Vitamin B12

Vitamin B12

The simultaneous discovery of vitamin B₁₂ by two research teams—one in the United States and one in England--was the culmination of an intensive worldwide search for a compound that could effectively treat pernicious anemia. Until the 1920s, pernicious anemia--a blood disorder in which the red blood cells fail to develop normally--was invariably fatal. Then two physicians, George Richards Minot (1885-1950) and William Perry Murphy, became inspired by George Whipple's (1878-1976) studies that showed beef liver could improve the formation of red corpuscles in anemic dogs. To test Whipple's findings, they began feeding their patients large amounts of beef liver and, in 1926, were able to announce that a daily diet of about a pound of liver could indeed control the deadly anemia. (For their work, Minot and Murphy, along with Whipple, shared the 1934 Nobel Prize in medicine and physiology.)

During the 1930s, researchers around the world began trying to isolate the "active principle" in liver that contained its curative properties. (The antipernicious anemia factor, as it was called, was believed to be a B vitamin and was even given the name B₁₂ long before it could be isolated.) Progress, however, was surprisingly slow. True, by this time patients could be fed extracts of liver rather than the liver itself, which they definitely appreciated. But for some reason, researchers could not seem to measure the amount of vitamin B₁₂ these liver extracts contained. They could only guess at the extracts' potency by measuring red blood cell growth in each patient's blood.

For years, Karl Folkers, an American chemist at a prominent pharmaceutical company, had been directing a research team that was working on the problem. In 1948, the group finally came up with a solution. They found they could measure the vitamin indirectly by measuring the growth rate of certain bacteria that needed vitamin B₁₂ to grow. This bacterial assay system speeded the purification process of the vitamin enormously. Shortly afterward, one of Folkers' teams-- E. L. Rickes and several coworkers--managed to purify vitamin B₁₂ into tiny red crystals. At almost the same time, E. Lester Smith and L. F. S. Parker in England made a very similar announcement.

The new vitamin proved to be such a large and complicated molecule (roughly four times the size of a penicillin molecule) that its structure could only be worked out through the aid of advanced technology. In 1956, Dorothy Hodgkin completed the elucidation of B₁₂'s chemical structure by using x-ray crystallography, receiving the 1964 Nobel Prize in chemistry for her work. Vitamin B₁₂ was finally synthesized by Robert Burns Woodward in 1971, after a ten year effort.

The isolation and synthesis of B₁₂—last of the vitamins to be discovered--removed pernicious anemia from the list of deadly medical problems and served to round out the remarkable half-century of vitamin research that began in the 1890s with Christiaan Eijkman. Pernicious anemia caused by B₁₂ deficiency still occurs in many parts of the world. In the early 1990's, such deficiencies were reported in Cuba as a result of the U.S. trade embargo. Between 1989 and 1995 the daily caloric intake for the citizens of this country went down a third, and serious problems with malnutrition, low birth weights, and vitamin deficiencies occurred as a result.