Robert R. Williams
Robert R. Williams in 1938. Courtesy Merck Archives, Merck & Co., Inc.
Beriberi is an ancient disease caused by a lack of vitamin B1 in the body. At one time it was a scourge upon parts of Asia, especially among sailors, prisoners, and other malnourished populations. The determination of the molecular structure of vitamin B1 by an American chemist named Robert R. Williams (1886–1965) enabled its commercial synthesis, helping to eliminate widespread epidemics of this debilitating disease.
By the 1880s suspicions that beriberi was in some way connected to diet began to emerge. A Japanese naval doctor proposed a connection between the diet of Japanese sailors, which consisted almost entirely of polished white rice, and the high incidence of beriberi among them. Acting on his hypothesis, he ordered sailors to increase their intake of vegetables, barley, fish, and meat. Within a decade, beriberi had been all but eliminated in the ranks of the Japanese navy. During the same period, a Dutch physician working in Java conducted experiments on chickens that demonstrated beriberi could be induced in animals that were fed a diet consisting exclusively of polished rice, whereas chickens fed unpolished (brown) rice remained healthy.
Some years later and a few islands over, in Manila, Williams was enlisted by the U.S. Bureau of Science to research the theory that beriberi was caused by a nutritional deficiency and to ascertain the substance in unpolished rice that apparently combatted the disease. Williams, the son of a missionary, was born in India; after earning his master’s degree in chemistry from the University of Chicago, he decided to return to Southeast Asia and found employment with the Bureau in the Philippines. Unable to determine the substance in brown rice that prevented beriberi, however, he came back to the United States.
Williams did not give up his research. In 1925, while employed at Bell Telephone Labs (now Bell Labs), he began to experiment in his garage, using his wife’s washing machine as a centrifuge and his own money to support his research. One year later two Dutch chemists, Barend Jansen and Willem Donath, crystallized the anti-beriberi factor (vitamin B1), which they called “aneurin,” from rice bran. Jansen and Donath were incorrect in the formula they deduced for the vitamin, however; they missed the sulfur atom, thereby making synthetic production impossible.
Williams continued researching vitamin B1. In the early 1930s he approached Merck and Company for funding and support of his work. Merck agreed to supply the needed crystalline vitamin and also provided lab space and assistants. The investment paid off shortly thereafter; in 1936 Williams made the correct structural determination of vitamin B1 and designed a synthesis for it. Williams named vitamin B1 “thiamin” and submitted it for addition to the American Medical Association’s publication New and Non-Official Remedies. The American Chemical Society added an e to the end of the name to reflect the amine nature of the vitamin. Thiamine, found in whole-grain cereals, meats, yeast, and nuts, acts as a cofactor in the enzymatic reaction that breaks down carbohydrates, alcohol, and some proteins.
In 1947 Williams was awarded the Perkin Medal by the Society of Chemical Industry, recognizing his determination of the structure of vitamin B1 and development of a commercially viable synthesis for the compound. Williams donated all his patent royalties from the synthesis of the vitamin to the Williams-Waterman Fund. This fund was administered through the Research Corporation (see Frederick Gardner Cottrell), a philanthropic foundation dedicated to funding scientific research and active in combating diseases of malnutrition in underdeveloped countries of the Western Hemisphere.