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The logic of medicine
The Logic of Medicine EDMOND
A. MURPHY,
One may regard the medical school as a professional academy for the cultivation of concerned, intelligent, responsible dispensers of the complicated art of healing. It draws on modern technics and the fruits of basic science. It is not clear why, apart from its tradition and its natural dignity, such a discipline should be in a university, any more than a conservatory of music, an academy of art or a school of ballet. Those who see a university as a seat of learning and not as a center for teaching (however sophisticated), will think that medicine as an “applied science” is out of place. It is laudable that American medical schools have fostered exchange between bedside medicine and the basic sciences. Alert practitioners of medicine maintain scientific interests. But the notions readily arise that the clinical arts are concerned with marketing the secure truths of human biology: that the creativeness of clinical medicine lies in adapting knowledge to practice and occasionally detecting intriguing problems for the scientist to solve. If the physician, dedicated fulltime to research, is not to use his medical training and must compete on an equal footing with the mathematician or the molecular biologist, one might wonder what point-apart from instilling a vague sentiment of commitment to mankind-there was in his attending medical school. The fundamental cause of this unbalanced view appears to be the lack of a strong philosophy of medicine. I used the word “philosophy” in a strict sense: not as a general attitude of purpose, but as a formal enquiry into the structure of medical thought. A distinguished medical historian has had some sense of this fundamental need [l]. I suspect, however, that history is not a discipline with the necessary abstraction and rigor of analysis to fulfill this function. We live in an age of medical reductionism, doubtless a reaction to vitalism and its mystical excesses. We un-
M.D.
critically hold certain views, such as, that all scientific rigor is metrical; that study of vital mechanisms can, and should, be resolved into the study of pure compounds; that multivariate processes can, without distortion, be condensed into simple quantities (like intelligence quotients or countless “diagnostic indices”]; that a medicine not intrinsically taxonomic is unthinkable: that the only alternative to determinism is chaos; that all uncertainty about outcomes is due to ignorance; that concepts are ontologic rather than heuristic: that it is better to be precisely wrong than roughly accurate; that cautious vagueness is a hallmark of mature wisdom, and much more. The peril of these views lies not so much in the fact that they may be untrue as that they are implicit: that they bespeak not so much affirmation as unreflecting assent. I could refute each of these assertions by counterexamples from human genetics, where the currently most rewarding fields are not metrical at all; where naive evolutionary theory is in decay; where ever more refined evidence of heterogeneity is sounding the death knell of comfortable taxonomies; where the formal laws of evidence are neither deterministic nor vacuous, but triumphantly probabilistic; where genetic prediction is precisely uncertain; where gratuitions vagueness in prediction is charlatanism. But such refutations skirt the main issue. Many lament that clinical medicine has become depersonalized; but if their plea is for humaneness and nothing more, there is some risk that it may degenerate into sentimentality or even discourage intellectual venturesomeness. However narrow, reductionism has at the least produced its demonstrable (and seductive) successes. The deficiencies of reductionism are more elusive than the successes. All that the study of components can tell us is what the components are like. It overlooks entirely the Aristotelian “category” of relationship.
Dr. Murphy is Professor of Medicine and Head of Medical Genetics at lohns Hopkins University. From his interests in theory of clinical genetics (especially of common diseases) he has written “Principles of Genetic Counseling” (1975). a monograph on problems of inference “The Logic of Medicine” (1976) and “Probability in Medicine” (1979).
June 1979
The American Journal of Medicine
Volume 66
907
MEDICINE, SCIENCE, AND SOCIETY-MURPHY
Compensatory scoliosis does not occur because the right leg is short, or the left leg is long, but because the legs are of unequal length. A fistula between a pulmonary and a subclavian artery is harmful in most, but life-saving in those with the tetralogy of Fallot. A hematocrit in the healthy people of the high Andes would cause consternation in New York [pollution or no pollution). No sensible clinician .believes that clinical data can in general be interpreted in isolation. Yet the very notion of the “normal range” is perilously close to denying the importance of context, and it is apt to be so misused by those who have neither a whole approach to medicine nor the corrective of painful experience. We have, somehow, become trapped by the fallacy that the components are more real than the ensemble; that the more readily something can be precisely defined the more real it is. (It would be thought absurd to talk about imaginary growth hormone, but not about imaginary pain. Unfortunately, the strongest counter which one hears to the latter solecism is that “pain is real for that person,” a rebuke mistakenly supposed compassionate although the very antithesis of corn-passion.) The fallacy lies in the word “real,” which currently has rhetorical but no veridical value. We have examined in some detail elsewhere [Z] the relationship between a sequence of four terms; coronary disease: high blood cholesterol level: a putative disorder, familial hypercholesterolemia; and a specific enzyme, 3-hydroxy-3 methylglutaryl (HMG) co-enzyme A reductase. This sequence recapitulates a progressive refinement of insight. But the question addressed by the last term is not the same as that addressed by the first. It is useless to declaim about which is the more “real” without a criteriology of reality. Geneticists welcome the Goldstein-Brown ‘model [3] with open arms. But the reader might well consider whether he would rather have ventricular fibrillation with normal HMG co-A reductase or be running a 4-minute mile with an abnormal enzyme. Death is at least as much a reality as an enzyme, a fact which the epidemiologist is not slow to point out in discoursing on hard endpoints. A narrow concern with single genes, biochemical compounds or the central limit theorem, however fruitful, destroys our vision of the human organism, which, even in purely physicochemical terms, is an elaborate system of interlocking, cybernetic mechanisms. Whether or not it will ever be possible to infer the properties of the whole from a detailed knowledge of the parts (the well known philosophical issue of emergence) remains open. There is no doubt, however, that clear inferences about the operation of a system, by unexceptionable arguments from undoubted facts, may be counterintuitive. I cite five examples. I can produce a pedigree in which the recurrence risk of a Mendelian disorder is less if there is a positive family history of the disease than if there is not. With a simple two-locus system, a gene may be preferentially selected for because it is harmful. The pursuit of the excellent can be
906
June 1979
The American Journal of Medicine
proved to be dysgenic. In certain conditions, the larger the mean size of family surviving to maturity, the more likely the dynasty is to become extinct. The most likely interpretation of a group of measurements is to put each patient in his own personal category [4]. (This last conclusion is as near a universal as statistical theory can provide: and the only escape from it is to involve some counter-value. This issue of “the one and the many” is the oldest problem in formal philosophy.) Such paradoxes arise in simple systems. There is no reason to suppose that intuition is any better guide when the full force of interaction is operating. The formidable mathematical problem of explaining fully the tertiary structure of protein is well known, a problem trivially simple compared with that of the body as a whole. The narrowly analytical approach to the‘fundamkntals of medicine is in some danger of leading us into elegant irrelevancies, and the purely synthetic approach is likely to prove intractable. It seems as if the traditional pattern of medical research is still the soundest: diverse types of study at multiple levels of resolution, mutually illuminating and mutually correcting. The full natural history of a rational medicine might be that the raw data of experience are analyzed down to the most elemental level, and a whole medicine resynthesized from them. But the success of this approach must be, as it has been, that each level of enquiry should be sound. No longer, then, can the physician look elsewhere for the means to put his own house in order: clinical practice would require coherently developed rules of clinical evidence and clinical research. And here we have reason to be concerned at our lack of progress in the busiest half century in the history of science. More than anything else, the clinical department of medicine is concerned uniquely and distinctively with the diagnostic process. Diagnosis becomes more and more complex. It is a required skill of every medical student. The expense of medical care cries out for improved diagnostic efficiency. But we cannot optimize what we cannot formulate. We cannot evaluate where we have developed no criteria. We cannot educate where we cannot articulate. Why is the diagnostic process not the most popular field of research in the academic department of clinical medicine? Yet the prevailing attitude is one of apathy. It is not merely that readymade tools have not been furnished to us by “the basic scientist”: it is the attitude that the topic is boring and foredoomed to failure. Besides there is no problem to solve: diagnosis is merely a matter of practice and experience. The fundamental tenet of science is that economical systematization of many particulars is possible. Yet there are several hundred hemoglobinopathies known and no reason to suppose the supply exhausted. Not all are of clinical importance, but that argument is merely temporarily reassuring. The overwhelming problem facing students is the numbing proliferation of fact. There must come a point of congestive failure, when the
Volume 66
MEDICINE, SCIENCE, AND SOCIETY-MURPHY
prodigious idiocy of the computer emerges triumphant. By now, several constraints must be evident. Specialization and superspecialization must not proliferate indefinitely. Perspective, comprehension, any sense of the totality of the patient would suffer. Nobody can know it all. But much of “it all” is not worth knowing and much frankly false. We cannot equip all physicians to be expert in evaluating scientific evidence. Policing what purports to be fact is a demanding and unrewarding task. But even fanatical editorial vigilence would be vitiated by the proliferation of seductive and often frankly irresponsible journals. Yet these problems are not novel or unsolved. One recalls Samuel Johnson’s two kinds of knowledge: “. . we know a subject ourselves, or know where we can find information upon it.” We may savor Poincare’s definition of mathematics as the art of giving the same name to different things. Then, perhaps, it occurs to us that we might contain our problems by investing in the
continued production of sound and usable principles, a fraction of what we squander on collecting facts. I have faith that we can nurture coherence in clinical medicine, by a logic or an epistemology (or whatever you wish to call it). But it is not a process which will happen of itself. Among other institutions, the journals have a clear responsibility to foster sound theory and not to dismiss papers (however germane] on the grounds that they contain no new fact. REFERENCES I.
Tcmpkin 0: The Double Face of Janus, Baltimore: The Johns Hopkins University Press, 1977. 2. Murphy EA. Kwiterovich PO: Genetics of the hyperlipoproteinemias. Hyperlipidemia: Diagnoses and Therapy (Rifkind BM, Levy RI, eds). New York, Grune & Stratton, 1977. 3. Brown AS, Goldstein JL: Familial hypercholesterolemia. Trans Assoc Am Physicians 90: 91. 1977. 4. Murphy EA. Boiling DR: Testing of single locus hypotheses where there is incomplete separation of the phenotypes. Am 1Hum Genct 19: 322,1967.
June 1979
The American Journal of Medicine Volume 66
909
A. MURPHY,
One may regard the medical school as a professional academy for the cultivation of concerned, intelligent, responsible dispensers of the complicated art of healing. It draws on modern technics and the fruits of basic science. It is not clear why, apart from its tradition and its natural dignity, such a discipline should be in a university, any more than a conservatory of music, an academy of art or a school of ballet. Those who see a university as a seat of learning and not as a center for teaching (however sophisticated), will think that medicine as an “applied science” is out of place. It is laudable that American medical schools have fostered exchange between bedside medicine and the basic sciences. Alert practitioners of medicine maintain scientific interests. But the notions readily arise that the clinical arts are concerned with marketing the secure truths of human biology: that the creativeness of clinical medicine lies in adapting knowledge to practice and occasionally detecting intriguing problems for the scientist to solve. If the physician, dedicated fulltime to research, is not to use his medical training and must compete on an equal footing with the mathematician or the molecular biologist, one might wonder what point-apart from instilling a vague sentiment of commitment to mankind-there was in his attending medical school. The fundamental cause of this unbalanced view appears to be the lack of a strong philosophy of medicine. I used the word “philosophy” in a strict sense: not as a general attitude of purpose, but as a formal enquiry into the structure of medical thought. A distinguished medical historian has had some sense of this fundamental need [l]. I suspect, however, that history is not a discipline with the necessary abstraction and rigor of analysis to fulfill this function. We live in an age of medical reductionism, doubtless a reaction to vitalism and its mystical excesses. We un-
M.D.
critically hold certain views, such as, that all scientific rigor is metrical; that study of vital mechanisms can, and should, be resolved into the study of pure compounds; that multivariate processes can, without distortion, be condensed into simple quantities (like intelligence quotients or countless “diagnostic indices”]; that a medicine not intrinsically taxonomic is unthinkable: that the only alternative to determinism is chaos; that all uncertainty about outcomes is due to ignorance; that concepts are ontologic rather than heuristic: that it is better to be precisely wrong than roughly accurate; that cautious vagueness is a hallmark of mature wisdom, and much more. The peril of these views lies not so much in the fact that they may be untrue as that they are implicit: that they bespeak not so much affirmation as unreflecting assent. I could refute each of these assertions by counterexamples from human genetics, where the currently most rewarding fields are not metrical at all; where naive evolutionary theory is in decay; where ever more refined evidence of heterogeneity is sounding the death knell of comfortable taxonomies; where the formal laws of evidence are neither deterministic nor vacuous, but triumphantly probabilistic; where genetic prediction is precisely uncertain; where gratuitions vagueness in prediction is charlatanism. But such refutations skirt the main issue. Many lament that clinical medicine has become depersonalized; but if their plea is for humaneness and nothing more, there is some risk that it may degenerate into sentimentality or even discourage intellectual venturesomeness. However narrow, reductionism has at the least produced its demonstrable (and seductive) successes. The deficiencies of reductionism are more elusive than the successes. All that the study of components can tell us is what the components are like. It overlooks entirely the Aristotelian “category” of relationship.
Dr. Murphy is Professor of Medicine and Head of Medical Genetics at lohns Hopkins University. From his interests in theory of clinical genetics (especially of common diseases) he has written “Principles of Genetic Counseling” (1975). a monograph on problems of inference “The Logic of Medicine” (1976) and “Probability in Medicine” (1979).
June 1979
The American Journal of Medicine
Volume 66
907
MEDICINE, SCIENCE, AND SOCIETY-MURPHY
Compensatory scoliosis does not occur because the right leg is short, or the left leg is long, but because the legs are of unequal length. A fistula between a pulmonary and a subclavian artery is harmful in most, but life-saving in those with the tetralogy of Fallot. A hematocrit in the healthy people of the high Andes would cause consternation in New York [pollution or no pollution). No sensible clinician .believes that clinical data can in general be interpreted in isolation. Yet the very notion of the “normal range” is perilously close to denying the importance of context, and it is apt to be so misused by those who have neither a whole approach to medicine nor the corrective of painful experience. We have, somehow, become trapped by the fallacy that the components are more real than the ensemble; that the more readily something can be precisely defined the more real it is. (It would be thought absurd to talk about imaginary growth hormone, but not about imaginary pain. Unfortunately, the strongest counter which one hears to the latter solecism is that “pain is real for that person,” a rebuke mistakenly supposed compassionate although the very antithesis of corn-passion.) The fallacy lies in the word “real,” which currently has rhetorical but no veridical value. We have examined in some detail elsewhere [Z] the relationship between a sequence of four terms; coronary disease: high blood cholesterol level: a putative disorder, familial hypercholesterolemia; and a specific enzyme, 3-hydroxy-3 methylglutaryl (HMG) co-enzyme A reductase. This sequence recapitulates a progressive refinement of insight. But the question addressed by the last term is not the same as that addressed by the first. It is useless to declaim about which is the more “real” without a criteriology of reality. Geneticists welcome the Goldstein-Brown ‘model [3] with open arms. But the reader might well consider whether he would rather have ventricular fibrillation with normal HMG co-A reductase or be running a 4-minute mile with an abnormal enzyme. Death is at least as much a reality as an enzyme, a fact which the epidemiologist is not slow to point out in discoursing on hard endpoints. A narrow concern with single genes, biochemical compounds or the central limit theorem, however fruitful, destroys our vision of the human organism, which, even in purely physicochemical terms, is an elaborate system of interlocking, cybernetic mechanisms. Whether or not it will ever be possible to infer the properties of the whole from a detailed knowledge of the parts (the well known philosophical issue of emergence) remains open. There is no doubt, however, that clear inferences about the operation of a system, by unexceptionable arguments from undoubted facts, may be counterintuitive. I cite five examples. I can produce a pedigree in which the recurrence risk of a Mendelian disorder is less if there is a positive family history of the disease than if there is not. With a simple two-locus system, a gene may be preferentially selected for because it is harmful. The pursuit of the excellent can be
906
June 1979
The American Journal of Medicine
proved to be dysgenic. In certain conditions, the larger the mean size of family surviving to maturity, the more likely the dynasty is to become extinct. The most likely interpretation of a group of measurements is to put each patient in his own personal category [4]. (This last conclusion is as near a universal as statistical theory can provide: and the only escape from it is to involve some counter-value. This issue of “the one and the many” is the oldest problem in formal philosophy.) Such paradoxes arise in simple systems. There is no reason to suppose that intuition is any better guide when the full force of interaction is operating. The formidable mathematical problem of explaining fully the tertiary structure of protein is well known, a problem trivially simple compared with that of the body as a whole. The narrowly analytical approach to the‘fundamkntals of medicine is in some danger of leading us into elegant irrelevancies, and the purely synthetic approach is likely to prove intractable. It seems as if the traditional pattern of medical research is still the soundest: diverse types of study at multiple levels of resolution, mutually illuminating and mutually correcting. The full natural history of a rational medicine might be that the raw data of experience are analyzed down to the most elemental level, and a whole medicine resynthesized from them. But the success of this approach must be, as it has been, that each level of enquiry should be sound. No longer, then, can the physician look elsewhere for the means to put his own house in order: clinical practice would require coherently developed rules of clinical evidence and clinical research. And here we have reason to be concerned at our lack of progress in the busiest half century in the history of science. More than anything else, the clinical department of medicine is concerned uniquely and distinctively with the diagnostic process. Diagnosis becomes more and more complex. It is a required skill of every medical student. The expense of medical care cries out for improved diagnostic efficiency. But we cannot optimize what we cannot formulate. We cannot evaluate where we have developed no criteria. We cannot educate where we cannot articulate. Why is the diagnostic process not the most popular field of research in the academic department of clinical medicine? Yet the prevailing attitude is one of apathy. It is not merely that readymade tools have not been furnished to us by “the basic scientist”: it is the attitude that the topic is boring and foredoomed to failure. Besides there is no problem to solve: diagnosis is merely a matter of practice and experience. The fundamental tenet of science is that economical systematization of many particulars is possible. Yet there are several hundred hemoglobinopathies known and no reason to suppose the supply exhausted. Not all are of clinical importance, but that argument is merely temporarily reassuring. The overwhelming problem facing students is the numbing proliferation of fact. There must come a point of congestive failure, when the
Volume 66
MEDICINE, SCIENCE, AND SOCIETY-MURPHY
prodigious idiocy of the computer emerges triumphant. By now, several constraints must be evident. Specialization and superspecialization must not proliferate indefinitely. Perspective, comprehension, any sense of the totality of the patient would suffer. Nobody can know it all. But much of “it all” is not worth knowing and much frankly false. We cannot equip all physicians to be expert in evaluating scientific evidence. Policing what purports to be fact is a demanding and unrewarding task. But even fanatical editorial vigilence would be vitiated by the proliferation of seductive and often frankly irresponsible journals. Yet these problems are not novel or unsolved. One recalls Samuel Johnson’s two kinds of knowledge: “. . we know a subject ourselves, or know where we can find information upon it.” We may savor Poincare’s definition of mathematics as the art of giving the same name to different things. Then, perhaps, it occurs to us that we might contain our problems by investing in the
continued production of sound and usable principles, a fraction of what we squander on collecting facts. I have faith that we can nurture coherence in clinical medicine, by a logic or an epistemology (or whatever you wish to call it). But it is not a process which will happen of itself. Among other institutions, the journals have a clear responsibility to foster sound theory and not to dismiss papers (however germane] on the grounds that they contain no new fact. REFERENCES I.
Tcmpkin 0: The Double Face of Janus, Baltimore: The Johns Hopkins University Press, 1977. 2. Murphy EA. Kwiterovich PO: Genetics of the hyperlipoproteinemias. Hyperlipidemia: Diagnoses and Therapy (Rifkind BM, Levy RI, eds). New York, Grune & Stratton, 1977. 3. Brown AS, Goldstein JL: Familial hypercholesterolemia. Trans Assoc Am Physicians 90: 91. 1977. 4. Murphy EA. Boiling DR: Testing of single locus hypotheses where there is incomplete separation of the phenotypes. Am 1Hum Genct 19: 322,1967.
June 1979
The American Journal of Medicine Volume 66
909