Wednesday, December 22, 2010

The Discovery of Penicillin

This is the beginning of a new series: Great Scientific Advances. Each week, we will look at an important scientific discovery, one that markedly improved our physical well-being and made our lives better. We start off with one of the most important discoveries of the twentieth century: Penicillin.
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We ought to have saints' days to commemorate the great discoveries which have been made for all mankind, and perhaps for all time—or for whatever time may be left to us. Nature ... is a prodigal of pain. I should like to find a day when we can take a holiday, a day of jubilation when we can fête good Saint Anaesthesia and chaste and pure Saint Antiseptic. ... I should be bound to celebrate, among others, Saint Penicillin...
Winston Leonard Churchill, prime minister of UK, 
Speech at Guildhall, London, 1947

A drop from the nose of Fleming, who had a cold, fell onto an agar plate where large yellow colonies of a contaminant had grown, and lysosyme was discovered. He made this important discovery because when he saw that the colonies of the contaminant were fading, his mind went straight to the right cause of the phenomenon he was observing—that the drop from his nose contained a lytic substance.
Sir Alexander Fleming
Personal recollections of Alexander Fleming by Lady Amelia Fleming. 
Quoted in Molecular Cloning (2001), Vol. 1, 153.

The Look of Penicillin: Penicillin core structure, in 3D. Purple areas are variable groups.
Credit: Benjah-bmm27, 2007.

We can't imagine a world without penicillin, the antibiotic that is routinely prescribed by physicians the world over, notably to young children for ear infections and strep throat. Although it might not now be the strongest antibiotic in the arsenal of medical science, its importance cannot be denied: it the first antibiotic and as such  bears remembering. In its early days (1940s and '50s), it was highly effective, for example, against such deadly infections as syphilis and Staphylococcus.  

As is common with many scientific discoveries, this discovery happened by initial good fortune and subsequent hard work after the initial discovery. It also involved the collaborative effort of a number of scientists, researchers and technicians, each dedicated to achieving a victory of sorts over killer diseases. All are necessary for scientific advancement.

When penicillin is cited, the name of Alexander Fleming, a Scottish bacteriologist, quickly comes to mind. His eureka moment, has served humanity well, and prevented untold misery and death. For his contribution, Fleming was awarded the Nobel Prize in Medicine in 1945; however, he was joined by British scientists Howard Walter Florey (Australian born pharmacologist) and Ernst Boris Chain (German born biochemist), whose achievements are as equally important as that of Fleming.

No doubt, Fleming deserves the fame and attention, including joining the list of Time magazine's 100 most influential people in the 20th century for his contribution to science, and in this case medicine. But it truly took an international team of scientists, both in Britain and the United States, to bring penicillin to market. 

Here are some of the relevant details. On the morning of Friday September 28, 1928, at his laboratory in the basement of St. Mary's Hospital in London (now part of Imperial College), Fleming made an observation, Time magazine pithily notes that would eventually contribute to humanity's betterment and change history:
In 1928 the young Scottish researcher Alexander Fleming sloppily left a lab dish growing bacteria on a bench when he went on vacation. It got contaminated with a Penicillium mold spore, and when he returned, he noticed that the mold seemed to stop the growth of the germs. His serendipitous discovery would eventually save more lives than were lost in all the century's wars combined.
Fleming serves well as a symbol of all the great medical researchers, such as Jonas Salk and David Ho, who fought disease. But he personally did little, after his initial eureka! moment, to develop penicillin.
To add further detail missing in the Time article, Fleming observed, as NobelPrize.org, explains,
[M]ould had developed accidentally on a staphylococcus culture plate and that the mould had created a bacteria-free circle around itself. He was inspired to further experiment and he found that a mould culture prevented growth of staphylococci, even when diluted 800 times. He named the active substance penicillin.

Nobel Laureate (1945): Alexander Fleming (L) receives the Nobel Prize n Medicine from King Gustavus Adolphus of Sweden, 1945.
Photo Credit
: Karolinska Institutet, Sweden, http://ki.se/ki/jsp/polopoly.jsp?d=11309&a=23624&l=sv

That must have been an inspiring moment. But not much happened. Fleming wrote a paper for a scientific journal, British Journal of Experimental Pathology, noting that penicillin could have therapeutic value if it could be produced in enough quantity. That was indeed the problem and the hurdle to overcome. 

Although Fleming kept at it assiduously for the next ten years, he had to pass the baton to four other British scientists — Cecil George Paine, Howard Walter Florey, Ernst Boris Chain, and Norman Heatley— to overcome the problems preventing penicillin's clinical trial and subsequent production, explains About.com:
It was not until 1939 that Dr. Howard Florey, a future Nobel Laureate, and three colleagues at Oxford University began intensive research and were able to demonstrate penicillin's ability to kill infectious bacteria. As the war with Germany continued to drain industrial and government resources, the British scientists could not produce the quantities of penicillin needed for clinical trials on humans and turned to the United States for help.
They were quickly referred to the Peoria Lab where scientists were already working on fermentation methods to increase the growth rate of fungal cultures. One July 9, 1941, Howard Florey and Norman Heatley, Oxford University scientists came to the U.S. with a small but valuable package containing a small amount of penicillin to begin work.
The American contribution is important, notably the work done by Moyer, Coghill and Raper at the United States Department of Agriculture (USDA) lab in Peoria, Illinois. By 1943, American scientists developed methods for industrialized penicillin production and isolated higher-yielding strains of the Penicillium fungus.   

A few months later, the scientists were able to increase the amount of penicillin required for clinical trials. By 1943, clinical trials were successfully done. And now was the need for mass production. American scientists, led by Jasper Kane, at Charles Pfizer & Co., then a relatively small chemical company in Brooklyn, New York, developed the practical, deep-tank fermentation method for production of large quantities of pharmaceutical-grade penicillin. Again, it was another breakthrough moment, recalls the American Chemical Society:
Pfizer's technological advances in using deep tanks for fermentation proved critical when Allied governments sent out the call for penicillin. Initially, Pfizer researchers, led by Jasper Kane, used shallow flasks and pans like those that were used for citric acid, and they made gradual progress in improving penicillin's potency and purity.
The breakthrough came when Kane suggested a different approach: the deep-tank method that proved successful for gluconic acid. They needed huge tanks that could hold thousands of gallons of "fermentation liquor." Pfizer purchased an old ice plant in Brooklyn that had the necessary refrigeration equipment and converted it into a penicillin factory which opened on March 1, 1944.
The plant contained fourteen 7,500-gallon tanks and soon the company was producing more penicillin in one month than it had in all of 1943. Most of the penicillin that went ashore with Allied forces on D-Day came from Pfizer's Brooklyn facility.

After the Second World war, in 1946, the price of production dropped and so did the cost for the public, to about fifty-five cents per dose. Penicillin soon became widely available, thereby saving many lives. By 1952, penicillin was available in oral pill form. 

Fleming might get the credit, but it was the combined efforts of scientists working collaboratively internationally that helped make the initial discovery in 1928, and publication  in 1929, by Alexander Fleming a springboard to success, whereby penicillin eventually became a common antibiotic. As Fleming remarked in his Nobel Laurate lecture on December 11,1945: "My publication in 1929 was the starting-point of the work of others who developed penicillin especially in the chemical field."

2 comments:

  1. I remember the world before penicillin, when people were terrified of the common cold because it might lead to pneumonia.
    Despite the invention of weapons of mass destruction, science has lengthened and improved human life--through medicine and through making life easier. Knowledge is easier to obtain, especially now that the internet exists. When the scientific method became established in the 17th century, democracy followed, needless to say. Democracy is the political realization of the scientific method, as I explain in this essay:
    http://www.jochnowitz.net/Essays/Blessed.html

    ReplyDelete
  2. Thank you. Prof Jochnowitz, for your thoughtful comments. I also applaud the scientific method and its contribution to democracy and humanity.

    ReplyDelete

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