The History of the discovery of Antibiotics
Middle Ages: The use of bread with a blue mold as a means of treating wounds was a staple of folk medicine in Europe since the Middle Ages. But still, millions of soilders on the battle field, farmers in the field, women giving birth, and children at play would end up dying a miserable, feverish death from simple wound infections
Mid - late 1800's: Louis Pasteur, a French chemist and microbiologist is remembered for his remarkable breakthroughs in the causes and preventions of diseases and his experiments supported the germ theory of disease. He's best known for inventing the process that prevented people from getting sick from milk and wine that became know as "pasteurization". But he also created the first vaccines... for rabies and anthrax.
But he did NOT discover antibiotics. The Institut Pasteur in Paris becomes the first major microbiology research center.
1871: Joseph Lister experimented with penicillum for his "Aseptic Surgery". He found that it weakened microbes but then he dismissed the experiment as not being of any importance.
1875: John Tyndall publishes a paper in the Royal Society about the antibiotic properties of the Penicillium mold. But apparently nobody paid much attention.
1897: Medical student Ernest Duchesne documented the antibiotic properties of bread mold in a paper submitted to the Pasteur Institute. But he was considered too young to be taken seriously and nobody paid much attention.
1915-1927: Costa Rican scientist and medical doctor Clodomiro (Clorito) Picado Twight reports his observations about the antibiotic properties of Penicillium to the Paris Academy of Sciences. Apparently nobody paid much attention.
(In March 2000, doctors at the San Juan de Dios Hospital in San José, Costa Rica published the manuscripts of Dr. Twight proving that his experiments were done much earlier that those done by Fleming.)
1928-1929: Scottish scientist Alexander Fleming accidently discovers that the mold on his sandwich bread exuded a substance that had antibiotic properties. Since the mold's scientific name is Penicillium notatum, he called the antibiotic substance; Penicillin. But most of the medical community was not immediately impressed and it wouldn't be used as a medical treatment for several more years. But nonetheless, Fleming becomes famous as the "father" and discoverer of antibiotics.
1939: the American microbiologist René Dubos demonstrated that a soil bacterium was capable of decomposing the starchlike capsule of the pneumococcus bacterium, one of the main causes of pneumonia... one of the major causes of death in the world. Dubos then found in the soil a microbe, called Bacillus brevis, from which he obtained a product, called 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.
1939: Domagk, Gerhard, German chemist and pathologist. Herr Doctor Domagk is a teacher successively at the universities of Greifswald and Münster, and 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.
1941: In England; The development of penicillin for use as a medicine is attributed to the Australian Nobel laureate Howard Walter Florey together with the German Nobel laureate Ernst Chain and the English biochemist Norman Heatley. 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!
Early during war ll : Penicillin is acknowledged as a major medical breakthrough and the Americans figure out how to make the product in large volume. I believe the production of large volumes of penicillin was first done in the large vats of a pickle factory in Brooklyn. For more information, google the history of the Pfizer company.
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. But 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.
The Americans are the first to use penicillin on thousands of patients during the North African and Italian campaigns. There are wonderfully interesting stories about the Mafia and the black market of this new miracle drug, and how, during the occupation of Italy, so much penicillin was used to treat soilders with the "clap" (gonorrhea or syphillis) that there wasn't enough left over to treat soilders with battle wounds.
1944: Selman Waksman and Albert Schatz, American microbiologists, isolate streptomycin and a number of other antibiotics from Streptomyces griseus.
Note; some of the information above comes from Prof. John Brown of Kansas State University, who writes that "Luckily, 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
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").
On This Page:
A little bit about the importance and history of antibiotics
At the bottom of this page; an interesting story of the Pfizer company's role in the early history of antibiotics
On Other Pages:
Pharmacy: about the medicines used in veterinary medicine
History of Veterinary Medicine in the United States
Denistry: why oral hygiene and health is so important and what you can do about it
Orthopedics: How I treat arthritis, pannus, hip dysplasia, and other problems of the bones and joints
Metabolic Diseases like Diabetes, Cushings Disease, Addison's Disease, and Thyroid Disease
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.
A tribute to Vannevar Bush 1890-1974
American electrical engineer and physicist. Student, professor, and eventually Dean (Engineering) at MIT during the 1930's
During this period he devised a network analyzer to simulate the performance of large electrical networks.
He is best known for his design of the differential analyzer, an analog computer that could solve differential equations with as many as 18 independent variables.
From 1939 until 1955 he was president of the Carnegie Institution.
From 1941 to 1945 he was also the director of the U.S. Office of Scientific Research and Development, where he administered the U.S. war effort to utilize and advance military technology.
He directed such programs as the development of the first atomic bomb, the perfection of radar, and the mass production of sulfa drugs and penicillin.
