Perspectives in Biology and Medicine

DECONSTRUCTING DISEASE: AN ANATOMY OF ILLNESS IN THE AGE OF MOLECULAR BIOLOGY PAUL H. PLOTZ* To the reader and writer of the medical literature, nothing looks quite so old as a book off the shelf, or ajournai from the bottom of the stack, or an old reprint. Old, meaning last year's. Perhaps the collector's heart lifts, but mine sinks. Old bindings—purple, tough, with gold lettering— lift my heart only if my father's or grandfather's name is written on the flyleaf. Otherwise they age me and make me want to pick off the polyethylene wrapper from this week's Science—or next week's. We are, it seems to us (and it seems to me undeniably so) living in the midst of a marvelous scientific revolution. There are more of us, and we are unwrapping secrets faster than ever and trying to let everyone else know so as fast as we can. When a woman from Chicago called me recently to offer her father's notes on his illness, it took all my manners to accept. When they came, along with a note asking that they not be returned, I found, in a creaky script on the pages torn from a spiral notebook, the dates of his illness. It began when I was a medical student—namely, only the day before yesterday or so. Everything about them was archaic. There are some simple explanations for this reaction. Paper yellows and brittles rapidly; the page size of the journal, the cover design, the layout, the column size, the advertisements, and, especially, the typeface trumpet last year's or last decade's or last generation's preferences. Photocopies mitigate this sensation only slightly, and not at all when one pays attention to the words. Our forebears in medicine—at least those since the overthrow of classical authority—would have had, I believe, the same kind of reaction to the observations of their predecessors. After all, that is—at least in part— what drives us on to correct, to emend, or especially, to enlarge their views. But at the heart of the reaction to these relics is a discomfort with the A version of this text was delivered as The Richard H. Freyberg Lecture at the Hospital for Special Surgery of New York Hospital on 2 November 1995. * National Institute ofArthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Clinical Center 9N244, Bethesda, MD 20892.© 1996 by The University of Chicago. All rights reserved. 0031-5982/97/3904-0980$01.00 1 60 Paul H. Plotz ¦ Deconstructing Disease very words—especially the names of diseases. The names embody the concepts and boundaries of the diseases that we encounter at the bedside, study in the laboratory, and treat. And insofar as the words convey concepts, both scientific and categorical, which have changed, sometimes ever so slightly, we feel uneasy. Of course there are new diseases abroad in the land. In this century for example, we have discovered new diseases: myocardial infarction at one end of the century, AIDS at the other. It is likely that we gained rheumatoid arthritis only after the return of the European explorers from the New World. And we have lost some diseases: smallpox, polio, rheumatic fever, perhaps even hysterical paralysis. More notable, however, is that we have reconstructed or rearranged diseases. We have lost—not the way we lost smallpox—Bright's disease and apoplexy. We have discovered collagen diseases and autoimmune diseases. We have rearranged things everywhere. At the center is a change in the way disease names are used and the kinds of data which are used to support divisions among diseases. Diagnostic labels are most important as guides to therapy. A disease name embodies a prognosis and a prescription. But modern biology has brought us more diseases than we have names for, and that is the quandary to which I address these remarks. I will begin with the question "Where is the disease?" On close examination , I will argue, what has mostly changed in these reconstructions and rearrangements—which are the product of the rise of rational and experimental medicine from the Enlightenment to the current molecular biological revolution—is our...