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Obituary: Sir James Black

Published on: 06/04/10

Sir James Black, the British physician and pharmacologist who discovered some of the biggest breakthroughs in medicine in the 20th century, has died at the aged of 85.

His most momentous inventions were the drugs propranolol, the first successful beta-blocker for heart problems (marketed as Inderal), and cimetidine (Tagamet) for stomach ulcers.

Sir James was also a pioneer of what is today is known as ‘rational drug design’, using scientific principles rather than serendipity or trial and error to guide his work.

These discoveries were not only significant advances for patients, but became hugely successful for the two British pharmaceutical companies which marketed them, ICI and Smith, Kline & French respectively.

His contribution to medical science was recognised in 1988 when he was awarded the Nobel Prize for Physiology or Medicine, sharing the prize with two scientists from Wellcome, Gertrude Elion and George Hitchings.

In 2000 he was awarded the Order of Merit - the highest honour which can be bestowed on an individual personally by the Queen.

Early life

Born in Uddingston in Lanarkshire, he grew up in Cowdenbeath, Fife, the fourth of five sons of a mining engineer.

Encouraged by his teacher at Beath High School, Black sat the entrance exam for St Andrews University, and won the Patrick Hamilton residential scholarship. Black qualified in medicine in 1946, and then joined the St Andrews physiology department and acquired the basic ideas which would inform the rest of his research career, including how blood flow acts as a metabolic throttle.

By 1950, Black was asked to set up a new physiology department, at the University of Glasgow and over the next eight years he built a state-of-the-art physiology laboratory with the most advanced cardiovascular technology available.

From that point on, Black would focus his research by targeting the source of disorders, rather than their symptoms. He sought to design molecules to interact with cell receptors, the proteins on the surface of cells or within them that control their behaviour.

In this way, he was among the first to pioneer today’s approach to targeted, rational drug design.

The ICI years and propranalol

Black wanted to develop cell receptor modulators for various disorders, but needed a multi-disciplinary team of scientists and resources to help him achieve his goal. He approached the ICI pharmaceuticals division for help, and was employed at ICI’s exciting new labs at Alderley Park, Cheshire.

He joined ICI in the summer of 1958 as a senior pharmacologist, and later said these years were “some of the most exciting of my life”.

Black said his head of research helped defend his pursuit of a scientific concept from pressures to focus on other, more apparently lucrative areas.

“Dr Garnet Davey (subsequently Research Director) constantly supported me and, I have no doubt, fought many battles on my behalf to keep the initially controversial programme going. All I ever promised was that I was sure I could develop a new pharmacological agent which might answer a physiological question. Any utility would be implicit in that answer.”

The result of their labours was propranolol. The drug is a non-selective beta blocker, i.e. it blocks the action of epinephrine and norepinephrine on both β1- and β2 - adrenergic receptors.

Black and his team derived propranolol from the early-adrenergic antagonists dichloroisoprenaline and pronethalol. The key structural modification was the insertion of a methoxy bridge into the arylethanolamine structure of pronethalol. This greatly increased the potency of the compound, and also eliminated the carcinogenicity found with pronethalol in animal models.

Known under numerous brand names, including Inderal and Avlocardyl, the drug became a major commercial success for ICI’s pharma divison, eventually renamed Zeneca, today part of AstraZeneca.

Smith, Kline & French and Tagamet

In 1964, he defected to ICI’s rivals Smith, Kline & French Laboratories to pursue another project that he had been thinking about for some time.

Histamine had once been widely used as a diagnostic test of a patient’s susceptibility to develop a peptic ulcer, as it strongly stimulated the production of gastric acid. Black believed that a drug that blocked the action of histamine could be very effective in treating ulcers.

Modelled on the same principles as the beta-blocker project, the work was controversial in the company, but by 1972, Tagamet (cimetidine) was in development, and was launched by 1976.

Tagamet was a huge commercial success, representing a significant advance in treating peptic ulcers. It became the first drug to exceed annual sales of $1 billion, and thus the first blockbuster.

British rivals Glaxo decided to develop a competitor drug, and refocused its research programme to produce Zantac (ranitidine).

By 1973, Black was seeking freedom from commercial demands, and became professor in pharmacology at University College London. He wanted to establish this new branch of pharmacology as an academic discipline. But after four years he accepted an invitation from John Vane, the director of the Wellcome Foundation.

1977-1984 Wellcome Foundation

In 1977 he returned to industry as director of therapeutic research at the Wellcome Research Laboratories. Then in 1984 he headed up a new academic research unit, funded by Wellcome but operating with total independence, at King’s College London in 1984.

He remained at King’s as professor of analytical pharmacology until 1993 and was appointed professor emeritus on his retirement. He served as chancellor of Dundee University from 1992 until 2006 and in the same year founded the James Black Foundation, a not-for-profit group of scientists engaged in new drug research.

Professor Anton Muscatelli, principal and vice-chancellor of the University of Glasgow, said: “Sir James was one of a handful of great scientists, who through his commitment, intellect and insight achieved a global impact and one which has improved the lives of many. Professor Richard Bond, a close friend and colleague, and fellow member of the British Pharmacological Society, observed: “To pilot one drug into the clinic is exceptional, to do so twice is a truly remarkable feat.

“There is little doubt that Sir James is one of the most prominent pharmacologists to have ever lived, and quite possibly the most prominent considering the number of people his inventions and discoveries have benefited.

“Sir James’ passion for receptor theory was also contagious, and all whose lives he touched will be affected forever.”

Sir James is survived by his wife Rona Mackie, whom he married in 1994, and a daughter, Stephanie, from his first marriage, to Hilary who died in 1986.

• Sir James Whyte Black, pharmacologist, born 14 June 1924; died 21 March 2010.

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