History of medicine exam notes

Lecture 1: History of anatomy

• Meaning of anatomy
o Anatomy as a science extends from the earliest examinations of sacrificial victims to the modern
sophisticated analysis of the body

• Prehistoric times
o Hunters were those who first had “inside view” in corpses of their prey
o Probably liver, brain, heart were first organs which were recognized and named
o But even, so, their function remained obscure and there is no evidence of any “anatomical” approach
towards them

• Beginnings of anatomy
o Around 1600 BC Edwin Smith Surgical Papyrus was probably completed
o Then Ebers Papyrus coming c.a. 1500 BC is transmitting to us some anatomical information
o There are some s.c. anatomical information in other Egyptian texts as well, showing basic orientation
in the position of organs, but still no sign of internal corps examination

• Anatomy in the Smith Papyrus

o This papyrus shows that the heart, its vessels, liver, spleen, kidneys, hypothalamus, uterus and
bladder were recognized, and that the blood vessels were known to emanate form the heart
o Other vessels are described, some carrying air, some mucus

• Mesopotamian hepatoscopy
o Inspection of the liver was always connected with astrological and mystical interpretation
o It served as a “map” which should show us our future
o It was never done for anatomical reasons or any scientific purpose of which we would know
o It is because of that we are facing here with ritual not medical hepatoscopy

• Anatomy in ancient India

o In the famous surgical treaty Sursuta-samnhita we are given quite precise information about human
bones and joints
o There is also close inspection of bladder, arm and leg muscles, some parts of skull and eye
o We hear about best techniques for full autopsies of human cadaver
o However, we cant find any completeness in work or anatomy

• Anatomy in ancient China was based on reasoning and intellectual speculation rather than dissection
or direct observation
o Since the philosophical and theological doctrines of Confucius forbade violation of the body, it
was not until the 18th century that the Chinese began direct anatomical studies
o Evan as late as the 19th century, anatomy was often taught by diagrams and artificial models and not
by autopsy

• Alcmaeon of Crotona (6th century BC) – author of first anatomical work + identified Eustachian tube
o Alcmaeon, is one the oldest known names in Greek Medicine
o He was pupil of Cnidus (Knidos) medical school
o Alcmaeon = author of the first anatomical work
o As far as we know he was very first in anatomical dissections, however no sign of human body
dissection is found
o Probably alcmeaon was the first to identify structure of inner ear known today as Eustachian tube

• Hippocrates of Kos (Tricuspid valve)

o Basic understanding of musculo-skeletal structure, and the beginnings of understanding of the function
of certain organs, such as the kidneys
• Tricuspid valve
o Some say Hippocrates was the very first to discover the tricuspid valve of the heart
o This discovery is documented in the treatise On the Heart which is a part of the Corpus Hippocraticum
o However, it is more possible that discovery should be credited to members of so-called Alexandrian
school

• Aristotle - made autopsy one of main tools for scientific investigation – purposely built nature
o Aristotole was aiming to make perfect system of science based upon concept of purposely built nature
o In his multilevel research he is dissecting and vivisecting hundreds of creatures, form mammals to
insects
o It is Aristotle who made of autopsy one of main tools for scientific investigation

• Heart or brain?
o One of his pupils- Praxagoras was convinced by master’s arguments, seeking for further anatomical
evidence
o Dissecting animals, he became aware that blood travels through veins and that there are other ducts
in organism - arteries, which, as he wrongly speculated were to transport, divine element - pneuma
o Arteries took the breath of life that is pneuma from the lungs to the left side of the heart

• School of Alexandria – founder = Herophilus – autopsies allowed by law for first time
o Herophilus = first scientist to perform legally and regularly dissections
o During third century BC the Medical School of Alexandria was born

• Herophilus – “first anatomist” (herophilas) (335-280 BC

o He was the first scientist to systematically perform dissections of human cadavers
o He is sometimes named the first anatomist
o His original writing perished but much information survived in works for later researchers

• Herophilus - Was pointing on the brain as central administrative organ and connected the nervous
system to motion and sensation

• Erasistratus (304 BC-250 BC) – valves of heart – heart functions as pump – arteries with pneuma
o He is credited for description of the valves of the heart before Galen
o He concluded that the heart was not the center of sensations, but instead it functioned as a pump
o He, as Praxagoras did, was convinced that the arteries were full or air and that they carried the
“animal spirit” (pneuma)
o Veins were solely responsible for blood transport

• Autopsy is forbidden
o Around 2 century BC autopsies of human cadavers were totally forbidden.
o In Mediterranean only animal bodies could be still dissected
o In ancient far east even that was out of discussion
o Religious and moral law was giving no excuse for such practice

• Galen’s Anatomical Procedures

o One of the most known and influential physicians of all times
o He made attempt to give full anatomy of a man, but as far as we know he did not make a single
autopsy of human cadavers
o His “De usu partium corporis humani” became for centuries a major book in anatomy and
physiology – first, however, false lecture on human anatomy

• Galen as anatomist
o Galen performed anatomical dissections focusing on pigs and primates; was vivisecting as well
o Galen took artistotelian concept of purposely built nature for granted and observations done during
work on animals were easily extrapolated on human anatomy
 o He also accepted a lot of information given by other authors in many occasions not even checking if
they are true or false
o It is because of that the Galenic writings are in many respects cleverly done compilation

• Galen working on pig

o For Galen the first and mort important is internal logic of his theoretical concepts
o Autopsy can be most helpful but it is always a secondary’ or “auxiliary” if composed with philosophical
reasoning
o Galen is a philosopher when dealing with biological structures of living organism

• Coping Galen
o At the end of antiquity and the beginnings of medieval times fame of Galen was steadily growing
o His deviation for Aristotelian philosophy was highly appreciated as Aristotle became one of most
important authorities in the realm of the medieval sciences
o However widely cited, Galen works was rather rarely analysed and studied
o Translations from Greek to Latin were nearly always poor in quality

• Arabic translations
o Hunayan Ibn was a renowned translator of Greek medical texts
o He translated major books of Anatomical procedures which were known under arabic name
o It became one of most important sources of knowledge for next generation of Muslim physicians

• Anatomy of Arabian Medicine

o Persian by birth physician Avicenna (980-1037) absorbed the Galenic teachings on anatomy
o In his famous book The Canon of Medicine (1020) he presented Galenic anatomy
o He was very influential thinker throughout the Islamic world and Christian Europe
o Avicenna – presented Galenic anatomy to Islamic world in book “The Canon of Medicine”

• Ibn Zuhr – first to have carried out human dissections and post-mortem autopsy legally
o The Arabian physician Ibn Zuhr (Avenzoar) (1091-1161) was probably the first physician known to
have carried out human dissections and post-mortem autopsy legally
o However Avenzoar was not dissecting much nor regularly and most of the autopsies were focused on
matters of legal medicine or practical surgery, not in deep studies on anatomy

• Ibn al-Nafis (1213-1288)– “The Comprehensive book on Medicine”

o The Avicenna’s Canon remained the most authoritative book on anatomy in the Islamic world until
13th century
o Credited with discovery of pulmonary circulation
o In his Commentary on Anatomy in Avicenna’s Canon, he presented many anatomical discoveries
which stood opposite to Galen and Avicenna
o His major work was The Comprehensive Book on Medicine, which he wrote over several decades

• Medical School of Salerno

o The most famous school of medicine in medieval Europe was Salerno
o The anatomy was learned upon texts of Galen and Avicenna
o The dissections were made but only of animal corpses

• Autopsies on human cadavers

o If they were performed it was only done for a small groups of anatomists and students
o For many centuries there were no public autopsies
o The very first were done at the beginning of 14th century
o Probably first official autopsy was held in 1315 AD in Bologna***

• Mondino De’Luzzi (1270-1326) – the restorer of anatomy; book “Anatomia corporis humani”
o Anatomist and surgeon living and lecturing in Bologna
o He was named an anatomiae restitutor- restorer or anatomy
 o He was a very first in Europe to give practical remarks on dissecting and anatomical investigation
o His textbook Anathomia corpsoris humani although was based on teaching of Galen and Avicenna

• Three spheres of human body

o The skull, or superior ventricle, enclosed the “animal members”
o The thorax, s.c. middle ventricle, was a house of “spiritual members”- heart and lungs
o The abdomen, that is inferior ventricle, was a sear for “natural members”- the liver and other visceral
organs

• Master Luzzi
o The earliest edition of the work was printed in Padua in 1478
o Over 40 editions exist in total to this day
o It was considered as a main textbook on anatomy as far as middle of 16th century

• Dissection as an illustration
o In 14th and 15th centuries dissections functioned like an extension of anatomical illustration
o It was to help students and physicians remember the text in which the knowledge was enclosed
o Its goal was not to build up knowledge concerning human anatomy

• Human skeleton
o Ricardus Hela in his Anathomia ossium corporis humani (Nüremberg 1493) give first picture of
full human skeleton (even though it looked cartoonish)
o Schematic in its character was more like artistic impression than real anatomical picture
o This way of depicting anatomical structures was quite typical for that epoch

• Johannes Peyligk (1499) - was venturing the construction of nervous system

o His work was based on speculation, however some of it on anatomical research as well
o Wrote: “naturalis compendium”

• Leonardo da Vinci (1452-1514) – mechanics and discovering general laws of nature

o From 1510 to 1511 he collaborated in his studies on human anatomy with the doctor Mercantonio
della Torre
o He was given permission to dissect human corpses at the Hospital of Santa Maria Nuova in Florence,
and later at hospitals in Milan and Rome

• Big Lady
o Pictures of internal female organs contains also some elements of animal anatomy and non-biological
features
o Drawn by Leonardo structures, however are reassembling “biological anatomy” are in fact work of an
engineer fascinated by “mechanics of nature”
o It is in fact plan of non-existent “living machine”!

• Anatomy in Italian Universities

o Jacobus Beregario da Carpi (1460-1530), professor of medicine in Padua coined phrase- anatomia
sensibilis- that is anatomy given by senses that is learned by observation
o Venetian Niccolo Massa (1485-1569) used phrase anatomia sensata
o Both scholars were still supporters of Galen’s lecture

• Primacy of Galen’s anatomy

o In 1525 in Venice edition of all known Galen’s works in original, that is greek language
o New Latin translations are now also available
o In 1531 Johann Günther von Andernach (1487-1574) edited in Paris then just discovered writings of
“ Greek Roman”- De anatomical administrationbus
o In whole 16th century there were no few than 590 editions of Galen’s texts!
• Andrea Vesalius
o 1543 Vesalius published famous De humani corporis fabrica (On the fabric of the human body)
o This book, marvellously illustrated, was a breaking point in anatomy and medicine
o It heralded new epoch not only in anatomy but also in the biological sciences

• De humani corporis fabrica

o Vesalius is responsible for the introduction of new attitudes towards anatomical dissections
o Now it was autopsy given first place before any intellectual speculations and cadavers became the
main or truly only source of knowledge
o Anatomy form this point should be empirical based on senses and practical science

• Andrea Vesalius
o Vesalius pointed that there are 200 severe mistakes and false presumptions in Galen’s anatomy
o In other words anatomy of Galen was deeply incorrect, and by that should be changed

• School of Vesalius Realdo Colombo (?-1559)

o First precise description of the pulmonary circuit (was not aware of Ibn all Nafis description or
work of Migulel Servet)
o Discovered that the main action of the heart was contraction, rather than dilation as had previously
been thought
o His De Re Anatomica (1559) was seen as just second in importance to Vesalius book

• Bartolomero Eustachi (1500 or 1514-1574); adrenal glands + inner ear structure

o Eustachi (named also) Eustachius discovered the adrenal glands
o He is the first who described the internal and anterior muscles of the malleus and the stapedius, and
the complicated figure of the cochlea
o He is known as a challenger of Galen and extended the knowledge of the internal ear by discovering
correctly the tube which bears his name

• Gabriele Falloppio (1523-1562) – Fallopian tubes

o Falloppio was especially interested in the anatomy of the head
o He described in detail the tympanum and its relations to the osseous ring in which it is situated
o He also described minutely the circular and oval windows (fenestræ) and their communication with the
vestibular and cochlea
o He made proper description of Fallopian tube, which leads form the ovary to the uterus and now still
bears his name

• Thatrum anatomicum
o First permanent anatomical theatre was established in 1594 at University of Pudua by Girolamo
Fabrizio (Frabrici) d’Acquapendente
o Fabrici is famous for his discovery of venous valves, although he did not get right answers concerning
their functions

• Lesson on Anatomy
o Anatomy started to be an important subjects of the sciences, arts on social life
o It became a symbol of new understanding of man’s place in the biological and historical context
o The anatomical lessons were neow the often theme for painters

• Jan Swammerdam (1637-1680) – pioneer of microscope anatomy; known for his anatomical preparations
o He was renowned botanist and biologist whose works on anatomy of insects and in the field of
embryology opened a new chapter in European sciences
o He was one of pioneers of microscope anatomy
o He was also well known for his anatomical preparations which were still highly valued many years
after his death
• Preperatory technique of Frederik Ruysch
o Dutch botanists and anatomist, made important achievements in the field of anatomical preservation
o His preparations were so precise that made him famous all over Europe
o It was now anatomical works were admired not only by physicians but also by ordinary people

• Is it Science or an Art?
o Ruysch founded his own museum of curiosities
o Among many objects there were a number of dioramas assembled from body parts and foetal
skeletons

• Microscopic and experimental anatomy

o Italian physician and biologist Marcello Malpighi (1628-1694) professor of Bologna University used
microscope as a main tool for anatomical investigations
o MARCELLO MALPIGHI = Father of Microscope Anatomy
o He was, as Swammerdam, one of important figures in the field of microscopic investigation
o Malpighi’s ability to connect results of experimental, microscopic and macroscopic investigation in the
field of biological sciences brought many fundamental discoveries

• Discoveries of Malpighi – erythrocytes; nets of tiny blood vessels = capillaries

o He was analysing blood structure discovering fibrin as a stable element and conducting experiments
on blood clotting phenomenon
o Using microscopic he could discover layer structure of blood clot and observed erythrocytes
o In De pulmonibus observationes anatomicae devoted to microscopic anatomy of lungs he discovered
nets of tiny blood vessels- capillaries

• Johann Nathanael Lieberkühn (1711-56)

o His De Fabrica et Actione villorum intestinorum tenium hominis (Leyden 1745) presented results of
injections done for microscopic research in the realm of anatomical structures
o Unseen before precision of picturing small vessel and beatable preparation technique made
Lieberkükn as famous as Ruysch
o His work was still valuable until the end of 19th century

• William Hunter – precise pictures of human fetus; gave evidence of independent fetal-placental circulation
o He was leading teacher of anatomy and the outstanding obstetrician of his day
o His greatest work was Anatomia uteri umami gravidi (The anatomy of the human gravid uterus
exhibited in figures) printed in 1774
o It give very precises pictures of human foetus

• Comparative anatomy
o Traité d’anatomie et de physiologie (1786) is credited as one of most influential books in history of
anatomy
o Iit was a real masterpiece “work of life” by Félix Vicq- d’Azyr (1746-1794)
o It brought new material and better understanding of correlation between anatomical structures and
organs of the living body
o Felix Vicq – d’Azyr = founder of modern comparative anatomy

• Morphological anatomy
o It is a time when anatomy, experimental physiology and pathology are the leading in biological
research
o It was influenced and was influencing in return growing steadily clinical medicine
o One of pioneers of this morphological medicine was Marie François Xavier Bichat (1771-1802),
who is responsible for the tissue theory as best explanation of organic organisation of life

• Bichat’s theory of life

o For Bichat life as “those set of functions which resist death”
o Organs contain particular tissues or membranes
 o He described 21 such membranes, including connective, muscle, and nerve tissue
o Bichat – tissue theory

• Josef Hyrtl (1810-1894) – Handbook on Topographical anatomy

o He was seen as most illustrious talented master of modern anatomical preparatory techniques many
of which were introduced and developed by himself
o Printed in 1847 multi-volume textbook Handbuch der Topogrpahichen Anatomie was regarded as best
book devoted to topographical anatomy
o He was a teacher to many and established powerful school of anatomy in Vienna.
o Museum für vergleichende Anatomie was a centre for anatomical preparations

• Jakob Henle (1809-1885) – loop of Henle

o He is credited with the discovery of the loop of Henle in the kidney
o Handbuch der systematichen Anatomie des Menchen (1855-1871) was his fundamental work

• Ludwik Karol Teichmann (1823-1895) made full description of lymphatic system

o Teichmann owed much to Henle and Hyrtl
o Having deep understanding of anatomy, physiology and chemistry he achieved great level of
sophistication in the field of anatomical research
o Ludwik Karol Teichmann was an inventor of new techniques and masses used for anatomical
injections

• Über Histologie und eine neue Eintheilung der Gewebe des Menschlichen Körpers
o The very frist use of term “histology” was used by Aigust Franz Mayer in 1819
o We can say that at beginnings histology was understood as “microscopic anatomy”
o This is true if we understand that histology was in fact anatomical research by use of microscope

• Cellular anatomy
o Theodor Schwann’s “Microscopic researches on the Conformity in Structure and Growth
Between Animals and Plants” (1839) with cellular conception of living organisms was the real
starting point for histology
o Schwann – postulated cell doctrine – plants and animals made up of millions of cells

• Robert Remak (1815-1865) – chicken embryos – cells come from pre-existing cells = mechanism of cell
division
o In 1841 Robert Remak, contrary to the prevailing opinion, that new cells arose spontaneously from
surrounding fluid, reported the red cells of chicken embryos were the result of a division of pre-existing
cells
o Remal’s concept was adopted by Rudolf Virchow and influenced his own cellular pathology concept

• Jan Evangelista Purkyne (1787-1869) – Purkinje cells and Purkinje fibres in heart conduction system
o Discovery of large nerve cells with many branching extensions found in the cortex of the cerebellum of
the brain- the purkinje cells
o Discovered fibrous tissue that conducts the pacemaker stimulus along the inside walls of the ventricles
to all parts of the heat- named to this day purkinje fibres

• Camillo Golgi and “the black reaction” – staining nervous tissue

o In early 1873, Goldi discovered a method of staining nervous tissue that would stain a limited number
of cells
o He first treated the tissue with potassium dichromate to harden it, and then with silver nitrate
o Under the microscope, the outline of the neuron became distinct from the surrounding tissue and cells
o Since cells are selectively stained in black, Golgi called the process black reaction

• Santiago Ramón y Cajal (1852-1934)

 o Discovery of the axonal growth cone
o He give the evidence that relationship between nerve cells is not one of continuity, but ratherof
contiguity
o It was a starting point for so called “neuron doctrine”

Lecture 2: History of physiology

• Physiologia
o The physis, meaning “origin or nature”, -logia, meaning “study of”
o In ancient Greece every study concerning rudiments of nature was a part of philosophy and by that it
Physiosology belonged ot the philosophers not to the physicians

• Anaximenes (ca. 570 BC)

o Anaximens of Miletus speculated that “pneuma” was essential for life.
o Pneuma stands for spiritual element
o “As our soul, being air, sustains us, so pneuma and air pervade the whole world”
o The idea of Anaximenes was for many centuries an important part of physiological teaching

• Thales and Empedocles (490-430 BC)

o Thalus of miletus - water as principal element of creation and source of life
o Empedocles seeking for arche - that is principal element of all existing things
o Proposed that all things are made up of four essential elements: earth, air, fire, and water.
o This concept was adopted by many thinkers- Hippocrates and Aristotle, among them

• Hippocratic humoral theory

o Hippocrates of Kos is considered as a first to construct physiological theory based on physical
elements of nature
o He took idea of four basic substances: earth, air, fire and water from Empedoclean school and idea of
harmonious interbalance between them from Pitagoras
o Probably under the influence of the works of Thales he paid attention on water (liquid) as the main
source of life power

• Humors
o Each substance has its corresponding humor: black bile, phlegm, blood and yellow bile
o All of them are in constant interaction which is ruled by natural balance
o The equilibrium between them is most important to maintain health
o This equilibrium is governed by proportion
o If one humors is overgrowing or descending then the illness occurs
o Life is struggle between two extrema named eukrasia (symmetry) and dyscrasia (lack of)

• Galen
o Galen was pointing on force and movement as most important in descriptions of life nature
o Galen was following traditional pattern of life organism, which consisted of three spheres based on
brain, heart, and liver
o The so called “dynamis” was acting as a interrelating force, giving the consistency of whole organism

• Paracelsus- road to physiology

o Paracelsus was philosopher, alchemist and physician
o Aceepting the principle of proportion and balance, criticized humoral theory as too general, and
therefore not suitable for the description of complicated life phenomena
o Paracelsus proposed the three basic elements named by him- tria prima- that is; sulphur, mercury,
and salt = alchemical principle, alchemical concept of biological life
o He could explain their mutual relations at the alchemical level
o The transmutation process was seen essential for all physiological and pathological changes in the
construction of life
• Paracelsus
o Principle of proportion and balance
- criticized humoral model – deemed it too general
- He proposed 3 basic elements – TRIA PRIMA – sulphur, mercury and salt
- explained their relationship at alchemical level
- the transmutation process was essential for all changes in construction of life

o All life processes in the human body could be interpreted trough the phenomena of boiling,
fermentation and rotting
o Paracelsus speculated that the internal force, namely internal alchemist- the so-called ARCHEUS
guards order and correct course of all life phenomena
o In a certain sense we can speak here about pre-metabolic theory
o This can be considered a significant beginning of s.c. latrochemistry

• Santorius (1561-1636) – experimental laboratory + Mechanics of digestion + roman weight + mathematics

- pioneer of iatromechanics (latromechanics)
o Santorio known under names sartorius or sanctorius performed experiments in which he made
measurements of temperature, respiration and wight
o He was a tireless inventor and designer of a vast number of measuring instruments, thus creating the
foundations for the experimental laboratory
o Although Santorius’s research methods have not yet been refined, he is undoubtedly one of the
pioneers of later experimental physiology
o First regular studies on digestion processes, which Santorius understood in the light of the laws of
mechanics, were in fact bases for so called iatromechanics

• Rudiments of physiological experiment

o In order to be able to work on what he called the “mechanics of digestion”, Sartorius constructed a
Steelyard balance, known alsoas the Roman weight, large enough to hold a table, chair and a man
sitting on it
o For nearly thirty years, Sartorius used it to measure the weight of his own body

• Mathematics and medicine

o What distinguishes the path taken by Santorius is the empirically checked repetition of observed
changes in different conditions in a pre-planned experiment, which makes his efforts similar to the
modern requirements for experimental work
o In order to organize the observation collected with such reverence, he referred to mathematics as a
precise language of description and conclusions
o Sartorius bringing math to medicine - very first to be named iatromathematician

• Jean Baptiste van Helmont (1577-1644) – concept of Gas introduced to science = coined the word gas
o Van Helmont - convinced that chemical reactions are fundamental for understanding the life functions
o Van Helmont referred his research to a broader, philosophical context
o van Helmont adopted the order of four concepts named by him as - Blas, Gas, Element and Ferment
as key to understanding and justifying the entire philosophy of nature

• Borelli’s biomechanics
o Borelli was essentially a mathematician and a physicist
o Borelli = one of the creators of modern biomechanics, seeking answers to questions related to the
physiology of movement and muscle action and looking upon his research as based on laws
formulated in the language of mathematics
o Wrote: De motu Animalium – describes mechanics of muscle movement

• Biomechanics of De motu Animalium (1685)

o Analytical methods developed by Galileo in the field of mechanics were now used by Borelli to show
biological mechanics
 o Borelli analysed the function of the locomotor apparatus on grounds of comparatist anatomy in man,
quadrupeds, birds, fishes, even worms and flies mechanical standpoint
o Then he carefully observed movement of peoples and animals- he carried out experiments, never
failed to make measurements

• First physiological experiment – William Harvey – 1628

o But for many historians the first “physiological” experiment was done in year 1628
o This moment was curtailed not only for history of physiology but was turning point for medicine itself
o Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus (1628) opened a new chapter in
biological sciences – beginnings of experimental physiology

• “Egyptian” Heart
o In ancient China, it was speculated, in accordance with the principles set out by the cosmogonic
theory of Ying-Yang balance, that the movement of blood in a circle mode is in fact present in the body
o The heart itself was poorly recognized, both in its structure and function
o Important progress was made in Medical school of Alexandria. Herofilus compared heart to the pump,
isolating its systolic and diastolic actions
o Erasistratos, was pointing at the close relationship between contractions and diastoles, and the pulse
felt on the arteries

• How the blood functions?

o From antiquity there was strong believe that blood is travelling in veins, while in arteries is pneuma-
divine element of life force
o For Galen, the arteries and veins should be connected in a number of places by means of, what was
then speculated, some kind of anastomosis
o This arteriovenous network is therefore organized into system, whose purpose is to distribute blood
throughout all body
o This was first impotant proposition concerning blood system
o For Galen, the blood system is open, shaped as tree with roots and branches coming out from
liver parenchyma

• How the blood goes?

o Galen was convinced that in the structure of the ventriuclar septum in the hear there are fine pores,
that allow free blood flow between the ventricles
o Roman physicina assumed that heart was a place where blood and pheuma, coming form lungs, were
mixing together

• Ibn-al-Nafis (1213-1288) - credited with discovery of pulmonary circulation of the blood

o Iba al-Nafis, having doubts about the description of the structure of the ventricular septum in the heart
proposed by Galen, claimed that blood must circulate in the lungs
o Work of Al-Nafic was discovered in 20th century

• Miguel Servet (1511-1553)

o Mieguel Servet (servetus), who lived over two centuries later, independently reach similar to al-Nafis
conclusions
o Servet was involved in astronomy, mathematics and theology, which he gave special significance
o In treaties entitled Christianismi Restitutio edited in 1553 in Vienna, when going through the discussion
about the nature of the Holy Trinity, Servet wrote about the pulmonary circulation

• Servet - argued that all blood flows through the lungs

o He also described the arteriovenous system in the lungs and its connection too the left ventricle
o He denied the natural porosity of the ventricular septum and claimed that pneuma mixes with blood in
the lungs, not in the heart, thus undermining the essence of Galen’s lecture
o Unfortunately, the work of Servet was not dedicated to medicine and became the focus of interest of
theologians, not physicians
• Josephus Struthius (1510-1568) – pulse measurements
o Author of Sphygmicae artis iam mille ducentos perditae et desideratae libri V. (1555)
o This book give him international fame – CARDIOVASCULAR SCIENCE
o He described 6 types of pulse and connected them to different types of disease
o He also made an observation that pulse should be connected with heart action

• Williams Harvey’s circulatory system

o Harvey was under strong influence of Francis Bacon’s empirical philosophy and Aristotle’s
philosophy of nature
o The blood system was still for Harvey in the shape given to it by Galen, till the moment when he
became interested on estimating how much blood is in fact in human body
o First detailed analysis of the overall structures of the heart was done. Then simple calculations
were involved

• Step by step
o Harvey tied a light ligature onto the upper arm of a person
o Blood flow was cut off from the arteries and the veins
o The famous experiment carried out using a tourniquet, showed that blood can travel only in one
direction and that the valves in veins, discovered by his teacher, Hieronymus Fabricius, are playing
crucial role in that process

• The work of William Harvey

o Conclusion that blood goes in closed system and that it circulates, all the time pumped by
action of heart which was recognized to be a muscle
o His work Exercitatio anatomica de motu cordis et sanguinis in animalibus (1628) became famous
o It is one of most important books in the history of modern sciences - beginnings of experimental
physiology

• Experiment and physiology

o Harvey opponents were showing the weak points of his work, followers sought further evidence
confirming the correctness of the Englishman’s arguments
o Regardless of the positions held, De motu cordis became the foundation of research on the physiology
of the arteriovneous system and the heart
o It heralded new way of scientific research, namely the experimental physiology

• Outlines of Physiology
o Albrecht von Haller (1708-1777) in six volumes entitled Elementa Physiologique Corporis Humani
(1757-1766) give first deep lecture in physiology

• Von Haller’s physiology – irritability in muscle; sensibility in nerves

o Experimenting on animals, Haller, was able to show that irritability is a specific property of muscle.
Evan a slight stimulus applied directly to a muscle causes a sharp contraction
o The second detected by Haller phenomenon was sensibility - a specific property of nerves

• Haller on Experimental Medicine

o Haller was first to make such progress in the field of modern experimental biology
o Haller’s complete delineaiton of nerve and muscle action laid the foundations for the future neurology
and showed that it is possible on experimental grounds to detect mechanism of physiological process
o He was looking upon physiollogy as a science applied to anatomy- anatomy animate

• Lazzaro Spallanzani (1729-1799)

o He made most important contribution to the regeneration process study
o Found lower animals have greater regenerative power than higher level animals
o Spallanzani also performed some of the first successful artificial insemination experiments on lower
animals and on a dog
 o He is credited with pioneering work on the practical possibility of transplantation performed by him
on lower animals
• Lazzaro Spallanzani od digestion – showed that major part of digestion = solvent action of fluids in stomach
o In 1770s Spallanzani conducted experiments on digestion
o He fed birds with food kept in perforated containers which had a long piece string attached
o Those perforated containers were recovered after some time by pulling on the string
o showed that a major part of digestion is the solvent action of fluids in the stomach

• Lazzaro Spallanzani and bats – navigation in darkness based on sound

o He became interested on the problem of navigation in complete darkness by bats
o Willing to solve this problem he performed a series of experiments
o In first step he blindfolded them and observed that they still manoeuvre not hitting obstacles and could
easily catch insects in air
o Then he plugged their ears and found that they bumped into obstacles and were not able to locate
their pray

• Electrophysiology
o Luigi Galvani (1737-1798) studied bioelectricity withing living organisms
o In year 2772, he observed, that the muscles of dead frogs legs twitched when struck by a spark
o Galvani concluded that animal tissue contained some vital force, which he termed “animal electricity”

• Science and Technology

o At the end of 18th and the beginnings of 19th century the progress in physics and chemistry was
giving a new hopes for natural sciences and new scientific equipment was now available for
experimental studies
o The experiment was now leading tool of science

• French school of physiology

o Founder = François Magendie (1783-1855), = pioneer of experimental physiology
o “The majority of physiological facts must be verified by new experiments, and this is the only means of
bringing the physics of living bodies out of the state of imperfection in which it lies at present”

• Physiology on the new route

o In 1813 Magendie opened an office as a practicing physician and organized a private course in
physiology
o He openly refused any theoretical speculations in his work
o Magendie was one of the first to observe anaphylaxis
o Magendie – proof that liver functions in detoxification
o Magendie - explained physiological grounds for the mechanism of vomiting

• Bell-Magendie law
o In 1811 Sir Charles Bell on the grounds of classical anatomical observation claimed that the anterior
roots of the spinal nerves are motor in function, while the posterior roots serve to
communicate sensory impulses
o In 1822 on experimental grounds Magendie confirmed Bell’s observations

• Claudes Bernanrd (1774-1842) – Scientific method & Milieu Interieur (homeostasis)

o “The best what i ever discovered was… Claude Bernard” (F. Magendie)
o Bernard established the use of the scientific method- experimental attitude in medicine
o In 1855 Bernard wrote book “Introduction to the Study of Experimental Medicine” one of most
important books in history of scientific methodology
o Nothing is sure and firm in science forever and all theories should be understood as only temporary
solution
o The real aim of research is to determine the relationship between the cause and the effect
• Introduction to experimental method
o Bernard’s works, of greatest importance, were focused on the role of the pancreas in digestion, on
establishing of the glycogenic function of the liver and on discovery and explanation of the regulation
mechanism of the blood supply by the vasomotor nerves
o “The stability of the internal environment- which Bernard named milieu intérieur- is the condition for a
free and independent life”
o Later milieu intérieur was named homeostasis

• Johannes Peter Muller (1801-1858) – physiology of optic system and vision sensations
o arguing that the physioogist must combine empirically established facts with philosophical thinking
o He opposed both empty theorizing and blind empiricism
o He was convinced that speculated by philosophers’ existence of vital force can be proven on the
grounds of experiment

• Physiology of optic system

o Muller’s special interest was the Physiology of the Visual Sense
o Each of the sense organs responds to different kinds of stimuli in its own particular way or, as Müller
wrote with its own specific energy
o It was the foundation of the so-called Law of specific energies

• Law of specific energies (Muller) 1835

o He stated the principle that the kind of sensation following stimulation of a sensory nerve does not
depend on the mode of stimulation but upon the nature of the sense organ
o No matter light, pressure, or mechanical stimulation if acting on the retina and optic nerve will
invariably producde luminous impressions
o It is to be known as law of specific energies

• Carl Friedrich Wilhelm Ludwig (1816-1895)

o We should look instead of biochemical reactions and biophysical actions which can explain all
physiological phenomena
o Founder of the physico-chemical school of physiology in Germany
o Ludwig - discovered the depressor and accelerator nerves of the heart and was first to measure
blood pressure in the capillaries

• Ludwig invented the Kymograph

o Revolving drum wrapped with a sheet of paper on which stylus moves back and forth recording
perceived changes of phenomena such as motion and pressure
o Invented and modified in 1840’s was the very first instrument

• Sensory physiology
o Another pupil of Müller, Hermann von Helmholz (1821-1894) = founder of sensory physiology
o He differed sensation (sensory level) from perception (as a mechanism of the interpretation of
sensation)
o He was one of the founders of Yound-Helmholtz Theory of Color Vision (we have receptors for red,
green, and blue wavelengths)
• Handbuch der Physiologischen Optik
o Helmholtz revolutionized the field of ophthalmology with the invention of the ophthamoscope
o Understanding of depth perception, color vision, and motion perception were given by him in proper
definitions

• Electrophysiology
o Emil Du Bois-Reymond was pioneer of modern electrophysiology (1818-1896)
o He pointed on importance of electrical impulses on reaction of the body
 o He gave evidence that electric impulses have their biochemical structure

• Russian School of Physiology

o Iwan Setschenow (1829-1905) was named by Ivan Pavlov “The Father of Russian Physiology”
o Sechenov’s major interest was neurophysiology, especially the brain structure, which resulted in
experimental evidence, that brain activity is linked to electric currents
o Further Setschenov’s investigation laid the foundations for the study of reflexes with firm rule
established, that Any irritation is ending in reflex- that is, a response of the nervous system
o Phenomenon of inhibition states that every nervous activity is consisted of interaction of two
processes- excitation and inhibition

• Conditioned (conditional) reflex

o Ivan Pavlov is known chiefly for his development of the concept of the conditioned reflex
o In a now-classic experiment, he trained a hungry dog to salivate at the sound of a metronome, bell or
buzzer, which was previously associated with the sight of food

• Pavlov’s experiment
o Pavlov came across classical conditioning unintentionally during his research into animals’ gastric
systems
o Whilst measuring the salivation rates of dogs, he found that they would produce saliva, when they saw
or smelt food in anticipation of feeding
o Then Pavlov’s attention was caught to the fact, that dogs react in the presence of the assistant
dressed in white lab coat, mach which was responsible for feeding them
• Understanding
o Pavlov, he now was purposely observing how playing different sounds to the dogs prior to feeding
them is triggering expected reaction, that is salivation
o Further research showed that animals could be conditioned to unconsciously associate neutral,
unrelated events. This phenomenon was named condition reflex

• Napoleon Cybulski and rise of Polish school of physiology

o Cybulski was studying medicine in Sankt Petersburg, Russia
o He was pupil of one of the best tutors in physiology Ivan Tarchanow
o Blood flow velocity measurements were done by him on the photohemotachometer, apparatus,
which was constructed by him when working on doctoral thesis

• Cybulski in Cracow
o In 1885 Cybulski having a good reference and strong support of Tarchanow was offered the position of
Professor of Physiology at the Jagiellonian University
o During over thirty years of active scientific work in Cracow Cybulski was conducting, in cooperation
with his assistants, experiments on different subjects
o One of topics was studies on the correlations between the increase in intracranial pressure and
disturbances connected with it in the brain blood flow
o Of first quality was experimental research on receptors taking part in taste sensations

• The adrenal glands

o It was italian anatomist Bartolomeo Eustachi who is credited with the first description of the adrenal
glands in 16rh century
o The first clinical and pathological facts showing the close relation between a deteriorating state
of health and adrenal failure was given by English physician Thomas Addison in 1855
o In 1893 and 1894 two English physiologists, George Oliver and Edward Schafer showed that adrenal
medulla contained a substance that provoked constriction of the arteries and by that elevated the
blood pressure

• About function of adrenal glands (1895)

 o Cybulski and Szymonowicz were the first to point on core of suprarenal glands as a place where
strong physiological substance was produced
o The give her name- suprarenin
o In fact we now know that it was adrenaline
o Cybulski = great impact on discovery of adrenaline
• Neurophysiology of brain
o Adolf Beck (1863-1942) was an assistant to Cybulski and later professor in Lemberg University
o When he was still in Cracow he discovered character of physioelectrical activity of brain
o One of the first EEG recordings of the cerebral cortex
o Adolf Beck = one of pioneers of neurophysiology of brain

• Fundamentals of electrocardiography
o In 1842 Carlo Matteucci - University of Pisa, demonstrated that electrical current accompanies
every heart beat in a frog
o 1877 - British Physiologist Augustus Waller published the first human electrocardiogram
§ Showed that electrical activity preceded ventricular contraction

• Wllem Einthoven’s electrophysiology – pioneer of modern electrocardiography

o Chairmen of the Department of Physiology at the University of Leiden Willem Einthoven refined the
capillary electrometer
o He was the inventor of the string galvanometer electrocardiograph and was able to demonstrate
five deflections which he named ABCDE – today PQRST pattern
o In 1893 during Dutch Medical Meeting the term “electrocardiogram” was coined by Einthoven -
used for the first time
o Einthoven’s main achievement was the description of the normal ECG
o In 1924 he received his Nobel Prize

Lecture 3: History of Theory of Diseases and Pathology

• Metaphysical theory of disease
o In the rudiments of human civilisation, the illness, as nearly all phenomenon, were connected
with supernatural forces
o Demons and cosmic influence were the real source of disease

• Medicine and Astrology

o Idea that catastrophic events have their roots in realms of stars in universe was not a new one
o In 9th century Arab physician Albumasar - Great conjunction of planets are responsible for
birth of pandemics
o In the 13th century natural philosopher Albert the Great from paris University wrote that
“conjunction of Mars and Jupiter provokes a great pestilence in the air”
o The very same explanation we find in the Parisian Compedium de Epidemia

• Medieval Physicians and Pestis AD. 1348

o The medical faculty in Paris was asked to give a precise report to the king of France Philip VI on
the nature of his horrible illness
o The authorities blamed the heavens. To be exact the form of a conjunction of three planets in
1345.
o This conjunction caused a “great pestilence in the air”
o That the plague was caused by bad air became the most widely accepted theory

• Religious Explanation
o Black Death was a punishment for sinful life
o It was a terrifying memento for everyone that life is short and then we must face the judgment of
God

• Hippocrates on Pathology
 o Humoral theory served very well in the realm of pathology (black bile, yellow bile, blood,
phlegm)
o Imbalance of four liquids was convincing and healing powers of nature could explain process
of regeneration of health = close to the idea of harmony (macrocosm-microcosm dualism)
of Pracelsus
o It fitted well to philosophical theories and give rational explanation
o It was adopted by Christian and Islamic scientists

• Hippocratic theory applied to pathology

o Based on physical elements (humors)
o Harmonious balance as a rule
o Illness it comes from nature, it is a part of nature, it is healed by nature
o Illness it is in its essence natural not supernatural as it was before

• On the Sacred Disease (Epilepsy)

o It should be regarded as one of the first recorded observations of epilepsy in humans
o It is clearly given that so called sacred disease (epilepsy) is no more sacred than other disease
o “Men regard its nature and cause as divine from ignorance and wonder because it is not at all
like to other diseases”
o Epilepsy begins with the accumulation of phlegm in the veins of the head

• Dogmatic school of Medicine

o It was one of the oldest of the medical sects in antiquity
o Most important personalities of this school were Diocles of Carystus and Praxagoras of Cos
o If the medicine was to be successful it must go after natural actions and different functions of
the human body
o The ultimate aim of medicine is to find all hidden causes of the diseases

• Empiric school of medicine – what matters is what cures the illness, not what causes,
investigation on diseases is fruitless
o Serapion of Alexandria and Philinus of Cos = founder of this school in the 3rd century BC
o Seeking for the hidden causes or natural actions is fruitless, because Nature is
incomprehensible
o What matters is not what causes, but what cures the illness which should be always
regarded as individual event
o There is no one universal model of disease existing

• No ninterest, quid morbum faciat, sed quid tollat – “who cares aobout what causes disease, what is
important is what eradicates it”
o Observation - History of illness - analogy was : so-called Tripod of Empirical Medicine
o It is because of that empirical physicians made a great progress in the field of the pharmacology
identifying a lot of herbal and mineral substance
o Ultimate goal was to make simple classification of substances which have curative effects,
those which are harmless but ineffective, and those which was poisonous
- empirical school laid foundations for later pharmacology and toxicology***

• Roman medicine as the beginnings

o In ancient Rome the medicine for centuries was a rather narrow subject of interest and a
folk or traditional home healing practices were seen as sufficient to maintain health
o GOOD HYGEINE - Bathing was regular practice, fresh water was obligatory and a proper diet
recommended
o Only surgery, especially military surgery, has some attention

• Roman tradition
o Aristocrat, politician and philosopher Cato the Elder strongly opposed Greek physicians
o He went as far as claiming that Greek physicians are in fact poisoning Romans
 o He was not the only one and for a long time there was no place for them in Roman society
• Cato the Elder about Greeks
o “They are quite worthless people, and an intractable one, and you must consider my words
prophetic. When that race gives us its literature it will corrupt all things, things, and even all the
more if it sends hither its physicians. They have conspired together to murder all foreigners with
their physic..”

• First Physicians in Rome

o Hellenistic medicine was slowly coming to Rome mostly through the purchase of prisoners of
war
o Noble Romans could afford the services of the educated slaves, who functioned as personal
doctors in the aristocratic homes
o It was even an element of prestige to have a Greek physician at home

• Asclepiades
o Asclepiades (c. 124 or 129-40BC) was a Greek physician born at Prusa of Bithynia in Asia
Minor
o Discarding the humoral doctrine of Hippocrates, he founded his medical practice on
modification of the atomic or corpuscular theory, according to which disease results from
an irregular or inharmonious motion of the corpuscles of the body
o His ideas were likely partly derived from the atomic theory of the philosopher Democritus
o He recommended the use of wine, and every way strove to render himself as agreeable as
possible to his patients

• Methodic school - founded by students of Asclepiades

o Themison of Laodicea was most famous among them
o It was founded in strong opposition towards Dogmatic and Empirical tradition
o Final shape for Methodic School was given by Thesaluss

• Method in Medicine
o Any illness can be classified and subordinated to a general group or type.
o Only 3 types of illness existing, based on claim that the structure of body organs is spongy,
with many pores through which particles are moving
> Status STRICTUS - if pores are squeezed and space is narrowed, then particle movement is
slower
> Status LAXUS – if pores are overextended, particle movement is inharmonious
> Status MIXUS – simultaneous narrowing and overextension of pores in different areas
o Status strictus, status laxus, status mixtus
o Therapy = “Cito, tuto, et iucunde” - firm, fast, and pleasant for the patient

• Aulus Cornelius Celsus

o Celsus was a 2nd century Roman philosopher and historian
o He considered one of the most important contributors to medicine and scientific thought during
the times of Roman Empire, and the most important source of present day knowledge of
Alexandrian medicine
o Celsus wrote De medicina acot libri, the most comprehensive history of medicine book, a
detailed description of medical and surgical procedures ever produced by a Roman writer
o In De medicina, Clesus references some 80 Greek medical writers, and he has been called
both the Roman Hippocrates and the Cicero of Medicine

• Claudius Galen (130-210)

o Galen was born in Pergamum (today west Turkey) in a wealthy family. When 15 years old he
already studied philosophy, especially Aristotle from Stagira.
o Legend say that his father had a prophetic dream in which God of Medicine, Asclepius himself
designated young Galen to be a physician
 o Obeying his father will Galen learned general medicine in Pergamum, anatomy in Smyrna and
Korinthos, pharmacology in Palestine, surgery and internal medicine in Alexandria
• Physician in the court of Emperors
o Galen was physician to Marcus Aurelius and Lucius Verus
o This gave him a high position in the court and opened wide doors for his teachings
o Galen was very good in self-promotion

• Galen
o Galen was author of nearly 400 written works, which were devoted to philosophy, mathematics,
dramatic and rhetoric and approximately 285 to medicine
o Only over 80 medical works are known to us today. Amongst Galen’s own major works are On
the Usefulness of the Parts of the Human Body and On temperaments
o They achieved and retained great popularity over centuries to come

• Humoral theory in Galen’s medicine

o He has great knowledge about Greek philosophy and medicine. He knew the works of
Hippocrates well.
o Hippocrates was teaching, that nature is dealing with illnesses by itself through actions of four
liquids
o He accepted the view that disease was the result of an imbalance between blood, phlegm,
yellow bile, and black bile
o Galen also believed in the healing power of nature, but he developed also treatments to restore
that balance of the four humors
• Galen and Aristotle
o He used Aristotelian philosophy doctrine from which it took conception of purposely build nature
o Methodology of Galen was based on Aristotelian teachings, which brought him to look upon a
human body as purposely made machinery
• Galen’s pathology – conviction that illness can be (general or local type = diseases must end in)
o That disease resulted from an internal imbalance of the four humors: air (blood), fire (yellow
bile), earth (blood bile), and water (phlegm)
o However unlike Hippocrates, who believed that disease resulted only from a humoral imbalance
throughout the body, Galen was convinced that a disease-causing imbalance could be
located within an organ as well (local illness)

• Lectures on Pathology
o Galen’s books entitled “On Diseases and Symptoms” and “Abnormal Tumors” are main source
for his teachings on pathology
o Here we find quite new idea of disease mechanics
o For Galen an illness occurs if certain functions of the body and the soul are not performed in a
proper way
o To certain degree we can say that it was psychophysical model of illness

• Medicine as Part of Philosophy

o As Hippocrates and Aristotle were giving the grounds for the method of examination of the
human body, Plato gave groundings for method which could give a proper understanding of
soul’s construction
o Galen was successful in combining Hippocratic and Platonic views into scientific definition which
could be set on in the realm of medical sciences
• Galen diagnosing powers
o Galen put great emphasis on clinical observation- examining a patient very thoroughly and
noting carefully symptoms
o He is remembered for identifying the sign of acute inflammation: heat (calor), redness
(rubor), pain (dolor), and swelling (tumor)
o Two thousand years after his death, students continue to memorize the terms he devised
• Medieval Medicine
o Galen remained very influential author throughout medieval times nearly on every field of
medical activates
o Because knowledge of classical Latin was steadily blurring, the quality of transcriptions was low.
It was main, although not the only source of mistakes and errors
o Under strong influence of astrology
• Astrology
o Astrology played an important role in scientific life
o Physicians too were trained in at least the basics of astrology to use in their practice
• Astrology and four elements
o Blood (sanguina) descending from fire, bile (chole) descending from air, mucus (flegma)
descending from water, black bile (melas chole) descending from earth
o In Medieval Time often associated with supernatural or astrological forces

• Reception of Galen’s Medicine

o Cassiodorus = one of the most influential thinkers of the early medieval epoch was truly under
great impression of galen’s work
o Paul of Aegina (625-690) was under great influence of Galen’s “philosophy of medicine”
o One of the greatest philosophers and scholars Islamic sciences - Maimonides - give in 12th
century, in his Medical Aphorisms, a brilliant lecture on galen’s medicine

• Medicine in point of stagnation

o Works of many ancient philosophers and scientists working in the medical field like Hippocrates,
Sonorius, Erasistratus, Celsus, and of course Galen were copied all over Europe
o Some comments were added but they were not supposed to be critical

• Monastic medical practice

o Monastic medical practice acknowledged that natural causes lead to illness and disease, and
monks commonly performed natural, physical treatments on patients
o Theory of disease is now a mixture of faith, philosophical speculations, astrology and traditional
beliefs

• Rise of Miasma Theory

o Miasma = greek word for pollution

• Miasma Theory
o There was no single definition describing and explaining what should be understood under the
notion miasmatic disease
o people thought diseases caused by presence of miasma element in the air – a poisonous
vapour full of particles of decaying matter
o The name of malaria disease has its roots in miasma term
o It was coined from two Italian words: mala (bad) and aria (air)

• Fracastoro’s Concept of Disease – coined the word “contagion”

o Girolamo Fracastoro (1478-1553) was trying to analyze the mechanism of transmission of
several diseases and the concept of contagion and infection
o Some diseases, for example, syphilis could be only transmitted by direct contact
o While others by fomites such as clothing which was previously in contact with the sick person
o Fracastoro pointed, that we find some disease, like smallpox, are capable of infecting persons
at a distance à could be transmitted by air directly from the sick

• Contagia animate = “seed-like beings”

o Fracastoro convinced that infections are caused by seed-like beings (contagia animata)
o Those beings were not microorganisms but chemical structures liable to evaporation and
atmospheric diffusion (so when conditions were proper for contagia animate to act, then
diseases started)
 o He introduced his own theory of disease - the so named “contagious one”

• New concept of disease

o Thomas Sydenham (1644-1689), named “the English Hippocrates”
o first said that each of the diseases is present by means of the different cause
o Sydenham held that disease was the result of the effort of the life functions of the organism to
expel “material elements”, which are constructing illness
o Symptoms are defensive reactions of the organism

• Nosological System – beginnings of modern nosology = medical classification of known to us disease

o Sydenham insisted that nearly all diseases had can be precisely defined and presented in
logical system as it was done with animal or plant species
o Pathology can be and should be arranged in the realm of the scientific classification
o By that Sydenham contributed to the natural history by his own accurate observation and
philosophical comparison of case with case and type with type

• Prehistory
o Smallpox is probably one of the oldest known to humankind disease
o There is convincing evidence that its history goes as far as 10 000 BC
o It was known nearly to every ancient civilization
o In Egyptian mummies from 3000 BC we can observe typical for smallpox changes

• Smallpox
o In China and India – oldest known to us attempts to fight and prevent smallpox
o The inoculation (aka Variolation) was first preventive method against smallpox
o It was done by scratching matter from a smallpox sore into a healthy person’s arm
o The nasal “insufflation” - blowing powdered smallpox material, usually scabs, up the nostrils
became later quite popular

• Smallpox in Europe
o It was present on our continent for many centuries but was most devastating in 18th century,
when it was killing each year 400 000 of Europeans
o Around 40% of adults which were infected died, an over 80% of children
o In the 20th century, up to 1970’s smallpox was responsible for 300-500 million deaths
o The last registered case of smallpox was present in 1979

• Variolation (Variolisation) in Europe

o Variolation came to Europe at the beginning of the 18th century with the arrival of travelers from
Istanbul
o In 1714, the Royal Society of London received a letter from Emanuel Timoni describing the
technique of variolation, which he had witnessed in Istanbul

• Lady Mary Wortley Montague (1689-1762) - responsible for the introduction of variolation in
England
o Lady Montague was determined to prevent the ravages of smallpox that she ordered the
embassy surgeon, Charles Maitland, to inoculate her 5-year old son; didn’t tell her husband until
variolation was successful

• Professional inoculation (1721)

o In 1721 Charles Maitland personally conducted the first professional inoculation in England
with full success (in presence of people from Royal Collage)

• Jenner’s vaccination
o Edward Jenner (1749-1832) = pioneer of smallpox vaccine, and is sometimes referred to as
the father of immunology
o Made his first vaccination in 1796
• First observations on cowpox
o Jenner has heard the tales that dairymaids were protected from smallpox naturally after having
suffered from cowpox
o Jenner predicted that protection could be transmitted from one person to another as a deliberate
mechanism of protection
• Vaccination method introduced
o An Inquiry into the Causes and Effects of the Variolae Vaccinae, a disease discovered in some
of the western counties of England, particularly Gloucestershire and Known by the Name of
Cowpox (1798)
o The latin word for cow is vacca, and cowpox is vaccinia; Jenner decided to call this new
procedure vaccination
• Around 1800
o Few physicians went to Jenner trail and their reports were positive
o In the meantime Jenner conducted a nationwide survey in search of proof of resistance to
smallpox or to variolation among persons who had cowpox
o The results of this survey confirmed his theory.
o Finally in 1800 vaccination was approved in England and then in other European countries

• New Tool = microscope

o In 1590 Dutch lens grinders Hans and Zacharias Janssen make the first microscope by
placing two lenses in a tube
o In 1667 Robert Hooke studied various objects with his microscope
o Hook’s Micrographia was first publication concerned with observation of microcosms

• Birth of Microbiology
o Anton van Leeuwenhoek (1632-1723) uses a simple microscope with only one lens to inspect
blood, insects, and many other objects
o He was first to describe, structure of muscle fibers, spermatozoa and red blood cells,
seen through his very small microscopes with, for his time, extremely good lenses (1676)

• Agostino Bassi (1773-1856)

o In 1835 Italian entomologist presented publicly results of his research on silkworms
o Bassi, from his observations, came to a general idea that finally expanded on a theory
explaining that many diseases of plants, animals, and human beings were caused by
pathogenic organisms.
o However bassi could not give any clear experimental evidence to his claims

• John Snow’s investigation on cholera

o Cholera came to Europe in 1830s and from the very beginning it was devastating. There were
many ideas circulating around and proposals how to fight against it but none were really
effective
o In 1840s English physician John Snow started his research on cholera being more and more a
skeptic of the then-dominant miasma theory
o Close observations of cholera epidemic in London’s districts especially in Soho, led him finally
to conclusion that it was water system, not air, transmitting undiscovered yet
“pathological element” of cholera
o Some historians are pointing on Snow’s investigation as a beginning of modern epidemiology

• Microbiology and Bacteriology

o The intuition that some diseases can be caused by “something invisible” was common from
ancient time through passing centuries
o This devastating factor was often called a “pestilence” which was something between material
particle and demonic force
o However no rational evidence could be given for its existence
o It was more in realm of metaphysical believes then on ground of science
• Louis Pasteur (1822-1895)
o His experiments supported the germ theory of disease
o First he became famous for investing a method to stop milk and wine from being rotten, a
process that came to be called pasteurization
o His discoveries reduced mortality from puerperal fever, and he created the first vaccine for
rabies and anthrax

• Doctor Roux and rabies vaccination

o The rabies vaccine was initially created by Emile Roux, a French doctor and a colleague of
Pasteur
o This vaccine was first used on a 9 year old Joseph Meister on July 6, 1885 after the boy was
badly mauled by a rabid dog

• Robert Koch (1843-1910) –

o He became famous for isolating Bacillus anthracis (1877), the Tubercle bacillus (1882), and
Vibrio cholerae (1883)
o He was awarded the Nobel Prize in Physiology or Medicine for his tuberculosis findings in 1905

• New Methods
o Koch was first to introduce agar to stabilize the in vitro bacterial cultures
o Robert Koch is widely known for his work with anthrax, discovering the causative agent of the
fatal disease to be Bacillus anthracis
o He discovered the formation of spores in anthrax bacteria, which could remain dormant
under specific conditions. However, under optimal conditions, the spores were activated and
caused disease

• Tuberculosis 1882
o In 1882 Koch published his findings on tuberculosis, in which he reported the causative agent of
the disease to be the slow-growing Mycobacterium tuberculosis
o However he failed on attempt at developing a drug to treat tuberculosis
o This drug was to be named tuberculin

• Cholera 1884
o Research conducted by Koch in Egypt, and subsequently in India enabled to determine the
causative agent of cholera, isolating Vibrio cholerae

• Koch’s Four postulates:

o The microorganism must be found in abundance in all organisms suffering from the disease,
but should not be found in healthy organisms
o The microorganism must be isolated from a diseased organism and grown in pure culture
o The cultured microorganism should cause disease when introduced into a healthy organism
o The microorganism must be reisolated from the inoculated, diseased experimental host and
identified as being identical to the original specific causative agent

• Emil Adolf von Behrin (1854-1917) - discover of diphtheria antitoxin in 1890

o He made a big contribution to study of immunity
o In 1901 he won Nobel Prize for developing a serum therapy against diphtheria
o Well known contribution to this discovery has Kitasato Shibasaburo and Emil Roux

• Ylia Metchnikoff (1845-1916) – phagocytosis

o He discovered amoeba-like cells that engulf foreign bodies such as bacteria - phenomenon
known as phagocytosis and a fundamental part of immune response
o In 1908 together with Paul Ehrlich he got Nobel Prize
• Charles Alphonse Laveran (1845-1922)
o In 1878 French military physician Charles Alphonse Laveran was posted in Algeria, then
controlled by France
o Malaria was a serious health problem and the ultimate objective for Laveran was to identify the
causal agent of the disease
o Laveran examining clinical and pathological data found that the only constant element was the
presence of granules of black pigment in the blood
o Laveran concluded that these pigmented granules were specific to malaria, and that they
originated in the blood
• Malaria (ROLAND ROSS)
o 1895 - Roland Ross began his quest to prove the hypothesis of Charles Alphonse Laveran. First
he described the early stages of malarial parasite inside a mosquito stomach
o 1897 – while dissecting the stomach tissue of a mosquito, which he fed four days previously on
a malarious patient, Ross clearly detected the malaria parasite
o 1898 - Ross had demonstrated that mosquitoes could serve as intermediate hosts for bird
malaria, which was a finishing touch to the model explaining the mechanism of vectoring
malaria by insects

• Paul Ehrlich (1854-1915)

o Ehrlich was an author of famous side-chain theory (Seitenkettentheorie)
o This theory explained the effects of the serum and enabled measurement of the amount of
antigen
o For his contribution to immunology he won the Nobel Prize in 1908

• Magic Bullet
o Ehrlich’s idea of so named “Magic Bullet” or in German Magische Kugel, describing ideal
therapeutic agent that annihilates only the targeted organism was at the beginnings of modern
chemotherapy
o 1909 together with his students Sahachiro Hata Ehrlich developed Salvarsan, a first effective
treatment against syphilis

Lecture 4 – History of pathological anatomy

• Magic, Criminals, and Witches

o Examining of pathological changes was not a subject of deeper injury for a physician, also
sometimes the autopsies of dead corpses had to be done when poisoning or black magic were
involved.
o As was commonly believed flesh of criminals was rotting already during lifetimes, so when
opened after their death it was full of pus, worms, and decomposing tissue and the odor coming
from it was unbearable.
o Potentially Pathological observations were obscured by putrefaction process and a lot confusion
was present there.

• Pioneering Works
o Aetius of Amida (502-575) - good description of carcinoma of the uterus and the rectum
cancer.
o Avenzoar (1070-1162) described cancer of the esophagus and the stomach quite accurately.
o Galen described cancer as a “crab-like” growing disease

• Birth of Pathological Anatomy (Antonio Benivieni)

o In the 15th century Italian physician Antonio Benivieni (1443-1502) used anatomic dissection
in purpose to determine cause of death.
o In some respects we can see in it the birth of pathological anatomy.
o First to perform post-mortem examination as a routine procedure for getting proper data
about causes of death – connect pathological and clinical evidence
 o Benivieni made many observations on the intestinal perforations and abdominal and thoracic
abscesses
o He also gave a description of the ruptured aorta, thrombosed vessels, and a case of gastric
carcinoma.

• Pathology by Vesalius
o There is one relations pointing that Andrea Vesalius (1514-1564) planned to publish his
pathological observations as a separate work
o However, no material remains of this work has been found

• Jean Fernel (1497-1558) – Medicina à Pathologiae Libri à clear classification of diseases

o Jean Fernel well trained in mathematics and astrology was, we can say, one of pioneers in the
field of pathology
o In his main work “Medicina” we can find separate chapter - Pathologiae Libri - which became
a standard lecture on this subject throughout Europe
o He made a clear classification of diseases as general and special ones, and distinguished
symptoms from signs, much as we do today

• First Steps
o Theophile Bonet (1620-1689) in his Sepulchretum Sive Anatomia Practica Ex Cadaveribus
Morbo Denatis (1679) shown that pathological changes found during autopsies can be useful in
medical examination.
o He made a great collection of about data obtained during 3,000 autopsies which he could
find in the literature.
o Theophile Bonet = “data collector” – from archives and libraries

• Pathological anatomy in medicine

o Giovanni Battista Morgagni (1682-1771) was an Italian anatomist who made theoretical and
practical references to human autopsies as a source for pathological information.
o We can see in him the very first modern anatomical-pathologist
o Giovanni Battista Morgagni = father of pathological anatomy
• De sedibus et causis morborum
o It is exactly 70 letters which constitute the De sedibus et causis morborum in 2 volumes
o It was given to the world as a systematic treatise in 1761 after twenty years of researches and
experiments
o Nearly 700 autopsies were conducted with aim to connect bed-side obtained data with
pathological changes observed in post-mortem autopsies
o Morgagni: if we want to know causes of diseases, we must find the physical place where
they settled (sedibus)*** = changes in organism

• Pathological research
o The symptoms of disease are always prefixed and discussed from the point of view of the
conditions found after death
o Every clinically obtained observation must be correlated with pathological examination

• Morgagni’s Attitude
o The autopsy is the only method to get scientifically correct data about any pathological
changes – if we want to know causes of diseases, we should connect symptoms with
specific pathological changes observed during autopsies in the structure of internal
organs
o They are the “real picture” of illnesses and only by them we can enter to the realm of proper
medical examination
o There is no place for any speculation, only firm material evidence is worth our attention

• Morgagni’s theory of medicine

 o The aim of medical investigation should go towards making a proper and complete model of
pathological changes based on deep study of anatomy
o Every illness or disease has its specific pathological feature which can be observed during
autopsy
o Physicians should “collect” those observations and group them in a nosological systems

• John and Willian Hunter

o Among many fields of scientific interests pathology played an important role
o John Hunter (1728-1793) has published two works which we can classify as concentrated on
pathological matters; Venereal Disease (1786) and “Treatise on the Blood and Inflammation and
Gunshot Wounds” (1794)
o He made experiments with transplantation of tissues under general heading of adhesive
inflammation

• Matthew Baillie – Morbid Anatomy (1761-1823)

o Hunters nephew, Matthew Baillie, made a remarkable work which can be held as one of the
most important textbooks on morbid anatomy
o The Morbid Anatomy of Some of the Most Important Parts of the Human Body (1793)
o Baillie was advancing in the field of pathological anatomy changing his attitude towards studying
the problem of diseases
o He focused on the comparison made between anatomically proper structures and those
pathologically changed so heralding modern morbid anatomy

• Tissue Pathology
o Marie Francois Xavier Bichat - first to introduce the notion of tissues as distinct entities
o He claimed that diseases attacked tissues rather than whole organs
o Anatomie generale (1801), was a chronicle of original research
o Credited as founder of tissue pathology

• Bichat’s theory of life

o Bichat was convinced that living organism is acting in the constant progress of assimilation
and dissimilation
o The aim of life was to get a proper balance between assimilation and dissimilation
o By that he claimed that there is no point in looking for static definition of life, but rather to see life
as constant progress of changes
o He preferred more functional (physiological) approach in scientific investigation which should
replace traditional static (anatomical) understanding of the organism construction

• Bichat’s influence on the disease research

o He is responsible for introducing the idea that we can look upon the body in other way then
combination of organs when studying grounds of the disease
o This is the idea that led to the tissue pathology (founder = Bichat)
o Great step in the field of medical research

• Rene Theophile Hyacinthe Laennec (1781-1826)

o A member of French school of medicine and a friend of Bichat
o He developed the understanding of the peritonitis and cirrhosis
o Coined the term melanoma and described metastases of melanoma to the lungs
o He also studied the problem of tuberculosis

• Richard Bright (1789-1858) - pioneer in the research of kidney disease

o What is known today as acute or chronic nephritis was named Bright’s disease
o It is typically denoted by the presence of serum albumin (blood plasma protein) in the urine, and
frequently accompanied by edema and hypertension.

• Hodgkin’s lymphoma
 o Thomas Hodgkin (1798-1866) was an English who discovered and gave description of cancer
originating from white blood cells called lymphocytes
o It is named Hodgkin’s lymphoma, previously known as Hodgkin’s disease

• Addison’s Disease – chronic adrenal insufficiency – not producing enough steroid hormones
o Thomas Addison (1793-1860) was English physician and scientist
o He gained immortal fame when in 1855 give proper clinical description of rare disease

• Addisonian anemia = hematological disorder later found to be caused by failure to absorb vitamin B12
o One of many types of the larger family of megaloblastic anemias

• James Paget (1814-1899)

o English surgeon and pathologist James Paget is known for his deep and precise research
o His works Lectures on Tumours (1851) and Lectures on Surgical Pathology (1853) were
landmarks in 19th century pathology
o He can be seen as a co-founder of modern pathology

• Paget’s disease = chronic disorder that can result in enlarged and misshapen bones
o The breakdown and formation of bone tissue causes affected bone to weaken
o As result patient suffers pain, local fractures and arthritis in the joints near the affected bones

• Intraductal breast cancer (Paget’s disease of the breast or Paget’s disease of the nipple)
o It is a form of the intraductal breast cancer spreading into the skin around the nipple.
o It was first described by paget in 1874

• Jonathan Hutchinson (1828-1913)

o Hutchinson’s teeth are a sign of congenital syphilis
o Hutchinson’s triad: it is a presentation for congenital syphilis
o It consists of three phenomena: interstitial keratitis, Hutchinson incisors, and eighth nerve
deafness

• New Pathology
o Friedrich Daniel von Recklinghausen (1833-1910) was German pathologist and scientist
o He coined the term haemochromatosis (iron overload) , and was the first to build bridge
between haemochromatosis and iron accumulation in body tissue
• Neurofibromatosis
o Neurofibromatosis NF 1 is also named von Recklinghausen disease
o It is disordered growth of ectodermic tissues, and is part of a group of disorders called
Phakomatoses (neurocutaneous syndrome)

• Carl von Rokitansky (1804-1878) made pathological anatomy separate field of scientific investigation.
o Medical studies in Prague and Vienna universities
o The studies on disease should be made solely on empirically given evidence
§ Rational (non-speculative grounds and critically analysed works of predecessors
o Rokitansky = founder of Second (or Younger) Vienna Medical School
• Methods in conducting autopsies
o Rokitansky became an expert in autopsy research, developing and improving his famous then in
situ method of dissection
o It was aimed to make investigation and proper description of dissected organ as long as
possible in its natural, anatomical position in the body
• Handbuch der allgemeinen pathologischen Anatomie (1842-1846) - Rokitansky
o In this book Rokitansky presented his theory of medicine
o He claimed that only anatomy and pathological anatomy are really important sciences
o We should seek for real causes of disease and it could be done on grounds of pathological
anatomy
• Younger Vienna Medical School
o Rokitansky found many followers which were very critical about medical theory and practice
o It has been estimated that Rokitansky performed more than 30,000 autopsies and reviewed
another similar amount - if not more. Some sources are even giving a total number of 100,000
autopsies!
• Rational And Empirical
o Medicine should be based rational grounds and any kind of speculation is ending with delusion
and fatal errors
o Observed in autopsies pathological changes should be starting point for deep and long-time
research
o Only firm and repeatable observations, that are obtained on empirical grounds of research can
be taken for consideration
o The goal is to find the source of all diseases
• Humoral pathology in Rokitansky science
o Some general disease are just not traceable in macroanatomy
o Then the blood must be considered as source of general diseases
o Rokitansky was now speculating, that so named blastema, which was understood as the
birthplace of all cells, sometimes affects the cellular structure of blood

• Diagnosis and Therapy

o Jospeh Skoda = “Master of Diagnosis” as was called through Europe - represented severe
scepticism towards therapy
o This scepticism was so strong that earned the title of therapeutical nihilism
o This became a Trademark of Vienna School
• Primum non nocere
o He rejected, not counting few, all drugs, relying like ancients on diets and healing power of the
nature itself
o When “pathological puzzles” will finally form clear picture of disease, then, and only then, we
can begin to scientifically approved therapy

• Joseph Dietl (1804-1878)

o Praktische Wahrnehmungen (1845), book written by Joseph Dietl became known as
“manifesto” of Younger Vienna School of Medicine
o Diagnosis and therapy, clinical and theoretical medicine should meet on the firm grounds of
scientific knowledge
o Anatomy, physiology and pathological anatomy are the real fields of interests - backbone of
new medicine

• Modern dermatology
o Ferdinand von Hebra (1816-1880) was one of the founders of modern pathological anatomy
o He specialized in skin diseases.
o His book Lehrbuch der hautkrankheiten (textbook of skin diseases) brought new presentation of
dermatology
o Credited with first proper pathogenesis and etymology of scabies

• Alfred Biesiadecki (1839-1889) = one of the pioneers of histopathology of skin

o His works upon skin diseases and their correlations with blood and lymphatic system were of
great importance in his times

• Rudolf Virchow = father of cellular pathology & pioneer of pathophysiology

o Rudolf Virchow (1821-1902) most widely known scientific contribution is application of the cell
theory to the pathological research
o It was built on the work of Theodor Schwann, who discovered and named cell
o He also accepted the conclusions coming from work of Robert Remak, who showed the
origins of cells was rooted in the division of pre-existing cells
• Cellular pathology
 o Virchow claimed that all disease are in fact dysfunction of cell or group of cells
o The illness means that the cellular system is ill
o Omnia cellula e cellula
o Virchow pointed on physiological level as most important for research in pathology - that is
pathophysiology
• Die cellularpathologie (1858) by Virchow
o This book became what we can name Bible for cellular pathology
o It had several editions and is known to be one of the most influential works in grounds of
medicine
o On its pages we can meet several important and crucial for development of medicine facts

• Leukemia à Virchow is cited as the first to recognize leukemia cells (1847)

o In 1845 Virchow published results of his research on characteristic clinical symptoms which he
confronted with pathological lesions and observations made on blood
o Examination of blood itself led to the discovery of abnormal concentration of a large number of
white blood cells, a change which he named Weisses blut - White Blood
• Inflammation
o The four classical symptoms of inflammation (redness, swelling, heat and pain) were now
completed by fifth - loss of function (functio laesa)
o In the pathogenesis of inflammation, Virchow highlighted the importance of the inflammatory
stimulus
o Virchow claimed that inflammation always begins on grounds of stimuli, which no matter of their
origin or nature, are lending to irritation, which can provoke inflammation process
• Thrombosis and embolism
o Virchow created the terms thrombosis and embolism
o He concluded that blood clot is a specific network of fibers where blood cells have become
imbedded
o He observed that clot in the pulmonary arteries or veins is not de novo but instead originates in
the peripheral vascular system
o In 1856 after deep injury Virchow described the consequences of a pulmonary embolus that
migrated from the venous circulation
• Virchow Triad = the 3 factors contributing to thrombosis
o The notion itself - Virchow Triad - was never used by Virchow himself, was generated later to
commemorate his achievements in the field of his research.
o The elements forming it are: Hypercoagulability, Endothelial injury (vessel wall injury), stasis
• Virchow’s work on cancer
o Virchow observing the mechanism of cell development came to the conclusion that it can occur
in two ways - either by increasing the number of cells (hyperplasia), or by increasing their
volume (hypertrophy).
o He identified cancer as the specific, pathological Hyperplasia coming from the activation of
dormant cells (stem cells) present from the birth of organism in mature tissues

• Gabriel Andral - founder of scientific hematology

o Andral is remembered as one of very first to carry out investigations on blood chemistry
o Andral’s extensive studies on blood demonstrated that blood composition varies in different
pathological conditions

• Experimental pathology
o The works of Virchow and his pathophysiological model of research give also grounds for what
finally became experimental pathology
o Experimental methods offered the possibility of safe induction and observation of pathological
process
o Especially important were tissue culture methods and transplantation methods which opened
ways for new investigations

• Julius Cohnheim (1839-1884)

 o Julius Cohnheim combined histology techniques with experimental manipulations to study
inflammation, making him one of the earliest experimental pathologists.
o Best known for: concluded that acute inflammation was the result of leukocytes, that
circulated to the site of the injury and then migrated through capillary walls to form collection of
blood cells that contributed to what had long been termed “pus”
o He was as well pioneering experimental studies on tuberculosis, and made important
contributions to the further studies on thrombosis and embolism
o Invented by Cohnheim, method of freezing tissue before slicing it into thin sections was
very useful for microscopical examination and became standard in pathological research

• Carl Weigert (1845- 1904) - remembered for his excellent staining techniques, then used widely in
microscopic investigation focused on the pathological changes in tissue
o He made deep experimental research on degeneration processes and necrosis
o Weigert’s law (1896) - the loss or destruction of tissue results in replacement and
overproduction of new tissue during the process of regeneration or repair

• Ludwig Aschoff (1866-1942) – Atrioventricular node & Aschoff bodies

o In 1904 in close cooperation with Japanese medical graduate Sunao Tawara, Aschoff started a
historical investigation on the heart structures which led to the discovery of atrioventricular
node, known today as Aschoff node or Aschoff-Tawara node
o Together with Tawara Aschoff discovered what is named Aschoff body - the small nodules
present in hearts of individuals in some cases of rheumatic fever

• Nikolay Nikolaevich Anichkov (Anitschkow) – cholesterol in atherosclerosis pathogenesis

o In his doctoral thesis entitled Inflammatory changes in myocardium: apropos of myocarditis
(1912) Anichkov described new type of cell - myocardial cell, known today as Anichkov cell
o He is credited with description of specific granulomas connected with rheumatic fever, known
then as Anitchkov bodies
o Discovered the significance and role of cholesterol in atherosclerosis pathogenesis

• Experiments on cancer
o Early experimental studies if Virchow were pointing on cancer as a product of chronic irritation,
while others surmised that cancer was caused by an infectious (or parasitic) agent
o 1911 - Francis Peyton Rous (1879-1970) reported that malignant tumor (sarcoma) growing on
a domestic chicken could be transferred to another fowl simply by exposing the healthy bird to a
cell-free filtrate
o After many decades his achievements were finally appreciated- 1966 he won his Nobel Prize

• Katsusaburo Yamagiwa (1863-1930) – carcinogens = chemical substances that can increase risk
o Japanese pathologist Katsusaburo Yamagiwa, working for three years in Virchow’s Institute in
Germany, became interested in von Volkmann’s study of skin cancers among coal tar workers
o In 1915 Yamagiwa inducted carcinoma on the ears of rabbits using coal tar, demonstrating that
coal tar has carcinogenic properties
o It was firm prove that carcinogenesis can be provoked by some chemical substances

Lecture 5: History of Internal Medicine- Diagnosis

• Eye and hand of the physician
o Listening to the patient’s own narration and his story about the disease was from most
ancient times present in medicine, being the primary source of knowledge for the physician
about illness
o = first step that helps physicians make a diagnosis
o Diagnostics was based almost exclusively on visible symptoms, which were sometimes very
accurately combined into a logical entity.

• Ancient India
 o In the books of Ayurveda, diagnosis should be based on the senses of sight and touch,
supported by questions asked by the physician and careful listening to the patient’s answers. ->
diagnosis should also include urine tests, listening to heart, inspection of the tongue and skin
physical examinations
o We hear about the already existing uroscopy- Mutra pariksha, or “the art of urine
examination”.
o Diagnostics is combined with medical prognostics, which is reflected in the canonical list of the
so-called signs (symptoms) predicting incoming death, which will later gain the Latin name
Omina mortis.
o Medical text known as Cikitsasarasangraha written by Vangasena, 13th century.

• The Four Pillars of Ancient Diagnosis in China

o First, a general overview of the patient’s condition (skin- discolouration, wounds, burns etc,
hair, nails, tongue)
o The second, auscultation
o Third, completing medical history and sometimes analyses of characteristic smells.
o Fourth, pulse examination- sphygmology
o An important part of diagnostics was careful listening to the patient’s narration, asking questions
and analyzing answers.

• Hippocratic Medicine
o Hippocratic medicine specifically pointed on the need to practice all senses available to man.
à urine sample, measuring pulse, regular checkup tests. This allowed the physician to discover
symptoms of disease
o At the same time, the value of extending the medical history by a conversation with the patient’s
relatives and friends was emphasized.
o All activities aimed at collecting detailed information were subordinated to the general
pathological theory (i.e humoral theory) and generalized symptomatic model.
o At the same time, however, the necessity of individualization of each case was assumed.

• Galen on Diagnosis and Prognosis

o Galen pointed out that diagnosing and prognosis are the most difficult art in medical practice. ->
since each organism has different conditions so it is impossible to predict changes caused by
the disease. Threat of making a mistake.
o The correctness and effectiveness of diagnosis and prognosis is determined by the proper
concentration of attention and sharpening of the doctor’s senses, as well as his experience and
knowledge -> margin of error is smaller
o The notion of “crisis” or the moment of solstice became the key one, to which Galen devoted a
separate treatise - On Critical Days

• Oneiroscopy- diagnosing the dreams – diagnosis based on dream examination

o Should be seen as one of the components of diagnostic and prognostic methods used in
Ancient medicine.
o Probable already practiced in prehistoric times. We know that it was constantly present in the
realm of Mesopotamian cultures.
o Oneiroscopy was close to religious and ritual practices.
o It was an inseparable part of magical practices and was seen as a “tool” for freeing oneself from
the factor of time.
o In ancient Greece, oneiroscopy was constantly present in the temples of Asclepius- god of
medicine. -> physicians often tried to provoke dreams (incubations). Trip to the temple where
the patient spent the night on the bed of sleep. Dream was to be memorized as much as
possible.
o Galen works on oneiroscopy proves that dream interpretation and its interpretation played a role
in practical medicine.
o In the Middle Ages, the official attitude to the interpretation of dreams was ambivalent.
 o Galen- “On Diagnosis of Dreams” focused on methods of oneiroscopy

• Uroscopy
o Urine inspection can be found in almost all ancient cultures.
o However, it was only in the medicine of the Byzantine civilization that it gained unprecedented
precision in its description.
o Urine collection is painless, non-invasive, cheap, easy.
o Could be sent to a doctor for remote diagnosis.
o Colour + smell of urine gave further possible indicators of possible disease
o Egypt of Pharaohs- 1st time pregnancy test was used: if seeds sprouted, + The way the seeds
sprouted indicated the gender.
o In Hippocratic writings it plays an important diagnostic and prognostic rule.
o Galen also gave uroscopy an important place in his lecture on medicine.
o Theophilus Protosphatharius ( ca. 610-641) was the author of the first basic uroscopy
textbook- De urinis
o Uroscopy was given a lot of attention, sometimes critical, in the texts of Islamic medicine,
including Avicenna and Rhazes.
o presence/absence of solid forms in urine observed
o Ruth (Bible) first described hematuria

• Uroscopy in the Late Medieval Epoch

o The 14th century brings a specific kind of fulfillment and at the same time the dusk of uroscopy
as a part of science and medical practice.
o Therefore, uroscopy is more and more often performed by ordinary craftsmen and barbers-
thought to be observed properly by anyone. Family and friends can deliver urine to urine
researchers and for a small fee can get a diagnosis. Urine can help determine not only the state
of health but foretell the future.
o With the invention of printing in the 15th century, the reproduction of coloured schemes-the
so- called uroscopic wheels- became more common, and thus diagnostics and prognosis
much simpler.
o Uroscopic wheel - facilitate urine examination for diagnosis and prognosis.

• Towards a chemical analysis of the urine

o Already in the 16th century Paracelsus postulated to look at urine from the side of its alchemic
(chemical) properties.
o Leonhard Thurneysser von Thurn (German alchemist 1530- 1590), a supporter of
Paracelsus, proposed a method of urine distillation to determine the mutual proportions of the
mass (weight) of three basic elements constituting matter: mercury, sulphur and salt (tria prima)
à anticipated future procedure to determine urine specific gravity
o The chemical analysis of urine components was also carried out by Jan Baptist von Helmont.-
measured specific gravity of urine, pioneer in study of quantitative urine composition
o In 1655, Robert Hook in “Micrografia” introduced urine crystals observed under microscope

• Sweet urine
o Thomas Willis (1621-1675), following van Helmont, performed a number of experiments and
came to the belief that “honey urine” is the effect of the accumulation of salt and sulphur.
o In 1776 the English physician Matthew Dobson (1732-1784) in his work Experiments and
Observations on the Urine in Diabetics proved the presence of sugar in urine in patients
suffering from diabetes mellitus.

• Blood
o William Hewson (1739-1774) in his research on the structure and function of the lymphatic
system in birds, amphibians and fish drew attention to the relationship between lymph and blood
= first steps towards modern hematology
o He was the first to define the correct shape of erythrocytes (flat discs with a concave surface)
and extracted white blood cells, describing them as colorless or central molecules.
 o He also conducted pioneering research into the mechanism of blood clotting and indicated
that it could be useful in clinical diagnostics.
o When coagulation is delayed, plasma can be easily separated from blood.
o RBC’s in children are larger than in adults
o From plasma, fibrinogen (coagulable lymph) can be isolated

• Pulse (Sphygmology)
o The art of heart rate measurement also has an ancient metric.
o Sphygmology was also an important part of diagnostics in ancient China, achieving a high level
of theoretical consideration and practical performance.
o The Indian physician Sage Kanada (VII/VI century B.C) wrote a treatise entitled “Science of
the Heart Rate” -> established 3 stage division for pulse dynamics. Disturbance in any 3
phases is related to disturbance ⅓ basic organic components: air, phlegm, bile
o Pulse measurement also had a permanent place in the tradition of Greek medicine.
o For Vang Cho Ho, pulse ratio is characterized by volume, strength, weakness and regularity.
o Each organ has a specific pulse pattern.

• Water Clock
o Herophilos (Alexandria Med School representative) was the first of the Greeks to measure
the pulse accurately using a special portable water clock.
o He was detecting normal and abnormal pulse rhythms and explained the heart function as a
pump.
o However, none of his contemporaries undertook any further research in this direction. (to see
the heart as a mechanism for blood pumping).
o Only Galen returned to systematic research into the nature of the pulse, determining a number
of pulse types and combining them with specific types of diseases.
o In pulse, look for: rhythm, frequency, size, tension
o Sphygmology became one of the foundations of Galen’s medical diagnosis.
o Arteries retain their own sphygmologic ability.

• Pulse Measurement
o Sphygmology + uroscopy
o In the 16th century, Santorius constructed the pulsilogium, an instrument for measuring the
pulse rhythm.
o The English physician John Floyer (1649- 1734) is the one who at the beginning of the 18th
century developed and constructed The Physician Pulse Watch- a watch for pulse
measurements.
o Allowed to measure pulse with second accuracy and gave change to make a series of precise
measurements.
o Floyer (like the Chinese physicians and Galen) aimed to prove each disease has its own pulse
signature

• Ricci & Korotkov

o In 1896 the Italian paediatrician Scipione Riva-Rocci (1863- 1937) connected the
sphygmomanometer with an inflatable cuff.
o Russian surgeon Nikolai Sergeyevich Korotokov (1874- 1920) modified the Riva-Rocci
method and enriched it with his own auscultatory technique.

• Clinic
o Teaching by the bedside was practiced already in ancient times
o Medicine as an art had to be based on the symptoms of the disease.
o Students gained practical knowledge by accompanying the master in his visits to the sick.

• Rudiments of Clinic
o First hospital in ~706 in Damascus (to provide care for the sick and those with chronic and
mental diseases)
 o It is believed that it was the Persian physician and philosopher Abu Bakr Muhammad ibn
Zakarijja ar-razi, known in European tradition as Rhazes (865-925), who gave clinical teaching
a framework for a well thought-out system for educating physicians.
o Teaching at the patient's bedside with clinical/medical programs started in the hospital of
Bagdad, Cairo, Cordoba.

• Bedside teaching in Europe

o Giovanni Battista da Monte (1498-1551), also known as Montanius, can be considered the
precursor of bedside teaching in Europe. - pioneered bedside teaching in Europe, pioneer of
clinical medicine.
o 1539- A professor of medicine at the University of Padua, he began his regular clinical classes
at the St. Francis Hospital.
o He lectured students and then visited the hospital to put his lecture into action.

• Medical School in Leiden

o Hermann Boerhaave (1668-1738) saw the need for a revision of the existing canon of practical
medicine. - founder of Medical School in Leiden, pioneer of clinical physiology.
o “Simplicity is a sign of truth”.
o Placing his hopes in then developing physics and chemistry, he was convinced that diseases
should be considered in the space of changed conditions of life functions as physiological
processes disturbed by various factors.
o This required constant confrontation of symptoms with the knowledge gained in the field of
natural sciences, and the most appropriate place for this place was the hospital room.

• First Clinical lectures

o In the summer of 1714, Boerhaave was given the first opportunity to conduct practical classes at
the patient's bedside
o The model of medicine presented by Boerhaave is described as empirical- rational; collecting
information at the patient's bedside- using the principle of analogy- introducing a predetermined
pathological system.

• Gerard Van Swieten (1700-1772) – established in Vienna first university medical clinic
o Since 1741, Vienna has had the hospital of the Holy Trinity (Spital der Heiligen Dreifaltigkeit),
which at that time had 45 beds.
o Gerard van Sweiten, who was favored by Empress Maria Theresa, reformed the teaching of
medicine in Vienna according to a new model.
o The first university medical clinic in Europe was opened in 1747, but it was not until 1753
that Gerard van Swieten decided to make bedside teaching an integral part of the university’s
medical curriculum.
o Bedside teaching in full swing

• Clinical Demonstrations for the students

o Van Sweiten Ordered a 12 Vet Clinic award at the City Hospital (Buergerspital) -> 2 rooms x 6
beds (for sick men and women)
o The ward performed mainly didactic functions, constituting a kind of ‘demonstrator’ for the
current needs resulting from the curriculum.
o Anton de Haen (1704-1776) became the first director of the university clinic.

• So named Older Medical School in Vienna

o Anton de Haen (1704-1776), under according to van Sweiten’s plan, gave an important start to
what later became the clinical Vienna School.
o Gerard van Sweiten and Anton de Haen, a bit later Maximilian Stoll and Anton van Störck,
became important personalities in the realm of medical training.
o New system of teaching introduced by them laid foundation of what to be firstly known as
Clinical Medical School of Vienna, then the Older (first) Medical School in Vienna.
o The successor of de Haen, Maximilian Stoll (1742-1787) finally formed the clinical curriculum.
 o Stoll eventually replaced de Haen as director.
o He was responsible for intensive studies based on lecturing, bedside teaching, autopsies and
preparing medical histories, which formed the basis for modern clinical system.
o Now students could study up to 700 patients monthly.

• Medical Percussion – Leopold Auenbrugger

o It can be assumed that a method of tapping on a Surface of the chest was already known in
antiquity, although it was used in practice only marginally.
o Therefore, Leopold Auenbrugger (1722-1809), first started working on this method in 1754, is
considered the father of medical percussion.
o In 1761 he published a treatise Inventum Novum with less than 100 pages. - complete and
ready to use manual on medical percussion. Described the method of properly performed
percussion, characteristics of sounds physicians can hear etc.

• Percussio
o Auenbrugger wrote that his observations allowed him to state that in case of pathological
changes there are sounds matched by percussion.
o Auenbrugger connected the dynamics of auscultatory changes directly with the system of
physical features of the pathological change itself.
o He differentiated between four basic percussion symptoms: normal, drum, weak and flat.
o Careful listening during tapping process allowed precise determination of position (and size) of
pathological change.

• Listening to Auenbrugger
o Although it was soon translated into French and Maximilian Stoll started using it at a university
clinic, often consulting Auenbrugger about the correct interpretation of its results, the percussion
did not attract much interest from physician.
o When Stoll died, Inventum Novum became abandoned for a long time.
o It was not until 1808 that when Jean Nicolas Corvisart had retranslated Inventum novum into
French, that the percussion became widely known.

• Edinburgh clinical school- Rutherford

o Already in 1748 in Edinburgh, John Rutherford (1675-1779), another pupil of the Leiden
School, proposed the introduction of permanent clinical lectures and obtained permission to
do so.
o Classes in rooms of the sick, twice a week in the lecture hall.
o In 1750, the university authorities decided to open a permanent, but not exceeding 10 beds,
clinical ward.

• School in Paris
o At the turn of the 18th and 19th centuries, the clinical model began to shape a new medical
school in Paris.
o The Paris School was built on the ruins of an old order, devastated by revolution.
o One of its prominent representatives was Jean-Nicolas Corvisart (1755-1821).

• Corvisart
o Improved percussioning technique
o Corvisart has devoted many years of his life to research on the psychological and pathological
image of the heart.
o He was involved in the classifications and differentiation of aortic aneurysms and heart
aneurysms.
o Corvisart is responsible for description of the clinical symptoms accompanying myocardial
infarctions.
o Corvisart was one of the pioneers of cardiology.
o Aneurysm: active or passive = widening of heart muscle’s structure:
§ Active: generated hypertrophy and elevated systolic strength
 § Passive: No hypertrophy and decreases systolic strength

• René- Théophile-Hyacinthe Laennec (1781-1826)

o Direct chest auscultating was already known as Hippocrates (ear to chest to hear heart -> chest
crackle -> pleural friction), Galen and Avicenna.
o However, in the 19th century it was not very popular among physicians, considering this method
to be of little use in diagnostics.

• Year 1816 – Laennec - Stethoscope (“Le Cylindre”)

o Using 24 sheets of paper tightly rolled up in a roll, Laennec used the technique of
intermediate (indirect) auscultation for the first time à amplified sounds and clearer and
deeper
o Laennec - invented intermediate/indirect auscultation and the stethoscope.
o He simply described his invention as “Le Cylindre”, later developed in wooden form.
o For several months he conducted comparative research, using various modifications of the
Cylindre, which soon became known as the stethoscope.

• Year 1819
o De l'Auscultation Médiate ou Traité du Diagnostic des Maladies des Poumons et du
Coeur. -> tuberculosis, pneumonia
o Within two years of intensive studies he examined nearly 3,000 patients, constantly comparing
the clinical observations with the autopsy findings.
o As early as 1821, De l’Auscultation Médiate was translated into English.
o In 1825 Irish position William Stokes (1804 -1878) published An introduction to the use of the
stethoscope

• Mediate percussioning
o Pierre Adolphe Piorry (1794-1879) is the author of the mediate (indirect) percussion method
introducing the so-called intermediate brass.
o Thanks to the work of a French physician, intermediate percussion strengthened the position of
the percussion as an equivalent diagnostic method in a medical clinic.
o Auscultation is more preferred than percussion.

• Adam Raciborski (1809-1871)

o Nouveau manuel complet d’auscultation et de percussion (1835)
o Raciborksi was keen to create a transparent and genuinely handy study for the needs of
practical medicine
o His work was welcomed and gained high scores.

• Joseph Skoda (1805-1881)

o Auscultation and percussion were gradually creating a diagnostic canon that will be accepted
both in Europe and in the Americas.
o His “Treaty of Percussion and Auscultation (Abhandlung über die Perkussion und
Auskultation)” (1839) became the basic textbook for diagnostics, which was now grounded
on the firm law of physics.

• Pierre-Charles-Alexandre Louis
o Creator of numerical method- stands at the beginning of medical statistics when examining
effectiveness of a phlebotomy in pneumonia.
o When comparing the vital observations and studies of pneumonia patients with the post-mortem
anatomo- pathological examinations, Louis showed that in such cases bloodletting has little
therapeutic value.
o He formulated his conclusions in 1828 based on 77 clinical cases of people with pneumonia
o Louis then applied a new method of evaluating clinical data, the so-called numerical method
(méthode numérique), which he had developed.
o Louis's work shows the beginning of clinical statistics
 o Phlebotomy useless in the pneumonia

• Quantification
o Quantification in medicine is part of the growing trust in numbers that has gradually affected all
aspects of social life during the past centuries (19th)
o It was a part of a process of objectification in clinical medicine
o Useful in medical climatology (the relation between climate and disease outbreak)
• Radiology
o In 1895 Wilhelm Roentgen accidentally discovered the penetrating radiation x-ray
o Gustav Kaiser (1871-1934), an assistant in the Viennese internal medicine clinic of prof.
Edmund von Neusser, was one of the first to draw attention to the medical possibilities of x-rays.
o Probably on 19th January 1896, after obtaining the professor’s consent, he took an x-ray picture
of the patient's hand
o Few years later the medical x-ray was born

• Roots of Tomography
o Professor Alfred Obalinski= the first X-ray in Poland in 1896
o In December 1913 Karol Mayer at that time working at the Department of Internal Medicine at
the jagiellonian University, worked on the problem of higher clarity of x-ray images.
o In 1914 Mayer proposed to move the X-ray tube during the examination in such a way as to
reduce the visibility of shadows from other organs as much as possible while extracting the
registered myocardial shadow.
o In 1916 he wrote separate paper on the subject
o The introduction of a static x-ray tube into the planned motion to obtain a sharp image of the
heart by deliberately blurring the structures of adjacent tissues was in fact the basis for the
later x-ray tomography
o Works of Karol Mayer are pioneering modern tomography.

• Computer Tomography (CT)

o The South African physicist Allan MacLeod Cormack (1924-1998) - University of Cape Town
in the early 1950s began to study the absorption of X-rays in various tissues.
o 1963 - Cormack presented the theoretical foundations of computed tomography.
o 1967 - Godfrey Newbold Hounsfield (1919-2004), employed at Central Research Laboratories
in EMI Ltd. constructed the first computed tomography.
o Both scientists were awarded the Nobel prize in 1979.
o First picture made in 1960s (CT)

Lecture 6 – History of internal medicine – therapy

• Dietetics and healing power of nature

o Vis medicatrix naturae- life forces and the power of recovery are given to nature itself
o In nature is constant struggle between health and disease
o Fighting the disease is in fact strengthening the body's forces by stimulating its vitality
o The Greeks were convinced (coined) “nature is the physician of all diseases”
§ “nature is the doctor of all diseases” “nature is a doctor of all diseases”
o The Greek noun (diaitia) can be translated as referring strictly to food and drink, but in the
Corpus Hippocraticum dietetics is what we call today a “healthy lifestyle”.
o Physician cures, nature fights disease
o Dietetics is starting point for medical prophylaxis (a way to maintain good health which opposes
threat of disease- preventive and active therapy)

• Pharmacognosy- natural medicines

 o The Egyptian pharmacopeia was not only significantly expanded but also well-organized
carrying over 800 recipes
o Medicines of plant, animal and mineral origin were known
o Milk honey wax = popular (herbs dissolved in wine, beer for UI tract, garlic)
o Magic spells are good for medicine and medicine is good for magic spells (Anonymous author)

• Acupuncture
o Emperor Shannung author of treatise almost fully devoted to plant-based drugs (oldest
pharmacopeia)
o Acupuncture (restoring internal organic balance) was a fully original therapeutic method born in
the circle of Chinese culture
o The conviction that there is an extensive system of energy channels (meridians) connecting
the surface of the body with internal organs was the grounding idea of acupuncture
o Blood (vital force) and qi, that is, the spiritual element, were to move in the system of channels
o Together (blood and qi) complimenting each other are creating a complete system
o The possibility of influencing this system was the basis of the original therapy, which became to
be known as acupuncture
o First Treatise devoted to this is written by ‘Yellow Emperor’ in 1st Century BC

• Ancient knowledge of drugs

o A student of Aristotle, Theofrast of Eresos (322-287 BC) was to create the basis for the
systematics and morphology of plants- father of botany
o In the Roman tradition of medicine, Dioscorides had a special place, as he made a
considerable effort to gather all the knowledge available to him at the time, about plants in terms
of their therapeutic properties
o The Pharmacopoeia, created by Dioscorides, became the binding basis for pharmacognosy for
centuries.
o Galen was guided by the quantitative principle as the basic one in determining the strength of
the effect of a given drug. -> 1 new ingredient in the original recipe could increase its power
o Galen is also responsible for the formulation of the principle- Contraria contrariis curantur
(opposite should be treated with opposite), which for many centuries became a determinant of
medical therapy.
o Galen also created “allopathic”. If the result of disease is heat and dryness, use drug ingredients
carrying cold and moisture.

• Medicines in the tradition of Islamic culture

o In Islamic culture pharmacology was based on translations of a number of treatises and writings
absorber from the Greeks, Romans and Hindu culture
o Rhazes was the first to use alchemy both for drug development and therapy
o In Islamic culture around 100 authors have paid more attention to healing and toxic substances,
leaving us with a great number of treaties.
o Ibn al Baitara (1197-1248), botanist and physician, who aimed to write a complete
pharmacopoeia and listed a total of nearly 1,400 medicaments in alphabetical order, about 300
of which were to be his own recipes.

• Paracelsus- sola dosis facit venenum

o For Paracelsus “drug theory” resulted directly from the iatrochemical model, in the light of
which both the structure and functions of the organism can be seen through the prism of an
alchemical laboratory
o Disease is a disorder of the basic chemical elements, and each disorder is a dynamic and
variable process
o It is not possible to analyze diseases at a generalized level, but it must be admitted that each
pathological process has its own specific characteristics.
o The principle of targeted therapy and dose factor- Omnia sunt venena, nihil est sine veneno.
Sola dosis facit venenum- “Everything is a poison, and nothing is a poison, because only a
dose makes a poison”.
 o Every substance known to nature can bring healing/death
o This was an important beginning of modern pharmacology and toxicology
o Aim of medicine: precise and individualized selection of proper therapeutic agent and precise
determination of the right dose

• Mechanical and chemical model

o In the middle of the 17th century, the first works of Swiss iatromechanic Johann Jacob Wepfer
(1620-1695), based on animal experiments, were created.
o Jacob Wepfer- pioneer of modern toxicology
o Wepfer formulated the principles of the so-called corpuscular toxicology.
o Friedrich Hoffmann (1660-1742) and his students, started from mechanistic positions, believed
that the effects of drugs and poisons could be described by means of a mechanical and
chemical model
o Anton von Störck (1731-1803), a student of Gerard van Sweiten and a representative of the
Viennese Senior High School, followed Paracelsus and his principle of dosis facit venenum in
his search for the best possible therapeutic values for the substances he examined. ->
poisonous plants (bleach, opium) & role in clinical therapy
o At that time, Störck took a three-stage experimental path: animal experiments, self testing and
clinical trials on patients.
o The Spanish physician Mattieu Orfila (1787-1853) conducted thousands of experiments on
animals, which resulted in the collection of detailed data which made the foundations for
modern forensic toxicology
o He studied mechanics of almost all known poisons at the time

• Phlebotomy- bloodletting
o Practiced in the middle ages
o The Egyptians Ebers papyrus contains fragments of text suggesting the use of incision of the
skin surface, i.e scarification, perceived as one of the medical procedures.
o In the Hippocratic era, bloodletting by means of venesections (vein incisions) were to restore
balance in the functions of the organism which correspond to the principles of humoral theory
o Vein incisions practiced in chronic fever and therapy of apoplexy
o Galen also referred to bloodletting, recommending it particularly in chronic inflammatory
conditions and to “calm the heart rhythm”.
o Arnold de Villanova (1235-1312) considered that bloodletting could be useful in the treatment
of all diseases known to mankind.

• Bloodletting in medical practice

o However, venesection was not always needed. In cases considered less sudden, it was
assumed that the attachment of leeches was an acceptable and sufficient solution.
o In particular the problem of phlebotomy in infectious diseases, especially those with epidemic
dimension, seemed to occupy the attention and minds of physicians
o Doubts arising from the statistically presented results of treatment in pulmonary diseases with
phlebotomy, which were clearly presented by the French clinician Louis, were widely ignored.
o Phlebotomy considered necessary during cholera epidemic in 1831
o Pneumonia and tuberculosis to be treated via bloodletting

• Phlebotomy revised
o In the years 1848-1849 over a hundred pages long work by (Jozef) Joseph Dietl, in which the
author summed up his clinical observations, which lasted a total of 5 years was published. (2
editions)
o Study covered 300 pneumonia patients
o Dietl’s clinical investigation compared with autopsy results of the deceased on pneumonia
indicated a deeper process of pulmonary degeneration when phlebotomy was administered
o Undoubtedly these were the first thorough clinical trials supported by the contemporary
knowledge of physiology and anatomopathological material, which proved not only
ineffectiveness but also harmfulness of phlebotomy in the treatment of pneumonia
 o Phlebotomy not only didn't support treatment of people with first-degree pneumonia but it also
increased the death risk

• John Hughes Bennett (1812- 1875)

o English internist Bennett provided evidence that the bloodletting performed in pneumonia
patients is associated with an increase in the death rate
o Bennett presented his conclusions publicly in 1855 during a lecture for medical students
o Nevertheless, the personal physician of Queen Victoria Richard Quain, At the beginning of the
last decade of the 19th century mentioned a dozen or so indications in which the phlebotomy
should be performed (pneumonia, menstrual disorders, fever, asthma)
o Common practice in Britain until 19th century to have healthy people do two phlebotomies a
year

• Transfusions
o Cura Medea- This is what was once called a direct blood transfusion procedure has its place in
the history of therapy
o The earliest information indicating the possibility of using a blood transfusion procedure dates
back to the modern era
o Hieronim Cardanus (1505-1576) or Magnus Pegel (1547-1619) may have been the first to
attempt blood transfusions and animals but we are lacking clear evidence here
o 1615: Andreas Libadius wrote about technical possibilities of transfusion

• Jean Baptiste Denis (1620-1704)

o Personal physician to king Louis Fortins
o In 1667 Denis administered the first fully documented human blood transfusion- The first
confirmed test with transfusion of animal blood to humans
o However first animal blood transfusion to human was regarded as successful, next transfusions
ended fatally (2nd to 4th transfusion patients died)
o End result the official band was given on all transfusions performed on humans in 1678
o 1665 Richard lower completed first blood transfusion on dog

• James Blundell (1790-1878)

o The English physician James Blundell experimenting on animals proved that an arterial blood
transfusion is as effective as venous blood and restoring life force- no knowledge on blood
groups
o Then by giving human blood to dogs he proved that it is lethal for them and thus animal blood
can be equally dangerous for humans-> decided to transfuse human blood only
o In 1818 he gave blood to man for the first time with the syringe with a good results for the sick
person
o The main problem apart from infection was the phenomenon of blood clotting, which Blundell try
to minimize by using a clever system of blood transport between the donor and the recipient: the
so-called gravitator
o 1828- during childbirth took blood from husband's shoulder vein to transfuse to labouring
female= first successful transfusion ever

• The birth of serology

o 1900- Karl Landsteiner, decided to determine the reasons why some transfusions run smoothly
and to the benefit of the patient, while others were fatal ->extracted RBC’s & mixed with plasma
where some coagulated
o Karl Landsteiner- discovered blood groups
o The results of the experiments led to the hypothesis that there are at least two types of
antibodies, which he labeled as A and B. He then supplemented this scheme with 3rd type- C
(later marked as O).
o Already in 1901 Landsteiner’s students Alfred von Decastello and Adriano Sturly showed the
existence of a fourth group, which was characterized by the presence of both antigens (A + B)
 in erythrocytes and thus called AB.

• Blood groups
o The key role in understanding the formation of blood groups and the principles of their
inheritance was established even before the first world war.
o Between 1907 and 1911, the German internist Emil Von Dungern (1867-1961) and the Polish
bacteriologist and serologist Ludwik Hirszfeld (1884-1954), based on the results of
experiments with animal and human blood, which they interpreted according to the theory of
receptors, came to the conclusion that blood groups are inherited, according to the laws
established by Mendel.
o The final, known to us today, blood grouping system was proposed by Hirszfeld.
o Hirszfeld- blood grouping system

• The Birth of Pharmacology

o 1791 – Friedrich Albrecht Carl Gren – made clear distinction between subject of
pharmacology (science of mechanics of the actions of drugs) and the classical Materia medica,
which he left with a systemic description and cataloguing of medicinal products
o Johann Christian Reil – said that medicinal substances introduced into living organism not
only affect its internal system (leading to changes in function), but also the composition of a
drug is subject to change as a result of the life action of the body

• Rudolf Buchheim (1820-1879)

o Handbook for Pharmacology = first handbook of experimental pharmacology

• Oswald Schmiedeberg (1838-1921) – created the foundations of modern pharmacology based on

experimental procedures
o Saw pharmacology as a field belonging to separate group of natural sciences
o Experiment is a right method and chemistry the right language
o Distinguished between methodology and goals set by pharmacologist and clinician

• Opium
o It was known already in ancient times and its analgesic and narcotic effects recognized by
healers of Mediterranean and Far East cultures
o Opium was well-known to Hippocrates, Dioscorides, Caelsus, Galen and Avicenna.
o In European medicine, opium became important mainly due to the works of Paracelsus, the
creator of the later famous Laudanum
o In the 18th century, opium was used in the treatment of nervous and mental illnesses.

• Morphine – Friedrich Serturner– isolated white crystalline substance – tested an animals = “sleep
inducing agent”; 1815 – named it morphine (after Greek God Morpheus)

• Organic Chemistry
o Friedrich Wöhler (1800-1882) introduced a lot of confusion into the world of science with his
discovery, which was quite accidental
o During the experiments with inorganic compounds he ended synthesizing urea from
ammonium cyanate.
o He proved that organic substance can be synthesized from inorganic in laboratory
conditions.

• First Synthetic drugs

o 1832 – Justus von Liebig – extracted chloral hydrate
o 1869 – Oscar Liebreich – showed chloral had a hypnotic and pain limiting effect
o Chloral hydrate used as sedative and popular as an intoxicant
o 1869 – Adolf von Baeyer – synthesis of barbituric acid
o 1903 – Emil Fischer – patented the drug Veronal
• Aspirin- Wonder Drug
o English pastor Edward Stone tried out extracts from white birch bark on patients
o Charles Frederic Gerhardt obtained acetylsalicylic acid
o Felix Hoffmann purified acetylsalicylic acid – given commercial name ASPIRIN
o Aspirin mechanism of action explained only in early 1970s by John Vane

• Paul Ehrlich (1854-1915) – side chains = antibodies

o Immune cells have these “side chains” present on cell surface – can bind pathogens and
neutralize them
o 1900 – Ehrlich introduced concept of receptor resulting directly from the theory of side
chains because it related to their essential function

• “Magic bullet” & Salvarsan (drug for syphilis)

o Ehrlich convinced that “side chain theory” would lead to development of drugs that, like a magic
bullet, destroy only pathogens without disturbing the tissues of living organism
o 1905 – Fritz Schaudinn & Erich Hoffmann identified spirochaete bacterium as pathogen
responsible for development of syphilis
o Research on creating effective agent against syphilis started

• Salvarsan
o Tens and later hundreds of different derivatives of arsenic compounds were tested. Eventually
the 606 test yielded the expected results. (in vaxxed against syphilis rabbits) - Sahahiro Hata
demonstrated this
o It was the moment of birth of Salvarsan (Arsphenamine) - “miracle drug” = cure for
syphilis

• Emilf Adolf von Behring (1854-1917)

o One of creators of serotherapy
o Work on anti-diphteria and anti-tetanus serums with Shibasaburo Kitasato

• The beginning of Antibiotic era

o 1928 – Alexander Fleming – Penicillin discovery

• Sulfonamides – Gerhard Domagk – 1935 – Protonsil = first sulfonamide enters clinical use
o Combination of red and orange azo dyes with sulfonamide radical

• Penicillin
o In 1940, Howard Florey and Ernst Chain , experienced with mould) finally proved the
usefulness of penicillin in combating bacterial infections. - Lanced Magazi
o They were also able to lay the foundations for drug synthesis
o In 1945 Florey, Chain and Fleming received the Nobel Prize

• Antibiotics
o 1942 – Selman A. Waksman coins term antibiotics
o 1943 – Albert Schatz – isolates streptomycin = effective in combatting tuberculosis
mycobacteria

• Insulin – Frederick Banting, Charles Best – discover insulin 1922

• Discovery
o The work began in May 1921. Over the next few weeks Banting and Best were struggling with
numerous technical and methodological problems.
o In the spring of 1922, the existence of a substance produced by the pancreas, called
insulin, was demonstrated, which actively reduced blood sugar and urine levels.
o In 1923 Banting and Macleod received the Nobel Prize.
o The Best was emitted by the Nobel committee.
 o “Internal secretion of pancreas”- first report about study 1922.
o Crystalline form of insulin obtained 1926 by John Abell

• After insulin
o The insulin discovery led to other works of hormone structure as a possible source for medical
therapy (Ex. Edward Kendell)
o The effort was undertaken to extract what was presumed to be ‘the hormone”, which could be
used in the treatment of Addison's disease
o The main technical obstacle was to obtain sufficient amount of an adrenocortical substance for
clinical trials.

• Kendall & Reichstein – work on hormone structure (1930s)

o Edward C. Kendall – compound E = cortisone
o Tadeusz Reichstein – pure crystalline form of cortisone

• Chlorpromazine (CPZ) = drug reducing shock and stress (Henri Laborit & Pierre Hugeunard)
o Henri Laborit – military surgeon – anesthesia methods
o Pioneering artificial hypothermy in surgical procedures

• Cholesterol
o 1784 - cholesterol was isolated from gallstones.
o 1913 - Nikolai Anitschkow fed pure cholesterol to rabbits. He could produce marked
hypercholesterolemia and severe atherosclerosis of the aorta.
o Late 1920s cholesterol structure was recognized.
o 1888- accurate molecular formula for cholesterol established
o 1910- Windows reported artherotic plaques from human aorta have 20 times higher cholesterol
concentration than normal aortas did.

• Birth of the statins

o Akira Endo – fungi can produce chemicals to ward off chemical organisms by inhibiting
cholesterol synthesis; fungi unaffected since their cell membranes made of ergosterol
o 1973 – Akira Endo – Mevastatin = first drug belonging to statin family

• Propranolol
o In the 1960’s- British researcher James W. Black developed propranolol, a drug which was to
be effective in the treatment of coronary artery disease and hypertension.
o 1768- William Heberden give the first description of angina pectoris (strong chest pain,
breathlessness)
o 1872- Lauder Brunton reported on the positive results when amyl nitrite was used to treat
angina pectoris
o 1879- English physician William Murrell published in Nature clinical report on the active role of
nitroglycerin in the angina pectoris treatment
o 1964- propranolol became the first major advance in the treatment of angina pectoris
since the introduction of nitroglycerin for that indication almost a 100 years earlier.

Lecture 7: History of Surgery

• Beginnings
o Oldest evidence present in prehistoric bone remains
o Simple surgery, bone fractures and dislocations, was taking place
o We can presume that traumatic surgery was already present
• Trepanation
o The word comes from Greek trypanon, which means drill
o It has been known in many parts of the ancient world and is still practiced in traditional
communities of Africa, Melanesia and Polynesia
o In South America special ritual knives called tumi were used
 o Trepanation could be performed for both sacral rituals and medical practice
• Mesopotamia
o Hammurabi’s code of law, in which we read about the doctor - titled Asu, which is using knife to
operate on the patient
o He was supposed to cure injuries of skull and bones, so Asu can stand for modern word
surgeon
o Treatment of superficial traumatic lesions was usually very conservative and operative surgery
was apparently rare
o Fractures were in most occasions not reduced and then immobilized by the surgeon, treatment
being restricted to bandages and oil dressing

• Surgery in Ancient Egypt

o Surgical conditions were often considered to be treatable and even curable, including those
caused by weapons
o Egyptian surgeon had access to needles and stitches
o There was high standard of hygiene and obstetrics was evaluated

• Sushruta = “The Father of Surgery”

o His work was first so evaluated books devoted to the theory and practice of surgery
o Sushruta samnita = first book devoted to surgery

• Plastic and reconstructive surgery

o It is believed that plastic and reconstructive surgery was performed in India and Egypt as long
as 3,000 years ago
o Sushruta was first to practice rhinoplasty, which was based on the use of a cheek flap, then
probably with use of forehead skin flap
o In modern times Gaspare Tagliacozzi of Bolognia (1545-1599) is credited for surgery in six
steps, ending in a total nasal reconstruction

• Lithotomy
o Sushruta performed his perineal lithotomy with a vertical incision lateral to the median raphe
o Of Sushruta surgical instruments, at least 125 types, we register additional 28 varieties of
catchers, sounds, and irrigation syringes
o Celsus gives us a detailed report on that subject
o Later Rhazes, probably relaying on Greek and Roman texts, was to include the lithotomy
techniques in his own works
o Book of Mariano Sancto - Libellus Aureus was specifically devoted to stone bladder cutting
techniques
• Anesthesia
o In 1846 Oliver Wendell Holmes (1809-1894) used the notion anesthesia which came from two
Greek words (without and senses)
o Dioscorides used opium or mandrake to minimize pain during surgery, however he was aware
that such therapies might be lethal or ineffective, or both.
o Rhazes was advocating for opium too
o In Americas Indians may have chewed coca leaves to reduce pain, but often failed, especially
when more radical surgery was involved
• First anesthetics
o Chinese Hua Tuo (145-220) was to produce anesthetic mixture - mafeisan, which was based on
wine and herbs
o In the Middle Ages, patients might sick liquid or breathe vapors which offered mandrake,
henbane and opioids, sometimes some other toxic substances
o Some surgeons were inducing narcosis by means of the so called sponge, spongia somnifera
• Laudanum
 o Paracelsus used a pain-killer made with opium, which he called Laudanum (tincture of
opium) - alcohol mixed with opium
o Laudanum was used over incoming centuries, and even as it was dangerous, it was produced
and sold well to 20th century
• Nitrous oxide
o In 1775 Joseph Priestley (1733-1804) published Experiments and Observations on Different
Kinds of Air, which can be seen as the first important book on the chemistry of gases. He
discovered nitrous oxide
o Thomas Beddoes (1760-1808) believed that different gases and their mixtures can have
curative effect on several diseases, especially lung diseases
o Henry Davy who was working with Beddoes observed pain-killing effect of nitrous oxide, but
soon focused his attention on other subjects
o In 1823-4 Henry Hill Hickman (1800–1830), experimented with inhaled carbon dioxide to
create a state, that he describes as “suspended animation” but obtained results aroused little
general or medical interest

• Horace Wells (1815-1848) – observed and tested anesthetic properties of nitric oxide (laughing gas)
o 1844 Wells connected fact of nitrous oxide inhalation with pain killing effect
o To check if he is right he asked his assistant John M. Riggs to extract the healthy tooth after he
would take some Nitrous oxide
o In 1845 Wells used nitrous oxide as anesthetic in his private dental practice

• Wells in Boston, 1845

o In January 1845 after Warren’s lecture, the medical students moved to an adjoining room for an
address by Wells
o When Wells, after making the patient inhale nitrous oxide, was removing his tooth, the man
cried in pain
o Wells was accused of cheatery and whole thing was reduced to “humbug”

• Ether
o In 1275 alchemist Ramon Llull discovered diethyl ether
o Valerius Cordus was to make first full synthesis of it, giving it the name - oleum dulce vitrioli
o The first description of its analgesic properties was to be done by Paracelsus
o Finally in 1730 Siegmund Fribenius named it “Ether”

• Crawford Long (1815-1878) - general ether anesthesia (1842) 1840s first introduced to surgery
o 1842, William Edward Clarke (1819-1898) was the first to use ether for dental extraction
when he tested it analgesic properties on his patient Miss Hobbie
o March 1842 the American surgeon Crawford Long was to use ether for general anesthesia
when operating neck tumor
o First written by him text on that subject was printed in 1849

• William Morton
o Considered one of pioneers of ether anesthesia
o On October 16, 1846, at Massachusetts General Hospital, Dr. Collins Warren painlessly
removed a tumor from Edward Gilbert Abbott’s neck after Morton administered mysterious then
Letheon
• Morton’s Letheon inhaler
o The name Lethon, coined by Morton, was to hide the ether compound, the only active
substance in it, so it could be now sold on high prices to others
o It was soon found out that Morton’s Letheon is in fact ether and dentist was now accused of
being indecent and acting against ethical rules which the physician should obey

• Chloroform - Sir James Young Simpson – discovered anesthetic properties of chloroform

 o In 1847, Simpson tested chloroform, relatively new compound, which was synthetized in 1831
by a French chemist Eugene Soubeiran

• First Local anesthesia - cocaine

o Analgesic properties of coca plant was known to Europeans from 16th century onwards,
however it was administered for medical use rarely, mostly as painkiller in toothaches or
headaches
o In 1860 German chemist Albert Niemann (1834-1861) was able to isolate an active principle,
which he named cocaine
o Its structural formula found not earlier than 1898 by Richard Willstatter (1872-1942)
• Local anesthesia
o In 1880 von Anrep published results of his experiments with cocaine for use as anesthetic
o In 1884 Viennese ophthalmologist Carl Koller (1857-1944) who was a friend to Freud, took a
part in a series of experiments with cocaine
o On September 1884 Koller performed the first operation using local anesthetic on a patient with
glaucoma

• William Halsted (1852-1922)

o In 1884 American surgeon WIlliam Stewart Halsted together with Richard John Hall became
interested in local anesthesia
o 1884 Hall published a report on the first successful nerve block

• Bleeding
o Traditional cautery is a medical practice of burning a diseased body part to remove it by using a
red heated metal rode
o It was used to stop bleeding as in cases of amputation and exsanguinous fluid

• Ligature
o The techniques of ligation used to stop bleeding were probably known in antiquity
o Techniques of ligation reintroduced by French surgeon Ambroise Pare in 16th century
o The modern method of ligation was finally established in 19th century by French surgeon
Jules-Emile Pean

• Ambroise Pare (1510-1590_

o Is considered one of the fathers of modern surgery
o His book The method of curing wounds caused by arquebus and firearms in 1545 changed
surgical practice significantly
o He rejected cauterization and proposed herbs for dressing instead
o Pare was starting the modern desmurgy
• Infection
o The real mechanism of infections was not discovered before 19th centuries and first reliable
statistics on operative mortality were published in 1841 by the Frenchman Jospeh F. Malgaigne
(1806-1863)
o In the 18th century an aggravation of wounds was carefully studied, but the cause remained
unclear. During this period the adjective “putrid” became to be used to determine infections and
putrid fevers referred to tetanus, pyemia and septicemia

• Hospitals
o At the end of 18th century growing number of hospitals, especially in big cities such as London,
Paris or Vienna became suitable places for infections to grow
o Lack of hygiene and presence of dissection rooms where physicians and students were
performing autopsies were provoking the waves of infections
o It was not rare habit to take autopsies directly in surgery room and there were no special aseptic
and antiseptic procedures present

• Puerperal fever – Ignaz Semmelweis – cadaverous particles

 o In 1840s visiting mothers who had just given birth immediately after autopsies were performed
in the same rooms resulted in a significant increase in fevers experienced by these patients
• What is wrong
o In 1846 Semmelweis just after receiving his medical diploma, was appointed as assistant to
prof. Johann Klein in the First Obstetrics Clinic of Vienna University
o The clinical ward was located in the Vienna General Hospital, were the Second Clinic was also
operational
o First clinic had an average maternal mortality rate of 10% due to puerperal fever. The Second
Clinic’s rate was considerably lower, averaging less than 4%
• Seeking for explanation
o Both clinics used almost the same techniques and had the very same rules for patients,
including even religious practices
o The only important difference was that First Clinic had the teaching service for medical students,
while the second Clinic was concentrated on courses for midwives only
• A turning point
o In 1847 the death of Semmelweis’s friend Jakob Kolletschka, who had been accidentally poked
with scalpel while performing a post mortem examination, was to be a turning point in the whole
story
o When the body of Koletschka was autopsied, then it became clear to Semmelweis, that
pathological changes then recorded are similar to those observed by him so many times during
postmortem examinations of the women who were dying from puerperal fever
o The only logical explanation was a connection between some factor rooted in cadaveric
contamination and puerperal fever
o Postmortem examinations were performed only in the First Clinic while midwifes receiving their
training in the Second Clinic were not attending the autopsies
• Solution
o Semmelweis explained that, as he expressed himself, “cadaverous particles”, were
carried on hands from the autopsy room to the examined then women
o He concluded that, still unknown to him “cadaverous material” is responsible for infection ending
in the childbed fever
o After some experiments with different substances Semmelweis finally found that chlorinated
lime (calcium hypochlorite) when used for washing hands between autopsy work and the
examination of patients is what was needed
o When in spring of 1847 the mortality rate in First Clinic reached dramatic over 18%, then after
few weeks when washing hands was introduced it was no higher than 2.2%
• Fate of dr Semmelweis
o The Semmeleweis’s hypothesis that childbed fever should be connected with some “cadaverous
particles” was in his times not so radical as it looks on first glance
o His concept, having clearly the positive statistical data, was finally rejected in medical
community of Vienna
o He was forced to leave the clinic, and then Vienna. He moved to Budapest.
o In 1865 his mental state was so serious that he was committed to an asylum. Here he died of
septic shock

• Joseph Lister (1827-1912)

o Semmelweis managed to print a book entitled “The etiology, the concept and the prophylaxis of
puerperal fever” (1861)
o Inn 1860s Joseph Lister Scottish professor of surgery at the University of Glasgow became
aware of a Pasteur’s works

• Antiseptic Principle of the Practice of Surgery, 1867

o Lister still being convinced, according to miasmatic concept, that infections spread through air,
he began spraying instruments, the surgical incisions, and dressings with a solution of
carbolic acid (phenol) – Joseph Lister
o The results were more than promising, clearly showing that 5% carbolic acid solutions are
working in protecting surgical wounds from suppuration
 o In 1867 Lister subsequently published his results in The Lancet in a series of six articles

• Aseptic surgery
o An antiseptic attitude was aiming at fighting germs, there was now a strong conviction that a
preventative, so aseptic procedures were needed which led in invention of surgical gloves and
masks, then the surgical instruments sterilization
o Austro-Polish surgeon Jan (Johann) Mikulicz-Radecki was an advocate of antiseptics, and
made much to popularize Joseph Lister’s antiseptic methods
§ He was first to use medical gloves during surgery, initially made of silk, then of
cotton, although his aim was to protect his skin from the austic effects of the phenol
disinfectant
§ In 1890 American surgeon William Steward Halstead turned to the Goodyear Rubber
Company with an offer to produce a pair of thin rubber gloves

• Mikulicz’s clinic in Breslau c.a. 1901

o In 1879 Charles Chamberland, Louis Pasteur’s pupil and collaborator, developed the first
pressure steam sterilizer or autoclave
o Two years later 1881 sterilization by boiling was introduced
o Now everything used during an operation was to be boiled, although some surgeons were still
following Lister’s method regarded by them as more effective

• Thoracic surgery
o In 1904 Jan Mikulicz was already working on differential pressure control, which was to enable
the patient to keep breathing during the surgery
o Ferdinand Sauerbruch, then assistant to Mikulicz, developed the negative differential
pressure chamber which enclosed in a hermetically sealed room the patient and the entire
surgical team
o In the same time German physician Brauer developed a positive pressure method

• Continuous breathing without respiratory motion

o In 1909 Samuel James Meltzer and John Auer came with idea of “continuous breathing without
respiratory motion” through endotracheal insufflation with a continuous stream of air and
anesthetic vapor
o The emergence of lung inflation by positive pressure enabled the future development of thoracic
surgery

• Forssmann’s history
o In 1929, while working in Eberswalde, young physician Werner Forssmann performed the first
human cardiac catheterization
o Under guidance of fluoroscopy he advanced the catheter the full 60cm into his right ventricular
cavity, this was then recorded on X-Ray film showing the catheter lying in his right atrium
• Nobel Prize
o In the 1940s Andre Frederic Cournand and Dickinson W. Richards were researching on heart
diseases, read the Forssmann communication which was printed in 1929
o They started to develop ways of applying his technique with very good results
o In 1954 Cournand, Richards and Forssmann won the Nobel Prize
• Transplant surgery - roots
o In 1869 the first major step towards modern transplant medicine came with the works of
Jacques-Louis Reverdin, who has showed that small, thin grafts can be used in therapy
o Neither Raverdin nor other scientists noticed the important differences between autograft and
homograft
o In 1912 Georg Schone studying grafts of skin determined that homograft always failed and that
subsequent grafts from the same donor failed more rapidly than the first transplant did

• Organ transplant - the beginnings

 o French Alexis Carrel is commonly credited with originating both vascular suturing and its use in
organ transplantation
o In 1904 co-working with the physiologist Charles Guthrie, carrel they successfully transplanted
the kidney, thyroid, ovary, heart, lung, and small bowel in animals
o Carre’s extensive experience with organ transplants in animals left no doubt that, although
autograph could be considered successful, homograph never was
• First human transplants
o In 1906 Mathieu Jaboulay performed the first two renal transplants in humans using a pig donor
for the first patient and a goat donor for the second person. Both ended fatally
o In 1933, the Soviet surgeon Yuri Voronoy performed the first human-to-human kidney
allotransplant which resulted in failure
o Between 1933 and 1949 four other human allotransplants that Voronoy performed also failed
o On 23 December 1954, Joseph Murrau bypassed the barrier of rejection by using the patient’s
identical twin as the donor for the first successful human kidney transplant
• Heart transplant
o In 1960 Robert hans Goetz successfully grafted the right internal mammary artery to the right
coronary artery, thereby performing the first coronary artery bypass graft
o 1967 Christiaan Barnard successfully performed the first ever human heart transplant

• Transplantation
o 1968 first successful bone marrow transplant
o 1981 first successful combined lung and heart transplant
o 1992 first successful adult segmental living-related liver transplant
o 2010 first full facial transplant

Lecture 8: History of Biochemistry

• Biochemistry
o Carl Alexander Neuberg = “Father of Biochemistry”
o He coined the term Biochemistry
o In 1910s he made experiments which led to the discovery of an enzyme called carboxylase
o He developed a theory of the alcoholic fermentation of glucose

• A Grandmother of Biochemistry - Alchemy

o Alchemy probably has its origins in ancient Egyptian-Kemet-meaning Black Land and depicting
the fertility of the flood plains around the river Nile valley
• Alchemy
o The final goal for many alchemists was to find the “elixir of life”, so connecting later
chemistry with biology
o To obtain the substance called the “philosopher’s stone”, which when heated and combined
with “base” (nonprecious metals such as copper and iron) would turn it into gold
§ philosopher’s stone = for alchemical transmutations
o Chrysopoeia, that is the transmutation of common minerals into “noble metals” - particularly gold
was only one of aims
o The biggest challenge was to discover the relationship of humans to the nature and cosmos
o Alchemical transmutation was now equal with cycle of life processes

• Between magic, philosophy and science

o Alchemists contributed much to the realms of human knowledge which would later be
recognized as chemical industries: the production of inks, dyes and paints, basic metallurgy and
metalworking, cosmetics and pharmacology
o The biggest known collection of alchemical texts was to be stored in Library of Alexandria, but
majority of it perished in great fire
 o Then the next “golden age” was to be connected with the works of Islamic scientists, with Jabir
ibn Hayyan (721-815) as the most important figure here

• Alchemical obscurity
o Alchemists often made their work hard to examine by modern researchers.
o The secrecy was the important factor of their methods.
o There is usually no distinction between purely chemical questions and the mystical or magical
aspects of their craft
o The next problem for modern scholars is lack of a universal scientific language for alchemical
concepts and processes
o The terms and symbols of biblical origin mixed with some pagan mythology, astrology, and
other spiritual arenas are big puzzle for us today

• Voynich manuscript
o Discovered in 1912 in one of libraries by Wilfrid Voynich (Michal Wojnicz) and from that moment
has been studied by many professional and amateur cryptographers, linguists and researchers
from nearly all branches of modern science
o Investigation was done by American and British best army codebreakers, however without
success
o It is now treasured in The Yale University’s Beinecke Rare Book and Manuscript Library

• What we know about Voynich manuscript?

o The vellum on which it is written has been carbon-dated to the early 15th century
o Dyes and ink are probably coming from the first half of 15th century
o Every page in the manuscript contains text, mostly in an unidentified language, with some
elements of Latin
o There are no indications of any errors or corrections made any place in the document
o It shows many aspects typical for alchemical texts

• Alchemy and life

o Artephius (12th century) wrote The Art of Prolonging Human Life which was to bring exact
measures for alchemical procedures giving in result prolonged life
o The strong conviction that alchemical transmutations (reactions) can influence and change
plan of nature was part of alchemical tradition
o This active attitude was rebelliously different from Hippocratic passive medicine

• Roots of Iatrochemistry
o The very first step to understand life as a chemical reactions were made by alchemy
o Alchemical concept of constant permutations leading to wholeness of universe and happiness
o The creation of an elixir of immortality or panaceas able to cure any disease were others
o It was a philosophical concept to make complete theory of everything

• Distillation
o Detailed instructions, ranging from the right times to collect herbs to the exact specifications for
constructing distillation equipment were to make “medicinal alchemy” accessible to ordinary,
however educated people
o In Hieronymus Brunschwig (1450-1512) work we can see the ground for future Paracelsus’s
investigations
o Hieronymus Brunschwig – one of first books devoted to distillation methods applied to needs
of medical practice

• Iatrochemistry is born
o Philippus Aureolus Theophrastus Bombastus von Hohenheim, known under the name
Paracelsus, was to be one of the earliest who applied his alchemical knowledge to the
problems of medicine
 o He can be described as the philosopher, alchemist and physician whose writings were a mixture
of different, sometimes contradictory, thoughts from which finally emerged new concept of
medical and biological problems

• Paracelsus philosophy of nature

o Paracelsus was familiar with the Hermetic Neoplatonic and Pythagorean philosophies, which
was quite natural in times of Renaissance
o Paracelsus rejected Aristotle’s and Galen’s teachings, as well as the Hippocratic theory of
humors
o However he accepted the concept of four elements: water, air, fire, and earth, seeing them as a
starting point for his own ideas

• Chemical structure of life

o Physicians, as he was convincing, required a solid academic knowledge in the natural realm of
sciences. The chemistry held here the most important position
o Combustible element, that is sulfur, a fluid and changeable element represented by mercury,
and a solid, permanent element salt formed the core of his theory of pathology
o All diseases originated from those 3 elements
o The s.c. tria prima also defined the human identity

• Tria prima (sulfur, salt, mercury)

o Sulfur embodied the soul, which was the seat of all emotions and desires
o Salt represented the physical body
o Mercury was emanation of the spirit, that is imagination and the higher mental faculties. The
moral virtues were also connected with mercury
o All of them were connected with each other by the will of God which is given in the Holy Trinity

• The new medicine

o Sickness and health are relied on the harmony of Man - microcosm and the harmony of Nature -
macrocosm
o In other words the macrocosm (universe) was represented in every person as a microcosm
o The harmony in the body is a proper balance of minerals, which when ruined provoked illness
o It is by that only chemical remedies could cure

• Paracelsus & Hippocrates

o As Hippocrates speculated about 4 liquids constituting organic life, so Paracelsus was with his 3
mineral elements
o As Hippocrates was teaching about proper balance in the scope of harmony, the same was
given in Paracelsus’s microcosm-macrocosm concept = imbalance of four liquids
o However paracelsus was trying to find proof of his ideas in alchemical lab on the grounds of
experiment which Hippocrates never did

• Homunculus - First time appears by name in alchemical writings attributed to Paracelsus

o The small human being artificially made in lab by means of alchemical procedures
o This idea was then present in many writings and was many ages after still present in genetic
engineering

• Chemical medicine founder – Philipp Ulstad of Nuremberg

o Philipp ulstad of Nuremberg wrote Coelum philosophorum seu de secretis naturae liber
(Fribourg, 1525) which was devoted to many alchemical problems and brought the rise of
modern distillation technology
o He was venturing to the field of chemical methods which can be used in practical medicine
• Iatrochemistry
o Flemish chemist Jan Baptista van Helmont (1579-1644) is regarded as a founder of
pneumatic chemistry
o Jan Baptist van Helmont was for many years performing alchemical transmutations during
which he was trying to find principles of combustion
o He coined the word gas as a product of burning coal, process he had observed for many years
o He properly identified “gas sylvestre” (carbon dioxide) and made presumption that it was
the same as that produced by fermenting must

• Chemical digestion
o From antiquity onwards the digestion was understood in mechanical or physical terms only
o Food digested due to the body’s internal heat was in Helmont’s Times most popular
explanation
o Helmont’s questions: How could cold-blooded animals live?
o He concluded that digestion was aided by chemical reagent - “ferment”, within the body,
such as inside the stomach
o He determined that acid was the digestive agent in the stomach

• Chemical physiology
o Helmont was the very first to describe all life functions as the chemical reactions of
effervescence, fermentation, and putrefaction
o We can say that he formed basis of chemical physiology
o In his Ortus Medicinae (1648) he gave full lecture on his medical theories

• Acids & alkali

o Franciscus Sylvius was follower of Hippocratic humoral theory explaining that all diseases
resulted from excess of the humors
o Although those excesses are chemically driven by imbalance of acid or alkali solution in the
body
o Acids and alkali were the essential elements of physiology

• Chemical nature
o Thomas Willis (1621-1675) observing the results of opiates has speculated that painless and
woozy feeling is resulting from interaction with a salt
o In his De fermentalione (1659) Willis argued that all natural phenomena are based strictly on
chemical features
o In Diatribae duae medico-philosophicae-quarum prior agit de fermentatione, a treatise on
fermentation, Willis saw in fermentation a mysterious key to transformations - from mash to beer
or from health to fevers
o Willis derived many of his conclusions from observations on distillation

• Chemical respiration
o Robert Boyle (1627-1691) was exploring the problem of respiration give evidence that air is
required for fire in combustion reactions and also needed for breathing of animals and
humans
o In his The Sceptical Chymist (1661) he advocated after chemistry as an integral part of natural
philosophy
o Using s.c. pneumatic engine (air pump) he give empirical evidence that air is crucial for living
and combustion processes

• Phlogiston theory
o In 1703 Georg Ernst Stahl, professor of medicine and chemistry at Halle used olf alchemical
notion - phlogiston, as a substance to be released in the process of burning
o Stahl worked intensively with various substances in order to separate phlogiston from them
o However, it was false, phlogiston theory became important bridge to modern chemistry
• Michal Sędziwój – “food of life” in the air à oxygen
o In 1605, Polish alchemist Michal Sedziwoj in his alchemical treatise A New Light of Alchemy
proposed the existence of what he has described as “the food of life” existing within air
o We know that it was later recognized as oxygen
• Oxygen
o In 1754 Scottish chemist Joseph Black isolated what he named fixed air (carbon dioxide)
o In 1766, English chemist Henry Cavendish isolated inflammable air (hydrogen)
o In 1773, Swedish alchemist Carl Wilhelm Scheele discovered fire air (oxygen)
o In 1774, English chemist Joseph Priestley independently isolated in gaseous state
dephlogisticated air (oxygen)
o Name “oxygen” finally given by Antoine Lavoisier

• Antoine Lavoisier
o In Considerations Generales sur la Nature des Acides (1778) Lavoisier demonstrated that the
air in the process of combustion is in fact the source of acidity too
o He claimed that air consists of two basic elements
o In 1779 he named those elements: oxygen, that is “acid former” and azote “lifeless”
o It was real end to phlogiston theory

• Pioneer of Modern chemistry

o Swedish scientist Jons Jacob Berzelius, trained physician, was one of the leading chemists in
the first half of 19th century
o He can be seen as a pioneer of modern chemistry

• Synthesis of urea
o In 1828 by pure accident German chemist Friedrich Wohler synthetized urea from inorganic
substance – showed that organic can be synthesized from inorganic
o This is regarded as a starting point for organic chemistry

• Chemical Vitalism
o Leopold Gmelin defined “Physiological Chemistry” as chemistry under the rule of vital force
o All biological functions of life are indeed in their character just a chain of chemical reactions

• The first steps

o Robert Kohler in his deep study of the history of biochemistry wrote: “1890s as the time when
biochemistry as we know began to acquire its conceptual and social organization”
o It was in the beginning realm of chemists, rather than biologists

• Fermentation
o Eduard Buchner – pioneering studies on enzymes
o He has shown that a cell-free extract of yeast cells still could ferment sugar
o On his works on fermentation process he gained Nobel Prize in year 1907

• Enzymatic way
o Kuhne explained that enzymatic action can take place in or out of organism
o He saw in them simple chemical reactions
o Around 1900 studies on enzymatic subject of life process became popular field of investigation
o We can say that it was a right time for biochemistry to be born

• Enzyme as catalytic factor

o Enzyme was understood as a catalytic factor which is acting in chemical processes responsible
for changes in biological realm of life (for example in fermentation process)
o So it was the first topic for physiological chemistry which later became known as biological
chemistry (biochemistry)
• What is a nature of Enzyme?
o Willstatter in early 1920s give a strong support to enzymatic research prophetically pointing on
enzymes to be a straightforward problem of organic chemistry in the nearest future
o Just a few years later new crystallization techniques gave strong evidence that enzymes are in
fact very large macromolecules

• Enzyme and cells

o In the opening years of 20th century cellular structure played more passive role in the eyes of
enzymologists
o Research in the matter of the “surface forces” gave cellular structure a more active role
o Otto Warburg pointed that the catalytic (enzymatic) process is in fact responsible for
respiration on the cellular level

• Metabolism
o Greek word metabole means a change
o In 13th century Ibn al-Nafis wrote that “the body and its parts are in a continuous state of
dissolution and nourishment, so they are inevitably undergoing permanent change”

• Jędrzej Śniadecki (1768-1838)

o Polish physician and chemist Jedrzej Sniadecki came with his original idea of organic functions
as the process of changes on the level of inorganic and organic substances
o He named this process as the “transformations of matter”, anticipating future metabolic
theory

• Justus von Liebig (1803-1873)

o Justus von Liebig’s Animal chemistry, or, organic chemistry in its applications to physiology and
pathology (1842) can be credited as the first presented chemical theory of metabolism
o Liebig saw similarities between plant and animal metabolism

• Hemoglobin
o From the beginning of 19th century there was much rumor about nature of blood
o In 1851 Otto Funke - described growing hemoglobin crystals
o The protein hemoglobin itself was discovered in 1840 by Friedrich Ludwig Hunefeld, who
detected it while viewing the blood of an earthworm

• Teichmann’s Test
o In 1853 he has described the preparation of microscopic crystals of hemin (Teichmann’s
crystals)
o The simple, specific test developed by Teichmann became widely used in forensic medicine in
the first place
o It opened ways to the discovery of the chemical structure of hemin

• Felix Hoppe-Seyler (1825-1895)

o Hoppe-Seyler was the first to describe the optical absorption spectrum of the red blood pigment
o He also recognized the function of hemoglobin as a “tool” binding the oxygen to erythrocytes

• Chlorophyll and Hemoglobin

o Edward Schunk together with Leon Marchlewski showed very close chemical relation between
derivatives of hemoglobin and chlorophyll
o This discovery was followed by works of Marchlewski and Marceli Nencki

• Molecular structure of hemoglobin

o Using X-ray techniques Max Perutz determined in 1959 the molecular structure of hemoglobin
 o In 1962 he received together with John Kendrew Nobel Prize in field of chemistry

• Modern biochemistry
o In 1930’s and 1940’s biochemistry of enzymes played still a major role in the research
programs
o However the problem of biochemical pathways was also carefully studied

• SIr Hans Adolf Krebs (1900-1981) - pioneered in modern study of cellular respiration, a
biochemical pathway in cells for production of energy
o He is remembered for presenting an important sequences of chemical reactions that take place
in the cells of humans and many other organisms, namely the citric acid cycle , which
eponymously is named the “Krebs cycle”
o A conception of the biochemical unity of the cell as a system of coupled metabolic cycles, with
ATP as a universal medium of energy exchanging
o He is remembered also for discovery of Glyoxylate cycle and urea cycle

• EMP - Embden-Meyerhof-Parnas
o The most frequent type of glycolysis found in the living body is the type that follows the EMP
Pathway, which was finally discovered by Gustav Embden Otto Meyerhof, and Jakub Karol
Parnas

• Cori cycle –
o American biochemists, Gerty Theresa and Carl Ferdinand Cori, husband-and-wife team
working on glycolysis discovered the metabolic pathway for lactate (Cori cycle)
o The cycle is known also under the name Lactic acid cycle
o In 1947 Gerty and Ferdinad Cori received their Nobel Prize
• Proteins
o Greek word - proteios stands for “primary” in English
o 1837 Dutch chemist Gerhardus Johannes Mulder discovered the protein molecule
§ Proteins were discovered in the first half of the 19th century!
o 1902 German chemist Emil Fischer and Franz Hofmeister independently proposed that
proteins are formed from amino acids

• Chemistry and biochemistry in clinic

o Otto Knut Folin (1867-1934) co-developed a method of assaying glucose in protein-free filtrates
of blood
o Donald Dexter Van Slyke (1883-1971) conducted explorations on blood and urine, what lead to
clinical methods of analysis

• Vitamin – coined by Casimir Funk

o 1747 Scottish surgeon James Lind discovered that citrus foods helped prevent scurvy
o 1897 Christiaan Eijkman discovered that feeding unpolished rice instead of the polished variety
to chickens helped to prevent a kind of polyneuritis that was equivalent of beriberi
o 1912 Polish-born biochemist Casimir Funk, working in London, isolated the same complex of
micronutrients and proposed the complex be named “vitamin”

• New realm of vitamins

o 1930s can be named the golden decade of vitamins.
o Many important discoveries were then born.
o In 1920s the active substances as vitamin B or E were detected
o 1928-1932 Albert Szent-Gyorgyi and Walter Haworth à vitamin C
GENETICS (Lecture 9)

Prehistory
- Selective breeding = observation that living things inherit physical and visible features from parents
- has been intentionally used to improve crops, plants, animals
- in many mythologies, sons and daughters of gods could inherit their physical and mental features; parents
were transmitting powers as well

PYTHAGORAS (500 BC)

- speculating that each organ of male, animal, or human can produce special kind of vapors, which mix with
each other to finally form embryo in female womb

EMPEDOCLES (504 – 433 BC)

- thought liquids can be essential – proposed that each body part produces a fluid
- the fluids coming from different body parts of both parents are mixed up and used in formation of embryo

BRICKS AND MORTAR theory – Hippocrates

- taxonomical material consists of physical substances originating from each part of the body and then
concentrated in the male SEMEN, which develops into human within the womb

PANGENESIS and DARWIN

- in antiquity – theory claiming that characteristics acquired during an organism’s life were heritable
- 2000 years later, CHARLES DARWIN coined term PANGENESIS
- pan = while; genesis = origin
- proposed that each part of the body continually produces its own type of small organic particle – gemmules
– that are assembled in the gonads, contributing heritable information to the gametes
- Blending inheritance – individuals can inherit a smooth blend of traits from their parents

ARISTOTLE – EPIGENESIS (term coined by Caspar Friedrich Wolff)

- male semen contributes to the “active” element of offspring, brining it to life, while female contributed only
nutritional material for offspring
- Aristotle was advocating the possibility of improving human health with eugenics, to bring more healthy and
strong individuals

Epigenesis (originated by Aristotle), claimed that an embryo continually develops

- an organism builds itself through a sequence of steps to form organs, which in turn are constituting complete
unity
- main source of epigenetic theory = “On the generation of animals”

Leonardo da Vinci:
- during his anatomical and physiological studies he became convinced that both parents, men and woman,
equally contribute in the mechanism of heredity of the offspring
- he was following the epigenetic path

Epigenesis and embryology

- Departing from Aristotle’s natural philosophy, epigenesis gained growing attention from the 17th century
onwards when modern embryology was coming to voice
- Embryology provided a perfect domain to study how organisms reach their maturity on by the development
- as a model organism Aristotle took the chicken – over 28 days, he systematically opened one developing egg
per day
Preformationism theory
- basis = conviction that organisms develop from miniature versions of themselves
- organisms are producing the exact and fully complete copies in succeeding generations which grow from
homunculi or animalcules, that have existed since the beginning of creation
- HOMUNCULUS – appears first time in alchemical writings by PARACELSUS
- the small human being artificially made in lab by means of alchemical procedures
- this idea was present in many writings and was many ages after still present in genetic engineering
- “Do natura verum” = method of creating homunculus

Preformation in modern era

- in17th century, preformation theory was present in the works of Dutch Jan Swammerdam and strongly
advocated by Italian Marcello Malpighi
- seemed to be convincing for majority of researchers

Preformation and epigenesis

- 18th century – debates b/w metaphysical materialists, which were close to preformationist idea and
epistemological epigeneticists, who accepted vitalism as the only explanation for driving mechanism – “from
not formed to formed”
- it was a matter more philosophical then biological discussion, but preformationist were winning the field

- CASPAR FRIEDRICH WOLFF (1733-1794) – coined term EPIGENESIS

- used example of plant root that despite its differentiated tissues, is able to regenerate a whole new plant if the
stem and leaves are removed, which was against then widely approved theory of preformation
- Wolff was convincing, that many organs and tissues which are originally absent can develop

KARL ERNST VON BAER (1792 – 1876)

- work on the nature of the mammalian ovum (egg)
- established that mammals, including human beings develop DIRECTLY FROM EGGS
- also concluded that embryos of one species can resemble embryos of another species, but not adults of
another, and that the younger the embryo the greater the resemblance
- in line with epigenetic idea – that development proceeds from simple to complex, from homogenous to
heterogenous

IMRE FESTETICS - hungarian

- The genetic law of the Nature
- described several rules of inheritance – when studying sheep inbreeding – formulated 4 laws
- Festetics “heredity” controlled by “physiological laws of nature”

GREGOR MENDEL – basic principles of genetics

- famous pea plant experiment – Mendel’s Laws
- identified basic characteristics : plant height, pod shape and color, seed shape and color, flower position color
- coined term “recessive” and “dominant”
- published a paper on existence of “invisible factors”= GENES - that provide for visible traits in predictable
ways
- it took 30 years for his work to be widely known
- 1900 – Hugo de Vries, Carl Correns, Erich von Tschermak – independently rediscovered his laws

WILLIAM BATESON – wrote - “A defense of Mendel’s principles of heredity”

- book was key event – showed law of segregation applied not only to plants but to animals
- was first to used the word “genetics” to describe separate science focused on problems of heredity

First microscope nuclei investigation

- CARL WILHELM VON NAGELI (1817-1891) = first to observe and describe thread like structures in the
nuclei of plant cells, what he called “transitory cytoblasts” – CHROMOSOMES
Speculations on hereditary elements

ERNST HAECKEL – idea that ontology recapitulates PHYLOGENY

- 1866 – speculated about the cell nucleus about place to store information necessary for inheritance

CHROMOSOMES
1880’s – WALTER FLEMMING – described behavior of characteristic, found in nucleus structures, during the
cell division process – soon to be named chromosomes
- FATHER OF CYTOGENETICS = Walter Flemming

CENTROSOME – Theodor Boveri - different parts of chromosomes carry different parts of hereditary
elements
- 1888 – discovered the centrosome

1902 – WALTER SUTTON & Theodor Boveri – propose that chromosomes = bearers of Mendelian factors
- Sutton convinced that they are the basis of heredity
- observed reduction of number during meiosis

THOMAS HUNT MORGAN – fusion of mendelian genetics and chromosomal theory

- Drosophila – fruit fly experiments
- genes carried on chromosomes & genes are basis of heredity
- book: “The Mechanism of Mendelian Heredity” – most important
- homologous chromosomes are able to make chiasmata and exchange strands = crossing over

1941 – GEORGE BEADLE and EDWARD TATUM (“one gene-one enzyme)

- proof that specific gene controls a biochemical reaction
- working on mold, they showed a single gene controls each step in a metabolic pathway
- led to “One gene-one enzyme hypothesis”

ERWIN SCHRODINGER – book = “WHAT IS LIFE” – 1944

- Gene nature is both heterocatalytic (enzyme catalyzing reaction) and auto-catalytic (when catalyzes reaction
that enables its own replication
- thought advanced physics can be used in realm of biological and medical sciences

1913 – Alfred Sturtevant – genes like beads are arranged on chromosomes in a linear order
1923 – Theophilus S. Painter – said there are 48 chromosomes; sex determination = X and Y
1956 – chromosome number corrected = 46 for humans – TIJO and LEVAN

HERMANN JOSEPH MULLER (1890-1967) – X-rays can lead to mutations

Johann Friedrich MIESCHER’S RESEARCH

- gave evidence that proteins and lipids are main components of cell cytoplasm
- 1869 – obtained for first time – crude precipitate of DNA
- discovered presence of nuclein in cells of other tissues – including sperm

Eduard Zacharias – showed nuclein is integral part of chromosomes

1881 – combined histological concept of chromatin with chemical substance nuclein

DNA interludium
- period of time after 1890s where there were little advances in field of nucleic substances as majority though
more complex proteins must be carriers of genetic information

1928 - FREDERICK GRIFFITH – Bacterial transformation experiment – “transforming principle”

- smooth (virulent) and rough (non-virulent) strains
- but thought the “transforming principle” was protein rather than DNA
1944 - OSWALD T. AVERY, COLIN MACLEOD and MACLYN MCCARTY – showed that transforming principle
was DNA and not protein
- transforming power lost when extracts containing DNA are destroyed

1952 – ALFRED HERSHEY and MARTHA CHASE – used viruses to confirm DNA as the genetic material
- showed that during infection, viral DNA enters cell while viral proteins do not
- showed viral DNA can be found in bacterial progeny

1933 – LINUS PAULING – proposed triple helix structure for DNA (obviously he was wrong)

1953 – ROSALIND FRANKLIN and MAURICE WILKINS

- used X-ray analysis to demonstrate that DNA has a regularly repeating helical structure
- PHOTO 51 – (May 1952) – precise X-ray diffraction image of crystallized DNA taken by Raymond Gosling
who was working under supervision of Rosalind Franklin

WATSON and CRICK – discovered molecular structure of DNA

- APRIL 1953 – Molecular Structure of Nucleic Acids – published in Nature

1957 – ARTHUR KORNBERG – discovers DNA polymerase

- awarded Nobel prize (1959)

1961-1966 – GENETIC CODE CRACKED

1977 – Frederick Sanger, Allan Maxam, Walter Gilbert – DNA sequencing methods
SANGER SEQUENCING – based on selective incorporation of chain-terminating dideoxynucleotides by DNA
polymerase during invitro DNA replication
1980 – Sanger wins Nobel prize
1982 – human insulin = first drug based on recombinant DNA – appears on market

GENOME SEQUENCING
1980 – program begins
1995 – first complete sequence of genome of free-living organism – Haemophilus influenzae
2000 – complete sequence of fruit fly discovered
2001 – almost complete human genome sequenced

LECTURE 10 – History of radiology

1895 (November 8) – WILHELM CONRAD RONTGEN – detects X-rays

- barium platinocyanide-coated screen began to glow when his cardboard tube was charged
- image of his wife’s hand presented on December 25th 1895 to Wurzburg society
- X-rays have immediate impact on society

1986 - ANTOINE-HENRI BECQUEREL – first person to discover evidence of RADIOACTIVITY

1903 – Nobel prize with Marie Curie and Pierre Curie

1986 – THOMAS EDISON – Fluoroscope – hand-held

- X-ray was still better, cheaper and safer than fluoroscopy

Commercial X-rays
X-ray Apparatus – widely available
-- “bone portraits” popular
-- shoe fitting
X-rays in DENTISTRY - OTTO WALKHOFF – made first picture of his own teeth
- exposed himself to radiation for 25 minutes

RADIOGRAMS
- moving-picture X-rays and military radiology images
- x-ray labs present in many hospitals

EDUARD HASCHEK and OTTO LINDENTHAL – filled arterial vessels of hand of corpse with TEICHMANN’S
SOLUTION – mix of chalk, cinnabar and paraffin = FIRST ANGIOGRAM / ANGIOGRAPHY – 1986

JOSEPH BERBERICH and SAMSON HIRSCH – first angiography on living human

- strontium bromide as contrast agent

First Poland medical X-ray – February 1896 – Alfred Obalinski

SURGERY X-RAY – 1897 – KARL GUSTAV LENNANDER – removed pistol bullet from occipital lobe of the
brain in a young man – one of first operations done using x-ray guidance

1904 – radiologists agreed that X-rays had hazards

- protection included – lead screens, heavy aprons

Gastrointestinal radiology – E. Lindemann – bismuth contrast agent in 1905

JOHN MACINTYRE – describe kidney stones radiologically

WILLIAM COOLIDGE – 1913 – NEW LAMP = COOLIDGE TUBE - with improved cathode structure
- “mother of all lamps” – more intense visualization of deeper structures in body
- emitted more rays and was able to control intensity

KAROL MAYER – rudiments in X-ray tomography

- moving x-ray tube during examination to limit visibility of shadows form other organs as much as possible,
while extracting recorded shadow of myocardium

1921 – ORIGIN OF TOMOGRAPHY – ANDRE BOCAGE – presented theoretical principles of tomography

ALBERT SALOMON – invents MAMMOGRAPHY (1913)

- demonstrated spread of breast cancer tumor to axillary lymph nodes

EGAL MONIZ – developed cerebral angiography (1927)

- also came up with the lobotomy

LAZZARO SPALLANZANI – discovery of ultrasounds via bat experiments

- first experiments that led to discovery of ultrasounds
- studies on bats – navigating in darkness just fine when blinded (1794)
LOUIS JURINE – plugging ears of bats caused total disorientation in bats

History of SONAR
1826 – Jean-Daniel Colladon – underwater bell – determine speed of sound in waters of Lake Geneva
1876 – Francis Galton – generated high frequency sound waves above level of human hearing – the Galton
Whistle
1880 - Piezo-electric effect in certain crystals - Pierre and Jacque Curie
1912 – first underwater sonar detection systems for navigation
Paul Langevin & Constantin Chilowsky – powerful high frequency ULTRASONIC echo sounding device
- Langevin noted destruction of school of fishes and record pain in hand when placed in tank of water
ultrasounded with high intensity waves

RADAR
1924 – Edward Appleton – used radio echoes to determine height of ionosphere
1935 – Radio Detection and Ranging system (RADAR) = active
1930’s – pulse-echo ultrasonic metal flaw detectors – originally used to check integrity of large ships

Medical ultrasounds
- Initially ultrasonography used in therapy
- 1920s – destructive powers of high intensity ultrasound recognized

Ultrasound Therapy
- neurosurgical tool
- William Fry and Russel Meyers – craniotomies using ultrasound to destroy parts of basal ganglia in patients
with parkinsonism
- 1953 – Jerome Gersten – ultrasound for rhematic arthritis

- 1940 – H. GOHR & Th. WEDEKIND – ultrasonic diagnosis based on echo-reflective methods similar to that
used in metal flaw detection
- KARL THEO DUSSIK – first experimental work conducted in ultrasound diagnosis field (1940)
- first important experiments with ultrasonic generator applied to medical diagnostic – 1940

DUSSIK EXPERIMENTS (1940s)

- locate brain tumors and cerebral ventricles by measuring transmission of ultrasound beam through the skull
1942 – Dussik presents results – method called hyperphonography
1948 – Dussik and Keidel – present papers to congress of ultrasound in medicine on medical diagnosis
1951 – Andre Denier – book – “Les ultras-sons appliques a la medicine”
1950 – GEORGE LUDWIG – Ultrasonic Locator device = first ultrasonic device for commercial use

1950 - WILD & NEAL

- unidirectional A-mode ultrasound investigations – to test thickness of surgical intestinal material and
properties of gastric malignancies
- noted that malignant tissue was MORE ECHOGENIC than benign tissue
1952 -WILD & REID build linear hand-held B-MODE instrument
1953 – Wild & Reid produce real-time images at 15mHz of cancerous growth of the breast
- introduced notions of “echography” and “echometry”
1956 – use linear B-mode for breast pathology examination

1952-53 - DOUGLAS HOWRY – two-dimensional cross sectional images of the body

1954 – SOMASCOPE – the effective scanner introduced – somagrams obtained

1954 – Howry and Holmes – elaborate on cross-sectional echography - principle of compound scanning –
moving transducer in two different motion pictures simultaneously

1957 – “Pan-scanner” – rotating transducer in a semicircular arc around patient

- filled with saline solution while transducer rotated through saline solution

1958 – IAN DONALD – built first successful ULTRASOUND DIAGNOSTIC MACHINE

1965 – REAL TIME SCANNERS – sold on the market

First real-time scanner = Fast B scanner – Walter Krause and Richard Soldner
1953 – Carl Hellmuth Hertz – correlation b/w movements of echo signals and heart activity
Hertz and Inge G. Edler - recorded first moving pictures of the heart – ULTRASOUND CARDIOGRAPHY
- October 1953 = first recorded echocardiogram (Hertz, Edler)

Doppler Sonography
Shigeo Satomura – developed first Doppler ultrasonic machine for clinical diagnostics
1959 – Robert Rushmer and Dean Franklin – used Doppler effect to measure blood flow

George Charles de Hevesy – method of radioactive tracers to study chemical processes – metabolism
1923 – Hevesy – study on use of radioactive lead tracer to follow chemical process in plants
Geroge Charles de Hevesy = PIONEER of RADIOACTIVE TRACER METHOD

ERNEST ORLANDO LAWRENCE – Father of nuclear medicine

- 1930 – Lawrence built cyclotron = origin of nuclear medicine
- 1936 – John H. Lawrence – first clinical application of radionuclide phosphorus-32 for leukemia
- 1946 – Sam Seidlin – radioactive iodine (I-131) successful l in treating thyroid cancer

1949 – BENEDICT CASSEN - first scintiscanner – creates images for detection of radioactivity within body

DAVID EDMUND KUHL – POSITRON EMISSION TOMOGRAPHY (PET)

Lecture 11 - History of hygiene and social medicine

• Hygieia
o The word hygiene comes from the name Hygieia, the Greek goddess of health, the “keeper
of health and honest life”
o Hygieia can be seen as a source of preventive actions aimed to guard health itself

• Hippocrates
o In Antiquity it was Hippocrates who was first to point, that soil conditions, quality of air and water
and the climate itself can deeply influence everyday life
o Diseases are primarily associated with environmental factors, diet, and habits
o In some respect works of Hippocrates can be taken as the fundamental for modern
environmental medicine

• Babylonians
o Babylonians were mixing water, cassia oil and alkali, which created a primitive soap
o The use of oil and a scraper, known as a strigil, was a more common way of cleaning the skin in
the Greek and Roman cultures
o Probably the first bath tubs were invented in Minoan Crete

• Sewage problem
o Sewage was always a problem, especially when humans started to settle in bigger groups
o The Romans built special sewers to collect rainwater and sewage
o The Romans even had a goddess of sewers called Cloacina
o Cloaca Maxima = one of the world’s earliest sewage system

• Lex Regia- known as the earliest Roman law concerning health matters, coming from the 8th
century BC
o The temple to Aesculapius was built so the sick would flock in order to get some healing
o It was built on an island on the Tiber river

• Public health case - Archiatri

o Archiatri medici publici had many privileges and besides their state salaries, they were also
paid well by prosperous private patients
 o There were also physicians dedicated to care of slaves and gladiators, and of course surgeons
serving in Roman Army

• Bath and aqueducts

o One of the most important public baths was the Baths of Caracalla, were built by Emperor
Caracalla between 212-216 AD
o Rome’s first aqueduct, the Aqua Appia, was built in 312 BC
o The water supplies were under permanent control
o Probably the first bath-tubs were invented in Minoan Crete

• Aqueducts and canalization system

o Romans were masters in organization of social life
o They built hundreds of km of aqueducts to obtain fresh water
o They also made their capitals very first fully canalized city in the world
o Systems of Terms (Baths) was common in whole empire
o There is little doubt that it was a time of rudiments for public and social medicine were born

• From where the devil comes?

o One major source of infection was bites from fleas and body lice
o In medieval Europe, infectious diseases easily spread by insects like fleas and body lice
o Another source for infection, especially in medieval times, was the use of rushes/straw on the
floors
o There was an obvious lack of canalisation and fresh water supplies in many medieval towns and
cities
• Simple and healthy life
o Diet, some medicaments and gymnastics were the practical remedies for keeping good health
and long life
o The fabric and color were most important if we concern cloth, much more that their cleanness
o In many households one could find wooden tubs for bathing

• Personal Hygiene
o From the 13th century in most cities there were public baths
o Organizing parties and having there good music and food was not a rare practice in
bathhouses, which were often named by moralists as sinful places

• Lice Problem
o Regimen Sanitatis Salernitanum (the Salernitan Rule of Health) was a popular advisor on
hygienic matters from medieval to modern times
o Combing the lice of hair was most common procedure used widely until 19th century in Europe
o The other method was to pick them up one by one with your own fingers
o Lice were permanent and unwanted inhabitants in human settlements

• Islamic civilization
o Islam stressed the importance of cleanliness and personal hygiene
o It was closely connected with religious habits and Islamic law
o Regular bathing and purification were obligatory

• Leper- Leprosy
o Probably the smallpox and leprosy were one of most ancient diseases affecting social life in
antiquity
o The oldest traceable evidence of leprosy dates back to ancient Egypt
o We find some discussion on it in Hippocratic texts
o The real nature of this horrible illness remained obscure for many millennia
o Therapy included often mercury or arsenic, sometimes such strange medications as elephant’s
teeth
• Mycobacterium leprae
o The causative agent of leprosy, Mycobacterium leprae, was discovered and for the first time
shown by G.H. Armauer Hansen in Norway in 1873

• The Regents of the Leper Hospital in Haarlem (1667)

o In Europe the pick of Leper problem was to be observed between the 11-15th century
o The strict isolation was the only solution and hundreds and then thousands of Lazar houses
were built in European cities and towns
o There were also closed villages for sick
o The strict rules were here erected and if the ill person did not obey them she or he had to leave
this place
o Any contact with healthy people was strictly forbidden, with exemption made for physicians and
some administrative wards

• Mass of Separation
o In the Middle Ages, many skin conditions were labeled as ‘leprosy’
o Those who had visible skin changes were often diagnosed as leper positive
o They had a choice - enter the Lazarus House (Leprosery) or take lonely life as beggars
o The so named Mass of Separation was conducted
o Ceremony included vowing not to enter any public places
o Leprous persons were forbidden to touch the rim or rope of a well, except with gloved hands
o They were also excluded from inheriting

• Leprosy and society

o They could not wash their clothes on the river banks above the cities
o They could not work with healthy people
o On approaching towns, cities, or villages they were ordered to ring small bells or even better
use rattle so they were bringing attention to their presence

• Hansen’s disease
o In the 18th century the hansen’s disease is slowly moving out of Europe
o In the 19th virtually disappeared in Western and Central Europe with some few exceptions
o Nevertheless it was leprosy which has one of the earliest impacts on what we can name social
health organizations
o But it was and still is present in other parts of the world

• Modern Treatment
o In 1981 The World health Organization began recommending MDT, a combination of three
drugs: dapsone, rifampicin, and clofazimine
o MDT with these drugs takes from six months to a year or even more, depending on strength of
leprosy infection

• Black Death – killed 30% of whole European population

o The Black Death was, as far as we know, the most devastating of pandemics in history
o It started in China and traveling by Silk Road to Crimea on spring year 1346
o Around 1347 was in Italy, reaching peak between 1348 and 1350 (14th century)
o Giovanni Bocaccio = Italian poet – gave written evidence of Black Death’s lethal force

• Starting point
o Most likely it was carried by oriental rat fleas living on the black rats
o Those animals were regular passengers on merchant ships traveling on Mediterranean Sea
o Researchers had estimated that the plague reached Sicily in October 1347 when twelve
Genoese galleys came here with goods from the East

• Dance macabre
 o We know that this plague could be a result of infections coming from Yersinia pestis bacteria
o Historians were pretty sure that it killed over 30% of European population
o It attacked many times in XVII century: Italian plague (1629-1631), the Great plague of Seville
(1647-1652), the great plague of london (1665-1666) and the great plague of Vienna (1679)

• Playing with death

o Washing walls and furniture, then bodies, with rose water or vinegar, was credited as a
preventative method
o Wearing garlands of flowers was seen by others a solution to the problem
o Many believes they could ward off illness if they did not eat, drink, or exercise too much
o Others were dancing, wearing colorful clothes, playing loud music to scare the evil away
o All were praying to God

• Here comes Plague

o Today we know three different type of plague
o The first one named Bubonic plague affects the lymph nodes
o Normally within 3 to 7 days of exposure to plague bacteria the first symptoms occur
o In the beginning ill person has flu-like symptoms such as fever, headache and chills
o Then comes pain of muscles and weakness
o Finally buboes can be clearly seen on the person’s body

• Septicemic Plague
o Symptoms include fever, chills, weakness, abdominal pain, shock, and bleeding underneath the
skin or in other organs
o Buboes, however do not develop
o Septicemic plague is rarely spread from person to person

• Pneumonic plague
o Symptoms usually develop within 1 to 3 days after exposure to plague bacteria
o Pneumonia is attacking quickly, with shortness of breath, chest pain, and cough
o Other symptoms include fever, headache, and weakness
o Only this form of plague is highly contagious

• Was Black Death then really a plague?

o There are serious doubts about real nature of disease which massacred Europe’s population
and which is traditionally connected with Yersinia pestis bacteria
o Most written evidence coming from the Times of Black Death fits its buboes form, so form of the
lowest contagious effect
o It just could not slaughter millions of people in relatively short time
o Some written testimonies are close to description of septicemic form

• Looking for Explanation

o It is possible that plague in Times of Black Death was different from forms which we know today
o Infection done by Yersinia pestis bacteria could have other nature
o However we must admit that bacteria is organism of rather stable construction and are not
suitable target for evolution process
o Ability tro fast reduplication and mutation is given virus
o Is it then possible that balck Death was a “lethal job” of some unknown to us virus?

• Was a balck Death a Medieval Ebola?

o The Great Influenza Pandemic in 1918 could kill even up to 100 million people, that is 55 of
the whole human population on globe
o It was fast and deadly and medicine was helpless in the same way as it was in 1347
o It out Times AIDS has killed over 25 million individuals and now we are facing threat from Ebola

• Balck Death could be caused by a Virus?

 o If we examine all data coming from the medieval times we must admit that symptoms then
observed are very close to that which we observe today when diagnosing people with positive to
EBVO (Ebola disease)
o Fever, headache, joint and muscle aches, weakness, chest pain, difficulty breathing and internal
and external bleeding
o It fits to most of symptoms observed during Black Death
o Even characteristic buboes are often present

• In the bone remains coming from the times of Black Death and latter plagues we can find evidence of
Yersinia pestis bacteria
o There is little doubt, that is should be blamed for the pandemic between 1347-1350
o But there is a possibility that yersinia pestis bacteria has an allay in its lethal job who remains
still unknown to us

• Plague doctors – mercenaries hired by city and town authorities

o A plague Doctor’s special uniform consisted of hat, bid-head shaped mask, a long overcoat,
gloves and shoes and wooden cane
o No doubt that it is first biohazard suit protecting physician in death zone

• Medico della peste, Pestarzt, Plague Doctor

o They weren’t just ordinary physicians, but in some sense “mercenaries” ready to serve for the
money to anyone and everywhere
o Hired by towns, when plague was near they played important role in the community
o The job was dangerous so the salaries were usually high
o Nobody really asked about their skills or knowledge, so their professional training left a lot to be
desired

• Smallpox
o Smallpox infection started within two weeks after exposure to the Variola virus
o Typical symptoms are fever and lethargy. Headache and vomiting were common as well
o Characteristic was fast raising rash which appeared on the skin all over the body
o Then sores were formed inside the mouth, throat, and nose
o Fluid-filled pustules would develop and expand covering large areas of skin
o In about the third week of illness, scabs are formed and then seperate form the skin

• Syphilis
o Exact origin of syphilis remains to us unknown
o One theory point on America from were syphilis was carried to Europe by the crew members of
Christopher Columbus ships
o Other researchers believe that it was present in European population but was not properly
diagnosed and recognized

• French Disease, Lues = congenital syphilis

o An outbreak of syphilis in Europe is of the late date and occurred during winter 1494/1495 in
Naples, Italy
o It was a time when French troops start to march back home after hard and bloody siege of
Naples
o It was that time when new illness got its name- “French disease”
o The second name- Lues- was given often given to it

• Syphilis or Morbus Gallicus

o In 1530 Italian physician and mathematician Girolamo Fracastoro wrote a poem in Latin entitled
Syphilic sive mobus gallicus
o It was a history of a young shepherd named Syphilus who insulted Greek god Apollo
o Angry Apollo punished him with a unknown but terrifying disease
• Syphilus and Stars
o Is this man on Albrecht Dürer’s drawing suffering from Morbus Gallicus (French disease)?
o If so it would be one of earliest graphical representation of this disease
o Dürer was accusing “conjunctions of planets” as responsible for this illness

• Phthisis
o Phthisis was the Greek word for Tuberculosis (TB)
o TB was probably present in prehistoric Times
o Earliest description of it was given in written form in ancient India and China
o Hippocrates made several important observations on TB nature

• Consumption
o In the Middle Ages that so named scrofula were described as disease affecting cervical lymph
nodes
o Because TB had devastating effect on the physical body condition, it gained a name-
Consumption
o The name Tuberculosis was finally coined in the middle of 19th century

• White plague = other name for tuberculosis

o In 18th century TB cases were growing in numbers
o The strongly anaemic pallor of people affected by TB triggered the new expression- “White
plague”
o The syphilis and tuberculosis had a great impact on the birth of the medical police

• Medicalization
o Medicine in Enlightenment decame for the very first time implanted to the social network
o The first unknown use of the term “medical police” is credited to German Wolfgang
Thomas Rau (1668-1719)
o The theoretical concept of Medizinischeopolizei so “Medical Police” was born in Germany in
1764, however no practical steps were taken at that time

• Some general idea of Medical Police

o It was a system of global observation of sickness based on data coming from hospitals and
private practice
o The second factor was standardization of medical knowledge and practice as it was done in
French Clinical Model
• Mortality ratio
o Samuel Auguste André David Tissot (1728-1797) was an author of Advice to people about their
health (1761) which became one of most popular books on healthy life in 18th century
o It had many editions and was translated to many languages
o It was focused on the lifestyle and environment as the main factors deterring quality of health
• Joseph Ignace Guillotin
o French physician Joseph Ignace Guillotin (1738-1814), for whom the guillotine was named,
insisted that all medical practice, medical education, health police, sanitary services and the
control of disease should be under the supervision by a permanent health committee
o Health Committee was established and led by Jean Gabriel Gallot, had jurisdiction over dieases
control and practice of inoculation against disease such as smallpox
• Health under control
o The great reform of the monarchy which was carefully planned and realized by Empress Maria
Theresa and her successor Joseph the Second was a right moment for medical police to be
born
o To achieve prosperity of human population and by state’s stability the health matters must be
under permanent governmental control
• Johann Peter Frank (1745-1821) – father of medical police
 o System einer vollständigen medicinishen Polizey (A Complete System of Medical Police), was a
comprehensice-9-volume treatise in which Frank was trying to present all aspects of hygiene
and public health
o Medical police should concentrate on subjects such as public sanitation, water supply issues,
sexual hygiene, maternal and child welfare, foor safety, just to name few main topics
o Frank is often named a “father of medical police”

• Medical Police
o He strongly advocated for necessity of medical police as a practical representation of the
responsibility of the state powers
o Formal system of public and private hygiene laws was seen as most valid and important
o Permanent control, regulation and police enforcement were the proper tools to achieve goals
o He was arguing after Valve of a person and the advantages of the population
o Frank advocated for government action aiming at the security and increases of the population
(form womd to tomb” (Rosen)
o Frank’s idea was to build stable but flexible system of health care which “could react” to any
threats which can infect society

• Johann Peter Frank’s idea

o Frank’s wish was to build stable but flexible system of health care which “could react” to any
threats which can infect health of society
• Medical authorities
o On the central governmental level in German speaking countries, especially in Prussia, the
system of administrative health control was constructed in which physicians were involved
o In 1817, the Prussian state set up a Veterinärpolizei (veterinary police) alongside a
Medizinische Polizei (medical police0
• The great sanitary awakening
o With increasing urbanization in the 19th century, filthy environmental conditions became
common in working class areas and the spread of disease became rampant
o Illness came to be associated with poor social and envirnoment conditions, as well as low moral
and spiritual way of life
o Cleanliness was embraced as a path both to physical and moral health
• Littering the environment
o In New York, as later as 1865, we can read that “the filth and garbage accumulate in the streets
to the depth sometimes of two or three feet”
o Industrialization, with its growing in numbers workforce and crowded dwellings, produced both a
population suitable for disease to spread and conditions in which disease was more easily
transmitted

• Poor Law Commission 1838

o Edwin Chadwick, a London lawyer, became the secretary of this commission
o General Report on the Sanitary Conditions of the Labouring Population of Great Britain come to
life in early 1840
o To fight disease Chadwick proposed to build a drainage network to remove sewage and waste
o He advocated for a national board of health and local boards in each district. Special medical
officers had to be appointed to accomplish this goal
o Edwin Chadwick = founder of health guarding system in Britain

• Medical Hygiene is born

o Finally in the second half of 19th century the Hygiene, as a specialized branch of medical
sciences came to life
o It became also a part of medical and social education at the same time

• Max von Pettenkofer (1818-1901) - father of modern medical hygiene”

o For him curing the diseases was the last option for physicians, first should be preserving health
and preventing sickness
 o Pettenkofer paid special attention to hygiene of water and air

• New hygiene
o Pettenkofer had studied pharmacy and medicine at the university of Munich
o With permanent application of the experimental method to the field of public health he
constructed new model of hygiene as a truly interdisciplinary subject of studies

• Pettnkofer in Munich
o Pettenkofer was successful in the systematical introduction of hygiene to academic realm
o It was in 1865 when Bavaria introduced hygiene to curriculum of medical studies
o Pettenkofer himself was appointed to the newly created chair and department for hygiene at the
University of Munich

• Hygiene and basic sciences

o Pettenkoffer argued that a healthy life involves clean air, clean water, clean ground, good
clothing, a healthy dwelling and good nutrition, which in its basics repeated the ancient ideas,
but now reworked in the light of physiology, pathology and chemistry

• Contaminated or polluted air

o Contaminated or polluted air was one of main source of health problems
o The very same was spoken by Pettenfoer about physical, chemical and microbiological features
of water
o German physician openly expressed himself as a “Fanatic of clean and fresh water”

• Food hygiene
o Pettenkofer was interested in the food and drink quality, so turned attention on daily menu of the
people which he connected with nutrition problem
o Together with the famous chemist Justus von Liebig and the physiologist Carl von Voit, he was
one of the founders of the Munich School of Metabolic Research
o In Royal Testing Institute for Food and Drugs, founded in 1884 in Bavaria, Pettenkofer
established program for examination of food and drug quality, still important function of modern
hygiene

• Communication
o Communication between experts and society was seen by Pettenkofer as most important
o Pettenkofer made a great effort to make results of hygienic investigations accessible not only to
physicians and professional researchers, but also to ordinary people through popular
publications and open lectures
o He was convinced only proper education and coordinated action can bring in effect healthy life
of society

• First chair and department for hygiene was organized in Munich

Lecture 12: History of natural healing and alternative medicine

• Different than usual medicine

o In modern times alternative medicine can be described as different theories and practice
pretending to achieve the healing effects, however lacking proper scientific grounds to be
proved as therapeutically effective and most often are not tested for side-effect hazards
o Alternative medicine can be described as healing theories and practices without proper
scientific, EBM based protocols

• Alternative way
o Alternative, that is different from main and officially accepted routine procedures, healing acts of
which some were already present in the past
 o For example the so named holistic medicine was rooted deeply in the ancient tradition and can
be seen as a compilation of many ideas coming from different cultures and civilizations

• Alternative as a part of tradition

o The medicine trough ages had some more or less widely accepted methods of diagnostic and
therapy procedures, as uroscopy or bloodletting, however their practical outcome could differ
much depending on skills and accepted theories

• Franz Joseph Gall (1758-1828) – concept of cranioscopy

o German Franz Joseph Gall pioneered in the study of the localization of mental functions in the
brain giving the grounds for a new science which was later named phrenology
o In his schooldays he noticed that his classmate with odd-shaped skull had advanced language
abilities
o It was a starting point for the idea that made a strong connection between mental and physical
factors of human life
• Roots of Phrenology
o Gall became forerunner of the idea named organology, which triggered the theory that the mind
is in fact a collection of independent entities housed withing the brain (Joseph Gall)

• 27 Gall’s faculties
o Gall observed that every skull has its own “geography” composed of bumps and uneven, which
as he speculated, are not just given in random arrangement
o According to Gall there were exactly 27 faculties. Among them were, mechanical ability, talent
for poetry and love of property, and even a murder instinct
o Gall’s cranioscopy later was named phrenology

• Spurzheim and phrenology

o From 1800 Johann Spurzheim who attended Gall’s public lectures was hired as an assistant to
help with public medical demonstrations
o Their cooperation lasted till 1813 when Spurzheim left Gall and went on his own to Brittan
o It was Spurzheim who used term phrenology, which was never accepted by Gall himself

• Physicians evaluating
o Physicians were evaluating theories of Gall as no-scientific at all, speculative and useless in
medical practice
o Finally in Austria Gall’s theories were officially banded
o Nonetheless they were still openly discussed in France and Brittan

• Phrenology after Gall

o However Phrenology was itself coming to the dead end, it was still influencing the next
generations of researchers
o Gall’s theories had an influence both on the Italian criminologist Cesare Lombroso and French
anatomist Paul Broca and was at the beginning of localization theory

• Franz Anton Mesmer (1734-1815) – “animal magnetism” – began experiments in Vienna

o Austrian Franz Anton Mesmer was speaking of the existence of a natural energy
transference, occurring between all animated and inanimate objects- this he called “animal
magnetism”
o He was speculating about existence of energetic tides going through human body exactly like
ocean tubes provoked by moon

• In 1774
 o In 1774 Mesmer claimed that was able to produce an “artificial tide” in his female patient, who
suffered from hysteria, by having her swallow a preparation containing iron and then attaching
magnets to various parts of her body
o But the Mesmer was not crediting magnets as a successful therapy tool
o Instead he claimed that it was his own powers, namely animal magnetism

• Astronomy, magnetism and medicine

o It was 1775 when Mesmer started his collaboration with Hungarian-born astronomer and the
director of Vienna Observatory Maximillian Hell, who became also fascinated with powers of
animal magnetism
o Hell was already practicing with different magnets as a potential source of therapy in the same
time as Mesmer, which was probably influenced by the Hell’s experiments

• Mesmer and exorcisms

o In the same year 1775 Mesmer was invited to Munich, were Academy of Science was
investigating the case of exorcisms performed by Johann Joseph Gassner, a catholic priest,
publicly known for his conviction, that the evil spirit could harm the body as well as the soul
o Mesmer’s opinion was, that the curves were performed by the animal magnetism and nothing
else, but was not willing confronting Gassner himself
o Johann Joseph Gassner = pioneer of modern hypnosis techniques

• In Vienna
o In Vienna Mesmer decided to treat blind Maria Theresa Paradis, who was an Austrian musician
and composer, with good connection with Imperial Court
o Then he moved to Paris
o Here he was struggling to make his theory accepted, but initially he met rather cold welcome

• Flow of energy
o Mesmer understood health as the free flow of the process of life through thousands of chanels
in our bodies, which was close to Chinese concepts of energetic channels with qi energy
traveling through them
o In such situation Mesmer aimed to aid or provoke the efforts of Nature

• Mesmeric seances
o Personality of Mesmer, who was seen by many as charismatic and the “mermeric practices”
were intriguing Parisians
o Aristocrats connected with Royal Court, and then even king himself, were among those
fascinated with ideas of Mesmer

• Animal magnetism researched

o An attempt to demonstrate animal magnetism before a meeting of the Academy of Sciences
failed to convince any of the attendees
o Mesmer’s concepts were neither approved by the Royal Society of Medicine
• In America
o In America one of Mesmer’s follower was Daniel David Palmer who opened Palmer’s School of
Magnetic Cute in state of Iowa, which became operational in 1890’s
o Thatcher’s Chicago Magnetic Company was convincing that iron present in blood is in fact
magnetic conductor of the body
o Wearing a magnetic garments, which company was selling in great numbers, should protect the
health and combat diseases

• The medicine
o The medicine in second half of 18th and the opening decades of next 19th century was
progressing and changing rapidly
 o However, if the therapy and effective curves were taken to consideration the picture was not so
promising
o Nature of tuberculosis and syphilis, which were havocking through society remained a mystery
which was explained on grounds of speculations and no final remedies were given

• Vincenz Priessnitz (1799-1851) = founder of hydrotherapy

o Vincent Priessnitz became convinced that his hydrotherapy method could be used in overall
healing practice
o Priessnitz was a peasant farmer in Gräfenberg who, as popular story tells, he was injured
seriourly when he broke his ribs in an accident with a cart
o He claimed that he cured himself using only pure water
o Various forms of hydrotherapy had been practiced in nearly all ancient civilizations
o However in 16th and then 17th century hydrotherapy was not anymore so popular, although
never totally excluded form medicine

• Prissnitz’s idea
o Priessnitz began healing animals on his farm and in his village. He was in most situations
successful, so he began developing techniques and protocols for healing people
o Pressnitz was convinced that his methods could cure most if not all of illnesses, including
paralysis, insanity and poisoning
o Hi fame was growing fast and now many people from others parts of country were ready to try
priessnitz’s cure
o To treat many diseases, he would wrap the patient in wet bandages and many layers of
blankets to cause heavy perspiration form the heat
o Then patient was instructed to bathe in cold water and drink plenty of water
o He believed that the rapid changes in temperature allowed the pores of the skin to open
and evacuate toxic substances traveling with blood
o Nevertheless there were some voices fully approving his ideas and methods
o Among them was professor Ortel, who strongly advocated after Preissnitz
o Hydrotherapy was becoming popular not only in Austria but in other European countries having
many proponents in France and England, then in United States
o Pressnitz has influenced German Sebastian Kneipp who was also convicted that water had
curative effect on many diseases
o But contrary to Preissnitz was after gentile methods of using it in therapy
o Kneipp was constructing his own, more sophisticated system of healing, in which water cure
was still important but as only one of elements
o The other were exercise, nutrition, herbalism, and the balance of mind and body

o Sebastian Kneipp health system = water and other important factors including exercise,
nutrition, herbalism, balance of mind and body with prayers

• Natural Cure Movement

o Kneipp’s healing program became a part of what was known as Natural Cure Movement of
Germany
o The core of the Natural Cure Movement was to advocate the view that nature should be
respected and to recognize the natural healing powers of sunlight, air, water and earth itself was
here essential

• Origins of Homeopathy (created by Samuel Hahnemann 1796)

o Homeopathy is generally based on the old Hippocratic concept that the body of powers of
nature can cure itself
o It was created in 1796 by Samuel Hahnemann and based on belief that a substance that
causes symptoms of a disease in healthy people would cure similar symptoms in sick people
o This doctrine was expressed in Latin as similia similibus curentur, or in English “like cures like”
 o This was in line with “law of similars”, which was already present in writings of Hippocrates and
Aristotle

• Like Cures Like

o Homeopathy-coined from two Greek words: hómoios meaning “like” mand pathos that is
“suffering”
o Hahnemann’s work The Organon of the Healing Art (1810) can be named fundamental for
homeopathic theory
o By a process he called “proving”, Hahnemann claimed to be able to compile a selection of
appropriate remedies

• Dynamisation and Potentisation

o Hahnemann’s homeopathic dilution was named “dynamisation” or “potentisation”
o It is a process in which a substance is diluted with alcohol or distilled water
o Then solution is shaken, which was called a “succession” procedure
o Succession was to activate the “vital energy” in the diluted substance
o Successive dilutions were aimed to increase the “potency” of the preparation

• Homeopatic America
o In 1835 the first American homeopathic medical school, namely The North American Academy
of the Homeopathic Healing Art, was founded in Allentown, Pennsylvania
o In the early 19th century Homeopathy was introduced India
o Calcutta homeopathic medical college - established in India 1871

• Electricity in Medicine
o Electric shocks were used in medical therapy since antiquity
o 46 AD - Roman physician, Scribonius Largus, personal doctor to Emperor Claudis, was
recommending patients stand on a live black torpedo fish
o In later times, John Hunter - analyzed anatomy and physiology of the torpedo fish
o 1743 - Johann Gottlob Kruger - first recorded treatment of patient by electricity (university
of Halle)
o One year later, former student of Kruger, Christian Gottlieb Kratzestein, reported successful
therapy of paralysis

• Electrotherapy in hospitals
o 1747 - John Wesley promoted electrical treatment as a universal therapy, but his claims were
rejected by mainstream medicine
o First medical treatments using electricity as a clinical procedure = London 1767 at
Middlesex hospital = first hospital to purchase electrostatic machine
o However, one of first papers written on electrical theory was in France 1775

• Electrical therapy
o From 1804 - electrical stimulation was applied to treat mental and neurological disorders
o Italian Giovanni Aldini, pupil of Luigi Galvani, was propagating electrical methods for cure of
diseases and physical disorders
o Went as far as to experiment on human corpses - was convinced he could resurrect the dead
with electrical shocks

• Electro Health
o In 19th century, electric belts and electric baths promised relief from many diseases, especially
those chronic ones
o Electric baths, which passed electric current through patient’s body, were supposed to help cure
processes
o Hundreds of products widely available on market were promising curing everything from cancer
to headaches
• Healing crystals
o Strong belief in magical healing properties of certain crystals was given to many civilizations
o Galen used Hematite to treat headache
o Pliny used crystals (hematite) to deal with blood disorders
o Lapidaries = texts about curative and other powers of crystals - remained popular in medical
realms from medieval to early modern Europe until 17th century
o In modern times, crystal healing is heavily associated with the New Age spiritual movement

• Vitalistic concepts
o The strong conviction about existence of autonomous force which is connecting all living
creatures was already present in antique though
o Vitalistic concepts could differ one from another, but principle that *all living organisms
distinguish themselves fundamentally from non-living entities, because they contain some non-
physical element = vital force
o Pneuma (from Stoic philosophy) = one of earliest scientific concepts which can be associate
with vitalism
o Galen said that in the lungs, penuma is separated from air and mixed with blood, and then
nourishes the internal organs
o Galen’s physiological concepts were easily absorbed by medieval medical though, giving the
grounds for so named ether concepts - idea of a medium, a space-filling substance, which
makes living processes possible

o German researcher Baron Carl von Reichenbach was still convinced that a vital force exists;
1845 coined term “ODIC FORCE”
o This force was somewhere between spiritual and physical
o All plants, animals, and humans are interrelated, as the whole nature is in fact a living entity,
and the special force - the Odic Force - is a connecting power enabling live processes to act
o Followers of Odic Force were convinced that it can be visible in total darkness
o It was shaped as coloured aura surrounding living things, but also crystals and magnets, but
only very sensitive people were able to see it

• Entelchy - Neo-vitalism (Hans Dreish)

o German physician Hans Dreisch claimed there must be some kind of force that can be
characterized as non-spatial, intensive and qualitative - called it entelchy
o Became hallmark of his neo-vitalism

• Neovitalistic medicine
o Term - neovitalism - coined by Johannes Reinke - more “soulful” biology
o Bernhard Aschner was advocating for constitutional therapy - was convincing that all diseases
are connected with suppressed excretory function which in turn affects the humor balance,
which is the core to biological life

• Acupuncture
o Form of alternative medicine
o Core component of Traditional Chinese Medicine (TCM)
o Since theories and practices of TCM are hard to be tested scientifically, acupuncture is on the
edge of modern medicine
o Cochrane Foundation - specializing in the collecting and systematizing of EDM data - reporting
that acupuncture is NOT effective for a wide range of conditions

o Most historical evidence shows that acupuncture began in China

o First widely approved texts dealing with theory of acupuncture credited to YELLOW EMPEROR
= greatest reformer of medicine in China
o Next major work written during reign of Ming Dynasty
o Entitled “The Great Compendium of Acupuncture and Moxibustion” formed the ground for
modern acupuncture
 o Describes full set of 365 points that represent the openings to channels (MERIDIANS)
through which needles could be inserted to modify the flow of Qi energy
o This became the standard rule for nearly all theoreticians and practitioners

• Needles
o Were probably originally made of bones or carved from flint stone
o Some evidence of obsidian as possible material
o Copper, bronze, and then iron needles introduced
o ***Most important needles made from Gold and Silver

• Moxibustion
o Belongs to traditional Chinese medicine therapy which relies on burning dried mugwort on
selected points on body
o Moxa should warm regions and meridian points with the intention of stimulating circulation flow
of blood and qi energy transport
o Half-legendary Chinese physician Bian Que - first specialist in moxibustion (500 BC)

o 1614 - Fernam Mendez Pinto wrote a book “Pilgrimage of Fernam Mendez Pinto”, where
acupuncture was mentioned
o 1680 - first valuation of acupuncture was done by Dutch physician Willem Ten Rhijne, employed
by the Dutch East India Company

• Acupressure
o Also originated in ancient China
o Less invasive than acupuncture
o For many showed superior therapeutic potential against numerous disease conditions