Deformities as Cues to Understanding Development of Form

PERSPECTIVES IN BIOLOGY AND MEDICINE Volume IV · Number 2 · Winter 1961 DEFORMITIES AS CUES TO UNDERSTANDING DEVELOPMENT OF FORM PAUL WEISS* Organic form—the architecture and texture of organisms—is better known than understood. Just how and by what mechanisms a mass of cells undergo that typical sorting and ordering in space which gives an organism its shape, is still one of the most obscure problems of living nature. Its study has gained momentum ever since experimentation started to supplement sheer description. Experiments reveal inner workings by establishing causal relations. They do this by decomposing a complex situation into component features and testing one at a time to ascertainjust what depends on what. But how is one to knowjust where to start when one is faced with a perplexing multitude of factors, all of potential relevance, and often, having singled one out for study, finding that it does not lend itselfto experimental variation, controllable at will? It is in this dilemma that acute observation of nature is of immense help; for it can register any departure of observable features from their standard norm, and, if we then succeed in pairing this deviation with a corresponding variation in the external circumstances, we immediately come to suspect a causal nexus deserving closer examination. Although such a pairwise correlation is not ofitselfproofofa causal relation, it is suggestiveand, ifcoincidence can beruled out, itcanserveas theequivalent * The Rockefeller Institute. This article is the text ofa Lowell Lecture delivered in Boston October 30, 1958. It is reprinted by permission of the publishers from Disease and the Advancement of Basic Science, Henry K. Beecher, editor; Cambridge, Massachusetts: Harvard University Press, copyright i960 by the President and Fellows ofHarvard College. I33 of a tentative experiment—in that case, an "experiment of nature." Of course, the more familiar we are with a class of objects, the smaller will be the deviations that we shall be able to perceive. Man, as our most intimate acquaintance, thus becomes the richest source of detectable distinctions, and the sharpened eye of clinical experience can justly take credit for having pointed the way to significant advances in the science oflife by having uncovered unsuspected, and having confirmed suspected, correlations. The study of development has shared extensively in these benefits. While it repays for them by delivering to clinical practice a more solid understanding of the growth and repair of tissues as guide to improved treatment and prevention of disease, it gratefully acknowledges the pointers and stimuli received. Form is the visible expression ofthe formative processes that have been instrumental in its shaping. The end result is but the residual record of its formative history. Clearly, then, changes in the standard pattern offormative processes leadto deviations from the standard form: deformations end up as "deformities." In this sense, "deformities" become valuable clues to the inner workings of formative processes. How instructive they have been can be documented by a long list ofexamples, from the nonviable double-headed or otherwise partially twinned bodies arising from single eggs, to such less detrimental aberrations as supernumerary digits, split palates, or fused joints. They have furnished crucial evidence against the theory of rigid prelocalization of distinct body parts in the germ and in support of the concept of embryonic development as an intricate assembly-line process in which the original material endowment ofthe egg is progressively transformed by chains ofdifferent and complicated interactions proceeding according to a definite inherited production schedule (1,2). This schedule has become so blueprinted by evolutionary experience that, given a standard range of environmental conditions (climate, nutrition, stresses, and so forth), it will lead to viable and reproductive individuals capable of passing on that pattern and schedule to successive generations. To yield viable results, these schedules must be sufficiently flexible to allow for adjustments to the unique and unpredictable fluctuations of conditions prevailing during the developmental period of any one individual. In other words, the genetic blueprint provides for tolerances. But the latitude of such tolerances is limited and narrowly defined, and, in general, the innumerable tributary processes 134 Paul Weiss · Deformity Cues to Development Perspectives in Biology and Medicine · Winter 1961 feeding into the assembly chain must not be too far offthe timing pattern...