Available online at www.annclinlabsci.org 196 Annals of Clinical & Laboratory Science, vol. 39, no. 2, 2009 A Note from History: Nobel Laureate Pathologists

Steven I. Hajdu Los Angeles, California

Keywords: Nobel Prize, Fibiger, Whipple, Dulbecco, Benacerraf, Warren, history of pathology

Alfred Nobel (1833-1896), Swedish chemical in 1895–directed that most of his assets should be engineer, inventor, and entrepreneur, patented over allocated for prizes in 5 areas: physics, chemistry, 300 inventions in 5 different countries. Nobel physiology or medicine, literature, and peace. He began to experiment with nitroglycerine and ordered that the prizes be given annually to those produced his first explosion in 1862. After his most living awardees who during the preceding year had important inventions–the detonator (to explode conferred the greatest benefit on mankind. nitroglycerine), dynamite (to stabilize nitroglycerine) Since 1901, when the first prizes were awarded, and ballistite (smokeless gunpowder)–he built over 800 Nobel Prizes have been granted. Among factory after factory in 20 different countries. Soon, the Nobel laureates there are many scientists and he became a mega-industrialist and multimillion- physicians who had some expertise in pathology, aire. but there have been only 5 physicians who Nobel never attended a university nor did he completed pathology training and entered the ever obtain any degree. He was a self-educated man practice of pathology. and a remarkable linguist. He spoke German, English, French, Italian, Russian, and Swedish. He Johannes Fibiger, a pathologist and professor took serious interest in English literature. Chemistry at the University of Copenhagen, Denmark, fed was his hobby. Despite his fame, Nobel remained a cockroaches–obtained from a Danish sugar lonely man all his life and never gained happiness. factory–to rats kept in his research laboratory. After He acquired houses in France, Russia, and Italy, 2 months of feeding, he discovered that most of the but regarded himself homeless. He worshipped his rats had developed tumors in the stomach. On mother and almost every year he returned to histologic examination of the stomach, a parasitic Stockholm on her birthday. worm belonging to the nematode group was found. Nobel was a pacifist and he considered his Fibiger repeated the experiment over and over again inventions so dangerous that making war had with the same results. The rats developed chronic become unthinkable. In order to establish gastritis, gastric papilloma, and carcinoma. He permanent peace he set aside funds from his estate discovered in the infected cockroaches the same for an annual peace prize. This gave him the nematode he found in the stomach of the rats. impetus to extend his generosity to the sciences for Fibiger received the Nobel Prize in Physiology the benefit of mankind. Nobel in his final will–a or Medicine in 1926 for the experiments he had one-page handwritten note that he drafted in Paris conducted more than a decade before when he produced gastric carcinoma in rats by feeding them Address correspondence to Steven I. Hajdu, M.D., 1759 Spiroptera-infected cockroaches. Although Fibiger Drumcliff Court, Westlake Village, CA 91361-1636, USA; and his associates were known as meticulous tel 805 496 0691; fax 805 496 0620; e-mail [email protected]. investigators with integrity, the cause and nature of 0091-7370/09/0200-0196. $0.90. © 2009 by the Association of Clinical Scientists, Inc. Pathologists who received the Nobel Prize 197 the gastric tumors were questioned in subsequent Renato Dulbecco was born in Catanzara, Italy, years by numerous researchers who failed to in 1914. At the young age of 22 he received his reproduce Fibiger’s results. It is still uncertain what M.D. degree from the University of Turin. After caused the tumors produced by Fibiger. It has been his training in pathology, he was drafted into the suggested that the tumors of the rat stomach Italian army. During the Second World War, he resulted from vitamin A deficiency or from served with the Italian army in France and Russia. contamination of their diet by a fungus, Fusarium, He was wounded and returned to Italy where he that produces carcinogenic mycotoxins. joined the Resistance against Mussolini. After the war, in 1947, Dulbecco joined the George Whipple was born in 1878 in Ashland, staff of the California Institute of Technology and New Hampshire, USA. After graduating from began work on animal viruses. In 1962, he moved college, he spent a year in Ossining, New York, at to the Salk Institute in La Jolla, California, where the Holbrook Military Academy, where he taught he discovered the interaction between DNA tumor mathematics and science and was in charge of the viruses and the genetic material of cultivated cells. athletic program. He then entered Johns Hopkins He found that the virus either led to destruction of Medical School, where his favorite subjects were cells and the release of virus particles, or to pathology, biochemistry, and pharmacology. At transformation of cells. He showed by molecular Hopkins, he came under the influence of Welch, techniques that the genetic material of viruses was Osler, Halsted, and Cushing. After graduation he incorporated into the genetic material of the remained at Hopkins as a trainee in anatomic transformed cells and represented the first phase in pathology and after the second year, he was granted carcinogenesis. a year to study tropical diseases in Panama. In the In 1975, Dulbecco was awarded the Nobel Canal Zone, he worked under the direction of Prize in Physiology or Medicine in recognition of General Gorgas. the research work he carried out at the California During his years as a pathologist at Hopkins, Institute of Technology and the Salk Institute. Whipple developed an interest in diseases of the Dulbecco shared the Nobel Prize with David liver and he attempted to produce liver cell necrosis Baltimore and Howard Temin of the USA. in dogs by chloroform injection. In 1914, he was offered a professorship in research medicine at the Baruj Benacerraf was born in 1920 in Caracas, University of California in San Francisco. There he Venezuela. He had his primary and secondary extended his liver injury studies to research on the education in Paris, France. He received his B.S. in production of hemoglobin. 1942 at Columbia University in New York City In 1921, he assumed the position as head of the and his M.D. in 1945 at the Medical College of department of pathology and dean of the new Virginia in Richmond. He trained in pathology at medical school in Rochester, New York. Within a the Columbia Presbyterian Hospital in New York few years after his arrival in Rochester, with the City and took a fellowship in Paris. After returning generous support of Mr. Eastman and his film to New York, he went into the banking business in manufacturing company, Whipple showed that which he failed. feeding liver to dogs, made anemic by blood-letting, In 1956, Benacerraf joined the faculty of New was a potent cure for anemia. He also demonstrated York University School of Medicine. There he that a liver fraction was useful in secondary anemia began developing the concept of immune response (pernicious anemia). (Ir) genes, which control the body’s response to In 1934, Whipple was awarded the Nobel Prize antigens in autoimmune diseases. In 1970, he was in Physiology or Medicine for his discovery that a appointed chairman of the department of pathology diet rich in liver cured pernicious anemia. He at Harvard University in Boston, where he remained shared the prize with George Minot and William until 1991. As an aside, after Benacerraf assumed Murphy of the United States. his position as chairman of pathology, he discarded the gross and microscopic teaching sets that had 198 Annals of Clinical & Laboratory Science, vol. 39, no. 2, 2009 been accumulated for medical students by his It was there, in 1979, that Warren first noticed illustrious predecessors. Benacerraf received the small curved bacteria in gastric biopsies. Over the 1980 Nobel Prize in Physiology or Medicine for his next 2 years he demonstrated that the organisms discovery, while at New York University, of the were usually related to chronic gastritis and ulcers immune response genes. He shared the Nobel Prize in the stomach or duodenum. Subsequently, Warren with George Snell of the USA and Jean Dausset of and Barry Marshall, a gastroenterologist, succeeded France. in culturing the previously unknown bacterial species, Helicobacter pylori. John Warren was born in Adelaide, Australia In recognition of this discovery, Warren in 1937. At age 18 he was diagnosed as suffering received the Nobel Prize in Physiology or Medicine from grand mal epilepsy. Despite this handicap, he in 2005. He shared the Prize with his Australian gained entrance to the medical school of Adelaide colleague and co-worker, Barry Marshall. University in 1955. After he completed training in pathology at the Royal Melbourne Hospital, he was In conclusion, it is gratifying that through appointed pathologist at the Royal Perth Hospital Nobel’s inspired prize system, these five pathologists in Perth, Australia. were richly rewarded for their scientific achieve- ments. As for Nobel, this lonely man’s reward has been enduring and well-earned fame.