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Inspiration from a Hammersmith Medicines Research report

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An innovative look at beta blockers
James Black Scientist
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The third bit of that wee story is a chap called Andy Vinton, whom I knew at Smith Kline, then recruited him at Wellcome, and he's a theoretical... a physical chemist interested in theory. But one of the problems in pharmacology is that you can have different substances, all quite different chemical structures, which all can do the same thing, and so you find that stimulating a receptor; many different structures can do it, and that's one of the unspoken problems of pharmacology: how does it happen? Well, what Andy... when I say Andy and I have been working on it, he does the work and I shout encouragement from the sidelines, or... or after I came here, give him financial help. But he has been developing the idea which both of you will remember from school science experiments, when you took a bar magnet and put a piece of paper over it and then sprinkled iron filings and then the iron filings all sorted themselves out into this field. So what we now know is that every small organic molecule produces an electrostatic field around itself, and that it gives it a bipolar structure. And what Andy's been working on is how to calculate that fields and how to represent it visually because it's very complicated. It's not simple shapes like the bow magnet, and so now he's developed the technology, set up a little business near Cambridge, and they... he's developed the software that allows him to take any small molecule, calculate all the likely confirmations of that molecule, calculate the fields for each of these con... confirmations, represent these fields three dimensionally in space as field points, as balls, and then he can now screen databases for field structures rather than for actual structures. So, when I got the grant, I then managed to get another small grant to pay Andy to work on this project with us, and... so, because we had many structures already patented we had a... a lot of information about what active structures were, he then calculated the fields of all these, established a pattern of field structures which looked as though it was common to beta-2 block, then he screened a 2 million collection of compounds on... for which he has calculated all their fields. So he's got field points for all the confirmers of 2 million compounds, and he's able to screen through that. And, on the first... he picked 40 compounds; of the first 10 we looked at we found three – no, one – and then in 40 we found three, so we've now found three active structures which are outside the patents, as far as we know; there's a lot of patents and I'm not certain but it looks likely that they are already outside the patent, and so we... if we can develop these properly we may get industrial encouragement and enthusiasm, and so on. There's also a fascinating genetic story behind all this, because... I mentioned bucindolol as one of the non-selective compounds which had been tested and that was the only trial which failed, but the authors showed that they had recruited... one third of their 4500 patients were American blacks, and if you took out the American blacks then the 2000 remaining, whatever it was, were indistinguishable in terms of their improvement compared to carbadolol. So, there is a problem running through this about the... the type of receptors you have and... and blacks look as though they're a different category.

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: Smith, Kline & French, Wellcome Foundation, Andy Vinton

Duration: 4 minutes, 37 seconds

Date story recorded: August 2006

Date story went live: 02 June 2008