It all started 30 years ago, deep in the Wasatch Mountains, a 40-minute drive along narrow, winding roads from Salt Lake City, Utah. It was early December 1984, and a blizzard was rolling in. Nestled amid the white-capped slopes, inside an isolated conference centre, a group of eminent scientists spent five days taking part in a workshop sponsored by the US Department of Energy. Their aim? The initial stages of what is now known as the Human Genome Project: identifying and sequencing all three billion chemical units in human DNA. With this, they hoped, it would be possible to find the roots of all diseases and develop effective treatments, ultimately eradicating them for good.
Nearly two decades later, the Human Genome Project — by then comprising the top geneticists from the UK, France, Australia and Japan — was declared complete. It was, announced Prime Minister Tony Blair, in a joint statement with US President Bill Clinton, ‘a revolution in medical science whose implications far surpass even the discovery of antibiotics’. For the next few years, however, the revolution ground to a halt. For though mapping the human genome was a momentous breakthrough, it only marked the beginning of its application in medical science. Studying the genome was one thing; but taking the theory from the laboratory to the bedside was to be a much greater challenge.
Fast forward ten years and much has changed. What the fathers of the Human Genome Project had hoped would be commonplace within months of their discovery is, at long last, being realised. Genetics is being used not only in the diagnosis of disease, but in its treatment; to determine which drugs a particular patient should take; which therapies will work and which won’t; how likely it is that a cancer will return. Barely a week goes by without another landmark trial or innovation in this sphere: a genetic-based smear test being developed for breast cancer detection; genetic profiling to determine whether we will live beyond 100; even smartphone technology that uses facial recognition to detect cellular mutations. Genetics — and its use in tailoring treatments to individual patients, a strand known as ‘pharmacogenomics’ — is vastly altering the landscape of medicine.
‘Historically, medicine has been an observational science based on the symptoms and pathology that could be seen or simply measured,’ explains Graham Ball, professor of bioinformatics at Nottingham Trent University’s John van Geest Cancer Research Centre. ‘It can now proceed on a molecular basis, getting to the core drivers or causal agents of the disease. This has the potential accurately to classify a disease into a given type, providing much more detail.’ Indeed, recent advances in genetic testing have given us not only personalised medicine, but a new genre altogether: instead of treating diseases once symptoms have developed, doctors are starting to embrace ‘preventative medicine’.
The simplest and most familiar application of this is in anti-ageing treatments. Pharmacy shelves are lined with products claiming a genetically based approach to skincare —Lancôme’s Génefique range, Olay’s Professional Pro-X lotions — which contain active ingredients that work on elements of our cellular make-up to minimise the signs of ageing. This same principle is applied in private clinics up and down the country, where genetic tests are carried out and treatments prescribed to delay the process of cellular degeneration.
At the SHA Wellness Clinic in Alicante, Spain, a pioneering health spa favoured by world leaders, film stars and supermodels, Dr Gloria Sabater leads an exclusive anti-ageing programme based on genetic profiling. ‘Twenty-five per cent of our predisposition to diseases is linked to our genes,’ she says. ‘There are many things about ourselves that we don’t know — all we do is give you the tools to find out what these are.’
Genetic tests of the sort carried out at SHA are straightforward and painless — a simple blood or saliva sample — but don’t come cheap. Consultations start at £120; a complete genetic profile — testing a patient’s predisposition to everything from alopecia to diabetes, glaucoma, osteoporosis and Alzheimer’s — will set you back £3,170. Dr Sabater can’t stop the advent of diseases picked up by the genetic tests, but she can help clients to modify their diet and daily activities to minimise the likelihood that they will develop. ‘If you are able to predict what to prevent in the future, you can manage your lifestyle better now.’
At the other end of the spectrum, such advice may seem frivolous. For advances in genetic profiling mean that pharmacogenomics is carving out a crucial role in the treatment of more serious illnesses. Dr Gianrico Farrugia, director of the Mayo Clinic’s Centre for Individualised Medicine in Rochester, Minnesota, says developments in this area have been a ‘transformational event’ in medicine, with genetics now used to treat obesity, depression, rheumatoid arthritis and epilepsy. The Mayo Clinic is successfully treating patients that other doctors are struggling to diagnose. ‘We have embedded genetic information in our electronic medical records,’ explains Dr Farrugia. ‘It allows specific information to be gathered that predicts risk of disease or protection against a disease. Patient satisfaction has been very high.’
Cancer treatment has been the key focus for genetic research in recent years. At the Mayo Clinic, the emphasis is on aggressive breast and prostate cancer. In Nottingham, Dr Ball’s team have concentrated on predicting drug responses in breast cancer, enabling experts to ‘piece together the jigsaw of… this complicated disease’. Research tends to centre on tumour profiling, whereby a biopsy is taken of a small section of a patient’s tumour, and this is tested for a broad range of proteins known as ‘biomarkers’ which, in turn, indicate whether a particular treatment is likely to be effective and hint at the tumour’s evolution.As Ian Walker, international vice-president of Caris Life Sciences, the world’s leading tumour profiling company based in Phoenix, Arizona, explains: ‘We’re moving away from the idea that you have “breast cancer” or “bowel cancer”. In many ways, your biomarkers are far more important in determining your treatments and your chances of survival. Your liver cancer might have more in common with someone else’s brain tumour.’
Caris’s profiling system has been used by 50,000 patients in the USA, and is being trialled by some UK oncologists, such as the team at Hammersmith Hospital in London. Most striking is its impact on longevity: a recent study showed a 46 per cent reduction in the risk of death post-profiling. The theory is certainly convincing. In practice, however, the roll-out of genetics-based cancer treatment has been skewed by geography: technological advances have spurred innovation in China, Singapore and Brazil; while funding for trials has been more readily available in the USA than anywhere else. In recent months, for example, one of the most significant developments has taken place at a top New York hospital, the Memorial Sloan Kettering Cancer Centre, in which genetic testing has been implemented as a standard treatment. Within the next year, doctors hope to sequence 10,000 patient tumours — the biggest such project to date — and group these patients into categories based on the mutations in their tumours (with less regard paid to the type of cancer).
Though it is slow, progress has not been entirely on hold in Britain. There are at present 32 NHS genetics centres here — though these tend to focus on rare genetic disorders, such as Marfan syndrome, rather than commonplace diseases. Last year the Royal Marsden Hospital in London piloted an ‘oncogenetic’ pathway for ovarian cancer patients, whereby 114 women were offered tests to establish whether they carried the gene mutation increasing susceptibility to the disease. This was carried out by the hospital’s new Translational Genetics Laboratory, which plans to extend testing to all cancer diagnoses within three years.
Pharmaceutical companies, too, are signing up to genetics research. In April a ground-breaking two-year clinical trial was announced, jointly funded by Pfizer, AstraZeneca and Cancer Research UK, which aims to sequence the tumours of 200 lung cancer patients and test the effectiveness of 14 different drugs, designed to target specific and rare mutations. Professor Charles Swanton, head of the Translational Cancer Therapeutics Laboratory at Cancer Research UK’s London Research Institute, says greater inroads have been made in this area in the past two years than the previous decade. ‘Our research is revealing unexpected diversity in solid cancer tumours, which accounts for treatment failure, drug resistance and poor outcomes for patients. Within the next ten to 20 years, I hope we’ll be able to predict the cancer’s next evolutionary move — and therefore forestall it.’
Patients benefit from individually tailored treatment, fewer side effects, cheaper drugs, better health and possibly a longer life. For hospitals and the healthcare system, however, the benefits are also manifold. Adverse drug reactions cause an estimated 100,000 deaths and 2.1 million serious injuries in the UK each year, costing the NHS around £2 billion. ‘In an NHS that is short of money and facing ever-increasing demands,’ says Alastair Kent, director of the patient-centred charity Genetic Alliance UK, ‘this is not trivial. We stand on the cusp of a revolution in healthcare.’
But challenges remain. The expense of a comprehensive adoption of genetic testing could take decades, not years. ‘European nations like Britain are incredibly slow to take up medical innovations,’ explains Ian Walker. ‘Companies who develop and market these exciting new services will move out and set up in emerging markets, and Europe risks becoming a backwater.’ As a result, much of the work to date has been carried out in discrete trials, funded by private companies. ‘The average UK patient is not even aware that such a service exists and could help them,’ adds Walker. The next stage, therefore, is to extend the reach — and public awareness of — pharmacogenomics. Tim Spector, professor of genetic epidemiology at King’s College London and author of Identically Different, a study of human genetics, says studies that predict and help us manage lifestyle factors — such as weight gain or skin conditions — may be the way forward.
So what does the future hold for the world of genetics, and what does it mean for patients? Professor Spector says we are moving towards a time when everybody’s genes will be fully sequenced at birth. ‘Within ten years,’ he says, ‘this could be a reality. Then, as people go through life, they can have regular tests to see how things are changing.’ Patients will no longer only be genetically tested after they have developed symptoms of a disease, but before. Indeed, this could be taken even further. A father in California made headlines recently after he mapped his unborn son’s genome five months before his birth. By obtaining a tissue sample from the placenta, the father-to-be — a geneticist himself — created a rough draft of his son’s genes, making the baby the first ever to be born with his entire cellular make-up deciphered in advance. Within the next decade, stories like this will no longer be news, but routine. Medical genetics is finally on the march. Much like the ‘completion’ of the Human Genome Project back in 2003, this is not the end of the road — it is only the beginning.