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Buckle up! It's time for a #PharmPhriday thread on penicillin 
Prior to the discovery of pencillin, arsphenamine was used to treat syphillis! I previously tweeted about this; in short, it worked, but it was far from perfect. 1/14
https://twitter.com/NeuroDrugDoc/status/1261268659441369094?s=20
Prior to the discovery of pencillin, arsphenamine was used to treat syphillis! I previously tweeted about this; in short, it worked, but it was far from perfect. 1/14
https://twitter.com/NeuroDrugDoc/status/1261268659441369094?s=20
In 1928, Bacteriologist Alexander Fleming returned from holiday and found moldy contamination in a petri dish of Staphylococcus. An area of dish surrounding the mold had no bacteria, suggesting the mold had antibacterial properties. This mold was Penicillium notatum. 2/14
In 1931, after years of trying, Fleming was unable to purify penicillin and sent the mold out for others to try. By 1939, Ernest Chain, Howard Florey, and Norman Heatley described conditions to grow and isolate penicillin, tested it in mice with minimal side effects. 3/14
Meanwhile, Albert Alexander was suffering from Staphylococcus and Streptococcus infection; he was covered in abscesses and had an eye removed. Florey’s wife brought the case to his attention. In 1941, he became the first person to receive penicillin via injection. 4/14
He had had a rapid recovery, but died soon after.
Why?
Penicillin was in short supply, too difficult to synthesize on a large scale. They were actually extracting penicillin from his urine to continue treating him. An estimated 2,000L would be needed to treat one person. 5/14
Why?
Penicillin was in short supply, too difficult to synthesize on a large scale. They were actually extracting penicillin from his urine to continue treating him. An estimated 2,000L would be needed to treat one person. 5/14
What else was happening in around this time? WW2! There were manufacturing capability limitations, but at the same time, infections were rampant, and there was a need for treatment.
So…Penicillium notatum could work but was not feasible. The search for a better mold began. 6/14
So…Penicillium notatum could work but was not feasible. The search for a better mold began. 6/14
Mary Hunt, a laboratory assistant, saw a cantaloupe with a golden mold. This turned out to be Penicillium chrysogenum, yielding 200 times the penicillin! (1000 times, after enhancement). By May 1942, 400 million units were manufactured! 7/14
So when people talk about Fleming and penicillin, I often "well, actually" and bring up Mary Hunt.
But we can't talk about this story in isolation. Something else has happening around this time-- the Tuskegee Syphilis Study went on from 1932 and 1972. 8/14
But we can't talk about this story in isolation. Something else has happening around this time-- the Tuskegee Syphilis Study went on from 1932 and 1972. 8/14
The purpose of study was to learn about untreated syphilis; the trial participants were African-American men.
"But Monica! You just said they were manufacturing penicillin on a wide scale by 1942. How were they studying untreated syphilis 30 years later?" 9/14
"But Monica! You just said they were manufacturing penicillin on a wide scale by 1942. How were they studying untreated syphilis 30 years later?" 9/14
Yep. Penicillin became the standard of care for syphilis in 1947, but the investigators decided to withhold treatment from the study subjects and continue their research. The study continued till 1972
NYT piece 1: https://www.nytimes.com/1972/07/26/archives/syphilis-victims-in-us-study-went-untreated-for-40-years-syphilis.html
NYT piece 2: https://www.nytimes.com/1972/09/12/archives/at-least-28-died-in-syphilis-study-reports-on-tuskegee-tests.html 10/14
NYT piece 1: https://www.nytimes.com/1972/07/26/archives/syphilis-victims-in-us-study-went-untreated-for-40-years-syphilis.html
NYT piece 2: https://www.nytimes.com/1972/09/12/archives/at-least-28-died-in-syphilis-study-reports-on-tuskegee-tests.html 10/14
Many died. Many gave it to their spouses. Many children were born with congenital syphilis. This isn't some thing in the past; people are still affected by what happened during the study.
Here's a piece on the study descendants: https://www.cbsnews.com/news/tuskegee-syphilis-study-descendants-speak-about-tragedy-call-for-action/ 11/14
Here's a piece on the study descendants: https://www.cbsnews.com/news/tuskegee-syphilis-study-descendants-speak-about-tragedy-call-for-action/ 11/14
In 1974, Congress passed the National Research Act, and HHS established the Office for Human Research Protections (OHRP) to oversee clinical trials.
Bill Clinton formally apologized to the study survivors in 1997. Five were present: 12/14
Bill Clinton formally apologized to the study survivors in 1997. Five were present: 12/14
However, in 1992, ABC PrimeTime Live's Jay Schadler interviewed Dr. Sidney Olansky, one of the study directors. If you're interested in finding out if he had a change of heart as time had passed following the trial's termination, go to the 2nd page http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.590.9738&rep=rep1&type=pdf 13/14
This is just one of countless atrocities that contribute to distrust in clinical research and medicine to this day. We need to work with communities to *earn* their trust and build long-term relationships; the work is neither quick nor easy, but it's necessary
14/14 #PharmPhriday
14/14 #PharmPhriday
