Penicillin – Animal Tests Mass Drug Production

Florey, Chain, Heatley – Mold Miracle of Penicillin Begins History

Mar 30, 2009
Donald Reinhardt

Dr. Ernst Chain Developed Penicillin Production T - PBS.org

It was a top secret project in many ways and ended up as a cooperative venture between England and the US. It is the story of penicillin in 1938-39 as Hitler begins WW2.

Some great, published ideas remain obscure for years, decades or centuries. Alexander Fleming's penicillin research at St. Mary's Hospital in England is one such story.

Nine years after Fleming's 1929 publication , an ever-inquisitive biochemist, Ernst Chain, working with Florey and Heatley, sought out the lysozyme studies of Fleming and his penicillin paper. Florey and Chain were studying the structure of bacterial cell walls. They wanted to determine ways to destroy bacteria. Initially, they had no interest in injectable cures for infectious disease. What happened next rapidly moved penicillin from the laboratory to the WW 2 battlefront and hospitals of the allies. Thousands were saved from permanent disability or death.

Penicillin the Mold Tested in Culture Liquid and Animals

Chain was at Oxford and soon obtained Fleming's original Penicillium notatum, the mold that produces the penicillin. The Penicillium was being used in some other Oxford labs to control bacterial contamination on agar plates.

Chain, together with Heatley, a biochemist, proceeded to:

grow the Penicillium in liquid culture in flasks – it grew well, but slower than bacteria
test for the presence of the antibiotic – it was there, but in small amounts
use various methods and chemicals to extract penicillin – they got pure crystals of the antibiotic
test purified liquid and crystals on cultures – it worked
dilute the antibiotic almost a million-fold – it was still effective
test 8 mice with streptococci: 4 mice, no penicillin, dead; 4 mice, with penicillin, alive

All the above were simply terrific results. Everything was fine, with two exceptions, they could not make large quantities of penicillin, nor do this quickly.

Florey and Heatley soon flew secretly, across the Atlantic, on a darkened plane, with an ice chest of mold cultures. Penicillin was ready to become a main event.

Commercial Production of Peniciilin Developed in America

The English and Americans knew that big wars cause massive casualties, wounds and infectious diseases. WW 1 was a recent, stark factual reminder.

Effective antibiotics could save soldiers' lives, rehabilitate them. Thus, that army could recycle more soldiers to go back and fight another day. Arriving on that secret plane with Florey, Heatley and mold was real hope that penicillin could be made soon, quickly and abundantly. The US was also already in the midst of WW 2 after the attack of the Pearl Harbor Naval Facility by Japan, on Dec. 7, 1941.

Within weeks, the English scientists were thrilled to see large mold growth tanks and facilities that were readied for mass production. Pfizer, Merck and Squibb were familiar names on the enlisted roll call of manufacturers. In Peoria, Illinois the USDA began to look hurriedly and everywhere for better penicillin-producing strains on moldy foodstuffs. Soon, on a cantaloupe, from a nearby market, Mary Hunt brought a strain of Penicillium chrysogenum that gave outstanding yields of penicillin. Colleagues honored her with the epithet "Moldy Mary". Corn steep syrup would serve as the major food for fungal nutrition and growth.

Epilogue

WW 2 ended. Many lives were lost and damaged. Lives were saved, too. The horrors would have been greater had not a wonderful doctor's discovery at a small hospital been resurrrected by Oxford researchers . The Nobel Prize was awarded to Dr. Fleming, Florey and Chain in 1945. A fitting tribute, indeed!

Penicillin helped overcome the scourges of staphylococci and streptococci, gonorrhea and even syphilis. Despite today's rising microbial resistance to all antibiotics, penicillin and its derivatives remain important to antimicrobial battles everywhere on the planet.