Serendipity—Code word for planning

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sary academic umbrella to all other qualified health facilities (such as community hospitals, sanitariums, clinics and psychiatric facilities) will be the necessary ingredient. The Kansas plan “Not Four Years But Forty” has been a success and can well be the

Serendipity-Code

prototype for initial efforts with the regional medical program. It is but a beginning, however, to the potential that can be gained by opening the medical school further and using medical education as the basis of the missing dialogue.

Word for Planning

DONALD S. FREDRICKSON, M.D., F.A.c.c.*

0

N an afternoon not so long ago I was finishing a discussion with the fellows and house staff of one of the teaching hospitals. The crowd had thinned down to a lone diehard who disentangled a copy of TIME from the stethescope in his white coat pocket and said with a grin, “Aren’t you worried about Li?” “Lee?,” I said. “I mean Li, the principle of social order,” he replied, opening up the magazine to the Foreign Affairs Section and pointing to a bit of italics over a column on Chinese antirevisionism. I read: “Li, or the principle of social order, prevents the rise of moral or social chaos as a A people who do away dam prevents a flood. with the old principle of social order meet with moral disaster.“-Confucius.’ It was that second sentence. The tone of our earlier discussions that afternoon meant that he was reading it something like, “A people who tinker with the old order of solving scientific problems court disaster.” This translation of Li is a common concern among many biomedical scientists. There is fear that the established mode of acquiring new scientific knowledge will be warped or even crippled by accelerated demand for practical applications, that support for basic research will dwindle as targeted missions increase. Such fear is not based on frivolous or selfish concern. I believe, however, that it is not free of misconception ; and I believe it will prove At least this is how I see to be unwarranted. this problem now in relation to cardiovascular research and the NationaI Heart Institute. First of all, as the custodian of the largest single sum provided anywhere in the world for cardiovascular research and training, all of it

public funds, the National Heart Institute is assuredly goal-directed. Its mission is to increase understanding of the cardiovascular system and its disorders so that the daily battle to which members of the cardiovascular community are dedicated will be fought with everForging better weapons increasing success. against disease is thus the ultimate objective of the activities we support. The need for practical improvements in our weaponry against cardiovascular diseases needs no further documentation here. How handy it would be today if we had a practical, reliable test for renal hypertension; or a way to determine precisely an itnminent threat to blood flow in one of the small vessels that supply the brain, especially to those areas whose functions preserve the fine distinction between vitality and helplessness. How much we would like to have instantaneous and certain means to clear a clot from the lung, or--taking the long view-to offset the effect of mutant genes that may spell early death from atherosclerosis. Or, consider myocardial infarction. At the present rate, about a quarter of us adults will die from this disorder. It claims on the order of 400,000 Atnerican lives a year, and the death rate is increasing even in younger age groups. Is there any cause to be satisfied with the available ways to ward off an infarct, to determine accurately the state and extent of muscle daInage as opposed to electrical disturbances? Can we make any claim to an understandiilg of the determinants of survival in cellular or molecular terms, and cannot we still find more rational measures to bring these determinants into favorable balance? No one quarrels with the urgent desire to see And with due credit to such problems solved. man’s ingenuity, few can doubt they ultimately

* Director, National Heart Institute, Bethesda. THE AMERICAN

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OF CARDIOLOGY

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Agencies

But there is always the question of how will be. to proceed most expeditiously. Given the seelningly inevitable combination of limited resotlrccs and unlimited needs, we shall always ha\.e to make decisions about the allocation of tinlc and money and people to the business of solving disease-oriented problems. At the present state of knowledge of biology, it is beyond debate that the distribution of support and the deployment of creative, observant people Inust be very broad indeed. The vast majority of our needs in fighting disease cannot he met by strictly targeted programs. Let us look, for example, at the history of one or two of the most potent new diuretics that have been developed. These invaluable drugs have made it possible for us to participate in a current revolution in management of congestive heart failure. Their story is not atypical of progress in medicine. It begall with simple curiosity on the part of puhnonary physiologists about how the lung managed to turn so much bicarbonate into carbon dioxide so quickly. Carbonic anhydrase was discovered. Quite unrelated curiosity about the side effects of sulfanilamide, observed when it was used as an antibiotic, led to recognition that sulfanilarnide was a carbonic anhydrase inhibitor. When renal physiologists saw in sulfanilatnide a way to assist them in examining the mcchanistns for acidification of urine, it was discovered that carbonic anhydrase inhibitors enhanced sodiuln excretion. &search was then set in motion to develop better inhibitors. Enter chlorothiazide. Finally, analogies with its chemical structure produced furosemide, one of the most potent diuretics yet developed. The initial discovery, then, like a stone dropped into a pool, set up perturbations that had distant and totally unforeseen effects. It illustrates the essentiality to medical progress of what in biology is commonly called basic or undifferentiated research. The epilogue to the story I have just told has a wry twist. The diuretic actions of chlorothiazide and furosemide are different; and their nlarvelous clinical effect will likely turn out, in the end, to have nothing to do with carbonic anhydrase inhibition. Some will seize upon such irony to emphasize a belief that scientific progress is determined by serendipity, the gift of unexpected pleasant discovery. But, alas, I fear this is shortsighted. Serendipity did not produce furosemide. It was produced by the progressive cross-fertilization of VOLI’MI?

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ideas and technics in a carefully cultivated bed. Each question asked and answered had its own minds derivatives. Trained and observant made connections between these derivatives. Eventually what were single threads became a fabric as the synaptic pattern widened and becanle more tneaningful. \Ve have already justified the undifferentiated research essential to one portion of this sequence. But it has no meaning to health unless provision is made for the completion of the chain. To a man who is ill, the discovery of a new chelnical compound is exciting only if it has been pro\red to be safe and helpful to him. In the process of turning new knowledge to the relief of disease, it is equally essential, then, that there always be in the neighborhood of discovery those who can foresee further application and accomplish it. The provision of environments where this can he so and the distribution of resources to maintain in balance all the components in the systenl of discovery is a primary concern of us all. In our own area of cardiovascular diseases this common concern merits several observations. One is that the demand for clinical exploitation of new information is greatly increasing. The reason for this is the expansion of opportunity. It grows in rough proportion to the expansion of new knowledge. In the cardiovascular field, the pressures are now expressed in many examples. Some arc large-scale clinical trials, requiring considerable stable support and skilled manpower for periods of three to ten years. These include the Coronary Drug Study, moving toward its ,goal of 8,500 patients needed to answer the question of whether certain lipid-lowering drugs can decrease the recurrence of myocardial infarction. The Diet-Heart Study, completing its feasibilit) phase, is another. Other collective research is dealing with such questions as the \.aluc of surgical correction of extracranial vascular occlusive disease in preventing recurrence of strokes, the effects of repairing renal artery disease, or of the ability of gamnla globulin to reduce the incidence of hepatitis after extracorporeal circulation. As expanded basic research increases the pressures for developmental research, the need for great selectivity in the commitment of resources and wisdom in the planning for their expansion becomes ever mor( acute. Apart from the problem of assigning priorities to specific targets, there is another important

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question: Have we made the best provisions for steady adaptation of new knowledge to solution of some problems in cardiovascular disease? In other words, can we profitably increase the likelihood of desirable collisions between prepared minds and answerable questions? To this end, the Heart Institute, acting on responsible advice from the cardiovascular comnlunity and with the support of Congress, is taking several steps. It is planning for the creation of a number of cardiovascular research and training centers. Special resources will be created in centers of excellence so that we may increase the proximity of skills in many disciplines to cardiovascular problems and also increase the number of highly trained scientists active in the broad area of cardiovascular research. With more directed intent, the Institute will make available this spring support for Myocardial Infarction Study Centers. This program, conceived mainly by the late Dr. Robert Grant, is designed to provide resources that will expand the capability for better gathering of data from patients with infarcts. It will encourage the application of new technics in physiology, biochemistry and pharmacology to the problem of myocardial insufficiency. This is a territory of the unknown into which pioneers in assisted circulation have ventured and reported a great need for more organized expeditions in search of knowledge. Greater oppor-

Discussion tunity for training needed specialists in c1inica.l research on infarction will be provided. .4nd it is intended that ways shall be found to draw attention of creative talents from other disciplines to a disease they have often ignored as a province of mystery and hopelessness. This is planning for serendipity. To achieve the ends that we all agree are desirable, it is possible that, from time to time, we may have to alter Li a little, but I feel certain that we can do it without inviting moral disaster. I should like to add one last note. Each scientist and clinician learns as he matures in his profession that the search for new knowledge and its use to save lives is a process that demands total involvement. To participate in one phase, one must share in the others. For the thrill of discovering, of healing, or of tutoring is exacted a stake in the critiques, the guidance, the planning and the decisions that affect not only one’s own activities but those of the whole. This poses demands that are heavy and ever As they pertain to the programs increasing. of the National Institutes of Health, the biomedical community has responded to these demands with great unselfishness. This alone augers exceedingly well for the future of our common endeavor. REFERENCES 1. Time Mngorine, 89:

27 (Jan. 27), 1967.0

Health Partnership Federal Privatism -The Creative Public Care

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JAMES L. GODDARD, M.D.*

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going to speak briefly this morning, and the limitations on my remarks are twofold. First of all, I consider, unlike many men of the cloth, that at this hour on Sunday I am no: going to save many souls with a long speech. And secondly, my role here is somewhat limited; so I am going to follow the old admonition that Basically, the shoemaker should stick to his last. I wish to raise with you this morning the question how we can improve patient care with respect to drugs and therapeutic devices. I will comment very briefly on several aspects AM

of this question. It will become obvious to you that I don’t have the answer, but I wish, by raising the question, to stimulate your thoughts and ideas so that we may indeed exchange points of view. First, it seems obvious that there is need for better information about our therapeutic agents, One of the whether they be drugs or devices. most striking deficiencies today, it seems to those of us who work day by day with the problem, is the lack of a comprehensive drug compendium. There is progress being made,

* Commissioner of Food and Drugs, Food and Drug Administration, Washington, D.C. THE

AMERICAN

JOURNAL

OF CARDIOLOGY