Experiments on formulated diets

In the meantime, research was under way into what constituted a physiologically complete diet. Lunin, a pupil of the Swiss biochemist Bunge, first showed in 1882 that laboratory animals failed to thrive when kept on an artificial diet comprising the then known constituents of food (fat, protein, carbohydrate, mineral salts and water) in purified form. Taking a similar approach of using isolated purified food ingredients, Pekelharing formulated a baked product containing only casein, albumin, rice flour, lard and a mixture of all the salts which ought to be found in food. When this product, plus water to drink, was provided as food for mice, the mice failed to grow and died. When other mice were provided with the same meal, but with milk to drink instead of water, they kept in good health. Pekelharing concluded in 1905 that 'There is an unknown substance in milk, which, even in very small quantities, is of paramount importance to nutrition. If this substance is absent, the organism loses the power properly to assimilate the well-known principal parts of food, the appetite is lost and, with apparent abundance, the animals die of want. Undoubtedly, this substance not only occurs in milk, but in all sorts of foodstuffs, both of vegetable and animal origin.' Stepp from 1909 to 1913 provided mice with a natural complete foodstuff (milk and bread) from which he had removed certain constituents by means of alcohol-ether extraction. He discovered thereby that milk and other foods contained some unknown alcohol-soluble dietary factor indispensable for life. As no-one had yet succeeded in isolating the factor, there was no proof of its existence and many doubts were raised concerning the validity of Pekelharing's conclusions. One school of thought was that the animals failed because of the mere monotony of the diet, or its lack of palatability, or to the absence of flavouring substances. Others thought that the cause was to be found in insufficient consumption or failure of absorption.

That a monotonous and unaccustomed food may be used successfully over long periods of time without ill-effects was proved by the experiments of Falta and Noeggerath, published in 1905. They maintained rats successfully for six months or more on monotonous diets of milk, milk powder or lean horsemeat.

We now turn to the work of Sir Frederick Hopkins in England. He fed young rats on an artificial food mixture containing caseinogen, starch, cane sugar, lard and inorganic salts. When these constituents were given in their crude condition, they were apparently adequate to maintain life and a certain amount of growth. When, however, they were subjected to careful purification, growth invariably ceased within a comparatively short time, and the rats died. By carefully determining the total energy consumption of his test rats, Hopkins was able to show that this failure was not due to an insufficient food intake. They ceased, in fact, to grow at a time when they were consuming food in more than sufficient quantity to maintain normal growth. Cessation of growth took place before any failure in appetite. Any effects upon the appetite must therefore have been secondary to a more direct effect upon growth processes. In his classic paper (Hopkins, 1912), Hopkins suggested the term 'accessory factors' for the missing nutrients, postulating that their necessity is a consequence of physiological evolution. Hopkins' work was the first to attract general attention to the existence of the hitherto unrecognized growth-promoting substances.

Casimir Funk, a Polish biochemist working at the Lister Institute in London, set out to isolate the anti-beriberi factor from rice polishings and obtained a biologically active, crystalline substance with the chemical properties of an amine. Funk believed that he had isolated the pure factor, but it was later realized that he had not. In 1912 Funk published a review of the existing knowledge of the diseases caused by nutritional errors (Funk, 1912). He proposed that beriberi, scurvy, pellagra and possibly rickets were caused by the absence from the diet of 'special substances which are of the nature of organic bases, which we will call vitamines'. His new word 'vitamine' was derived from vita (meaning life in Latin) and amine. Funk postulated the existence of an anti-beriberi vitamine, an anti-scurvy vitamine, probably an anti-pellagra vitamine and possibly an anti-rickets vitamine. Later, in 1922, Funk wrote, 'I must admit that when I chose the name vitamine I was well aware that these substances might later prove not to be of an amine nature. However, it was necessary for me to choose a name that would sound well and serve as a catch-word.'

The year 1912 was a landmark in the history of vitamins and heralded a new era in vitamin research. Hopkins' celebrated paper and Funk's review, published a few months earlier, attracted world-wide attention and, finally, a general acceptance of the existence of vitamins. In his review Funk commented, 'There is perhaps no other subject in medicine where so many contradictions and inexact statements were made, which, instead of advancing the research, retarded it by leading investigators in a wrong direction.'

The importance of the pioneering experiments of Eijkman and of Hopkins was finally recognized by the award to them jointly of the Nobel Prize for Physiology or Medicine in 1929.

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