PHYSICIANS have struggled with cancer since man’s earliest beginnings. For example, a mummy dating from the V Dynasty, 2500 years B.C., bears the unmistakable stigmata of osteosarcoma, and the Edwin Smith Papyrus, a surgical record written about 1700 years B.C., describes what is probably cancer of the breast and acknowledges the incurability of the disease [l]. In their efforts to treat cancer, physicians have used methods which have ranged from innocuous to lethal, from ridiculous to repulsive. In the 18th century, for instance, a Dr Pitfield had the following to say about the use of toads for the local treatment of breast cancer [l]: “The animal is put into a linen bag, all but its head, and that is held to the part. It has generally instantly laid hold of the foulest part of the sore, and sucked with greediness until it dropped off dead.” As for other forms of therapy, Hippocrates is credited with writing [2] that it was better not to treat internal cancer at all, lest the effects of the therapy be worse than the disease; his advice still needs to be recalled from time to time. The invention of the microscope and its application to biological problems ended the era of almost total ignorance about cancer. The study of clinical material ushered in a golden age of pathology, instructing the physician that cancer is, in its essence, an abnormal growth of abnormal cells. Positive feedback developed as the study of tumors led to increased knowledge of cellular biology, while the burgeoning biological sciences enriched the study of malignant disease. Koller [4] has described those abnormalities of the nucleus which are the hallmarks of malignant cells. I would like to transpose his comments to a single illustrative clinical situation so that the participants of this Conference, who are of widely diverse backgrounds, will be constantly reminded of the extraordinary clinical implications of our knowledge of the nucleus, as well as of the challenging limitations which still confront us. In 1832, six years before Schleiden and Schwann formulated the cell theory, a Scottish physician named Hodgkin described a new disease in an article entitled “On Some Morbid Appearances of the Absorbent Glands and
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