Mellanby, Edward

views updated May 23 2018

MELLANBY, EDWARD

(b. West Hartlepool, Durham, England, 8 April 1884; d. Mill Hill, near London, England, 30 January 1955)

biochemistry, physiology, biomedical research and administration.

After pioneering work on dietary deficiency diseases, particularly rickets, Mellanby served as secretary (chief executive) of the Medical Research Council from 1933 to 1949. He was the fourth son and sixth and last child of John Mellanby, an amateur boxing champion from Yorkshire who managed the shipyard of the Furness-Withy Company in West Hartlepool, and his wife, Mary Isabella Lawson of Edinburgh. Reared in religious nonconformity of an evangelical cast, all three sons who survived to maturity became professors in scientific or technical disciplines. The eldest, Alexander Lawson Mellanby (1871-1951), held the chair in civil and mechanical engineering at the Royal (1878-1939), was a distinguished physiologist Oxford. Edward taught physiology at King’s (later Queen Elizabeth) College for Women from 1913 to 1920 and held the chair in pharmacology at the University of Sheffield from 1920 to 1933.

Like his two older brothers, Mellanby attended Barnard Castle School with support from a bursary. He spent four years there, leaving in 1902 as head boy, having also won the upper school prize and a prize for theoretical and practical physics. He enjoyed perhaps even greater celebrity as an athlete, not only as captain of the cricket and football teams but also in track and field. In the Michaelmas term of 1902, he entered Emmanuel College, Cambridge, where he had won an open exhibition in natural science and where his expenses were further defrayed by a leaving exhibition from Barnard Castle School. At Cambridge, Mellanby took a second class in part I of the natural sciences tripos in 1904 and a first class in part II in 1905, his special subject being physiology.¹ After graduating B. A. in 1905, he remained at Cambridge with a research studentship from Emmanuel College and pursued biochemical research under Frederick Gowland Hopkins, who had been his college tutor.

In 1907, to complete his clinical training and become medically qualified, Mellanby went to St. Thomas’s Hospital, London. While in London he continued to receive prizes and degrees from Cambridge-the Walsingham Medal (1907), the Gedge Prize (1908), and the Raymond Horton-Smith Prize (1915), as well as the M. A. (1910), M. B. (1910), and M. D. (1915) degrees. From 1909 to 1911 he was demonstrator in the department of physiology at St. Thomas’s Hospital, where from 1910 to 1912 he also held a Beit memorial fellowship for medical research. In 1913 Mellanby published a study of metabolism in lactating women and joined the faculty of King’s College for Women, a constituent institution of the University of London “founded to provide an education in household science with a genuinely scientific basis and a full academic status.² The following year he married May Tweedy, a fellow student at Cambridge who had taken a second class in both parts of the natural sciences tripos in 1905-1906, and who had since begun her own career in biomedical research at Bedford College, London. Their long and happy partnership, which had no issue in the usual sense, extended into the laboratory.³ No proper study of Mellanby’s career should overlook the important contributions of his wife, who survived him

Even though Mellanby studied under Hopkins (who in 1929 won a Nobel Prize for his work on vitamins), and even though his own initial research concerned disordered metabolism, his work on rickets did not evolve directly from his earlier interests. His first publications (1907-1908) dealt with the metabolism of creatine and creatinine under embryonic, normal and pathological conditions. He was particularly struck by the fact that creatine (ordinarily stored in voluntary muscle) appeared in the urine of patients with hepatic cancer, whereas creatinine alone was excreted in the urine of those with healthy livers or with such noncancerous hepatic diseases as cirrhosis. On this basis, Mellanby hoped that urinary creatine could serve as an aid in the diagnosis of cancer of the liver. During the next decade he pursued his interest in creatine metabolism and (partly in collaboration with Frederick Twort) investigated the possible role of intestinal bacteria in the destruction of creatine, in the production of histamine, and in etiology of infantile diarrhea and cyclical vomiting. He turned to rickets only when invited to do so by the Medical Research Committee (forerunner of the Medical Research Council) in 1914. According to Henry Dale, then a member of the Committee, it was Hopkins who urged that rickets be made an object of special study and that Mellanby be asked to undertake it.⁴

Beginning with the vague mandate to study “experimental rickets and its relations to conditions of oxidation.” Mellanby early concluded that nondietary factors played no more than a secondary, contributory role in the etiology of rickets. In his search for the specific dietary factor involved, he conducted hundreds of feeding experiments on puppies kept for the purpose in the Field Laboratories of Cambridge University. The South Kensington laboratories of King’s College for women served as the main site for the associated biochemical, histological, and X-ray work, through which the existence and severity of induced rickets could be determined quite precisely. Between 1918 and 1921, using the curde and time-consuming process of elimination then characteristic of much nutritional research, Mellanby established that while meat and certain vegetable juices had some inhibitory effect on rickets, such animal fats as cod-liver oil, butter, and suet had the most striking preventive action. Of the three “accessory food factors” or vitamins then known, only the” fat-soluble A” had a similar distribution in natural foods. Mellanby therefore suggested that the antirachitic factor was either fat-soluble A itself or a substance closely related to it. At the same time, however, he discussed several possible objections to their absolute identity,⁵ and his work formed part of the background for the further separation of fat-soluble A into the carotene derivative how known as vitamin A and the specifically antirachitic vitamin D complex, normally produced through solar irradiation of certain sterols.

By most accounts, Mellanby’s work had an immediate and dramatic impact on the prevention and treatment of rickets in England. Indeed, for Henry Dale, Mellanby’s achievement represented a major milestone in the emergence of sciencebased therapy.⁶ Nonetheless, many clinicians had already linked rickets empirically with a deficiency of fats; and cod-liver oil had long been prescribed for its antirachitic properties. While acknowledging the work of his clinical predecessors, Mellanby insisted that competing theories and therapies had allowed rickets to remain a prevalent disease and a probable contributor to high infant mortality among the urban populations of Great Britain and the United States. By the early 1930’s, presumably as a result of the impact of Mellanby’s work, no case of rickets could be found in the London clinics for trials of commercial vitamin D.⁷

Toward the end of World War I. while conducting his work on rickets, Mellanby undertook another” mission-oriented” research project-this time at the request of the Liquor Control Board (established out of governmental concern over the effects of drunkenness on the war effort). Once again with financial support from the Medical Research Committee, he studied the “comparative rates of absorption of alcohol into the blood from different kinds of drinks, and when taken in different relations to food of various kinds.”⁸ In 1920 Mellanby accepted the newly established chair in pharmacology at the University of Sheffield, attracted partly because of the clinical privileges made available to him through his simultaneous appointment as honorary physician at the Sheffield Royal Infirmary. In fact, his career often reflects his concern to reap practical benefits from basic research and to promote the “interaction of clinical and experimental work,” a phrase that served as the subtitle for his book Nutrition and Disease (1934).

For some time after he became secretary of the Medical Research Council in 1933, Mellanby spent his weekends at Sheffield, engaged in productive research. Later, both while serving as secretary and after his retirement from the Council in 1949, he worked in its new nutrition building at Mill Hill. Especially during the 1930’s Mellanby and his associates directed their efforts partly toward cancer, some of their results being recorded in the annual reports of the British Empire Cancer Campaign for 1934 through 1937. But most of Mellanby’s later research had its roots in his work on rickets. During the early 1920’s, for example, he reported that dogs on rachitic diets often developed thyroid growths histologically similar to those of patients with exophthalmic goiter. He therefore treated such patients with cod-liver oil, claiming that it had a beneficial effect, especially when combined with the iodine therapy recommended by others.

More generally, although he took no direct part in the chemical separation of “fat-soluable A”into vitamins A and D, Mellanby did much to clarify their action and mutual relations. Having early noticed the directly rechitogenic action of certain cereals, even in dogs that seemed to have sufficient dietary vitamin D, he argued that such cereals must contain a toxic substance that actively interfered with the calcifying role of vitamin D. In the late 1930’s, after a long search for this” toxamin,”Mellanby and his collaborators implicated phyticacid, which in certain cereals blocks calcium absorpotion by forming highly stable calcium phytate.

A decade later Mellanby excited popular interest by exposing the possible toxicity of wheat flours bleached with nitrogen trichloride as part of the Agene process. In particular, he showed that the ingestion of such flours was regularly associated with “canine hysteria.”Although no decisive evidence established the toxicity of agenized flours in human diets, the process was eventually banned in Britain and the United States. Especially because of this work on agenized flours, the toxicity of which his associates traced more specifically to methionine-sulfoximine, Mellanby issued a prophetic warning against “the chemical manipulation of food”

Perhaps the most fundamental and interesting outgrowth of Mellanby’s work on rickets was his study of the effects of vitamin A on infections, nerve degeneration, bony malformation, and embryogensis. Although his search for specifically anti-infective properties in vitamin A was less than conclusive, it reinforced his conviction that improper nutrition plays a significant role in the etiology of infectious diseases. He achieved more decisive results in his investigation of the nerve degeneration and bony malformation associated with vitamin A deficiency. In an elegant series of papers, Mellanby and his collaborators linked the ataxia of vitamin A deficiency with nerve degeneration, especially in the cranial nerves and central tracts of the special senses. These degenerative changes were later traced to the destructive compression of the nerves and their ganglia by improper development of the skull bones and upper vertebrae–and ultimately to distorted events in the osteoblasts and osteoclasts.

Toward the end of his life Mellanby joined Hon or Fell of the Strangeways Research Laboratory, Cambridge, in studying the effects of excess vitamin A on embryonic tissues cultivated in vitro. Among their exciting results, perhaps the most striking was the induced production of ciliated mucous–secreting epithelium from chicken ectoderm grown in a medium with high vitamin A content, followed by its reversion to normal skin when transferred to a normal medium. These and other metaplastic effects of vitamin A led Mellanby to suggest that it could be considered the “director”of basal cell development, comparable with the “organizers”in embryological growth. To the end of his life–even on the day of his death-Mellanby continued to pursue these studies of the role of vitamin A in embryogenesis and metabolism, having turned at the very end to its effects on sulfate metabolism.

As Henry Dale emphasized, Mellanby’s distinguished career in research becomes all the more impressive when one realizes that he simultaneously held, for sixteen years, the most important post in the administration of medical research in Great Britain. To be sure, when he succeeded Sir Walter Morley Fletcher as secretary of the Medical Research Council in 1933, he inherited a stable, efficient, and highly regarded organization. But the immense expansion of funds for medical research, together with the heavy burdens placed upon the Council during World War II, made his task a demanding one. Some appreciation of its full dimensions can be gained from the annual reports of the Council and from A. L. Thomson’s two-volume history of the Council.⁹ At the time of his selection as secretary, Mellanby was already a member of the Council, with which he had been associated as a major recipient of research funds and as a leading contributor to its work since its origins as the Medical Research Committee. According to Thomson, his selection as secretary “was virtually settled by the scientific members in private meetings”;¹⁰ and he accepted with the understanding that every possible provision would be made to enable him to continue his own research with support from the Council. As secretary he was criticized for his brusque manner toward subordinates and outsiders, and for an alleged partiality toward the nutritional and applied fields in which he had made his own greatest contributions. His leading asset was his ability to distinguish promising avenues of research from other, less fertile competitors for Council funds.

During World War II, Mellanby played a major role in the administration medicine and in the setting of dietary standards for British civilians and military personnel. He was a leading international force in efforts to improve nutrition and in the standardization of vitamins, and he undertook advisory missions to South Africa. India, Australia, and New Zealand. Elected fellow of the Royal Society in 1925 and fellow of the Royal College of Physicians in 1928, Mellanby was named K.C.B. in 1937 and G.B.E. in 1948. He received the full whose career was perhaps unique for the extent to which it combined stature in biomedical administration with eminence in creative research.

NOTES

1. J.R. Tanner, ed., Historical of the University of Cambridge (Cambridge, 1917), 787, 790. H. H. Dale “Mellanby,”196) incorrectly states that Mellanby took first-class honors in both parts of the natural sciences tripos.

2. H. H. Dale, “Mellanby,”200. According to dale (ibid.) Mellanbywent to King ’s college for Women as professor of physiology, but B.S. Platt (in Dictionary National Biography) says he went there as lecture and only later attained the chair.

3. For an early example of their cognate and complementary research, see May Mellanby, “An Experimental Study of the Influence of Diet on Teeth Formation,”in Lancet (1918), 2 767-770, esp. 770: “This work, taken in conjunction with the experiments of E. Mellanby on rickets, puts the close relationship between hypoplastic teeth and rickets on to an experimental basis”

4. Dale, op, cit., 201.

5. See, for instance, Mellanby’s “An Experimental Investigation of Rickets,”esp.409-410.

6. Dale, op cit., 202-203.

7. See ibid., and B. S. Platt, “Prefatory Chapter,”399

8. Dale, op, cit., 204.

9. A. L. Thomson, Half A Century of Medical Research.

10.Ibid., 1, 299.

BIBLIOGRAPHY

I. Original Works. Mellanby published two books: Nutrition and Disease: The Interactiom Of Clinical and Experimental Work (Edinburgh, 1934: and A story of Nutritional Research: The Effect of Some Dietary Factros on Bones and the Nervous System (Baltimore, 1950). In addition, he published almost 100 papers, including several originally delivered as invited lectures. Full bibliographies appear in the articles by Dale and Platt (see below), of which the latter is slightly more valuable. Mellanby’s most significant papers on rickets are “The Part Played by an ’Accessory Factor’ in the production of Experimental Rickets,”in Journal of Physiology,52 (1918), xi-xii;” A Further Demonstration of the Part Played by Accessory Food Factors in the Aetiology of Rickets,” ibid., liii-liv; “An Experimental Investigation Rickets,”in Lancet (1919), 1 407-412: “Experimental Rickets,” Special Reports Series, Medical Research Council, no. 61 (1921); and Their Interaction With Other Factors of Diet and Environment in Producing Rickets,” ibid., no. 93 (1925).

II. Secondary Literature. Of the available accounts of Mellanby’s life and work, the most extensive and valuable is Henry H . Dale, “Edward Mellanby, 1884–1955,” in Biographical Memoirs of Fellows of the Royal Society, 1 (1955), 193–222, with bibliography. Another fairly lengthy account, which includes autobiographical remarks by Mellanby, is B. S. Platt, “Prefatory Chapter . Sir Edward Mellanby, G. B. E., K. C. B.. M. D., F. R. C. P., F. R. S. (1884– 1955) : The Man, Research Worker and Statesman,”in Annual Review of Biochemistry, 25 (1956), 1–28, with bibliography, repr.in The Excitement and Fascination of Science : A Collection of Autobiographical and Philosophical Essays (Palo Alto, Calif., 1965), 381 –405 . See also British Medical Journal (1955), 1, 355–358 : Lancet (1955), 1, 309–310 : and B. S. Platt, “Sir Edward Mellanby, G .B .E., K .C .B ., F.R.S.,”in Nature, 179 (1955), 530–532 : and “Sir Edward Mellanby,”in Dictionary of National Biography, 1951 – 1900, 731–732. On the work of the Medical Research Council under Mellanby’s direction, see Arthur Landsborough Thomson, Half’ A Century of Medical Research, I (London, 1973), passim.esp. 229–230.

Gerald L. Geison

Complete Dictionary of Scientific Biography

Mellanby, Edward

views updated Jun 11 2018

Mellanby, Edward

British physician
1884–1955

The British physician and pharmacologist Sir Edward Mellanby was born in West Hartlepool, England, the youngest son of John Mellanby, a shipyard owner, and his wife Mary Isabella Lawson. Mellanby attended Barnard Castle School and Emmanuel College in Cambridge, England, where he studied physiology . After working as a research student from 1905 to 1907, Mellanby studied medicine at St. Thomas's Hospital in London, and he held a fellowship for medical research from 1910 through 1912. He was married in 1914 to May Tweedy, of London, who was also a researcher in physiology. The following year Mellanby became a medical doctor.

From 1913 to 1920, Mellanby served as a lecturer at King's College for Women in London, where he later became a professor in physiology. In 1914, the Medical Research Committee of the college asked Mellanby to investigate the cause of rickets , a bone disease characterized by bone pain, skeletal deformity, impaired growth, and weakness.

Searching for a dietary deficiency that caused rickets, Mellanby decided to test porridge, the staple food of Scotland, by feeding a group of dogs a diet consisting exclusively of oats. Inadvertently, the dogs were kept indoors, without exposure to sunlight, during the experiment. In 1919, Mellanby reported that he produced rickets in the dogs through the restrictive diet. He then cured the dogs of rickets by adding cod-liver oil to their diet. Mellanby concluded that a component of cod-liver oil that the oats did not contain was essential in preventing rickets.

As a result, Mellanby proposed that rickets was caused by the absence of a dietary factor.

Scientists would later discover that rickets is prevented by vitamin D , which can either be consumed as a dietary factor or produced naturally by the body when exposed to sunlight. Mellanby's work laid the foundation for this conclusion, since the cod-liver oil fed to the dogs was a good source of vitamin D and the dogs were raised without exposure to sunlight.

In 1920, Mellanby was appointed chair of the pharmacology department at the University of Sheffield in England, and as an honorary physician to the Royal Infirmary. He held these positions until 1933, when he became secretary of the Medical Research Council, which had been established by the British government in 1913. He was closely involved with the planning of the new Institute of Medical Research, which opened in 1950 in London.

During World War II, Mellanby was involved with programs to create a wartime diet as well as programs to promote the welfare of both military and civilian personnel. After retiring from the Medical Research Council in 1949, he traveled to India, Australia, and New Zealand to serve as an advisor. After his return to England, he gave several public lectures. Mellanby died on January 30, 1955, while working in his London laboratory.

see also Rickets.

Karen Bryla