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

Indian Council For Re–Writing Secular, Rational, Scientific–Tempered History (ICRH)!

Those readers who have been following the trail of this blog would remember that it all began with the post “Should We Re–Write Indian History?” The secular, rational, scientific–tempered historians who have been re–writing history would have us believe that the objective for ‘re–writing’ is to present a secular, rational, scientific–tempered (SRST) version of India’s history and not to ‘Twist Facts To Suit Theories’ as alleged by ever–whining Sanghi Bhakts. 

In keeping with its avowed principles of SRST, the newly elected government (in 2004) reconstituted the Indian Council of Historical Research (ICHR) as the ‘Indian Council For Re–Writing Secular, Rational, Scientific–Tempered History’ (ICSRSH). The ICSRSH has been tasked to re–write India’s history as ‘secular, rational, scientific–tempered history’ (SRSTH). The doyenne of SRST historians, Ruma Li was appointed its Chairperson with similarly qualified and distinguished SRSTHs Irf Ha, Aud Tsk and Ran Gu as its members. The chairperson and members will have no fixed tenure but will be in office till the ICSRSH completes its job of re–writing India’s history and bringing it up to date. Other SRSTHs will be co–opted to write chapters related to specific periods.

It is not that there was no unofficially–officially curated history before, or that these eminences were not associated with history–writing earlier. There was and they were. Like all quasi–government bodies, the ICHR too was autonomous on paper but in actual practice it was the government that called the shots. It appointed its members and controlled its purse strings.

In the short interregnum of six years between 1998 and 2004 a ‘reactionary’ non–left government was in power and it attempted to make some changes in history–writing. The attempts were unsuccessful of course. The ecosystem—fuelled by power and pelf—the previous governments planted took deep ideological roots and it would need determined efforts of a massed army to undo their handiwork. All that the short–lived government achieved was a few screaming headlines denouncing its ‘toxic’ efforts to saffronise history–writing and Op–Eds predicting doomsday if the trend was not reversed.

As everyone knows, just as the history of the USA began in the eighteenth century, so did India’s history began in the tenth century. India had no history before then. The Council decided that Ruma Li and Irf Ha would write the history from the beginning till the reign of Shah Jehan. Aud Tsk would write from the reign of Aurangzeb onwards. The historians have the necessary research experience into the history of the periods. Besides they have knowledge of languages like Sanskrit and its allied languages like Prakrit; Avestan and its allied languages like Old and New Persian; Turkish and its dialects like Chagatai. They have acquired intimate knowledge of epigraphy in various languages and dialects; archaeology and architecture to be able to accurately decipher and interpret stone edicts and archaeological relics.

The Council also decided that Ran Gu would write the modern parts of India’s history beginning with Gandhi and Nehru. As Nehru was a talented cricket player—which he played with his English cohorts while in England—it was felt Ran Gu’s intimate knowledge of the game would stand him in good stead in interpreting the sporting streak in Nehru’s psyche. Nehru’s classmates in Cambridge recall that he was a sportive player who played the game not for winning but for the game’s sake. When he bowled he pitched the balls not to hit the stumps but to fall at the feet of the opposing batsmen to enable them to strike them off the field. When he batted he let the balls that were pitched at his feet alone to enable opposing bowlers to score maidens. By the by, not many know but in the field of horse racing, the word maiden is used to denote a horse that never won a race!   

Ruma Li began at the beginning, when Mohamed Ghazni began distributing hoarded temple wealth to the masses. How did Ghazni distribute hoarded temple wealth if India had no history before the tenth century? Only bigoted Sanghi Bhakts who lack rationality and scientific–temper (SBWLRAST) ask such impudent questions. Ghazni found the wealth in the form of forbidden infidel idols made of gold, studded with priceless stones. Each idol was estimated to cost several hundred thousand dinars. He also found wealth estimated at millions of dinars, hidden in temple vaults groaning and begging to be liberated.

Ghazni was a socialist, whose heart bled and bled for the weak and downtrodden. What? The concept of ‘socialism’ did not exist in in the tenth century the way it was since the nineteenth century? You SBWLRAST! The word might not have been used then but it is the spirit of the noble thought that is to be understood and interpreted by true SRSTHs. As a true patriot, Ghazni took away the wealth to be distributed to the people of his country. He gifted a part of it to the Caliphate but it was not because he was a bigot but because of his true allegiance to his religion. 

The noble, scientific–tempered visionary Ghazni reasoned, quite appropriately, that if the wealth was distributed locally in Hindustan, it would make people lazy and stunt the progress of the society. With the noble intention of providing employment to masons, sculptors and other artisans Ghazni ordered the Sri Krishna temple in Mathura be doused in naphtha, burnt and razed to the ground. It was estimated that it would take two hundred years to recreate the architectural splendor and sculptural grandeur of the temple. The altruist Ghazni wanted thousands of masons, sculptors and other artisans to be gainfully employed for the next two hundred years! He also understood that any new construction on such scale would uplift the economic mood of the society. Earlier historians missed this noble streak in the character of Ghazni. In order to set right the imbalance Ruma Li devoted a chapter to nuance his character.

Ruma Li meticulously chronicled the good deeds of the subsequent conquerors. There was neither Ganga nor Yamuna before Babur arrived in north India and of course there was no Ganga–Yamuna tehzeeb. First Babur dug the Ganga and two harems later his grandson Akbar dug the Yamuna. In between them they planted the tehzeeb comprising nazrana, jabrana, shukrana and ‘drink, dance and make merry’.

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Disclaimer: This is a purely fictional, satirical piece.