Doctors hailed a landmark in the advance of personalised medicine yesterday with the first case in which the sequencing of a patient's complete genome revealed the genetic cause of his disease.
The advance demonstrates for the first time that the technology of gene sequencing, touted as the future of medicine for a decade, is robust enough to yield clinically significant results. Fewer than 10 people in the world have had their personal genomes completed, and most of these were done as an intellectual exercise.
But the technology may herald a new era of medical neurosis rather than a new dawn of better health. Learning in advance of the risk of suffering diseases in the future might help prevent their occurrence, but would also lead to a lifetime spent worrying about them.
The latest advance solves a 20-year puzzle for the patient, James Lupski, who as vice chairman of molecular and human genetics at Baylor College of Medicine in Houston, Texas, also led the research.
Dr Lupski inherited a rare condition which affects the nerves in the hands and feet called Charcot-Marie-Tooth syndrome from his parents. In 1991 he and his team identified the first genetic mutation that gave rise to the disease and 40 more genes have since been implicated by other researchers. But none of them accounted for the disorder that affects Dr Lupski himself and some of his siblings.
To help Dr Lupski in his quest, Richard Gibbs, director of the Human Genome Sequencing Centre, offered to sequence all of his genome. The researchers found two "compelling" mutations in the gene SH3TC2, among those known to be implicated in the syndrome, which caused the condition in him. The results are published in the New England Journal of Medicine (NEJM).
Dr Lupski said he had known he had a genetic disease for 40 years, but now he knew the gene at fault. "This is the first time we have tried to identify a disease gene in this way. Currently we only know the function of 5 to 10 per cent of the approximately 25,000 genes in our genome that it takes to make a human being. What this paper tells us is that the data are robust enough that we can start to use it to interpret clinical information in the context of the genome sequence," he said.
Unlocking the secrets of the genetic code for individuals to reveal their risk of developing specific diseases has been limited by the high cost. But it is falling dramatically. Decoding the complete genome of Nobel prize winner James Watson, joint discoverer of the double helix structure of DNA, in 2008, cost $1 million (£600,000). Dr Lupski's genome was sequenced for $50,000 (£30,000). An editorial in the NEJM says the "spectacular" reductions in cost will continue, as a result of competition and innovation, and will be "at most one tenth of the current cost" within two years. Even today, using a different technique that shrinks the target for sequencing (covering 1 per cent of the genome but which still accounts for 90 per cent of all mutations with large effects), the cost of decoding Dr Lupski's genome could have been achieved for $4,000 (£2,800). "It is increasingly clear that the cost is fast approaching a threshold at which DNA sequencing will become a routine part of the diagnostic armamentarium," the journal says.
However, the new developments raise a host of ethical questions. Among them is how information about genetic risks of disease should be presented to individuals, and what the implications may be for insurance and employment.
Women affected by the genes BRCA1 and 2, which are known to raise the lifetime risk of breast cancer to 80 per cent, can protect themselves by having regular mammograms or by opting for prophylactic surgery to remove the breasts.
But for Huntingdon's disease, an inherited progressive neurodegenerative disorder, there is no cure. Alerting people affected by the gene that causes the disease means they live for longer under its cloud. While some may prefer to know, others may want to live in ignorance, until their symptoms develop. Couples trying for a child may wish to know if the foetus is affected so they can opt for abortion if they choose.
The Association of British Insurers agreed a moratorium on the use of genetic test results in 2001, which has twice been extended and is now due to expire in 2014.
The moratorium allows consumers to obtain insurance for themselves and their families without having to disclose adverse results of predictive genetic tests that might indicate a risk of serious disease in the future.
Single gene mutations that cause more than 2,000 mostly rare diseases have been identified so far. Mutations in multiple genes that increase the risk of common diseases are also being discovered.
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