Fletcher, Walter Morley

(b. Liverpool, England, 21 July 1873; d. London, England, 7 June 1933)

physiology.

Fletcher was the youngest of six sons in a family of ten children born to Alfred Evans Fletcher and his wife, Sarah Elizabeth Morley, cousin of the philanthropist Samuel Morley and of the future prime minister H. H. Asquith. Both parents were Congregationalists from Yorkshire. Fletchcer’s father, who in 1851 had won the gold medal in chemistry at University College, London, was inspector of alkali works for the local government board in Liverpool and later served as chief inspector in London.

Fletcher was educated at University College School in London, where he did not win great distinction, and in 1891 matriculated with a subsizarship at Trinity College, Cambridge. An elder brother, Herbert, had preceded him at Cambridge and, before going on to a medical career, had briefly pursued physiological research in the laboratory founded and directed by Michael Foster. Although Walter also intended to qualify for medical practice, physiology was from the first his chief aim.

Fletcher’s intellectual powers matured rapidly in the Cambridge setting, and he took a first class in both parts of the natural sciences tripos in 1894 and 1895. After graduating B.A. in 1894, he was elected to the Coutts Trotter studentship in 1896 and to fellowship of Trinity College in 1897. In the same year he won the Wallingham Medal and an open scholarship at St. Barholomew’s Hospital, where by 1900 he had completed the clinical studies required for medical qualification. During this period Fletcher also taught at Cambridge. He received the M.A. from Cambridge in 1898, M.B. in 1900, M.D. in 1908, and Sc. D. in 1914. He was named senior demonstrator in physiology in 1903 and served as tutor at Trinity College from 1905 to 1914. He was elected a fellow of the Royal Society in 1915 and gave the Croonian lecture in the same year. Of the students strongly influenced by Fletcher, the most notable is A. V. Hill, who won the Nobel Prize in medicine or physiology in 1922.

Fletcher left Cambridge and original research in 1914, when he was appointed first secretary of the Medical Research Committee, created in 1913 under terms of the National Insurance Act of 1911. He had already demonstrated his organizing powers in administrative work for Trinity College and the University of Cambridge. This previous experience was fortunate, for Fletcher was almost immediately required to mobilize the Medical Research Committee for the war effort. His success was recognized by the award of the K.B.E. in 1918. Of the work done for the committee during the war, Fletcher was particularly intrigued by that which established the cause of rickets, and he thereafter took a special interest in research that offered solutions to nutritional problems.

After the war Fletcher played an important role in securing a new charter for the committee, by which it was freed from the control of the Ministry of Health and established as the independent Medical Research Council under the aegis of the Privy Council (1920). He was criticized for a certain impatience with research that had no immediate practical benefit and for his sometimes naïve optimism about the clinical value of some basic research, but his contributions were on the whole very highly regarded. Until his death in 1933, he wrote an admirable introduction to each of the annual reports of the committee (and later the council).

Fletcher also served on a number of other important government bodies, including the Royal Commission on the Universities of Oxford and Cambridge (1919–1922) and the Indian Government Committee on the Organization of Medical Research (1928–1929), of which he was chairman. In the latter role he helped secure a private gift of £250,000 for research on leukemia. The trustees of the Sir William Dunn Foundation and the Rockefeller Foundation depended heavily on his advice in giving funds for biochemical laboratories at Oxford and Cambridge and for the London School of Hygiene and Tropical Medicine. Fletcher was appointed C.B. in 1929 and received honorary doctorates from the universities of Oxford, Edinburgh, Glasgow, Leeds, Birmingham, and Pennsylvania. In 1904 he married Mary Frances Cropper, who later attracted attention for her popular writing on religion, and by whom he had one son and one daughter.

Like his brother Herbert, Fletcher was a distinguished athlete in track and field, and this may have encouraged his interest in the problem of muscular metabolism and fatigue. All of his published research papers, with the exception of two early notes dealing with minor aspects of the involuntary nervous system, are devoted to this problem. His first major investigation, published in 1898, was the basis for his election to the Trinity fellowship. It presented a serious challenge to the prevailing conception of muscular metabolism, for which the German physiologists Ludimar Hermann and E. F. Pfluger were chiefly responsible. They supposed that there was in muscle a large and complex “inogen” molecule which stored up intramolecular oxygen and then exploded upon contraction to yield the recognized end products of muscular metabolism, chiefly carbon dioxide, water, and lactic acid. This basic conception had been extended by Max Verworn to other tissues, and the general phenomena of cellular metabolism were considered so complex as almost to defy experimental analysis.

The work that led to these ideas was open to the same general criticism that Claude Bernard had applied to the way some German physiologists approached the study of digestion. Their exclusive concern with the initial and end points of the process, said Bernard, was like trying to find out what went on in a house by observing what went in the door and what came out the chimney. Similarly, but without overtly discussing the theoretical implications of his work, Fletcher showed in 1898 that the prevailing theory of muscular metabolism was based on an inadequate understanding of the events taking place between the beginning and the end of the process. He was able to prove this point by adapting for his own uses a sensitive apparatus recently devised by the Cambridge plant physiologist F. F. Blackman for studying the gaseous exchange of leaves. With this apparatus, which made it possible to measure the discharge of even small quantities of carbon dioxide at frequent intervals, Fletcher showed that there was no sudden discharge of carbon dioxide upon contraction but, rather, that most of it was discharged gradually during the process of recovery from fatigue.

All of Fletcher’s later research can be considered an extension of this paper. In 1902 he showed that an excised frog muscle would contract and relax in the absence of oxygen but that oxygen greatly facilitated its recovery from fatigue. The next important step was to measure simultaneously the discharges of carbon dioxide and of lactic acid during and after contraction and to study the relationship between them. For this work, which required the development of new methods, Fletcher secured the cooperation of the eminent Cambridge biochemist Frederick Gowland Hopkins.

In 1907 they showed that the confusing and often contradictory results obtained by earlier workers on lactic-acid fatigue could be traced largely to their treatment of the muscle before or during extraction. All of the previous methods—maceration, boiling, and alcohol solutions—tended to stimulate the artificial production of lactic acid and thus to obscure the entire process. They found that the muscle could be preserved in a truly resting and uninjured state by plunging it into ice-cold alcohol. In such a muscle they found very little lactic acid. As the muscle was stimulated to a series of contractions, they found a steady increase in the amount of lactic acid up to a certain maximum, at which irritability was lost. If the fatigued muscle was then placed in oxygen, the lactic acid was greatly reduced, irritability was restored, and carbon dioxide was evolved. The process could be repeated endlessly with the same results. Fletcher and Hopkins concluded that “excised but undamaged muscle when exposed to sufficient tension of oxygen has in itself the power of dealing in some way with the lactic acid which has accumulated during fatigue” (“Lactic Acid in Amphibian Muscle” p. 297).

In 1914, with G. M. Brown, Fletcher showed that none of the processes leading to the discharge of carbon dioxide was directly related to muscular contraction itself. In an extension of his earlier paper with Hopkins, he argued that the absorption of oxygen and the evolution of carbon dioxide were related instead to the removal of lactic acid and other fatigue products. With this established, Fletcher finally criticized the “inogen” theory directly. In a joint Croonian lecture to the Royal Society in 1915, Fletcher and Hopkins incorporated all of this and other work into a new synthesis. They emphasized above all that the main biochemical processes involved in muscular contraction were really quite simple and amenable to experimental analysis. No resort need be made to some complex and hypothetical “inogen” molecule. This point of view greatly stimulated further work on muscular metabolism and on cellular metabolism in general, and Fletcher’s basic conception and approach have survived the alterations in detail which that further work inevitably produced.

BIBLIOGRAPHY

I. Original Works. Fletcher’s scientific papers are few enough that all may be cited here: “Preliminary Note on the Motor and Inhibitor Nerve Endings in Smooth Muscle,” in Journal of Physiology, 22 (1898), xxxxvii–xl; “The Vaso-Constrictor Fibres of the Great Auricular Nerve in the Rabbit,” ibid., 259–263 “The Survival Respiration of Muscle,” ibid., 23 (1898) 10–99; “The Influence of Oxygen Upon the Survival Respiration of Muscle,” ibid., 28 (1902), 354–359; “Preliminary Note on the Changes in the Osmotic Properties of Muscle Due to Fatigue,” ibid., xli–xlii; “The Relation of Oxygen to the Survival Metabolism of Muscle,” ibid., 474–498; “The Osmotic Properties of Muscle, and Their Modifications in Fatigue and Rigor,” ibid., 30 (1904), 414–438; “Lactic Acid in Amphibian Muscle,” ibid., 35 (1907), 247–309, written with F. G. Hopkins; “On the Alleged Formation of Lactic Acid in Muscle During Autolysis and in Post-survival Periods,” ibid., 43 (1911) 286–312 “Lactic Acid Formation, Survival Respiration and Rigor Mortis in Mammalian Muscle,” ibid., 47 (1913) 361–380The carbon dioxide Production of Heat Rigor in Muscle, and the Theory of Intra-molecular Oxygen,” ibid., 48 (1914), 177–204, written with G. M. Brown; and “Croonian Lecture (1915): The Respiratory Process in Muscle and the Nature of Muscular Motion,” in Proceedings of the Royal Society, 89B (1917), 444–467, written with F. G. Hopkins.

II. Secondary Literature. Maisie [Mary Frances Cropper] Fletcher, The Bright Countenance: A Personal Biography of Walter Fletcher (London, 1957), a sometimes silly book by Fletcher’s widow, at least bears an apt title. It also contains a complete bibliography of his writings, a list of his honors and of his obituary notices, and a valuable forty-page supplement by Sir Arthur MacNalty, which is particularly notable for the excellent survey it gives of the work done by the Medical Research Committee (Council) during Fletcher’s period as secretary.

T. R. Elliot, who also worked in the Cambridge physiological laboratory at the turn of the century, has contributed three valuable sketches of Fletcher’s life and work: Dictionary of National Biography (1931–1940), pp. 284–285; Nature, 132 (1933), 17–20; and Obituary Notices of Fellows of the Royal Society of London, 1, no. 2 (1933), 153–163.

See also The [London] Times (8 June 1933), p. 14; Cambridge Review (13 Oct. 1933); Lancet (1933), 1 , 1319; and British Medical Journal (1933), 1 , 1085.

Gerald L. Geison