Miscellaneous treatments, II: niacin and heparin: unapproved uses, dosages, or indications

Abstract

NA (also known as “niacin,” a term introduced to avoid confusion between the vitamin and the alkaloid nicotine) is a member of the B group of vitamins. It was initially studied because of its association with pellagra. Although the disease was described in 1735 as “mal de la rosa” by the Spanish physician, Don Gaspar Casal, as having the classic symptoms of dermatitis, diarrhea, dementia, and eventual death (“the four Ds”) and although the specific agent (niacin) that cured the disease was discovered by Elvehjem and Fouts in 1937, it is Joseph Goldberger who will always be remembered as the “unsung hero of American clinical epidemiology” who solved the secret of the malady.1–4 Joseph Goldberger was born to a Jewish family on July 16, 1874, in Giralt, Hungary, then part of the Austro-Hungarian empire. They immigrated to the United States in the late 1880s. He earned his MD degree from Bellevue in 1895 and between 1902 and 1912, he battled epidemic diseases, among them yellow fever, typhoid fever, dengue fever, and others. In 1914, while he was fighting an outbreak of diphtheria in Detroit, Michigan, he was asked by the Surgeon General to head an investigation on pellagra. Goldberger’s theory on pellagra contradicted the commonly held medical opinions. His observations in mental hospitals, orphanages, and cotton mill towns convinced him that germs did not cause the disease, because the inmates of institutions contracted the disease but the staff never did. Given that germs could not distinguish between inmates and employees, the answer would have to lie elsewhere. When fresh food was given to ill inmates, the results were dramatic: all those who were fed this diet recovered from the disease. Although many scientific colleagues sang Goldberger’s praises, even mentioning a Nobel nomination, there were others who criticized his experiments for want of their being able to part from the germ theory of pellagra. Angry and frustrated, Goldberger would not admit defeat in trying to persuade his critics and conducted a dramatic experiment that he hoped would convince them. On April 26, 1916, he injected 5 cm of a pellagrin’s blood into the arm of his assistant, Dr George Wheeler, who in turn, injected 6 cm of “pellagra-contaminated” blood into Goldberger. Then they swabbed the secretions of a pellagrin’s nose and throat and rubbed them into their own noses and throats. They swallowed capsules containing scabs of pellagrin’s rashes. Others, including his wife Mary Goldberger, also participated in his experiments. None of the volunteers acquired pellagra. Despite Goldberger’s heroic efforts, a few die-hard physicians remained staunch opponents of the dietary theory of pellagra. If Goldberger’s theory had been true and if the poor diet resulting from the poverty among Southern tenant farmers and mill workers had been the root cause of pellagra, then the only real cure would have been social reform, especially changes in the land tenure system. The social reform and the land reform that Goldberger believed to be necessary to eliminate pellagra was indeed accomplished, not by the influence of scientific reasoning but by the invasion of boll weevils. The insect destroyed cotton fields and forced Southerners to diversify their crops. By growing a variety of food crops, Southerners improved their diets, and fewer suffered from pellagra. Goldberger continued his research on pellagra but never discovered precisely what was missing in the diets of pellagrins. He died on January 17, 1929, of From the Dermatology Unit, Kaplan Medical Center, Rechovot, Israel; the Cerrahpasa Medical Faculty, University of Istanbul, Istanbul, Turkey; and the Department of Dermatology, Trakya University, Medical Faculty, Edrine, Turkey. Address correspondence to Ronni Wolf, MD, Dermatology Unit, Kaplan Medical Center, Rechovot 76100, Israel E mail: wolf_r@netvision.net.il