Nature Medicine10, 1307 - 1320 (2004)
Published online: 3 December 2004; | doi:10.1038/nm1159
An innately interesting decade of research in immunology
Ronald N Germain
Ronald N. Germain is in the Lymphocyte Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. rgermain@nih.gov
"Nature has provided, in the white corpuscles as you call them—in the phagocytes as we call them—a natural means of devouring and destroying all disease germs. There is at bottom only one genuinely scientific treatment for all diseases, and that is to stimulate the phagocytes." So opined B.B. in G.B. Shaw's The Doctor's Dilemma1 in a dramatic restatement of a key portion of Ilya Metchnikoff's Nobel Prize address: "Whenever the organism enjoys immunity, the introduction of infectious microbes is followed by the accumulation of mobile cells, of white corpuscles of the blood in particular which absorb the microbes and destroy them. The white corpuscles and the other cells capable of doing this have been designated 'phagocytes,' (i.e., devouring cells) and the whole function that ensures immunity has been given the name of 'phagocytosis'"2. Based on these insights into the foundation of resistance to infectious disease, Metchnikoff was awarded the 1908 Nobel Prize in Physiology or Medicine together with Paul Ehrlich (Fig. 1). Although both were cited for discoveries in immunity, the contributions of the two men seem worlds apart. Ehrlich's studies did not deal with generic responses to infection, but rather with the highly specific nature of antibodies and their relationship to the cells producing them: "As the cell receptor is obviously preformed, and the artificially produced antitoxin only the consequence, i.e. secondary, one can hardly fail to assume that the antitoxin is nothing else but discharged components of the cell, namely receptors discharged in excess"3. But biological systems are just that—systems—and the parts need to work together. And so we arrive, a century later, at an appreciation for just how intimately related these two seemingly disparate aspects of host defense really are.
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