In the 19th century when the basic principles of nutrition were established, the main work was done first in France and then in Germany. In each country dogs were the overwhelming choice as the model experimental animal. In France the complexity of nutritional requirements first came to be appreciated and the inadequacy of
gelatin as a substitute for
muscle protein was identified. In Germany quantitative balance procedures for nutrients were developed and it was shown that balance could be achieved at many levels after a period of adaptation. In the U.S.A. at the beginning of this century, Russell Chittenden showed that dogs could do well when fed
low protein diets so long as they contained some nonprotein factors that were provided by meat and milk. On the basis of that work Joseph Goldberger developed a diet which produced a condition analogous to
pellagra in dogs. This led to the discovery that yeast was a potent preventive of the disease and to the eventual identification of
niacin as the primary active factor. Work in Britain with dogs as models for experimental
rickets gave apparently conflicting results, with either environmental or dietary changes apparently protecting from the disease. Further work showed that calciferol could be obtained either by irradiation of the skin or by the consumption of another animal's store. Lastly, Edward Mellanby's continued work on the rachitic effect of cereals led to the spin-off finding that wheat flour improved with
nitrogen chloride, although nontoxic to rats, was responsible for the problem of canine
hysteria in dogs that had developed in the 1930s and 1940s. Its use by millers was than banned.