The History of Antibiotics


Version One:

Back in 1929, penicillin was re-discovered by a Scottish researcher named Alexander Fleming (penicillin was originally discovered by a French medical student by the name of Duchesne).

It wasn't until 1941 in England, that an Australian (Howard Florey) and an Englishman (Ernst Chain) developed commercial methods to produce penicillin for human use. The TOTAL amount of penicillin available for use in the clinical trial on humans at that time, was LESS THAN the amount one would receive in a single shot, today!

At that time, of course, World-War II was in progress, and there was a major effort to try to make penicillin available to all of the British, U.S., and other allies involved with fighting Germany, Japan, and Italy. Because England did not have the industrial capacity necessary for large-scale production, nor protection from bombing raids, the entire process was moved to the United States. It is for this reason primarily, that the pharmaceutical industry became so well-established in the U.S.

Initially, only military personnel were allowed access to this life-saving material. Eventually, prior to the end of World-War II, penicillin was made available to the general public.

Luckily for me, (this is written by Prof. John Brown, from Kansas State University) on my death-bed suffering from measles (a virus) and from bacterial pneumonia as a child in 1944, I was allowed to have penicillin because my father was in the Army - saved my life. Thank you, Drs Fleming, Florey, and Chain for your wonderful science.

(You may wish to look at the action of this antibiotic. Please see Jim Sullivan's Cells Alive! <http://www.cellsalive.com> information and look at the effect penicillin has on a dividing bacterium: )

Copyright John C. Brown, 1995
All of the "Feature Articles," and the articles in "What the Heck is...???" and in "General Interest" were written by me, and therefore, any mistakes are mine, alone. I have tried to be as accurate as possible within the limits of providing the information in a "reader-friendly" format. Therefore, please forgive any latitude I have taken with the pure science discussed. With these caveats in mind: in keeping with the spirit of the "Web" and Internet, and the fact that this institution has been established for, and is devoted to, learning, all of the articles on these Pages are for anyone's use, as long as the use is for non-profit only, and this statement accompanies any copies.

Dr Jack Brown is a professor of molecular biosciences at Kansas State University; and has a neat web site about all kinds of interesting disease, bacterial, and viral subjects of interest.  He writes for the general public in these articles...all of which begin with "What the heck is...."
His web site: http://people.ku.edu/~jbrown/bugs.html



History of Antibiotics:

Another Version

Although for centuries preparations derived from living matter were applied to wounds to destroy infection, the fact that a microorganism is capable of destroying one of another species was not established until the latter half of the 19th cent. when Pasteur noted the antagonistic effect of other bacteria on the anthrax organism and pointed out that this action might be put to therapeutic use.

Meanwhile the German chemist Paul Ehrlich developed the idea of selective toxicity: that certain chemicals that would be toxic to some organisms, e.g., infectious bacteria, would be harmless to other organisms, e.g., humans. 

In 1928, Sir Alexander Fleming, a Scottish biologist, observed that Penicillium notatum, a common mold, had destroyed staphylococcus bacteria in culture, and in 1939 the American microbiologist René Dubos demonstrated that a soil bacterium was capable of decomposing the starchlike capsule of the pneumococcus bacterium, without which the pneumococcus is harmless and does not cause pneumonia. Dubos then found in the soil a microbe, Bacillus brevis, from which he obtained a product, tyrothricin, that was highly toxic to a wide range of bacteria.

Tyrothricin, a mixture of the two peptides gramicidin and tyrocidine, was also found to be toxic to red blood and reproductive cells in humans but could be used to good effect when applied as an ointment on body surfaces. Penicillin  was finally isolated in 1939, and in 1944 Selman Waksman and Albert Schatz, American microbiologists, isolated streptomycin  and a number of other antibiotics from Streptomyces griseus.



Pfizer Company ... a small chemical company prior to World War ll saves hundred of thousands of lives with it's invention/technique of mass producing penicillin.  Pfizer later grows into one of the largest pharmaceutical companies in the world.

Though penicillin was discovered by Alexander Fleming in England in 1928, he couldn't figure out a way to produce enough for medical use, and penicillin remained nothing more than a laboratory curiosity.

In the late 1930s, with the onset of World War II, scientists saw potential to resurrect Fleming's work to make a germ-killing medicine to save the lives of Allied soldiers.

In 1941 the U. S. and British governments issued a challenge to the American pharmaceutical industry: Develop a way to mass produce penicillin to help the soldiers.

Each company chose a different method. Charles Pfizer & Co.  ... a relatively small chemical company based in Brooklyn ... gambled on fermentation, drawing from the unique expertise it developed 20 years earlier to mass produce citric acid.

Citric acid is a key ingredient in foods and beverages; notably soft drinks. It is a natural preservative that adds a pleasantly acidic or sour taste.

Charles Pfizer & Co had made citric acid the traditional way since 1880: from unripe citrus fruit, mainly imported from Italy, but World War I interfered with the supply.

In 1917 Pfizer hired James Currie, a food chemist, who had the daring idea of producing citric acid without using citrus. Currie knew that fermentation of a fungus, or mold, called Aspergillis niger could convert sugar into citric acid. Currie also understood that Aspergillis niger is aerobic, meaning it needs air to grow.

Aided by Jasper Kane, his precocious 16-year-old laboratory assistant from Brooklyn, Currie tried to grow the mold in a large flat pan purchased at the five-and-ten, but had limited success. He cut the pan into smaller, shallower pans, and immediately increased the yield. Still, the process was unpredictable and subject to a number of difficult variables: The quality of the mold spores, the purity of the cultures, contamination of air and the medium, humidity and temperature, and many others.

Currie plugged on, and in 1919 Pfizer opened a pilot plant using his fermentation process, named SUCIAC —"Sugar Under Conversion to Citric Acid."

By the mid-1920s the output of citric acid using fermentation far outpaced the production from lemons and limes. The price of citric acid, $1.25 a pound in 1919, dropped to 20 cents.

Pfizer began applying fermentation to other products, such as gluconic acid (used as a food preservative and cleanser) and ascorbic acid (Vitamin C), and experimented with innovative technologies to increase the yields. Eventually the company began to use a fermentation process in deep tanks rather than shallow pans and flasks.

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 World War II, Pfizer applied its deep-tank fermentation to manufacture streptomycin, an important antibiotic discovered by Dr. Selman Waksman and colleagues at Rutgers, and then to Terramycin®, the first antibiotic developed exclusively by the company's scientists.

Terramycin, which proved effective against a wide range of deadly bacteria, was developed from a microorganism in soil from the American Midwest ("Terramycin" is derived from the Latin for "earth fungus").

















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I hope you find the story about Pfizer's role in mass producing penicillin interesting.  The story is on this page towards the bottom.







Someone else who deserves recognition, but didn't get much seeing as he was on the losing side of the war and worked for the infamous Farben Industry Labs:


Domagk,  Gerhard
     1895-1964,

German chemist and pathologist.
A teacher successively at the universities of Greifswald and Münster, he became (1927) director of research at the I. G. Farbenindustrie laboratory at Wuppertal.

Because of a Nazi decree he was obliged to decline the 1939 Nobel Prize in Physiology or Medicine.

In 1947 he received a gold medal in lieu of the prize money. The award was made for his discovery of the efficacy of prontosil, the forerunner of the sulfa drugs, in treating streptococcal infections.

2008: Speaking about Pfizer; after being available in Europe, Australia, Canada, Mexico, and Japan, The FDA approves Pfizer's new 3rd generation antibiotic injection that lasts 14 days.
It's called Convenia and it's solved the problem of being unable to get a pill down hard to handle cats and dogs.




































The
History
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Antibiotics




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