James Black invented a new class of drugs to treat heart disease – beta blockers, and a new class of drugs to treat stomach ulcers – histamine antagonists. He was awarded the Nobel Prize for Medicine in 1988.
Black created these potent drugs using an entirely new approach to medical issues: he built synthetic molecules to block natural molecules from sites in the body where they cause problems.
Beta blockers and histamine antagonists rank among the most important new drugs of the twentieth century. Beta blockers were described as the greatest advance in treating angina for two centuries and have saved millions of lives. Black was first motivated to research heart drugs after seeing his father die of cardiac arrest.
The drugs Black created – their scientific names are propranolol and cimetidine – were the most prescribed drugs of their era. Cimetidine became the first prescription drug to realize more than a billion dollars’ worth of sales.
Black is known as the founder of analytical pharmacology.
Beginnings
James Whyte Black was born on June 14, 1924 in the small town of Uddingston, Scotland, UK. He was the fourth of five sons in a working class family.
His father had left school at age 14 to become a coal miner and had later studied mining engineering at night school.
James was still an infant when his family relocated to the mining village of Auchterderran in the county of Fife, where his father had been appointed manager of a colliery.
James’s mother was an enthusiastic Baptist. On Sundays the family would attend both morning and evening church services. Life at home was never too pious – someone was always playing the piano or some other instrument. James loved singing.
James’s father, like many miners, hoped his sons would not follow in his footsteps. He encouraged them all to get a good education and avoid the coal mines.
School
James was educated at Auchterderran Primary School followed by Cowdenbeath Secondary School, now renamed Beath High School.
His math teacher, Dr John Waterson, spotted James’s potential and urged him to enter, at age 15, the competitive entrance exam for the University of St Andrews. This surprised James, who despite studying music and math avidly, had thought of himself as taking life easy at school.
Studying Medicine
James’s brother William had already studied medicine at St Andrews. James had enjoyed leafing through his medical books and decided he would like to study medicine too. He passed the exam and was admitted to St Andrews.
The residential scholarship he won gave him free board at a hall of residence.
St. Salvator’s Hall – James Black’s residence at St Andrews.
He arrived at St Andrews in October 1940 with Britain under attack from Nazi Germany. A year earlier, Poland had been invaded by the Nazis from Germany and the Communists from the Soviet Union, starting World War 2.
People all over the United Kingdom were on full invasion watch.
At age 16, James Black started his medical degree. In his freshman year,he came into contact with the outstanding mathematical biologist and public polymath Sir D’Arcy Wentworth Thompson. Black regarded Thompson, who was in his eighties, as an intellectual giant. Inspired by the great man, Black worked tirelessly on his medical courses and won a series of academic prizes.
Hospital Doctors – No Thanks
In 1946, age 22, Black received his degree in medicine. He had studied for six years, but his scholarship had been for four years. He borrowed money for the final two years putting him in debt, which he hated.
Hospital doctors were well paid, but he believed they lacked respect for their patients. He grew alienated from the profession as a result of incidents such as hearing surgeons refer to people as ‘the duodenal ulcer in bed 10′ rather than by their names.
Black began work as a research assistant in St Andrews’ physiology department, but soon decided to work overseas where he could earn more money and eliminate his debt. He traveled to Singapore, where he spent three years as a physiology lecturer at the King Edward VIII College of Medicine.
The Invention of Beta Blockers
An Idea
In 1950, Black returned to the UK debt free and was appointed chair of the physiology department at the University of Glasgow Veterinary School. He carried out two pieces of research that bore on his future drug creations. He studied:
- the effects of serotonin on gastric acid secretions, and
- how to increase the supply of oxygen to prevent cardiac arrest in people suffering from narrowed coronary arteries, i.e. angina. Black was hit by an inspired thought. Rather than increase oxygen to the heart, which was difficult, what if the effects of the body’s natural adrenaline could be blocked, reducing the heart’s need for oxygen? While he was a medical student, Black saw his father die of a heart attack after a minor traffic accident. His father suffered from angina, and Black wondered if the adrenaline released into his father’s body after the accident – the famous fight or flight effect – had led to the cardiac arrest that killed him.
Angina is caused by fatty deposits narrowing the arteries that carry blood to the heart. Cardiac arrest can happen when a release of adrenaline causes the heart to demand more oxygen, but partially blocked arteries cannot carry enough blood to supply the oxygen.
Alpha and Beta
In 1948, Raymond Ahlquist had discovered two types of adrenaline receptors – he called these alpha and beta. Both are present in various body cells including heart cells. Ahlquist’s work was universally ignored until Black read Ahlquist’s paper in 1954.
Black began wondering if Ahlquist’s adrenaline receptors were the key to reducing the heart’s oxygen demand. He reasoned that if these receptors could be deactivated, the heart would ignore adrenaline, lowering its need for oxygen.
By 1956, Black was looking for a molecule that:
- was sufficiently like adrenaline to bind to the adrenaline receptors, blocking them to adrenaline
- was sufficiently unlike adrenaline to not activate the heart’s fight or flight mode
The Pitch for a Beta Blocking Molecule
Synthesizing molecules was impractical at the veterinary school, so in 1958 Black pitched his idea to the UK’s biggest chemical company, ICI.
Soon he was leading a research group at the newly established ICI Pharmaceuticals at Alderley Park, Cheshire. He credited one of his group, John Stephenson, an organic chemist, with shifting his scientific approach from physiology to pharmacology.
Black’s was an entirely new approach to designing a drug. Previously, scientists would screen many different types of molecule to see if any were useful. Black, however, was trying to make a specific molecule.
A fellow scientist likened his approach to using a rifle bullet when everyone else was scattering shotgun pellets.
The result was propranolol, patented in 1962 and approved for medical use in 1964.
A Tale of Two Molecules
Adrenaline
Model of the adrenaline molecule.
Propranolol
Model of the propranolol molecule. Part of this molecule is sufficiently like adrenaline to block its receptor sites in the heart, but propranolol does not incite the heart to demand oxygen.
Black described his method for inventing new drugs as:
1. Identify the clinical problem.2. Identify the underlying biological processes.
3. Identify the regulatory molecules and receptors involved.
4. Design molecules which antagonize this process by acting through the same receptor pathway.
What are Beta-blockers used for?
It’s not only heart disease that benefits from blocking adrenaline. Beta blockers also help to:
• lower blood pressure
• reduce performance anxiety
• reduce tremors
Tens of millions of beta blocker prescriptions are issued every year. They have saved or improved the lives of millions of people.
“I have (taken beta blockers) before giving lectures. The effect is very interesting… concert pianists tell me that when they take beta blockers they give a much more even and intellectual performance throughout. The same is true with lecturing… you lose all heart pounding and dryness in your throat before you go on stage.”
Tagamet: The World’s Most Prescribed Drug
The principle of seeking a suitable blocking molecule led to Black’s next ground-breaking drug, cimetidine. He did this after moving to another company, Smith, Kline and French, where he worked from 1964 – 1973.
Black looked for a molecule that would mimic histamine. Histamine, produced naturally in our bodies, stimulates the production of digestive acid in the stomach, which worsens stomach ulcers.
Black hoped he could find a way of blocking histamine receptor sites. He achieved this with cimetidine. Under the brand name of Tagamet, cimetidine became the first drug ever to achieve annual sales of more than $1 billion. For a time it was the most prescribed drug in the world.
“I didn’t set out to make these companies vast fortunes. I simply wanted to solve the problem I saw in front of me.”
Molecular Structures
Histamine and Cimetidine
Histamine
Cimetidine
Making new molecules requires organic chemists to make adroit selections of starting chemicals, solvents, and appropriate catalysts to encourage starting molecules to react in precisely the correct locations to produce target molecules.
Return to Academia
In 1973, Black left industry for good. He had made his employers billions in profits, but his inventions had not brought him great wealth. He carried out a variety of research projects as Chair of Pharmacology at University College London, Director of Therapeutic Research at the Wellcome Research Laboratories, Professor of Analytical Pharmacology at King’s College London, and at his own James Black Foundation. In 1992, age 68, he became Chancellor of the University of Dundee, stepping down in 2006.
Honors
1976: Lasker-DeBakey Clinical Medical Research Award
1976: Elected Fellow of the Royal Society
1978: Mullard Award
1979: Artois-Baillet Latour Health Prize
1981: Knighted by Queen Elizabeth, becoming Sir James Black.
1982: Wolf Prize in Medicine
1983: Scheele Award
1988: Nobel Prize for Medicine
1997: Wellcome Gold Medal
2000: Order of Merit
2004: Royal Medal
“I wished I had some of my beta blockers handy.”
Personal Details and The End
James Black met Hilary Joan Vaughan, a biochemistry student, at St Andrews in 1944. He described her as intellectually the most exciting person he had ever known.
They married in 1946. Their daughter Stephanie was born in 1951. Hilary died in 1986.
Black married Professor Rona MacKie in 1994.
In 2002, Black was diagnosed with prostate cancer. He was given two years to live. He lived four times as long.
James Black died at age 85 on March 22, 2010 in London. He was survived by his daughter Stephanie, his wife Rona, and two stepchildren from his second marriage.
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Further Reading
Thomas A. Bass
Reinventing The Future: Conversations With The World’s Leading Scientists
Basic Books, 1994
John Simmons
Doctors and Discoveries: Lives that Created Today’s Medicine
Houghton Mifflin Harcourt, 2002
Joanna Lyall
James Black: Nobel Prize winning pharmacologist who invented β blockers
British Medical Journal, Vol. 340: p. 867, 2010
Stephen Pincock
James Whyte Black
Lancet Vol. 375 May 15, 2010
Alan McGregor
James Whyte Black: 14 June 1924 – 22 March 2010
British Journal of Pharmacology, Vol. 160 (Suppl. 1) S3-S4, 2010
James A. Angus
Mentorship ‘par excellence!’
British Journal of Pharmacology, Vol. 160 (Suppl. 1) S11-S14, 2010
James Black
A Life in New Drug Research
British Journal of Pharmacology, Vol. 160 (Suppl. 1) S15–S25, 2010
Creative Commons
Image of Sir James Black courtesy of UCL Pharmacology under the Creative Commons Attribution 4.0 International license.