Some Other Serendipitous Discoveries in Dermatology

Sir,

The interesting special article “serendipity in dermatology”[1] motivated us to enrich it further.

“Accidental” elevation in erectile function observed in angina pectoris patients administered test compound of sildenafil prompted its use in erectile dysfunction.[2]

Griseofulvin[3] got marketed (1959) as the first oral antifungal after a quarter century of development pursuant to observing failure of growth of newly planted conifers on Wareham Heath, Dorset, during the 1930s, purportedly due to the presence of a toxin in the local soil. During the Second World War, Brian, Hemming and McGowan detected depleted common soil microbes and abundant Penicillium janczewskii. The latter mold yielded Griseofulvin, a metabolite previously isolated from Penicillium griseofulvum.

In an attempt to identify the cause of pellagra, Bartolomeo Gosio isolated a crystalline product akin to phenol from a mold growing on spoiled maize, named it as “mycophenolic acid” (1913), tested it as an antibacterial against anthrax organism and found it too toxic for clinical use. Non-competitive inhibition of inosine monophosphate dehydrogenase causing cessation of purine synthesis was subsequently observed which led to its evaluation as an immunosuppressant in transplant surgery and psoriasis. Its morpholinoethyl ester, “mycophenolate mofetil,” enabled oral dosing and enhanced bioavailability.[3]

Sirolimus,[3] as also the earlier described macrolide cyclosporine, was isolated as an antifungal from Streptomyces hygroscopicus and named “rapamycin” after Rapa Nui, local term for the Easter island from where the soil containing this Streptomycete had been collected earlier by the Canadian medical expedition. This powerful immunosuppressant was eventually licensed in 1999 by Federal Drug Authority for use in kidney transplantation.

Terfenadine,[3] synthesized initially (1973) as a tranquilizer, was unable to enter the central nervous system. Subsequently Richard Kinsolving developed it—based on resemblance to diphenhydramine—as the first non-sedating antihistamine.

Zidovudine,[3] synthesized as a potential antileukemic drug, was found to be too toxic. A decade later, Wolfram Ostertag in cultured mouse cells found it to inhibit replication of the Friend leukemia virus belonging to the group of retroviruses, then unknown in humans. Isolation of HIV in 1983 prompted evaluation of zidovudine samples at the US National Cancer Institute by Samuel Broder and Hiroaki Mitsuya.

Use of tranexamic acid[4]—a plasmin inhibitor—by Nijo Sadako in 1979 to treat a patient with chronic urticaria who had melasma lead after 2–3 weeks to the “accident” of significant reduction of hyperpigmentation, eventually leading to the first oral drug for melasma.

Inspired by Koch's success with the methylene blue stain, Ehrlich tried to devise counterstain in the acid fast technique wherein an acid decolorizes only specific cells of a previously stained specimen permitting greater differentiation. He experimented during 1878–88 with a number of dyes to stain the TB bacillus until chance intervened one morning in the form of accidental lighting of a stove by his housekeeper in his home laboratory wherein stained preparations to dry were kept overnight. Inspecting these slides in great alarm Ehrlich was pleasantly astonished to see the tubercle bacilli standing out in bold color.[5]