Whose genes are they anyway?

The Progress Educational Trust (PET) has a reputation for being ahead of the game when it comes to engaging the public with new developments in genetics and related areas of science. Even so, as director Sarah Norcross highlighted in her welcome address at the charity's annual conference, it seemed uncannily good timing that an event devoted to the role of commerce in genetics and fertility treatment should coincide with the launch of 23andMe's controversial 'personal genome service' (PGS) in the UK.

The Google-backed company is offering a drastically pared-down version of the direct-to-consumer genetic testing service originally offered in the USA. Its health-related genetic tests were recently withdrawn from the US market following an FDA directive after the regulatory body stated that 23andMe had not 'analytically or clinically validated the PGS for its intended uses' (reported in BioNews 733). It was also concerned about how customers might interpret results about their risk of hereditary breast cancer and other rare genetic conditions. Is the FDA protecting the consumer or denying people access to vital healthcare information? These and other issues lie at the heart of the current genomics revolution, and were the focus of the second session at PET's conference, which asked: 'Whose genes are they anyway?'

The first speaker, Dr Kári Stefánsson, founder and chief executive of deCODE Genetics, is no stranger to controversy. In the late 1990s, the company lobbied the Icelandic government for the creation of, and subsequent sole access to, an opt-out database containing the medical records, family trees and genetic information of all of the country's 270,000 inhabitants. There has been little immigration to Iceland since the arrival of the Vikings 1,000 years ago, and deCODE aimed to exploit the country's unique heritage to identify genetic influences on disease.

Stefánsson recounted some of deCODE's numerous research successes, which include the identification of genetic variations that affect the risk of type 2 diabetes, heart disease and schizophrenia. He also highlighted the importance of the environment — for example, an MC1R gene mutation that increases risk of skin cancer in Spanish individuals has no effect on people living in Iceland (a country in which prolonged exposure to sunshine is less of a problem). Other findings include the identification of genetic variants that affect a person's compulsion to smoke, and thus their risk of lung cancer.

On a lighter note, there appears to be a genetic component to crossword puzzle addiction, though Stefánsson says its effect on enthusiasm does not extend to ability. He also touched upon genetic ancestry studies, which show that present-day Icelanders are genetically very different to their ancestors. These ancient settlers were much more similar to the present-day inhabitants of their homelands, Britain and Scandinavia. Stefánsson speculates the rapidly changing genetic make-up of Icelanders may be the result of adapting to their harsh environment.

Next up was Vivienne Parry, head of engagement at Genomics England, the company established by the UK Government to carry out the 100,000 Genomes Project. Parry started by outlining details of the scheme, which aims to probe the genomes of patients affected by cancer, rare conditions and infectious diseases. Despite the project's name, it aims to recruit 75,000 invited participants by 2017. The reasons for the lower number are that two samples will be analysed from each cancer patient, one from the tumour and another from blood. This will allow researchers to compare the two, and identify the exact genetic changes responsible for the cancer and its progression. In addition, for rare diseases, the genomes of patients plus two of their closest relatives (ideally both parents) will be analysed. In this way, scientists hope to identify which of the many genetic differences between individuals is the one responsible for the patient's condition.

Parry admitted that the pilot project had taken longer and been far more technically difficult than anticipated, but remains optimistic about the potential of genomics to transform healthcare. Through the creation of 12 new Genomics Medicine centres, the project aims to provide 'a lasting legacy for patients, the NHS and the UK economy', as well as a rich resource for researchers.

Parry spent some time addressing public concerns over privacy, stressing that access to the project's database would be highly controlled — the police, HMRC and marketing companies will all be forbidden from accessing the data. Interestingly, she said that participants were less worried about commercialisation, recognising that this was one route through which the findings may be translated into new medicines.

On the issue of 'incidental findings' — that is, information unrelated to the medical condition being investigated — the researchers will only alert patients' clinicians if they have one of a small number of genetic mutations that cause a 'serious and actionable condition'. One such example is familial hypercholesterolaemia, in which levels of 'bad' low-density lipoprotein (LDL) cholesterol in the blood are higher than normal from birth, increasing the risk of heart disease at an early age. Others include mutations in the genes involved in rare forms of inherited cancers, such as BRCA1 and BRCA2.

Balancing the vision of personalised future healthcare based on genomic information offered by the first two speakers, general practitioner Dr Clare Gerada offered a 'reality check' on how the changes may affect those working in primary care and their relationships with patients. Will the forthcoming 'health revolution' make the role of GPs as guardians of medical information irrelevant, in the same way that the printing press supplanted the priests of the middles ages, she asked? She stressed the uniqueness of every patient encounter, and, as a stark reminder of the limits of medical knowledge, added in the subsequent discussion that the most common cause of death in her own practice was 'loneliness'.

Gerada went on to argue that too much choice in any area of life can lead to 'anxiety and paralysis', and that care was needed to ensure doctors and their patients were not burdened with excessive information without being told how best to use it. She also warned against the dangers of shifting responsibility for health from society to the individual, which could lead to 'discrimination for making the wrong choices'. Gerada finished with a reminder that medicine is as much an art as a science, and that doctors need to remember their roots as carers and healers.

The final speaker was Dr Stuart Hogarth, a researcher at King's College London who is looking at how post-genomic science enters clinical practice. Speaking about novel biomarkers in general, rather than just genetic information, he told the audience that we are on 'the brink of a molecular taxonomy of disease'. Although this may revolutionise healthcare and the diagnostic industry, he highlighted the need for 'maps to guide us through the alien landscape of planet biomarker'.

Hogarth said that despite the torrent of new biomarkers identified in recent years, very few have yet made it into clinical practice. Why, he asked, was there no pathway for the testing and development of new biomarkers analogous to that established for new drugs? He gave the example of diagnostic tests for cervical cancer screening based on HPV testing. Although there are 125 such tests available worldwide, only 10-15 percent of these have been evaluated in clinical trials. It seems that the regulatory landscape is more relaxed in the European Union, where 79 are on the market, compared to the USA, where the FDA has approved just four. Hogarth cautioned that there may be a 'price to pay' for leaving it to private companies to invest in trials of new biomarkers, as not all would do so.

A lively discussion followed the presentations, ably chaired by Fiona Fox, director of the Science Media Centre and chair of trustees at PET. Additional issues raised included the challenges of living with uncertainty, whether the UK should legislate against genetic discrimination, the need for more training in primary healthcare, the responsibility of journalists to provide accurate information about new developments, the utility of diagnosing diseases with no cures, and the impact of increasing privatisation within the health service. There are no easy answers to these questions, but one thing is certain: the need to allow everyone to raise concerns, express their opinions and engage in the debate has never been greater.

The Progress Educational Trust (PET) is grateful to the conference's sponsors - Merck Serono, the Anne McLaren Memorial Trust Fund, the Edwards and Steptoe Research Trust Fund, Ferring Pharmaceuticals, the London Women's Clinic and the Medical Research Council.

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