Key Facts & Summary
- A lot of research was carried out before the discovery of Penicillin.
- Three Scientists, H. Florey, B. Chain, and Flemming were the brains behind the discovery.
- The discovery of Penicillin was a really important discovery in medicine since it impacted on many lives and help save hundreds of millions of lives.
The medical revolution represented by the discovery of sulfonamides and especially penicillin was preceded by a very long search. Alexander Fleming was in 1928 incontestably the man of penicillin. It must be remembered, however, that in 1897 a medical from Lyon had already attracted attention to the relationship that existed between molds and microbes. Indeed, on the 17th December 1897, at the Lyon Faculty of Medicine, Ernest Duchesne, a student of the School of the Military Health Service had defended a thesis entitled: “Contribution to the study of vital competition in microorganisms, the relationship between molds and microbes “.
Unfortunately, since the Penicillium was not offensive to typhoid bacilli, Professor Gabriel Roux, Director of the Hygiene Office of the City of Lyon, did not pursue that particular research. Aymé Camelin in 1958 assumed that Gabriel Roux “had been forgotten in his own city and hence could not bring credit to his research on molds.”
- Florey and B. Chain: stable and purified penicillin
On August 24, 1940, an article by Howard Walter Florey and Boris Chain was published. H. Florey was an Australian, born in Adelaide in 1898 and had shown a keen interest in science, especially chemistry.
He obtained a scholarship founded by Cécile Rhodes that led him to Oxford University. He developed an interest in all physical and chemical subjects him and in 1925, the Rockefeller Foundation sent him to the United States where he worked in many laboratories. He made many friends, including Dr A.N. Richards of the University of Pennsylvania.
Returning to England, he came across Fleming’s work in 1929. In 1935 he was appointed a professor of pathology at Oxford. It was a top institute, with much better laboratories than Saint-Mary’s, having, in particular, a biochemistry laboratory.
Florey, as soon as he was appointed, invited Ernst Boris Chain to come and organize and lead its biochemistry section. The chain was born in Berlin in 1906 to a Russian father and a German mother. His father was indeed an industrialist in chemistry. Chain, German Jew, and the doctor left for England in 1933. He worked successively in London than in Cambridge, where the director of the Institute, Sir Frederick Gowland Hopkins, appreciated his work.
That is how Sir Frederick asked him in 1936 if he would like to go to Oxford to practice biochemistry. The chain was delighted. He was then a young man, twenty-nine years old, black hair, bright-eyed, and vivacious. The chain went to see Florey who told him about the importance he attached to biochemistry. He suggested to Chain to explain the mode of action of a bacteriolytic substance, lysozyme.
Among the communications that Lut Chain had, the most interesting one to him was that of Fleming in 1929 on penicillin that had on lysozyme the superiority of destroying dangerous microbes without being toxic. Chain confirmed that the anti-bacterial substance was very unstable. However, this instability itself made Chain be curious.
Chain thought that penicillin must be an unstable enzyme. But he had at his provision the very simple principle of lyophilization which is that in the vacuum the solutions Frozen aqueous products pass directly from the solid state to the gaseous state. It was a way to save penicillin.
By freeze-drying, the culture liquid, Chain obtained a brown powder that contained impurities with penicillin. He diluted the solution with water and recoiled again with lyophilization. All the extraction technique was done at 0 to 5 degrees, cold technique. He thus obtained a perfectly purified penicillin. He could try it on a mouse and found that it was very safe.
Florey, very interested, immediately repeated this experiment which revealed the nontoxicity of the substance. So Oxford scientists had penicillin finally concentrated, stable and purified. They concluded that it should be used as an antibiotic.
The crucial experiment was made on May 25, 1940, on three groups of mice infected with Staphylococcus, Streptococcus and Clostridium septicum. In June 1940, it was time for great German offensive, that of Dunkerque. The final experiment was made on July 1st on fifty mice. The results were published on August 24, 1940.
As a result, the Oxford team was formed. We could appreciate the work in collaboration to develop an idea already known. Fleming said that for something to be born from something completely new, you need an event. He himself had seen a mold destroy microbes and his mind was sufficiently prepared to interpret this experience and understand practical possibilities.
Upon reading Florey’s and his associates’ communication, Fleming had the vision of what he had wished for, the discovery of the purified penicillin. He rushed to Oxford where he met for the first time Chain. He exclaimed, “But I already thought you were dead!” Fleming then said,” You were the best chemist scientists that I would have liked to work with me in 1929 “.
All this happened at the time of the Germans’ attempt to invade England. It was now necessary to try penicillin treatments on human infections. Florey went to see the leaders of a big chemical factory and asked them if they were ready to produce it. After some thought, the chemists refused for the war occupied them entirely.
However, after having produced sufficient quantities of penicillin, it was possible to treat two wounded who healed completely. Unfortunately, England in 1941 was under constant shelling and the production of penicillin in industrial quantities was impossible. Florey then left in June 1941 for the United States by Lisbon. He was carrying away the lining of his clothes boxes of mold.
Start of industrialization in Peoria
In New York, Florey found an American friend who directed him to a laboratory in Peoria, Illinois. This laboratory was created to do research in order to use organic by-products of agriculture that polluted rivers of the Middle West. The goal was to convert this waste into a usable fermentation product.
Chemists had concentrated their efforts on Penicillium chrysogenum. The shot Nitrogen source was the corn steep liquor of corn soaking. They had succeeded in drawing gluconic acid. Florey then explained to the Americans the considerable interest of penicillin in the therapy of previously fatal infections. Americans were stunned by the fact that no patent had been taken by the English to protect their discovery. The Americans suggested this “corn steep liquor” as a medium for similar crops. They obtained at once yields twenty times higher than those of Oxford. A little later, glucose replacement with lactose accelerated again the yield.
Florey was a pilgrim to the United States and Canada, so he went back to England with the promises of two American homes that had committed to producing ten thousand liters of penicillin each and send to Oxford for research medical.
Florey also had the approval of Dr. Richards, chairman of the Medical Research. So he had the support of the American government. During Florey’s successful trip to America, the team, under the direction of Chain, had worked a lot. This work was done despite the bombings that severely damaged Fleming’s houses and laboratories.
A real factory had been organized in Oxford with young girls who were called “penicillin girls” who were covered with wools and warmly gloved to live in cold rooms. So, did they have at their disposal a small stock that allowed to try the treatments before owning the ten thousand liters in America?
There was a huge number of infected wounds, including bad burns and streptococcal fractures. No valid effect was obtained with the sulphonamides. The first patient treated with penicillin was a young New Zealand officer.
Pulvertaft, a surgeon in Cairo, had noted that for six months in bed, having fractures complicated of both legs, this patient was to die soon. He had then about ten thousand units of penicillin that he distributes into local injections in the legs, with three bites a day. From the first treatment, he found the streptococci inside the leucocytes. This seemed to him a real miracle. In ten days, the left leg was cured, and in a month the young man was on his feet.
September 25, 1942, was a conference where the five major American firms: May and Baker, Glaxo, Welcome, British Drug Houses and Boots collaborated on Medical Research Corporation. Other companies, Imperial Chemical Industries, Kenball, Bishop were in direct contact with the Oxford team, Florey and Chain.
All of them agreed to give all the necessary explanations for the start-up of the English fabrications. Many English scholars went to the United States to study progress made. The massive production of penicillin started only slowly. The firm Charles Pfizer, who had great experience in manufacturing, sent one of his managers in Brooklyn to study the healing of the sick, especially infectious endocarditis.
Since 1943, American factories began to produce large quantities of penicillin, but initially, they were reserved only for the army. It was also necessary for Florey to recall that the first step to be taken was to a culture of infectious germs and a test of their sensitivity to penicillin. The treatments appeared at the beginning really miraculous, especially on gas gangrene but also on seriously infected wounds.