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THE WORM AND THE TUMOR: REFLECTIONS ON FIBIGER'S NOBEL PRIZE WILLIAM C. CAMPBELL* My friend Fibiger was right. In the 1950s he and I were graduate students, members of a diverse group thrown together in the Old Governor's Mansion in Madison, Wisconsin, for purposes of intellectual cross-fertilization. He was a mathematician and I was a parasitologist, so he achieved a memorable , if unintentional, bit of one-upmanship when he remarked casually that his uncle had got the Nobel Prize for research on a parasitic worm. I was nonplussed. I knew of Nobel Prizes associated with parasitic protozoa, but if such an honor were linked to a parasitic worm, why did our professors and textbooks not brag about it? The answer, it soon became clear, was that they had no wish to flaunt a laurel given for what appeared to be spurious science. My friend's uncle wasJohannes Fibiger of Denmark, who was awarded the 1926 Nobel Prize in Medicine and Physiology. His work, which was indeed centered on a parasitic worm, is worth recalling for two reasons: first, it constitutes a significant episode in medical history; and, second, it may even merit some reexamination on scientific grounds. The object of Fibiger's attention was a nematode worm of the genus Gongylonema, found mostly in rats. It is not important in human medicine or in veterinary medicine and is not commonly used as a model in parasitological research. The Nobel Prize reflected not the importance of the worm, but the importance of cancer. Johannes Fibiger got the Prize for finding a link between the worm and a malignant tumor. It was not the first reported link between cancer and infection, and it was by no means the last. The association between certain cancers and microorganisms is now widely accepted, if not wholly understood, and indeed has taken on new importance as more viruses and bacteria have been implicated. ReThis paper is based on a talk presented to the Medical History Society of New Jersey, 22 May 1996. *Research Institute for Scientists Emeriti, Drew University, Madison NJ 07940.© 1997 by The University of Chicago. All rights reserved. 0031-5982/97/4004-1025$01.00 498 William C. Campbell ¦ The Worm and the Tumor ported links involving macroscopic parasites, however, continue to be few and enigmatic. Within the Phylum Nemathelminthes (roundworms), the Superfamily Spiruroidea seems to be uniquely endowed in this respect, and special significance thereby attaches to Fibiger's historic findings. Fibiger's investigations began in 1907, when he dissected three wild rats and found growths in their stomachs and roundworms in the growths. Together with a colleague he described the worm as a new species, Spiroptera (Gongylonema) neoplastica, and showed that it was transmitted by cockroaches [I]. (The adults live in the adventitia of the aorta and nearby esophagus; the larvae encyst in muscles ofthe insect vector.) These observations led to a series of experimental studies on the nature and causation of such tumors [2, 3]. From the medical point of view, two of Fibiger's conclusions were of special importance: 1.The tumors were caused by the worms. Fibiger could feed infected cockroaches to rats or mice and induce tumors in the epithelial lining of the stomach (and tongue, in case of rats) . 2.The tumors were not benign. Fibiger stressed that the worms often did cause simple hyperplasia of the epithelium. The tumors to which he wished to call attention , however, were large and well defined. They were not mere papillomata, and they were not granulomata caused by foreign-body irritation. They were malignant epitheliomata. They were keratizing squamous-cell carcinomata that grew invasively into adjacent tissues. They metastasized and appeared in organs (especially lungs) where there were no worms. They were transplantable into other animals, and the transplants (withoutworms) grew invasively into the organs of the recipient animals. This was, of course, sensational. It was not the first time that parasitic worms had been linked to cancer, and Fibiger knew about the association between Schistosoma haematobium and bladder cancer in humans. He was also familiar with Borrel's observations, in 1906, ofworms that were closely associated with tumors in rats, and with Borrel's unsuccessful...