-Antibiotic substance created by the mold Penicillium notatum

-Kills bacteria by inhibiting the bacterial enzymes that synthesize the cell wall and by activating other enzymes that break down the cell wall

-Is the first antibiotic to successfully treat bacterial infections

-Penicillin now comes in liquid and capsule forms

-Bacteriologist for St. Mary’s Hospital in London

-Doing research to find an antibiotic—inspired by the conditions of WWI where more often than not soldiers were dying because of infection rather than in outright battle

-Antibiotic: A substance produced by a microorganism which harms or kills another microorganism

Fleming's First Research

-Began first experiments in 1922 by culturing bacteria from nasal secretions

-While examining a mature culture plate, a tear fell onto the bacteria in the culture

-He later noticed that the bacteria around where the tear had landed were dead

-Determined that the tear contained an enzyme thatdestroyed bacteria

-Named the enzyme lysozyme

-Lysozyme only killed relatively harmless bacteria, so he had to look elsewhere for an antibiotic

Continued Research

In 1928, Fleming was studying staphylococci bacteria and left some of his culture trays out in the room when he left for his vacation

He c ame back to find that a mold was growing on one of the cultures and noticed that the bacteria surrounding the mold was dead

Determined the mold to be part of the Penicillium genius and named it Penicillium notatum

Began testing the mold for its properties after growing mold colonies of his own to begin researching

After he had grown enough mold, he simmered the mold in a broth to extract the antibiotic

He tested the broth against streptococci, pneumococci, staphylococci, the bacilli of diphtheria, syphilis, gonorrhea, scarlet fever, influenza, and typhoid fever

His results showed that it was highly effective against streptococci, pneumococci, staphylococci, the bacilli of diphtheria, syphilis, gonorrhea and scarlet fever, but uneffective against influenza and typhoid fever

He repeated the tests with different concentrations of penicillin and found that concentrations diluted to one eight-hundredth of the original was still lethal to bacteria

To see its toxicity effects, he tested on healthy rabbits: he injected 20cc of the penicillin broth into one healthy rabbit and 20cc of regular broth into another rabbit

Both rabbits were still perfectly healthy after the treatments

Fleming tried without success to convince doctors to use the medicine in treatments

Published results in the British Journal of Experimental Pathology and presented his results at a meeting of bacteriologists, but his article was still overlooked

The reason for this was because he didn’t have any conclusive human test results and he could not produce enough mold to make enough penicillin to give a patient a full treatment

Fleming stopped his research, but continued to grow the mold in his laboratory

Howard Florey

Ernst Chain

Norman Heatley

Fleming’s work was picked up in 1938 by Howard Florey, professor of pathology at Oxford University, and Ernst Chain, who was working under Florey

They began working with a borrowed sample of Fleming’s original mold colony

They had the same problem as Fleming: theycould not grow much mold. They used what they had for small experiments. They first tested toxicity by injecting the broth into mice—the mice were healthy before and after

Happy to see the same results as Fleming, Florey began the construction of a research team

The Oxford Team

In 1940, the team had enough penicillin to perform tests on mice infected with streptococci bacteria.

Eight mice were infected with 110 million bacteria. Four mice began receiving penicillin treatments one hour later and then every three hours for one day and one night.

By the afternoon, the four infected mice were showing signs of illness, and eventually began to die after midnight. All four of these mice were dead by 3:30 am, while the other four remained perfectly healthy.

The team also found from this experiment that the body doesn’t retain penicillin for very long, meaning frequent treatments are needed.

Norman Heatley

A member of the Oxford Team who was responsible for researching different growing methods to increase the amount of usable penicillin

Discovered that bedpans from the Radcliff Infirmary (a hospital near Oxford University) were most effective in growing mold and designed new ceramic culture trays modeled after the bedpan

Made contributions to the understanding of the purification process, which increased the amount and strength of penicillin from each batch

The increase in mold allowed for more broth to be made for testing and enabled more treatments and testing

Mice just after infection

Mice at 3:30 am

Test 1

Albert Alexander, a London policeman, cut his face while shaving and developed a staphylococcus infection. He was given doses of penicillin every three hours for five days. He made great improvements over his treatment, but the penicillin ran out on the last day. The last dose that the Oxford Team scraped together came too late.

Test 2

A child developed a hemolytic strep infection and was expected to die within 48 hours. However, because of the penicillin, he stayed alive. The supply ran out during this treatment as well, but the last dose was administered just in time.

From the results of these tests, Florey determined that it was the job of drug companies to produce the penicillin in the large quantities needed for treatments.

Dr. A. J. Moyer was one of the Team members working on solving the problem of penicillin mold yields. While checking the experimental medium flasks, he noticed that one was producing an average of 200 units per cubic centimeter (200 times the previous yield). The flask contained corn-steep liquor as the medium.

With production up, the Team was finally able to create enough penicillin to support the treatment of several patients. Now they just needed the way to prescribe the medicine. Howard Florey’s wife, Ethel, had been a practicing doctor in Australia before moving to England. Florey told her that she was back in practice and was going to prescribe penicillin to patients who might benefit from it. Ethel Florey took doses to the Radcliff Infirmary and gave them to patients with streptococcus infecions, osteomyelitis, empyema, meningitis, bacterial endocarditis and septicemia.

In all cases, the patients were cured.

By the end of that year, there were 187 successful and carefully documented treatments that Florey could finally use to convice doctors and drug companies of the medicinal qualities of penicillin

Spreading the Good News

Florey and Heatley flew to the US to spread the results to drug companies

They went to Peoria, IL to meet with the Fermentation Division of the Northern Regional Research Laboratory

The group accepted the proposal made by the pair and began research and development

New mold strains were brought in from all over the world to analyze for production their production yields

“Moldy Mary” Hunt provided the most useful strain, found on a molded cantaloupe from the Peoria fruit market—the new mold doubled the yield of units of penicillin

Comparing production rates:

1943-400,000,000 units made in first five months of production

1943 (end of year)-9,194,000,000 units per month

1948-Eight million million units per month (8,000,000,000,000,000,000)

Bacterial infections are now easily cured with penicillin treatment

Caused others to begin research into the use of other molds as potential medicines or treatments

Dr. Alexander Fleming, Howard Florey, and Ernst Chain were awarded the Nobel Prize in Medicine in 1945, as well as being knighted