As the Government announces a huge, pioneering project to sequence 100,000 genomes, Mark Henderson looks at what needs to happen to make the technique live up to its promise
A pioneering project to map 100,000 genomes will revolutionise medicine in Britain
A few years ago, I spat into three test tubes and dispatched them special delivery to companies that will now, for a few hundred pounds, test your genes for clues to your future health. Though each service examined the same DNA, and evaluated the same diseases, each set of results was dramatically different. My lifetime risk of glaucoma, an eye condition, was as low as 2 per cent or as high as 36 per cent, depending on which service I chose to believe. One company thought my chances of a heart attack were twice as high as another.
Mine was the sort of experience that has fed a growing sense that the sequencing of the human genome, heralded by Bill Clinton in 2000 as the future of medicine, has failed to deliver on its promise. While DNA has since become much cheaper and simpler to read – the cost of a human genome is dipping below the magical figure of $1,000 a time – its meaning remains devilishly difficult to interpret. As my results demonstrate, this is especially true of the conditions that are the greatest causes of morbidity and mortality – diabetes and heart disease, stroke and mental illness.
Mine was the sort of experience that has fed a growing sense that the sequencing of the human genome, heralded by Bill Clinton in 2000 as the future of medicine, has failed to deliver on its promise. While DNA has since become much cheaper and simpler to read – the cost of a human genome is dipping below the magical figure of $1,000 a time – its meaning remains devilishly difficult to interpret. As my results demonstrate, this is especially true of the conditions that are the greatest causes of morbidity and mortality – diabetes and heart disease, stroke and mental illness.
More than a decade on from the sequencing of the genome, we remain unable to use it to predict with any confidence which common diseases an individual is likely to develop, and the genomic age has not yet yielded new drugs with which to treat them. Given headlines that once promised personalised gene screening and therapies, it is easy to understand why figures such as Lord Winston and Professor Steve Jones have attacked the idea of a genomic revolution as nothing but hype.
Why, then, is the Government today announcing an investment of almost £300 million in Genomics England, a new initiative to read and decipher the genetic codes of 100,000 NHS patients? The answer is that the critics of genomics are right that it does not represent the future of medicine. It is actually the present.
It is correct that science has not made as much progress as had been hoped in unlocking the genetic factors that contribute to most common diseases. But quite staggering progress has been made elsewhere. In three areas in particular – cancer, rare congenital diseases and infections – the plummeting cost of reading DNA and science’s growing ability to interpret it is already transforming medical practice. The Genomics England project is about bringing these benefits to NHS patients, and enabling further scientific discoveries to emerge from their care.
Many of the patients who are sequenced by Genomics England will be sick with cancer. A disease of the genes, cancer is caused by mutations in DNA that cause cells to divide unchecked. By analysing these mutations, doctors can get a better idea of the character of a tumour – how it is likely to grow, what the prognosis might be, and, critically, how best to treat it. A small battery of precision drugs that target tumours carrying particular mutations is already available – some, like the melanoma drug vemurafenib, developed in short order with direct insights from the human genome sequence. Genomics England will allow more patients to benefit from what is already known about cancer genomics, and generate fresh insights that will benefit others in future.
The other group whose lives are already being transformed by genomics are families afflicted by congenital disorders. While individually rare, these are collectively common, and they are heartbreaking. A child is born with a developmental disorder, typically involving learning difficulties and skeletal abnormalities. While the cause is clearly genetic, doctors are often unable to give the syndrome a name, let alone give parents a prognosis, or tell them whether future children might be affected. The child will undergo test after invasive test to find out what is wrong. Answers are rare.
Genomics is changing that. The Deciphering Developmental Disorders project, funded by the Wellcome Trust and the Department of Health, has already shown that by sequencing the DNA of parents and child, it can be possible to pinpoint the mutation that is responsible. This rarely suggests a treatment, but it has huge benefits nonetheless. Parents can be advised whether future children could be affected. They can also find out how other children with the same mutation have developed, and thus what the prognosis for their loved one might be. It can make it simpler to obtain a statement of special educational needs. Above all, there is peace of mind.
The other group whose lives are already being transformed by genomics are families afflicted by congenital disorders. While individually rare, these are collectively common, and they are heartbreaking. A child is born with a developmental disorder, typically involving learning difficulties and skeletal abnormalities. While the cause is clearly genetic, doctors are often unable to give the syndrome a name, let alone give parents a prognosis, or tell them whether future children might be affected. The child will undergo test after invasive test to find out what is wrong. Answers are rare.
Genomics is changing that. The Deciphering Developmental Disorders project, funded by the Wellcome Trust and the Department of Health, has already shown that by sequencing the DNA of parents and child, it can be possible to pinpoint the mutation that is responsible. This rarely suggests a treatment, but it has huge benefits nonetheless. Parents can be advised whether future children could be affected. They can also find out how other children with the same mutation have developed, and thus what the prognosis for their loved one might be. It can make it simpler to obtain a statement of special educational needs. Above all, there is peace of mind.
Infectious disease is the next frontier. By sequencing the DNA of germs that cause disease, it is now possible to track the routes by which infections are transmitted, and to identify the drugs to which a pathogens are resistant. This improved diagnosis will be key to containing outbreaks of hospital superbugs, such as MRSA and protecting the antibiotics to which too many diseases are developing resistance.
Genomics, then, is changing lives and improving health today. But it is doing so principally for people touched by illness in some way – cancer patients, children with developmental disorders and their families, and people with infectious diseases. It is not, yet, bringing advances of much significance for the worried well. The type of consumer tests I took, with such divergent results, are a distraction from the real story, which is of targeted clinical diagnostics and treatments for serious diseases, which are already having a real impact. These applications of genomics have not been oversold. If anything, they have received rather less attention than they properly deserve. The big challenge is not to live up to the hype, but to ensure that as many patients as possible actually benefit.
