Edward Mellanby and the Rickets Experiments

Table of Contents

1. Rickets in Industrial Britain
2. Competing Theories: Sunlight, Hygiene or Diet
3. The 1914 Medical Research Committee Assignment
4. The Cambridge Dog Experiments
5. Cod Liver Oil and the Fat-Soluble Factor
6. The 1919 Lancet Paper
7. Vitamin A or Something Else? McCollum’s 1922 Separation
8. The Glasgow Opposition
9. Sunlight and Diet Reconciled
10. From Experiment to Clinic
11. Key Research Papers
12. Connections

1. Rickets in Industrial Britain

Rickets is a disease of growing bone. Bone is built in two stages: first a soft protein framework is laid down, and then it is hardened with calcium and phosphate. In rickets the second stage fails. The new bone stays soft, so the long bones of the legs bend under the child’s weight, the ends of the bones near the wrists and ankles widen, the skull can soften and the junctions of the ribs swell into a row of knobs that doctors called the “rickety rosary”. In severe cases a deformed pelvis could later make childbirth dangerous.

The disease was not new. The pediatric historian Kumaravel Rajakumar notes that rickets was common in seventeenth-century England, and that Francis Glisson’s treatise on the disease, published in 1650, described its clinical and anatomical features in great detail. What had changed by 1900 was its scale. Rajakumar describes rickets at the turn of the twentieth century as rampant among poor children in the industrialised and polluted northern cities of the United States, and the same was true of the crowded, smoky cities of Britain. The physician and historian Russell Chesney, reviewing the animal research of 1880–1930, notes that in some places 60–90% of children in the industrialised world were affected.

A disease without an explanation

For all that clinical experience, the cause of rickets was still a mystery in the early 1900s. It was more common in cities than in the countryside, in the north than in the south, in poor and crowded families, and among children kept indoors. Each of those patterns pointed to a different explanation, and each explanation had its supporters. That is the puzzle Mellanby was asked to solve.

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2. Competing Theories: Sunlight, Hygiene or Diet

Rajakumar summarises the state of opinion: by the late nineteenth and early twentieth century, rickets was being blamed on faulty diet, on a faulty environment — poor hygiene, lack of fresh air and sunshine — or on lack of exercise. Chesney adds that rickets was also associated with infections, crowding and life in northern latitudes, and that all of this had to be reconciled with a well-known clinical fact: cod liver oil was observed to prevent or cure the disease.

The sunlight clue

One of the most important early clues came not from a laboratory but from a medical missionary. In 1890 Theobald Palm compared the frequency of rickets in the cities of northern Europe with that in comparable places in Japan and other tropical countries, and concluded that exposure to sunlight prevented the disease. Chesney, who has written a history of Palm’s observation, describes it as the seminal discovery that sunlight matters in the prevention of rickets, although it remained somewhat obscure for years.

The folk-medicine clue

The other clue was cod liver oil. Rajakumar lists the folklore that advocated its benefits among the threads that eventually solved the disease. Fishing communities and physicians in northern Europe had given the oil to children for generations, but nobody could say why it worked or whether its effect was real. The site’s page on the history of cod describes how the fish and its liver oil entered European diets.

The vitamin idea

A third idea was new. At Cambridge, Mellanby’s teacher Frederick Gowland Hopkins was showing that animals need small amounts of “accessory food factors” — later called vitamins — to grow normally. If a disease such as scurvy or beriberi could be caused by something missing from food, perhaps rickets could too. Testing that idea properly needed controlled feeding experiments.

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3. The 1914 Medical Research Committee Assignment

In 1914 Britain set up a Medical Research Committee, funded with public money, to support research into disease; in 1920 it became the Medical Research Council. According to the Royal College of Physicians’ obituary of Mellanby, one of the new committee’s early decisions, made on Hopkins’s suggestion, was to ask Mellanby to investigate rickets.

He was then a physician and physiologist who had trained under Hopkins at Cambridge, qualified in medicine at St Thomas’s Hospital in London and, in 1913, taken a post in physiology at King’s College for Women in London. In the same year as the commission he married the physiologist May Tweedy, who as May Mellanby would carry out parallel research on diet and teeth.

How the work was organised

The Royal College of Physicians records that the dietary trials were done on dogs at field laboratories in Cambridge, while the histology (the microscopic study of the bones) and the biochemistry were done in London. Puppies grow quickly, so changes in growing bone show up during the course of an experiment. The nutrition historian Kenneth Carpenter, in a review of the dog’s contribution to nutrition science, notes that dogs were used as models for experimental rickets in Britain in this period.

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4. The Cambridge Dog Experiments

Mellanby’s method was simple in outline. He kept young puppies in cages and fed them carefully controlled diets, changing one ingredient at a time, and then examined their bones for the signs of rickets — by their outward appearance and by chemical and microscopic study of the bones.

The basic rickets-producing diet was restricted and leaned heavily on cereal, with a large part of it made up of oatmeal porridge. Puppies raised on it developed rickets. That in itself was an important result: it showed that rickets could be produced at will by diet, which made it possible to test what prevented it.

Testing one change at a time

Having found a diet that reliably produced the disease, Mellanby added single foods to it and watched what happened. The question each time was whether the addition prevented rickets in puppies that would otherwise develop it, or cured rickets already present. This was the experimental logic that Hopkins’s laboratory had used for growth: keep everything else constant, vary one thing, and see whether the disease appears.

The oatmeal detail

One feature of the results looked minor at first and turned out to matter a great deal later. The diets that produced rickets most readily were the ones heaviest in cereal. Mellanby came to believe that cereals were not merely failing to protect the bones but actively making things worse — a line of research that he followed for thirty years and that ended with the identification of phytic acid in grain. That story is told on Cereals, Phytic Acid and Teeth.

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5. Cod Liver Oil and the Fat-Soluble Factor

The decisive result came when fats were added to the rickets-producing diet. Cod liver oil prevented the disease, and it could also cure puppies that had already developed it. Certain other fats, butter among them, also protected the bones. From these findings Mellanby concluded that rickets was a dietary-deficiency disease caused by the lack of a fat-soluble accessory food factor — a substance present in some natural fats, and especially rich in cod liver oil.

His biographer B. J. Hawgood, writing in the Journal of Medical Biography in 2010, dates the conclusive evidence to 1918, when Mellanby was working at King’s College for Women in London, and describes it as proof that rickets is a dietary deficiency disease due to lack of a fat-soluble vitamin.

A natural source with a long history

The result gave experimental support to what the folk remedy had long suggested. Cod liver oil is pressed from the livers of cod, and fish liver oils are among the richest natural food sources of what is now called vitamin D. The site covers the food itself on its pages on cod liver and on vitamin D and cod liver oil. Mellanby’s experiments were among the first to show, under controlled conditions, that the protective effect belonged to a specific fat-soluble substance rather than to the oil’s general nourishment.

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6. The 1919 Lancet Paper

Mellanby published the main results in The Lancet in March 1919 under the title “An experimental investigation on rickets”. The paper set out the dog experiments and his conclusion that rickets resulted from the lack of a fat-soluble dietary factor. A fuller account followed in 1925 as a Medical Research Council monograph, Experimental Rickets.

A nutrition classic

The 1919 paper is regarded as one of the founding documents of vitamin D research. It was reprinted as a “Nutrition Classic” in Nutrition Reviews in 1976, and again in the journal Nutrition in 1989, where it appeared with an accompanying discussion. The historians John Parascandola and Aaron Ihde examined the paper and its background in a 1977 article in the Bulletin of the History of Medicine, “Edward Mellanby and the antirachitic factor”.

Chesney places Mellanby’s dogs among the six animal models — studies in lion cubs, dogs and rats among them — that between 1880 and 1930 established nutritional deficiency as a cause of rickets. Those studies, he writes, showed the importance of cod liver oil and of an antirachitic substance later termed vitamin D, showed that fats in the diet were required, and showed that the substance was different from vitamin A.

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7. Vitamin A or Something Else? McCollum’s 1922 Separation

When Mellanby did his experiments, only one fat-soluble vitamin was known: the “fat-soluble A” that the American biochemist Elmer McCollum and others had described a few years earlier as necessary for growth. Cod liver oil and butter were both rich in it. It was natural, then, for Mellanby to conclude that the antirachitic factor in his fats was vitamin A, and at first he did.

Two vitamins in one oil

The answer came from McCollum’s own laboratory at Johns Hopkins University. In 1922 McCollum, Nina Simmonds, J. Ernestine Becker and P. G. Shipley published “Studies on experimental rickets” in the Journal of Biological Chemistry, reporting that the antirachitic activity of cod liver oil survived treatment that destroyed its vitamin A. The oil, in other words, contained two different substances: one needed for growth and the eyes, which kept the name vitamin A, and a second that promoted the deposit of calcium in bone. The second was soon called vitamin D.

This is why historians are careful about how they describe Mellanby’s role. He did not discover vitamin D as a distinct substance; he identified a fat-soluble dietary factor that prevented rickets, believed it was vitamin A, and was corrected by later work. But his experiments provided the clear demonstration that a factor in food prevented rickets — the result on which the separation of vitamin D was built. His work led to the discovery of vitamin D rather than making it.

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8. The Glasgow Opposition

Mellanby’s dietary theory did not win immediate acceptance. Its strongest critics were in Glasgow, a city with severe rickets and a strong school of physiologists and clinicians who favoured environmental explanations — hygiene, fresh air and exercise — over a dietary one.

The historians D. F. Smith and M. Nicolson studied this dispute in a 1989 article in the Proceedings of the Royal College of Physicians of Edinburgh, “Chemical physiology versus biochemistry, the clinic versus the laboratory: the Glaswegian opposition to Edward Mellanby’s theory of rickets”. As the title indicates, they frame the conflict as one between scientific traditions — chemical physiology against biochemistry, and the clinic against the laboratory.

Conflicting dog experiments

Part of the difficulty was that the animal evidence itself seemed to point both ways. Carpenter’s review notes that British work with dogs as models for experimental rickets gave apparently conflicting results, with either environmental or dietary changes appearing to protect animals from the disease. To each side, the other’s results looked like an error of method.

Looking back, both sides had hold of part of the truth. A dog kept indoors without sunlight and a dog fed a diet short of the fat-soluble factor were, it would turn out, short of the same thing by two different routes. Mellanby himself later received an honorary degree from the University of Glasgow, in 1946.

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9. Sunlight and Diet Reconciled

The resolution came within a few years of Mellanby’s paper. Researchers in several countries showed that ultraviolet light — from the sun or from lamps — could cure rickets in children and animals, and that irradiating certain foods made them antirachitic. Carpenter summarises the outcome for the dog work: further research showed that the antirachitic substance (calciferol) could be obtained either by irradiation of the skin or by eating another animal’s store of it, as in fish liver oil.

The biochemist Hector DeLuca, in his history “The vitamin D story” (1988), dates the discovery of vitamin D and of its production in skin and foods by ultraviolet irradiation to 1919–1924, and writes that these discoveries led to the elimination of rickets as a major medical problem. Chesney’s history of Palm’s observation traces how, over the forty years after 1890, the sunlight clue led to an understanding of ultraviolet light and its role in vitamin D synthesis.

One vitamin, two sources

The two camps of the rickets debate had therefore been describing the same deficiency. A child in a dark, smoky industrial city made little vitamin D in the skin; if the diet also contained little of it, rickets followed. Cod liver oil supplied the vitamin through food; sunlight let the body make it. Chesney concludes that by the end of this period a nutritional deficiency of vitamin D, resulting from a poor diet or lack of adequate sunshine, was firmly established as a cause of rickets.

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10. From Experiment to Clinic

The Royal College of Physicians’ obituary of Mellanby credits his rickets work with leading to the rational treatment of rickets in infants and its near-elimination in Britain within a few years. Historians such as Rajakumar and DeLuca describe the conquest of rickets as the joint achievement of the dietary and sunlight discoveries; Rajakumar writes that with the discovery of vitamin D and the delineation of the antirachitic properties of cod liver oil by the 1930s, it became possible not only to treat but to eradicate rickets in the United States.

Where the story went next

The experiments set the course of Mellanby’s own career. From 1920, as professor of pharmacology at Sheffield, he followed the oatmeal clue into the chemistry of cereals and calcium; with H. N. Green he took up vitamin A as an “anti-infective” agent; and much later his continued dog-feeding work produced the agene flour finding of 1946. Those chapters are told on Cereals, Phytic Acid and Teeth and Vitamin A, Agene Flour and Edward Mellanby’s Legacy.

The vitamin itself went on to a long scientific history of its own, from its chemical identification to the discovery that the body converts it into a hormone. The site tells that story on Vitamin D3: History and Discovery, and describes the disease today on Rickets in Children.

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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. Mellanby E. Nutrition Classics. The Lancet 1:407-12, 1919. An experimental investigation of rickets. Edward Mellanby. Nutr Rev. 1976;34(11):338-40. PubMed PMID: 794773
3. Mellanby E. An experimental investigation on rickets. 1919. Nutrition. 1989;5(2):81-6; discussion 87. PubMed PMID: 2520279
4. Parascandola J, Ihde AJ. Edward Mellanby and the antirachitic factor. Bull Hist Med. 1977;51(4):507-15. PubMed PMID: 343840
5. 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
6. 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
7. Chesney RW. Early animal models of rickets and proof of a nutritional deficiency hypothesis. J Pediatr Gastroenterol Nutr. 2012;54(3):322-7. PubMed PMID: 22134552
8. 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
9. Rajakumar K. Vitamin D, cod-liver oil, sunlight, and rickets: a historical perspective. Pediatrics. 2003;112(2):e132-5. PubMed PMID: 12897318
10. Chesney RW. Theobald palm and his remarkable observation: how the sunshine vitamin came to be recognized. Nutrients. 2012;4(1):42-51. PubMed PMID: 22347617
11. 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
12. Carpenter KJ. Contribution of the dog to the science of nutrition. J Nutr. 1991;121(11 Suppl):S1-7. PubMed PMID: 1941202

PubMed Topic Searches

1. Mellanby E [Author] and rickets
2. History of rickets and cod liver oil
3. Rickets, sunlight and the discovery of vitamin D
4. Animal models in the history of rickets

Further Reading

• Mellanby E. Experimental Rickets. Medical Research Council Special Report Series No. 93. London; 1925.
• Royal College of Physicians. Sir Edward Mellanby. Munk’s Roll, Volume V, p. 279. history.rcp.ac.uk

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Connections

• Sir Edward Mellanby: Rickets, Cod Liver Oil and the Road to Vitamin D
• Edward Mellanby: Life and Career
• Cereals, Phytic Acid and Teeth: The Mellanbys’ Food Science
• Vitamin A, Agene Flour and Edward Mellanby’s Legacy
• Nutrition and Orthomolecular
• Frederick Gowland Hopkins
• Vitamin D3
• Vitamin D3: History and Discovery
• Rickets in Children
• Cod Liver
• Vitamin D and Cod Liver Oil
• Calcium

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