By Associate Professor Allan Blackman

This article was orignally published in the Otago Daily Times
on Tuesday 7 February 2012.

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Location: Science II, 5n4

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blackman@chemistry.otago.ac.nz

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I was feeling a bit poorly a couple of weeks ago, so I crawled from my
sickbed and made one of my relatively infrequent trips to the Doctor, who
prescribed a course of antibiotics. While remaining bedridden and feeling very
sorry for myself, I had occasion to recall the interesting genesis of the first
synthetic antibiotic. It’s all to do with dyes, and a father’s great love for
his daughter.
Up until a couple of hundred years ago, brightly coloured clothes were almost exclusively the domain of the rich, as the dyes used had to be sourced from either plants or animals. The colouration of one of Julius Caesar’s purple robes, for example, reputedly came from the extracts of 10,000 molluscs, while to dye anything crimson required lots and lots of cochineal insects from far-off Mexico.
However, all this changed thanks to William Perkin, who in 1856, at the
ridiculously young age of 18, patented the first synthetic dye, the
purple-coloured mauveine. His discovery changed the chemical industry overnight,
and spurred an enormous amount of research into other synthetic dyes – indeed,
the chemical giant BASF was founded in 1865 for this very purpose.
In 1925, BASF, along with five other chemical companies, merged to form I.G.
Farben (‘Farben’ is an abbreviation of the German word for ‘dye industry’) and
it was to here that the German pathologist Gerhard Domagk took a leave of
absence from his Professorship at the University of Münster in order to further
his studies on bacterial infections. He was working on a virulent form of
streptococcus, and wanted to be able to ‘stain’ the bacteria so they could be
easily visualised. For this, he used a class of simple, highly-coloured
molecules called azo dyes, and found to his surprise that some of these showed
promising activity against the bacteria. Chemical modification of one particular
azo dye gave a molecule called Prontosil, and in 1932, Domagk showed that this
protected mice against lethal doses of streptococci.
While this was a huge breakthrough, it was by no means certain that Prontosil
would be as effective in humans. And here, fate intervened. In 1935, Domagk’s 6
year-old daughter, Hildegard, pricked herself with a needle and suffered a
streptococcal infection – in those days, such infections were often fatal. She
was rushed to the doctor, who recommended amputation of the arm to save her
life. Domagk, aghast at the suggestion, gave her a dose of Prontosil – two days
later the infection had subsided and, soon after, she was discharged from
hospital. This incident, along with other somewhat more controlled clinical
trials, confirmed Prontosil as the world’s first effective synthetic
antibiotic.
Domagk was awarded the Nobel Prize in Physiology or Medicine in 1939.
However, a law passed by the Nazis forbade any German citizen from accepting the
award, and he did not make the journey to Stockholm until 1947. Sadly, while he
was awarded the diploma and the medal, he didn’t receive the monetary portion of
the prize.
While Prontosil was soon overtaken by Penicillin as the antibiotic of choice,
Domagk’s work laid the foundations for all modern synthetic antibiotics. For
this, we should be very grateful.