History And Evolution Of Pathology Notes

Introduction To Common Terms And Definitions

Study Of Pathology:

The word ‘Pathology’ is derived from two Greek words – pathos (meaning suffering) and logos (meaning study). Pathology is, thus, the scientific study of changes in the structure and function of the body in disease.

Read And Learn More: General Pathology Notes

In other words, pathology consists of the abnormalities in normal anatomy (including histology) and normal physiology owing to disease.

• Another commonly used term with reference to study of diseases is ‘pathophysiology’ (patho=suffering, physiology=study of normal function).
• Pathophysiology, thus, includes study of disordered function (i.e. physiological changes) and the breakdown of homeostasis in diseases (i.e. biochemical changes).
• Knowledge and understanding of pathology is essential for all wouldbe doctors, general medical practitioners, and specialists because unless.
• They have knowledge and understanding of the scientific basis of diseases and the language used in pathology laboratory reports, they would not be able to treat patients and prevent diseases which are the two ultimate goals of all doctors.
• For the student of any system of medicine, the discipline of pathology forms a vital bridge between the initial learning phase of preclinical sciences and the final phase of clinical subjects.
• The role and significance of learning of pathology in clinical medicine are quite well summed up by Sir William Osler (1849–1919), acclaimed twentieth-century physician and teacher in medicine regarded as ‘Father of Modern Medicine’, by his famous quote “Your practice of medicine will be as good as is your understanding of pathology”.

Health And Disease:

Before there were humans on earth, there was a disease, albeit in early animals. Since pathology is the study of disease, then what is disease? In simple language, disease is the opposite of health i.e. what is not healthy is disease.

• Health may be defined as a condition when the individual is in complete accord with the surroundings, while the disease is loss of ease (or comfort) to the body (i.e. disease).
• However, it must be borne in mind that in health there is a wide range of ‘normality’ for example, In height, weight, blood and tissue chemical composition, etc.
• It also needs to be appreciated that at the cellular level, the cells display a wide range of activities within the broad area of health similar to what is seen in diseased cells.
• Thus, a disease or an illness means a condition marked by pronounced deviation from the normal healthy state. The term syndrome (meaning running together) is used for a combination of several clinical features caused by altered physiologic processes.

Common Terms For the Study Of Diseases:

It is important for a learner of the study of diseases to be familiar with certain commonly used terms:

• The patient is the person affected by the disease.
• Lesions are the characteristic changes in tissues and cells produced by disease in an individual or experimental animal.
• Pathologic changes or morphology consist of examination of diseased tissues.
• These can be recognized with the naked eye (gross or macroscopic changes) or studied by microscopic examination of tissues.
• Causal factors responsible for the lesions are included in the etiology of the disease (i.e. ‘why’ of disease).
• The mechanism by which the lesions are produced is termed the pathogenesis of the disease (i.e. ‘how’ of the disease).
• Functional implications of the lesion felt by the patient are symptoms and those discovered by the clinician are the physical signs.
• Clinical significance of the morphologic and functional changes together with results of other investigations help to arrive at an answer.
• To what is wrong (diagnosis), what is going to happen (prognosis), what can be done about it (treatment), and.
• Finally, what should be done to avoid complications and spread (prevention) (i.e. ‘what’ of disease).

History And Evolution Of Pathology

The history of pathology has deep roots in common with other medical specialties. Since the beginning of mankind, there has been a desire and need to know more about the causes, mechanisms, and nature of diseases.

• The answers to these questions have evolved over the centuries — from supernatural beliefs to the present state of our knowledge of modern pathology.
• Due to advancements in neighboring branches of medicine and owing to technological developments.

The history and evolution of pathology are traced sequentially under the following headings:

1. From prehistoric times to the medieval period,
2. Human Anatomy and Era of Gross Pathology,
3. The era of technology development cellular pathology, and modern pathology.

1. Prehistoric Times To Medieval Period:

Present-day knowledge of primitive culture which was prevalent in the world in prehistoric times reveals that religion, magic, and medical treatment were quite linked to each other in those times.

• The earliest concept of disease understood by the patient and the healer was the religious belief that disease was the outcome of a ‘Curse From God’ or the belief in magic that the affliction had a supernatural origin from the ‘Evil eye of spirits.’
• To ward them off, priests through prayers and sacrifices, and magicians by magic power used to act as faith healers and invoke supernatural powers and please the gods.
• Remnants of ancient superstitions still exist in some parts of the world. The link between medicine and religion became so firmly established throughout the world that different societies had their gods and goddesses of healing;

For example, Mythological Greeks had Aesculapius and Apollo as the principal gods of healing,

• Dhanvantri is the deity of medicine in India and orthodox Indians believe in Mata Sheetala Devi as the pox goddess. The insignia of healing, the Caduceus, having a snake and staff, is believed to represent the god.
• Hermes or Mercury, according to Greek mythology has the power of healing since a snake has regenerative powers expressed by the periodic sloughing of its skin. The God of Greek medicine, Aesculapius, performed his functions with a staff having a single serpent wound around it.

Later (around AD 1800), however, the Caduceus got replaced with twin-serpents wound around a staff topped by a round knob and flanked by two wings and now represents the symbol of medicine instead of cross

The earliest historical documentation of disease comes from remnants of 5,000 years old. Egyptian papyri contained little and limited recorded information on pathologic anatomy from embalmed mummies (papyrus is a thick paper-like sheet made from the stem of a water plant and was used for writing and painting during the ancient Mediterranean world).

• The lasting contribution to anatomy and pathology, however, began around three centuries BC by the Alexandrian Greeks. Philosophical concepts were introduced by great Greek philosophers, Socrates, Plato, and Aristotle, initially for all natural phenomena.
• Subsequently, a rational approach was applied to disease by the methods of observations by Greek healers of the disease led by Hippocrates (460 – 370 BC), the great clinical genius of all times and regarded as ‘The father of medicine’.
• Hippocrates and his school dissociated medicine from religion and magic. Instead, he and his school firmly believed in the study of patient’s symptoms and described methods of diagnosis.
• He recorded his observations on cases in the form of collections of writings called Hippocratic Corpus which remained the mainstay of learning of medicine for nearly two thousand years.
• However, the humoral theory of diseases first proposed by Hippocrates (based on an imbalance of 4 humors in the body—blood, phlegm, yellow bile, and black bile or melancholy) was flawed and later abandoned.
• Hippocrates also propagated rational and ethical attitudes in the practice and teaching of medicine and is revered by the medical profession even today by taking the ‘Hippocratic oath’ at the time of entry into the practice of medicine.
• There is evidence to support that his contemporary Greek scientist Herophilos (335–220 BC) practiced human dissection. Pupils of Hippocrates exported Greek medicine to Rome (now Italy) which controlled the Greek world after 146 BC and, therefore, Roman medicine dominated the field of medicine in ancient
• Europe then. In fact, since old times, many tongue-twisting terminologies in medicine have their origin in Latin language which was the official language of countries included in ancient

Roman Empire (Spanish, Portuguese, Italian, French, and Greek languages have their origin in Latin).

The earliest Roman medical writer was Cornelius Celsus (30 BC–38 AD) who described four cardinal signs of inflammation ‘Rubor et tumor, cum calorie et dolore’ i.e. Redness and swelling, heat and pain, which are learned by every medical student even now.

• Another pupil of Hippocrates and a giant in Roman medicine was Claudius Galen (130–200 AD); he described the ‘crab-like’ growth as cancer and added ‘Loss of function’ as the fifth sign of inflammation.
• Contributed greatly through his enormous writings which directed the teaching and practice of medicine for over a thousand years until the Middle Ages. The hypothesis of disequilibrium of four basic elements in the body (earth, air, water, and fire) in disease is mentioned in ancient.
• Indian medicine books compiled about 200 AD —Charaka Samhita, the finest collection by Charaka on medicine listing 500 remedies, and Sushruta Samhita, a similar book of surgical sciences by Sushruta.
• The period between Galen and the Middle Ages was influenced by Arab physicians, dominated by the greatest writer of Arab medicine Avicenna (980–1037 AD) which continued to be followed until the fifteenth century.
• The end of the Medieval period was marked by backward steps in medicine. There were widespread and devastating epidemics that reversed the process of rational thinking again to supernatural concepts and divine punishment for ‘Sins.’
• The dominant belief propagated during this period was that life was due to influence of vital substances under the control of the soul (theory of vitalism).

2. Human Anatomy And Era Of Gross Pathology:

The backwardness of the Medieval period was followed by the Renaissance period i.e. revival of learning.

The Renaissance began in Italy in the late 15th century and spread to the whole of Europe: 

During this period, there was a quest for advances in art and science. Since there was freedom of thought, there was an emphasis on philosophical and rational attitudes again.

The beginning of the development of human anatomy took place during this period with the artworks and drawings of human muscles and embryos by famous Italian painter

• Leonardo da Vinci (1452 – 1519):  This led to the emergence of several brilliant and renowned anatomists in the sixteenth century who described pathological structures by their names. Vesalius (1514 – 1564) introduced human dissection on freshly executed criminals.
• His pupils were Gabriel Fallopius (1523 – 1562): Who described human oviducts (Fallopian tubes), and Fabricius who discovered lymphoid tissue around the intestine of birds (bursa of Fabricius). Further popularised the practice of human anatomic dissection for which special postmortem amphitheaters came into existence in various parts of ancient Europe.
• William Harvey (1578 – 1657): William Harvey Published his concepts on causes of disease by describing the circulation of blood and the function of the heart and demolished the humoral theory of diseases prevailing for about 1500 years.
• Antony van Leeuwenhoek (1632 – 1723):  A cloth merchant by profession in Holland, during his spare time invented the first ever microscope by grinding the lenses himself through which he recognized male spermatozoa. As tiny preformed men (or “homunculi”) and other unicellular organisms which he called animalcules. He is known as ‘the father of microbiology’.
•  Marcello Malpighi (1624 – 1694):   Marcello Malpighi used a microscope extensively and observed the presence of capillaries and described the malpighian layer of the skin, and lymphoid tissue in the spleen (malpighian corpuscles). Malpighi is known as ‘the father of histology.

Eighteenth-century medicine became more sophisticated:

The credit for the beginning of the study of morbid anatomy (pathologic anatomy) goes to the pioneering work of Italian anatomic pathologist,

• Giovanni B. Morgagni (1682 – 1771):  Morgagni was an excellent teacher in anatomy, a prolific writer, and a practicing clinician.
  • Through his work, Morgagni demolished the humoral theory of diseases prevailing for about 1500 years.
  • He published his lifetime experiences based on 640 postmortems and their corresponding clinical findings.
  • He, thus, laid the foundations of clinicopathologic methodology in the study of disease and introduced the concept of clinicopathologic correlation (CPC).
  • Establishing a coherent sequence of cause, lesions, symptoms, and outcome of disease.  Morgagni is known as ‘the father of CPCs’.

•  Sir Percivall Pott (1714 – 1788): A famous surgeon in England, described arthritic tuberculosis of the spine (Pott’s disease). And identified the first ever occupational cancer (cancer of scrotal skin) in the chimney sweeps in 1775. And discovered chimney soot as the first carcinogenic agent.
• John Hunter Or father Of Museum In Pathology:   Two pioneering Hunter brothers from England – John Hunter (1728 –1793). An extraordinary student of Sir Percivall Pott, the greatest surgeon-anatomist of all times.

• • And his elder brother  William Hunter (1718 –1788), a reputed anatomist-obstetrician.
  • Together started the first-ever museum by collecting of surgical specimens from their flourishing practice, arranging them into separate organ systems.
  • Made comparison of specimens from animals and plants with humans, and included many clinical pathology.
  • Specimens as well, and thus developed the first museum of comparative anatomy and pathology in the world.
  • Presently as the Hunterian Museum at the Royal College of Surgeons in London
• John Hunter was Edward Jenner (1749–1823): Among many pupils of whose work on inoculation in smallpox is well known. Another prominent English pathologist
• Matthew Baillie (1760–1823): The nephew of the Hunter brothers published the first-ever systematic textbook of morbid anatomy in 1793. The era of gross pathology had three more illustrious and brilliant physician-pathologists in England who were colleagues at Guy’s Hospital in London
•  Richard Bright (1789–1858):  He described kidney disease with edema, later termed glomerulonephritis or Bright’s disease
•  Paul Ehrlich  Or Father Of Clinical Pathology (1854–1915):  German physician, conferred the Nobel prize for his work in immunology, described Ehrlich’s test for urobilinogen, staining techniques of cells and bacteria, and laid the foundations of hematology and clinical pathology

• Thomas Addison (1793–1860):   Who gave an account of chronic adrenocortical insufficiency (Addison’s disease) and first recognised pernicious anemia; and
• Thomas Hodgkin (1798–1866):  They observed the complex of chronic enlargement of lymph nodes, often with enlargement of the liver and spleen, later called Hodgkin’s disease.

Towards the end of the 18th century:

• Xavier Bichat (1771–1802):  An army surgeon in France during the French Revolution, got permission to investigate the guillotined bodies and observed that organs were composed of 21 types of tissue, thus laying the foundation of tissue-based disease.
• R.T.H. Laennec (1781–1826):  Another French physician, dominated the early part of the 19th century by his numerous discoveries. He described several lung diseases (tubercles, caseous lesions, miliary lesions, pleural effusion, and bronchiectasis), chronic sclerotic liver disease (later called Laennec’s cirrhosis), and invented a stethoscope.

Thus, up to the middle of the 19th century, correlation of clinical manifestations of disease with gross pathological findings at autopsy remained the major method of study of disease.

3. Era Of Technology Development And Cellular Pathology:

Mid-nineteenth century onwards, the future of pathology was shaped by newer technologies.

• Advances in machinery manufacture for cutting thin sections of tissue, improvement in the microscope, and development of chemical industry and dyes for staining, together with knowledge of the cellular basis of disease, all resulted in pathology developing as a diagnostic discipline.
• The discovery of the existence of disease-causing microorganisms was made by French chemist Louis Pasteur (1822–1895), thus demolishing the prevailing theory of spontaneous generation of disease and firmly establishing the germ theory of disease.
• Subsequently, G.H.A. Hansen (1841– 1912) in Germany identified Hansen’s bacillus in 1873 as the first microbial causative agent for leprosy (Hansen’s disease).
• While the study of infectious diseases was being made, the concept of immune tolerance and allergy emerged which formed the basis of immunization initiated earlier by Edward Jenner. Metchnikoff (1845 – 1916), an earlier by Edward Jenner.
• Metchnikoff (1845 –1916), a Russian zoologist, introduced the existence of the phenomenon of phagocytosis by human defense cells against invading microbes.
• Developments in the chemical industry helped in the switch over from earlier dyes of plant and animal origin to synthetic dyes; aniline violet being the first such synthetic dye prepared by Perkin in 1856. This led to the emergence of a viable dye industry for histological and bacteriological purposes.

The impetus for the flourishing and successful dye industry as applied to pathology came from the works of numerous pioneers:

• Paul Ehrlich (1854–1915):  German physician, conferred the Nobel Prize in 1908 for his work in immunology, described Ehrlich’s test for urobilinogen using Ehrlich’s aldehyde reagent, staining techniques of cells and bacteria, and laid the foundations of clinical pathology
• Christian Gram (1853–1938): Danish physician, who developed bacteriologic staining by crystal violet.
• D.L. Romanowsky (1861–1921):  Russian physician, who developed stain for peripheral blood film using eosin and methylene blue derivatives.
• Robert Koch (1843–1910):  German bacteriologist, besides Koch’s postulate and Koch’s phenomena, developed techniques of fixation and staining for identification of bacteria, discovered tubercle bacilli in 1882 and cholera vibrio organism in 1883.
• May-Grünwald: May-Grünwald in 1902 and Giemsa in 1914 developed blood stains and applied them for the classification of blood cells and bone marrow cells.
• Sir William Leishman (1865–1926):   Described Leishman’s stain for blood films in 1914 and observed Leishman-Donovan bodies (LD bodies) in leishmaniasis.
• Robert Feulgen (1884–1955):  Described Feulgen’s reaction to DNA staining and laid the foundations of cytochemistry and histochemistry. Simultaneous technological advances in machinery manufacture led to the development and upgrading of microtomes for obtaining thin sections of organs and tissues for staining by dyes to enhance the detailed study of sections.
• Rudolf Virchow (1821–1902) Or Father Of Cellular Pathology: German pathologist who proposed a cellular theory of disease and initiated biopsy pathology for the diagnosis of diseases.

• Karl Landsteiner (1863–1943) Or Father Of Blood Transfusion: An Austrian pathologist who first discovered the existence of major human blood groups in 1900 and was the recipient of the Nobel Prize in 1930.

• George N Papanicolaou (1883–1962) Father Of Exfoliative Cytology: Was an American pathologist, who developed a Pap test for the diagnosis of cancer of the uterine cervix.

Employing a microscope, normal cells comprising living tissues were first established by F.T. Schwann (1810–1882), the first neurohistologist.

• Application of this concept on diseased tissues by use of a microscope was simultaneously started by two famed German Pathologists, Carl F. von Rokitansky (1804–1878), and his one-time pupil Rudolf Virchow (1821–1902).
• Although Rokitansky described diseases such as acute yellow atrophy of the liver, diseases of arteries, and congenital heart defects he considered disease states more due to abnormalities in the blood and believed that chemical pathologists might resolve the unknown pathology.
• Ultimately, it was Rudolf Virchow who is credited with the beginning of microscopic examination of diseased tissue at the cellular level and thus began histopathology as a method of investigation.

Virchow hypothesized cellular theory has the following two components:

1. All cells come from other cells.
2. The disease is an alteration of the normal structure and function of these cells.

Thus, pathology from organ-based diseases entered a new era of cell-based diseases. This gave birth to biopsy pathology and thus emerged the discipline of diagnostic surgical pathology which was further propagated by numerous brilliant successive workers.

• For his contribution, Virchow was revered as the Pope of pathology in Europe and is aptly known as the ‘father of cellular pathology’.
• Virchow also described several other pathologic processes, For example, the Etiology of embolism (Virchow’s triad—slowing of blood-stream, changes in the vessel wall, changes in the blood itself), metastatic spread of tumors (Virchow’s lymph node), and components and diseases of the blood (fibrinogen, leukocytosis, leukemia).
• The concept of frozen section examination, while the patient was still on the operation table, was introduced by Virchow’s student, Julius Cohnheim (1839–1884). In fact, during the initial period of development of surgical pathology around the turn of the 19th century, the frozen section was considered more acceptable by surgeons.
• The concept of surgeon and physician doubling up in the role of pathologist which started in the 19th century continued in the early part of the 20th century too in most clinical departments.
• Assigning biopsy pathology work to some faculty member in the clinical department was common practice; that is why some of the notable pathologists of the first half of the 20th century had a background of clinical training For example, James Ewing (1866–1943), A.P. Stout (1885–1967) and
• Lauren Ackerman (1905–1993) in the US, Pierre Masson (1880–1958) in France, and R.A. Willis in Australia.

A few other notable developments in the first half of the 20th century towards our understanding of diseases are as follows:

• Karl Landsteiner (1863–1943): Karl Landsteiner Described the existence of major human blood groups in 1900 and is considered the ‘father of blood transfusion’; he was awarded the Nobel Prize in 1930.
• Ruska and Lorries: Ruska and Lorries in 1933 developed the electron microscope which aided the pathologist in viewing the ultrastructure of cells and its organelles.
• The development of exfoliative cytology for the early detection of cervical cancer began with
• George N. Papanicolaou (1883–1962): George N. Papanicolaou was a Greek-born American pathologist, in the 1930s and is known as the ‘Father of Exfoliative Cytology’.
• Another pioneering contribution to pathology in the 20th century was by an eminent teacher,
• William Boyd (1885–1979): Psychiatrist-turned-pathologist, whose textbooks —‘Pathology for
• Surgeons’ (first edition 1925) and ‘Textbook of Pathology’ (first edition 1932), dominated and inspired the students of pathology for a few generations all over the world due to his flowery language and lucid style.
• M.M. Wintrobe (1901–1986):  A pupil of Boyd who discovered the hematocrit technique, regarded him as a very stimulating teacher.

4. Modern Pathology:

Between the latter half of the 20th century and current times, the pace of discovery has been much more rapid and accelerated the addition of scientific knowledge.

• Advancements in fixation, embedding, section cutting, microscopy, special and immunohistochemical staining, molecular methods image processing, etc have all made it possible to study diseases.
• At a genetic and molecular level, and provide an evidence-based and objective diagnosis that can enable the physician to institute targeted therapy.
• The major impact of advances in molecular biology is in the field of diagnosis and treatment of genetic disorders, immunology, and cancer.

Some of the revolutionary discoveries during this time are as under:

• Discovery of immunofluorescence techniques by Albert Coons in the 1940s.
• The invention of flexibility and dynamism of DNA (jumping genes) by Barbara McClintock in the 1940s for which she was awarded the Nobel Prize in 1983.
• Description of double helix structure of DNA of the cell by Watson and Crick in 1953 and were conferred the Nobel prize in 1962.
• Identification of chromosomes and their correct number in humans (46) by Tijo and Levan in 1956.
• Identification of Philadelphia chromosome in chronic myeloid leukemia by Nowell and
• Hungerford in 1960 was the first chromosomal abnormality in any cancer.
• In situ, hybridization (ISH) was introduced in 1969 in which a labeled probe is employed to detect and localize specific RNA or DNA sequences ‘in situ’ (i.e. in the original place).
• Its later modification employs the use of fluorescence microscopy (FISH) to detect specific localization of the defect on chromosomes.
• The recombinant DNA (hybridoma) technique for the production of monoclonal antibodies was developed in 1972 by Kohler for which he was conferred the Nobel Prize in 1984.
• The introduction of polymerase chain reaction (PCR) i.e. “xeroxing” of DNA fragments by Kary Mullis in 1983 has revolutionised the diagnostic molecular genetics for which he was conferred the Nobel Prize in 1993.
• PCR analysis is more rapid than ISH, can be automated by thermal cycles, and requires a much lower amount of starting DNA.
• Mammalian cloning was started in 1997 by Ian Wilmut and his colleagues at Roslin Institute in Edinburgh, by successfully using a technique of somatic cell nuclear transfer to create the clone of a sheep named Dolly.
• Reproductive cloning for human beings, however, is very risky besides being unethical.
• The era of stem cell research started in the 2000s by harvesting these primitive cells isolated from embryos and maintaining their growth in the laboratory.

There are 3 sources of stem cells in humans:

Embryonic stem cells, amniotic fluid, and adult stem cells.

1. Stem cells are seen by many researchers as having virtually unlimited applications in regenerative medicine and therapeutic cloning.
2. Stem cells have vast potential for the treatment of many human diseases such as Alzheimer’s disease, Parkinson’s disease, diabetes, many cancers, spinal cord injuries, strokes, etc.
3. At some point in time, stem cell therapy may be able to replace whole organ transplants, and instead stem cells ‘harvested’ from the embryo may be used.

Although embryonic stem cells are most numerous, in view of the ethical issues involved, currently stem cell lines from alternative non-embryonic sources have received more attention for example  Reprogrammed adult stem cells and the use of amniotic fluid.

Definitions, History, and Evolution of Pathology:

• Pathology is the study of structural and functional changes in disease.
• Pathologic changes present with clinical features (symptoms, signs) in the patient.
• In pathology, we study causes (etiology), and mechanisms (pathogenesis) and arrive at final diagnosis by various laboratory methods; gross and microscopic examination of tissues is the major method.
• The Caduceus representing ancient Greek gods is the symbol of medicine.
• Understanding of diseases has evolved over the last 5000 years; starting from embalmed
• Egyptian mummies, it was dominated at different times by Greek medicine, Roman medicine, and then by the rest of Europe and the USA.
• Pathology is the study of structural and functional changes Over the centuries, concepts in diseases have progressed from initial observations on the whole body to organ-based diseases, to cell-based diseases.
• The father of medicine’ is Hippocrates; the father of modern medicine’ is Sir William Osler.
• The study of diseases at the cellular level began about 100 years back by Rudolf Virchow who is called the ‘Father of pathology’.
• ‘Father of CPCs’ is Giovanni B. Morgagni; ‘Father of museum’ is John Hunter; ‘Father of clinical pathology’ is Paul Ehrlich; ‘Father of blood transfusion’ is Karl Landsteiner;
• ‘Father of cytology’ is George N. Papanicolaou. Modern pathology involves the study of diseases at the genetic and molecular level too