18 Perspectives in Drug Therapy FRED W. SCHUELER
Downloaded by UNIV OF PITTSBURGH on May 14, 2016 | http://pubs.acs.org Publication Date: January 1, 1964 | doi: 10.1021/ba-1964-0045.ch018
Department of Pharmacology, Tulane University School of Medicine, New Orleans, La.
The technique of "molecular modification" in drug design and development is analogous to the technique of variation as employed in other sciences and the arts. Indeed, it is through the technique of variation applied to prototypes that nature as well as mankind operates toward the full realization of potentialities in various areas of evolution. Molecular modification followed by pharmacologic testing and selection is thus seen to be analogous to biologic development via cross fertilization or mutation followed by survival-selection on the one hand, and dress design through variation and survival-selection in the world of taste basic to the garment industry. The layman is keenly aware of the salient roles that variation and selection play in the realization of useful varieties in animal husbandry and agriculture. The richness of life forms of the animal and plant world, for food, labor, and esthetic appreciation are all primarily the result of the processes of variation and selection whether applied consciously or unconsciously by man and nature. The artist is keenly aware of the technique of variation and selection as in the development of themes into symphonies in music, in the plastic and pictorial arts, and in architecture. City planning, cooking in the home, adaptation of natural resources such as the harnessing of river systems, and children at play, all share methodologically a common bond with molecular modification and pharmacologic selection. Those who would degrade the technique of molecular modification by reference to it as mere "manipulation" capable of achieving only "me too" products in the pharmaceutical industry, thus show not only a profound ignorance of the concretely demonstrable results of modern therapeutic research but also their ignorance of a profound method that is everywhere one of the most powerful creative resources in both man and nature. The present symposium has demonstrated, by outstanding presentations, the force of the above arguments by examples drawn from some of the major medical advances of modern times. Through presentations by some of the foremost chemists and physicians in America today, we have seen, in bold relief, advances in the areas of: infectious disease; cardiovascular disease; control of pain; mental disease; diabetes; and the control of fertility. Moreover, it is clear that these advances are the direct result of systematic modifications and pharmacologic testing such that advances in several of the above-named six areas of human suffering are bound immediately to the method of molecular modification through variation in a given series of chemically related products. By way of example, we have seen how the discovery of the antibacterial 221 Schueler; Molecular Modification in Drug Design Advances in Chemistry; American Chemical Society: Washington, DC, 1964.
MOLECULAR MODIFICATION IN DRUG DESIGN
Downloaded by UNIV OF PITTSBURGH on May 14, 2016 | http://pubs.acs.org Publication Date: January 1, 1964 | doi: 10.1021/ba-1964-0045.ch018
222
properties of sulfanilamide has, through molecular modification, yielded key drugs in the treatment of congestive heart failure, essential hypertension, and diabetes. Systematic molecular modification of the early antihistamine drugs has led to major breakthroughs in the control of mental illness and a revolution of formerly prison-like mental institutions to modern hospitals, at the same time freeing the community of enormous expense in the care of thousands of patients who can now pursue their lives in a normal, or nearly normal, way as valuable members of the community. With products already available through the method of molecular modification of the sex hormones, we now have agents highly potent in the control of fertility but devoid of serious effects referential to secondary sexual characteristics. Their actual employment in the amelioration of what many consider a most serious problem facing all of mankind—overpopulation—is, of course, a decision to be made in the social context of the various centers of overpopulation. Perhaps even more important for the future are the new science and technology that have grown immediately out of the accumulating information concerning the relationship between the chemical constitution of molecules and their pharmacologic effects. It is through the latter that chemists are now able to predict with a remarkable degree of certainty in given areas of drag design, that substances not yet synthesized will have given qualitative effects and often quantitatively estimate with surprising reliability their potency relative to already known drugs. It is the development of such predictive theoretic methods that marks the coming of age of any science. It is also this coming of age as a predictive science that can be seized upon by concerns which would easily develop "me too" drugs with minimal effort. While such mean employment of the science is possible, it should not in any sense reflect a deprecatory note upon molecular modification as a method. Indeed, that such use of the predictive capacity of a science is possible is actually a measure of the power of that science! Criticism should be leveled rather at those who employ the method for mean ends rather than at the method per se. In further future perspective, a most serious problem yet to be satisfactorily resolved is the systematic centralization, organization, and retrieval of information, resulting from the method of molecular modification and pharmacologic testing. Here again, the difficulty is not due to the method, for the machines and devices for informative processing, retrieval, and correlation already exist. The difficulty is the human one of making the critical decision to use the machines and devices for the benefit of all while safeguarding rightful ownership. Some years ago the organization of a chemical-biological coordination center represented a step toward the centralization and dissemination of information in this area on a national level. It is unfortunate that this program was discontinued, apparently because of lack of funds. Overfall, the criticisms leveled at molecular modification, a technique that has yielded a new science, have been quite erroneously aimed at the value of the subject when they should have been directed at human manipulators. The case for molecular modification is clearly summarized in the fact that it has yielded, in the last 25 years, more potent and more useful drug agents in various areas of therapeutics than have been reported in all previous history. RECEIVED December 9, 1963.
Schueler; Molecular Modification in Drug Design Advances in Chemistry; American Chemical Society: Washington, DC, 1964.
