Genomics revolution: UK could miss the boat, scientists warn
Better data collection and NHS backup is needed for day when it will be cost-effective to carry out whole genome tests on patients
Sarah Boseley, health editor
The UK has a huge opportunity to lead the world in disease discovery, treatments and cures. But support from the NHS and better data collection is needed if Britain is not to lose out in the coming genomics revolution, leading scientists believe.
The cost of whole genome sequencing – mapping the DNA code of any human being – is dropping through the floor, from £750m for the first-ever sequence to probably as little as £1,000 soon. Experts say it will soon be as cost‑effective to carry out a whole genome sequence on a patient as to do one or two genetic tests. They see a time in the not too distant future when it could be normal to sequence the genome of every newborn baby.
But, says Sir John Bell, regius professor of medicine at Oxford University and chair of the advisory Human Genomics Strategy Group, data about a patient’s DNA tells you little without standardised information on their disease. At the moment, the NHS does not hold that in a way that allows comparisons. Even the definition of a recurrence of a cancer – the point at which it is considered to have come back – varies from one hospital and specialist to another.
“I keep saying to people – don’t think about today, think about tomorrow. There’s no question it’s going to be really, really, really cheap. The real question is what are you going to need from the back office?” Bell said.
“Even if we got started flat-out today we’d still be behind the curve because there’s a lot of stuff that’s going to need to be done. People have to concentrate on the problem. People have been saying well, we can buy a machine – it’ll all be fine. Well, it won’t all be fine. There’s no informatics, there’s no capabilities of proper data analysis of whole genomes, insufficient clinical informatics to make this all work and all that’s got to get fixed.” But, he added, Britain has “a huge opportunity. The truth is we could lead the way in this space.”
While scientists say they can see a day coming when genome sequencing at birth will be the norm, they agree it would not be useful yet. Where it is useful for now is in patients, not the healthy. “Should we start being sequenced? I was always taught at medical school that you should never do a test unless you could do something with the result,” said Sir Mark Walport, director of the Wellcome Trust, the UK’s biggest funder of genomics research.
“So the question is, are there useful things that we can do with the results of a genome sequence that would bring benefit? And the answer is, today, should the majority of people go and have their genome sequenced? Probably not. But are there particular circumstances in which genome sequencing is really helpful? Yes, there are.”
Genome sequencing has shown its potential in revealing genetic triggers for developmental disorders in children. It may not help the child, at least at the moment, but it can help the parent, by letting them know if any future child might be at risk.
Bell talks of revelatory work by scientists in Canada, which showed that in a group of people with schizophrenia, all had different genetic mutations in areas associated with neurodevelopment. “We used to think this is a disease. What it probably means is this isn’t a disease. Everybody who has got it has got a different disease, but the mutations that produce the disease occur somewhere in those pathways associated with the development of the nervous system,” he said, adding: “You won’t find any psychiatrist who believes that story at the moment – there are lots of reasons why they don’t want to believe it – but the genetic data is quite compelling.”
Whole genome sequencing will also be useful in cancer, said Walport. Tumours can themselves be sequenced and drugs are increasingly being made to target particular genetic mutations. The patient then needs a genetic test to ensure they have that “biomarker”, such as the HER2 test that shows whether Herceptin will be useful in breast cancer.
Thirdly – and Bell called it the lowest-hanging fruit – great strides are already being made in sequencing bacteria such as MRSA and Clostridium difficile.
“We have these old-fashioned names for infection which come from looking at how they grow on agar plates and looking at them under the microscope,” said Walport, “but we increasingly realise there is enormous variation within the bugs that infect us … It will also tell you how likely they are to respond to particular antibiotics and it is possible to work out how they are transmitted from one person to another.
“So we’re learning how infections are travelling around the world and, sadly, how cholera in Haiti was brought in by UN peacekeeping forces from south Asia.”
While the genetic detective hunt can sometimes tell doctors what has gone wrong, there are few examples yet of testing that has improved patients’ lives.
The work of Andrew Hattersley in Exeter in collaboration with Frances Ashcroft, a professor at the department of physiology, anatomy and genetics at Oxford, is an exception. Hattersley, a professor of molecular medicine and consultant diabetologist, has shown that type 1 diabetes is not one disease but several. Identifying a genetic change in people who were diagnosed with diabetes as small babies, less than six months old, has transformed lives.
Those with neonatal diabetes have normal beta cells in the pancreas that are capable of producing insulin. Hattersley found a genetic mutation that disrupted part of the insulin-secreting pathway which Ashcroft had identified as key to neonatal diabetes. It meant that any child or adult with the genetic mutation could be taken off injected insulin and given simple pills instead. Only a small number of people with diabetes have the mutation, but for them, it has been life-changing.
“Anybody, anywhere in the world, diagnosed under six months, we will offer a free test for and we will do that rapidly for the two genes where we know it will alter treatment. The medical advance has spread throughout the world very rapidly because it makes such a difference,” said Hattersley. So far, he said, they have tested samples from 78 different countries.
Yet Hattersley has some reservations about the usefulness of whole genome sequencing. It is exciting to be able to obtain complete genetic information, but interpreting it is more difficult.
“There is already a difficulty where your genetics says you should have this disease but you don’t,” he said.
A mutated gene might explain something, but it might be a mistake or might not be causative after all. Disease is usually an interaction between genes and an individual’s environment – genes give you a predisposition, not a prediction.
What matters, says Hattersley, is “the prior likelihood” of disease. “I would urge caution [on whole genome sequencing]. It may be as cheap to do it that way, but we have still got to use the information appropriately. I’m not arguing this is information nobody should be allowed to know, just that we need to know what that information means.”
And even if you find a genetic mutation that is causative, “the real question is going to be, how do I use this information to help patients?” he said.