Understanding diseases: truths exposed by a microscope

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Emergence of a microscope

Origin of microscope is shrouded in controversy. Various traders and workmen used lens for magnification as early as 12th-13th centuries. However, it would take four centuries for first crude microscope to take shape. Some historians claim that Zacharias Janssen invented microscope and telescope between 1580 and 1618. Others believe that it was Galileo in 1609 who described it without really using it. Nonetheless, telescope, useful to seafarers and astronomers became famous earlier, while microscope still had a few years to go. We were on the verge of visualising, many previously unseen particles.

Two scientists, born within years of each other were first to discover joy of visualising tiny fragments of life through a microscope. Antonie Van Leeuwenhoek (1632-1723), and Robert Hooke (1635-1703). Hooke was an English physicist, studied at Oxford, became assistant of Boyle. He coined the term “cell” in his book Micrographia in 1665. This book was a scientific best-seller in its time. In contrast Leeuwenhoek was a Dutch businessman, self-taught in science. Microscopy was his hobby. He was first to identify single-cell organisms, which he called animalcules. He announced his discoveries in letters to British Royal Society, and never wrote any scientific papers. Yet, discoveries made by Leeuwenhoek are path-breaking, as he was the first to find and describe bacteria and protozoa.

Two fathers are born: Pathology and Microbiology

We know Rudolf Virchow, a German physician and pathologist as “Father of modern pathology” and Louis Pasteur, a French chemist and microbiologist as “Father of microbiology”. Both were contemporaries, born within a year of each other in 1821 and 1822 respectively. Virchow coined various medical terms such as leukaemia, embolism, and thrombosis. Some clinical phenomenon named after Virchow include are Virchow’s nodes (a left supra-clavicular lymph nodes) and Virchow’s triad (a triad of stasis, endothelial injury, and hypercoaguable state).

Pasteur and his legacies

Pasteur developed concepts of vaccination, pasteurisation, and germ theory of disease. He, along with Leeuwenhoek and Robert Koch share the title of “father of microbiology” Pasteur was an academic, and by 1857 he had become director of the Grand Ecole University in Paris. Pasteur explained various concepts and introduced new terminologies for the first time. He also coined various terms in chemistry, and was later described as “chemical linguist“.

His concept of molecular asymmetry laid foundation for stereochemistry, now a distinct branch of chemistry. Pasteur performed extensive studies on fermentation of alcohol, to prove that this was all due to micro-organisms. His work on fermentation was genesis for pasteurisation. Pasteurisation, a process described by Pasteur and named after him, revolutionised food industry in the years to come. He proved that microbes are not generated spontaneously. These discoveries led to germ theory of disease, and laid foundation of infectious diseases.

Edward Jenner, developed first human vaccine against small-pox. However, the credit for scientific reasoning behind this process goes to Pasteur. He discovered that bacterial virulence can be reduced. Pasteur helped develop vaccines against cholera, anthrax, and rabies between 1881 and 1885. In 1887, he established Pasteur institute, which he headed until his death in 1895.

How cells work: Metchinikoff and Cajal

Elie Metchinikoff was a Russian biologist. He was inspired by both Pasteur and Virchow. He worked in Odessa in his early years, and at Pasteur institute in Paris after 1888. Metchinikoff discovered phagocytes – tiny cells in tissues that engulf and kill bacteria (a process known as phagocytosis, which he discovered). Discovery of phagocytes won his Nobel prize in 1908. He pioneered concepts of immunity, and beneficial effects of lactobacilli – probiotics.

Ramon Y Cajal was a Spainish histologist, who in 1887 had become interested in neurobiology. He identified various neural cells, axons, and dendrites. His work improved our understanding of nervous system, and how do neural signals work. He was jointly awarded Nobel prize in Medicine in 1906, along with Camello Golgi. Neural cells present in gut (Interstitial cells of Cajal) are named after him.

Legacy of Pasteur and Metchnikoff: Haffkine and Livadetti

Waldemar Haffkine was a Russian-French biologist. He was initially trained under Metchinikoff in Odessa, and later under Pasteur in Paris. Haffkine developed vaccines for Cholera, and later Plague. He put-forth concept of mass-vaccination for Cholera, which was rejected in France, but implemented in India. Haffkine lived in India from 1893 to 1915, where he demonstrated benefits of Cholera vaccine. His plague laboratory in Parel (Mumbai) was renamed in his honour as Haffkine’s institute.

Constantin Livadiiti was a Romanian physician and microbiologist. He worked with Metchnikoff at the Pasteur Institute. In 1909, along with Carl Landsteiner, he discovered Poliovirus. This work would later pave way for development of polio vaccines bye Salk and Sabin. Landsteiner had given concept of blood-groups a few years earlier in 1900, and laid foundation of transfusion medicine.

Age of bacterial discovery

Gerhard Hansen, a Norwegian physician discovered Mycobacterium leprae, causative agent of Leprosy. Hansen announced this discovery in 1873. Hansen however could not prove at that time that these organisms are infectious. He continued to work among patients of Leprosy, and much later the disease was renamed after him. Before this discovery, Leprosy was considered hereditary.

Jean Vincent a French physician discovered a bacteria (Borrelia vincentii) that causes mouth infection. We named this disease after Jean Vincent (Vincent’s angina).

A leap forward: Robert Koch

Foundations of microscopic methods were already in place in 1866, when Robert Koch completed his medical education. Trained as a physician, and after a tenure in Prussian army, he started using microscopy as a hobby. He developed technique of oil-immersion and achieved higher magnifications on microscopy. In 1876, he discovered anthrax bacillus and around the same time developed techniques of growing bacteria in agar-based media. His pathbreaking discovery was of Mycobacterium tuberculosis in 1882. Before this discovery, majority view was that tuberculosis is a hereditary disease. Koch not only identified the organism, he also demonstrated that inoculating the organism in healthy animals produced the same disease. This was the genesis of Koch’s postulates.

From microscopy to molecular

By the end of 19th century, microscopists had shown us the unseen. We knew cause for various diseases. Pathology and Microbiology are two pillars of medical diagnosis today, and continue to unravel previously unknown truths.

Further developments in microscopy were to happen in the second half of 20th century – improved magnification, fluorescent, scanning and electron microscopes. More recent additions are digital magnification and digitisation.

We discovered microbes in late 19th century, and in next fifty years we were treating infections with antibiotics. We could identify molecules, and treat diseases at this level towards end of 20th century. Today, we have moved from microscopic to molecular medicine.