The strides made in the latter half of 20th century until the beginning of 21st century have made it possible to study diseases at molecular level, and provide an evidence-based and objective diagnosis and enable the physician to institute appropriate therapy.
- Description of the structure of DNA of the cell by Watson and Crick in 1953.
- Identification of chromosomes and their correct number in humans (46) by Tijo and Levan in 1956.
- Identification of Philadelphia chromosome t(9;22) in chronic myeloid leukaemia by Nowell and Hagerford in 1960 as the first chromosomal abnormality in any cancer.
- In Situ Hybridization introduced in 1969 in which a labelled probe is employed to detect and localize specific RNA or DNA sequences ‗in situ‘ (i.e. in the original place).
- Recombinant DNA technique developed in 1972 using restriction enzymes to cut and paste bits of DNA.
- In 1983, Kary Mullis introduced polymerase chain reaction (PCR) i.e. ―xeroxing‖ DNA fragments which revolutionized the diagnostic molecular genetics.
- Flexibility and dynamism of DNA invented by Barbara McClintock for which she was awarded Nobel prize in 1983
- In 1997, Ian Wilmut and his colleagues at Roslin Institute in Edinburgh, successfully used a technique of somatic cell nuclear transfer to create the clone of a sheep; the cloned sheep was named Dolly. This has set in the era of mammalian cloning. Reproductive cloning for human beings, however, is very risky besides being absolutely unethical.
- In 1998, researchers in US found a way of harvesting stem cells, a type of primitive cells, from embryos and maintaining their growth in the laboratory, and thus started the era of stem cell research.
- In April 2003, Human Genome Project (HGP) consisting of a consortium of countries, was completed which coincided with 50 years of description of DNA double helix by Watson and Crick in April 1953. The sequencing of human genome reveals that human genome contains approximately 3 billion of the base pairs, which reside in the 23 pairs of chromosomes within the nucleus of all human cells. Each chromosome contains an estimated 30,000 genes in the human genome, contrary to the earlier estimate of about 100,000 genes, which carry the instructions for making proteins
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Developments in chemical industry helped in 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 emergence of a viable dye industry for histological and bacteriological purposes. The impetus for the flourishing and successful dye industry came from the works of numerous pioneers as under:
- Paul Ehrlich (1854–1915), German physician, conferred 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 who, 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-Grunwald in 1902 and Giemsa in 1914 developed blood stains and applied them for classification of blood cells and bone marrow cells
- Sir William Leishman (1865–1926) who described Leishman‘s stain for blood films in 1914 and observed Leishman-Donovan bodies (LD bodies) in leishmaniasis.
- Robert Feulgen (1884–1955) who described Feulgen reaction for DNA staining and laid the foundations of cytochemistry and histochemistry
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INTERSECTING FACT OF VIRCHOW
Until the end of the 19th century, the study of morbid anatomy had remained largely autopsy-based and thus had remained a retrospective science.
Rudolf Virchow (1821–1905) in Germany is credited with the beginning of microscopic examination of diseased tissue at cellular level and thus began histopathology as a method of investigation.
Virchow gave two major hypotheses:
- All cells come from other cells.
- Disease is an alteration of normal structure and function of these cells.
Virchow came to be referred as Pope in pathology in Europe and is aptly known as the ‘father of cellular pathology’
- A few other landmarks in further evolution of modern pathology in this era are as follows:
- Karl Landsteiner (1863–1943) described the existence of major human blood groups in 1900 and was awarded Nobel prize in 1930 and is considered father of blood transfusion
- Ruska and Lorries in 1933 developed electron microscope which aided the pathologist to view ultrastructure of cell and its organelles.
- The development of exfoliative cytology for early detection of cervical cancer began with George N. Papanicolaou (1883–1962), a Greek-born American pathologist, in 1930s who is known as ‗father of exfoliative
cytology
- In the 20th century was by an eminent teacher-author, 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 all over the world due to his flowery language and lucid style for about 50 years till 1970s
