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Being offered the Nuffield chair of medicine


Using new DNA hybridization methods and continued work on globin
David Weatherall Scientist
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And then, at the same time, we started reading about these new methods that were being used for DNA hybridisation, but the idea where you would make complementary DNA based on an RNA template, label it, and then you could mix it with DNA and see if you could get hybridisation due to sequence immology, and it had been, started to be used in the States for a lot of evolutionary genetics by then, and a number of other things, and we wondered if there were deletions of globin genes, whether you could show them by this method, and the obvious one was going to be alpha thalassemia. The not so obvious question, how do you get the material? So this was another trip to Thailand, and, because they get a lot of these hydropic babies and what we needed to show, A, was that the hydropic baby didn’t make any alpha chains at all, it didn’t seem to make many, and the other thing of course, was could we get DNA for our hybridisation. So we did, we got some highly labelled material and found it absolutely no alpha chain synthesis at all, and no sign of any peptide fragments or anything, and we didn’t know how to do molecular DNA hybridisation, there were very people in the UK who doing it, but John Paul in Glasgow, at the Beatson was doing it, so I wrote to John, and said we have this material, could you help us, because I think it’s a good question now to ask whether this baby’s got any alpha genes. So we trundled up on the train, and to Glasgow, and had a long talk, and he had a number of, couple of bright post-docs in his lab at that time, one of whom was Bob Williamson, and the, and they decided to, that they would provided we got this stuff properly labelled and purified, they would have a go, and it worked out very nicely, because the hybridisation curves showed that there must be virtually no alpha chains at all. And so this was nice, because it was the first demonstration of a deletion in a human being. So that went off to the, and it was easy to get things into "Nature" those days, and, but completely unbeknown to us, YW Kan the Hong Kong Chinese geneticist haematologist who’d moved to the States, very bright, in fact, later he became an FRS here, because it was Hong Kong citizenship, and thank- he’s the only, there’s two Chinese FRS’ in the register, one was an, a kind of emperor who was passing though sometime, and YW, anyway, YW had got together with a, with a group in, in San Francisco, Harold Varmus who was working there, you know Bishop and Varmus who got the Nobel prize for the work on oncogenes, and Bishop was using this DNA, um, CDNA hybridisation, so he helped YW just to, in the same way as John Paul had helped us, and got the same result, so they came out back to back, in "Nature", which was, which was nice. And I think that was what you might call really the end of the, what you might call, protein RNA DNA hybridisation era, and again, all we were doing was following the molecular biologists with new technology, and of course, things blew completely in the late '70s when Ed Southern developed southern blotting, and, and, but our interests were expanding in other directions as well at that time, because I guess we’d always been fascinated by the old Haldane hypothesis, about, you know, why these disorders were so common, and although there’s been a lot of work done on sickle, a bit on thalassemia, we were, the story was by no means clear cut, so, and by the time you’d been through and a number of other nice people who we had in the lab at that time, people like Knox-Macaulay, you remember- Yes. He, because Huxley, I got a letter from Boston about Huxley who, I saw this Huxley, Knox-Macaulay and I, they never told me where he’d come from, and of course I thought it was some kind of posh English public school boy is going to appear, and this fantastic looking black guy arrives, and he was wonderful value, he used to sing hymns didn’t he, while he was doing his experiments, and so we did quite a bit of work on red cell metabolism in thalassemia at that time, and we did what we could in the foetal haemoglobin field, and some of that of course, as you know, took us to the Middle East, and we had Thailand, and so we were building up these kind of connections all over the world, and that really was a way of starting in, to start to have a serious look at the population genetics of globin.

British Scientist Sir David Weatherall (1933-2018) was a world renowned expert on blood diseases, in particular thalassaemias, and used his expertise to help control and prevent these diseases in developing countries. He founded the Institute of Molecular Medicine at Oxford in 1989 and was knighted in 1987.

Listeners: Marcus Pembrey

Marcus Pembrey, now Emeritus, was Professor of Paediatric Genetics at the Institute of Child Health, University College London and consultant clinical geneticist at Great Ormond Street Hospital for Children London. He is a visiting Professor at the University of Bristol UK, where he was the Director of Genetics within the Avon Longitudinal Study of Parents and Children until 2006. A past president of the European Society of Human Genetics, he is also the founding Chairman of the Progress Educational Trust.

Duration: 6 minutes, 1 second

Date story recorded: July 2007

Date story went live: 02 June 2008