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Gene sequencing and mental illness research (Part 2)


Gene sequencing and mental illness research (Part 1)
James Watson Scientist
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So you know, up to now, I've benefitted from knowing my genome. Craig learned he had one apolipoprotein E4 variant. And he's now 60, so people with one tend to be affected in their, you know, maybe in the late 70s and 80s. So he may regret knowing it. So how we're to, you know, move into - you know, then my genome cost $1 million, so one wasn't worried about what would happen when very large numbers of people have their genome sequence. And - because NIH has given money to companies to promote finding, developing technologies which lead to the cost being only $1,000 for a genome, which will be, you know, much less than the cost of actually analyzing the genome. So - and that day is likely to arrive maybe as close as three to five years from now. The cost has been reduced down to roughly $20,000. Using now the dominant machine that was developed here in the UK by a company that started out at the chemistry department at Cambridge University, Silexa [?]. Then [unclear] produced a machine which sequenced cheaper than 454 and it was bought by the DNA chip company, Illumina, American company. And there, when we got the machine, a genome was $200,000. Now it's about $20,000. So at $20,000, it would probably be worthwhile even at that cost to sequence large numbers of the mentally ill, because what we've learned now, certain genes now have been shown to cause individual cases of mental illness. But it doesn't seem that anyone is going to be - mental illness won't be like cystic fibrosis, being caused by a single gene. Quite possibly as many as several hundred could lead to the weakened brain which then becomes prone to psychosis. And it doesn't look like even the most common changes are more than 1% of the disease. So it's going to be hard to be sure since there's lots of natural variation spotting the variation which is new. And one way would be to sequence individuals both of whose parents have no trace of mental illness and look for new mutations in the offspring. And then by sequencing pretty large numbers, hopefully to find repeats. And best would be the use of large families of - where mental illness goes through a number of generations, where you can compare the sequence of affected members and unaffected. But it's made difficult that the - it's clear already that the penetrance of the genes which we're studying, one in particular which causes either schizophrenia or major depression and one case with bipolar, does not have 100% penetrance. It's sort of semi-dominant. Some individuals appear, but some people that are thought to be totally no sign of mental illness still carry the gene. So it's not as clean as we would like, but there's a family in Scotland that - people in the genetics department at Edinburgh University assembled over many years, which has 180 members, and we're collaborating with them and have sequenced the first two. We started, they may have almost finished sequencing - that is getting the raw data now, the first two personal genomes of the mentally ill. So I was in front of, went to see Senator Tom Harkin about getting a congressional hearing for the need of more money to find out what's wrong genetically in the seriously mentally ill, bearing the grim news that basically the medicines for treating mental illness have not substantially improved over the past 45 years. They have become maybe marginally better, but the only thing we're sure of is that they're much more expensive. But they don't, you know, lead to a child who can really go back into society with schizophrenia. You know, I'm saying, there are exceptions, but on the whole. We want to find drug targets, such as has been possible by doing the genes behind cancer. So we want to understand mental illness, which will be like cancer, involve many genes. Might consider, $1 billion. So I think we'll get a hearing and then the problem is that unlike cancer, families which have, you know, multi-generated in families don't really - like to reveal themselves, because you know, if you know that, you know, your son has schizophrenia and his, say, uncle had it and so on, you don't talk about it because maybe, you know, it'll make people worry whether the sister of the boy who has schizophrenia has it. And no one wants schizophrenia in the family.

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: Walter Gratzer Martin Raff

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

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



Duration: 8 minutes, 6 seconds

Date story recorded: November 2008 and October 2009

Date story went live: 18 June 2010