Shiga Toxin: The Legacy of Kiyoshi Shiga and His Pioneering Work in Microbiology

Shiga toxin, named after the Japanese bacteriologist Kiyoshi Shiga, marks a significant milestone in the history of microbiology and public health. In 1897, Shiga made a groundbreaking discovery by identifying the bacterium Shigella dysenteriae as the causative agent of dysentery, a severe and often deadly intestinal infection. Dysentery, characterized by diarrhea, fever, and abdominal pain, was a major public health issue at the time, particularly in regions with poor sanitation. Shiga's identification of the bacterium not only enhanced the diagnosis and treatment of dysentery but also shed light on a broader understanding of bacterial pathogens.

Kiyoshi Shiga's work laid the groundwork for modern bacteriology and infectious disease research. His discovery of Shigella dysenteriae was pivotal in the fight against dysentery, as it allowed for targeted interventions to control the spread of the disease. Beyond identifying the bacterium, Shiga’s research led to the discovery of a potent toxin produced by this pathogen, now known as Shiga toxin. This toxin is a ribosome-inactivating protein that disrupts protein synthesis in host cells, leading to cell death and contributing to the severe symptoms associated with dysentery.

The impact of Shiga’s work extends far beyond his initial discovery. He developed innovative methods for isolating and identifying bacterial pathogens, which have become fundamental techniques in microbiology. His contributions have had a lasting influence on public health, particularly in the development of treatments and preventive measures against bacterial infections. In recognition of his pioneering research, the toxin produced by Shigella dysenteriae was named Shiga toxin, honoring his legacy and enduring influence on our understanding of bacterial diseases and their impact on human health.
Shiga Toxin: The Legacy of Kiyoshi Shiga and His Pioneering Work in Microbiology

Unraveling Glycolysis: A Cornerstone of Biochemistry

The discovery of glycolysis, a fundamental metabolic pathway, has its roots in the 19th century and represents a pivotal achievement in the history of biochemistry. Glycolysis, which is the process of breaking down glucose into pyruvate, was elucidated through the combined efforts of several pioneering scientists. The journey began with the work of French scientist Louis Pasteur, who, in the 1850s, conducted extensive studies on the fermentation process in yeast. Pasteur’s experiments demonstrated that microorganisms, such as yeast, could convert sugars into alcohol and carbon dioxide in the absence of oxygen. His work laid the foundation for understanding how cells extract energy from glucose, even in anaerobic conditions, and marked the first significant step toward unraveling the complex series of reactions that comprise glycolysis.

The pathway was further detailed by three German biochemists: Gustav Embden, Otto Meyerhof, and Jakub Karol Parnas. Their collaborative research in the early 20th century significantly advanced the understanding of this metabolic process. The work of Embden, Meyerhof, and Parnas led to the identification and naming of the Embden-Meyerhof-Parnas (EMP) pathway, now recognized as the most common form of glycolysis. They meticulously mapped out the ten enzymatic reactions that occur during glycolysis, wherein glucose is systematically converted into pyruvate, producing ATP (adenosine triphosphate) and NADH (nicotinamide adenine dinucleotide) as byproducts. ATP serves as a primary energy currency in cells, while NADH is crucial for further energy production in the mitochondria.

Glycolysis is significant because it is one of the most ancient and universal metabolic pathways, present in nearly all living organisms. This universality underscores its evolutionary importance, suggesting that glycolysis emerged early in the history of life. The fact that glycolysis occurs in the cytosol of cells and does not require oxygen makes it a crucial process for energy production under anaerobic conditions, such as in muscle cells during intense exercise or in certain microorganisms that thrive in oxygen-poor environments. The discovery and detailed understanding of glycolysis have had profound implications for biochemistry and medicine, providing essential insights into cellular respiration, energy production, and metabolic disorders. For instance, defects in glycolytic enzymes can lead to various metabolic diseases, including certain forms of anemia and cancer, where glycolysis is often upregulated to meet the high energy demands of rapidly proliferating cells.

The elucidation of glycolysis marked a milestone in biochemistry, highlighting the intricate and efficient nature of cellular processes. It serves as a cornerstone of metabolic studies, forming the basis for our understanding of more complex metabolic pathways, such as the citric acid cycle and oxidative phosphorylation. Despite being discovered over a century ago, glycolysis continues to be a vital area of research, with ongoing studies exploring its regulation, its role in different physiological and pathological contexts, and its potential as a target for therapeutic interventions.
Unraveling Glycolysis: A Cornerstone of Biochemistry

Discovery of vitamin B9

Folic acid (vitamin B9) is important in a number of human metabolic pathways as well as being needed for nucleic acid synthesis, growth and the healthy development of a foetus. Folate and its role in human biochemical functioning was first identified by researcher Lucy Wills in 1931.

Wills was born in 1888, near Birmingham England, and in 1911 became one of the first women in the country to get degrees in botany and geology from Cambridge University.

In 1930, she was working as medical research scientists in India having been especially interested in the problem of severe anemia in pregnant poor textile workers. She became aware that poor female textile workers in India were suffering in large numbers from anemia.

Wills demonstrated amazing accuracy and insistence in her investigation excluding the infectious and parasitic nature of anemia and having come to the conclusion that it was linked to bad monotonous nutrition.

In 1931, her studies in rats suggested two things seemed to help: liver supplements and a spread called Marmite. It’s made from brewer’s yeast and it’s especially rich in B vitamins. Unknown substances possessing antianemic action together with improving the pregnancy outcomes at first was designated as “the Wills Factor”.

It wasn't until late in the 1930s that folates (compounds with the same vitamin activity including naturally occurring folates and folic acid) were discovered to be the active agent in the cure of anemia.

Over time, other names were applied for this essential substance—vitamin M (“necessary for normal hemopoiesis in monkey”), vitamin Bc (“required for chicken growth”), Lactobacillus casei growth factor (“supporting Lactobacillus proliferation”), and vitamin B9.

It was first isolated via extraction from spinach leaves by Herschel K. Mitchell, Esmond E. Snell, and Roger J. Williams in 1941. (“folic” originates from Latin “folium” translating as “a leaf”).

Bob Stokstad isolated the pure crystalline form in 1943, and was able to determine its chemical structure while working at the Lederle Laboratories of the American Cyanamid Company. The cycle of industrial synthesis of folic acid was developed in 1945.
Discovery of vitamin B9

History of brucellosis

Brucellosis is a zoonotic disease of great animal welfare and economic implications worldwide known since ancient times. People with brucellosis may develop fever, sweats, headaches, back pains, and physical weakness. In severe cases, the central nervous system and the lining of the heart may be affected.

Brucellosis-type illnesses were recognized by Hippocrates in his Epidemics writings; the Apostle Paul is considered to have been infected following his being shipwrecked on the Island of Malta.

The prevalence of brucellosis was reported in the Mediterranean region and it was historically related with war campaigns. A British army surgeon, George Cleghorn, documented details of disease in the year 1751 in his literature with the title ‘Observations on the Epidemical Diseases in Minorca from the Year 1744 to 1749’.

The disease was described as a separate clinical entity as early as during Crimean war on the island of Malta. It came to the attention of British medical officers serving on the island after the Crimean War.

In Malta, David Bruce, a British army surgeon, saw first-hand an illness that caused the sufferers’ temperatures to soar to 41 degrees Celsius at night, only to normalize during the day. In 1886 he isolated a cocco-bacillus that he named “Micrococcus melitensis” from the spleen of a man who had died of “Malta Fever”.

The work of Dr Themistocles Zammit in 1905 showed that infected goats transmitted brucellosis and that banning use of their milk would be effective. Themistocles Zammit, a scientific member of the Bruce-led Mediterranean Fever Commission, proved that the reservoir for the organism was goat’s milk.

In 1897, Bernard Bang, a physician-veterinarian, studied a disease of cattle in Denmark referred to as “contagious abortion” and isolated an organism that he named Bacillus abortus.

Evans revealed that Micrococcus melitensis (Brucella melitensis) isolated from cows and pigs belonged to same genus and nomenclature of genus as Brucella was suggested in honor of army Major-General Sir David Bruce.
History of brucellosis

History and discovery of pellagra

Pellagra is a nutritional disorder that occurs as a result of niacin deficiency. The term pellagra is derived from the Italian words “pelle agra” meaning rough skin.

The term “pellagra” derives from the Lombard dialect of Northern Italy and clearly highlights the most readily evident clinical sign of the disease.

It was identified among the peasants, in the Asturia region of Spain by Don Gaspar Casal, Spanish physician. Casal described this nutritionally deficient disease in 1735 as “mal de la rosa” with classic symptoms of dermatitis, diarrhea, and dementia, with death as the eventual outcome.

In his posthumously published encyclopaedic treatise on the “Historia Natural y Medica de el Principado de Asturias” (1762), there is a chapter on “De affectione quae vulgo in hac regione mal de la rosa nuncupatur”, where Casal refers to pellagra using a Spanish designation that refl ected the characteristic sunburn-like skin erythema.

The first publication on the disease appeared in 1755 an 1762, which contained an exact description of the condition; at that time it was ascribed to spoiled maize.

Its appearance in Italy was probably 50-100 years later. The disease continued to be widespread in Italy throughout the nineteenth century, e.g. data from 1862 report 39 000 cases in Lombardy in a population of 2.5 million.

It was not until early in the 20th century that Serbia and Southern Russia could have been described as ‘suffering a heavy visitation’.

The first report in which the term “pellagra” was probably used for the first time, was from Milan, Italy in 1771 when pellagra was given its name, meaning "rough skin".

The name of pellagra attached of the disease was suggested by Frappoli in 1771. He referred to it as of ancient origin at that time and probably identical with the “pellarella” reported in Milan in 1578.

In the first half of the 19th century, the social basis of pellagra became a major focus of attention as shown in the studies of Liberali (1831) on the manic dementia of pellagrins.

Pellagra had disappeared from Southern France by about 1880. After 1900, pellagra decreased greatly in Italy for reasons that are unclear, and by 1916 the disease had almost disappeared in the country

In 1922, Goldberger and Tanner suggested that pellagra was an amino-acid deficiency. For his pellagra studies in the first quarter of this century, Joseph Goldberger an American physician and epidemiologist is considered a hero of American clinical epidemiology.

In 1937 it was discovered that pellagra was caused by a deficiency of the B vitamin niacin (nicotinic acid). The body's synthesis of this vitamin depends on the availability of the essential amino acid tryptophan, which is found in milk, cheese, fish, meat and eggs.
History and discovery of pellagra

The history of Campylobacter

The first description of Campylobacter is believed to have been made in 1886 by Theodore Escherich. He observed and described a non-culturable spiral shaped bacterium, which he found in the colon of children with an enteric disease called “cholera infantum”, he then recognized this bacterial as fast emerging pathogens.

Campylobacter was identified for the first time on February 2, 1906 when two British veterinarians, John McFadyean and Stewart Stockman reported the presence of “large numbers of a peculiar organisms” in Loeffler’s blue-stained smears of uterine mucus of a pregnant ewe.

Campylobacter jejuni is a leading cause of enteritis and enterocolitis, worldwide. Although Theodor Escherich himself provided drawings of campylobacters back in the 1880s, Campylobacter jejuni was not identified until the 1950s.

The genus Campylobacter was first proposed in 1963 by Sebald and Véron, distinguishing them from the “true” Vibrio spp. After that, the study of Butzler raised the interest in Campylobacter by noting their high incidence in human diarrhea.
The history of Campylobacter

Discovery of tuberculosis

The disease of tuberculosis, has been known for centuries. Mummies from the Egyptian pre-dynastic era and the Peruvian pre-Columbian era show typical vertebral lesions. Tuberculosis was well known in classical Greece, where it was called phthisis. Hippocrates clearly recognized tuberculosis and understood its clinical presentation.

The oldest evidence for human tuberculosis was found in a Neolithic infant and woman in a 9000-year-old settlement in the Eastern Mediterranean.

In 1720, for the first time, the infectious origin of tuberculosis was conjectured by the English physician Benjamin Marten, in his publication “A new theory of Consumption.”

Both terms consumption and phthisis were used in the 17th and 18th centuries, until in the mid-19th century Johann Lukas Schönlein coined the term “tuberculosis”.

Understanding of the pathogenesis of tuberculosis began with the work of Theophile Laennec at the beginning of the 19th century and was further advanced by the demonstration of the transmissibility of Mycobacterium tuberculosis infection by Jean-Antoine Villemin in 1865.

Mycobacterium tuberculosis, then known as the "tubercle bacillus," was first described on March 24, 1882 by Robert Koch. Using the methylene blue staining recommended by Paul Ehrlich, he identified, isolated and cultivated the bacillus in animal serum. Finally, he reproduced the disease by inoculating the bacillus into laboratory animals.

Mycobacterium tuberculosis is the etiologic agent of tuberculosis in humans. Humans are the only reservoir for the bacterium. Robert Koch presented this extraordinary result to the society of Physiology in Berlin on 24 March 1882. Further molecular analysis of these very first isolates confirmed the identification of M. tuberculosis and indicated that Koch’s isolates belong to the ‘modern’ lineage of M. tuberculosis.

Clemens von Pirquet developed the tuberculin skin test in 1907 and 3 years later used it to demonstrate latent tuberculous infection in asymptomatic children. In the late 19th and early 20th centuries sanatoria developed for the treatment of patients with tuberculosis.
Discovery of tuberculosis

History discovery of free radicals

Free radicals are chemical species which have unpaired electrons on the boundary (atomic or molecular) orbitals.

The term “radical” was first introduced by Guyton de Morveau in 1786 and later used by Gay-Lussac, Liebig, and Berzelius to indicate groups of atoms which were found unchanged in many substances.

For the first time in 1900, Moses Gomberg, Professor of Chemistry at the University of Michigan, speculated the existence of an organic free radical, triphenyl methyl radical (Ph3C•) in the living system.

He published a sensational article entitled ‘Triphenylmethyl, a case of trivalent carbon’, having initiated a new field in organic chemistry, namely, the chemistry of free radicals in solutions.

The scientific community began recognizing the importance of free radicals in 1929, when Friedrich Paneth and Wilhelm Hofeditz produced the methyl free radical, CH3. They prepared the free radical methyl (⋅CH3), by pyrolysis of tetramethyl lead using an adaptation of the system used by Bonhoeffer to study atomic hydrogen.

Later in 1954, Gershman proposed “free radical theory of oxygen toxicity”, according to which, the toxicity of oxygen is due to its ability to form free radicals.

In the same year, the electron paramagnetic resonance (EPR) studies by Commoner in 1954 confirmed the presence of free radicals in biological materials.

In medicine, understanding free radicals, particularly those formed by oxygen, has illuminated the nature of oxidative stress — damage that results when free radicals form faster than the body removes them. This, in turn, has revealed ways human health can be improved — for example, by using antioxidants.
History discovery of free radicals

Short biography of Gerhard Henrik Armauer Hansen (1841-1912)

He was well known for his pioneer study of leprosy - a prominent disease in the history of human sufferings.

Armauer Hansen was the discoverer of the causative agent of leprosy. Armauer Hansen was born in 29 July 1841 in Bergen, Norway. He entered the University of Christiana to study medicine in 1859. He obtained his degree in medicine in 1866, and completed his internship at the National Hospital in Christiania. After about two years at Bergen’s Leprosy Hospital he underwent a period of study in Vienna, where he became familiar with the ‘germ theory’ of disease.

 

Returning to Bergen, Hansen was by now convinced that leprosy was a specific communicable disease. In 1873, he discovered rod-shaped bodies later identified as M. leprae. He published his observations in 1874. By improving his staining technique in 1879, he was able to show great numbers of rod-shaped bacteria typically aggregated in parallel.

In 1880 Hansen named the organism causing leprosy as Bacillus leprae. When Lehman and Neumann erected the new genus Mycobacterium in 1896, it was transferred to this genus and henceforth ahs be known as Mycobacterium leprae.

He believed that the bacillus was the etiological agent of leprosy, which proved to be true. Hansen’s publication from 1874, Preliminary Contributions to the Characteristics of Leprosy, is the earliest description of a microorganism as the cause of a chronic disease.
Short biography of Gerhard Henrik Armauer Hansen (1841-1912)

Theobald Smith and the discovery of Salmonella

The existence of transmission links between insects and animals, and insects and humans, was demonstrated first by Patrick Manson’s elucidation of the causes of filariasis (1878), second by the discovery of the tick-borne nature of Texas cattle fever by Theobald Smith (1893).

Theobald Smith was better known for his discovery of Salmonella, and also his work of cattle fever.

Salmonella was originally discovered by Theobald Smith (1859-1934) a technician in 1885; however, it was named after the technician’s research leader, Daniel E. Salmon(1850-1914), who was a veterinarian.

Smith isolated what became known as Salmonella choleraesuis from the intestine of a pig. At that time he named the organism “Hog-cholerabacillus.”

French bacteriologist Joseph Leon Marcel Lignieres suggested in 1900 that the group of bacteria represented by the swine-cholera organism should be termed “Salmonella” on honor of Salmon.

Salmonella was known by many names before its official title was chosen, It had been called TPE, or thypoid-parathypus-enteritis. A German bacteriologist name Karl Joseph Eberth referred to it as Eberthella thypi.

Salmonella is the genus name for a bacterium that is responsible for causing illness worldwide. Species in the genus Salmonella are categorized as facultatively anaerobic Gram-negative rods within the family Enterobacteriaceae.
Theobald Smith and the discovery of Salmonella

Influenza virus: History and discovery

While the medical profession had started to recognize flu as an infectious disease in the early 1890s, four decades of laboratory work had failed to determine its cause or put its diagnoses and control on firm laboratory footings. The term “influenza” was coined by an Italian in the mid-1700’s to connote a disease resulting from miasma (bad air).

The human disease is thought to have arisen about 6000 years ago. When the influenza pandemic struck in 1918, most scientists and doctors believed it was caused by bacteria. Killing up to 100 million people worldwide, the pandemic was the deadliest in history.

A human influenza virus was not isolated until 1933. Wilson Smith, Christopher Andrews, and Patrick Laidlaw first identified the virus that causes human influenza. They discovered that they could use ferrets to isolated a ‘filterable virus’ from flu patients and with this research animal, begin to determine flu’s identity as a ‘virus disease’. Their finding was publishing in The Lancet, a British medical journal.

Seven years later, the influenza B various was isolated and 10 years after that influenza virus was isolated.

The twenty-first century’s first influenza pandemic caused by the commonly referred ‘swine flu’ virus strain (H1N1) 2009 has had a major economic impact across the world and accounted for 414,000 confirmed cases and 5,000 death worldwide.

The 2005 completion of the entire genome sequence of the 1918 H1N1 pandemic influenza virus represents both a beginning and an end. Investigators have already begun to study the virus in vitro and in vivo to better understand its properties, pathogenicity, transmissibility and elicitation of host responses.

Influenza virus: History and discovery

Discovery of Mycobacterium leprae by Armauer Hansen

Although by the sixteenth century European physicians and scientist had begun to challenge how Galen described then human body and its illnesses, no one succeeded in replacing his explanation for leprosy until 1873, when Norwegian physical Armauer Hansen described an organism subsequently known as Mycobacterium leprae.

The first known mycobacterium was not M. tuberculosis but one isolated from a skin node of a leprosy patient is a leprosarium in Bergen Norway, described as early as 1873 by Armauer Hansen and later renamed Mycobacterium leprae.

Due to the lack of suitable standing methods, Hansen demonstrated this bacterium a native smear releasing the intracellular by treatment with a hypotonic solution.

Hansen had been conducting research on leprosy because the number of cases of the illness had been increasing in Scandinavia during the nineteenth century.

The name Mycobacterium means ‘fungus-bacterium’ and arose from the characteristic fungus-like produced by the tubercle bacillus when grown on liquid media.
Discovery of Mycobacterium leprae by Armauer Hansen

History of schistosomiasis

Bilharzia or schistosomiasis is more insidious that sleeping sickness, for it is a debilitating disease rather than a killer. It is named after Dr. Theodor Bilharz (1825-62) who is discovered the parasites Schistosoma mansoni and S. haematobium and their small snail hosts in 1851.

Schistosomes have infected man for of over four millennia, Papyrus of Kuhn hieroglyphics were believed to refer to hematurria, a clinical sign of urinary schistosomiasis and the Ebers Papyrus was said to give remedies for its cure.

Bilharzia originated in the waters of the Lake Plateau of East Africa and traveled down the Nile to infect the dynastic Egyptians and their pharaohs.

Schistosome eggs have certainly been found in Egyptian mummies from as early as 1200 BC.

The first avian schistosome life cycle was described by Oiso (1927) for Bilharziella yokogawai from domestic ducks. In the American scientific literature, Cort (1950) was the first to demonstrate that swimmer’s itch was caused by the cercarie of non-human schistomiasis in 1928.
History of schistosomiasis

Sir John Robert Vane and aspirin

Aspirin is the most widely used painkiller in the world. It has been used to treat toothaches, headaches, arthritis, and other painful maladies for 100 years. Credit for influencing physicians to prescribe aspirin for heart problems must be given to Sir John Robert Vane (1927-2004).

In 1971, the Journal Nature published three papers of the group of John Vane, the then Professor of Pharmacology at the Royal College of Surgeons of England.

In his pioneering articles, Vane demonstrated for the first time a new mode of action of aspirin that was able to explain its anti-inflammation and antipyretic actions by one single pharmacology mechanisms: inhibition of biosynthesis of prostaglandins, a group of pro-inflammatory pain mediators.

The action prevents blood from clumping together to produce a clot. Thus aspirin is referred to as an anti-platelet agent that is a mild blood thinner.

John Vane’s breakthrough discovery was followed by several other discoveries which also helped to build up the full picture of how aspirin worked.

These findings of John Vane and the discovery of prostacyclin 5 years later were honored by the Nobel Prize for Medicine awarded to him in 1982.
Sir John Robert Vane and aspirin

History of leishmaniasis

Leishmaniasis is caused by several species of the genus Leishmania called hemoflagellates and is transmitted by sand flies, which are often prevalent in desert areas.

Representations of skin lesions and facial deformities have been found on pre-Inca pottery from Peru and Ecuador dating back to the first century AD. There are evidences that some forms of leishmaniasis prevailed as early as this period.

Also there were descriptions of the oriental sore were found on tablets belonging to King Ashurbanipal in the seventh century BC but were likely taken from information first recorded in 1500-2500 BC.

There are detailed descriptions of oriental sore by Arab physicians including Avicenna in the tenth century, who described it as Balkh sore from Northern Afghanistan, and there are later records from various places in the Middle East including Baghdad and Jericho.

New Word cutaneous and mucocutaneous leishmaniasis was well depicted in fifth century AD sculptures and sixteenth century Spanish missionary writings.

In 1901, Scottish army doctor William Leishman identified certain organisms in smears talent from the spleen of a s patient who had died from ‘dum-dum fever’.

It was not discovered until 1921 that Leishmania was transmitted by a vector. The search leading to the implication of a specific vector was sought for a number of years, before the Sergent brothers Edouard and Etienne, demonstrated through experimental proof the transmission to humans from sand flies of the genus Phlebotomus.
History of leishmaniasis

History of Campylobacter

Campylobacter species have been causing illness for several centuries although they were only recognised a shaman pathogens in the 1970’s.

Campylobacter species have long been associated with the cause of veterinary diseases such as diarrhoea and septic abortions in cattle and sheep. It was first identified in the fecal tissue of aborted sheep in 1913, but was not isolated from stool samples of patients with diarrhoea until 1972.

The first observation of Campylobacter organism may have been as early as 1886 by Theodor Escherich, who described spiral organisms in the large intestine of children who had died of diarrhoea disease, and he called it ‘cholera infantum’.

Later Smith and Taylor described the vibrionic abortion in cattle and named the agent Vibrionic fetus. The association of V. fetes with enteric disease was first reported by Elizabeth King in 1957, and she preferred to name as ‘related vibrios’. In 1959, Florent showed that a form of the infection known bovine infections infertility was caused by V. fetes transmitted from carrier bulls to cows during coitus.

The genus name Campylobacter a Greek word for ‘curved rod’ was eventually proposed by Sebald and Veron (1963) to include microaerophilic bacteria that were different form Vibrio cholera and other species of vision in a number of respects.

In 1970s Campylobacter was successfully isolated from the stools of humans with accurate enter colitis. The isolation of Campylobacter from feces was accomplished in 1968 and published in 1972.
History of Campylobacter

Leprosy in modern history

Leprosy is also known as Hansen’s disease or neurodermatitis and is caused by a rod-shaped bacterium Mycobacterium leprae, that is spread in droplets of nasal mucus.

According to historical and archeological evidence leprosy was first spread to the Middle East in the days of Alexander the Great, during the years 324-325 BC, and was not known before.

The Greek word lepra was most likely used to mean a variety of severe skin diseases. Greek medical writings later than the third century BC provide the earliest clinical references to modern leprosy.

In medieval Europe, leprosy patients had to carry a ‘clapper’ to warn others that a person with leprosy was approaching. Even as late as 1913, state Senator G.E Willet of Montana was forced to give up his seat after he was diagnosed with leprosy.

In the 1870s, Armauer Hansen discovered microbe that causes the affliction and treatments were eventually developed. A prominent dermatologist in Norway, Daniel Cornelius Danielsen, wrote the first extensive description of leop0rsy, it was this description that Hansen used 20 year later as the basis for his studies of leprosy.

In the 1980s, a set of drugs was discovered that together can stop the progress of the disease. Today, 75% of all cases of leprosy occur in South East Asia, primarily in India.
Leprosy in modern history

History of phenacetin

Phenacetin (or acetophenetidin) is used as an analgesic and antipyretic drug for human and animals.  It was widely used between its introduction in 1887 and the 1983 ban imposed by the FDA on its use in the United States.

Phenacetin was marketed in 1888 and it could be stated that the development of phenacetin should be regarded as the beginning of the pharmaceutical industry in its modern form. It was introduced by the Bayer Company.

Phenacetin was first prepared by C. Hinsberg in 1887 who was seeking a use for a quantity of p-nitrophenol that he had a accumulated as a byproduct of dye works. Bayer’s chemists synthesized some derivatives of which the 4-epoxy acetanilide was less toxic, and was marketed as an analgesic and antipyretic under the name of phenacetin.

Phenacetin was a highly successful product and established the Bayer Company as a leading pharmaceutical manufacturer.

Phenacetin was first produced in the United States in the 1920s. Total annual sales of phenacetin for medical use were estimated to be less than 640,000 kg by the late 1970s.

Phenacetin was widely used for about 90 years until mounting concerns over carcinogenicity and kidney-damaging properties in chronic treatment.
History of phenacetin

Red corpuscle of blood

The blood is a complex organ that circulates cells and nutrients throughout the body. One important function of the blood is carrying oxygen from the lungs to the various cells and tissues throughout the body.

In the 1490s, Leonardo da Vinci wrote that the circulatory system is ‘a tree of veins’. He also stated that: All the veins and arteries arise from the heart.

Knowledge of the nature of blood was advanced by the work of Jan Swammerdam (1637-1680), a Dutch experimenter with microscope.

Swammerdam studied at Leiden University, completing a degree in medicine at age 30, with a dissertation on human breathing.

In about 1658 he was the first to describe the red corpuscles of blood from a microscope inspection of the blood of frogs.  Swammerdam described about red blood corpuscles in his famous Bibiia Naturae which was published only in 1738 by Boerhaave, many years after the author’s death in 1680.

Unaware of this work, Anton van Leeuwenhoek provided another microscopic description in 1674, this time providing a more precise description of red blood cells, even approximating their size. He estimated their size to be, in modern terminology, 8.5 microns in diameter (the correct value is 7.7 microns).

Leeuwenhoek found that red blood corpuscles settled at the bottom when sedimented and would lyse when water was added.

In 1901 Karl Landsteiner published his discovery of the three main blood groups – A, B and C (which he later renamed to O).
Red corpuscle of blood

Discovery of morphine by Friedrich Sertürner

The use of a wide of variety of opium alkaloids, obtained from the dried sap of Papaver somniferum, has been reported ins several cultures. The potential of opium was known and used in ancient Greece, Rome as well as Arab cultures.

Morphine, which is the benzylisoquinoline alkaloid, occurs in significant amounts in opium.

Friedrich Wilhelm Adam Sertürner (1783-1855) was a German pharmacist who discovered and isolated morphine from opium in 1804. He named the compound morphine, after Morpheus, the Greek god of dream.

Morhium or morphine is generally accepted as being the first medicinal alkaloid isolated from any plant.

The achievement was the most important ‘quantum leap’ in the history of pharmacology and represents the beginning of the true chemical investigation of plants.

Joseph Caventou (1795-1877) and Pierre Pelletier (1788-1842) were French pharmacist who applied the methods of Friedrich Wilhelm Adam Sertürner and were among the first to isolate a number of extremely toxic, yet medicinally important alkaloids  including emetine in 1817, strychnine in 1818, quinine 1820 and veratrine in 1821.

With the invention of the hypodermic needle in 1853, morphine’s use became widespread. Decades alter, heroin was synthesized by Dresser by diacetylating morphine.
Discovery of morphine by Friedrich Sertürner