University of Pavia
Prof. Paolo Mazzarello
HISTORY OF MEDICINE
Some of the main medical ideas and theories and the main discoveries which have characterized
Western medicine in its history
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WHAT IS MEDICINE
It is very difficult to give e precise definition of Medicine.
However a possible definition could be considered this: “The study and treatment of diseases and
injuries”.
Medicine is a vast field and it includes various aspects, among which science (medical science),
art (medical art), technique, humanism and anthropology.
Medical science. Medicine is the point of intersection of many different fields of science
(chemistry, physics, biochemistry, anatomy, physiology) which overlap “polyphonically” resulting
in the complete science of the human body. It includes methodological and theoretical aspects
proper of the scientific approach:
1) Refusal of authority principle. No “a priori” truth should ever hinder scientific
knowledge. However, a distinction should be made between scientific knowledge and
scientific practice, which, on the contrary, is submitted to ethical limitations.
2) Experimental method. In order to obtain meaningful answers, one has to ask nature
specific questions. Well-pondered, logically rigorous experiments can lead to brilliant
insights.
3) Induction. The process of logical thinking that moves from the experimental data to the
hypothesis.
4) Hypothetic-deductive method. Scientific inquiry proceeds by formulating a hypothesis
in a form that could be falsified by a test on observable data.
5) Integration of points 3 and 4: observation of experimental data leads to formulate a
hypothesis, which is then tested on experimental data.
6) Statistics. Medicine is a science of complexity, and knowledge often springs from
statistical correlation more than from clear-cut and evident causality.
Medical art. Medicine is a form of knowledge based on intuition. Since intuition can also
deceive, one should always be careful of perceptive distortions. Medicine is rooted not only in
cognitive intuition but also in emotional intuition, namely empathy, the capability to share and
understand the patient’s emotions and feelings.
Technique. Téchne is a Greek word signifying both art and applied science. Medical technique is
based on the practical application of scientific principles, coupled with devices suggested by the
practitioner’s experience and intuition.
Humanism. Medicine concerns about human beings in all their aspects and its goal is to guarantee
physical and mental welfare.
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Anthropology. Medicine is the study of human beings, everywhere and throughout time.
It is thus clear that medicine and its history are the point of intersection between the scientific and
the humanistic world, the real common ground of these two aspects of human culture.
The triple aims of medicine and the Hippocratic triangle
Medicine goals can be summed up in three points: to cure diseases, to prevent diseases, and to
improve health. Medicine regards healthy people but overall it deals with the sick. The sick is
therefore the barycentre of medicine. Hippocrates, father of the Western and Arabic medicine (IVV cent. BC.), was the first one to express the concept of medicine as the relationship among three
subjects, which is known as the Hippocratic triangle:
DOCTOR
PATIENT
MEDICINE
ILLNESS
METHODOLOGICAL CASE: HOMEOPATHY
Homeopathy from ancient Greek ὅµοιος, “omoios”, similar, and πάθος, pathos, sufferance.
(Not to be confused with herbal medicine)
Homeopathy was introduced by a German physician, Samuel Hahnemann (1755-1843). While he
was translating a book of the Scottish medical doctor William Cullen into German, was struck by
what he read on the properties of the cinchona bark (chinabark), imported from Perù and used
against fevers mainly malaria. According to Cullen workers employed on the processing of
cinchona bark, developed symptoms which resembled malaria. Intrigued by this fact, Hanhemann
began to take extracts of cinchona bark repeatedly at different doses, then he did the same with
other substances used as drugs at that time. In every case Hahnemann thought it always had the
same effect: substances used therapeutically, when administered to a healthy subject, always
reproduced the symptoms of the diseases for which they had been administered.
Thus he formulated the two “laws” of homeopathy:
1) The law of the «similar». With a first presupposition unsupported by any real experiments,
Hahnemann stated that: «among the different drugs, the one which in its effects produces
symptoms similar to a particular disease will also be the best homeopathic remedy for that
disease».
2) The law of the «infinitesimal». Hanhemann understood that it is not possible to treat patients
with high doses of substances that are often lethal poisons. With a second unsupported
presupposition, he stated that the substance is also active at low doses up to infinitesimal.
According to Hahnemann the disease increases sensitivity to the drug, so the drug is more
effective.
So, he turned the common therapeutic paradigm of the time (Hippocratic paradigm) upside down.
From ancient time it was followed the aphorism Contraria contrariis curantur (“Opposites are
cured by opposites”) of the Hippocratic medical tradition (from the Greek physician Hippocrates
V-VI cent. BC) or “Allopathic Medicine”: disease can be treated by drugs which produce effects
opposite from those produced by the disease under treatment, i. e. fever with ice, diarrhoea with an
astringent – styptic and so on).
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On the contrary, according to Hahnemann, Similia similibus curantur (“Likes are cured by
likes”). Homeopathic Medicine: disease can be treated with drugs, in minute doses, thought to be
capable of producing the same symptoms in healthy people as the disease itself.
What Hahnemann did: hydro-alcoholic extract of a substance diluted 100 times (solution A).
A small amount of solution A diluted again 100 times and so on. This procedure was repeated
up to TENTH, TWENTIETH, THIRTIETH centesimal. Every time the diluted substance
underwent a «succussion», a vigorous shaking of the diluted homeopathic preparation in order to
“activate” the medicinal substance.
Practical example of the results, in term of number of molecules, obtained at the end of a
homeopathic procedure: Calcium Carbonate (CaCO3) molecular weight =100
A mole of Calcium Carbonate (100 g.) = n° Avogadro molecules 6.02 x 10 23
1 litre of a solution 1 molar contains an Avogadro number of Molecules 6.02 x 10 23
1) Take 1 ml 6.02 x 10 20
2) Diluted 100 times 6.02 x 10 18
3) We can repeat this procedure 10 times 0.0602 molecules at the end of the subsequent
dilution!!!
4) If we repeat this procedure 20 or 30 times, as was suggested by Hahnemann and as it is done
today by homeopathic producers we dilute water with water.
To repeat a dilution 30 times to 100 of a gr. of Calcium Carbonate is equal to diluting that gr. in a
volume of liquid equal to 714 millions of billions times the volume of the sun!!
The molecular basis of modern pharmacology states that for every substance there is a therapeutic
dose and a toxic dose. Without a molecule and a receptor on which it acts there is no
pharmacological action. From a methodological point of view homeopathy is thus against all the
principles of modern scientific pharmacology and against the experimental method.
From a Lancet meta-analysis (2005) on 110 published papers on homeopathy the conclusion was
that “the clinical effects of homeopathy are nothing more than placebo effects”.
So why homeopathy was so frequently used and still is so frequently used?
When it was introduced homeopathy seemed similar to the vaccination procedure. Moreover there
were some apparent successes of this medication during the cholera epidemics of 1831 and 1854.
These successes were due to the fact that, at those times, therapies for cholera were more harmful
than useful (e.g. induction of vomiting, bloodletting etc.). Then a harmless medicine that seemed
to let free rein to "vis medicatrix naturae" (“healing power of nature”), appeared, at times,
seemingly effective.
In the modern time the success of homeopathy is due to some reasons:
1) System based on very simple principles.
2) Emphasis on an approach apparently “natural and “gentle”.
3) In a sense a non-reductionist and not materialistic view of the world.
4) Sometimes to undergo the homeopathic cures, it is necessary to interrupt chronic treatment that
induces side effects and then the suspension is accompanied by a relief of the symptoms.
5) Strong placebo effect, in fact it works more in those diseases in which the psychological
discomfort is more evident.
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PALEO-ANTHROPOLOGY – Evolution of human being
Homo Neanderthal
200 thousand years,
extinction 40.000 years ago
The tree of human evolution
Homo habilis Homo erectus
2 million years 1,7 million years
Australopithecus
4,5-1,8 million years
(Lucy, Johanson 1974
in Ethiopia)
Homo floresiensis
12 thousand years ago
Homo sapiens sapiens
Flourished about 100
thousand years ago
Cultural change: fire and Neolithic revolution
Two major cultural events resulted in important demographic consequences:
– The discovery of fire by Homo Erectus (400-800 thousand years ago) allowed to
warm up caves, to keep predators at a safe distance and to cook and smoke food, thus
improving nutrition;
– The Neolithic revolution consisted in the transition from hunting and gathering food
to agriculture and domestication of animals, which resulted in settlement. This process
first took place in the fertile crescent Iraq, Siria, Lebanon, Egypt (wheat, barley) in
Cina (rice, millet), in Perù and Mesoamerica (maize, beans, pumpkin, tomatoes,
potatoes).
Consequences of the Neolithic revolution were a significant expansion of human population,
due to the fact that agriculture can sustain a population from 10 to 100 times larger with respect to
the virgin earth, and a general improvement in quantity and quality of nutrition thanks to the
help of domesticated animals, which provided milk, meat, manure and muscle strength.
However, Neolithic revolution also lead to the explosion of infectious diseases:
a) Farmers lived in close contact with their waste, rubbish and feces, which could pollute
the sources of water of the community;
b) Settlements attract rodent (mice) that are vehicles of diseases;
c) Deforestation leads to marshland, which houses the mosquito Anopheles causing the
development of malaria;
d) The increase in population results in increased possibility of contagion.
This consideration apparently leads to a paradox: if such diseases developed in crowded societies
that did not exist before, where did they originate? Molecular biology investigations on bacteria
and viruses allow us to answer these questions: in fact, many similar infective agents were
identified in domestic animals.
Some examples:
Smallpox – linked to cowpox
Flu virus – from analogous viruses of duck and pig
Whooping cough (Bordetella pertussis) – from similar bacteria in pigs and dogs
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Malaria - from analogous protozoa in birds
Koch bacillus (tuberculosis) – similar to a cow bacteria
PALEO-PATHOLOGY - Evolution of diseases
Paleo-pathology, which investigates the diseases of the past and their evolution, relies on both direct
and indirect sources. Direct sources are, for example, human bones, teeth, human and animal
mummies and parasites; indirect sources are cultural material such as ancient writings.
– A clear example is that of Otzi, the Similaun man (3300-3100 BC), whose teeth show signs
of erosion, abscess and piorrea. From the isotopic composition of the tooth enamel it has
been possible to establish that Otzi probably lived in a different place from the one where he
was born.
– The analysis of beau lines of nails reveals the velocity of nail growth in the last months,
giving information about the state of health.
– Bones paleopathology allows to ascertain the presence of tumors (osteoma, osteosarcoma
etc), fractures, broken bones and regenerative processes, arthritis and arthrosis, bone erosion
and inflammation; it is possible to perform molecular-biological research.
– Skull bones give information about one of the oldest “medical” practices: bone trepanation
(or trephination). Some hypotheses of their function are therapeutic aim, ritual purposes,
amulets, or remnants of cannibal practices.
MEDICINE IN THE ANCIENT CIVILIZATIONS
THEURGIC or MAGIC-RELIGIOUS MEDICINE
Theurgic, magic-religious medicine believes in the influence of God (Theurgia = Theós: God +
Èrgon: work) or other forces on the human body. Magic is here defined as the art that purports to
control or forecast natural events, effects, or forces by invoking the supernatural.
Diseases are often considered a punishment produced by the invasion of devils, and recovery itself
is obtained through magic.
Theurgic and magic-religious medicine was practised in prehistory and in all the ancient
civilizations: Egypt, Assyro-Babylonian civilization, Hebrew world, Persian Empire, Ancient India,
pre-Columbian America.
CHINESE MEDICINE
Chinese medicine can be understood only considering the philosophical and religious context in
which it developed. One of the fundamental cultural principle of Chinese civilization is Thaoism,
founded by the ancient master Lao-Tsu (VI sec. BC.). Thao means “cosmic way”, a dynamic
mutation which leads the world continuous auto-poiesis (self generation).
Two opposite polarities are at the base of such natural order: Yin and Yang, which describe
opposing qualities in phenomena. Yin is usually characterized as slow, soft, insubstantial, diffuse,
cold, wet, and tranquil. Yang, by contrast, is characterized as hard, fast, solid, dry, focused, hot, and
aggressive. They are represented together in the T’ai-chi T’u, the "diagram of the supreme
ultimate", the circle of continuous cyclical change and interaction between the two opposite
manifestations of the whole. Each area also contains a small circle of the opposite colour at its
fullest point, forecasting how each will transform into the other.
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Wealth is regarded as the balance between Yin and Yang. The harmony between opposite qualities
is kept by a continuous flux of vital energy (Ch’i) which flows in 12-14 “meridians”, or channels,
throughout the body. Along the channels are 365 points acting on which it is possible to influence
the local amount of Yin and Yang, for example through acopuncture, a practice older than thaoism
which was absorbed by this philosophy. However, no correspondence of such channels with any
anatomical structure has been found, even though effectiveness of acopuncture in case of chronic
pain seems to be linked to the stimulation of production of endorphins.
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University of Pavia
Prof. Paolo Mazzarello
HISTORY OF MEDICINE
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GREEK MEDICINE: INTRODUCTION
Many foundations of modern Western medicine lie in Classical Greece. The so-called classical
period lasts from the fifth century B.C. to 323 B. C. (death of Alexander the Great).
Early Greek philosophy focused on the role of reason and inquiry. Such ideas spread throughout the
Mediterranean world, and their influence has remained strong in the West to this day. Thus Greek
philosophy paved the way to modern science, to modern medicine and to modern philosophy.
Greek Medicine started out as theurgic and religious medicine. Then it evolved into a more
rational, naturalistic and secular medicine (Hippocratic medicine), while that of Hellenistic age is
referred to as Post-Hippocratic medicine.
RELIGIOUS MEDICINE IN GREECE
Religious medicine became firmly established in ancient Greece, similarly to Egypt and
Mesopotamia. It was based on the worship of Asclepius,
a god son of the nymph Coronis and of
the god Apollo. He was symbolized by
a cock, which means vigilance, or
a snake as a symbol of
regeneration, of health, and of the length of life. Moreover the snake, coming from the depth of
earth, was believed to bring the power of medicinal vegetables. This is the reason why the serpent
entwined around a staff became the symbol of medicine and in general of the art of healing.
Other gods of Greek medicine were the children of Asclepius: Hygeia (health), which represented
hygiene and preventive medicine, and Panacea (all healing), goddess of therapy, with whose name
the alchemists used to call the universal drug able to cure every disease.
According to religious medicine, diseases were feared as punishment. So sacred healing was
practised through prayers, rituals and sacrifices to the gods. In particular, Asclepius was worshipped
in temples (called Asclepieions) to which patients went to be cured.
They were usually built in
salubrious spots near springs. The first appeared in the VIth century and by the IVth century they
were spread in all Greece. The most famous were those of Epidaurus, Kos and Korinth.
An Asclepieion was a group of buildings, including the temple with statues of Asclepius, Hygeia
and Panacea; the tholos, a round edifice (perhaps a mausoleum or a terrarium for the sacred snakes
or an astronomical edifice); and an Abaton or room for incubation. In the Abaton the patients would
pray to the god, and sleep waiting for Asclepius to appear in their dreams and bring the cure.
The illnesses cured were recorded on the thousands of votive offerings that were presented to the
temples and also on ex-voto.
Some votive tablets and an inscription in Epidaurus testify that the serpents oral cavity was put in
contact with superficial skin lesions, to speed the tissue reparation. The serpents so exploited were
of the genus Elaphe, whose saliva has been found to contain epidermal growth factor, which would
explain the apparent miracle.
HIPPOCRATIC MEDICINE
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In the V century, besides the religious medicine of Asclepius, a secular medicine linked to the name
of Hippocrates started developing. Hippocratic medicine and temple-healing coexisted without
antagonism; they were rather regarded as complementary.
Hippocrates of Kos (460 BCE - 370 CE)
Hippocrates taught and practiced medicine throughout his life, travelling across Greece and maybe
Libya and Egypt. According to some sources, he learned medicine from his father and grandfather.
The two sons of Hippocrates, Thessalus and Draco, and his son-in-law, Polybus, were his students.
The Corpus Hippocraticum is made up of about sixty works, only formally ascribed to him.
With Hippocrates, medicine became a science (knowledge based on a precise method) and a
profession (discipline and rigorous practice). He separated medicine from religion, arguing that
disease was not a punishment inflicted by gods but rather the product of environmental factors, diet
and living habits.
Hippocratic medicine was influenced and nourished by:
– Rational philosophy (mainly Ionian);
– Experience of the instructors of exercise, bathing, massage, gymnastics and diet
(Olympic games are recorded as early as 776 BC);
– Experience gained dealing with traumatic injuries during battles;
– Ancient eastern civilizations;
– The tradition of religious (templar) medicine.
A more accurate analysis of Hippocrates’ significant innovation follows, subdivided in 5 points.
1) Separation of medicine from religion
Hippocrates’ work was characterized by a naturalistic attitude. “No one disease is either more
divine or more human than another ... no one disease arises without a natural cause...” (On Airs,
Waters, and Places). In particular, he declared that epilepsy, which was considered at the time the
prototypical “sacred” disease, had a natural cause.
2) Methodological revolution
Hippocrates based his diagnoses on the detailed observation of the patient (Observatio et ratio).
From his acute observations and descriptions derive some Hippocratic eponyms such as the
Hippocratic face (facies Hippocratica), the change produced in the face by impending death.
Anatomical observations were based on animal dissection because human dissection was forbidden.
The corpse was considered a source of pollution, impurity or miasma. The perpetrators were
considered polluted and polluting, a source of danger for the whole society. According to the saying
“Visible is a sight of the unseen”, only the direct observation of the body was allowed, and
therefore inspection, palpation and auscultation were performed.
3) Humoral physiopathology
The human body was thought to contain
four vital elements and humours: blood,
phlegm (or
lymph), yellow bile, black bile (or atra bile, atra=black, or mélan colé).
Human beings were equated to a vase where the four humours were mixed. Sickness derived from
excess (materia peccans) or deficit of one of these humours.
– Phlegm was associated with winter, the season of colds, bronchitis and pneumonia;
– Blood was associated with spring, when there was spring fever (benign terzan malaria),
dysentery and nose-bleeds. Blood was associated with life since Homeric times; yet
even blood was expelled naturally from the body, as in menstruation or spontaneous
nose bleeding. Such natural evacuation probably suggested the practice of blood-letting;
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– Yellow bile was associated with summer, the season of severe fever (malaria);
– Black bile was associated with autumn, when there were more cases of melancholy.
Encephalocentrism: Hippocrates set the brain at the centre of mental function, and also for Plato
the brain was the site of the rational part of the soul. Aristotle, instead, supported cardiocentrism.
This dichotomy last until the end of the Middle Ages.
“Men ought to know that from nothing else but the brain come joy, delight, laughter and
jokes, and sorrow, grief, despondency, and complaints. And from the brain, above all, we
acquire wisdom and knowledge, and we see and hear, and know what is bad and what is
good, what is pleasant and what is unpleasant; ... And from the same organ we go mad and
delirious, and fears and terrors assail us ... Because of this I am of the opinion that the brain
exercises the greatest power in man.” (On sacred disease, Hippocrates)
4) Therapy
Hippocrates based therapy on two theoretical principles:
– Physis (Greek for nature) should be the reference base of clinical practice;
– Vis medicatrix naturae: the physician must help the healing power of nature, which acts
either as a general (fever) or a local reaction (inflammation). The body contains within itself
the power to re-balance the four humours and heal itself.
And two practical principles:
– Primum non nocere: first, do nothing which could be harmful;
– Contraria contrariis curantur: treat with the contrary, hot with cold, moist with dry (fever
with ice, diarrhea with astringent etc.). It is the basic principle of allopathic medicine, the
opposite of Samuel Hahnemann’s homeopathy (Similia similibus curantur).
Minor orthopaedics and surgery: fractures were to be immobilized with splints and bandages.
Wounds should be kept dry, but suppuration was deemed essential for healing. The pus supposedly
derived from vitiated blood which needed to be expelled from the body. Pus was thus a desirable
evacuation (this idea hindered the development of surgery).
Female diseases were dealt by special medical literature. Gynecological examinations were carried
out by midwives. Practitioners were mostly interested in the womb (hystére), especially its neck
(hardening, inflammation, coldness), cured through “pessaries” soaked with substances and cast in
vagina. Destructive pessaries to produce abortion were forbidden.
Beverages: most common were infusions, decoctions,
beverages with grapes (wine, must,
vinegar), mellicrate or hydromel (honey and water) and oxymel (honey and vinegar) which was
supposed to favor expectoration of excess phlegm from the lungs and respiratory tract, open the
bronchi, and ease breathing.
Blood-letting was performed at specific points: elbow, ankle, under the tongue, in the head.
Evacuation was commonly practiced: vomiting, but also enemas, purges, laxatives (hellèborus or
hellebore, a plant which could be also poisoning).
Cauterize with the fire by using an incandescent metal rod.
Diet was the cornerstone of the healing art because it had the aim to maintain the correct proportion
of all body constituents. It involved the entire lifestyle: nutrition, physical activity,
correct sleep,
regular sexual life, harmony of behaviour, thermal therapy.
5) Foundation of medical deontology
The Hippocratic Oath, traditionally ascribed to Hippocrates, is considered as one of the first
statements of a moral conduct to be used by physicians, claiming respect for all human life. It is a
collection of principles and regulations that the physician must respect exercising his profession
It has been the pillar of medical deontology, but since modern medicine now faces problems that
were completely unimaginable at the time Hippocrates lived, for many physicians today it has
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ceased to be a moral force or a guiding ideal.
– To keep the well-being of the patient as the highest priority;
– Professional secrecy;
– Refusal of euthanasia (“I will not give a lethal drug to anyone if I am asked, nor will I advise
such a plan”);
– The refusal of abortion (“I will not give a woman a pessary to cause an abortion”);
– Prohibition against having sex with patients both female and male, be they free or slaves.
We recall a wise aphorism by Hippocrates: Life is short, art is long, fleeting opportunity, illusory
experience, difficult judgment.
POST-HIPPOCRATIC (HELLENISTIC) MEDICINE
The Hellenistic period for European and Near Asian territories describes the era that followed the
conquests of Alexander the Great (who died in 323 BC). At this time, Greek cultural influence was
at its zenith in Europe and Asia. It would last until 30 BC. (Roman conquest of Egypt).
Alexandria of Egypt was founded by Alexander the Great in 332-331 BC and was then ruled by
the Ptolomies. It became an extraordinary pole of attraction for Egyptians, Greeks, Jews and
Syrians. According to some historians its magnificent Royal Library contained about 700.000
scrolls of papyrus. These documents were destroyed in different periods: in 48 BC after Julius
Caesar's Fire in The Alexandrian War, as a consequence of a decree of the bishop Theophilus in AD
391 and finally after the Muslim conquest in AD 642. The Royal Museum included reading rooms,
astronomical observatory, zoo, botanical garden.
In this period we find the first, but also the last in a thousand years, systematic dissection of human
cadavers for research purposes.
Apart from this period, cutting open a deceased human being was beyond any culturally acceptable
limit: according to the sacred laws of ancient Greek, corpses were sources of pollution or
contamination and opening them was considered a profanation. People who broke the law were
considered impure and they were forbidden to enter a sacred temple. Inviolability of human corpses
was a sort of dogma.
This dogma was broken by two anatomists: Herophilus of Chalcedon (330/320 - 260/250 BC),
called “Father of Anatomy”, and Erasistratus of Chios (330-250 BC), “Father of Physiology”.
It was a unique occasion. Only in the XV century pope Sistus IV would allow physicians and artists
to dissect the bodies of executed criminals and unidentified corpses.
To Herophilus, in particular,
we ought many anatomical discoveries: the torculari Herophilus (site
of confluence of the dura mater sinuses in the occipital part of the skull), the cerebral lateral
ventricles III e IV, and seven pairs of cranial nerves.
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University of Pavia
Prof. Paolo Mazzarello
HISTORY OF MEDICINE
3
ROMAN MEDICINE
a) THEURGIC MEDICINE
Ancient Roman medicine started out with the veneration of several local gods (Salus, Febris,
Angina…). Medicine was practiced by the “pater familias” (head of a family). A significant
influence came from Etruscans, who exploited the medical properties of vegetables. But it was the
penetration of Greek culture in Rome which lead to the development of laical medicine after the
third century.
b) LAICAL MEDICINE
Asclepiades of Bithynia (124 – about 40 B. C.) taught that disease results from constricted or
relaxed conditions of the pores of the body, through which atoms flow. “Gymnastic of the pores”
could be performed through thermalism.
Galen
Galen was born in Pergamum in Asia Minor in the year 129 C.E. After receiving medical training in
Smyrna, Corinth and Alexandria, he gained fame as a surgeon to the gladiators of Pergamum. In
162 he was summoned to Rome to be the physician of the Emperor Marcus Aurelius. There, Galen
spent the rest of his life writing an enormous corpus of medical works until his death in Pergamon
around 200.
The bases of Galen’s doctrine were the following:
– Traditional knowledge (especially hippocratic): humour doctrine, observatio et ratio at the
base of the diagnostic procedure, primum non nocere, vis medicatrix naturae;
– Dissection of animals, particularly pigs and Macacus rhesus;
– Occasional observations of the internal structure of the human body: as a doctor of
gladiators he could deepen his anatomical and surgical expertise;
– Teleological vision (from the Greek “Télos” aim, scope, purpose): Galen thought that the
universe was divinely ordered.
In the human body “nothing could be better designed”: it is
perfect in maintaining life, generating it and improving its quality. The whole Nature was
the great project of a Demiurge who left nothing to chance.
Galen adopted a scientific method, thus based on experience and reason. He made many original
anatomical observations, such as the great vein of Galen in the brain, and seven pairs of cranial
nerves, the superior and inferior laryngeal nerve, and the anastomosis between them (anastomosis
of Galen).
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Physiological principles
1. Humoral doctrine. There is a relationship among organs, humours, temperaments and seasons.
Organ
liver
brain
gallbladder
spleen
Humour
blood
phlegm
yellow bile
black bile
Temperament
sanguine
phlegmatic
bilious
melancholic
Season
spring
winter
summer
autumn
His physiopathology, like Hippocrates’, was based on the doctrine of humours. This lead to the
harmful concept of “Pus bonum et laudabile”: pus is a good sign because it represents the materia
peccans the body is eliminating.
2. The pneuma (Latin, Spiritus) The pneuma, the breath of the cosmos, was modified by the three
principal organs into three different spirits: the liver, which made blood, was the seat of natural
spirit (pneuma physicòn); the heart, source of innate heat, was the seat of vital spirit (pneuma
zoticòn); and the brain produced animal spirit (pneuma psychicòn). Pneuma were distributed along
three systems of vessels, the veins, the arteries and the nerves (which Galen considered empty
ducts).
3. Hepatocentric haematopoiesis. All the food ingested (apart from the amount transformed in
faeces) was transformed into blood in the liver. So in a day about 2 to 5 Kg of food (considering
also the water ingested) were converted to blood, which was then attracted by the diverse organs,
like a magnet attracts metal, to be continuously consumed. The term “circulation” is thus wrong for
this model.
Galen’s wrong anatomo-physiological conceptions remained dominant in Europe and the Islamic
world up to the Renaissance. Two anatomical mistakes were particularly critical for the future:
– The existence of interseptal (interventricular) pores through which blood could pass from
the right to the left ventricle;
– The existence of an privileged anatomical site, the rete mirabile at the base of the brain. It
was a network of vessels which he found in calves. Human dissection was forbidden, but
Galen thought that humans had a similar anatomical characteristic of some animals.
According to him, the rete mirabile was the site where vital spirits turned into animal spirits.
Therapeutic principles
Galen referred to some concepts already developed by Hippocrates:
– Primum non nocere
– Vis medicatrix naturae
– Contraria contrariis curantur (antagonize the pathological element)
– Blood letting, cupping, vomiting, enema.
The leech Hirudo medicinalis is an annelid with a triangular mouth and 80-90 teeth. It injects an
anti-coagulative substance. It was used for blood letting during the Middle Ages up to the
Nineteenth century.
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Galen’s blood-pneuma simplify model of diffusion inside the body
ORGANS
BLOOD
Arteries and Veins
LEFT
RIGHT
LIVER
HEART
HEP. PORTAL VEI N
Faeces
.
STOMACH - INTESTINE
FOOD
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2-5 kg
University of Pavia
Prof. Paolo Mazzarello
HISTORY OF MEDICINE
4
FROM ANTIQUITY TO THE MIDDLE AGES
Alexandria was the main medical centre and Galen was the most influential author. Galen’s
writings became viewed as scripture rather than scientific treatises, and his views took on a "quasitheological" status. Although this wasn’t his desire, Galenism became a sort of theology of its own,
virtually immune from reasoned challenge. Thus, when findings were uncovered that did not
coincide with Galenist theory, they were marginalized instead of being viewed as true, challenging
anomalies.
The turning point was the fall of the Western Roman Empire in 476 AD (last emperor Romulus
Augustulus), which marked the beginning of the Middle Ages.
ARAB WORLD
Islam was born in 610 from the revelation of Muhammad (570-632), prophet of the Muslims.
According to a hadith (sayings of Muhammad), he said: “look for knowledge even in China”. Thus,
at the beginning of its expansion, the Islamic society opened up to knowledge.
Alexandria was conquered in 642 by a general of the caliph Omar. Islamic power conquered all
North Africa, Persia and subsequently Spain.
Important centres of Islamic culture developed in Persia, in Iraq (Bagdad), Syria (Damascus), Egypt
and Spain. Bagdad became a capital of culture and, under the caliph Al- Mamum, the scholars of
the “House of Wisdom”, a sort of University, performed translations from Syriac, Palhavi, Sanskrit.
The Persian civilization was very important since it included pagan philosophers expelled from the
Byzantine world at the time of Justinian (he closed the Plato academy in 529 AD), heretic
Christians (Nestorians) and followers of Indian philosophies. Arabic translations (IX-X cent.) of
many Galenic writings were diffused. Great Islamic doctors were:
– In Persia, Ibn Sinā, known in the West as Avicenna (980-1037), followed Aristotle’s
cardiocentrism even if he was, in general, an important exponent of Galenism;
– In Cordoba (Spain), Ibn Rushd known in the West as Averroes (1126-1198);
– In Cordoba, then in Egypt, Moses Maimonides (Jew, 1138-1204) authors of the “Guide for
the perplexed”, and of the “Medical Aphorisms”;
– In Damascus, then in Egypt, Ibn al Nafis (1213-1288) who described the pulmonary
circulation and denied the porosities of the interventricular septum.
Arabs organized hospitals (Bimaristan) which became structures adapt to learn medicine. They had
separate wards for men and women, they were very concerned about hygiene, made careful
registration of the clinical cases and developed some kind of pharmacy. It was an Arab medical
doctor to introduce alcohol as a disinfectant. They made use of sponges soaked in opium (extract of
the Papaver somniferum), containing morphine, codein, papaverine, and of hashish (a resin
collected from the plant Cannabis), containing cannabinoids.
However they followed the
Hippocratic and Galenic therapeutic precepts, and adopted practices such as phlebotomy for bloodletting.
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CHRISTIAN WORLD
The Christian world divided in a double destiny.
Bizantium, Eastern Roman Empire
Bizantium started a slow decadence. However, the Byzantines preserved part of Hellenistic and
classical science, and particularly many original Galenic texts.
Latin world, Western Roman Empire
Barbarian invasion caused the Western Roman empire to collapse. This was catastrophic for Latin
civilization, including the teaching and practice of medicine. European city life transformed into a
landscape dominated by castles and cathedrals, with literate men and women confined to
monasteries. Monasteries became cultural centres, fundamental for saving at least a small part of
ancient science, medicine and literature. Most of it, however, was irreparably lost.
What survived of the ancient Greek and Latin culture reached us through three different ways:
1) Translation in Arabic of Greek writings;
2) Preservation of the Greek heritage in Costantinople and the Byzantine world;
3) Translation in Latin from Greek and Arabic in the medieval monasteries.
At the end of the first millennium things began to change. The first organized medical school in
Europe was founded in Salerno. Its golden age included the period between 1096 -1270. Also
women could learn and teach medicine. In Salerno many translations were made, especially from
the Arabic.
At the beginning of the second millennium
a new mercantile mind exploded with the birth of a
monetary economy. Two factors triggered the rebirth of medical culture:
– XII- XIII century, foundation of Universities (Bologna, Padua, Oxford, Paris, Montpellier,
Cologne). The University of Pavia was founded in 1361;
– Foundation of Hospitals linked to charity organizations. San Matteo Hospital was founded in
1446.
Dissections
In the Middle Ages the corpse was considered the site of the soul. To open a cadaver was thus
considered a sacrilegious act. However, in this new cultural environment the taboo of the
inviolability of the cadaver began to be overcome. The first attested dissection for anatomical
purposes as a support of teaching activities was performed by Mondino de’ Liuzzi (1275-1326),
who taught in Bologna and wrote a textbook of Anatomy.
The beginning of anatomical investigations was supported by the Church. In fact, it was the bull of
pope Sistus IV, in 1472, which allowed for the use of corpse for anatomical purposes. Italy thus
became the barycentre of the anatomical studies and of science at large.
Public dissections were performed during the coldest months (January-February) in order to avoid
the quick decomposition of the body. The dissections were performed on people who had been
condemned to death immediately after the execution.
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RENAISSANCE
Some events dramatically changed the horizons of the West:
1. The discovery of America (1492) closes the Middle Ages;
2. The invention of the printing press with mobile letters (Gutenberg, 1400-1468);
3. The fall of Granada (1492), last presence of the Islamic power in Spain;
4. The conquest of Costantinople by Turks (1453).
Human beings start realizing the creative potential of their mind. Discussions and disputes on every
aspect of life, nature and cosmos arise. Art perfectly represents the surface of the body, while
anatomy explores the deep inner structure. At last, anatomists begin to understand how wrong
Galen was in his anatomical and physiological tenets.
Leonardo da Vinci (1452-1519)
He summarizes the spirit of the new age. He was interested in the external expression of bodies as
well as in their inner structure. This passion made him a great anatomist and prominent scientist. He
studied the cerebral ventricles with fused wax, the fetus, muscles and bones. He could therefore
begin to disprove Galen on some minor aspects of human anatomy.
He collaborated with Marcantonio della Torre a professor of Medicine at the University of Pavia.
Berengario da Carpi (1470-1530)
He made the first important confutation of Galen: there is no structure like the rete mirabile at the
base of the brain.
VESALIUS (1514-1564)
Vesalius was the most important anatomist of the XVI century. Born in Brussels, he studied at
Lovanius, Paris and Padua, where he obtained his doctorate. Immediately after the graduation he
was nominated professor of surgery. He regarded dissection as a pathway to knowledge: finally the
master descended from his chair and directly performed dissections with his own hands. He made a
huge number of observations differing from Galen. In particular, he did not observe the pores in the
interventricular septum and the rete mirabile at the base of the skull.
Vesalius’ masterpiece, De humani corporis fabrica, was published in 1543. It included more than
300 figures realized by professional painters and artists of the Titian school. The most important
was Jan Stephan van Kalkar. Rigorous anatomical representation wasn’t just an appendix to the
text, but a powerful instrument for scientific investigation.
Galileo Galilei
With his formulation and practice of the experimental method (a mixture of observations,
hypotheses, mathematical reasoning, confirmatory experiments) he opened the way to the scientific
revolution:
– The world is a great book written in a mathematical language;
– Measurement is the application of mathematics to the study of nature to quantify
phenomena;
– Refusal of the authority principle, because the knowledge of nature is not subjected to any
authority apart from reason;
– The simple Hippocratic observatio et ratio is not enough: new experiments have to be
conceived in order to decodify and check the results.
The new experimental attitude based on the quantification of nature lead to an important
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physiological consequence: THE DISCOVERY OF BLOOD CIRCULATION by William
Harvey.
1. Ibn Al Nafis, arabic medical doctor of the XIII century, described the small circulation.
2. Vesalius denied the existence of the pores in the interventricular septum.
3. Girolamo Fabrizio D’Acquapendente published “De venarum ostiolis” (1603) in which he
described venous valves, even though he didn’t understand their function. He thought that
valves slowed down blood flow from the heart to the peripheral organs.
4. Gaspare Aselli, professor of anatomy at Pavia University, in 1622 proved the existence of the
chiliferous vessels against Galen tenets according to whom the intestinal absorption of food
occurred only through the hepatic portal venous system.
5. Michele Servetus had the intuition of the small circulation.
6. Realdo Colombo, from Cremona, was a student and the successor of Vesalius in Padua. In his
book De re anatomica he clearly described the small circulation, the absence of pores in the
interventricular septum and the function of cardiac valves.
7. Andrea Cesalpino introduced the term “circulation” referring to blood movement. He
supposed that the extreme divisions of the arteries and the extreme divisions of the veins were
connected by sorts of capillaries which he named “capillamenta”.
WILLIAM HARVEY (1578-1657)
He studied in Cambridge but moved to Padua in 1599, when the chair of anatomy and surgery was
held by Fabrici d’Acquapendente. He graduated at Padua University in 1602. He went back to
England where he became the medical doctor of the kings James I and Charles I.
In 1628 Harvey published his scientific masterpiece: Exercitatio anatomica de motu cordis et
sanguinis in animalibus (Anatomical Essay on the Motion of the Heart and Blood in Animals), a
book of 72 pages based on the dissection of more than 40 species of animals.
Harvey saw the heart and blood as a functional unit, and from this belief he moved to demonstrate
the system of blood circulation. Apart from the relevance of his discoveries in physiology, Harvey’s
work was so important because he introduced the quantitative and mathematical reasoning in
biology.
The first part of the Exercitatio is dedicated to the movement of the heart, and it includes the refusal
of the interventricular passage of the blood. Moreover, Harvey discovered that the actual active
movement of the heart is the systole (contraction) and not the diastole (dilatation) as Galen thought.
To observe the movements of the heart during vivisection, he used cold blood animals with a slow
heart movement like eels, frogs.
The second part is dedicated to the movement of the blood and it is subdivided into three
hypotheses.
1) First hypothesis: the amount of blood which flows through the heart is higher than the
amount that could be supplied by the ingestion of food.
According to Galen, all the ingested food (apart from that transformed in faeces) is transformed into
blood in the liver and than sent to the various organs which consume it continuously. Consequently,
about 3-5 Kg/die of food and liquids should be transformed into blood.
But Harvey calculated that the amount of blood which is pumped by the heart in the aorta in the unit
of time is more or less the amount kept in the left ventricle, therefore 6 grams. Thus 6 g multiplied
by the number of heart beats per hour (about 4000) results in the amount of blood passing through
the heart in one hour, 24 kg of blood – clearly superior to the weight of foods and liquids ingested
in a day.
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So, Harvey mathematically demonstrated the contradictions of Galen’s system. In a hour the
amount of blood which flows through the heart is far superior to the quantity of the food ingested in
the whole day, roughly corresponding, according to Galen, to the blood transferred to the various
organs. Where does this blood come from? The answer of Hurvey was from itsef. It is the same
blood that continuously circulates in the body, to and from the heart.
This was the fundamental quantitative demonstration obtained by Harvey. It was the first clear
application of the new Galileian quantitative approach to nature in medicine and biology.
2) Second hypothesis: blood reaches the limbs through the arteries and flows back through
the veins. Galen thought that the blood reached the limbs through both arteries and veins. Harvey
disproved him by selectively tying the vessels with a tourniquet.
If the tourniquet is rapidly applied very tightly (as was the practice in preparation for amputation),
the arm goes pale and veins do not become turgid. It stops both the arterial and the venous blood
(the vessel wall is completely compressed).
Following a light application of a tourniquet on the arm, however, the veins become turgid since
only the vein wall collapse under the tourniquet. Instead arteries have thicker walls than veins (due
to the fact that the blood flows through the arteries at a much higher pressure) and thus do not
collapse in this condition of light application of the tourniquet. So, blood continues to move towards
the hand but could not come back to the heart in the veins because it is blocked by the compression
of the tourniquet, hence the turgidity of the vein beyond the tourniquet towards the periphery.
When the tourniquet is released, the subject feels a cool wave rising towards the armpit (because the
cooler venous blood goes back to the heart).
3) Third hypothesis: venous valves make the blood flow unidirectional.
Harvey proved the true function of venous valves. However, he couldn’t understand how veins were
filled by arteries. He postulated the existence of small capillaries between arteries and veins, but
these were not discovered until 1661, a few years after Harvey died, by Marcello Malpighi, one of
the pioneers of microscopy.
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University of Pavia
Prof. Paolo Mazzarello
HISTORY OF MEDICINE
5
THE BIRTH OF MICROSCOPY AND ITS EARLY DEVELOPMENT.
THE CELL THEORY
Single lens magnification date back to the Middle Ages.
Microscopy was born between the end of the Sixteenth and the beginning of the Seventeenth
century. The person who is credited, above all, with the invention of the first compound microscope
(that is a microscope composed of at least two lenses) is a Dutch spectacle maker optician,
Zacharias Janssen. The first compound microscopes were not very powerful, at the most they
magnified 10 times.
Galileo also built a microscope that he called “Occhialino”, “little eye”.
The English physicist and natural philosopher Robert Hooke published the first book on microscopy
titled “Micrographia” (1665). The most important discovery contained in this book was the
description and the illustration of some spaces in the structure of the cork (cut in thin slices), which
he named cells from the Latin name cella, small room. By analogy, Hooke applied the term cells to
the thickened walls of the dead cells of the cork. Although Hooke used the word differently to later
cytologists (he thought of the cork cell spaces as passages for fluids involved in plant growth), the
modern term “cell” comes directly from his book.
Other important microscopists of the Seventeenth century were Marcello Malpighi whose name
became an eponym of the “Malpighian corpuscle” observed by him in the cortex of the kidney and
Antony van Leeuwenhoek who used a simple lens microscope and was the discoverer of
microorganisms.
In the subsequent Eighteenth century the cell structure of some vegetables and animals was again
observed. In 1831 the Scottish botanist Robert Brown, while dealing with the orchid cells, noted the
existence of a structure within them that he termed “the nucleus”. However only in the middle of
the Nineteenth century these various observations were collected together becoming the base of cell
theory.
Firstly formulated by Theodor Schwann and Mathias Schleiden (1838-39) and further developed by
Rudolf Virchow and Robert Remak who showed that cells are formed through scission of preexisting cells, it became the basic structural theory of living being. It affirms that all living things
are single cells or composed of a federation of cells or/and a product of their activities.
EVOLUTION OF THE CONCEPT OF PATHOLOGY
The oldest idea of disease was the theurgic and magic-religious, which was followed by the
humoral concept of pathology (Hippocrates and Galen; imbalance of humours causes diseases).
Between the Seventeenth and the Eighteenth century, among the medical doctors, the idea emerged
that, if they could perform human dissection on the corpses of their patients after their death, they
would have understood the anatomical alteration that causes the diseases.
This scientific program was pursued by Giovan Battista Morgagni the founder of the so called
“organ pathology”. In many diseases he found relationships among alteration of the organs and
clinical symptoms. He published a historical masterpiece in medical sciences, De sedibus et causis
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morborum per anatomen indagatis (“On the causes and sites of diseases through anatomical
investigations”) where he collected case histories, with their most striking symptoms and autopsy
results. In this way it was possible, for example to associate cyanosis (blueness of the skin) with
pulmonary failure, hepatic cirrhosis with jaundice, brain tumours with paralysis etc.
Morgagni, according to the medical historian Roy Porter, “shifted emphasis from symptoms to the
site of disease”. His anatomical thought showed that “diseases were located in specific organs”, and
that such morbid organ changes were responsible for disease”.
In Pavia the program of Morgagni was followed by his last pupil, the important anatomist Antonio
Scarpa whose name is associated with many discoveries on the structure of the ear, the nerves of the
heart, the pathological process of arterial aneurism.
Morgagni introduced the concept of organ pathology, but organ are composed of tissues. This was
the idea introduced at the beginning of the Nineteenth century by the French anatomist François
Xavier Bichat (who is considered the founder of histology). So, tissue alteration became the site of
the pathological phenomena (Tissue pathology).
But tissues are composed of cells. After the introduction of cell theory, cells became the building
block of tissues. At this moment (middle of the Nineteenth century) cells became the site of the
pathological lesions of diseases. This was the basic concept of cellular pathology of Rudolf
Virchow. Diseases derive from alteration of cells. According to Virchow “Since cells are the basis
of all vital manifestations, they are also the sites of all diseases” (Cellular Pathology, 1858). Thus,
with the cell theory, a single physiopathological unitary concept became the interpretative code of
an enormous amount of different morbid changes. The histo-pathological observation made with the
microscope allowed the pathological processes to be seen as the result of successive cellular
generations. A dynamic concept of morbid phenomena developed at that moment. This was
particularly useful to understand the phenomenon of tumour growth and metastasis (the spread of
pathological cells from one organ to another non adjacent, via blood circulation or lymphatic flux).
Only after the introduction of cellular pathology, the microscope became the basic instrument for
pathological examination of tissues.
As a consequence of this methodological revolution also a sort of terminological revolution took
place with the introduction of a taxonomical nomenclature based on the morphological alteration of
cells like: hypertrophy (increased mass and volume of the cells), hypotrophy (the contrary), atrophy
(partial or complete wasting away of a tissue), infiltration (penetration of cells in the surrounding
tissue), necrosis (the process of a pathological cell or tissue death) etc.
However, since all cells are composed of molecules, at the base of morbid changes there is a further
pathological level, the level of the molecules (Molecular pathology). The proponent of this
concept was the British clinician Archibald Garrod. He described some diseases due to failure of
enzymatic pathways, like alkaptonuria, and envisaged a sort of chemical pathology.
The American chemist Linus Pauling further developed this idea. He discovered that an abnormal
version of a subunit of haemoglobin produced the sickle cell anemia. Many other example soon
followed in every sector of pathology.
In summary we have this evolution of the concept of pathology
1) Theurgic-magic-religious concept of diseases
2) Humoral pathology
3) Organ pathology
4) Tissue pathology
5) Cellular pathology
6) Molecular pathology
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University of Pavia
Prof. Paolo Mazzarello
HISTORY OF MEDICINE
6
THE MICROBIOLOGICAL THEORY OF INFECTIOUS DISEASES
In the first century BC the Latin poet Lucretius hypothesized that “corpuscles” of biological matter
could transmit contagious diseases.
In the Sixteenth century the physician Gerolamo Fracastoro (1478-1553), in order to explain the
transmission of syphilis, supposed that this disease was caused by “seminaria”, that is “small living
invisible corpuscles” able to spread the disease.
The alternative theory, which was dominant up to the first half of the Nineteenth century, was the
miasmatic theory of diseases which maintained that contagious diseases were caused by a miasma
(ancient Greek for “pollution”), a noxious form of “bad air”. Miasma was considered to be a
poisonous vapour or mist filled with particles from decomposed matter (miasmata) that caused
illness.
Miasma could explain the rapid diffusion of a disease in a population. This idea was experimentally
demonstrated to be wrong only in the Nineteenth century when the microbiological theory of
infectious diseases was developed.
The first scientist to translate aetiological (causal) ideas on the microbiological genesis of diseases
into an actual research program was Agostino Bassi (1773-1856). Graduated at the University of
Pavia, he experimentally demonstrated that a type of silkworm disease was due to a “parasitic
fungus”. He successfully isolated the parasite and used it to infect a healthy animal. Moreover Bassi
made an important generalization: “all contagious diseases of vegetables and animals including
mankind, are caused by parasites”.
The further development of medical microbiology is linked with two great scientists who made their
important microbiological discoveries in the second half of the Nineteenth century: the French
Louis Pasteur (1822-1895) and the German Robert Koch (1843-1910).
Louis Pasteur was trained as a chemist but soon he was involved in investigating into medicobiological topics. According to Pasteur microorganisms were responsible for infectious diseases
(germ theory of infectious diseases) as well as putrefaction and fermentation. He was able to
develop the first vaccination procedures (for chicken cholera, anthrax and rabies) after the smallpox
vaccination introduced by Edward Jenner (see below). The term pasteurization (semi-sterilization of
many products, especially milk) is named after him.
The Pasteur’s vaccination against human rabies was a triumph for medicine. In 1885 a boy, Joseph
Meister, was bitten 14 times by a rabid dog. Previously Pasteur had developed vaccination (a term
which he introduced) against rabies only in animals. He used infected nervous tissue from infected
rabbit and was able to attenuate it. In fact he discovered that nervous tissue dried for two weeks
became non-virulent. Then he injected this fourteen day old rabbit tissue into some healthy dogs;
the next day he injected a thirteen day old rabbit tissue and so on. At the end the dog was able to
receive the full infectious material without developing the disease. During the sequential injection,
the dogs were progressively vaccinated. When Pasteur was asked to try the rabies vaccination
procedure on Joseph Meister he decided to take the risk. Since he was not a qualified medical
doctor he was assisted by two other physicians who performed the series of injections. Joseph
Meister survived and did not develop rabies.
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The second important champion of the microbiological theory of infectious diseases was Robert
Koch. He transformed bacteriology into a scientific discipline. He developed some of the
fundamental method of microbiology like the cultural procedures especially in solid media (at the
beginning potato slices, then standard broth solidified by adding gelatine, and finally with agaragar, an extract of Japanese seaweed). He discovered the causative agent of anthrax (Bacillus
anthracis), of tuberculosis (Mycobacterium tuberculosis), cholera (Vibrio cholera). Koch also
developed the concept of “healthy carriers” (a microbe could be necessary but not sufficient to
cause the disease, so there are individuals that harbour an infective agent without clinical
symptoms). He observed healthy carrier for cholera.
He is also known for having introduced the so called “Koch postulates” to demonstrate that a
microbe is the cause of a disease:
1) the microbe must be discovered in all organisms affected by that disease but not in healthy
individuals;
2) the microbe must be extracted from the affected body and grown in pure culture (that is a
culture containing only that species of organism);
3) the cultured microorganism reproduce the disease when injected in experimental animals;
4) the microbe could be retrieved from the infected animal and newly cultured.
There are many exceptions to Koch’s postulates; for example Koch observed healthy carriers of
cholera and, then, of typhoid fever (exception to postulate 1); certain organisms cannot be grown in
pure culture like Treponema pallidum (agent of syphilis); some diseases are caused by
multiple/variety of microbes; some microbe cause several different diseases.
However when for a microbe and a disease we fulfil Koch’s postulates we are sure that the agent is
the cause of that specific disease. In conclusion, to establish causation, the evidences that are in
accordance with Koch’s postulates are sufficient but not always necessary. There are diseases in
which causation have been proved even if Koch’s postulates are not satisfied (AIDS virus is an
example).
In the second half of the nineteenth century medical microbiology developed with the identification
of many causative agents of infectious diseases. Thus the theory, firstly developed in the
bacteriological field, was soon extended to protozoa, fungi and then to the viruses.
HISTORY OF SOME INFECTIOUS DISEASES
Syphilis
It was the most important venereal disease before the advent of AIDS.
Syphilis was a real metaphor of transgression and of the dissolute life. In a sense, it was also a
“cultural” disease, very present in the world of ethics and literature.
Syphilis is a sexually transmitted disease caused by the spirochetal bacterium Treponema pallidum.
The route of transmission of syphilis is almost always through sexual contact, although there are
examples of congenital syphilis via transmission from mother to child in uterus.
When did the disease appear?
Until the XVth century there weren’t sure observations. The disease exploded during the military
campaign of Charles the VIII, king of France, in the Italian peninsula (1494). As Naples fell before
the invading French army a new contagious disease broke out among the French troops. When the
army disbanded shortly after the campaign, the troops, composed largely of mercenaries (from
many European countries) returned to their homes and spread the disease across Europe.
Where did it come from?
The French troops besieging Naples may have caught it via Spanish mercenaries who were infected
through a chain of transmission up to the Spanish sailors under Christopher Columbus. In fact the
“Columbus exchange” theory (or American theory) holds that syphilis was a New World disease
(chronic for native American population) brought back to Europe by Columbus and by the first
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explorers of the new continent. The American Treponema would have been modified (becoming
more aggressive) during the contact with the European population.
Syphilis was called the “French disease” in the Italian peninsula and Germanic countries, the
“Italian disease” in France, the Russian called it “the Polish disease”, the Turks “the Christian
diseases” etc. So, these national names are due to the disease often being spread by foreigners. The
disease was also called “the Great Pox”.
As Jared Diamond wrote (Guns, Germs, and Steel: the Fates of Human Societies): “When syphilis
was first recorded in Europe in 1495, its pustules often covered the body from the head to the knees,
caused flesh to fall from people’s faces, and led to death within a few months”. Then it became a
chronic disease less severe than at the beginning of its diffusion.
The name syphilis was coined by Girolamo Fracastoro, an Italian physician and poet. He wrote a
poem in Latin entitled “Syphilis sive morbus gallicus” (Syphilis or the French disease) in 1530
where the protagonist is a shepherd named Syphilus infected by the disease. Fifteen years later,
Fracastoro also hypothesized its transmission through microscopic “corpuscles”. To treat this
disease specific hospitals, especially in the towns with ports (in Italy Genova and Savona), were
founded.
Syphilis was treated with mercury and a special vegetable coming from America, Guaiacum used as
decoction and inhalation.
But the effective treatment, the real therapeutic solution of this disease was obtained only with the
introduction of penicillin (isolated by the Scottish microbiologist Alexander Fleming in 1928 but
available only from 1943).
The agent Treponema pallidum which is the cause of the disease, was discovered only in 1905 by
the bacteriologist Fritz Schaudinn.
Bubonic plague
The plague is an infectious disease caused by the enterobacteria Yersinia pestis named after the
Swiss microbiologist Alexander Yersin (also called Pasteurella pestis to honor Louis Pasteur). The
disease is spread to humans via fleas and carried by rodents (especially by rats).
Probably present from ancient time, in Europe its presence before the Fourteenth century is
doubtful. The epidemic struck from 1347 to 1351, named also the Black Death, was a devastating
pandemic which originated in Central Asia that, subsequently, swept through Asia, Europe and
Africa. This disease became a metaphor of fear, terror, horror and death in the late medieval times.
Origins of the 1347 pandemic. In 1347 the Genoese colony of Kaffa, an important trade center on
the Crimean peninsula located in the Black Sea, came under siege by the Tartars warriors. The siege
was protracted and during the military operations the Tartars were hit from a new strange disease.
At the end the attackers, reportedly withering from the contagious sickness, used the infected
corpses as a biological weapon. So, the cadavers were catapulted over the walls of Kaffa infecting
the inhabitants.
When the siege was interrupted the Genoese traders fled back to Europe transferring the plague via
their ships into Italy, and from there it rapidly spread into the continent. In 1347-1351 the plague
killed between 25 to 35 % of European population.
Other important outbreaks of the disease occurred in Italy in 1630 and in London in 1664-65 (this
outbreak was interrupted by the great fire of London in 1666). Yersinia pestis infects the lymphatic
system as a consequence of the bite of an infected flea Xenopsilla cheopis (the rat flea). The
bacterium goes through the lymphatic system to the nearest lymph node were it replicates itself.
With the development of the disease the lymph node becomes inflamed, swollen, painful and
necrotic; it can hemorrhage and suppurating open sores can follow.
There is also a specific human flea, Pulex irritans, which could be responsible for the inter-human
transmission. The vital cycle of the flea is active between spring and autumn, the same seasons as
the development of the plague.
There are three forms of the disease
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1) Bubonic form, the most frequent, with a mortality rate of 70-80%
2) Septicemic form, the so called “Black plague” (characterized by a vasculitis with cutaneous
and visceral hemorrhages). The skin is scattered with petechial hemorrhage (broken blood
vessels), at the beginning red; then they become darker and from this color derives the term
“Black Death”.
3) Pulmonary form due to inter-human contact as a consequence of the transmission via saliva
droplets. It causes rapid epidemic diffusion and death.
At the time of the explosion of this disease the physician wore a mask with a long nose
containing some aromatic substances believed to protect them from the disease. The real
effective treatment was obtained only with antibiotics.
Smallpox
It is named in this way to distinguish it from the “Great Pox” which is Syphilis.
The origin of smallpox is probably very old and perhaps goes back to the demographic explosion of
10 thousand years ago. The mummy of the pharaoh Ramses V (active around 1150 a.C.) who died
at young age, shows the signs of the disease.
Good descriptions of smallpox are in the text of Ibn Sina (Latinized name “Avicenna”), the Canon
of Medicine, and in the writings of the Persian physician Rhazes.
It was a very diffuse disease in the European countries; in England in the Eighteenth century about
30% of the population bore the signs of the disease and 70% of blind people were blind because
they had been infected by smallpox (as a consequence of corneal ulceration).
Smallpox was a disaster in history. Probably the most shocking episode was the destruction of the
Aztec empire by the Spanish headed by Hernán Cortes. He introduced smallpox in 1520 during an
unsuccessful assault on Techotitlan, the Aztec capital, now Mexico City. Historians agree that this
introduction was accidental. Within few months, the Aztec empire was defeated by Cortes army
(composed of only few hundred conquistadors).
Smallpox is a DNA virus transmitted through inhalation of droplets from the oral, nasal, or
pharyngeal mucosa of an infected person (through the “Flügge droplets” emitted when speaking,
coughing or sneezing). Contagion is also possible with a direct contact of infectious materials
(dust).
The infection starts at the Oropharyngeal mucosa or the respiratory mucosa regional lymph
nodes, spleen 12 days (end incubation) biphasic fever.
1° phase: fever, muscle pain, indisposition, headache, prostration, nausea and vomiting. By days 1215 the first visible lesions – small reddish spots called enanthema – appear on mucous membranes
of the mouth and throat. Temperature falls to near normal.
2° phase: high fever and development of papules (circumscribed solid elevation of skin)
vesicles pustules deeply embedded in the dermis crusts or scab. By days 16-20, scabs have
formed over all the lesions, which have started to flake off, leaving de-pigmented scars.
There are two strains of smallpox virus
1) Variola maior (25-30% mortality)
there are two further variant of this strain a) Confluent variola (80% mortality); b) Hemorrhagic
variola, a severe form of smallpox with bleeding into the skin and mucous membrane. Given the
transformation of hemoglobin to meta-hemoglobin the skin looks black (a form of smallpox known
as “black pox”).
Variola minor (1% mortality).
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University of Pavia
Prof. Paolo Mazzarello
HISTORY OF MEDICINE
7
VARIOLATION
Deliberate exposure to a mild form of smallpox virus (Variola minor) in order to create a mild
infection able to generate immunity against further severe infection.
In Asia (Thailand and China), practitioners developed the technique. Dried smallpox scabs (kept for
some weeks) were pulverized and inhaled through the nose by an individual who then contracted a
mild form of the disease. (Probably the time elapsed before the inhalation attenuates the virulence
of the virus). With this kind of variolation there was a mortality rate between 1% to 2%.
In contrast in the Ottoman Empire some local doctors and some expert old women inoculated
infected material from a mild form of smallpox (Variola minor) through an injection in the skin.
In 1717 the wife of the British ambassador in Costantinople, Mary Montagu reported how Turkish
peasant women held smallpox gatherings at which they routinely performed inoculations. In 1721
under the advice of lady Montagu the procedure became available in Europe. To test the safety of
variolation, several prisoners and abandoned children were inoculated by having mild form
smallpox inserted under the skin. Several months later, the children and prisoners were deliberately
exposed to smallpox. When none contracted the disease, the procedure was deemed safe and also
the members of the royal family were inoculated. As a prophylaxis against the severe form of
smallpox, the procedure then became fashionable in Europe and was widely practiced before the era
of vaccination.
EDWARD JENNER AND VACCINATION
Edward Jenner (1749-1823), an English country physician, used folk knowledge to find an
alternative to variolation. He knew that cowpox was a mild infection of cows. It manifests itself
with blisters and pustules on the cow’s udder and is transmitted from infected animals to humans. It
was known that milkmaids working regularly with cattle to obtain milk were often spared during
smallpox outbreaks.
Jenner postulated that the pus in the blisters that milkmaids received from the cow protected them
from smallpox.
On May 14, 1796 Jenner started the fundamental experiment. He inoculated the eight year old
James Phipps with some matter taken from the cowpox pustule of a milkmaid whose name was
Sarah Nelmes.
The boy developed a similar pustule and a slight fever from which he soon recovered. Six weeks
later Jenner inoculated the boy with smallpox infected material (Variolation); the inoculation did
not cause smallpox.
For the first time he had demonstrated that:
--the administration of cowpox to a healthy individual impedes the development of smallpox. The
cowpox immunized against smallpox;
--it is possible to transmit cowpox from an individual to another.
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The book of Jenner was translated in all main European languages and attracted immediately the
attention of the medical doctors.
The procedure was soon diffused in England with thousands of people who were vaccinated.
It was also transferred to America by arm-to-arm vaccination through a chain of transmission from
individual to individual (in general orphans boarded on ships). In France Napoleon made
vaccination compulsory for his army in 1805. In Lombardy important campaign of vaccination were
performed by Luigi Sacco, a medical doctor from Pavia.
According to the World Health Organization (WHO), in 1967, there were fifteen million people
affected by smallpox with a number of dead of two million in that year. So WHO organized a
campaign with the aim of eradicating the disease. After ten years the program obtained a complete
success: the last natural case occurred in Somalia in 1977. Nowadays the virus is still kept for
research purposes at the Center for Disease Control, Atlanta, Georgia and at the State Research
Center of Virology and Biotechnology in Koltsovo, Novosibirsk, Russia.
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University of Pavia
Prof. Paolo Mazzarello
HISTORY OF MEDICINE
8
ANTISEPSIS
Antisepsis could be defined as “the destruction of pathogenic microorganisms to prevent infection”.
The story of antisepsis is deeply linked with that of Ignac Semmelweis (1818-1865), assistant in the
first Obstetric clinic at the University of Vienna.
At that time a scourge affected maternity wards: puerperal fever. Within a few hours after delivery,
this disease began as a local infection of the genitals of the mother and soon was followed by the
diffusion throughout the body. The mothers presented high fever, intense pain in the genitals, rapid
pulse and his abdomen became distended. The disease was often lethal: at least 10 % of the women
hit by puerperal fever died as a consequence of this infection.
Semmelweis then made a curious observation. There were at the time two wards of obstetrics in his
hospital and the death rate in each was very different. In a maternity ward was 10% while in the
other was 3%. Semmelweis noticed that the first ward was the teaching area for medical students:
doctors and students made clinical examination, with gynecological exploration, after they had
spent hours in the anatomical room, dissecting cadavers. On the contrary the second ward was used
for the training of midwifes who did not perform autopsies. Semmelweis then suggested the theory
that puerperal fever was the consequence of a sort of “cadaver poisoning”, i.e. the transmission of
particles from the cadaver to the genitals of the women, via the medical students and doctors (184748). As a result he argued that medical staff and students should wash their hands with chlorinated
lime solution to prevent contamination. This procedure was successful; in 1848 the mortality of the
first ward was less than that of the second.
Only after his death, Semmelweis procedure became accepted, when Louis Pasteur and Robert
Koch developed the microbiological theory of contagious diseases, offering a theoretical framework
for Semmelweis’s statements.
Another important figure in the history of antisepsis was Joseph Lister (1827-1912) who
successfully introduced carbolic acid (phenol) to sterilize the wounds and the surgical instruments.
This procedure led to a marked decrement of post-operative infections and, thus, surgery became
safe for patients.
A further fundamental advance in the story of antisepsis was the introduction of rubber gloves by
the American surgeon William Halstead around 1890, subsequently used by surgeons and nurses
all over the world.
ANTIBIOTICS
The Scottish microbiologist Alexander Fleming, who was already known for the discovery of the
antibacterial enzyme “lysozyme” present in the saliva, observed a Petri dish (a flat cell-culture dish
with a cover) where some Staphylococcus aureus had grown that contained a mold of Penicillum
notatum, which apparently killed the bacteria. The mold developed accidentally on the culture and,
around itself, a bacteria free-circle was created. Fleming named the active substance of the mold
“penicillin”.
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This discovery became therapeutically available only when the Australian Howard Florey and Ernst
Boris Chain, a refugee from the Nazi-Germany, were able to develop a mass production of the
substance.
Fleming, Florey and Chain jointly obtained the Nobel prize in 1945.
DISCOVERY OF INSULIN
The discovery of Insulin marked an era in medicine. It was firstly linked with the name of two
Canadian, the surgeon Frederick Grant Banting and the medical student Charles Best at the
University of Toronto.
Diabetes (from a Greek word meaning “to pass through”) is a debilitating disease due to the
inability to metabolize sugar. Untreated patients suffer of terrible thirst, polyuria (excessive
production of urine), intense hunger, and a continuous loss of weight.
Semi-starvation was the only treatment until 1922, the year in which it was introduced insulin to
cure diabetes. The aim of the diet was to keep patients relatively free from sugar. However this was
not an effective treatment and before insulin the life expectancy of children diagnosed with diabetes
was in the order of one year or less.
It was known that the removal of pancreas from experimental animals caused diabetes. This was
related to the presence of special cells, inside the “Islets of Langerhans”, which produce a substance
able to lower blood sugar (glucose). However many attempt to inject pancreatic extracts to diabetic
animals were ineffective.
In October 1920 Banting had a good idea. He learnt from a paper that a dog gets diabetes if you
remove its pancreas, while it does not get diabetes if you just tie off the duct through which
digestive juices leave the pancreas. The pancreas became atrophied but not the islets of Langerhans.
So he suspected that something in the juice of the pancreas was able to destroy the active substance.
To obtain the active substance Banting designed these experiments:
1)
Tying off the ducts through which digestive juices leave the pancreas;
2)
Wait some weeks for the development of the atrophic process in the pancreas;
3)
Remove the pancreas, so that the dog became diabetic;
4)
Inject the extract of the atrophied pancreas in the blood of the dog.
Banting and his collaborator Best, after many attempts, were able to obtain an extract active to
lower the level of glucose in diabetic dogs. Then they extended the experiments to cattle obtaining a
larger supply of pancreas. With the help of the director of the laboratory John Macleod and with the
work of a biochemist, Bertram Collip, the team was able to obtain a purified extract containing the
active substance, then named “insulin.” In January 1922 the extract was injected on a boy near
death and the result was a complete success. The patient, Leonard Thompson, was saved and so
were other patients immediately treated. It was one of the momentous discoveries in the history of
medicine, something like a miracle for the patients saved. Insulin became immediately the standard
drug to treat diabetes.
In 1923 the Nobel committee awarded the Nobel prize to Banting and Macleod.
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