Journal of Toxicology and Environmental Health
ISSN: 0098-4108 (Print) (Online) Journal homepage: http://www.tandfonline.com/loi/uteh19
Comment: Preventive toxicology in the service of medicine Harold C. Hodge To cite this article: Harold C. Hodge (1978) Comment: Preventive toxicology in the service of medicine, Journal of Toxicology and Environmental Health, 4:4, 631-636, DOI: 10.1080/15287397809529685 To link to this article: http://dx.doi.org/10.1080/15287397809529685
Published online: 20 Oct 2009.
Submit your article to this journal
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View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=uteh20 Download by: [University of Florida]
Date: 06 November 2015, At: 03:27
COMMENT
PREVENTIVE TOXICOLOGY IN THE SERVICE OF MEDICINE Harold C. Hodge Department of Pharmacology, School of Medicine, University of California, San Francisco, California and Department of Community and Environmental Medicine, University of California, Irvine, California
Downloaded by [University of Florida] at 03:27 06 November 2015
INTRODUCTION The service areas of the toxicologist can be divided into five general categories: medical, environmental, industrial, pesticidal, and military. Medical toxicology. The treatment of acute poisoning, emerging as one of the newest medical superspecialties, draws on the practices of emergency medicine and of psychiatry. Forensic toxicology is closely allied, strongly chemical in nature, a modern version of the "coroner's chemist" of 50 yr ago. Clinical toxicology—that is, the practice of a clinical pharmacologist specializing in the diagnosis of adverse drug reactions and their therapy—is another superspecialty just emerging. These poisonings, especially in long-continued therapy, are characteristically insidious, unpredictable, multiform, mimicking any of a number of diseases, testing the acumen of the astute diagnostician. Public health toxicology in a technologically advanced society embraces an almost limitless list of hazards, some naturally occurring and some anthropogenic. Toxicological evaluation of new materials and old is a relatively recent advance. Only 70 yr ago Ehrlich synthesized one organic arsenical after another in his search for the "magic bullet" against syphilis. He tested each new compound on a syphilitic rabbit; if a compound appeared to be active, his diener carried some across the street to the nearby clinic of Herxheimer, who tried it on the next syphilitic patient to come in for treatment. Such a primitive arrangement strikes us as nearly unbelievable in the face of the present profusion of animal toxicity tests (and, for new drugs, tests in patients prior to marketing) required by law for drugs, food additives, and a few other classes of products. Most recently, the Toxic Substances Control Act requires evidence of toxic properties sufficient to permit an estimate of hazard and to recommend safe handling procedures; this act in principle applies to chemicals in general, a task gargantuan in scope. No medical problem is fraught with more emotional impact than those Requests for reprints should be sent to Harold C Hodge, Department of Pharmacology, School of Medicine, University of California, San Francisco, California 94143.
631 Journal of Toxicology and Environmental Health, 4:631-636, 1978 Copyright © 1978 by Hemisphere Publishing Corporation 0098-4108/78/0404-0631 $2.25
Downloaded by [University of Florida] at 03:27 06 November 2015
632
H. C. HODGE
surnamed "genesis": terato-, muta-, carcino-, and iatro-. I will say more about this later. This view of the medical aspects of toxicology gives quite a different picture from the one that E. Fingl and D. Woodbury offer in their introduction to Goodman and Gilman's text.1 Pharmacology, in their opinion, "embraces the knowledge . . . of drugs." They define a drug as any chemical agent that affects life processes; pharmacology is thus all-inclusive. "Toxicology is that aspect of pharmacology that deals with the adverse effects of drugs." Would not a definition of pharmacology as the science of the beneficial, therapeutically useful effects of chemicals on living systems, and of toxicology as the science of the injurious, dangerous effects of chemicals on living systems serve today's purposes better? Environmental toxicology. Toxicologists' activities deal not only with the toxins naturally occurring in minerals, plants, or animals, but also with toxic hazards arising from human activities. We use food additives, some to improve the appearance or the flavor of food, many to preserve food and to permit its processing and distribution by our complex system of food technology. The incompletely evaluated facts of air and water pollution draw ever increasing attention to a host of intricate and pressing problems. Household toxic hazards are relatively unexplored. Ecological toxicology, now in its infancy, calls for insight into the chemical risks to the quality of our coexistence in the biosphere. Radiation toxicology, less than a century old, has come of age, but in the atomic age it deals with risks of almost unimaginable dimensions. Space toxicology, which begins in our own stratosphere, moves with the astronauts to the moon, and may one day extend to other planets of our solar system or beyond, can best be described as primitive. Industrial toxicology. This furnishes the evidence on which industrial disease can be recognized and treated, and, more importantly, on which disease can be prevented and workers' safety ensured through appropriate standards of exposure. Toxicology of pesticides. As toxicologists develop more specific and more effective pesticides, simultaneously procedures must be developed for safe handling and for the treatment of accidental overexposures as well as for control measures guaranteeing minimal risks to those incidentally exposed. Military toxicology. The development of superior chemical, biological or radiological agents demands equally superior defenses. PREVENTIVE TOXICOLOGY Some toxicologists search for agents of greater lethality or of greater disabling potential (e.g., pesticides and warfare agents). In most toxicological activities, however, the aim is to prevent injury, to ensure 1
L. S. Goodman and A. Gilman. 1970. Pharmacological Basis of Therapeutics, 4th ed., Chap. 1. New York: Macmillan.
Downloaded by [University of Florida] at 03:27 06 November 2015
PREVENTIVE TOXICOLOGY
633
safety. Thus, the goals of most toxicologists lie in preventive toxicology, and their work contributes to the mission of preventive medicine. These are familiar goals: (1) providing working conditions such that earning a livelihood does not endanger the worker's health or life whether he or she works in the factory, the field, or the home; (2) providing foods that nourish and medicines that heal without causing illnesses that destroy; and (3) providing food, clothing, and recreation for a burgeoning population while maintaining an environment of optimal quality. Accepting for the moment these dimensions of the field of toxicology, let us turn again to medical toxicology and ask, What can toxicology do for us, for clinical pharmacology, for the profession of medicine? While the answers provide no panacea, they do emphasize toxicology's future role. Research in the several aspects of medical toxicology is contributing increasingly to our health, often in well-publicized ways. Let us seek some examples, therefore, in the less well known, emotion-laden problems of "genesis." The "genesis" familiar to every toxicologist comprises four chapters of terror: terato-, muta-, carcino-, and iatro-. In each of these chapters, toxicologists are striving along with specialists in sister sciences to identify the potential risks, to reduce the frightful toll of injury and death, and to protect the health and well-being of men, women, and children. Teratogenesis Less than a score of years ago, there was the shattering realization that a "nontoxic," remarkably effective sedative, thalidomide, had blighted the bodies and lives of thousands of children and brought lasting heartache to them and to their families. In the ensuing years, despite intense study, only a few human teratogens, a half-dozen or fewer classes of compounds (antifolates, androgenic hormones, thalidomide, phenytoin), have been reliably identified, although hundreds of animal teratogens are known. The systematic study of toxic threats to the pregnant woman and the fetus, evaluating risks from drugs and chemicals singly or in combination, has hardly begun. Work on this sensitive problem must continue despite almost insuperable obstacles; any perceptible risk must be avoided. Two pressing instances of exposures may be mentioned: (1) women in industry are taking jobs in production areas once almost exclusively held by men and are thus subjected to an unprecedented degree to all manner of known or potentially toxic exposures; and (2) drug abuse by women, typically involving several drugs taken simultaneously, introduces on occasion dangerously high concentrations of pharmacologically active drugs into the circulation. What of the risks to the embryo and the fetus? Mutagenesis A more recent chapter of horror features the mutagenic changes induced by a rapidly growing list of chemicals. Changes in chromosomal
634
H.C.HODGE
materials raise terrifying specters in the popular imagination second only to the hysteria surrounding cancer: at stake are normal children and their children versus the specters—deformed monsters and imbeciles. And in truth, transmissible alterations of the genetic code by chemicals must be regarded as fearsome toxic responses whether they are eventually repaired and disappear, or induce tumor formation, genetically determined disease, or lethally blighted embryos. Attempts to discover and to identify chromosomal aberrations or DNA abnormalities occupy a central position in toxicology today. The significance for humans of mutagenic properties is clear; the applicability of the results of various laboratory mutagenic tests has not been evaluated.
Downloaded by [University of Florida] at 03:27 06 November 2015
Carcinogenesis Historically, while chemical carcinogenesis has been known for a couple of centuries, only in the past 50 yr has its identification as a property of molecules become increasingly a focus for toxicologists. There are times when it seems that the fear of the devil and of hellfire in the hereafter, not so long ago compelling forces in millions of lives, has been replaced by fear of cancer, in particular environmental cancer, here and now. There is a pervasive impression abroad that most chemicals are carcinogens. The popular press features smoking (the leading environmental cause of cancer), obesity, dietary fiber deficiency, aflatoxin, sex hormones, vinyl chloride, asbestos, coke oven effluents, and, most recently, saccharin. No small part of the adversive response written into legislation affecting food, air, and water quality comes from the "zero concept." This applies to amounts of the carcinogen: if small is beautiful, zero is exquisite, the peak of perfection. Translated into daily operations, zero means none detectable. Discussions about the zero concept have an unreal, ethereal, will-o'-the-wisp, metaphysical cast. The behavior of the rat appears to be accepted as the valid predictor for human cancer risk. Records of human exposure without cancer incidence, such as vinyl chloride exposures in one industrial company, may be ignored. The newspaper prediction that there will be some 1300 more cancer deaths per year due to saccharin, if its present level of human use is continued, is really a prediction of about 1300 more cancer deaths in 100 or 200 million rats given equivalent doses. Statistical prediction of rat cancer deaths by extrapolation assumes that smaller and smaller doses in the rat are proportionately less carcinogenic and that minute doses of saccharin are qualitatively and quantitatively like the much larger intake from the 5% saccharin diet that produced bladder cancers in the rat. This is the famous assumption ceteris paribus, other factors remaining constant—in this case, when the dose is decreased. There is, however, considerable evidence, not specifically concerning saccharin, for ceteris non paribus when certain carcinogenic and other toxic substances are given in diminishing doses. Protective mechanisms—metabolic processes—have been
PREVENTIVE TOXICOLOGY
635
Downloaded by [University of Florida] at 03:27 06 November 2015
demonstrated in the cell that is capable of handling safely minute amounts of potentially dangerous materials. These amounts are greater than zero. Demonstrating a safe amount is equivalent to demonstrating a threshold: some real amount below which injury, including carcinogenesis, does not normally occur. The most promising area for research by toxicologists is in elucidating mechanisms and discovering the quantitative bases for carcinogenesis. latrogenesis The fourth chapter of the genesis of toxic injury dates from antiquity; we have made an accommodation with this source. There is nothing metaphysical or foreign or mystical about iatrogenesis. The statistics are familiar: 1 in 20 hospital medical admissions is the result of an adverse drug reaction; 1 in 10 hospitalized patients suffers from an adverse drug reaction severe enough to require a prolonged hospital stay. The cost just for additional hospital occupancy is estimated to be $3 billion a year, a cold statistic that overlooks the cost of pain and suffering, and even of the recently estimated 9000 deaths annually. Would it be too much to ask to have iatrogenesis from drugs declared a disaster area of medicine? These days the great interest in roots directs our attention to three great taproots of iatrogenic disease. (1) The remarkable increase in the healing power of drugs is accompanied by marked increases in the potential for injury. (2) Prescription writing by physicians, perhaps often enough demanded by the patient, has been characterized as lax. Patients are permitted to continue on a drug for long periods of time. Over all stands the "irrational polypharmacy" of today's practice. (3) Some physicians have an inadequate understanding of adverse reactions, their identification, their mechanisms, the predisposing factors in the patient, the drug interactions sometimes involved. The times call for preventive toxicology, an ancient concept we are all familiar with; to quote Hippocrates, "As to diseases, make a habit of two things—to help, or at least to do no harm." The famous dictum primum non nocere is the heart of preventive toxicology. What can toxicology offer? First, physicians must face their responsibility: their patients must be persuaded that a prescription is not always required or advantageous. In a letter from an old physician to a young friend just entering practice can be found a clear statement of the dilemma: "I frequently find it more difficult to persuade my patient not to take a drug than to take one."2 Second, the toxicologist can help educate the physician. It is predictable that a teacher would propose some educational remedy. This might be described as a pedagogical reflex, analogous to the drug reflex, that almost automatically produces a prescription when a patient hits a 2
Dr. Jackson, Boston, 1855.
Downloaded by [University of Florida] at 03:27 06 November 2015
636
H.C.HODGE
physician in a sensitive spot with a symptom. The teacher is vulnerable by training and instinct. An old rabbi summed it up: "The need of a calf to suck is as nothing compared to the need of the cow to suckle." Instruction in toxicology can easily be introduced during the medical course in pharmacology. Unfortunately, too many pharmacology courses in medical schools today fail to include instruction in toxicology at all. A promising alternative approach would be to offer a course in clinical toxicology separately. In preclinical medical pharmacology, students are introduced to the vocabulary of drugs, to their important effects and uses, to the mechanisms of beneficial actions, to the fate of drugs in the body. On this foundation, refreshing the students' memories of objective pharmacology, the toxicologist could give students early in their clinical experience descriptions of adverse drug reactions and their patterns, of the known mechanisms of these dangerous responses, and of antidotal or supportive treatments. The clinical toxicologist can introduce the art of diagnosis and treatment of these poisonings. Later the toxicologist can help keep the physician current in the rapidly developing field of clinical toxicology through continuing education. The aim is timeless. Primum non nocere.
ISSN: 0098-4108 (Print) (Online) Journal homepage: http://www.tandfonline.com/loi/uteh19
Comment: Preventive toxicology in the service of medicine Harold C. Hodge To cite this article: Harold C. Hodge (1978) Comment: Preventive toxicology in the service of medicine, Journal of Toxicology and Environmental Health, 4:4, 631-636, DOI: 10.1080/15287397809529685 To link to this article: http://dx.doi.org/10.1080/15287397809529685
Published online: 20 Oct 2009.
Submit your article to this journal
Article views: 3
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=uteh20 Download by: [University of Florida]
Date: 06 November 2015, At: 03:27
COMMENT
PREVENTIVE TOXICOLOGY IN THE SERVICE OF MEDICINE Harold C. Hodge Department of Pharmacology, School of Medicine, University of California, San Francisco, California and Department of Community and Environmental Medicine, University of California, Irvine, California
Downloaded by [University of Florida] at 03:27 06 November 2015
INTRODUCTION The service areas of the toxicologist can be divided into five general categories: medical, environmental, industrial, pesticidal, and military. Medical toxicology. The treatment of acute poisoning, emerging as one of the newest medical superspecialties, draws on the practices of emergency medicine and of psychiatry. Forensic toxicology is closely allied, strongly chemical in nature, a modern version of the "coroner's chemist" of 50 yr ago. Clinical toxicology—that is, the practice of a clinical pharmacologist specializing in the diagnosis of adverse drug reactions and their therapy—is another superspecialty just emerging. These poisonings, especially in long-continued therapy, are characteristically insidious, unpredictable, multiform, mimicking any of a number of diseases, testing the acumen of the astute diagnostician. Public health toxicology in a technologically advanced society embraces an almost limitless list of hazards, some naturally occurring and some anthropogenic. Toxicological evaluation of new materials and old is a relatively recent advance. Only 70 yr ago Ehrlich synthesized one organic arsenical after another in his search for the "magic bullet" against syphilis. He tested each new compound on a syphilitic rabbit; if a compound appeared to be active, his diener carried some across the street to the nearby clinic of Herxheimer, who tried it on the next syphilitic patient to come in for treatment. Such a primitive arrangement strikes us as nearly unbelievable in the face of the present profusion of animal toxicity tests (and, for new drugs, tests in patients prior to marketing) required by law for drugs, food additives, and a few other classes of products. Most recently, the Toxic Substances Control Act requires evidence of toxic properties sufficient to permit an estimate of hazard and to recommend safe handling procedures; this act in principle applies to chemicals in general, a task gargantuan in scope. No medical problem is fraught with more emotional impact than those Requests for reprints should be sent to Harold C Hodge, Department of Pharmacology, School of Medicine, University of California, San Francisco, California 94143.
631 Journal of Toxicology and Environmental Health, 4:631-636, 1978 Copyright © 1978 by Hemisphere Publishing Corporation 0098-4108/78/0404-0631 $2.25
Downloaded by [University of Florida] at 03:27 06 November 2015
632
H. C. HODGE
surnamed "genesis": terato-, muta-, carcino-, and iatro-. I will say more about this later. This view of the medical aspects of toxicology gives quite a different picture from the one that E. Fingl and D. Woodbury offer in their introduction to Goodman and Gilman's text.1 Pharmacology, in their opinion, "embraces the knowledge . . . of drugs." They define a drug as any chemical agent that affects life processes; pharmacology is thus all-inclusive. "Toxicology is that aspect of pharmacology that deals with the adverse effects of drugs." Would not a definition of pharmacology as the science of the beneficial, therapeutically useful effects of chemicals on living systems, and of toxicology as the science of the injurious, dangerous effects of chemicals on living systems serve today's purposes better? Environmental toxicology. Toxicologists' activities deal not only with the toxins naturally occurring in minerals, plants, or animals, but also with toxic hazards arising from human activities. We use food additives, some to improve the appearance or the flavor of food, many to preserve food and to permit its processing and distribution by our complex system of food technology. The incompletely evaluated facts of air and water pollution draw ever increasing attention to a host of intricate and pressing problems. Household toxic hazards are relatively unexplored. Ecological toxicology, now in its infancy, calls for insight into the chemical risks to the quality of our coexistence in the biosphere. Radiation toxicology, less than a century old, has come of age, but in the atomic age it deals with risks of almost unimaginable dimensions. Space toxicology, which begins in our own stratosphere, moves with the astronauts to the moon, and may one day extend to other planets of our solar system or beyond, can best be described as primitive. Industrial toxicology. This furnishes the evidence on which industrial disease can be recognized and treated, and, more importantly, on which disease can be prevented and workers' safety ensured through appropriate standards of exposure. Toxicology of pesticides. As toxicologists develop more specific and more effective pesticides, simultaneously procedures must be developed for safe handling and for the treatment of accidental overexposures as well as for control measures guaranteeing minimal risks to those incidentally exposed. Military toxicology. The development of superior chemical, biological or radiological agents demands equally superior defenses. PREVENTIVE TOXICOLOGY Some toxicologists search for agents of greater lethality or of greater disabling potential (e.g., pesticides and warfare agents). In most toxicological activities, however, the aim is to prevent injury, to ensure 1
L. S. Goodman and A. Gilman. 1970. Pharmacological Basis of Therapeutics, 4th ed., Chap. 1. New York: Macmillan.
Downloaded by [University of Florida] at 03:27 06 November 2015
PREVENTIVE TOXICOLOGY
633
safety. Thus, the goals of most toxicologists lie in preventive toxicology, and their work contributes to the mission of preventive medicine. These are familiar goals: (1) providing working conditions such that earning a livelihood does not endanger the worker's health or life whether he or she works in the factory, the field, or the home; (2) providing foods that nourish and medicines that heal without causing illnesses that destroy; and (3) providing food, clothing, and recreation for a burgeoning population while maintaining an environment of optimal quality. Accepting for the moment these dimensions of the field of toxicology, let us turn again to medical toxicology and ask, What can toxicology do for us, for clinical pharmacology, for the profession of medicine? While the answers provide no panacea, they do emphasize toxicology's future role. Research in the several aspects of medical toxicology is contributing increasingly to our health, often in well-publicized ways. Let us seek some examples, therefore, in the less well known, emotion-laden problems of "genesis." The "genesis" familiar to every toxicologist comprises four chapters of terror: terato-, muta-, carcino-, and iatro-. In each of these chapters, toxicologists are striving along with specialists in sister sciences to identify the potential risks, to reduce the frightful toll of injury and death, and to protect the health and well-being of men, women, and children. Teratogenesis Less than a score of years ago, there was the shattering realization that a "nontoxic," remarkably effective sedative, thalidomide, had blighted the bodies and lives of thousands of children and brought lasting heartache to them and to their families. In the ensuing years, despite intense study, only a few human teratogens, a half-dozen or fewer classes of compounds (antifolates, androgenic hormones, thalidomide, phenytoin), have been reliably identified, although hundreds of animal teratogens are known. The systematic study of toxic threats to the pregnant woman and the fetus, evaluating risks from drugs and chemicals singly or in combination, has hardly begun. Work on this sensitive problem must continue despite almost insuperable obstacles; any perceptible risk must be avoided. Two pressing instances of exposures may be mentioned: (1) women in industry are taking jobs in production areas once almost exclusively held by men and are thus subjected to an unprecedented degree to all manner of known or potentially toxic exposures; and (2) drug abuse by women, typically involving several drugs taken simultaneously, introduces on occasion dangerously high concentrations of pharmacologically active drugs into the circulation. What of the risks to the embryo and the fetus? Mutagenesis A more recent chapter of horror features the mutagenic changes induced by a rapidly growing list of chemicals. Changes in chromosomal
634
H.C.HODGE
materials raise terrifying specters in the popular imagination second only to the hysteria surrounding cancer: at stake are normal children and their children versus the specters—deformed monsters and imbeciles. And in truth, transmissible alterations of the genetic code by chemicals must be regarded as fearsome toxic responses whether they are eventually repaired and disappear, or induce tumor formation, genetically determined disease, or lethally blighted embryos. Attempts to discover and to identify chromosomal aberrations or DNA abnormalities occupy a central position in toxicology today. The significance for humans of mutagenic properties is clear; the applicability of the results of various laboratory mutagenic tests has not been evaluated.
Downloaded by [University of Florida] at 03:27 06 November 2015
Carcinogenesis Historically, while chemical carcinogenesis has been known for a couple of centuries, only in the past 50 yr has its identification as a property of molecules become increasingly a focus for toxicologists. There are times when it seems that the fear of the devil and of hellfire in the hereafter, not so long ago compelling forces in millions of lives, has been replaced by fear of cancer, in particular environmental cancer, here and now. There is a pervasive impression abroad that most chemicals are carcinogens. The popular press features smoking (the leading environmental cause of cancer), obesity, dietary fiber deficiency, aflatoxin, sex hormones, vinyl chloride, asbestos, coke oven effluents, and, most recently, saccharin. No small part of the adversive response written into legislation affecting food, air, and water quality comes from the "zero concept." This applies to amounts of the carcinogen: if small is beautiful, zero is exquisite, the peak of perfection. Translated into daily operations, zero means none detectable. Discussions about the zero concept have an unreal, ethereal, will-o'-the-wisp, metaphysical cast. The behavior of the rat appears to be accepted as the valid predictor for human cancer risk. Records of human exposure without cancer incidence, such as vinyl chloride exposures in one industrial company, may be ignored. The newspaper prediction that there will be some 1300 more cancer deaths per year due to saccharin, if its present level of human use is continued, is really a prediction of about 1300 more cancer deaths in 100 or 200 million rats given equivalent doses. Statistical prediction of rat cancer deaths by extrapolation assumes that smaller and smaller doses in the rat are proportionately less carcinogenic and that minute doses of saccharin are qualitatively and quantitatively like the much larger intake from the 5% saccharin diet that produced bladder cancers in the rat. This is the famous assumption ceteris paribus, other factors remaining constant—in this case, when the dose is decreased. There is, however, considerable evidence, not specifically concerning saccharin, for ceteris non paribus when certain carcinogenic and other toxic substances are given in diminishing doses. Protective mechanisms—metabolic processes—have been
PREVENTIVE TOXICOLOGY
635
Downloaded by [University of Florida] at 03:27 06 November 2015
demonstrated in the cell that is capable of handling safely minute amounts of potentially dangerous materials. These amounts are greater than zero. Demonstrating a safe amount is equivalent to demonstrating a threshold: some real amount below which injury, including carcinogenesis, does not normally occur. The most promising area for research by toxicologists is in elucidating mechanisms and discovering the quantitative bases for carcinogenesis. latrogenesis The fourth chapter of the genesis of toxic injury dates from antiquity; we have made an accommodation with this source. There is nothing metaphysical or foreign or mystical about iatrogenesis. The statistics are familiar: 1 in 20 hospital medical admissions is the result of an adverse drug reaction; 1 in 10 hospitalized patients suffers from an adverse drug reaction severe enough to require a prolonged hospital stay. The cost just for additional hospital occupancy is estimated to be $3 billion a year, a cold statistic that overlooks the cost of pain and suffering, and even of the recently estimated 9000 deaths annually. Would it be too much to ask to have iatrogenesis from drugs declared a disaster area of medicine? These days the great interest in roots directs our attention to three great taproots of iatrogenic disease. (1) The remarkable increase in the healing power of drugs is accompanied by marked increases in the potential for injury. (2) Prescription writing by physicians, perhaps often enough demanded by the patient, has been characterized as lax. Patients are permitted to continue on a drug for long periods of time. Over all stands the "irrational polypharmacy" of today's practice. (3) Some physicians have an inadequate understanding of adverse reactions, their identification, their mechanisms, the predisposing factors in the patient, the drug interactions sometimes involved. The times call for preventive toxicology, an ancient concept we are all familiar with; to quote Hippocrates, "As to diseases, make a habit of two things—to help, or at least to do no harm." The famous dictum primum non nocere is the heart of preventive toxicology. What can toxicology offer? First, physicians must face their responsibility: their patients must be persuaded that a prescription is not always required or advantageous. In a letter from an old physician to a young friend just entering practice can be found a clear statement of the dilemma: "I frequently find it more difficult to persuade my patient not to take a drug than to take one."2 Second, the toxicologist can help educate the physician. It is predictable that a teacher would propose some educational remedy. This might be described as a pedagogical reflex, analogous to the drug reflex, that almost automatically produces a prescription when a patient hits a 2
Dr. Jackson, Boston, 1855.
Downloaded by [University of Florida] at 03:27 06 November 2015
636
H.C.HODGE
physician in a sensitive spot with a symptom. The teacher is vulnerable by training and instinct. An old rabbi summed it up: "The need of a calf to suck is as nothing compared to the need of the cow to suckle." Instruction in toxicology can easily be introduced during the medical course in pharmacology. Unfortunately, too many pharmacology courses in medical schools today fail to include instruction in toxicology at all. A promising alternative approach would be to offer a course in clinical toxicology separately. In preclinical medical pharmacology, students are introduced to the vocabulary of drugs, to their important effects and uses, to the mechanisms of beneficial actions, to the fate of drugs in the body. On this foundation, refreshing the students' memories of objective pharmacology, the toxicologist could give students early in their clinical experience descriptions of adverse drug reactions and their patterns, of the known mechanisms of these dangerous responses, and of antidotal or supportive treatments. The clinical toxicologist can introduce the art of diagnosis and treatment of these poisonings. Later the toxicologist can help keep the physician current in the rapidly developing field of clinical toxicology through continuing education. The aim is timeless. Primum non nocere.
