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Work on polycystic kidney disease


Discovering a connection between haemoglobin H and mental retardation
David Weatherall Scientist
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Just before I got- left Liverpool, I got a phone call from a technician from a hospital over on the Wirral, saying that, he’d had a blood from a child, a mentally retarded child, and seen some lumps in the red cells and could they be haemoglobin H. A bloomin’ good technician actually. So, I, so and he sent over a sample, and this was clearly mild haemoglobin H disease, and I went over and saw the family and the parents, and it didn’t look kind of quite right. The child- Inherited the pattern in the parents, and I, I didn’t know what to make of this, so like a lot of these things, I put it away in the drawer, and just after moving to Oxford I got a letter, again, out of the blue, from a Colonel Nicholas Bethlenfalvay from some military hospital in the Deep South of the States. He said he’s got a patient that he thought had haemoglobin H disease, and he was mentally retarded, could we help him sort it out. So, I remembered the Liverpool one, and then I saw a paper in some rather obscure haematological journal, which clearly had been rejected by most of the other journals, about a group in Scandinavia where they’d seen a patient with H disease and a mental retardation, and was just thrown into a group of patients with H disease. So I began to wonder, and so we worked up these, we got samples from the Scandinavian family, we worked up these families as best we could, and the mental retardation varied very widely, there were two of them were quite mild, one was quite severe and had dysmorphic features, and, but, and we did the biosynthesis and we obviously at that stage could, I think we could just, I’m not sure whether we were quite ready with Southern Blotting, I think we were, and we couldn’t find alpha thalassemia in some of the parents, that was the problem, oh, at least, not that we could identify at that stage. So I thought, well, should, you know, should we just sit on this, or should we write a paper, and I thought I will write a very cautious paper entitled Mental- "Haemoglobin H Disease Mental Retardation – A True Association or A Chance Association?" And they, we sent it to the "New England Journal", rather cheekily, and of course, Americans don’t like kind of, sexy titles, and they didn’t like the title at all, and they were going to reject it anyway, and I have to say that the paper would not have got published, except David Nathan, who’s on that editorial board, he thought there might be something, he told them they had to publish it, so they did. And of course, once something happens in a journal like that, you start to get sent patients, and they started to come in, and we had a series of very bright post-docs, Andrew Wilkie particularly, and Richard, and two or three others actually at the time, I think Richard came a little later, and they gradually started to take this apart. Andrew was particularly helpful phenotyping because he was, unlike me, a proper geneticist by then, and they did good genetic studies, and collected long series, and then did the genetics, and it became clear there were two types. There was one that was coded on the chromosome 16, usually due to deletions, and then the more interesting one, which was coded by the X chromosome. And then, much to their credit, they isolated the gene, and it’s been a very interesting story, hasn’t it? Indeed. So, but that again, it was just a kind of, having a look at something that doesn’t quite make sense at the beside, kind of approach, but I, I think that’s a good approach actually, sometimes, but anyway.

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: 4 minutes, 34 seconds

Date story recorded: July 2007

Date story went live: 02 June 2008