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Gene sequencing and mental illness research (Part 1)


Having my own genome sequenced (Part 2)
James Watson Scientist
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They told me I also was homozygous for a change which - gene where you have Cowland’s Disease [?], which - in some way would be a very bad fate. In fact, I probably shouldn't be here if I had it in any way. And only earlier this week in Edinburgh did I learn that someone had looked at my genome sequence and concluded that my mutations in it were not the disease causing one but, you know, one removed from the disease causing one. So I didn't worry about it because I was 80, but again, if I'd been told that at 20 I might have, you know, thought, my life won't be very good. But of more value, and that came from Craig Venter who published his own gene sequence soon afterward, which he did by the old fashioned way. So we calculated that he must have spent at least 20 of his shareholders' money sequencing himself, if not more. But they published an article which compared his cytochrome p450 genes with Craig's and Craig was superior to me and that he had normal variants, but in one of them, cytochrome C2P6 or P2C6, yes, yes- but anyway, it's the cytochrome which metabolizes beta blockers and also converts codeine into heroin, that I have an Asian variant. I was homozygous for an Asian variant, which means I metabolize them about 10-fold less, slower. And that immediately explained why when beta blockers had been given to me to control my blood pressure, they controlled my blood pressure, but you know, within a week or so I was just totally asleep during the middle of the day. So when the doctor knew this, he gave me another beta blocker that did the same thing, but he didn't think in terms of the fact that, you know, I might be - have genes which led to the enzymes being sort of inactive. So that's greatly benefitted, now I take a beta blocker, you know, once every eight or nine days instead of once a day. And they control my blood pressure just as well. The initial announcement didn't tell me that I had only one good copy of the lactase gene, so I'm somewhat milk intolerant, which explained why in 1953 when I was at Clare College the year we worked out the DNA structure, my stomach was always giving me gas problems. And you know, I went to the local prominent GP who, you know, sort of thought it was psychosomatic. And in those days, no one associated constant gastric problems or intestinal problems with inability to do milk. When I then got that news, I looked up the literature on lactase, including one paper which concluded that very, very likely Charles Darwin's mysterious disease was that he was homozygous for it. He did have one good copy and so four or five hours after a meal, he would just feel desperately ill and probably drank lots of milk because Down House had a farm. But even though these articles appeared, the sort of Darwin world hasn't seized upon it. They always thought, did he pick up some parasite when he was in South America? Because I think the problems - he didn't have those problems until he returned from the voyage of the Beagle. So that's why they thought it was something he picked up. But often, you sort of slowly lose when you're - what you lose is your ability as an adult to lac, as a young child you have a different promoter doing it. So Darwin may have, you know, had smaller amounts by the enzyme and by the time he got really old, it stopped being made. So I now carry with me lactase pills which I take if I know I'm going to, you know, going to eat a lot of ice cream or something like that.

American molecular biologist James Dewey Watson is probably best known for discovering the structure of DNA for which he was jointly awarded the 1962 Nobel Prize in Physiology or Medicine along with Francis Crick and Maurice Wilkins. His long career has seen him teaching at Harvard and Caltech, and taking over the directorship of Cold Spring Harbor Laboratory in New York. From 1988 to 1992, James Watson was head of the Human Genome Project at the National Institutes of Health. His current research focuses on the study of cancer.

Listeners: Martin Raff Walter Gratzer

Martin Raff is a Canadian-born neurologist and research biologist who has made important contributions to immunology and cell development. He has a special interest in apoptosis, the phenomenon of cell death.



Listen to Martin Raff at Web of Stories



Walter Gratzer is Emeritus Professor of Biophysical Chemistry at King's College London, and was for most of his research career a member of the scientific staff of the Medical Research Council. He is the author of several books on popular science. He was a Postdoctoral Fellow at Harvard and has known Jim Watson since that time

Duration: 6 minutes, 4 seconds

Date story recorded: November 2008 and October 2009

Date story went live: 18 June 2010