History and Geography

Leukemia was identified as a new disease in 1845 by two independent observers. John Hughes Bennett, lecturer in clinical medicine and pathologist to the Royal Infirmary at Edinburgh, published his observations in the Edinburgh Medical Journal of Octo ber 1845, a month before Rudolph Virchow published his findings under the title Weisses Blut. Two years later, Virchow named the disease leukemia, Greek for "white blood," and Bennett in 1851 called it leucocythemia, Greek for "white cell blood." Both men, who were keen observers and in the early stages of what were to become distinguished careers in medicine, made their observations at the autopsy table. However, it is unlikely that the disease was new in 1845, for there had been earlier reports of what was described as peculiar conditions of the blood, pus in the blood, and "milky" blood, with some symptoms compatible with those of leukemia. David Craigie in Edinburgh and Alexandre Donné in Paris, among others, were physicians who in the decade previously were alert to something odd in the condition of the blood of certain patients.

The microscope at that time was a crude instrument, and there was no satisfactory means of illuminating the specimens being observed. In fact, what is remarkable is that the disease was recognized at all, when one considers its rarity, on the one hand, and the continual epidemics of infectious diseases as well as chronic ailments of the last century which occupied the medical profession, on the other. But after recognition, reports of suspected or actual cases of leukemia began to appear in the literature, slowly revealing its worldwide distribution. Case reports from Europe and America also indicated the ineffectual nature of any known therapy.

Two breakthroughs occurred in the last half of the nineteenth century. The first was the discovery by Ernst Neumann in 1868 of the importance of the bone marrow in the formation of blood; a year later, he published his report on the changes in the bone marrow in leukemia, which introduced the term myelogenous leukemia. The second came in 1877, when Paul Ehrlich, a medical student at the time, developed a stain that permitted the cells to be clearly defined. By then, the microscope had been improved, and the new technique of staining enabled features of the blood to be studied that had hitherto been unseen or unsuspected.

Thus began a new era in hematology, but it was to be nearly 70 years before any progress was to be made in the treatment of leukemia. This began with the realization that folic acid was important to blood cell formation, and that its lack caused anemia and, significantly, a decrease in the white cells. Ensuing experiments showed that some preparations containing folic acid inhibited growth of experimental tumors, whereas other observations indicated that it might stimulate the growth of leukemic cells. This led a group of researchers in the United States to develop a series of new drugs that were designed as antagonists of folic acid for trial in the treatment of human cancers. Aminopterin was one of these new drugs and was used with much success in the treatment of acute leukemia by Sidney Farber and his group at Boston Children's Hospital in the late 1940s. Much research followed in a quest for new and more successful drugs to combat leukemia, with the result that by the late 1980s there was an established armamentarium of drugs used mostly in combination to achieve a remission and to maintain it.

Leukemia is a disease of major interest in both hematology and cancer research where much progress has been and is still being made, measured in terms of patient survival. Moreover, the outstanding "problem areas" of research are now more clearly defined and recognized, and current research efforts (in both pure and applied settings) within the fields of cell and molecular biology, immunology, cytogenetics, and virology are directed toward investigating such problems as the following:

1. Application of molecular mechanisms in therapy to destroy leukemic cells

2. Role of viruses in influencing the development of the disease

3. Nature of environmental triggers of leukemia

4. How to achieve earlier recognition of leukemia

5. How to understand the scientific basis for remission and thus how it can be maintained

6. How to eliminate residual disease

It is hoped that improved therapy for both adult and childhood cases will result from these complex and concentrated research efforts and that survival rates will be increased even more. Virchow wrote the following in 1858: "I do not wish by any means to infer that the disease in question [leukemia] is absolutely incurable; I hope on the contrary that for it too remedies will at length be discovered." Today there is optimism that Virchow's hope will be realized.

Gordon J. Piller

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