Paracetamol: From Discovery to Widespread Use

The development of paracetamol began with the discovery of the fever-lowering effect of acetanilide, a finding that eventually led to the development of phenacetin by Bayer. Paracetamol, also known as N-acetyl-p-aminophenol, was synthesized by Bayer’s chemists in 1888. Despite its synthesis, it was not initially tested for its medicinal properties.

In 1893, paracetamol was clinically evaluated by Dr. Josef von Mering, a student of Oswald Schmiedeberg. Dr. von Mering discovered that the drug produced methemoglobinemia, a condition where hemoglobin is converted to methemoglobin, which cannot carry oxygen effectively. However, he mistakenly attributed this adverse effect directly to paracetamol, leading to the compound being ignored for its potential medicinal benefits.

Nearly a century later, paracetamol was reinvestigated in the United States at Yale University by David Lester and C. A. Greenberg. Their research demonstrated that paracetamol was the major metabolite of acetanilide and phenacetin and was relatively safe as an analgesic and antipyretic. This reinvestigation sparked renewed interest in the compound's potential.

Simultaneously, researchers Flinn and Brodie found that even at high oral doses, paracetamol did not result in the formation of methemoglobin. This finding further supported the safety profile of paracetamol, paving the way for its acceptance as a therapeutic agent.

In 1950, the first paracetamol product, a combination of paracetamol, aspirin, and caffeine, was introduced to the United States market under the name Triagesic. This combination product marked the beginning of paracetamol's widespread use as a pain reliever and fever reducer.

Today, paracetamol is one of the most commonly used over-the-counter medications for pain relief and fever reduction, recognized for its efficacy and safety when used as directed. Its journey from an overlooked compound to a household staple highlights the importance of revisiting and reevaluating scientific findings with fresh perspectives and advanced research methods.
Paracetamol: From Discovery to Widespread Use

Discovery of measles

Measles is a highly contagious disease caused by the morbillivirus, also known as the rubeola virus. Measles is characterized by a reddish brown rash that lasts for five to six days. Although a rare side effect, post-infection encephalitis can lead to permanent brain damage.

The first description of measles as a disease different from smallpox is attributed to Persian physician Rhazes of Baghdad in the tenth century. The Persian physician, Muhammad ibn Zakariya ar-Razi (860-932), known to the West as "Rhazes", published a book entitled The Book of Smallpox and Measles (in Arabic: Kitab fi al-jadari wa-al-hasbah).

Rhazes referred to measles as ‘hasbah’ (eruption) and regarded it as a modification of smallpox. One distinction noted was that ‘anxiety of mind, sick qualms and heaviness of heart oppress more in the measles than in the smallpox. Repeated epidemics of illness characterized by a rash are recorded in European and Far Eastern populations between AD 1 and 1200.

The first written record of measles in the United States was in 1657 by a citizen of Boston, Massachusetts. John Hull, in his personal journal, stated "the disease of measles went through the town, but fortunately there were very few deaths".

Francis Home, a Scottish physician, demonstrated in 1757 that measles is caused by an infectious agent in the blood of patients. He first attempted to make a vaccine. By then, measles was a worldwide killer.

In roughly the last 150 years, measles has been estimated to have killed about 200 million people worldwide. In 1954 the virus that causes measles was isolated in Boston, Massachusetts, by John F. Enders and Thomas C. Peebles.

Many of the basic principles of measles epidemiology and infection were elucidated by the studies of Peter Panum, a Danish physician who went to the France Islands in 1846 during a large-scale measles epidemic. Panum deduced the highly contagious nature of the disease the 14-day incubation period, the lifelong immunity present in older residents, and postulated a respiratory route of transmission.

By the 1950s, measles deaths had dropped to only 400 to 500 a year, thanks to the availability of antibiotics and improvements in sanitation, medical supportive care and nutrition.
Discovery of measles

Francis Home

Discovery of macadamia nut in Australia

The macadamia nut has originated in Australia, more precisely in the rain forests of the south­eastern Queensland and north­eastern New South Wales.

Aboriginal groups showed the tree and nuts to the explorers and botanists. In early contact with European settlers Macadamias were a major item of trade in exchange for tobacco, tommy axes and rum.

Alan Cunningham may have been the first explorer/botanist to record Macadamias near current day Beenleigh.

Baron Sir Ferdinand Jakob Heinrich von Mueller (1825-1896) , and Walter Hill (1820-1904), first director of the Brisbane Botanic Gardens, collected the yet undescribed plant in 1857 along the Pine River in the Moreton Bay area in Queensland, Australia.

Walter Hill erroneously believed the hard shell had to be removed to allow them to germinate and be planted. He gave the job to a young assistant and told him not to taste them as they were very bitter and probably poisonous.

Ferdinand von Mueller, a German-Australian physician and botanist decided to name the genus after a colleague. His name was Dr. John Macadam. Von Mueller was a noted chemist and physician who encouraged macadamia nut cultivation.

Mueller, who received his doctorate from the University of Kiel, Germany, came to Australia in 1847 upon being advised to go to a warmer climate.

Macadamia was introduced to Hawaii by W. H. Purvis in 1881, by the Jordan brothers in 1892, and by the Territorial Board of Agriculture between 1891 and 1895.

Macadamia nuts trees were imported to Hawaii for cultivation in the 1880s where it was first used for reforestation and as an ornamental plant and later in 1930; its commercial potential for dessert nut was developed by university of Hawaii. Nowadays, most macadamia plantations thrive in Hawaii.

Ernest Van Tassel, of the Hawai’i Macadamia Nut Company, began commercial planting of the nuts in 1921. After facing many adversities in growing healthy trees, Van Tassel was finally able to begin processing the nuts in 1934.
Discovery of macadamia nut in Australia

History and discovery of X-ray

X-rays were discovered in 1895 by Wilhelm Conrad Röntgen who was a professor at the University of Wurzburg, Bavaria.

On 8 November 1895, Röntgen wrapped some black cardboard around a Crookes tube attached to a Ruhmkorff induction coil, in other words a step-up transformer excited by repeated electrical pulses. Every pulse produced an electric discharge in the low-pressure gas in the tube.

After turning off the lights in the room, he noticed that some crystals of barium platinocyanide, near a discharge tube completely enclosed in black pepper, became luminescent when the discharge occurred.

By examining the shadows cast by the rays, Rontgen traced the origin of the rays to the walls of the discharge tube.

Röntgen delivered the news on the 28th of December 1895. Emil Warburg relayed it to the Berlin Physical Society on the 4th of January.

He suggested the name “X-ray” for his discovery, arguing that since the origin of the rays was unknown, it was appropriate to refer to them as X, the mathematical term for the unknown.

For his work x-rays, Röntgen received the first Nobel prize in physics, in 1901. It was the first of six to be awarded in the field of x-rays by 1927.

On January 13, 1896, Röntgen traveled to Berlin, Germany, to demonstrate the production of X-rays to Emperor Wilhelm II. On January 23, 1896, Roentgen presented his paper and demonstrated the production of X-rays to the Physical Institute of Wurzburg in his only public lecture on this topic.

The obvious similarities with the light led to the crucial tests of established wave optics: polarization, diffraction, reflection and refraction.

With limited experimental facilities, Röntgen and his contemporaries could find no evidence of any of these; hence, the designation “x” (unknown) of the rays, generated by the stoppage of anode targets of the cathode rays, identified by Thompson in 1897 as electrons.

The essential wave nature of x-rays was established in 1912 by Laue, Friedrich, and Knipping, who showed that x-rays could be diffracted by a crystal (copper sulfate pentahydrate) that acted as a three-dimensional diffraction grating.

William Lawrence Bragg proposed a simple but powerful equation – which became known as Bragg’s law – showing the connection between the wavelength of the X-rays, the distance between the planes and the angle at which the X-rays are reflected.

In 1908, Barkla and Sadler deduced, by scattering experiments, that x-rays contained components characteristics of the material of the target; they called these component K and L radiations.
History and discovery of X-ray

Discovery of nylon at DuPont

Nylon is a polymer obtained by the condensation of diamines with bicarboxylic organic acids, or from omega-amino acids. In more specific terms, it is a polyamide.

The first nylon, nylon 6,6, was synthesized using diamines on February 28, 1935 by Wallace Hume Carothers at DuPont's research facility at the DuPont Experimental Station. It was called fiber 66 because each of its components had six carbon atoms. Diamines from C2 to C18 were synthesized and reacted with aliphatic and aromatic dicarboxylic acids to make polyamides, which were then melt spun and evaluated as fibers.

The process was technically complex, involving new raw materials, new fiber-forming techniques and unfamiliar materials of construction. The first nylon filament plant was built in 1939 at Seaford, Delaware, and nylon stockings went on sale nationally on May 15, 1940.

Early in 1940 the company announced plans to construct a second plant at Martinsville, Virginia; and in July 1948, it opened a third plant at Chattanooga, Tennessee.
Discovery of nylon at DuPont

Dr. von Mering and paracetamol

Paracetamol had been synthesized in 1877 at Johns Hopkins University in Baltimore. It had no evidence medical value and thereafter had simply sat on a shelf for sixteen years.

In 1893, P-hydroxy-acetanilide was evaluated clinically by Dr. von Mering (1849-1908), who found that the drug produced methemoglobinemia.

Von Mering collaborated with the Bayer Company in a clinical trial of P-hydroxy-acetanilide, which it was postulated to be a metabolite of phenacetin by Trefuel and Hinsberg in1894.

He published a paper reporting on the clinical results of paracetamol with phenacetin, another aniline derivative. Von Mering claimed that, P-hydroxy-acetanilide to be effective antipyretic and analgesic, but believed it also had a tendency to produce methemoglobinemia.

Paracetamol was then quickly discarded in favor of phenacetin. It would remain, unused and apparently useless, for nearly half a century until it was rescued.

Von Mering's claims remained essentially unchallenged for half a century, until two teams of researchers from the United States analyzed the metabolism of acetanilide and paracetamol.

Paracetamol was reinvestigated half a century later by David Lester and Leon Greenberg from Yale University, who showed that it was indeed a metabolite of phenacetin in humans. In 1947 they found strong evidence that paracetamol was a major metabolite of acetanilide in human blood.

Lester and Greenberg demonstrated that paracetamol was the major metabolite so acetanilide and phenacetin and was relatively safe as an analgesic and antipyretic. In a subsequent study they reported that large doses of paracetamol given to albino rats did not cause methemoglobinemia.
Dr. von Mering and paracetamol

History of vitamin D

The discovery of vitamin D arose from research into rickets – a bone disease of infancy and early childhood that reached epidemic proportions on the industrial cities of Europe and the United States of America during the industrial revolution.

The first scientific description of a vitamin D-deficiency, namely rickets, was provided in the 17th century by both Dr. Daniel Whistler (1645) and Professor Francis Glisson (1650).

It was not until 1822 that a Polish physician noted that children living in the city of Warsaw were likely to have rickets than children living in the countryside which led him to prescribe sunlight as a cure for the disease.

The major breakthrough in understanding the causative factors of rickets was the development in the period 1910 - 1930 of nutrition as an experimental science and the appreciation of the existence of vitamins.

In 1919 Mellanby discovered the nutritional importance of animal fats for the normal calcification of bones by raising dogs affected with rickets through a special diet and by curing the animals with animal fats.

In 1921 he wrote, "The action of fats in rickets is due to a vitamin or accessory food factor which they contain, probably identical with the fat-soluble vitamin." Furthermore, he established that cod liver oil was an excellent antirachitic agent.

In 1919, Huldschinsky cured four children with severe rickets by exposing by exposing them to the rays of a mercury quartz lamp, thus demonstrating that UV radiation form an artificial source was equally effective as solar radiation.

Shortly thereafter E.V. McCollum and associates observed that by bubbling oxygen through a preparation of the "fat-soluble vitamin" they were able to distinguish between vitamin A (which was inactivated) and vitamin D (which retained activity).

From the work of Mellanby and McCollum, vitamin D became known as an essential nutrient.

In 1923 Goldblatt and Soames clearly identified that when a precursor of vitamin D in the skin (7-dehydrocholesterol) was irradiated with sunlight or ultraviolet light, a substance equivalent to the fat-soluble vitamin was produced. Hess and Weinstock confirmed the dictum that "light equals vitamin D".

The focus of many researchers from 1930 to 1960 was the role of vitamin D in mineral metabolism, i.e. calcium and phosphate absorption and excretion and bone formation and mobilization.

In parallel studies, Steenbock and Black found that rat food which was irradiated with ultra violet light also acquired the property of being antirachitic. However, because of the rapid rise of the science of nutrition -- and the discovery of the families of water-soluble and fat-soluble vitamins -- it rapidly became firmly established that the antirachitic factor was to be classified as a vitamin.

1960’s research demonstrated that vitamin D is precursor of a steroid hormone.
History of vitamin D

How coffee was discovered?

Coffee has been enjoyed by humans for more than 1,000 years. Throughout history coffee has been touted as a medicinal cure-all, and condemned as the devil’s brew.

Legend has it that back in 850 AD, a goat herder named Kaldi noticed his herd was full of energy and eating berries he had never noticed.

The goat were running about, butting one another dancing on their hind legs, and bleating excitedly.

Since the goats seemed to have such a reaction, the herder decided to give it a try. It must be the trees that maddened his goats.

First he chewed on a few leaves. They tasted bitter. As he masticated them, however, he experienced a slow tingle. Moving for his tongue down into his gut, and expanding to his entire body.

Next he tried the berries. The berries gave him a burst of energy and he began to feel very happy.

Kaldi told his father about the magical trees, the word spread and soon coffee became an integral part of Ethiopian culture.

In fact it was in Ethiopia that coffee was first grown and a beverage made from it. It was exported to the other side of the Red Sea in Aden in the fifteenth century.

Actually, the story of the goat herder isn’t the only legend surrounding this discovery. It is also said that an Arabian man was banished to the deserts with his followers to die of starvation.

His men became very desperate for nourishment and before long, they were boiling and eating the product of an unknown tree.

The broth that was produced by this unknown substance saved the lives of the men. In the nearest town, Mocha, many took their survival to be a religious sign. Because of the discovery, the drink was then named Mocha.

There is also and Eastern legend which ascribes the discovery of the berry to a Dervish named Haji, Omar, in the year 1285, being driven out of Mocha, was induced, in the extremity of hunger, to roast the berries which grew near his hiding place.

He ate them, as the only means of sustaining life and steeping the roasted berries in water to quench his thirst, he thus discovered their agreeable qualities and also that the infusion was nearly equal to solid food.

Today coffee is the world’s most popular beverage and it is a world commodity that is second only to crude oil.
How coffee was discovered?

Discovery of Paracetamol

The development of paracetamol began with the discovery of the fever lowering effect of acetanilide, a founding that resulted in the development of phenacitin by Bayer.

Paracetamol, N-acetyl-p-aminophenol, was a derivative synthesized by Bayer’s chemists in 1888 by Bayer but never tested for medicinal properties.

In 1893, it was evaluated clinically by Dr. von Mering, Schmiedeberg’s former student, who found that the drug produced methemoglobinemia.

However he believed mistakenly that it produced methemoglobinemia as an adverse effect and the compound was ignored.

A century later, paracetamol was reinvestigated in the United States, at the University of Yale by David Lester and C. A Greenberg, who demonstrated that paracetamol was the major metabolite of acetanilide and phenacetin, and was relatively safe as an analgesic and antipyretic.

At the same time, Flinn and Brodie found that even at high oral doses, paracetamol is not attended by the formation of methemoglobin.

In 1950 the first paracetamol product – a combination of paracetamol, aspirin and caffeine was in the United States market under the name Triagesic.
Discovery of Paracetamol