches, and more so, perhaps, in the general field of medicine than in those of the more fundamental disciplines. It must be clear, in any case, that the need for such teamwork has been growing,...

  3. Preface
    (pp. xi-xii)
    C. H. B.
  4. Table of Contents
    (pp. xiii-xvi)
  5. Introduction
    (pp. xvii-xx)

    How pleased the friends of Professor Best will be to see this collection of his papers on insulin! Busy doctors will be thankful that here they can find a condensation of more than 70,000 articles on the same subject. Indeed how indebted will be the whole world, because, by his journeys to fifty lands, he has so publicized diabetes that most nations have become vitally concerned with its control. His later publications I shall label “Volume II,” thereby protecting him from the dangers of retirement and a pension.

    I suspect no one living can appreciate these articles as much as...

  6. 1. A Canadian Trail of Medical Research. 1959
    (pp. 1-20)

    The depth of my appreciation of this first award of the Dale Medal will, I trust, be apparent in the course of this lecture, with which your Society for Endocrinology has honoured me. Sir Henry Dale appears many times on my pathway through or around the obstacles which one meets in nearly forty years of medical research and, indeed, on several occasions he has blazed a trail for me. His great influence on the development of Canadian physiology in this century has been accomplished in large part by his publications and his innumerable discussions with biochemists, physiologists, and pharmacologists who...

  7. [Illustrations]
    (pp. None)
  8. ParT I: Insulin and Glucagon

    • [Part I: Introduction]
      (pp. 23-24)

      It so happens that many of ourhandwritten records and the original manuscript of the first communication concerning insulin are still in existence. I thought it might Toe of historical interest to reproduce as Paper 2 at least a few pages of the manuscript which Banting and 1 used at the first presentation of the findings to our colleagues in the Medical Building of the University on November 14, 1921, at a regular meeting of the Physiological Journal Club. Later we revised this slightly to put it in the form in which it appeared in the Journal of Laboratory and...

    • 2. The internal secretion of the pancreas (selected pages of the original manuscript). 1921
      (pp. 25-36)
    • 3. The Internal Secretion of the Pancreas. 1920-1922
      (pp. 37-41)
      F. G. BANTING and C. H. BEST

      1. Intravenous injections of dog’s pancreas, removed from seven to ten weeks after ligation of the ducts, invariably exercises a reducing influence on the percentage sugar of the blood and the amount of sugar excreted in the urine.

      2. Rectal injections are not effective.

      3. The extent and duration of the reduction varies directly with the amount of extract injected.

      4. Pancreatic juice destroys the active principle.

      5. Extracts made 0.1 per cent acid are effectual in lowering the blood sugar.

      6. The presence of the extract enables a diabetic dog to retain a much larger percentage of injected sugar...

    • 4. The Internal Secretion of the Pancreas. 1922
      (pp. 42-60)
      F. G. BANTING and C. H. BEST

      The hypothesis underlying this series of experiments was first formulated by one of us in November, 1920 [F. G. B., then Assistant in Physiology at the University of Western Ontario, London, Ontario], while reading an article dealing with the relation of the isles of Langerhans to diabetes [56], From the passage in this article, which gives a résumé of degenerative changes in the acini of the pancreas following ligation of the ducts, the idea presented itself that since the acinous, but not the islet tissue, degenerates after this operation, advantage might be taken of this fact to prepare an active...

    • 5. Pancreatic Extracts. 1922
      (pp. 61-72)
      F. G. BANTING and G H. BEST

      In a previous paper [40] we have reported experiments which justify the conclusion that some constituent of the pancreas destroys the active principle of the internal secretion of the gland when extracts are made of the gland by the usual methods. To eliminate these digestive substances, extracts were prepared from degenerated pancreatic tissue ten weeks after ligation of the ducts of the pancreas by which time the acinar but not the insular cells are said to have disappeared. From this material we secured small quantities of very active extract. The question of a more rapid and economical method of securing...

    • 6. Preliminary Studies on the Physiological Effects of Insulin. 1922
      (pp. 76-88)
      F. G. BANTING, C. H. BEST, J. B. COLLIP and J. J. R. MACLEOD

      In two previous papers a brief outline of the preparation of pancreatic extracts has been given. Active anti-diabetic extracts of degenerated gland, exhausted gland, foetal gland, and finally adult beef gland, were made. The main problem in the preparation was to get rid of or avoid the presence of proteolytic enzymes.

      The first extract used was obtained by ligating the pancreatic ducts of the dog, and waiting from seven to ten weeks for degeneration of the acinar tissue. The remnant, which contained healthy insular tissue, was removed and macerated in ice-cold Ringer’s solution. By this procedure a non-toxic extract which...

    • 7. Pancreatic Extracts in the Treatment of Diabetes Mellitus: A Preliminary Report. 1922
      (pp. 91-100)

      Since the year 1890, when von Mering and Minkowski [561] produced severe and fatal diabetes by total removal of the pancreas in dogs, many investigators have endeavoured to obtain some beneficial effect in diabetes mellitus, either by feeding pancreas, or by administration of pancreatic extracts.

      Minkowski, Sandmeyer [665], Pflüger [619], and others found that feeding pancreas was followed by negative or even harmful results. More recently, Murlin and Kramer [584], Kleiner [459] and Paulesco [614] have tried the effects of aqueous extracts of the pancreas intravenously, on depancreatized animals and have found transitory reduction in the percentage of blood sugar...

    • 8. The Effects of Insulin on Experimental Hyperglycaemia in Rabbits. 1922
      (pp. 102-115)

      In a previous paper it was shown that a marked fall occurs in the percentage of blood sugar in normal rabbits when they are injected subcutaneously with insulin. Taken in conjunction with the fact that insulin also reduces often to the normal level, or even below it, the high percentages of sugar found in the blood of depancreated dogs and of diabetic patients, it would appear that its action must be a fundamental one in the control of the blood sugar level [48]. The present investigation was undertaken to obtain further evidence of the scope of the action of insulin...

    • 9. The Preparation of Insulin. 1923
      (pp. 117-130)
      C. H. BEST and D. A. SCOTT

      When the Insulin Committee suggested that we should report on the recent progress in the preparation of insulin an extensive review of the history of pancreatic extracts was at first contemplated. Macleod [538], Dale [237], and others, however, have recently reviewed certain parts of the literature, and since a study of that portion of this literature which describes the preparation of the extracts shows that many of them are of minor significance in the present connection, we have decided to refer only to those investigators whose work, in our opinion, led them very near to the solution of the problem....

    • 10. The Effect of Insulin on the Dextrose Consumption of Perfused Skeletal Muscle. 1926
      (pp. 133-139)

      The experiments of Hepburn and Latchford [385], which have been confirmed by Burn and Dale [157], show that insulin accelerates the rate of disappearance of dextrose from the fluid used to perfuse the isolated mammalian heart. Burn and Dale also demonstrated that insulin greatly increases the rate of disappearance of dextrose from the circulating blood of the decapitated and eviscerated cat. Cori, Cori, and Goltz [226], working on rabbits, and Lawrence [485] and Pemberton and Cunningham [615], from clinical studies, have reported that insulin increases the loss of sugar from the blood during its passage through a limb. Frank, Nothmann,...

    • 11. The Fate of the Sugar Disappearing under the Action of Insulin. 1926
      (pp. 140-154)
      C. H. BEST, J. P. HOET and H. P. MARKS

      The apparent disappearance of sugar injected into normal animals has for a long time puzzled physiological investigators (Bang, Meltzer and Kleiner, Palmer, Woodyatt). When insulin was discovered it was apparent that an agent was available by which the normal processes could be exaggerated, and therefore more easily studied. It was soon shown that the administration of sugar and insulin to the diabetic animal resulted in an increased combustion of carbohydrate and the accumulation of glycogen in the depots. When, however, attempts were made to trace the fate of the sugar which disappears from the blood of the normal animal under...

    • 12. Oxidation and Storage of Glucose under the Action of Insulin. 1926
      (pp. 155-168)
      C. H. BEST, H. H. DALE, J. P. HOET and H. P. MARKS

      Experiments published by three of us (B., H., and M.) [92] have demonstrated that, in a spinal animal with the muscles at rest, a large part of the glucose disappearing from the circulation under the action of insulin is deposited as glycogen in the muscles. The view that the remainder, which was in most cases the larger, and in some cases the much larger part, had been oxidized, was quite compatible with the observations of Burn and Dale [157], who had measured the oxygen consumption, but not the glycogen increase, under similar conditions. It was important, however, to put this...

    • 13. Insulin in Tissues other than the Pancreas. 1932
      (pp. 170-178)
      C. H. BEST, C. M. JEPHCOTT and D. A. SCOTT

      A review of the literature, in which the distribution of insulin or insulin like substances has been discussed, reveals the fact that numerous investigators have reported the presence of these active materials in a great variety of animal and vegetable tissues. With the procedure originally used to obtain insulin from the pancreas, insulin was not obtained from other tissues (Banting and Best [41]). It was perhaps not surprising that the improved methods of extracting pancreatic insulin when applied to other animal tissues should apparently yield definite amounts of active material (Collip [211; 212; 213]; Best and Scott [114; 115]; Best,...

    • 14. Diet and the Insulin Content of Pancreas. 1939
      (pp. 180-191)

      It is well known that fasting, or feeding diets rich in fat and poor in carbohydrate, leads to a change in the metabolism of sugar as judged by (1) the glucosuria following glucose administration, (2) the diabetic type of sugar tolerance curve when glucose is given, and (3) the absence of the normal rise in respiratory quotient after glucose administration. There is evidence that the administration of insulin at least partially restores the normal metabolism of carbohydrate. An excellent review of the relevant literature has recently been published by W. H. Chambers [185].

      We have reported in a preliminary communication...

    • 15. Insulin Extractable from the Pancreas and Islet Cell Histology. 1954
      (pp. 193-203)

      The characteristics of diabetes mellitus in man have long been compared, either directly or by inference, with those of diabetes produced in animals by experimental means. From the earliest studies in this field by von Mering and Minkowski [561], in the work leading to the discovery of insulin [40] (1921), and in many later investigations, the dog has occupied a prominent and productive place among experimental animals. In recent years, special aspects of the spontaneous diabetes of dogs have come under study of this laboratory and in that of Professor Henry Ricketts in Chicago. It is the purpose of this...

    • 16. Extractable Insulin of the Pancreas and Effectiveness of Oral Hypoglycaemic Sulphonylureas in the Treatment of Diabetes in Man—A Comparison. 1956
      (pp. 204-211)
      G. A. WRENSHALL and C. H. BEST

      The effectiveness of l-butyl-3-p-aminobenzene-sulphonylurea (BZ-55, U-6987, carbutamide) and l-butyl-3-p-tolylsulphonylurea (U-2043, orinase) in lowering the blood glucose level and the excretion of glucose in the urine of some but not all diabetic human subjects has been reported [67; 309] and confirmed [457; 564; 568]. The positive response to these Sulphonylureas of some but not all diabetic subjects has been interpreted in terms of the presence or absence of a significant supply of endogenous insulin, the effectiveness of which, if present, is restored or enhanced by the sulphonylurea therapy [67; 309; 570].

      The purpose of this paper is twofold: (1) to indicate...

    • 17. A Study of the Prevalence of Diabetes in an Ontario Community. 1951
      (pp. 213-228)
      A. J. KENNY, A. L. CHUTE and C. H. BEST

      Diabetes mellitus is not a reportable disease and an accurate estimate of its prevalence is difficult to obtain. Death rates are available for most countries and for several large cities. These figures have been used to calculate the incidence of diabetes. There are, however, two main sources of error for which allowance must be made in such a calculation. First, because the diagnosis of diabetes is frequently omitted from death certificates in cases dying from another cause, mortality figures may understate the incidence. Joslin [433] showed that this understatement may be as high as 37 per cent. Secondly, the calculation...

    • 18. The Prevention of Diabetes. 1941
      (pp. 230-243)
      R. E. HAIST and C. H. BEST

      An article under the title, “The Prevention of Diabetes” was published some eight months ago from our department. The paper was expected to provoke discussion and this expectation has been realized. We are anxious to stimulate interest in the possibility of preventing diabetes, since from the point of view of public health this is the most important aspect of the diabetic problem. Because the discussion of this problem had centred around treatment rather than prevention we brought together certain experimental data which indicated that, in animals, diabetes produced by the only means at present available can be prevented by certain...

    • 19. The Protein Anabolic Effect of Testosterone Propionate and its Relationship to Insulin. 1953
      (pp. 245-250)

      Since Kochakian and Murlin [461; 462; 463] performed their fundamental experiments on castrate dogs it has been well established that administration of androgenic substances causes a fall in the non-protein nitrogen (NPN) level in blood and at the same time lowers the nitrogen excretion in the urine. It is well known also that insulin has a very similar effect when injected into the diabetic organism (Falkenhausen [297], Chaikoff and Forker [182])—in other words, insulin and the male sex hormone may, under certain circumstances, exert a similar protein anabolic effect. The interrelationship between testosterone propionate and insulin has therefore been...

    • 20. The Pathologic Effects of Large Amounts of Glucagon. 1957
      (pp. 252-259)

      The work of Ingle [415] and Cavallero [178] has shown that glucagon will produce a temporary or mild glucosuria in partially depancreatized animals and in animals pretreated with cortisone, but a significant diabetogenic action of glucagon administered alone to intact rats has not previously been shown.

      The results of early attempts made in our laboratory to show a diabetogenic action of the pancreatic hyperglycaemic factor were disappointing. We reinvestigated the problem using much larger doses of glucagon attempting, at the same time, to prolong its activity by suspending it in corn oil and administering it subcutaneously at eight-hour intervals. Glucagon...

    • 21. Glucagon and Metaglucagon Diabetes in Rabbits. 1960
      (pp. 261-268)

      Early attempts in this and other laboratories to demonstrate a diabetogenicaction of glucagon have met with limited success. It was found that in order to produce a temporary diabetes with glucagon it was necessary either to force-feed [662; 178] the animals or to administer cortisone simultaneously [490].

      Investigations described here differ from previous ones in that glucagon administration began on the second postnatal day and was continued for many months. Our purpose was to obtain additional information concerning the atrophy of alpha cells which follows prolonged treatment with glucagon [508]. We were, however, surprised to find that the anorexia produced...

    • 22. Effect of Insulin and Glucagon on Tumour Growth. 1958
      (pp. 270-274)
      J. M. SALTER, R. DE MEYER and C. H. BEST

      During the past few years we have been working on certain problems related to both insulin and glucagon (Salter and Best [660]; Salteret al.[661; 662]; Davidsonet al.[247]). There is considerable evidence in the earlier literature that insulin may cause some inhibition in the growth of malignant tissue (Piccaluga and Cioifari [621]; von Witzleben [812]; Silbersteinet al.[704]; Gomes da Costa [325]).f The results of experiments carried out in this laboratory are in general agreement with these earlier reports. We find that, although the effects of giving insulin to rats bearing the Walker carcino-sarcoma vary considerably,...

    • 23. Effect of Prolonged Administration of Tolbutamide in Depancreatized Dogs. 1959
      (pp. 276-285)

      In a preliminary communication [712] we have reported that depancreatized dogs treated with tolbutamide for prolonged periods showed derangements of liver function. The present paper gives a detailed account of our studies on twelve depancreatized dogs treated orally with various doses of the drug. When given relatively large doses, the animals required appreciably smaller amounts of exogenous insulin to maintain a standard degree of control.

      The series represents a total of sixteen dogs and consists of the following groups of animals:

      1. Depancreatized adult dogs :

      (a) Two dogs maintained on 150 mg per kilogram body weight of tolbutamide; (b)...

    • 24. A Clinical Assessment of Foetal Calf Insulin. 1961
      (pp. 287-291)
      J. M. SALTER, O. V. SIREK, M. M. ABBOTT and B. S. LEIBEL

      Early in their original work with insulin, Dr. Banting and Dr. Best were confronted with the problem of discovering a source of the hormone to meet the inevitable demands of the diabetic population throughout the world. At that time, the extraction of insulin seemed to depend upon the prior elimination of the external secretory portion of the pancreas. With this in mind Banting and Best, while working alone, explored the possibilities that foetal pancreas, before the development of its exocrine function, might provide a useful source of the hormone. Although foetal calf insulin was prepared in 1921 and used with...

    • 25. The Late John James Rickard Macleod (Obituary). 1935
      (pp. 292-293)
      C. H. BEST

      John James Rickard Macleod spent ten of the most active years of his life in the University of Toronto. His research work was extensive and productive and his lecturing programme heavy. He was a particularly able teacher and his classes will long be remembered by those students who were fortunate enough to pass through his hands.

      Professor Macleod was born in Cluny, near Dunkeld, Scotland, September 6, 1876. He received his early education in Aberdeen Grammar School and later graduated in Medicine from Aberdeen University. He was awarded the Anderson Travelling Fellowship and spent a year in the Physiology Institute,...

    • 26. Frederick Grant Banting, 1891-1941. 1942
      (pp. 294-301)
      C. H. BEST

      Frederick Grant Banting was born on November 14, 1891, on a farm near the town of Alliston, Ontario. His father, William Thomas Banting, was of Irish extraction, and his mother, Margaret Grant, of Scottish ancestry. Banting attended the rural school and the high school in Alliston. He had a remarkably robust physique and a most inquiring mind, both of which were to stand him in good stead in later life. He was fond of athletic exercise in his early days, but in later life spent little time in recreations with the exception of drawing and painting. He entered the University...

    • 27. Reminiscences of the Researches Which Led to the Discovery of Insulin. 1942
      (pp. 305-310)
      C. H. BEST

      The Editor’s invitation to contribute some “personal notes” for the Banting Memorial Number of theCanadian Medical Association Journalstimulated me to look over the notebooks which Banting and I kept in the Department of Physiology from May 17, 1921, to January 1, 1922.

      Banting’s modesty was apparent from the very start of the investigations. Our first problem was to look over the literature in the attempt to get a better idea of the various operative procedures which had been used in work on the pancreas. Professor Macleod informed me that Banting felt he would have to depend entirely upon...

    • 28. The Banting Memorial Lecture: Insulin and Diabetes—in Retrospect and in Prospect 1945
      (pp. 311-323)
      C. H. BEST

      In this fourth Banting Memorial Lecture we again pay tribute to the accomplishments of our late colleague. As I wrote at the time of his death, his chief monument will be in the minds of young men stimulated by his brilliant and fearless career and in the hearts of successive generations of diabetics who owe so much to him. The number of more tangible tributes steadily increases. In addition to those in our own University¹ which are well known to you, there are: the Banting Memorial Lecture of the American Diabetes Association, the Banting Memorial Home for Convalescent Diabetics—projected...

    • [Illustrations]
      (pp. None)
    • 29. The Banting Memorial Lecture: Insulin. 1952
      (pp. 324-339)

      The personality of Frederick Grant Banting made such a lasting impression upon those of us who knew him well that it is difficult to realize that it is more than eleven years since he left us. These memories, obtained from many points of vantage, will all be clear and in the forefront of our minds. Some of you knew him when he was fulfilling the promise of his earlier years. A few of us knew him before he became Canada’s most famous scientific son. I have my own vivid memories, particularly of our work together in the spring, summer, and...

    • 30. Diabetes since 1920. 1960
      (pp. 340-349)

      I would like to begin by making one deferential bow to the past, to the work of Professor Oskar Minkowski who, with von Mering, laid the foundation for the study of experimental diabetes [561]. The University of Toronto donated all of its rights for insulin in Germany to an Insulin Committee formed in that country in 1922, and Professor Minkowski was the first chairman. Recently my friend, Dr. Martin Goldner, told the story of his own observations on the day when Professor Minkowski received his first small parcel of insulin from Toronto. The professor held up a vial of insulin...

    • [Illustrations]
      (pp. None)
    • 31. Insulin and Glucagon: A Review. 1960
      (pp. 350-359)

      Ever since 1921 successive attempts to delineate the place of insulin in the physiology of the mammalian organism have been characterized by marked shifts in emphasis as new aspects of its action have come to light. The pace of discovery has been accelerating in recent years, but much remains to be elucidated. By what mode, or modes, of action insulin brings about its bewildering variety of effects will not, in all probability, be known for many years. Neither the mechanism of its secretion from the beta-cell, nor the factors concerned with “resistance” to the hormone are well understood.

      The discovery...

    • 32. The Future in the Field of Diabetes. 1962
      (pp. 360-364)

      Many people have asked me what advances are likely to be made in the field of diabetes. Predictions in this field cannot be made with any more certainty than other prognostications, but after forty years I may be justified in hazarding some guesses as to the course developments will take. In recent years I have recorded a series of unsolved problems which the presentations of my colleagues and surveys of the literature have brought to my mind. Hundreds of useful investigations became obvious but I shall attempt here to list only a few of the important advances which will, I...

  9. Part II: CholinE and Lipotropic Phenomena

    • 33. A Brief History of the Discovery of the Lipotropic Factors. 1962
      (pp. 367-374)

      Professor G C. Lucas, Dr. Jessie H. Ridout, and I had planned for many years to write, and had even started, a book entitled “Choline and its Dietary Precursors: The Lipotropic Factors” The following account of certain historical aspects and of the personalities involved in the lipotropic story is taken, with the consent of my colleagues, from that unborn monograph.

      The centres of interest in the ground to be covered are now so numerous that some aid to orientation is a necessity for newcomers to the field. It may be helpful to mention some of the explorers whose efforts have...

    • 34. The Effect of Lecithine on Fat Deposition in the Liver of the Normal Rat. 1932
      (pp. 375-384)

      The very interesting effects of some component of crude lecithine upon the condition of diabetic animals have been discussed in previous communications from this laboratory (Hershey [387]; Hershey and Soskin [388]; Best and Hershey [89]). The symptoms exhibited by these animals and the autopsy findings indicate that the characteristic condition is largely attributable to failure of liver function. The results of these studies suggested that an investigation of the effect of lecithine on deposition of fat in the livers of normal animals might be profitable. The literature relevant to this subject has been reviewed in the monographs by Leathes and...

    • 35. The Effects of the Components of Lecithine upon Deposition of Fat in the Liver. 1932
      (pp. 385-391)

      The results of the experiments in which purified lecithine from two sources, egg-yolk, and fresh beef liver, has been shown to prevent deposition of fat in the livers of normal rats (Best, Hershey, and Huntsman [91]) have led us to study the effects of feeding various components of lecithine. It appeared possible that the oleic or other unsaturated fatty acid, the glycerophosphate, the choline, some combination of two or more of these factors, or die whole lecithine molecule, might be the active agent. The general procedure in this series of experiments has been to substitute for the lecithine in the...

    • 36. Choline and the Dietary Production of Fatty Livers. 1934
      (pp. 392-403)

      The production of fatty livers in rats by the administration of a diet consisting of mixed grain and 40 per cent of beef fat has been demonstrated by Best, Hershey, and Huntsman [91]. The work of other authors has shown that fatty livers may be produced by feeding animals on diets containing cholesterol. Thus the results of Chalatow [184], Anitschow and Chalatow [14], Bailey [36], McMeans [543], Yuasa [823], and Kimura [452] all show directly or indirectly that diets containing cholesterol cause a change in the nature or an increase in the amounts of the liver lipoids. More recently Okey...

    • 37. The Distribution of Choline. 1935
      (pp. 404-411)

      Interest in the total choline content of animal and plant tissues has been aroused by recent investigations which have demonstrated the importance of choline as a dietary constituent. Previous estimates of the choline content of various tissues have been largely concerned with the determination of free choline (Alles [11]; Guggenheim [337]). More recently there have been some attempts to measure free and bound choline separately. The methods used for the separation of free and bound choline are complex and tedious and the separation is apparently unnecessary for the purpose of dietetic experiments on normal animals. Consequently an attempt has been...

    • 38. The Effects of Cholesterol and Choline on Liver Fat. 1936
      (pp. 412-418)

      The results of the first investigation of this problem (Best and Ridout [111]) indicated that large doses of choline or betaine inhibited the deposition of “fat” in the liver produced by feeding cholesterol. These results were confirmed and extended by Best, Channon, and Ridout [80], who noted that under certain experimental conditions the esters of glycerol were more readily affected than those of cholesterol. Channon and Wilkinson [194] found, however, that in certain short-term experiments the rate of removal of cholesteryl esters was not accelerated by choline, while a very slight effect was exerted on the glyceride fraction. These results...

    • 39. The Effect of Anterior Pituitary Extracts on the Liver Fat of Various Animals. 1938
      (pp. 419-436)

      In a previous investigation Best and Campbell [78] studied the action of a ketogenic extract of the anterior pituitary gland which produced an intense infiltration of fat and a rapid increase in the size of the livers of fasting rats. Daily administration of this extract for a period of 3 days to forty-seven fasting white rats resulted in a fourfold increase in total liver fat over the corresponding value in the same number of control animals. The subsequent observations of MacKay and Barnes [529] and of Fry [313] have confirmed these results.

      The present study is chiefly concerned with the...

    • 40. A Study of the Source of Liver Fat Using Deuterium as an Indicator. 1938
      (pp. 437-451)

      One of the many problems arising out of the recent researches carried out in the Department of Physiology and in this department is the source of the fat which accumulates in the liver when animals are maintained on a diet poor in lipotropic factors and when certain extracts of the anterior pituitary gland are administered. This problem may be attacked by the use of “labelled” fatty acids. While there are several methods of preparing these “ear-marked” molecules, none of these possesses all the advantages which may be secured by the use of deuterium.

      This communication consists of two parts. In...

    • 41. The Lipotropic Action of Methionine. 1940
      (pp. 452-457)

      In 1937 Tucker and Eckstein [760] demonstrated that methionine exerts a lipotropic effect. This has been confirmed in our laboratory¹ and by Channon, Manifold, and Platt [189]. The latter workers have shown that methionine, under the conditions of their experiments, exerted very little effect upon the deposition of fat in the liver unless the basal diet was such that large amounts of fat were deposited in the livers of the control animals. We have been interested in the lipotropic effects ofd-andlmethionine and in the failure of large doses of the racemic mixture to produce greater effect than...

    • 42. The Mode of Action of Lipotropic Agents. Proof of the in Vivo Incorporation of Triethyl-β-hydroxyethyl-ammonium Hydroxide into the Phospholipid Molecule 1947
      (pp. 458-473)
      C. S. McArthur, C. C. Lucas and C. H. Best

      Several theories have been proposed to account for the lipotropic action of choline, betaine, methionine, inositol, and other compounds which exert similar effects on the deposition of lipids in the liver. The discovery (Hershey [387]; Hershey and Soskin [388]) reported from the laboratory of one of us (C. H. B.) that lecithin prevents the accumulation of excessive amounts of fat in the liver of depancreatized dogs seemed to offer support for the hypothesis, originally advanced by Leathes, that fatty acid transport involves incorporation of these compounds into the phospholipid molecule. The demonstration by Best and Huntsman [94] that choline is...

    • 43. Hypertension of Renal Origin in Rats Following less than One Week of Choline Deficiency in Early Life. 1949
      (pp. 474-479)

      The production of arterial hypertension by dietary deficiency alone has not previously been demonstrated. Since the report by Griffith and Wade [335] it has been well established that choline deficiency produces severe renal lesions in young rats (György and Goldblatt [342]; Engel and Salmon [289]; Handler [352]; and others). A careful study of the blood pressures of rats maintained for long periods on diets low in choline has been made by Sobin and Landis [718], who found no evidence of hypertension. The results of earlier studies by Honorato and Vadillo [395] apparently support this same conclusion. Stimulated in part by...

    • 44. Liver Damage Produced by Feeding Alcohol or Sugar and its Prevention by Choline. 1949
      (pp. 480-493)

      One of the first suggestions that over-indulgence in alcoholic beverages may damage the liver was made in 1836 by Thomas Addison [6] physician to Guy’s Hospital, London. He wrote: “With respect to the causes of this fatty degeneration of the liver, very little, or absolutely nothing, is known. In most of the cases which I have met with, there has been either positive or strong presumptive evidence that the individual had indulged in spirit drinking; and indeed the most exquisite case I ever saw in a young subject occurred in a female who had for some time subsisted almost exclusively...

    • 45. Effects of Dietary Protein, Lipotropic Factors and Re-alimentation on Total Hepatic Lipids and Their Distribution. 1955
      (pp. 494-509)

      Interest in the distribution of fat within the liver lobule has been stimulated by the observation that in the widespread disease kwashiorkor the stainable fat is found predominantly in the periportal regions. This subject has recently been reviewed by Brock [149]. It is, of course, a long step from the distribution of fat in the liver of the human infant to that seen in the rat, even when an attempt is made to utilize diets similar to those that produce the characteristic lesions in the human liver. The initial distribution of fat under standardized experimental conditions may not be the...

    • 46. Lipotropic Dose-Response Studies in Rats: Comparisons of Choline, Betaine and Methionine 1956
      (pp. 510-517)

      Some years ago a comparison of the potency of the lipotropic agents was made by Best, Lucas, Ridout, and Patterson [105]. The basal diet fed to their rats is now known to have been deficient in the newer B vitamins. Moreover, the protein mixture adopted was purposely designed so that the rats would merely maintain their weight. This was done because Griffith and his co-workers [333; 583] and Beveridge, Lucas, and O’Grady [122] had noted that factors which affect appetite and rate of growth influence the choline requirement of an animal. The effect of caloric intake on the requirement was...

    • 47. Kwashiorkor Type of Fatty Liver in Primates. 1958
      (pp. 520-526)

      Kwashiorkor is today one of the most serious and widespread diseases of infancy in the world. The nutritional basis for the disease is generally accepted but debate continues as to whether the malady is due primarily to a disproportion between total protein and caloric intake, whether an imbalance of amino acids is involved, or whether a deficiency of some unidentified food factor contributes to the problem. Clinical studies are being conducted in many centres but with the exception of one preliminary report [549] no experimental investigations using primates are known to us.

      One of the characteristic features of kwashiorkor is...

    • 48. The Croonian Lecture: The Lipotropic Agents in the Protection of the Liver, Kidney, Heart and Other Organs of Experimental Animals. 1956
      (pp. 527-544)

      The award of the Croonian Lectureship has given me exceptional pleasure and a sense of great responsibility. In selecting a title I have considered the principal subjects in which I have endeavoured to keep abreast, and the choice has thus been narrowed to insulin and experimental diabetes, heparin and thrombosis, and the dietary factor choline and its precursors, which we have termed the lipotropic agents. Certain of the effects of these three substances might be discussed in a single lecture, since they all affect either the formation, distribution, or the sate of fat in the body. The action of a...

  10. Part III: Other Physiological Studies

    • 49. Observations on Olympic Athletes. 1929
      (pp. 548-556)

      The results of the experiments of Furusawa, Hill, and Parkinson [316] at Cornell indicated that observations, by electrical timing methods, on the world’s fastest sprinters, might be of considerable physiological interest. One of us (C.H.B.) had hoped to collaborate with Hill in studies of this kind at the Amsterdam Olympic Games, but it was found impossible to make the necessary arrangements. At these games the 100-metre and the 200-metre events were won by Percy Williams, who since has several times equalled the world’s record for the indoor 60-yards race. The women’s 400-metre relay event was won by the Canadian team,...

    • 50. The Nature of the Vaso-Dilator Constituents of Certain Tissue Extracts. 1927
      (pp. 558-577)
      C. H. BEST, H. H. DALE, H. W. DUDLEY and W. V. THORPE

      It has long been known that simple watery or alcoholic extracts of various organs of the body produce a pronounced depressor action when injected intravenously, especially in the carnivora. Oliver and Schäfer [605] observed such an action with an extract of thyroid gland, Mott and Halliburton [580] with extracts of brain and nervous tissues, Vincent and Sheen [775] with extracts from liver, muscle, and various glandular organs, and other observers with a wide range of organs from different species. The suggestion that these effects were explained by the presence of choline in such extracts was shown to be inadequate by...

    • 51. The Disappearance of Histamine from Autolysing Lung Tissue. 1929
      (pp. 578-585)

      The presence of histamine in extracts of normal lung accounts for a very large proportion of the vasodilator activity of these extracts. The physiological significance of the occurrence of histamine in normal tissue has been discussed by Best, Dale, Dudley, and Thorpe [82]. The question of changes in the amount of histamine in lung tissue during autolysis has not previously been investigated, and it was thought that interesting information might be obtained from a study of this problem. The effect of autolysis of minced lung tissue on the naturally occurring and on added histamine is recorded in this communication. It...

    • 52. The Inactivation of Histamine. 1930
      (pp. 586-609)
      C. H. BEST and E. W. McHENRY

      The transient effects produced by the intravenous or subcutaneous injection of small or moderate doses of histamine suggest that the body may possess an efficient means of elimination or inactivation of this substance. When histamine is slowly injected intravenously, relatively large amounts can be administered without the appearance of the characteristic signs which the more rapid injection of small quantities to the same animal produce. It has been reported that very little histamine is found in the urine even after the intravenous injection of large doses of the substance (Oehme [602]). The possibility that the amine may be eliminated by...

    • 53. Preparation of Heparin and its Use in the First Clinical Cases. 1959
      (pp. 613-623)

      Many of us who were friends of the late Dr. Jay McLean, had looked forward with great pleasure to seeing him again at this time and to discussing the problems which occupied so much of his attention. We all join Dr. Wright in paying tribute to Dr. McLean, the discoverer of heparin, and to Professor W. H. Howell and his colleagues, who extended this work and focused our attention on many of the most important problems in this field. A number of years ago Dr. McLean wrote to me and asked if we would take the responsibility for his collection...

    • 54. Heparin and the Thrombosis of Veins Following Injury. 1937
      (pp. 624-644)
      G. D. W. MURRAY, L. B. JAQUES, T. S. PERRETT and C. H. BEST

      While it is well established that heparin increases the coagulation time of blood, little or no experimental work on the effect of this anticoagulant on the thrombosis of blood vessels resulting from injury to the intima has been carried out. It has been shown by Zahn [824], Eberth and Schimmel busch [277], Welch [790], and Zurhelle [830] that thrombosis of blood vessels may be produced by the application of caustics or by mechanical injury to the intima. These procedures result in the accumulation of blood platelets on the wall of the vessel at the point of injury. Leucocytes then collect...

    • 55. Heparin and the Formation of White Thrombi. 1938
      (pp. 645-654)

      The results of a previous investigation of the action of heparin in preventing thrombosis of blood vessels in dogs (Murrayet al.[589]) led us to make a further study of this problem. In this paper we wish to discuss the effects of the anticoagulant upon the formation of white thrombi, which takes place with great regularity when blood is made to pass through glass, collodion, or cellophane tubes. The only previous investigation of this aspect of the problem is that of Shionoya [701]. Rowntree and Shionoya [655], using rabbits as experimental animals, studied the accumulation of platelets when the...

    • 56. Heparin and Coronary Thrombosis in Experimental Animals. 1938
      (pp. 655-660)
      D. Y. SOLANDT and C. H. BEST

      It has recently been shown that thrombosis of peripheral veins in dogs, produced by chemical or mechanical injury to the intimai surface, may in large part be prevented by the administration of solutions of highly purified heparin (Murray, Jaques, Perrett, and Best [590]). The accumulation of platelets which takes place in a glass shunt inserted between an artery and a vein in the monkey, dog, or cat is much reduced when the animal is adequately heparinized (Best, Cowan, and Maclean [81]).

      In embarking upon a study of study of thrombus formation in arteries our attention was focused on the coronary...

    • 57. Experimental Exchange Transfusion Using Purified Heparin. 1938
      (pp. 661-669)

      A description has already been given of experimental “exchange” transfusions between nephrectomized and normal dogs (Thalhimer [748]). Purified heparin injected intravenously as an anticoagulant prevented thrombus formation, in some experiments for many hours, and caused no toxic symptoms. The purpose of the experiments was to determine whether blood-urea could be reduced in the nephrectomized dog, and whether this non-protein nitrogenous substance which the normal dog received would be excreted rapidly. Although only a comparatively small amount of blood was exchanged in each direction, the results indicated that the study might profitably be extended, using a pump which made possible the...

    • 58. The Canadian Project for the Preparation of Dried Human Serum for Military Use. 1942
      (pp. 671-676)

      Canadian project for the preparation of serum for military use was in the Departments of Physiology and Physiological Hygiene after the outbreak of war. The expenses were secured from the funds which were available for use in the Departments. The were obtained from the members of the undergraduate body of the As the demands of the work became greater, an application grant in aid was made to the Blood Storage Committee of the National Council of Canada. This organization provided a part of the for a period of some three months, and then recommended that Department of National Defence should...

  11. Part IV: General Papers

    • 59. A Short Essay on the Division of Naval Medical Research in the Royal Canadian Navy. 1962
      (pp. 679-683)

      The “keel” of this Division was laid in the autumn of 1940 when it became evident, as a result of several trips to sea, that a group trained in various aspects of medical research could make valuable contributions to many operational problems confronting the Navy, This plan was discussed with the Medical Director General of the Royal Canadian Navy, Surgeon- Captain Archie McCallum, and with the Hon. Angus L. MacDonald, Minister of Naval Affairs. I well remember the evening on which Fred Banting and I went to see Angus L. The Minister and his wife gave us a warm welcome...

    • 60 The Organization of Physiology. 1954
      (pp. 684-689)

      We are all proud to work in such a vital and rewarding field, and we look back with considerable pleasure on what has been accomplished. . . . One could describe, in the fields with which he is most familiar, many advances which probably will be made in the next five years.... I am thinking first of research; but our subject — Physiology — will, of course, advance by good teaching, which will train our successors, quite as much as by contemporary research. Indeed the two are usually inseparable.

      We should be concerned here not with the titles given to the university...

    • 61 Convocation Address at the University of Maine, August 12, 1955. 1956
      (pp. 690-696)

      President Hauck, Members of the Faculty, Ladies and Gentlemen:

      The very great honour which you have just given me is most deeply appreciated. I have always valued my intimate associations with this truly beautiful state of Maine, where my Canadian parents were living when I was born and where I spent a very happy childhood. Now, as an Honorary Alumnus of the University of Maine, I shall have an even keener interest in what goes on here, particularly, of course, in teaching and research in the biological fields. When one is born in this country of Canadian parents, one has...

  12. Part V: EPILOGUE
    (pp. 699-700)

    The selection of the papers to be reprinted brought clearly to my mind all my former colleagues and graduate students with whom I have worked over the last forty-two years. These scientists are now in some thirty different countries and the accounts of their visits to us and ours to them have been carefully preserved in my wife’s diary. My visits to England would not be the same without my former mentors, Sir Henry Dale and Professor A. V. Hill in London. Over the years I have had many good discussions of our mutual scientific interests with Professor Frank Young...

  13. Bibliography
    (pp. 701-723)