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History of Nutrition

Harriette Chick and the Problem of Rickets¹

Department of Nutritional Sciences, University of California, Berkeley, CA 94720-3104

^* To whom correspondence should be addressed. E-mail: kcarp{at}berkeley.edu.

	Introduction

TOP Introduction London's Lister Institute Chick's First Nutritional... Vitamin-Rich Supplements for... Surprising Results with... The Admonishment of McCollum Rickets: The Controversial... Malnutrition in Vienna The Rickets Research Program Findings at a Larger... The Significance of the... LITERATURE CITED

 
Harriette Chick (1875–1977) grew up in Victorian England at a time when women were assumed to be unsuited for any senior administrative position and did not even have the right to vote. For national elections, this right was finally conceded in 1920 in most European countries as well as in the USA after much agitation and even imprisonment of activists, but Chick "was one of those who earned the enfranchisement of women, not by militancy but by evoking sheer respect of their capacity" (to reuse a quotation originally penned in honor of someone else). By 1920, she herself was in charge of a large international research project designed to find out how best to deal with the problem of rickets that was affecting so many infants growing up in the industrial cities of Northern Europe and North America. This article recounts how her education and subsequent experience at a research institute led to her being selected for a responsibility that would normally not have been given to a woman at that time.

Harriette went to a girls' high school in a London suburb where, unusually, the principal encouraged the teaching of science, and Harriette then enrolled as a science student at University College London in 1894. After graduation, she stayed on to gain a doctorate in bacteriology, working part of the time in Vienna and in Munich where she must have become familiar with spoken German (1,2).

	London's Lister Institute

TOP Introduction London's Lister Institute Chick's First Nutritional... Vitamin-Rich Supplements for... Surprising Results with... The Admonishment of McCollum Rickets: The Controversial... Malnutrition in Vienna The Rickets Research Program Findings at a Larger... The Significance of the... LITERATURE CITED

 
In 1905, Harriette Chick became the first woman to obtain a position at the Lister Institute of Preventive Medicine in London (Fig. 1). This was the only medical research institute in Britain at that time and had been established in 1891 as a private charity, with the wealthy Guinness brewing family as their leading supporters. It was hoped that sales of the sera and vaccines that they developed would also help to keep the institute solvent, as with the Institut Pasteur in Paris. Charles Martin was made its first director in 1903 and by 1905 it had become an active research center (3).

View larger version (142K): [in this window] [in a new window]   FIGURE 1  Harriette Chick (courtesy of Vanderbilt University).

She then worked with Martin on a project related to his studies on the recent outbreaks of bubonic plague in India. By then it was fairly well established that plague was carried by rats and transferred to humans by bites from fleas that had been living and feeding on infected rats. However, previous studies elsewhere had indicated that some kinds of rat fleas would not bite humans. Martin and Chick (identified by their initials in the final report) and 6 others (probably also workers at the institute) then repeatedly offered their arms to be bitten by a hungry rat flea (Ceratophyllus fasciatus). Just over one-half of 118 fleas, offered one at a time, bit Chick and the rest of the group (6). In a further test, each member of the group put an arm into a cage containing altogether 100 fleas to see how many would bite. "H.C." had the highest score of 18 and it was noted that "they could be felt at once to bite vigorously." There was no longer any doubt as to what either these fleas, or the Victorian lady working with them, was capable of doing.

	Chick's First Nutritional Research

TOP Introduction London's Lister Institute Chick's First Nutritional... Vitamin-Rich Supplements for... Surprising Results with... The Admonishment of McCollum Rickets: The Controversial... Malnutrition in Vienna The Rickets Research Program Findings at a Larger... The Significance of the... LITERATURE CITED

 
With the outbreak of World War I in August 1914, the whole staff volunteered its services to the Army Medical Department and the medically qualified men were posted to serve overseas. Chick was at first put in charge of testing and bottling tetanus antitoxin for the army and then of preparing agglutinating sera for the diagnosis of diseases prevalent among the Allied troops (3).

In 1916, Martin was in the Middle East working at a military hospital and saw cases of both scurvy and beriberi that he believed resulted from the restricted range of foodstuffs in the army rations (7). He sent a message back to Chick asking her to organize animal feeding trials that would indicate what foods would be of practical use in supplying the nutritional factors that were deficient in these rations.

This was not the first time that research in this field started at the institute. In 1910, the Polish biochemist, Casimir Funk, served as a guest worker for 2 y in the biochemistry department and in 1912 published the first paper using the term "vitamine" for the dietary factors needed to prevent the occurrence of scurvy, beriberi, and pellagra (8–10), but no one at the institute was working on the subject when Martin asked Chick to take it up.

	Vitamin-Rich Supplements for Military Rations

TOP Introduction London's Lister Institute Chick's First Nutritional... Vitamin-Rich Supplements for... Surprising Results with... The Admonishment of McCollum Rickets: The Controversial... Malnutrition in Vienna The Rickets Research Program Findings at a Larger... The Significance of the... LITERATURE CITED

 
Chick immediately recruited a group of women to work with her, using pigeons for the assay of the antineuritic potency of foods and guinea pigs for the assay of antiscorbutic potencies (11). They concluded that for the prevention of beriberi, good additions to army rations would be whole-grain cereals, pulses, dried eggs, and yeast, but not milk or cheese. For the prevention of scurvy, where fresh vegetables and fruits were not available, they recommended fresh meat and freshly germinated pulses. The latter had been found useful in the Californian Gold Rush, but her group seems to have been the first to confirm their value with guinea pigs (12). Interestingly, as a consequence of their publication, germinated beans were used successfully in 1918 to treat Serbian soldiers suffering from scurvy (13).

They were also the first to dissect rice grains and to separate enough of the tiny germs to carry out a pigeon assay and to demonstrate that this was where most of the antineuritic potency of a whole rice grain was concentrated (14). Eijkman (8), in his classic work first demonstrating its loss of antineuritic potency when brown rice was further processed, had assumed that this came entirely from the removal of the branny layers from the grain.

	Surprising Results with Traditional Antiscorbutics

TOP Introduction London's Lister Institute Chick's First Nutritional... Vitamin-Rich Supplements for... Surprising Results with... The Admonishment of McCollum Rickets: The Controversial... Malnutrition in Vienna The Rickets Research Program Findings at a Larger... The Significance of the... LITERATURE CITED

 
For the animal assay of anitiscorbutics, they followed the general procedure of earlier workers and used guinea pigs as their experimental species but found that providing the animals with autoclaved cow's milk (that was not itself antiscorbutic) in addition to their dry diet of grains resulted in their growing faster and remaining healthier, when supplemented with an antiscorbutic, than had been the case in previous studies (15).

Although guinea pigs had been used for the study of vitamin C deficiency for some years, Chick's group appears to have been the first to measure the relative potencies of different sources of the vitamin at a range of levels (16). Chick (and probably her colleagues also) had no previous experience in carrying out nutritional studies with animals, but she did, of course, have experience of designing quantitative assays when measuring the potencies of biological materials in her earlier work on disinfectants.

	The Admonishment of McCollum

TOP Introduction London's Lister Institute Chick's First Nutritional... Vitamin-Rich Supplements for... Surprising Results with... The Admonishment of McCollum Rickets: The Controversial... Malnutrition in Vienna The Rickets Research Program Findings at a Larger... The Significance of the... LITERATURE CITED

 
During this period, E.V. McCollum was regarded, understandably, as the authority on the subject of vitamins, having been the first to demonstrate the existence of the fat-soluble factor (Factor A) and of at least something very like the water-soluble antineuritic factor (Factor B) being required for the growth of rats (12). However, when he began studying scurvy, he found that rats would continue to flourish on a diet that would be scorbutic for humans. Because he had been advocating the use of results with rats as a guide to human nutritional requirements, this was a problem for him. He had "assumed as a working basis that all animals as highly developed as mammalia should require the same chemical complexes in the diet if growth and well-being are to be maintained" (17).

In McCollum's own work with guinea pigs, together with a new collaborator, a group of 4 animals consumed rolled oats and fresh cow's milk ad libitum. Of these, 2 lived and continued to gain weight for an observation period of 13 wk. The remaining 2 died with signs of scurvy after 4 and 7 wk, respectively, and an autopsy revealed they had "the cecum greatly distended with putrefying feces." After further trials with the same basic diet, but supplemented with a choice of laxatives, again about one-half thrived and the remainder died with signs of scurvy. The author's conclusion was that the deaths had resulted from "intestinal auto-intoxication as a result of constipation" and more generally "the significance of this interpretation is far reaching. It removes from the list 1 of the syndromes [scurvy] which has long been generally accepted as due to dietary deficiency" (18).

Chick would have none of this. Her group had already found that guinea pigs would drink fresh cow's milk and obtain a little antiscorbutic activity from doing so, but if the milk were allowed to go sour they would no longer touch it (15). When they fortified the basal diet with autoclaved milk, scurvy was the consistent result, and with lemon juice added, the animals all remained healthy. They suggested that much of the variability in McCollum's results was due to differences in milk consumption by individual animals and that it was essential to measure this daily if a trial were to be properly controlled (19). [We now know, of course, that a cow's milk does not have to be rich enough in vitamin C to provide her calf's needs, because it can synthesize the vitamin for itself (12).]

	Rickets: The Controversial Background

TOP Introduction London's Lister Institute Chick's First Nutritional... Vitamin-Rich Supplements for... Surprising Results with... The Admonishment of McCollum Rickets: The Controversial... Malnutrition in Vienna The Rickets Research Program Findings at a Larger... The Significance of the... LITERATURE CITED

 
Rickets is a disease of young children characterized by abnormally low mineralization and thus of low mechanical strength in the developing bones. The most obvious sign of the condition is that when the child stands, its weight causes the leg bones to distort so that it becomes either "bandy-legged" or "knock-kneed." Originally it was known as "the English disease," but by the late 19th and early 20th century it had become an increasingly serious problem in large cities throughout both Northern Europe and North America (20).

One of the traditional folk treatments for rickets among fishing communities in Scandinavia and the Netherlands had long been the administration of cod liver oil (CLO). Early in the 19th century it was taken up by the medical profession in France and then elsewhere in Europe, where it had, in some places, been in use already for the treatment of rheumatism. However, by 1900 it had fallen out of favor, partly it seems because using animal organs in medicine had medieval associations: "more suited for the witches' cauldron in Macbeth than for scientific treatment," and, in terms of the chemical analyses of the day, it was just "another fat, and a rather nauseating one" (21).

There was a general move therefore toward recommending that the infant's diet be richer in fat of any kind at the expense of carbohydrate (21). This may have been related also to the disease being less common in breast-fed infants than in those receiving "patent foods" that contained more of the cheaper carbohydrates. However, clinical studies gave conflicting findings and a more scientific way forward seemed to be the use of an animal model so that 1 factor could be varied at a time and all others kept constant.

In Glasgow, Scotland's largest city, rickets was particularly serious. In 1908 Lionel Findlay of the university's medical school reported that puppies fed on oatmeal and whole milk would develop rickets if kept indoors, but would remain healthy if given exercise by being taken out for walks without any change in their diet (22). The workers in Glasgow linked these findings to observations that the disease was most prevalent in the crowded slum areas of the city where young children were mostly kept indoors in unhygienic conditions and found no reason to believe that the disease was linked to diet.

During WWI, when such great advances were occurring in the knowledge of vitamins, no one claimed to be able to produce a model of the disease by restricting the diets of either rats or guinea pigs, the species that had been found most productive in work on deficiency diseases. However, it seems that Gowland Hopkins, a powerful figure in biochemical circles in England, still believed that rickets would prove to be one. He encouraged, and found funding for, his former student Edward Mellanby to study the relation of rickets to diet in puppies. And Mellanby reported in his first communication that his puppies, all kept indoors under the same conditions and fed on grain and a small quantity of whole milk, would develop rickets unless given certain supplements that included butter fat, CLO, and margarine (made from animal fat at that time) but not linseed oil; he concluded that "rickets is a condition primarily due to the lack of an accessory factor in the diet, though deficiency in one element may mean the ineffectiveness of another" (23).

There continued to be a strong difference of opinion between the English and Scottish schools on this subject. At the same time, the ultimate problem was how best to treat infants rather than puppies. With the end of WWI, Martin returned to the Lister Institute and funded Helen Mackay's study of rickets at the out-patient department of a children's hospital in London. In her report, she concluded that "it was impossible to obtain data of sufficient accuracy to give any conclusive results because of errors in the histories given me, irregular attendances and unreported changes in the feeding of the subjects," and it was "absolutely essential that an investigation of a supposed dietetic disorder should be institutional" (24). But where and how could such a study be organized?

	Malnutrition in Vienna

TOP Introduction London's Lister Institute Chick's First Nutritional... Vitamin-Rich Supplements for... Surprising Results with... The Admonishment of McCollum Rickets: The Controversial... Malnutrition in Vienna The Rickets Research Program Findings at a Larger... The Significance of the... LITERATURE CITED

 
After the end of WWI, there continued to be a great deal of hunger and malnutrition on the continent of Europe as a result of the Allied blockade that was maintained, at least in part, until the German signing of a peace treaty and also because of breakdowns in normal trading relations. Vienna was particularly hard hit; it had been the capital of the Austro-Hungarian Empire and had obtained most of its food from nearby Hungary. However, at the end of the war, there had been a revolution and declaration of independence in Hungary and it ceased to supply food across the border with Austria (25,26).

In 1918 the Medical Research Committee, newly formed by the British government (and soon to be renamed a Council), had established, together with the Lister Institute, an Accessory Food Factors committee that was charged with gaining and spreading information on what we would now call vitamins, with Gowland Hopkins as chairman and Harriette Chick as secretary (27). The origin of the studies in Vienna is best described in Chick's own words:

"The idea was conceived of sending a mission to investigate the state of nutrition in Vienna and to ascertain whether specific diseases might be connected with lack of specific vitamins in the scanty food supplies. An important possibility thus offered itself for ascertaining whether the results of experimental work with animals, gathered in the previous decade, might be applicable to the nutrition of human beings. Accordingly, in the autumn of 1919, the committee decided to send its secretary to Vienna with Dr. Elsie Dalyell, a medically qualified colleague from Australia.... The medical and scientific professions in Central Europe had been cut off from foreign scientific journals...(and) the new discoveries about vitamins were regarded with the greatest scepticism" (27).

Chick gave a lecture in German, "The Newer Knowledge of Nutrition," at a specially convened and well-attended meeting of the Vienna Medical Society. Dalyell cured 1 child of an ulcer on the eyeball by giving it butter fat and quickly relieved another of severe pain from scurvy with a preparation made from lemon juice. "Some of the leaders of the medical profession received the visitors with sympathy and encouraged them to put the new theories to practical tests in Viennese hospitals and clinics...." (3,27).

They were invited by Charles Pirquet, director of the University of Vienna's Kinderklinik (children's hospital), to make use of his facilities (and specifically of a clinical ward of 20 cots) to test their ideas, even though he himself at that time believed rickets to be an infectious disease, comparable to tuberculosis, that infants could not always resist under conditions of overcrowding and poor hygiene (28). The hospital was a model of cleanliness and Pirquet already had in place a carefully controlled and standardized system of feeding for all the patients. Additional accommodation in a hut with space for 40 cots was offered at the Amerikanische Kinderheilståtte (a children's sanatorium supported by American funds but also under the direction of Professor Pirquet) on the outskirts of the city.

This was an extraordinary offer and a unique opportunity to determine finally whether or not rickets was a deficiency disease. After Pirquet's death 10 y later, Chick spoke at his memorial: "In Vienna, after the end of the war, it was a time of hunger, poverty and depression, but Professor Pirquet was the exception – he was active and hopeful – a ‘diffuser of life’ in those sad days, supervising the vast American relief program that he had organized so admirably" (29).

	The Rickets Research Program

TOP Introduction London's Lister Institute Chick's First Nutritional... Vitamin-Rich Supplements for... Surprising Results with... The Admonishment of McCollum Rickets: The Controversial... Malnutrition in Vienna The Rickets Research Program Findings at a Larger... The Significance of the... LITERATURE CITED

 
On the return of Chick and Dalyell to London, the Accessory Food Factors Committee planned an elaborate investigation in Vienna, to last, if necessary, 2 y, to elucidate the cause of rickets and the part played by diet. The first aim of the work would be to determine whether rachitic infants would respond to CLO under controlled conditions and with untreated control infants for comparison (27). There was no direct evidence then for there being more than 1 fat-soluble vitamin (i.e. A) and, because Mellanby's work indicated the value of animal fats for puppies with rickets and CLO was recognized as a particularly rich source of vitamin A as well as being a folk treatment for rickets, this seemed a straightforward approach.

The work, under Chick's direction, with Helen Mackay and Elsie Dalyell as well as 2 colleagues from the institute who were not medically qualified, began in the fall of 1920 and continued for 2 y. Finding funds was a continual struggle with Austria in the grip of crippling inflation and most aid organizations being chary of "experimenting with children." However, the Society of Friends was a major supporter with further help from the League of Red Cross Societies and the Lister Institute itself (30).

In all, 75 infants who entered the hospital or sanatorium at <5 mo of age and remained for at least 4 mo were included in the main study. Infantile scurvy was another widespread problem in Vienna at the time, but all these infants received a daily supplement of either citrus juice or expressed vegetable juice, and iron salts were given to correct the development of anemia (31). The ward was airy and brightly lit from sunshine coming through window glass and electric light when necessary (Fig. 2).

View larger version (137K): [in this window] [in a new window]   FIGURE 2  The ward used for the investigation of rickets at the Vienna University Kinderklinik (33, Fig. 1).

The development of rickets was followed exclusively by examination of X-ray photographs of the children's forearms and legs from the knee down, with particular attention to the degree of calcification of the epiphysis [upper end] of the tibia (Fig. 3) (34). This method had the advantage of being objective (in contrast to a clinical impression), with the plates remaining available for independent reexamination by later investigators.

View larger version (113K): [in this window] [in a new window]   FIGURE 3  Radiographs of the lower leg of case M.D. at 8 mo, showing rickets that developed in hospital on diet I (A) and at 10.5 mo, after both CLO supplementation and outdoor exposure, with rachitic lesions healed (B). (33, plate 4).

View larger version (62K): [in this window] [in a new window]   FIGURE 4  Case H.G. at 8.5 mo with rickets (A) and at 10 mo after exposure outdoors, with rachitic lesions healed (B). (32, Fig. 6).

Six other infants with rickets who received diet I were given a few minutes of irradiation from a mercury vapor quartz lamp 3–4 times per week. The total irradiation times ranged from 2 to 5 h and all were healed at the end of the treatment periods. Lastly, 5 rachitic infants received 10 g CLO as a daily supplement to diet I and they too healed rapidly. It was concluded therefore that dietary treatment with CLO and irradiation with UV light (from either unfiltered sunshine or a quartz lamp) were equally effective treatments for rickets, whereas neither sunshine filtered through window glass nor generally hygienic conditions were protective. The antirachitic activity of UV light had, in fact, already been reported by Huldschinsky in Berlin (36), but the group seemed to have been unaware of this. Because of the great inflation of the Austrian currency, Viennese doctors could not afford to buy international journals.

	Findings at a Larger Institution

TOP Introduction London's Lister Institute Chick's First Nutritional... Vitamin-Rich Supplements for... Surprising Results with... The Admonishment of McCollum Rickets: The Controversial... Malnutrition in Vienna The Rickets Research Program Findings at a Larger... The Significance of the... LITERATURE CITED

 
The situation during the main study was, of course, highly unusual with such skilled attention and detailed recording concentrated on a relatively small number of infants. It was of interest therefore to learn whether the use of CLO would be equally successful in treating or preventing rickets under more usual conditions. This was investigated at Vienna's Landes Zentral-Kinderheim, a large public institution containing 200 beds for nursing mothers and 500 cots for infants. In practice, they were mostly unmarried mothers arriving within 3 wk of the birth of their firstborn child and the infants were breast-fed for at least 3 mo whenever possible. The work was hampered by infectious outbreaks that forced some wards to close.

It was also impossible to use radiographic evaluations. Diagnosis of rickets was therefore made on clinical evidence only, with special attention to craniotabes (shallow pitting of the cranial bones) and a rachitic rosary (the appearance of beads or nodules at the front of the ribs). It was accepted that individual examiners would (and did) differ as to the extent of such changes that were needed to be considered a definite manifestation of the disease (37).

As in the main study, there were striking differences between the results in the summer and winter seasons, but here, of the 109 infants that had been receiving CLO, 43 were still diagnosed clinically as being rachitic, most on the basis of only 1 sign (usually craniotabes, with the highest incidence in infants 5–8 mo old), but 7 infants had 2 signs. This result contrasts with the finding in the main study that all of the infants that had been receiving CLO were diagnosed as being free from rickets (38). How could the difference be explained? The possibilities included: 1) some of the mothers were not regularly giving CLO to their baby; 2) the CLO used was not as potent (and there was no method of assay for potency at that time); and 3) the clinical method of diagnosis classified a borderline infant as rachitic when X-ray diagnosis would not.

The last explanation seems the most likely and indeed in the main study, some of the babies considered to be cured, as judged by their radiographs, still showed slight craniotabes. It is interesting that Alfred Hess, the leading research worker on rickets in the USA who was limited to outpatient studies, had also found that, although providing CLO for mothers to give to their infants greatly reduced the incidence of rickets, it did not completely eliminate it, as judged again by clinical criteria (38).

	The Significance of the Vienna Study

TOP Introduction London's Lister Institute Chick's First Nutritional... Vitamin-Rich Supplements for... Surprising Results with... The Admonishment of McCollum Rickets: The Controversial... Malnutrition in Vienna The Rickets Research Program Findings at a Larger... The Significance of the... LITERATURE CITED

 
One could say that the project discovered nothing absolutely new. And that is true, but at the same time it reconciled a whole field of previously warring ideas that seemed to be in contradiction to each other. We had seen this most strongly in the confrontations between Mellanby and Findlay implying: "If I am right, you must be wrong." Even in 1922 we have on the one hand "Diet is the most predominant factor and environment is of secondary importance" (39) and, on the other "... diet has nothing to do with it. We should get away from the idea of lack of something" (40). From then on it was clear that, in a sense, both sides were right: there was more than 1 way of either treating or preventing rickets and the controversy was ended.

Of course, it remained a mystery as to how the 2 very different treatments could have the same effect and, strangely, the solution to this problem began with another paper from the Vienna program. Margaret Hume had been testing the ‘fat-soluble vitamin’ value of samples of both breast milk and cow's milk consumed by infants in the trials, using rats fed on a deficient diet. She also found that UV irradiation of her rats prolonged their period of growth. (With hindsight, therefore, it would appear that her rats were deficient in vitamin D as well as vitamin A.) She then found, to her further surprise, that the same favorable effect could be obtained by irradiating the rats' glass jar containers while the rats were removed from them (41). Unfortunately, Hume misinterpreted these findings as resulting from the activation of the air in the jars. However, Harry Steenbock in Wisconsin repeated her experiments and showed that, actually, the result was explained by the activation of scraps of vitamin-deficient feed lying in the jars (42). This led to a race to identify the chemical changes occurring as a result of irradiation and these were finally tracked down to a reaction in traces of sterols present in both tissues and foods that resulted in their becoming at least similar to the antirachitic molecules in CLO (43).

The fact that rickets can be treated or prevented with a substance now named vitamin D makes it understandable that nutritionists should class it as a nutritional deficiency disease and, for those with an interest in the history of research, to assume that Mellanby was the winner in his controversy with the Scots. But was he really? The distribution of the disease showed little or no relation to diet but was concentrated in cities and industrial areas at a time when the burning of coal (for both home heating and power production) caused a continuous layer of haze overhead that selectively absorbed the UV portion of the sun's rays (44,45). It is more truly therefore the first air pollution disease (46).

To return to Harriette Chick, the organization and writing up of the findings of the Vienna project was probably the high point of her career. But she was then made head of a new Division of Nutrition at the institute and concentrated on deficiencies of water-soluble vitamins. She was particularly interested in pellagra and produced a comparable condition in pigs. After retirement, she continued to write thoughtful reviews and lived to the age of 101 with her mind remaining sharp. She gave an invited lecture to the British Nutrition Society in her 90s and I, myself, caught a glimpse of her, at 99, working her way alone across a crowded London Underground platform.

	ACKNOWLEDGMENTS

 
I thank Dr. George Wolf for giving me additional material relating to Harriette Chick, the library staff at the Wellcome Library in London for guiding me to relevant material, and Ed Liu for skilled transfer of digitalized figures.

	FOOTNOTES

 
¹ Author disclosure: K. J. Carpenter, no conflicts of interest.

Manuscript received 8 November 2007. Initial review completed 15 December 2007. Revision accepted 8 March 2008.

	LITERATURE CITED

TOP Introduction London's Lister Institute Chick's First Nutritional... Vitamin-Rich Supplements for... Surprising Results with... The Admonishment of McCollum Rickets: The Controversial... Malnutrition in Vienna The Rickets Research Program Findings at a Larger... The Significance of the... LITERATURE CITED

 

1. Morrisseyn S. Dame Harriette Chick D.B.E. (1875–1977). In: Bindman L, Brading A, Tansey T, eds. Women physiologists. London: Portland Press; 1993

2. Copping AM. Dame Harriette Chick. In: Widdowson EM, ed. The Nutrition Society 1941–1991. London: CAB International; 1993.

3. Chick H, Hume M, Macfarlane M. War on disease: a history of the Lister Institute. London: André Deutsch; 1971.

4. Chick H. An investigation of the laws of disinfection. J Hyg (Lond). 1908;8:92–158.

5. Chick H, Martin JC. On the ‘heat coagulation’ of proteins. J Physiol. 1910;40:404–30.[Free Full Text]

6. Chick H, Martin JC. The fleas common on rats in different parts of the world and the readiness with which they bite man. J Hyg (Lond). 1911;11:122–36.

7. Chick H. Charles James Martin 1866–1955. Biogr Mem Fellows R Soc. 1956;2:173–208.

8. Carpenter KJ. Beriberi, white rice and vitamin B. Berkeley: University of California Press; 2000.

9. Cooper EA, Funk C. Experiments on the causation of beri-beri. Lancet. 1911;181:1266–7.

10. Funk C. The aetiology of the deficiency diseases. J State Med. 1912;20:341–68.

11. Chick H, Hume M. The distribution among foodstuffs (especially those suitable for the rationing of armies) of the substances required for the prevention of (a) beriberi and (b) scurvy. Trans Soc Trop Med Hyg. 1917;10:141–78.

12. Carpenter KJ. The history of scurvy and vitamin C. New York: Cambridge University Press; 1985.

13. Wiltshire HW. A note on the value of germinated beans in the treatment of scurvy. Lancet. 1918;2:811–3.

14. Chick H, Hume EM. The distribution in wheat, rice and maize grains of the substance, the deficiency of which causes polyneuritis in birds and beri-beri in man. Proc R Soc (Lond) Ser B. 1919;90:44–60.

15. Chick H, Hume EM, Skelton RF. The anti-scorbutic value of cow's milk. Biochem J. 1918;12:131–53.[Medline]

16. Chick H, Hume EM, Skelton RF. The relative content of antiscorbutic principle in limes and lemons: an experimental enquiry. Lancet. 1918;2:735–8.

17. McCollum EV, Kennedy C. The dietary factor operating in the production of polyneuritis. J Biol Chem. 1916;24:491–502.[Free Full Text]

18. McCollum EV, Pitz W. The "vitamine" hypothesis and deficiency diseases. J Biol Chem. 1917;31:229–53.[Free Full Text]

19. Chick H, Hume EM. Note on the importance of accurate and quantitative measurements in experimental work on nutrition and accessory food factors. J Biol Chem. 1919;39:203–7.[Free Full Text]

20. Hess AF. Rickets. Philadelphia: Lea & Febiger; 1929.

21. Ihde AJ. Studies on the history of rickets. II. The roles of cod liver oil and light. Pharm Hist. 1975;17:13–20.[Medline]

22. Findlay L. The etiology of rickets: a clinical and experimental study. BMJ. 1908;2:11–12.

23. Mellanby E. An experimental investigation on rickets. Lancet. 1919;1:407–12.

24. Mackay HMM. Observations on cases of rickets in an out-patient department. BMJ. 1920;2:929–32.[Free Full Text]

25. Surface FM, Bland RL. American food in the world war and reconstruction period: operation of the organizations under the direction of Herbert Hoover 1914 to 1924. Stanford (CA): Stanford University Press; 1931.

26. Fry AR. A Quaker adventure. New York: Frank-Maurice; 1926.

27. Chick H, Hume EM. The work of the Accessory Food Factors Committee. Br Med Bull. 1956;12:5–8.[Free Full Text]

28. Pirquet C. Preface. Med Res Counc Spec Rept Ser. No. 77. 1923;5–6.

29. Chick H. Tribute at memorial for Professor Pirquet. Box PP/CHI/B.7, Wellcome Library, London.

30. Correspondence from Chick (11/15/1920) and Martin (2/10/1921): Medical Research Council file FDI/3776, Kew (England): National Archives.

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