COVID–19 and the endless search for ‘scientific serendipity’!

Many scientific discoveries were indeed serendipitous and medical science is no stranger to serendipity. The word serendipity is derived from Senrendip (an ancient name for Sri Lanka) and is applied for discoveries that were accidentally stumbled upon. The word is sometimes translated as ‘happy accident’. A number of products from nitroglycerine (in its medical use, not in blasting powder); the first antibiotic penicillin; the local anaesthetic lidocaine; several analgesic drugs, anti–psychotic drugs, anti–cancer drugs, tranquilisers; the use of an antihistamine as an appetite stimulant; several pesticides like malathion and the sticky Post–it have been serendipitously found.

We all know that Alfred Bernhard Nobel made his millions with the discovery of nitroglycerine a component of dynamite, and other explosive substances. In 1895 he developed a condition called angina pectoris and died of cerebral haemorrhage in 1896. When blood vessels which supply blood to the chest muscle are constricted, depleted blood supply and the resultant depletion of oxygen supply cause chest pain known medically as angina pectoris.

The reason for Alfred bequeathing the bulk of his estate for the endowment of the famous Nobel Prizes is not clear. According to a theory, when in 1888 his brother Ludvig died in France, a French newspaper mistaking him to be Alfred reported, “The merchant of death is dead.” (The expression used in the Indian context was not original, after all!) It was possible Alfred wanted to make reparation for his probable posthumous notoriety.

In 1944 Antoine Balard working at the Sorbonne observed that inhalation of isoamyl nitrate gave him headache. Other researchers like Frederick Guthrie in Owen’s College, Manchester experimented with nitrates. Thomas Lauder Brunton, a researcher who worked at the Edinburgh Royal Infirmary put nitroglycerine to use. It was William Murrell’s work at the Westminster Hospital (his findings were published in The Lancet) that confirmed nitroglycerine dilates blood vessels, reduces blood pressure and relieves pain caused by angina pectoris. In the initial days British doctors took care to see that patients were not unduly scared if they found out that the tablets they were prescribed were the same compound that was used in dynamite. The longer acting form of nitroglycerine (pentaerythritol tetranitrate) was introduced in 1896 on an experimental scale and its applicability was finally announced in 1901. Had it been in use in 1896, it would probably have saved Alfred Nobel’s life! The active form of the drug known as isosorbide is prescribed (for sublingual use for faster absorption) even today.

While on the subject of angina pectoris, the multinational pharmaceutical company Pfizer, which experimented with sildenafil citrate, was unable to obtain desired results. It did not reduce cardiac pain as the researchers hoped. However the researchers were pleasantly surprised by an unintended effect the drug caused. In some patients it caused penile erections. Enthused by a study conducted in the Johns Hopkins University, Pfizer continued work on sildenafil. An enzyme called nitric oxide synthase (NOS) localised in the penis produces the neurotransmitter nitric oxide, which is responsible for penile erection. Sildenafil was found to reverse the action of NOS inhibitors. Thus was borne the blue pill known the world over as Viagra! What is less known is that Viagra is equally effective in women, in inducing clitoral erection. It is particularly useful for women with sexual dysfunction caused by a class of antidepressant drugs known as selective serotonin reuptake inhibitors (SSRIs).

Another drug minoxidil which was originally intended to lower blood pressure turned out to have an unintended consequence. In initial trials it caused body hair growth in some female patients. Continued trials with the drug proved that it is useful for hair regrowth in what is known as ‘male pattern baldness’. There are other drugs with a similar ‘side effect’ but are limited in their use because of other concomitant adverse effects. The advantage with minoxidil is that it is available as a lotion and can be locally applied.     

What is strange in the current scenario is for researchers trying to look for anti–viral properties in every conceivable drug. In the absence of a preventive vaccine for the COVID–19 virus, researchers have experimented with hydroxychloroquine an anti–malarial drug, also found to be useful in the treatment of rheumatoid arthritis, azithromycin an anti–biotic and remdesivir an anti–viral drug—with varying results. As the pandemic grips the whole world, there is prestige involved in being the first to find a remedy for it.

 

The latest candidate drug under experimentation is dexamethasone. A group of researchers at the University of Oxford said “trial results show the drug [dexamethasone] reduced death rates of the most severely-ill Covid-19 patients by around a third.” The British Prime Minister hailed it as the “biggest breakthrough yet” in the fight against the disease. However, as per a report published in the Independent, US experts led by Dr. Kathryn Hibbert, director of the intensive care unit at Harvard’s Massachusetts General Hospital expressed scepticism about the findings of the trial. They cited the recent publication and withdrawal of a study in The Lancet, the results of a trial with hydroxychloroquine as a cautionary tale. (“Dexamethasone: US doctors cast doubton UK’s coronavirus ‘breakthrough’”, June 17, 2020.)

 

Dexamethasone belongs to a group of drugs called glucocorticoids. As the name suggests the primary function of glucocorticoids is to conserve glucose for use in times of stress. The glucocorticoids convert carbohydrate into glycogen and store it in the liver. But corticosteroids are also known immunosuppressants. It is for this reason they are prescribed along with other immunosuppressive drugs like cyclosporine and azathioprine to prevent donor organ rejection in organ transplant cases. An earlier commentary article published in The Lancet (“Steroids could do more harm than good in treating coronavirus”, February 6, 2020) highlighted the immunosuppressant property of the drug and advised caution in including it in treatment regimens for COVID–19.

 

As experts and researchers grapple with finding a remedy for the corona virus infection that has changed the world forever, the last word on the subject is yet to be said!

This is a slightly modified version of the article originally published in The Time Of India Blogs

Labels: Analgesics, Azithromycin, Anti–cancer drugs, Antihistamines, Anti–psychotic drugs, Corticosteroids, Dexamethasone, Glucocorticoids, Hydroxychloroquine, Isosorbide, Lidocaine, Minoxidil, Nitroglycerine, Nobel, Penicillin, Post–it, Remdesivir, Tranquilisers, Serendipity, Sildenafil, Viagra