| Author: | Stefano |
|---|---|
| category: | Chemistry |
Penicillin. This is definitely one molecule that conquered the territories of the grim reaper.
Before Penicillin, a minor wound infection could mean a gangrene (followed by amputation), death, or all of them if you were particularly unlucky. People used to die for minor skin scratches. Falling, handling a rose, sewing, were all potentially deadly activities. Many other diseases we now solve with a couple of pills were a death sentence before the '40s.
The effects of some molds as healing agents was known since the middle ages. Saddles were kept in conditions to promote mold formation, because it was common lore that scratches on horses recovered better when a moldy saddle was used. It was however only in 1897 that a young French physician, Ernest Duchesne, observed and formally tested antibiotic effects of molds, performing formal trials during his doctoral work. Experiments confirmed his findings, but his young age and military involvement prevented him to establish the findings as relevant to the scientific community.
Fast forward 20 years. Andre Gratia and Sarah Dath observed in the 20's that molds of Penicilliumin inhibited growth of certain bacteria. They made a paper who received little to no attention, and they pursued different research directions.
Time passes again. It is 1929, and Alexander Fleming is annoyed by the contamination produced by airborne molds on his Petri dishes of Staphylococci. He was rather untidy researcher, but apparently it paid off, since his lack of proper care lead him to the discovery of lysozyme (actually, a rediscovery. Laschtschenko characterized it 13 years earlier). Thanks to his previous experience with productive mistakes, he noticed that where the mold was growing the bacteria were unable to survive. The mold turned out to be part of the genus Penicillium
After some more experiments, helped by colleagues, Fleming isolated the substance related to the antibacterial effect (also using his previous experience with Lysozyme) and publishes his results, but it was no breakthrough. Fleming was not particularly excited over his discovery, and continued working on other projects basically forgetting about it. In fact, there were some considerable issues of primary importance to solve:
- The amount of active component was small, too limited to be profitable for the industry and functional on humans. The production of amounts with therapeutic effect would have required huge quantities of mold, and growing it was very difficult.
- Penicillin is chemically very fragile. It works on a Petri dish and in guinea pigs, but there was no guarantee it could stay active in sufficient quantity to deliver antibacterial effects in humans.
- Penicillin had to be injected, and the body eliminates it in urine after a few hours. To keep its concentration high enough to kill bacteria, attempts were made to recover it from the patient's urine and re-inject it, but even then the amount was not sufficient in most cases.
As the Second World War was approaching, there was strong demand for substances showing antibiotic properties. The only available drug on this respect was Prontosil, but it wasn't well received both because of side-effects and because of low commercial payback (it was already off-patent). Thanks to the effort and determination of Howard Florey, Ernst Chain, and Edward Abraham, production of Penicillin moved from laboratories in Britain to the United States, where an initial mold strain obtained from a cantaloupe was optimized by progressive selection to produce huge amounts of active component.
Chemically, Penicillin is a beta lactam, a cyclic compound with a characteristic square core. The particular shape of the molecule blocks the enzyme transpeptidase, whose role is to tighten the knots of the molecular net that keeps the bacterium whole: the cell wall. During bacterial growth, and in particular at the end of duplication, a consistent section of the wall is created. With a broken transpeptidase this step is no longer possible: the bacterium is, so to say, unable to duplicate, and the infection cannot spread further.
Penicillin triggered extensive research on antibiotic drugs and the pharmacological research as we know today. In particular, bacteria evolve methodologies to fight the action of drugs, at the limit of becoming completely unaffected, hence new strategies and substances must be developed, tested, and released for public usage.