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Adrenaline makes your heart beat faster and harder when you are scared or exercising. That is useful when running from danger, but for a heart with narrowed arteries the extra work can bring chest pain. James Black asked a simple question: what if a drug could stop adrenaline from pushing the heart so hard? The answer, propranolol, changed how drugs are designed. This post covers his idea, the receptor science behind it and the numbers from a major trial.
Who was James Black?
His Nobel facts page says he was born on 14 June 1924 in Uddingston, Scotland, and died on 21 March 2010. He shared the 1988 Nobel Prize in Physiology or Medicine with Gertrude Elion and George Hitchings "for their discoveries of important principles for drug treatment".
In his Nobel biography he says he "coasted, daydreaming" through much of school, until a mathematics teacher pushed him to sit the entrance exam for the University of St Andrews. He won a scholarship, studied medicine, then taught physiology in Singapore and at the University of Glasgow's veterinary school.
What idea did he build on?
Adrenaline makes some smooth muscle contract and other smooth muscle relax. In 1948 the American pharmacologist Raymond Ahlquist proposed, in a paper on the adrenotropic receptors, that these opposite effects run through two kinds of receptor, which he called alpha and beta.
The 1988 Nobel press release explains Black's insight. Earlier heart drugs tried to increase the oxygen supply to the heart. Black wanted to reduce the heart's oxygen demand instead, by blocking its beta receptors so that adrenaline could not drive it as hard. His biography says that by 1956 he had set this aim, based on Ahlquist's hypothesis, and approached the company ICI, which employed him to pursue it.
How was propranolol made?
A blocker has to fit the receptor without switching it on, like a key that slides into a lock but will not turn. The press release says Black's team started from isoprenaline, a known stimulant of beta receptors, and modified it. Their first useful blocker, pronethalol, came in 1962, and propranolol followed in 1964, reported in The Lancet. It was the first clinically useful beta blocker, used for angina, fast heart rhythms and later high blood pressure.
Did it save lives?
The press release cites a large trial. The Beta-Blocker Heart Attack Trial, published in JAMA in 1982, gave propranolol or a dummy pill to 3,837 people who had recently had a heart attack. The trial was stopped nine months early because the result was clear. Over an average of 24 months, total deaths were 7.2% with propranolol and 9.8% with placebo.
Worked example: three ways to read 7.2% versus 9.8%
Absolute risk reduction: 9.8% − 7.2% = 2.6 percentage points.
Relative risk reduction: 2.6 / 9.8 = 0.265, so about 27% fewer deaths.
Number needed to treat: 1 / 0.026 = 38.5, so about 39 patients treated for roughly two years to prevent one death.
All three are correct. "27% fewer deaths" sounds bigger than "2.6 points fewer", so always ask which one a headline is quoting.
What came next?
Black then turned to histamine, which drives acid secretion in the stomach. Ordinary antihistamines did not block that effect. The press release says that in 1972 he characterised a new group of histamine receptors, H2 receptors, reported in Nature, and then developed cimetidine, the first clinically useful H2 blocker, which brought a new way to treat peptic ulcers. Later, Barry Marshall and Robin Warren showed that most ulcers are caused by a bacterium, and acid-reducing drugs became part of the cure alongside antibiotics.
Which ideas link to your syllabus?
Hormones act through receptors. Our guide to chemical coordination and hormones covers adrenaline as an emergency hormone.
Agonist versus antagonist. An agonist switches a receptor on; an antagonist occupies it without switching it on.
What can a student take from Black's way of working?
Change the question. Everyone asked how to get more oxygen to the heart. He asked how to make the heart need less.
Start from a theory. Ahlquist's receptor idea told him what target to aim at.
Design, then test. Molecules were changed step by step and judged by how they acted on tissues.
For the other half of the 1988 prize, read about Gertrude Elion and rational drug design. If risk and percentage questions trip you up, the Fermi Problem Library has worked problems with a step-by-step solver that explains the reasoning rather than printing an answer.
Try it now: if a drug cuts a risk from 20% to 15%, work out the absolute reduction, the relative reduction and the number needed to treat.
