The age of chance
Drug development is a rational, scientific endeavour, but many drugs have been identified by fluke
After treatment with iproniazid, patients with tuberculosis sometimes became unusually happy. Iproniazid turned out to inhibit an enzyme, now known as monoamine oxidase, which breaks down serotonin and other neurotransmitters. This led to the monoamine oxidase inhibitors class of antidepressants.
Valproic acid – part of Depakote, which is 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 in the placebo group. 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 sizes 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 in the discovery of cyclosporin, which is used to help prevent organ rejection. Employees at Sandoz were encouraged to collect soil samples when on holidays 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; however, extracts were later 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 made 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.
While luck may have provided the lead, it still took insight to spot these opportunities and a great deal of work to produce usable products. As Louis Pasteur put it: “Fortune favours the prepared mind.”