Sir Edward Mellanby: Rickets, Cod Liver Oil and the Road to Vitamin D

Sir Edward Mellanby (1884–1955) was a British physician and pharmacologist whose experiments with puppies, oatmeal porridge and cod liver oil showed that rickets — the bone-softening disease that bowed the legs of children across industrial Britain — was a disease of diet. Puppies fed a restricted, cereal-heavy diet developed rickets; puppies given cod liver oil or other fats such as butter did not. Mellanby concluded that the protective fats carried a fat-soluble “accessory food factor”, and his 1919 paper in The Lancet became one of the founding documents of the vitamin D story.

He did not discover vitamin D himself: he believed at first that the protective factor was vitamin A, and it was Elmer McCollum’s group in the United States that separated a distinct calcium-depositing vitamin in 1922. But his work led directly to that discovery, and the rest of his career kept returning to food as the source of health and disease — the cereals that made rickets worse because of their phytic acid, vitamin A as an “anti-infective” agent, and, in 1946, the finding that a chemical used to bleach flour caused fits in dogs. Between 1933 and 1949 he also ran Britain’s Medical Research Council. This wing tells his story in four deep-dive articles; this page is the overview.

Table of Contents

  1. Deep-Dive Articles
  2. Who Edward Mellanby Was
  3. The Rickets Discovery on One Page
  4. The Natural Source: Cod Liver Oil, Fats and Cereals
  5. Vitamin A and the Agene Flour Finding
  6. Timeline at a Glance
  7. Later Significance
  8. Key Research Papers
  9. Connections
  10. Featured Videos

Deep-Dive Articles

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Edward Mellanby: Life and Career

From a West Hartlepool shipyard family to Cambridge under Gowland Hopkins, the Sheffield chair of pharmacology, sixteen years as Secretary of the Medical Research Council and a lifelong research partnership with May Mellanby.

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Edward Mellanby and the Rickets Experiments

The dog experiments with oatmeal diets and cod liver oil, the fat-soluble factor, the vitamin A mistake, McCollum’s 1922 separation of vitamin D and the Glasgow opposition.

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Cereals, Phytic Acid and Teeth: The Mellanbys’ Food Science

Why oatmeal made rickets worse, phytic acid identified in 1939, vitamin D activity in ergot of rye, and May Mellanby’s Nobel-nominated research on diet and teeth.

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Vitamin A, Agene Flour and Edward Mellanby’s Legacy

Vitamin A as an “anti-infective” agent and the interwar trials, the 1946 agene flour finding and its toxic factor, and how vitamin D and vitamin A science developed after him.

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1. Who Edward Mellanby Was

Edward Mellanby was born on 8 April 1884 in West Hartlepool, County Durham, the youngest of six children of John Mellanby, the manager of a shipyard there. Two of his brothers also became professors — one in engineering at Glasgow and one, John Mellanby, in physiology. Edward went from Barnard Castle School to Emmanuel College, Cambridge, in 1902, took first-class honours in the Natural Sciences Tripos and came under the influence of the biochemist Frederick Gowland Hopkins, one of the pioneers of the idea that foods contain small but essential “accessory factors”. His first substantial paper, on creatine and creatinine, appeared in 1908.

He finished his medical training at St Thomas’s Hospital in London (MB 1910, MD 1915), worked with the bacteriologist Frederick Twort on gut bacteria that make histamine, and in 1913 moved to King’s College for Women in London. In 1914 he married May Tweedy, a physiologist he had met at Cambridge; as May Mellanby she became a leading dental researcher, and the two worked side by side for the rest of his life. In 1920 he took the chair of pharmacology at the University of Sheffield, which he ran in effect as a department of experimental medicine, and from 1933 to 1949 he was Secretary of the Medical Research Council, advising the government on food policy during the Second World War. He was knighted (KCB) in 1937 and made GBE in 1948. He died suddenly on 30 January 1955, still doing research — according to the Royal College of Physicians’ obituary, on the day of his death.

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2. The Rickets Discovery on One Page

In the early twentieth century, rickets was common among children in Britain’s industrial cities, and doctors disagreed about its cause. Some blamed lack of sunlight and fresh air or poor hygiene; others suspected diet. In 1914 the newly formed Medical Research Committee (later Council), acting on Hopkins’s suggestion, asked Mellanby to investigate. He kept litters of puppies in cages and fed them restricted diets in which oatmeal porridge was prominent. The puppies developed rickets. When cod liver oil, or certain other fats such as butter, was added to the same diet, the disease was prevented or cured.

From these experiments Mellanby concluded that rickets was a deficiency disease caused by the lack of a fat-soluble accessory factor, and he published the main results in The Lancet in 1919. The biographer B. J. Hawgood dates the conclusive evidence to 1918. Mellanby thought the factor was the fat-soluble vitamin A that had recently been described; in 1922 McCollum and his colleagues showed that cod liver oil contained a separate calcium-depositing factor, soon named vitamin D. At about the same time other researchers showed that ultraviolet light could also cure rickets, and the dietary and sunlight explanations were eventually reconciled. Not everyone accepted Mellanby’s dietary theory at first: historians have documented strong opposition from physicians and physiologists in Glasgow who favoured an environmental explanation.

The full story — the competing theories, the dog experiments, the 1919 paper and the Glasgow controversy — is told in Edward Mellanby and the Rickets Experiments.

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3. The Natural Source: Cod Liver Oil, Fats and Cereals

The protective substance in Mellanby’s experiments came from food. Cod liver oil had been used as a folk remedy for rickets in northern Europe long before anyone could explain why; Mellanby’s dog work provided experimental evidence that it worked and pointed to a fat-soluble factor as the reason. The site’s pages on cod liver and on vitamin D and cod liver oil cover the food itself.

The other half of the story was the food that made rickets worse. The rachitic diets in Mellanby’s experiments were heavy in oatmeal, and he and his co-workers spent decades asking why cereals interfered with the calcification of bone. In 1928 Mellanby and H. N. Green described a rat technique for measuring this “interfering effect” of cereals, and in 1939 Mellanby and D. C. Harrison identified phytic acid — a phosphorus-storing compound in the outer layers of grain — as the rickets-producing factor. Hawgood summarises the Sheffield finding: in an unbalanced diet, phytic acid reduced the availability of calcium. In 1929 the Sheffield group also reported vitamin D activity in ergot, a fungus that grows on rye.

May Mellanby, working for the Medical Research Council from 1918, studied how diet before and after birth affects the structure of teeth and the incidence of dental caries; her work favoured diets rich in vitamin D and low in cereals. According to Hense and colleagues, she was nominated for the Nobel Prize and judged “prize-worthy” by the Nobel Committee, though she never received it. These threads are told in Cereals, Phytic Acid and Teeth.

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4. Vitamin A and the Agene Flour Finding

In 1928 Green and Mellanby published “Vitamin A as an anti-infective agent” in the British Medical Journal, followed by reports on vitamin A in puerperal septicaemia (1929) and on diet as a preventive against puerperal sepsis (1931). The historian Richard Semba describes the “anti-infective” idea as largely championed by Mellanby, and counts at least 30 trials between 1920 and 1940, usually using cod liver oil, against respiratory infections, measles, puerperal sepsis and other conditions. Semba notes that the early trials generally lacked randomisation, masking and placebo controls, that results were mixed, and that interest waned once the sulfa drugs arrived — while modern trials of vitamin A in children in developing countries have reported reduced illness and death.

In 1946, still pursuing his long study of cereals in dogs, Mellanby reported in the British Medical Journal that flour treated by the agene process — bleaching and “improving” with nitrogen trichloride — produced “canine hysteria”, or running fits, in dogs. The nutrition historian Kenneth Carpenter records that agenised flour was not toxic to rats and that millers’ use of the process was later banned. Chemists isolated the crystalline toxic factor in 1949–1950, and in 1951 Campbell, Work and Mellanby reported isolating a toxic substance from agenised wheat flour; one of Mellanby’s last papers, published in 1956, studied the compound methionine sulphoximine. These later chapters, along with his tissue-culture work on vitamin A with Honor Fell, are in Vitamin A, Agene Flour and Edward Mellanby’s Legacy.

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5. Timeline at a Glance

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6. Later Significance

Mellanby’s 1919 paper is still reprinted as a nutrition classic. The Royal College of Physicians’ obituary credited his work with leading to the rational treatment of rickets in infants and its near-disappearance from Britain within a few years; historians such as Rajakumar and DeLuca describe the conquest of rickets as the joint result of the dietary and ultraviolet-light discoveries made between 1919 and 1924, of which Mellanby’s was the first. DeLuca traces the line from those discoveries to the identification of the active hormonal form of vitamin D decades later.

His other legacies run through modern food science: the calcium-binding action of phytate in grains, the place of vitamin A in resistance to infection, and the safety of chemicals added to everyday foods — a concern he set out in his 1951 lecture on the chemical manipulation of food. As Secretary of the Medical Research Council through the Second World War he also shaped British medical research and, according to Hawgood, influenced the food policy that maintained the nation’s nutrition during the wartime blockade.

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Key Research Papers

  1. Mellanby E. An experimental investigation on rickets. The Lancet. 1919;193:407-412. DOI: 10.1016/s0140-6736(01)25465-8
  2. Hawgood BJ. Sir Edward Mellanby (1884-1955) GBE KCB FRCP FRS: nutrition scientist and medical research mandarin. J Med Biogr. 2010;18(3):150-7. PubMed PMID: 20798415
  3. Parascandola J, Ihde AJ. Edward Mellanby and the antirachitic factor. Bull Hist Med. 1977;51(4):507-15. PubMed PMID: 343840
  4. Smith DF, Nicolson M. Chemical physiology versus biochemistry, the clinic versus the laboratory. The Glaswegian opposition to Edward Mellanby’s theory of rickets. Proc R Coll Physicians Edinb. 1989;19(1):51-60. PubMed PMID: 11612466
  5. McCollum EV, Simmonds N, Becker JE, Shipley PG. Studies on experimental rickets. Journal of Biological Chemistry. 1922;53(2):293-312. DOI: 10.1016/s0021-9258(18)85783-0
  6. Green HN, Mellanby E. A rat technique for demonstrating the interfering effect of cereals on bone calcification. Biochem J. 1928;22(1):102-12. PubMed PMID: 16743983
  7. Harrison DC, Mellanby E. Phytic acid and the rickets-producing action of cereals. Biochem J. 1939;33(10):1660-1680.1. PubMed PMID: 16747083
  8. Hense L, Hugger A, Hansson N. Excellence in dental research: nominated scholars for the Nobel Prize 1901-1950 with a focus on Lady May Mellanby (1882-1978) and Walter Hess (1885-1980). Br Dent J. 2022;232(11):825-829. PubMed PMID: 35689067
  9. Green HN, Mellanby E. Vitamin A as an anti-infective agent. Br Med J. 1928;2(3537):691-6. PubMed PMID: 20774205
  10. Semba RD. Vitamin A as “anti-infective” therapy, 1920-1940. J Nutr. 1999;129(4):783-91. PubMed PMID: 10203551
  11. Mellanby E. Diet and canine hysteria; experimental production by treated flour. Br Med J. 1946;2(4484):885-7. PubMed PMID: 20278492 (the PubMed record spells the first word “Dist”)
  12. Carpenter KJ. Contribution of the dog to the science of nutrition. J Nutr. 1991;121(11 Suppl):S1-7. PubMed PMID: 1941202
  13. Rajakumar K. Vitamin D, cod-liver oil, sunlight, and rickets: a historical perspective. Pediatrics. 2003;112(2):e132-5. PubMed PMID: 12897318
  14. DeLuca HF. The vitamin D story: a collaborative effort of basic science and clinical medicine. FASEB J. 1988;2(3):224-36. PubMed PMID: 3280376

PubMed Topic Searches

  1. Mellanby E [Author] and rickets
  2. History of rickets and cod liver oil
  3. Phytic acid and calcium absorption
  4. Agene and canine hysteria

Further Reading

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Connections

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