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Una fascinante revisión de los conceptos clave de la patología y un análisis minucioso de las ventajas de enseñar esta disciplina a todo estudiante de las ciencias de la salud y no solo a los médicos.
Una fascinante revisión de los conceptos clave de la patología y un análisis minucioso de las ventajas de enseñar esta disciplina a todo estudiante de las ciencias de la salud y no solo a los médicos.
Una fascinante revisión de los conceptos clave de la patología y un análisis minucioso de las ventajas de enseñar esta disciplina a todo estudiante de las ciencias de la salud y no solo a los médicos.
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
421422 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 arguedPathology 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, in424 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
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‘among the Biological Sciences (in prep-
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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
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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.,
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Sreinaus, E. A. A Call to Inverte-
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Vincnow, R. Die Cellularpathologie,
4th ed, (p. 25). Berlin: A. Hirsch-
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