Celebrating the lives of two giants of medicine

Sir James Black wit the portrait of himself by George Devlin.
Sir James Black wit the portrait of himself by George Devlin.
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Professor Michael Barrett of Glasgow University on moves to commemorate one of its most famous former staff, who along with a colleague created the notion of a ‘blockbuster drug’.

The University of Glasgow, currently in the midst of a £1 billion redevelopment, is renaming its West Medical building – central to teaching and research at the university for nearly 100 years – as the Sir James Black Building.

It honours one of its most famous former staff, a Nobel Laureate who pioneered ways to invent drugs to treat common diseases.

Black’s career paralleled that of another great Scottish drug discoverer, Sir David Jack, and between them they introduced many of the most important drugs known to mankind.

Both were born in 1924, they grew up in Fife and were the sons of miners. They took turns to introduce the world’s best-selling medicines and transformed the pharmaceutical industry, creating the notion of the “blockbuster drug”, saving millions of lives while making billions of dollars for their companies.

Black, born in Uddingston, attended Beath school in Cowdenbeath. Jack, born in Markinch, was schooled 16 miles east at Buckhaven High.

Aged 15, Black won a scholarship to study medicine at the University of St Andrews. Jack turned down his first chance of going to university to work as an apprentice pharmacist in Boots in Cupar. Only later did he sit a degree in chemistry and pharmacy at what is now the University of Strathclyde.

After university, Black decided that medical research, above practice, would allow him to have maximum impact on the alleviation of human suffering. But like many working-class medical students, he graduated with substantial debts.

He was obliged to take the first suitable work that came along, and took a post with the University of Singapore where he set up a department of physiology. After four years he returned to Scotland, establishing a physiology department at the vet school at Glasgow University. Black then took an unusual career pathway, exchanging academic and industrial positions, seeking to satisfy both his intellectual curiosity and a desire to move ideas from his mind to the clinic.

It was at ICI in the 1960s that his first major breakthrough came, with the discovery of compounds that could dampen the excitatory effect of adrenaline on the heart, by binding to the beta receptor for this molecule. These so-called beta-blockers diminished the heart’s use of oxygen and with it downplayed the inflammatory responses that can lead to cardiac disease. Propranolol, the leading compound from the work, has saved the lives of millions of people. It soon became the world’s best-selling drug.

It was for the transformational concept that Black was awarded the Nobel Prize for Physiology or Medicine in 1988.

David Jack was among those inspired by his work. His first job at Glaxo in the early 1950s had involved seeking new formulations of penicillin to improve its ability to remain in the body.

Jack’s interests had always been at the practical end of delivering pharmaceuticals that could alleviate common symptoms in masses of people. His first great commercial innovation was salbutamol (ventolin) – which blocked specific histamine receptors in the lungs and, when delivered by an inhaler, gave immediate relief to asthma sufferers. The product was launched in 1969 and remains the biggest ever selling drug used against asthma.

In the 1960s, Black too had turned to histamine receptors – believing that by blocking the H2 type in the stomach he could inhibit acid secretion that led to gastric ulcers – and by 1977, now at Smith, Kline and French, Black created a new drug, cimetidine, marketed as tagamet. It blocked those histamine receptors precisely as Black had hoped and was the saviour of millions of people suffering gastric ulcers. It soon became the number one selling drug globally.

Good as it was though, tagamet had problems. It was quickly cleared from the body so needed to be given frequently and showed some undesirable side-effects.

Up stepped Jack and his team at Glaxo, following closely on Black’s shoulder, tinkering with derivatives based on tagamet’s structure, to create longer lasting, more potent and less toxic versions.

Eventually they created ranitidine, branded as zantac, and launched in 1981. It became the first $1 billion-a-year selling drug, and opened the way for Glaxo to expand its research.

I recently met Lady Rona Black, Sir James’s widow – herself a distinguished physician-scientist who publishes under the name of Rona Mackie. We discussed “Jim”, whom she had met through mutual friends at the Glasgow vet school. Mackie has just donated a portrait of Black, by George Devlin, to the University of Glasgow, where it will take pride of place in the new building.

The Sir James Black Building will sit adjacent to the Davidson building, which, remarkably, was named after Rona’s father –Norman Davidson, professor of biochemistry . The Devlin portrait shows Black in a reflective moment.

“He had a remarkable capacity to think in three dimensions,” Mackie told me. This makes sense: drugs work by making a three-dimensional fit into the proteins they target. Today, high-powered computers can predict such interactions, but 50 years ago only a few brilliant human brains were capable of such insight.

Mackie recalled with fondness a meeting at the Royal Society where Nobel prize winners were being introduced to the Queen. Black was uncomfortable with the notoriety and Mackie had to work hard to filter the unrelenting invitations for him to speak and lend his name to endless causes. However, the Royal Society event was one where he could engage with some equally brilliant minds.

One small group of Laureates hob-nobbed with the cream of the British establishment. Black, however, was tucked away in a corner, along with two other maverick Nobel prize awardees.

The three of them were engaged in deep reflection, drawing structures of drugs and the targets to which they bind. The other two included Cesar Milstein, an Argentine who had invented a process to produce what we call monoclonal antibodies. The other mischievous laureate was Max Perutz, a Jewish scientists who had fled Nazi Germany. Perutz won the Nobel prize for creating X-ray images of meticulously crystallised proteins, which enables us to determine the actual shape of these tiny molecules.

Black was a scientist through-and-through, although he also loved music and the arts. Mackie told me how Black’s father had introduced his five sons to classical music, each fortnight saving money to take himself and one of them to a concert.

At one time, whilst working his notice period at ICI, Black took up the guitar. He also became friendly with fellow Nobel laureate, Irish poet Seamus Heaney, to whom he had the pleasure of awarding an honorary degree at the University of Dundee in 1993, when he was chancellor. Black would be delighted that Dundee today is the world’s leading academic institution for drug discovery.

David Jack too grew up with music. At school he played the cornet and remained a great enthusiast for live concerts and opera. Jack was a talented golfer and also enjoyed football, following his favourite club, Raith Rovers. Black too kept an eye on the progress of his local team, Cowdenbeath, long after he had moved to England.

In spite of the enormous wealth they created for their companies, neither Black nor Jack cared much for material gain. Both were driven by a desire to create drugs to ameliorate widespread suffering caused by chronic and, then, poorly treated diseases.

After creating tagamet for Smith Kline and French, Black returned to academia, first at University College London, where he found the research councils sceptical of funding his innovative approach to research. So, he returned to industry, first to the Wellcome Research laboratories, but clashed with another Nobel laureate, Sir John Vane, and so moved again to Kings College in London before, finally, in the year he won the Nobel prize establishing his own research centre with funding from the pharmaceutical company Johnson & Johnson.

Jack did work briefly after graduation in academia at the University of Glasgow before entering industry where he remained for the rest of his career. The research group he created at Allen and Hanbury’s small site in Hertfordshire, became the engine of Glaxo’s global machine – making other new medicines for asthma, migraine, sickness, hypertension and more. Shortly after his death in 2011 Glaxo named the site The David Jack Centre.

Although much of his greatest work was in carried out in England, Sir James Black always felt he owed Scotland for his education and stoking his curiosity. It was his wish to be buried in Scotland.

The intertwining of Sir James Black and Sir David Jack is remarkable. More remarkable still is that these sons of miners, born within four months of each other and schooled just miles apart, transformed the pharmaceutical industry into the global giant it is today.