Great Drugs of the 20th century – the Age of Chemotherapy-1935.

GIMME RED! PRONTOSIL – 1935.

prontosil
An early sample of Prontosil.,

Less than a century ago, mankind had no defense against bacterial infections. Frequently, patients would die after surgery, due to post-operative sepsis. Even a simple wound could get severely infected and result in amputation or death.

In the early years of the 20th century, Germany was the global leader in synthetic dyes. IG Farben, a large conglomerate of dye manufacturers, was one of the world’s largest chemical companies at the time. One of the companies that formed IG Farben was Bayer Chemical Co.

The Bayer lab in IG Farben undertook a research program to screen thousands of dyes for medicinal properties. In 1932, a research group led by chemists Josef Klarer and Fritz Mietzsch, patented a red dye called sulfamylchrysoidine, as a potential anti-bacterial agent.

Gerhard Domagk2
Gerhard Domagk, circa 1935.

Bayer bacteriologist Gerhard Domagk established that this dye was very effective against gram-positive bacteria. Domagk named the dye Prontosil.

This red dye became the world’s sulfonamide and the first man-made chemical agent against bacterial infections.

And so began the age of Chemotherapy.

Strictly speaking, Prontosil is a pro-drug. By itself it is inactive, but in the human body it quickly breaks down to produce Sulfanilamide, which is the molecule that has antibacterial properties.

Sulfas inhibit bacteria’s ability to make folic acid, a critical element in the bacterial life-cycle. Technically, sulfas are bacteriostatic drugs, i.e. drugs that prevent bacteria from growing, as compared to bactericidal drugs, that actually kill bacteria.

Sulfas still retain a place of importance in modern chemotherapy and remain the primary drugs of choice in some infections.

Gerhard Domagk received a Nobel in 1939.  His red dye is still doing what it used to do sixty years ago – killing bugs and saving lives.

ALEXANDER’S BUMMER – PENICILLIN – 1943.

penicillin1
Fleming’s penicillium plate. Source: British Journal of Exp Pathology, 1929, x:p226.

One fine morning in 1928, in his lab at St Mary’s Hospital, London, bacteriologist Alexander Fleming realised he had made a mistake. His bacterial culture plate was contaminated by an unwelcome fungus that had killed the original bacteria in the plate. Fleming realised that the invading fungus was secreting a powerful substance that could kill bacteria.

He identified the fungus as Penicillium notatum and named the unknown substance as Penicillin.

Fleming had stumbled upon the first antibiotic.

The Antibiotic Era took several years to take off, since Fleming couldn’t extract pure penicillin.  This remarkable feat was achieved in 1939 by organic chemists Howard Florey, Ernst Chain and their team in Oxford University.  Since Britain was financially drained by the on-going World war, Florey and his team sought help from the Americans.  In 1941, Florey & co. moved to a research lab set up by the US Department of Agriculture in Peoria, Illinois. fleming-chain-florey-medicine-1945-7

The extraction and purification of large quantities of penicillin was perfected at Peoria, clinical trials were hastily done and penicillin officially released to the US armed forces in 1943.

Hailed as a ‘magic bullet’, penicillin saved countless Allied lives during the last years of WW-2.penicillin

Penicillin belongs to a class of drugs called the beta-lactam antibiotics. Beta-lactams work by preventing bacteria from creating their cell-walls, thus exposing the contents of the bacterial cell and killing it.

In 1945, Florey, Chain and Fleming shared the Nobel in medicine.

penicillin ad2
Unbelievable!

Unfortunately, doctors and the public quite simply went berserk with penicillin. The drug was prescribed indiscriminately, even for infections not caused by bacteria. It was used by recklessly by manufacturers who added penicillin to all kinds of products, including lozenges, toothpaste, shaving creams and even chewing gum.

The result was – bacterial resistance. Today, penicillin is almost useless as an antibiotic since every pathogenic species has developed a strong resistance to it.

All the same, penicillin’s place in human history is undisputed.

There are several new antibiotics available today, but if one were to single out the drug that changed the course of humanity, it would be – Alexander’s bummer, Penicillin.

 

to be continued …

 

 

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