We need to talk about genomics
Professor Charlie Gourlay at Edinburgh University's Institute of Genetics and Molecular Medicine.
While our current healthcare system treats the symptoms of disease, medical researchers are now realising that our individual DNA has the potential to become a "manual" for the human body which doctors can use to better diagnose, treat and prevent disease.
Understanding disease is no longer just about examining tissue samples under a microscope, but also about examining the genetic signatures of those samples which are then analysed and cross-referenced against other human genomes and electronic healthcare records in a bid to understand better what makes us tick - and sick.
Although 99.95% of every human's genetic code is identical, within the remaining 0.05% are genetic variants and mutations that determine how we look and may even influence which diseases we are susceptible to. There are some people, for example, who are protected by their particular genetic background against the norovirus that causes diarrhoea and vomiting. The NHS could, when there is an outbreak of the bug, screen all staff to see who has this natural immunity and can therefore be sent on to the wards with impunity.
Our genes also affect how we respond to drugs. Right now, 6.5% of all hospital admissions in the UK are caused by adverse reactions to prescribed drugs, costing the NHS £1 billion per year. What's more, 25% of drugs prescribed for cancer are ineffective, as are 50% of those for arthritis, 57% of those for diabetes, 60% of those for asthma and 62% of SSRI's prescribed for depression. The drugs fail not because they are poor drugs, but because they are given to the wrong patients. The point is that every person metabolises drugs differently: in the absence of deeper information, doctors have to rely on trial and error to work out which drug will suit which patient.
In a bid to save money and lives, the NHS in Scotland and England are looking for better ways to deliver healthcare, and the hope is that "personalised medicine", labelled "stratified medicine" in Scotland - where our genes are used to match us to appropriate treatments - will become standard medical practice.
"We need to welcome the genomic era and deliver the genomic dream," wrote Sally Davies, the chief medical advisor to the UK Government, in a report published earlier this year calling on the expansion of genomic healthcare.
When Dr Charlie Gourley started treating ovarian cancer 12 years ago, all ovarian cancers were treated the same. Today, thanks to genomics, he now knows there are five different types of ovarian cancers, and the genes of each individual tumour will further determine how it will respond to treatment.
"Scotland was ahead of the game," says Gourley. "We were one of the first countries in the world to offer sequencing to all our ovarian canver patients."
This push forward came in 2008-09 when Scotland partnered with pharmaceutical company Astrazeneca to test Olaparib, an ovarian cancer drug used to treat patients with BRCA1 and BRCA2 mutations whose cancer had come back. These are the same mutations that Angelina Jolie had, and that prompted her to have a preventative mastectomy.
Back then it was thought that BRCA1 and 2 mutations were only found in patients with a family history of breast and ovarian cancers, so only those patients had their genomes sequenced. But Gourley wasn't convinced this net was big enough.
For the past 30 years, Edinburgh had kept a detailed record of every patient that had had ovarian cancer. Looking back through time, Gourley noted that there were other red flags - namely the organs to which the cancer had spread - that seemed to point to other women having BRCA mutations. Gourley convinced a genomics team to analyse the genes of 20 patients who did not have a family history of cancer: seven women were found to have the mutation. Given that Olaparib is highly effective in treating ovarian cancers in such patients, that was seven more lives potentially saved.
"This is a good example of how molecular profiling can be used to identify patients for a particular drug. But BRCA mutations only account for a quarter of ovarian cancer patients, so the question now is what can we do for other patients," says Gourley.
Scotland is positioning itself to become a centre for a new wave of drug development. The Queen Elizabeth University Hospital in Glasgow houses a genetic biobank, genetic sequencers and an analysis centre. In Edinburgh, at the £60m Institute for Molecular Medicine at the Western General, it's not doctors who fill the floors, but bio-informaticians who use super-computers to make sense of human genes.
The task is too complex and daunting for anyone to work alone, and increased collaboration between universities, the NHS and the private sector are set to become the new normal. Stratified Medicine Scotland have created a one-stop shop which will allow private drug companies to gain access to Scottish genomes - always anonymised - for medical research.
Interestingly Scotland's attractiveness does not just lie in its technological readiness, but in its somewhat unhealthy population.
"Scotland has a high incidence of diseases that the pharmaceutical companies are interested in," says Diane Harbison, CEO of Stratified Medicine Scotland, listing heart disease, cancer, diabetes, respiratory diseases, chronic obstructive pulmonary disease, irritable bowel syndrome and multiple sclerosis.
One of the first private companies to sign up is Astrazeneca. Currently only 10% of drugs in development make it to market. One of the reasons that the failure rate is thought to be so high is because they have been testing good potential drugs on the wrong people.
"We now realise that we may have been testing Alzheimer's drugs on people who have symptoms of Alzheimer's, but not the actual disease," says Menelas Pangelos, executive vice-president of Astrazenca's innovative medicines and early development biotech unit.
The hope is that using genetic markers to identify disease and the people most likely to respond to the treatment, the number of new drugs that make it to market will double.
But is it an unholy alliance? The NHS and universities are often billed as the good guys, working in the interests of the public, while Big Pharma is often much malinged for being motivated by profit.
Dr Charlie Gourley is pragmatic.
"There is a danger that the people might think that if you are facilitating drug companies that is bad. But to get a clinical trial through to license costs hundreds of millions of pounds. The universities cannot afford to develop a cancer drug all the way through."
Professor Graeme Laurie, chair of medical jurispudence at Edinburgh University, points out that attitudes to Big Pharma differ widely depending on who you are.
"Research has shown that younger and middle-age groups who are healthy tend to be sceptical, but if you speak to patient groups with long-term chronic conditions and rare disease groups, they have much more tolerance for the involvement of Pharma. We need to have grown-up conversations about the involvement of commercial entities," he says.
It's just the tip of the ethical iceberg.
Your genomic information is the code of who you are. As our understanding of the human genome deepens, it is expected that we will be able to know things about ourselves - or our unborn children - that we never knew before.
"We can actually predict someone's age and smoking status from their genetic data," says Stephen Beck, professor of medical genomics at University College London (UCL), who thinks the NHS is moving too fast in harvesting this information.
"We need a public-facing project so that people can begin to have real ethical arguments about whether we want this as a human race."
To this end, Beck started the Personal Genome Projects in the UK in 2013 where people can openly share their genomes and health data, without any promised protection of their identity, so that we can begin to understand what it means to have this kind of information in the public domain.
It's not a moot point. Throughout history - and still today - we see people excluded or eliminated because of their religion, disabilities or sexual preference.
Sir John Burn, professor of clinical genetics at Newcastle University and former chair of Britsh Society for Genetic Medicine is frank. "Because the Nazis killed all those with genetic mutations first, there is serious concern around the world about governement having ownership and access to genetic data."
Already genomics is having an impact in-utero. Down's syndrome has until recently been difficult to screen for because of the risk of miscarriage from the procedure, which involved inserting a needle into the womb to draw off some of the amniotic fluid. Now thanks to advances from genomics, a non-invasive pre-natal test can be used that can detect the foetus's genetic abnormality in a sample of the mother's blood. This has already been introduced in the Netherlands and will be available on the NHS in 2018.
Last Septemeber a letter writer to a Dutch newspaper espoused Nazi-like thinking, arguing that all expectant mothers found to be carrying Down's children should have moral duty to abort, since those children will be a financial burden on society.
We are at the threshold of a new world where what we can do may forever change what we believe we should do, and scientists worry that if we don't have robust public debate about these ethical questions, genomic healthcare may crash before it has taken off.
"Some things peak too soon and are then a disaster. Think GM food," says Tim Aitman, director of the centre for genomic medicine and experimental medicine in Edinburgh, referring to how in the 1990s, public unease towards genetically modified crops and their potential health risks led supermarkets to pull all GM foods from their shelves.
"We have to be better at explaining the benefit of genomics to the population," says Andrew Morris, former Scotland chief scientist and now director of the Farr Institute, which uses big data to innovate in healthcare.
England provided a textbook case of how not to do it. In 2013, NHS England made all electronic patient records, including details of GP visits, available for medical research.
All data would be anonymised, and people could opt out, but which organisations could have access to these records, and for what kind of research, was not properly communicated. Rather NHS England put a flyer through the letter boxes of the nation, which many never see, thrown away with junk mail. Trust in NHS England plummeted, and outrage skyrocketed.
While it might feel right and fair for the NHS to ask our permission to use our healthcare records for medical research, in terms of the law in Scotland, and the rest of the UK, individuals do not own their healthcare records or genomes.
"You have rights to have your privacy protected, but we don't see people, or people's healthcare information in terms of property," explains Laurie. With this in mind, Laurie suggests it is time for a new national debate on how we think about these records.
"As citizens, we take a lot from the NHS, but we don't give much back. We benefit from a public system, so why should we not be contributing to it? I don't think people should be forced to take part, but what if you thought of this data s not yours, but as part of a public resource?"
Scotland is taking a novel approach to public inclusion. Four of the largest NHS boards - Greater Glasgow and Clyde, Grampian, Lothian and Tayside - have teamed up to create the Scottish Health Research Register (SHARE), an opt-in database through which the public can give consent for their healthcare records and leftover blood samples, to be used for future genomic research.
Some 180,000 people have already signed up to SHARE, including Brian Glass, 59, a paramedic training officer from Arbroath. Glass's family has a history of Marfan syndrome, which can cause abnormally long limbs, bad eyesight and heart defects, from which his brother died. Glass himself has a disorder with his pituitary gland and has to give regular blood samples.
All SHARE volunteers give their consent for their data to be used for future medical research. "We call it giving broad consent, because at the time of donating, you can't be sure for what research, or by whom, your genome will be used," explains Laurie.
Glass is comfortable not knowing what kind of research is being done on his samples, but whether researchers should report back on their short-term findings is an ethical issue for researchers.
If researchers stumble upon genetic variants in a sample that indicate high risk of disease, should researchers tell the otherwise healthy person, who has volunteered their sample, that they are at risk of a disease?
The UK Biobank - another genomic research database that accepts volunteer donations - would not. It has been set up purely for research on the understanding that no findings will ever be returned to participants.
But SHARE is not sure if that is the best model for Scotland. "We are actively considering this," says Brian McKinstry, professor of primary care e-health. It's very complicated and depends on the condition, if there's treatment and how predictive this is. If you have a clear-cut risk factor associated with high cholesterol that we can treat, it's an easier decision. Bit it's a vaguer thing if you find something that potentially predicts dementia. But what happens if 30 years down the line, you find out that SHARE knew all along that you had the risk? You'd be pretty cheesed off."
This become trickier still when you consider the genetic data's inherent connection to kinship. If you have a genetic variant or mutation, it's possible that one of your siblings or offspring will also have it. Whose responsibility is it to tell your sibling? And what if they would prefer not to know? Do they have the right to stay wilfully ignorant to risks that may or may not affect them?
There are no clear answers in this brave new world, just a pressing need for debate.