Sunday 25 April 2021

The "Gold Maker" and the Unlikely Triumvirate

Human race is in the middle of one the most widespread global pandemics in history. Interdisciplinary and international teams of scientists and multinational conglomerates have embarked on a race against time for developing ways to immunize people against many, if not all, coronaviruses. Without downplaying the the gravity of the crisis, it may be noted that while some of the pandemics that ravaged humanity in previous centuries particularly affected young children and babies, for some reason or the other, the coronavirus has mostly spared them. We were at college when another deadly pandemic appeared to make a re-entry through Surat, India in 1994. Immediate intervention, in the form of prevention and treatment avoided the spread of the disease far and wide and fewer than 1,200 people were diagnosed with the plague, which was contained in 2 weeks. Tetracycline had hit the headlines then, as the life saver, just as Covishield and Covaxin now. Panic stricken people thronged medical stores and tetracycline tablets were sold out in no time. The 325-crore Indian Drugs and Pharmaceuticals Limited, which had accumulated huge losses and had been contemplating stopping production of the antibiotic, had to run three shifts in its two plants to meet the public demand.  

The first tetracycline antibiotic was the Aureomycin. The drug has an interesting history behind it. A team of most unlikely triumvirate had collaborated in the development of the drug. A reclusive immigrant who was refused citizenship, had recruited the son of a Confederate officer for the discovery and the most famous black doctor in America, the son of a freed slave, to conduct the clinical trials in the development of the drug, one of the major milestones in disease control and eradication in human history. 

Circa 1942, Dr. Benjamin Duggar, an American plant physiologist, received a call from the Chief of Research of a small pharma company in New York, Lederle Laboratories, enquiring if he would like to take up a role in the research to develop the next broad-spectrum antibiotic. The 70-year-old had been advised to go into retirement by his University as he was “too old” and because his specialty was no longer needed there. The Chief saw “experience” in what others judged “too old” and thought that in Dr. Duggar he might have found Lederle’s “antibiotic hunter.” One day in 1945, while extracting molds from soil samples, Dr. Duggar noticed one with an unusual gold-color. With the Chief overseeing his work, he tested the mold he had labeled A-377. To the elation of the team, A-377 proved effective in halting the growth of both Gram-positive and Gram-negative bacteria, including the microbes responsible for bubonic plague, tuberculosis, typhus, and Rocky Mountain spotted fever. The quest for the first broad spectrum antibiotic since streptomycin had been realized. However, with the limited manpower and resources available, it took them another three years of testing, before Duggar was confident enough with his finding to publish a paper. In the paper the antibiotic organism he discovered was given the name ‘streptomyces aureofaciens’, the “gold maker.” His colleagues liked the name and gave the drug its brand name, Aureomycin (Aureo is Latin for gold). The paper notified Lederle’s much bigger competitors that they had lost the race to find the first post-war broad-spectrum antibiotic. If Fleming's pencillin was effective only against gm +ve bacteria and Vaksmann's streptomycin was effective only against gm -ve bacteria, it was the Aureomycin which was the first to counter both. 

Lederle Labs did not have an agreement with any top testing hospital or medical school for conducting the human tests. The Chief and Dr. Duggar decided to approach Dr. Louis Tompkins Wright, a New York based Surgeon and Civil Rights Activist, whom they considered eminently qualified to conduct the tests. He had by then published nearly 90 papers in leading scientific journals, 35 of them about antibiotics. Dr. Wright, who had just returned to work after a three-year leave of absence to recuperate from a severe bout of tuberculosis, was enthusiastic about undertaking the trials. He started his trials of Aureomycin on patients with infections that had resisted all other treatments. He went on to publish more than 30 papers on his trials with the antibiotics and his research paved the way for the drug to earn FDA approval for manufacturing and widespread use. 

However, tragically, by the time Aureomycin was ready to go on sale in December 1948, Lederle’s Chief of Research was no longer alive to celebrate it. He had passed away in August, at the age of 53, unheralded and virtually unknown beyond a small group of researchers. His colleague Doron K. Antrim paid a touching tribute with the following lines: "You've probably never heard of him; yet because he lived you may live longer". 

Millions of people around the world live a longer and healthier life because of folic acid vitamins, tetracycline antibiotics, and anti-filarial (the drug Hetrazan which was used by WHO against filariasis) and anti-cancer drugs (Methotrexate is still in widespread clinical use today), developed under the tutelage of this wizard of wonder drugs. Besides the conquest of many illnesses that had troubled mankind for centuries, he had contributed to the understanding of life processes such as muscular contraction which gets the living world's work done. He was in the Harvard tradition "the brain" and could perhaps have claimed that the boys he had guided and inspired were just so many "hands". But that would have been unfair to them as it would have been so unworthy of himself. "The victories of science are rarely won single handed," he insisted. "No one man should get the credit." His last expressed wish to colleagues was: "If God will spare me another couple of years, maybe we can cure another disease." 

He is not famous, he had an extremely difficult childhood, he passed his matriculation examination in his third attempt, and overall, he had a tragic life worth a biopic like The Man Who Knew Infinity. But the contributions of the Chief of Research of a that small pharma firm in New York, Dr. Yellapragada Subba Rao, in biochemistry and medicine keep performing a million good turns for mankind each day, around the world. And his rather unlikely team reiterated the fact that scientific collaboration knows no boundaries other than those of knowledge itself.