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The future of drug research (Part 1)

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My theory on the gastrin antagonist
James Black Scientist
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So this compound is not losing its potency, and the problem is: why, if it's still blocking gastrin receptors, why does the pH not... well, I have a theory for that, and that is that when gastrin stimulates the ECL cells we know that it stimulates the release of histamine and also switches on the synthesis of a number of peptides, many of them related to a peptide, a big thing called chromogranin A which breaks down into an poly... pancreatic polypeptide and a number of other things. Now... so on day one, if you block the action of gastrin, you block the release of histamine, but you don't block this synthesis of... because that takes time to come on. Now, my model is that these peptides inhibit... I beg your pardon, stimulate the secretion of bicarbonate. Now, there's one man who spent his life working on bicarbonate secretion and we know that it's a regulated process. So your stomach secretes mucus, but mucus is not a good buffer, but it secretes bicarbonate, and the more acid the more bicarbonate you secrete. So if you come back, then, to day one with a proton pump inhibitor, you switch off the acid, but the bicarbonate secretion is still going on, and by day seven you should start... bicarbonate is still going on, so the bicarbonate is there to raise the pH. But if you take a gastrin antagonist it blocks on day one, but we haven't yet inhibited the bicarbonate secretion so the pH rises, but by 24 hours later, though no one's mentioned it, the bicarbonate secretion will be inhibited and then the pH won't go up, but the volume will be down. So I... I... we now know from the gastrin levels that these drugs – this drug – will be a better inhibitor of acid secretion than the H2 antagonist, I think. So that is now my passion to sell this message.

The late Scottish pharmacologist Sir James W Black (1924-2010) revolutionised medical treatment of hypertension and angina with his invention of propranolol, the first ever beta blocker. This and his synthesis of cimetidine, used for the treatment of peptic ulcers, earned him the Nobel Prize in Physiology or Medicine in 1988.

Listeners: William Duncan

After graduating with a BSc Bill Duncan went on to gain a PhD from Edinburgh University in 1956. He joined the Pharmaceuticals Division of ICI where he contributed to the development of a number of drugs. In 1958, he started a collaboration with Jim Black working on beta blockers and left ICI with him in 1963 to join the Research Institute of Smith Kline & French as Head of Biochemistry. He collaborated closely with Black on the H2 antagonist programme and this work continued when, in 1968, Duncan was appointed the Director of the Research Institute. In 1979, he moved back to ICI as Deputy Chairman (Technical), a post he occupied until 1986 when he became Chairman and CEO of Coopers Animal Health. He ‘retired’ in 1989 but his retirement was short-lived and he held a number of directorships in venture capital backed companies. One of his part-time activities was membership of the Bioscience Advisory Board of Johnson and Johnson who asked him to become Chairman of the Pharmaceutical Research Institute of Johnson and Johnson in New Jersey. For personal reasons he returned to the UK in 1999, but was retained by Johnson and Johnson until 2006 in a number of senior position in R&D working from the UK. From 1999 to 2007 he was a non-executive director of the James Black Foundation. He is now fully retired.

Tags: Gastrin antagonist, gastrin, chromogranin A, histamine, bicarbonate

Duration: 2 minutes, 42 seconds

Date story recorded: August 2006

Date story went live: 02 June 2008