Frederick Hopkins’s discovery of tryptophan, an essential amino acid in human diets, led to a better understanding of diet and nutrition in humans.
In the late nineteenth and early twentieth centuries, the field of biochemistry
Hopkins’s background in the area of biochemistry and the cell started with protein chemistry.
Hopkins’s initial work with proteins dealt primarily with the pure chemical properties of the proteins. In his initial research he was concerned with the isolation and crystallization of proteins. His keen analytic background enabled him to devise a new technique to crystallize pure albumin protein from egg white, and this was the topic of his first published work from Cambridge University. This led to his joint work with Sydney W. Cole, which led to the isolation of tryptophan. A paper that reported on their research in 1901 dealt with purely chemical techniques that showed the Adamkiewicz “acetic acid” reaction resulted from an impurity in the acetic acid. This was proposed because Hopkins had obtained a sample of acetic acid that gave no Adamkiewicz reaction.
In a second paper published in 1901, Cole and Hopkins discussed an undescribed product of protein digestion that was responsible for the Adamkiewicz reaction. Again, Hopkins’s analytic chemistry skills played a large role in the isolation of this product. After the researchers isolated this product, they tested it and found that it gave the tryptophane reaction; thus it was the product that was giving the Adamkiewicz reaction. Cole and Hopkins concluded, then, that the product of the protein digestion was, indeed, tryptophan. The final paper in the series, published in 1903, described the structure of the tryptophan molecule. Hopkins and Cole concluded that the structure was a skatole-amido-acetic acid (later researchers revised this in 1907 to indole-amido-acetic acid structure). This paper was important because it described the first research to employ bacterial decomposition as an aid in determining the structure of a chemical molecule. This, in turn, led to the start of bacterial biochemistry, which was pursued by Marjorie Stephenson, a student of Hopkins.
Hopkins subsequently published several papers on proteins, but then his interest turned from the purely chemical nature of proteins to nutritional studies of proteins. In the nineteenth century, it was known that gelatin, a protein, would not support life if it was the only source of protein in a rat’s diet. It was later found that gelatin is deficient in the amino acids tyrosine and tryptophan.
Hopkins also published two papers in 1906 on the dietary role of individual amino acids. The first proposed the role of tryptophan as a precursor (starter molecule) for the synthesis of adrenalin. The second paper, published in the Journal of Physiology, alluded to the concept of the “essential amino acid” and was titled “The Importance of Individual Amino-Acids in Metabolism: Observations on the Effect of Adding Tryptophane to a Dietary in Which Zein Is the Sole Nitrogenous Constituent.” The research used zein—a protein from corn—that was made deficient in the amino acid tryptophan. Young mice fed a diet of this protein were unable to maintain growth. Addition of tryptophan enabled the mice to prolong their survival, but they were still unable to maintain growth. In comparison, the addition of tyrosine, an amino acid present in zein, did not prolong survival. Hopkins concluded from this that tryptophan is an important dietary constituent. The following passage shows the scope of Hopkins’s research: “A deficiency in a nitrogenous dietary need not necessarily be one of quantity; the form in which the nitrogen is supplied may determine its efficiency.” Hopkins thus realized that not only the quantity of protein but also the quality of the protein is important.
Further research that Hopkins conducted with Harold Ackroyd in 1916 showed that other amino acids were also essential in the diet. This work with the amino acids arginine and histidine indicated that they were important in nucleic acid metabolism (the genetic material). Exclusion from the diet resulted in nutritive failure. When either one or the other was restored to the diet, normal bodily maintenance and growth of the organism occurred. Hopkins reviewed this research in a lecture presented to the chemical society in which he discussed the fate of protein in the body. As the father of biochemistry in England, Hopkins was gratified to deliver a lecture on the chemistry of animals.
Hopkins remained active in his career. In 1914, he became the first professor in the new department of biochemistry at Cambridge University. After World War I, biochemistry began to be taught at the entry level in colleges throughout the English university system. In 1925, Hopkins was knighted and awarded the Copley Medal of the Royal Society. His most impressive distinction came in 1929, when he shared the Nobel Prize in Physiology or Medicine
Hopkins performed research studies in many other fields of biochemistry and physiology. His research with Walter Fletcher showed that muscle activity and lactic acid production are correlated with each other. Hopkins later worked to discover sulfur-containing vitamins and discovered a tripeptide (three amino acids linked together) called glutathione. He then published a series of papers on the structure and function of the molecule. Hopkins’s impact on the field of biochemistry was immense; at the time of his death in 1947, seventy-five of his students occupied professorial positions around the world.
Knowledge concerning the “essentiality of amino acids” has been important in the history of diet and nutrition throughout the world, and Hopkins’s work was at the forefront of this area of research. Hopkins realized that proteins differ and that the differences lie in the amino acid building blocks. By 1935, the last of the essential amino acids (threonine) was isolated by an American biochemist, William Cumming Rose. In continuing the research that Hopkins had begun, Rose found that of the twenty amino acids found in proteins, ten were essential to the diet of rats. He then utilized graduate students in his nutritional experiments, feeding them isolated amino acids. He found only eight amino acids to be essential and then calculated the minimum daily requirement for each amino acid. Rose thus firmly established what Hopkins had begun regarding the essentiality of amino acids.
The findings from Hopkins’s pioneering work have been refined greatly since the beginning of the twentieth century. It is now known that human adults require nine essential amino acids and infants require ten essential amino acids in their diet. The nutritional quality of a protein depends on the content of the amino acids found in the protein (as Hopkins suggested) and how well it is digested.
Most animal proteins
Although plant proteins alone, such as corn protein, may not provide an adequate supply of amino acids, some combinations of plant proteins can provide an adequate and balanced mixture of amino acids. For example, the mixture of beans (which are low in tryptophan but high in lysine) and corn (which is low in lysine but contains enough tryptophan) called succotash, used by New World Indians, provides a nutritionally adequate supply of amino acids. Another combination used by Asian populations is soybeans and rice. These combinations provide the essential amino acids required in a diet and can be almost equivalent to milk protein.
High-quality nutrition is a worldwide problem because in most parts of the world animal protein is not readily available, and the plants contain low amounts of protein and are usually lacking in essential amino acids. In areas of the world where population growth is outstripping food production, chronic protein deficiencies (called kwashiorkor, or “weaning disease,” in Africa) are occurring. In Central and South America, where protein deficiency is common, an international nutrition board has introduced caparina, a mixture of corn, sorghum, and cottonseed meal. Separately, these plant proteins are poor, but together they have the protein value of milk. Much research continues in the area of nutrition in the early twenty-first century. The pioneering work of Hopkins was only one step toward a better understanding of diet and nutrition.
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Asimov, Isaac. “Sir Frederick Gowland Hopkins.” In Asimov’s Biographical Encyclopedia of Science and Technology. 2d ed. Garden City, N.Y.: Doubleday, 1982. Useful contribution to a volume containing brief, easy-to-read biographies of more than fifteen hundred scientists from ancient times to the early 1980’s. Some of the biographies are cross-referenced to major advances in the subjects’ fields. -
Baldwin, Ernest. “Frederick Gowland Hopkins.” In Dictionary of Scientific Biography, edited by Charles Coulston Gillispie. Vol. 6. New York: Charles Scribner’s Sons, 1972. Well-written, detailed biography of Hopkins for nontechnical readers. Includes references. -
Carpenter, Kenneth J. “A Short History of Nutritional Science: Part 2 (1885-1912).” Journal of Nutrition 133 (April, 2003): 975-984. This second part of a four-part series examines the period in the history of nutritional science when Hopkins was conducting his groundbreaking research. Places Hopkins’s work in the context of nutritional science in general. -
Needham, Joseph, and Ernest Baldwin, eds. Hopkins and Biochemistry. Cambridge, England: W. Heffer & Sons, 1949. This book for the general reader contains Hopkins’s uncompleted autobiography as well as selected addresses and excerpts from his papers, with commentaries. Gives the reader a good overview of Hopkins’s accomplishments.
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