In 1784, Horase Walpole introduced a new word to the English language – Serendipity. When a medical student was asked its meaning, he stated that it was a combined word for serenity and stupidity! The word was coined based on a fairy tale entitled, “The Three Princes of Serendip (an old name for Sri Lanka)”. As the Princes traveled they made many discoveries by accident and not by design. Thus, we have serendipity in the discovery of America by Columbus, the theory of gravity by Newton when an apple fell on his head, and the discovery of penicillin by Fleming, to mention but a few examples of serendipity.
Of relevance in our context today, we have many serendipitous discoveries in trichology.
As usual our ancestors led the way. An interesting event took place in South America many decades ago. In Venezuela and Brazil there exists a certain variety of Lecythis trees called, ‘coco-de-mono’ which produces tasty almond-like nuts, which are found within the hollow wooden pods on the branches of the tree. The locals call this the ‘monkey-puzzle tree,’ first because monkeys find it difficult to climb these trees, because of the rough surface, and second, even when the monkey reaches the pod it cannot get at the nut because the opening is too small for its finger and gets stuck. Finally after all this ado if it does manage to extract the nut and eat it death overcomes it! The natives have therefore learned to shun them however tasty the nuts may be and also warn the visitors to that area not to eat them. An explorer ignored the warning, like Adam did in the gardens of Eden and ate the nuts. Not only did he develop tremors and shivering but within a fortnight lost all his hair. In 1965, Francisco Kerdel-Vegas, then professor of Dermatology, University of Venezuela, isolated the active principle in the nut and identified it as the selenium analog of the sulfur amino acid cystathionine, called Cysta Selinonine (CS), and showed that the soil in that area was rich in selenium leading to chronic seleniosis. CS inhibits mitosis and probably interferes with the utilization of L cystine required for hair keratin, exerting depilatory and cytotoxic effects.
Minoxidil is a potent peripheral vasodilator used for hypertension. While taking it, many patients, both male and female, developed hypertrichosis. This was the basis of trying topical Minoxidil, which has been a boon for millions of patients with androgenetic alopecia (AGA).
Similar to minoxidil, finasteride was discovered by accident when it grew hair on the bald scalp in men treated for enlarged prostate. On December 22, 1997, the FDA approved a 1 mg dose of finasteride for the treatment of AGA.
Cyclosporin A (Cy.A) is an immunomodulatory drug with many indications, but is particularly used in transplant patients. A large number of renal transplant patients on long-term Cy.A become quite hirsuite. It probably prolongs the anagen phase of the hair cycle and also decreases the perifollicular lymphocytic infiltrate. Therefore, it was but natural to try the drug topically for both AGA and alopecia areata. However, it has not lived up to its reputation, producing at best a patchy regrowth on topical application.
Takigawa et al. accidentally discovered that mice treated with alpha difluoromethyl ornithine (DFMO), an ornithine decarboxylase (ODC) inhibitor, had markedly reduced hair growth. The study was extended to dogs and cats, which also developed alopecia. ODC was present in large quantities in the lower part of the follicular bulb in the anagen phase, but not in the catagen or telogen phase. Therefore, the next logical step was to develop a topical DFMO, eflornithine hydrochloride, for removing unwanted hair. Not surprisingly, there was a significant decrease in hair growth in hirsute women. Theoretically it can be used in pseudofolliculitis barbae and as a chemopreventive agent for actinically-induced skin tumors.
Thiazolidinediones (TZD) constitute a new class of medication used in the treatment of type II diabetes mellitus. They interact with peroxisome proliferator–activated receptor y (PPARy) to increase insulin sensitivity in various tissues. As the polycystic ovary syndrome (PCOS) is typically associated with abnormal glucose metabolism, it is but natural to try glitazones for PCOS. Surprisingly, not only did the free testosterone level decrease, but the hirsuitism accompanying the PCOS also improved significantly. In recent times, they have been found to play a role in treating lichen plano pilaris (LPP), as PPARy is involved in the pathogenesis of LPP.
Serendipity is defined as, “The faculty of making happy and unexplained discoveries by accident.” However, luck alone is not enough. You need to be a good observer. Jane Austen wrote in Emma, “A lucky guess is never mainly luck; there is always some talent in it.” As that great benefactor of humanity Louis Pasteur stated, “In the field of observation chance favors only the prepared mind.” Therefore, as clinical dermatologists let us always keep our minds prepared for serendipitous discoveries. Like the princes of Serendip, let the princes of trichology discover a lot more!