A Course in Pathology for Non-medical Students* GUIDO MAINO, BLD.t Harvard Medical School, Boston, Massachusetts By a century-old tradition, the study of pathology is almost synonymous with the study of medicine. Unlike biochem- istry, physiology, and other basic ‘medi- cal’ sciences, which are also taught at the college level, pathology has remained, by and large, a privilege of medical doctors. This may have been appropriate as long as the study of disease was rela- tively off-limits for anyone who did not have a medical degree. Since those days, however, the balance of the medical sci- ences has radically changed. ‘THE STUDY OF DISEASE: PAST AND PRESENT During the last 300 years, the study of disease has progressed through several levels of complexity. It began on crude autopsy tables, then took a great stride with the advent of the microscope. This pioneering work was largely in the hands of medically trained men, who came to be professionally characterized as pathologists. Then, in the last few decades, our understanding of living matter went far beyond the level of the microscope, into the world of biochemis- try and biophysics. With the knowledge of life came new knowledge of disease, knowledge of novel complexity, which + In the summer of 1961, the Department of Pathology at Harvard Medical School of- fered a new course entitled “Introduction to General Pathology,” open to students and investigators in the biological field who did not have a medical background. This article gives a brief account of this experiment and of the reasons which lead to undertake it, Associate Professor of Pathology. could no longer be the monopoly of pathologists. Large numbers of non-medi- cal investigators began to deal with fun- damental aspects of disease. Nowadays, most of these investigators hold a Ph.D. degree in one of the basic ‘medical’ seiences; paradoxically, few if any have had a formal introduction to what we call pathology (1). In the meanwhile, the pioneer group— though somewhat bewildered—has still retained one privilege: pathologists alone are trained to recognize disease at the level of tissues. Given a fragment of abnormal tissue, they are still the experts who are most likely to provide some basic information on what is wrong with it, Microseopic diagnosis remains fundamental as a starting point fez further, more complex studies. ‘We have therefore reached a dichot- omy: on the one hand, this group of medical specialists, who know about ill- ness in general, and can recognize a dis- eased organ when they see it; on the other hand, a vast group of non-medical investigators, who know little or noth- ing about pathology, but are contribu- ting enormously to our knowledge of disease, each in highly specialized, ‘sub- microscopic’ areas. Exchange between these two groups seems to have occurred in one direction only—pathologists have been drawing heavily on the techniques and findings of the non-medical scientists, but have done very little to give these nonmedical colleagues a broader outlook over disease. As a matter of fact, it is now possible to obtain a Ph.D. degree in any one of 421422 Journal of Medical Education the me sciences, and perform opera- tions on animals, deal with exteriorized organs, clamped vessels, incubated cells, and biochemical analysis of structurally complex tissues, without any first-hand knowledge of wound healing, inflamma- tion, thrombosis, or cellular disease; with- out necessarily having enough morpho- logic background to appreciate the cellular significance of biochemical events. A Ph.D. in bacteriology, virology, or im- munology may have little knowledge of infection and less of inflammation. The resulting waste of human labor is all too apparent in the literature, since the study of function, not adequately ground- ed in morphology, amounts to elaborate misinformation. Among the fields which have become estranged from pathology are also those of biology and zoology. Scholars in these fields work and teach within a framework which is, as a rule, completely remote from pathology; yet they have cont uted much of what we know about cellu- lar proliferation, chemotaxis, phagocyto- sis, regeneration, transplantation — all acknowledged chapters of general path- ology. At the college level these subjects must be approached with no reference to pathology, because the latter is out of reach, like obstetries or any other medi- cal specialty. If there is anyone to blame for this anomalous state of affairs, it is the pa- thologists themselves, rho have reduced @ great branch of biology—the science of disease—to the level of a medical spe~ cialty. As matters now stend, in order to be initiated to pathology, it is prac- tically a requirement to take the Hippo- eratie oath. A graduate student or a Ph.D. who wishes to learn the essentials of pathology (otherwise than from text- books) would be obliged to take the mas- sive course given in medical schools, a course which is not geared to their needs, and which they can usually not Vou. 37, May, 1962 afford to take anyhow. It is not our purpose, at this time, to discuss the rea- sons which led to the present situation (1). It is obvious, however, that the first remedy which suggests itself is to offer courses in pathology for non-medi- cal students, teachers, and investigators in the biological field. ORGANIZATION OF THE NEW COURSE Prompted by the reasons outlined above, this department decided to or- ganize, on an experimental basis, a eourse in pathology for non-medieal stu- dents. Under the title of “Introduction to General Pathology” the course was offered for the first time in the sum- mer of 1961. General plan of the course.—Because of the particular nature of the class, and because of limitation of time (it was generally felt that the first trial should not exceed 3 weeks), it was decided that the course should deal only with funda- mentals—i.e. with general pathology, rather than with specific diseases. In the curriculum of this medical school, general pathology covers approxi- mately the first third of the over-all course and consists mainly of 30 lecture- laboratory ‘periods’ (a I-hour lecture followed by a 2%4-hour histopathology laboratory) and six to seven demonstra- tions of human organs. About two-thirds of this program was compressed into 3 weeks by teaching 6 mornings and 2 afternoons a week, In selecting and presenting the topics, the following criteria were used: @) Cellular pathology would be given a large share of the program, because it ‘was anticipated that the class—how- ever heterogeneous —would have a ‘common interest in cells. b) Only key topics would be presented— ive,, topies fundamental to the under- standing of all others. Thus, ‘omitted radiation injury and nutri- ‘tional disturbances, beeause we arguedPathology for Non-medical Students/Majno that our students could competently study these chapters later by them- selves, once they had been introduced to the basic aspects of cellular respon- ses. Six areas were finally selected: cellu- lar pathology; inflammation; cirenta- tory disturbances; tumors; allergy, and infeetion (Table 1). ¢) There would be two types of lectures: systematic, fairly elementary lectures, and “seminars” by guest lecturers, providing examples of study in depth on selected topics. d) There would be histopathology labora- tories as with the medical students; demonstrations of gross specimens, human and experimental; but no ‘experiments run by the students, since it appeared unnecessary to stress the experimental approach with a class ‘composed largely of investigators. The presentation of morphology to non-morphologists.—The course was in- tended for individuals who could be ex- pected to have little or no morphologic background. It becomes difficult, of course, to correlate structure and fune- tion in disease, when normal structure is not known, We met this problem in the following way: After each lecture there was 1 hour of projection, during which the lecturer showed normal and abnormal tissue preparations related to the lecture. Care was taken to present the normal structures first, then to point out how these had been modified by dis- ease. In this way the normal was re- viewed before the abnormal. This pro- jection session was most important; many participants commented on the faet that they would have been lost in the subsequent histopathology labora- tories without this introduction.t 1 We used a Bausch and Lomb arc projec- tor, which ean easily cope with an audience of 0, and has two features which greatly simplify the task of the operator: the ad- vaneenent of the carbons is electronically controlled, and the condensers change auto- matically for each objective. 423, TABLE 1 ‘Topics TREATED IN THE COURSE ‘Tortes Lectures Enboratories Seminars Disease at the evel of cells Inflammation Circulatory disturbances Infection Tumors Allergy 4 ries Bemis me mente Be Laboratory work—Every morning or afternoon period consisted of a 1-hour lecture, followed by 1 hour of projection, and 1% hours of Iistopathology labora- tory. The latter was conducted as for the medical students, with one instructor for every ten students. Demonstrations of kuman organs ob- tained at autopsy were held every week. ‘The class was subdivided into groups of ten or fifteen. To professional patholo- gists a total of three demonstrations will sound like sub-liminal teaching. How- ever, the main purpose was to create an awareness of the problems, not a diag- nostic ability, and the class felt unani- mously that this exposure was adequate. We also used another type of !abora- tory, planned ez novo for the course: autopsies of animals bearing ‘unknown’ lesions (unknown, that is, to the class). Four albino rats were dissected and demonstrated by an instructor to a group of three to four students; the le- sions, prepared in advance, were the fol- lowing: (a) Acute liver injury induced by carbon tetrachloride, (b) unilateral hydronephrosis, 2 weeks after ligature of the ureter, (c) necrosis, abscess for- mation and sequestration, as illustrated by septic fragments of rat liver im- planted 1-4 weeks previously in the peri- toneal cavity of other rats (2), and (d) peritoneal adhesions induced by a sus- pension of talcum powder injected 1 month previously. Some of these rats also reeeived, 1 month in advance, a small subcutaneous injection of carbon black on the dorsal surface of a paw, in424 Journal of Medical Education order to demonstrate the transport of foreign particulate matter to the re- gional lymph nodes. The instructors used the first animal to demonstrate ether anesthesia, as well as normal anatomical structures and re Jationships for the benefit of those not familiar with rat anatomy. The proper way of fixing specimens—particularly membranous structures—was also shown. ‘The original plan had been to let the students dissect the animals; limitation of time induced us to present this exer- cise as a small-group demonstration. It worked effectively and was well received. A whole afternoon (rather than the planned 2 hours) would have been pref- erable. Other experimental animals were dem- onstrated during lectures, in order to illustrate specific points: (a) the in- creased vescular permeability of acute inflammation in the rabbit (a local i jury was indueed by painting the depi lated flank with xylene, after an i.v. in- Jection of 1 per cent trypan blue); (b) the reticuloendothelial system and the removal of particulate matter from the blood stream of the rabbit (one animal had been given injections i.v. 3 times in 1 week with trypan blue, the other with carbon black); (¢) the breakdown of hemoglobin in a hematoma, in the rat; a Selye pouch was first induced with cro- ton oil (4), then filled with human (out- dated) whole blood and let stand for 10 days; the outer surface of the dissected pouch was then painted with ammonium sulfide to demonstrate reactable iron, and the content was extracted with chlor- oform to demonstrate bilirubin (3). Seminars—The seminars, timed to correlate with the current lecture topic, were the following: (a) Interaction be- tween cells and their environment (Dr. Paul Weiss, Rockefeller Institute) ; (b) The chemical control of the nature of the cell (Dr. W. Eugene Knox, Harvard Vou. 37, May, 1962 Medical School); (¢) Cellular changes induced by iron (Dr. Goetz W. Richter, Cornell University Medical School) ; (d) Normal and defective connective tissue: biochemical and morphologic approaches (Dr. Jerome Gross, Harvard Medical School) ; (¢) The structure and develop- ment of viruses (Dr. Councilman Mor- gan, Columbia University, College of Physicians and Surgeons); (/) The ac- tivation of infectious processes (Dr. René Dubos, Rockefeller Institute). Recruitment and selection of the class, —The course was first announced by leaflets distributed at the April meetings of the Federation of American Societies for Experimental Biology; as a result we received about fifteen inquiries. With two last-minute announcements in Sei- ence (May 5 and May 12) the total num- ber of inquiries reached close to 200. Most of these were from Ph.Ds; a few were from graduate students, or tech- nicians in various fields. Each individ- ual received a simple application form. Admission policies were intended to be as broad as possible; hence no specific requirements were stated, except that the applicant should be able to demon- strate a clear-cut need for the course. Consequently, one of the most informa- tive sections of the application form— for the purpose of selection—was that under the heading “Reasons for taking the course.” In view of the unexpectedly large number of requests, the size of the class was set at 30, with ten other ap- plicants admitted as auditors. The lec- tures and the projection sessions would have been compatible with a larger class; limiting factors, however, were the demonstrations of gross material (not effective with groups larger than ten to fifteen) and the number of in- struetors available for supervision in the histopathology laboratories. ‘The composition of the class by pro- fession is shown in Table 2.Pathology for Non-medical Students/Majno TABLE 2 COMPOSITION OF THE CLASS BY PROFESSIONAL CATEGORIES (including 30 regular students and ten auditors) aterory Investigators with a Ph.D. degree College professors* Graduate students Non-Ph.D/s with senior laboratory responsibility Doctors in dental science Biochemistry Bacteriology, Immunology Virolory Cytology, or Histology Physiology and Biochem Nutrition and Biochem Goll Physiology Chemistry Physiology Zoology and Physiology Zoolo Zoology Bacteriology Physiology and Cytology Anatomy Biochemistry Biostatistics Immunology Electron microscopy, Experimental pathology Virology Dental seience Field Number and Embryology 3 foe HetoIo Hees Heer 2 ‘Toran: 40 * This category overlaps, of course, with “Investigators.” It merely emphasizes the academic affiliation. ‘COMMENTS ‘The most important aspect of this course, in our opinion, was not the course itself, but the proof that there is a large group of teachers and re- searchers without an M.D. degree who feel the need to be instructed in the fun- damentals of pathology. Interestingly enough, the overwhelming majority of inquiries did not come from graduate students, but from senior faculty mem- bers or investigators—ie., from indi- viduals who had already experienced the difficulty of working with experimental animals without being familiar with the basic elements of pathology (and often even of anatomy). As for the course per se, it had been organized as an experiment, and we feel entitled to state that the over-all experi- ment was a clear-cut success. The com- ments of the class members (both in- formally and in a specific questionnaire) constituted more than ample reward for our efforts, and we also learned, of course, the pitfalls to avoid in 1962. In the preparatory phase of this course, we did have one serious doubt— namely, that it might turn out to be difficult or impossible to discuss pathol- ogy with a class lacking the preparation in normal anatomy, which is—or should be—characteristic of the medical stu- dents. This fear was soon dissipated. In the first place, a group such as we had is highly motivated to learn, Fur- thermore, one teaching device proved in- valuable, almost to the point of becoming the key to the success of the entire course: this was the hour-long projec-426 Journal of Medical Education tion of histological sections which fol- lowed each lecture. Sometimes resented by medical students, who consider it ‘spoon feeding,’ this method becomes essential with an audience unfamiliar with morphology. During the first 3 days, devoted to cellular changes (which do not Iend themselves well to projec- tion in this form), we took the oppor- tunity to review the essentials of normal histology; and thereafter, on all slides, we always made an effort to point out the normal features before the patho- logie. These precautions proved sufficient for two-thirds of the class, The re- mainder still felt that they could have done better with additional tutoring in normal histology and suggested that this opportunity be offered either as an op- tional 3- to 4-day period prior to the onset of the course, or during the free time within the present schedule. Another fear which proved to be groundless was that we might not find the proper teaching level, in view of the almost appallingly heterogeneous nature of the class, which included full profes- sors as well as students, and specializa- tions ranging from statistics to food technology. In practice, the substance and language of our lectures, though al- most the same as for the medical stu- dents, proved adequate. Besides, most members of the class felt that the heter- ogeneity of the group was one of the assets of the course (one dissenting member voiced the opinion that the group was too homogencous—‘“too many Bostor 1s”). With regard to the proper teaching level, however, we did fail to anticipate the importance of seminars by guest lec- turers. Originally designed to be no more than an interesting sideline, these six seminars actually played a major role in the course. The reason should have been obvious a priori, but it became ap- parent to us from the questionnaires. Vou. 37, May, 1962 With a class largely composed of senior teachers and investigators, an ‘elemen- tary’ or introductory course needs to be bolstered by examples of information in depth. In other words, it is necessary to teach at two levels: one series of lec- tures should provide the basic, elemen- tary concepts, which will be readily ab- sorbed; interwoven with this series there should be other lectures tuned to a different register (such as our semi- nars) in which the basic concepts are developed to the ultimate degree. This was one of our most significant “find- ings,’ and we plan to organize our next course according to this plan, Among the comments and suggestions derived from the questionnaires the fol- lowing were particularly useful. The choice of topics was found satisfactory, and no others were suggested (at least not by more than one person). How- ever, infection (see Table 1) should re- ceive more ample treatment, possibly at the expense of allergy. The sections on Cellular Disease, on Inflammation, and particularly on Circulatory Disturbances should be expanded by one lecture each. ‘To our surprise (in view of the hot summer season) the majority of the class felt that the schedule could have been heavier and that some of the free time should have been used for addi- tional lectures, as well as for group dis- cussions at the end of each section, with a class member as a leader. The latter appears to be a very worth-while sug- gestion. ‘The total duration of the course was ‘just about right’ for four-fifths of the participants; but the same number added that they could have afforded to come for 4 weeks. ‘The students were not alone in bene- fiting from the course, All the instruc- tors, who were accustomed to teaching medical students, found that it was ‘re- freshing’ to teach this class. The dif-Pathology for Non-medical Students/Majno ference, I submit, was not only in the pleasure of dealing with a group of dis- tinguished teachers and investigators. ‘The breath of fresh air eame from hav- ing opened a breach in the barrier which separates pathology from the surround- ing fields of biology. ‘We were reminded that pathology has broader horizons than those of a medical specialty; that it should include the study of all living beings. We were re- minded that our present concept of pa- thology refers to a few higher verte- brates, whereas over 97 per cent of the animal species on earth are inverte- brates (5); and, to quote E. A. Stein- haus further, “who knows what secrets pertaining to disease in man lie hidden, but answerable, in disease as it occurs in invertebrates?” (5) ‘Through the course it became once again apparent (a truism, perhaps, but not sufficiently recognized on this side of the Atlantic) that pathology should be cultivated at two levels of equal im- portance: applied pathology, for the im- mediate benefit of patients; and general pathology in which the patient is the cell, be it a cell from a human patient, a cell from a wilting vine leaf, or (why: not?) a bacterial cell struggling with penicillin. To achieve this goal we must abandon our clannish medical isolation, and create a two-way flow of experience bors, on a far broader front than yet conceived. Virchow was the first to view the cell as the focal point of synthesis in the study of living matter, normal and ab- normal. It is probably fair to say that Virchow was also the last. Which other pathology book, other than the “Cellular Pathology,” begins and ends with ex- amples taken from botany? “Let us ex- amine, for instance, a young lilac sprout, as may be brought forth by warm days in February...” (6). 427 In closing, we' wish to point out that not all the returns of this course can be stated in terms of pure science. Ex- perimental biology has become a huge Tower of Babel, with barriers scientific complicating the linguistic, and with journals erupting from some 50,000 sep- arate sprouts? There is a particular pleasure in meeting fellow biologists from another rung of the tower, and rediscovering that there remains a per- manent common language—not in terms of pathology, or anatomy, or biochemis- try, but in terms of health and disease, of life and death. ACKNOWLEDGMENTS ‘The idea of organizing this course erys- tallized from discussions with our friend and colleague Dr. Morris J. Karnovsky, to whom we are very much indebted. Our heartiest thanks also go to Dr. Arthur T. Hertig, Head of the Department of Pathol- ogy, to Dr, Erie G. Ball, Chairman of the Division of Medical Sciences, and to the many colleagues who encouraged us with their advice and contributed generously in terms of teaching effort—particularly to Dr. D. G. Freiman, Dr. E. B. Taft, and Dr. B. H. Waksman for their lectures; Dr. E, E, Hellerstein, Dr. A. E. Szulman, Dr. S. M. Shea, and Dr. M. H. Flax for help in the laboratories; Dr. Renate Miller, Miss Gutta Schoefl, Dr. Si-Chun Ming, Dr. F. von Lichtenberg, and Dr. W. G. J. Putschar for help with the demonstrations. ‘A large portion of the expenses was mét through a grant from the Public Health Serica (Pathology Training Grant No. 2G- 113). 2 Nobody knows how many ‘medical? jour- nals are published throughout the world, but 50,000 is a reasonable guess. The National Library of Medicine has just passed the 13,000-mark for current serials. (We are indebted to Mr. Harold Bloomquist of the Harvard Medical Library for this informa- tion.) These figures would imply that ‘medi- cal’ papers may well be published at a rate of the order of ten per minute,428 Journal of Medical Education REFERENCES, 1. MAINO, G., The Place of Patholozy ‘among the Biological Sciences (in prep- aration). 2, Masno, G.; La Garrura, Mi and ‘Tomson, T. E. Cellular Death and Necrosis: Chemical, Physical and Mor- Phologie Changes in Rat Liver. Vir- chows Arch. path. Anat, 333:421-65, 1960. 3, Scnuuspences, H., Manual of Experi- 4 VoL. 37, May, 1962 ments in Pathology. Lab. Investigation, 811011 (Exp. 19), 1959. SeLye, H. Use of “Granuloma Pouch” Technic in the Study of Antiphlogistic Corticoids. Proc. Soc. Exp. Biol. & Med., '82:928, 1953. Sreinaus, E. A. A Call to Inverte- brate Pathologists. J. Insect Path., 3:i, 1961. Vincnow, R. Die Cellularpathologie, 4th ed, (p. 25). Berlin: A. Hirsch- wald, 1871.