20091217

Antibiotics

After bacteria was discovered and germ theory was accepted scientists turned their minds to the possibility of treating disease caused by bacteria and vira. If you want to kill bacteria selectively, ie, with low side effects, there has to be a principle for why this would be possible. A difference between bacteria and man.

Paul Erlich (1854-1915), a German medical scientist, and a student of Robert Koch, tested different dyes on human, animal and bacterial cells and found that he could find dyes that discriminated between these variants. He thus had an idea to work on to find selective toxins against bacteria. He thus started the field of synthetic chemotherapy in the late 1880s. In 1908 he developed Salvarsan together with his student Sahachiro Hata that was active against syphilis.

Enter industry, with Gerhard Domagk (1895-1964) a German pathologist and bacteriologist who got the Nobel Prize in physiology and medicine 1939 for the first commercially available antibiotic, a sulfonamide called Prontosil (Bayer). Domagk was forced by the Nazi regime to turn down the prize because the 1935 Nobel Prize, given to a Nazi critic Carl von Ossietsky, had angered them and they had outlawed German citizens to accept the prize.

Sulfonamides were revolutionary at the time but were replaced by the cell wall toxic penicillin that had better effect and fewer side effects. Bacterial cell walls are unique to bacteria. Penicillin opened the field for naturally occurring antibiotics. The antibacterial effect of Penicillum spp was first described by John Tyndall in England in 1875. Unfortunately, his finding went unnoticed until Alexander Fleming found penicillin in 1928. Again its therapeutic potential was not used until Ernst Chain and Howard Florey, pursuing another naturally occurring antibiotic called gramicidin, became interested in penicillin. Chain, Florey and Fleming shared the 1945 Nobel Prize in Physiology and Medicine.

Bacteria unfortunately have a tendency to become resistant against available antibiotics. Luckily this year's Nobel Prize in chemistry is awarded for the crystal structure of the ribosome. It so happens that the ribosomes of bacteria and those of humans differ significantly and that this has shown to be the basis for many of the naturally occurring antibiotics that bind and inhibit the bacterial ribosome and thus inhibits bacterial proteins synthesis which kills the bacteria. The detailed structure of the ribosome can now be used to develop a new generation of synthetic drugs that bind to new sites on the bacterial ribosome according to a lock-and-key model.

Data from Wikipedia

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