The age of chance
Drug development is a rational, scientific endeavour.
But many drugs have been identified by sheer fluke.
After treatment with iproniazid, patients with tuberculosis
sometimes became unusually happy. Iproniazid turned out to inhibit
an enzyme that breaks down serotonin and other neurotransmitters.
This led to the monoamine oxidase inhibitors class of
antidepressants.
Valproic acid, part of Depakote, used to treat bipolar disorder,
was discovered when it was used as a solvent in trials of a
possible epilepsy drug. The treated group improved - but so did
those on placebo. The effect was due to the solvent not the
drug.
The cancer treatment cisplatin was discovered when researchers
began studying the effects of electric currents on the growth of
bacteria. The bacteria grew to great size but never divided.
Further studies revealed that it was not the electric field having
an effect but the action of ammonium and chloride ions on the
platinum electrode, forming cisplatin.
Dedicated staff were instrumental to the discovery of
cyclosporin, used to prevent organ rejection. Employees at Sandoz
were encouraged to collect soil samples when on holiday or trips,
as part of the search for new antimicrobial agents. An unusual
fungus discovered this way, Tolypocladium inflatum, produced
interesting chemicals but none looked suitable for further
development. Later though, extracts were sent for a general
screening programme and turned out to be very good at suppressing
the immune system.
Warfarin began life as a rat poison. Its use as a blood thinner
originated in a failed suicide attempt by a US army cadet.
The use of lithium as a treatment for depression arose from a
study of uric acid metabolism. A water-soluble salt, lithium urate,
was used, and it was the lithium rather than the urate that
actually had medical benefits.
However, while luck may have provided the lead, it took insight
to spot the opportunity and a great deal of work to produce usable
products. As Louis Pasteur put it, "Fortune favours the prepared
mind".