April 13, 2010

UK: Sir James Black, pharmacologist, died aged 85

LONDON, England / The Economist / Science & Tecnology / April 13, 2010 


Sir James Black

Sir James Black, pharmacologist, died on March 22nd, aged 85

ANYONE who has tasted the stress of modern life—who has got up, bolted a coffee, run for the train, missed the connection, come late for the meeting, raced through the presentation, lunched on a lager and a greasy burger—has reason to be grateful to Sir James Black. For Sir James invented the little white or pink capsule of the beta-blocker propranolol which, taken every day before breakfast, slows down the racing heart, lowers the blood pressure, soothes migraine headaches and calms stage-fright. And he also invented the round white pill of cimetidine, marketed as Tagamet, which stops ulcers forming in the stomach and acid indigestion burping up the windpipe. Take both, and the result is serenity—of body, at least.

This “couple of successes” would evoke a modest burst of laughter from Sir James. Although he won a Nobel prize for them in 1988, and though people called propranolol the most effective heart medicine since digitalis, he never thought them prizeworthy. Their importance lay not in the science, he said, but in the “accident” that they had made an awful lot of money—for ICI Pharmaceuticals and Smith Kline, naturally, rather than for him. Propranolol, first marketed in 1965, became the best-selling drug in the world until Tagamet, launched in 1976, displaced it. Both have their detractors, but neither has been supplanted.

Fame and attention made Sir James writhe with embarrassment, and wish aloud that he had some beta-blockers in his pocket. As the curious, genius son of a family of five generations of coalminers in rural Scotland, he had been schooled in self-effacement, and taught to give credit to others rather than himself. He therefore pointed out that other people, chemists, doctors, biologists, had done the groundwork for him. They had discovered that messenger molecules, or hormones, could recognise an affinity with cells and then “switch them on”, and that those two properties could be separated. He wondered, then, as he “walked round” the molecules, whether, if he cut here and trimmed there, he could change the messenger molecules’ behaviour: whether he could keep the affinity and get rid of, or suppress, the subsequent effects.

In propranolol’s case, he began by wanting to stop the overexciting effects of adrenalin on the heart. He therefore developed a chemical similar to adrenalin, which would bind with protein receptors for that hormone in tissues such as heart muscle. Thus bound, the receptors cannot react to adrenalin as well, so the hormone’s effects are reduced. In cimetidine’s case, his self-appointed task was to stop histamine molecules stimulating the cells of the stomach to make acid. He supposed these researches might be beneficial, but he never set out to make superdrugs, and scorned—in his gentle but insistent way—profit-seeking institutions that set dozens of researchers to synthesise thousands of molecules in case one might be useful. He built drug molecules because he had an idea, and was passionate to test it.

The drugs he invented acted as “blockers”, and 20% of the $825 billion annual turnover of the global pharmaceutical industry is earned by drugs developed on his principle. It took six years to develop propranolol, nine to make cimetidine, by a slow, dogged process of “bioassay” of his modified molecules on living tissue. He called his work “medicinal chemistry”, a cross between physiology, chemistry and the doctor’s career he had imagined he would follow when he first went, fizzing with nerves at 16, to take up his scholarship at St Andrews.

Minds, not money

His career was spent half in academia, half in industry, and he had problems with both. ICI (1958-64) and Smith Kline (1964-73) gave him lab space and support, but tried to rope him into team development and promotion of his inventions when Sir James, a natural loner and daydreamer, preferred to be wandering freely after the next idea. On the other hand, academia—St Andrews, the new physiology department at Glasgow, and University College, London—lacked the cutting-edge challenge of industry, distrusted his curricular ideas and, in latter years, seemed to borrow from the corporate world an obsession with making money out of science. Sir James was happier working independently in his own lab with a small team, an arrangement he found after 1984, with Wellcome Foundation funding, in King’s College, London. He was happiest of all in a room, or a pub, shooting the breeze with around two dozen young, fresh, inquiring minds.

“A pharmaceutical toolmaker” was how he humbly described himself, as if he was still in his forefathers’ mining trade. But statistics showed he was a lifesaver. In 1978, 255 in every 100,000 British men aged 35-74 died of coronary heart disease; by 2007, that figure had fallen to 65. By the time Sir James died, propranolol was also being tried on patients with post-traumatic-stress disorder. It was found to inhibit not only heart activity and the production of adrenalin, but also the action of norepinephrine, which consolidates memories. Stress, hypertension, indigestion, had all been conquered by “the country boy from the coalfields of Fife”. He did not live to find out whether he had also conquered the demons of the past. [rc]

Copyright © The Economist Newspaper Limited 2010.

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