NORMAL YOUNG MEN ROGER J. WILLIAMS, Ph.D., D.Sc. (hon.)* There have been hundreds ofoccasions in connection with medical programs when groups ofnormal, healthy young men have served as "controls ." These young men have been free from organic disease and have often been selected from among students or other available personnel on the assumption that, since they were normal individuals, they would yield valuable norms with respect to blood, urine, or any other physiological or biochemical item or process under examination. However, on the basis ofstudies carried out in our laboratories, as well as other considerations, I propose a concentrated and follow-up study ofthe values obtained from such young men for a very different reason. It appears certain that such studies will yield insight into the etiology of many diseases of obscure origin as well as contribute insight into diseases about which we already have substantial information. The laboratory findings which have indicated the desirability of such investigation include the discovery that each individual has a distinctive "metabolic pattern," as reflected, for example, in the distinctive composition ofhis saliva, urine, and blood and in his taste sensitivities for various common substances (i, 2). The existence of such "metabolic patterns" is more important than is any particular way of gaining evidence with respect to them. Our findings with respect to blood have not been published in detail (2) but offer substantial support for the concept. There are also collections ofdata in other laboratories which probably would, ifassembled , support the same thesis. When we speak of"metabolic patterns," we refer to the pattern ofchemical operations going on within each and every organ and tissue in the body. Such patterns are mirrored very im- * Director, Biochemical Institute, University ofTexas, Austin, Texas. Contribution from the Clayton Foundation for Research, the Biochemical Institute, and the Department ofChemistry, University ofTexas, Austin, Texas. 97 perfectly by any set ofmeasurements we are now able to make; they are much more deeply rooted than their observed outward manifestations might suggest. The existence, however, ofdistinctive patterns in urine, in saliva, in duodenaljuice (3), and in blood constitutes cumulative evidence that basic metabolic patterns exist. There is a large body ofevidence—anatomical, genetic, physiological, pharmacological, biochemical—which also supports this idea (4) and bears out the conclusion that the differences between the patterns of two normal individuals may be large and of far more than academic interest. A basic consideration which bears upon the existence ofmetabolic patterns is the clear-cut evidence, which applies throughout the biological kingdom, that genes in a sense beget enzymes and that partial genetic blocks are very common and may result in impaired enzyme efficiencies involving different degreees of impairment. Since normal human individuals have distinctive genetic backgrounds, it follows that the details of their body chemistries must be distinctive, with many possibilities ofdifferences which are predominantly quantitative rather than qualitative. An anatomical basis for postulating the existence ofdistinctive genetically determined metabolic patterns is the fact that each individual has organ sizes, including endocrine glands, which fall into a distinctive pattern. The study of645 normal male rabbits ofsimilar breeding by Wade Brown and co-workers (5) showed that the weights of the hearts, livers, kidneys, testicles, brains, thyroids, parathyroids, pituitaries, and adrenals, after correction for differences in body weights, varied over a 9.4-fold range on the average, with a 7.1-fold median range. Comparable ranges for normal human beings are not readily available, but they are probably not radically different. Along with these gross anatomical differences are microscopic differences with respect to the cell composition, for example, of the endocrine glands. The extensive biochemical evidence (4) cannot be reviewed here; it indicates that, while healthy young men of the same height and weight may resemble one another in their over-all oxygen consumption, specific chemical reactions may take place, under basal conditions, five or ten times as fast in one individual as in another. Probably the most direct extensive evidence on this point is based upon differences in enzyme levels and enzyme efficiencies. Perhaps next to this in importance is the fact that there are wide individual differences among "normals" with respect to several 98 RogerJ. Williams · Normal Young Men Perspectives...