I see a long life and a healthy one... New Scientist vol 176 issue 2370 - 23 November 2002 Over-the-counter gene testing is set to become big business, but do the tests on offer really tell you anything useful about your future health? Gail Vines reports THE DNA revolution is finally here. Tests on our genes can now tell us which diseases we risk developing decades before we get any symptoms. And forewarned is forearmed - by changing our lifestyle, taking a medicine or even having pre-emptive surgery, we stand a chance of avoiding our genetic fate. That's the sales pitch of a new breed of biotech entrepreneurs who are marketing genetic tests directly to the public. Thanks to them, we no longer have to make a trip to the doctor to learn the secrets of our DNA. Increasingly, these tests are available through the post or the Internet, and they've even been found in high-street shops. On offer are tests to tell you your risk of cancer, heart attack, stroke, osteoporosis, allergies, and more. But many doctors and scientists are unhappy about do-it-yourself gene tests. They say that without the right medical advice people are likely to misunderstand the results. And some tests are based on shaky scientific grounds, they believe. Some firms stand accused of exploiting people's fears about their health, peddling tests that are no better than genetic palm-reading. Members of the Human Genetics Commission, who advise the British government on DNA issues, are worried too. A few months ago, the Commission hurriedly convened a special panel to investigate whether there should be stricter controls on over-the-counter genetic tests, which is due to report early next year. Until now, GPs and clinical geneticists have controlled access to genetic tests. Typically, a doctor would tell you what tests are available, help you decide if you need one, and then tell you what, if anything, to do about the results. At reputable genetics clinics, patients get counselling before and after every test, to try to ensure they understand the full implications of the results. But commercial gene-testing companies are now proliferating at an astonishing rate, and their target consumers are the worried well. Biotech entrepreneurs are harvesting the early fruits of the human genome project and are banking on millions of health-conscious people being eager to find out whether or not they risk developing particular diseases. But will we lose an important safeguard by cutting out the medical middleman? "At the moment, the public doesn't understand enough about genetics to interpret the test results," says bioethicist Tom Shakespeare of the Policy, Ethics and Life Sciences Research Institute at the University of Newcastle upon Tyne. There's a real risk that people could become unnecessarily frightened, fatalistic or falsely reassured, he says. These consequences aren't minor. People who mistakenly think they have a low risk of cancer, say, might ignore early symptoms, a delay that could cost them their lives. Or someone told they have high-risk genes might spurn a healthy lifestyle, on the grounds that they're doomed anyway. Psychologist Theresa Marteau of King's College London has carried out extensive research into the impact of genetic testing. She says a likely fallout is false reassurance. "If you get a result and find you don't have one particular mutation, you may falsely think that you're invulnerable, and at no risk at all." Speaking at a conference in London last week on over-the-counter genetic tests, Marteau pointed out how common it is for patients to misunderstand test results' significance, even after long talks with specialist counsellors. The trend towards marketing tests directly to the public is exemplified by Myriad Genetics of Salt Lake City, Utah. For years, this leading biotech firm has offered, through doctors, tests for mutations in two genes, BRCA1 and BRCA2, that are strongly linked to inherited forms of breast cancer. These mutations cause only a small number of breast cancer cases - fewer than 5 per cent of the total. But if breast cancer seems to run in your family, you might want to know whether you too have a BRCA mutation. Some healthy women have even had both breasts removed to try to avoid dying the way their mothers did. But Myriad isn't content with its current market. It is planning to advertise these tests directly to the public. In September, Myriad started piloting TV adverts in Atlanta and Denver that showed attractive women telling the viewer: "Breast cancer runs in my family... I wondered if it would be inevitable. I found it didn't have to be." A spokesman for Myriad defended the campaign, saying: "Asking physicians to be the lone factor in determining whether a family history of disease exists is both paternalistic and ineffective." And the firm still requires women to get a doctor's approval before it carries out the test. But critics warn that, in the US at least, persistent patients can usually get a doctor to order any test they want, whether or not they've had proper counselling. And they question whether blanket advertising is appropriate for a mutation only carried by one in a thousand women. Paolo Vineis, an epidemiologist at the University of Turin in Italy says: "To offer the test to the population broadly is extremely dangerous and unethical. Testing should be offered only to families [with a history of the disease] or other high-risk groups." But perhaps Myriad is the least of our worries - the firm's marketing strategy may be questionable, but at least the BRCA tests are established products backed by reputable scientific research. The latest batch of genetic tests to reach the market may not all be able to make that claim. Unlike medicines, new genetic tests don't have to be approved by regulatory bodies such as the Medicines Control Agency in Britain or the Food and Drug Administration in the US. Scientists fear that some of the new tests don't actually do what they're claimed to do. A case in point is a test that supposedly tells people their risk of osteoporosis, the brittle bone disease that strikes many women after the menopause. Vitamin and mineral supplements or hormone-replacement therapy lower the risk of osteoporosis, so a way to identify susceptible women would be useful. But will the OsteoGenomic Profile test offered by Great Smokies Diagnostic Laboratory (GSDL) of Asheville, North Carolina, actually tell you anything useful? Spurious science? It includes, for example, an analysis of your gene for the vitamin D receptor (VDR). This receptor protein is essential for the action of vitamin D, vital for building and maintaining strong bones (deficiency in childhood leads to the tell-tale bow legs of rickets). The trouble is that although some studies have found a link between variants of the VDR gene and bone density in adults, others have not. GSDL says: "Our medical science team through peer review has determined it to be an extremely valuable [test]." But in 1999 one study of nearly 10,000 women concluded that analysing the VDR gene is "not a clinically useful test for the prediction of fracture risk" (Journal of Bone and Mineral Research, vol 14, p 1637). GSDL's tests, sold in Britain mainly through complementary therapists, have come under fire from GeneWatch UK, a small non-profit organisation that lobbies for genetic technologies to be used in the public interest. "We have serious concerns about such tests," says deputy director Helen Wallace. "People need to know that the science is still poorly understood, and many genetic predictions of their future health are spurious." She is equally scathing about some of GSDL's other tests, pointing to similar inconsistencies in published research. John Ioannidis, a molecular epidemiologist at Tufts University in Boston, is worried that many of the links claimed between genes and diseases are overstated. Last year he published a large statistical review, or meta-analysis, of 36 supposed associations between particular genes and diseases, involving 370 studies in all (Nature Genetics, vol 29, p 306). For 26 of these genes, the first study published showed a strong association with a disease, but later studies suggested a much weaker link. Ioannidis says: "We have to be cautious in adopting this information for everyday use. Some tests may have no prognostic power at all when we get a more rounded picture of them." No one is suggesting that there aren't any links between genes and disease. But this research field is a highly contentious one, where different studies produce markedly different findings. And firms are reluctant to describe the full range of scientific opinion in their promotional material. Moving still further away from tests likely to be recommended by your doctor, "lifestyle" genetic testing has now entered the marketplace. Last November the British-based biotech company Sciona, in Hampshire, began selling test-kits in certain Body Shop stores, a retail chain better known for selling make-up and face-creams. For £120 you could post your DNA to Sciona, along with a lifestyle questionnaire. The firm analyses nine genes that it claims reveal clues about what sort of diet you should eat. But the tests got a poor reception from independent scientists. For example, one gene they analyse codes for the enzyme methylene tetrahydrofolate reductase (MTHFR), which helps the body metabolise folate, one of the B vitamins important in cell division. Say you have a particular variant of the MTHFR gene that is considered less efficient, Sciona recommends eating more foods rich in vitamin B, such as liver and leafy green vegetables, to compensate. But many scientists are sceptical of this interpretation - they point out that everyone should eat up their greens. Chris Martin of Sciona says: "The science is in an early stage, but there are some specific areas where the genetics is powerful and useful." He offers to produce over 300 peer-reviewed papers that back up his tests, and cites nutritional studies in which researchers have detected differences in blood biochemistry that correlate with certain genes. But Wallace of GeneWatch and other critics point to a mountain of conflicting or inconclusive findings. One study of 126 Welsh men, published last year, found that eating more veg or taking vitamins did not benefit the circulatory system, whatever their MTHFR genotype (Journal of the American College of Cardiology, vol 38, p 1799). Tailoring your diet to your genes makes as much sense as consulting a palm-reader, they argue. Wallace calls Sciona's product "an expensive way to be told to eat more vegetables". Some canny companies are selling more than just DNA tests. GeneLink, based in Margate, New Jersey, first analyses people's genetic "oxidative stress profile" (whatever that is), then flogs them targeted vitamin supplements and skin-care products. It sounds like the marketing gimmick of the century, but Wallace condemns this strategy: "It's marketing fear - telling people you'll get these diseases if you don't buy such-and-such." You might think that such firms are doing little worse than relieving the gullible of their cash, but any kind of genetic testing has serious implications. Any widespread use of genetic tests to set insurance premiums could generate an underclass of people unable to get mortgages, loans, life insurance, or private health cover. At present, British insurance firms cannot insist that customers declare the results of a genetic test (for most policies), but that may not always be the case. The government has only agreed a voluntary five-year moratorium, which doesn't prevent tests taken now being used to set premiums in future. So far only a few countries - notably Austria, France, the Netherlands and Norway - have made new laws to prevent insurers from finding out genetic test results. The insurance implications are worrying for those taking medical genetic tests, but even "lifestyle" tests could reveal more than a customer bargains for, as genes commonly have multiple effects. Someone who takes a test during a youthful health craze could find themselves regretting it 10 years later when they apply for health insurance. So what are the prospects for tighter controls on over-the-counter gene tests? In the US, firms can rest easy for the moment. President Bush has recently disbanded the government's Advisory Committee on Genetic Testing, just as it was about to investigate how the Food and Drugs Administration might regulate the emerging gene-testing industry. Government spokesman William Pierce has denied rumours that the committee was shut down because its recommendations were at odds with the president's views. He said the move was part of a general "restructuring" and a new committee would be created to address a "broader range of genetic technologies". British regulators were caught on the hop when Sciona's tests first went on sale. No one had foreseen that consumers would suddenly be able to learn something about their genes without a doctor's agreement, or even knowledge. The official guidelines were woefully outdated. The code of practice drawn up by the government's Human Genetics Commission in 1997 was designed for relatively straightforward tests to detect carriers of hereditary diseases such as cystic fibrosis. Alarm bells Sciona's tests and others like them set alarm bells ringing at the HGC. Embarrassingly, Sciona had just won a £130,000 Smart Award through the Department of Trade and Industry's small-business service, for spotting such a profitable niche in the market. There was a flurry of bad publicity, and the commission hastily launched an inquiry into over-the-counter genetic tests - both medical and lifestyle ones. Although no laws had been broken, the Body Shop pulled Sciona's tests from its shelves, citing lack of demand. The tests now can only be ordered through dieticians or a few GPs. The HGC inquiry is still ongoing. Philip Webb, chair of the panel carrying it out, told New Scientist that, without wishing to prejudge the debate: "The feeling is there is insufficient evidence at present. The matter is so complex, given the interactions between genes, environment and diet, that to start giving individual advice is somewhat premature." One clinical geneticist close to the HGC, who asked not to be identified, went further: "It's like testing one component in your car, and drawing a conclusion about the health of the engine. The science just isn't up to it - the companies are jumping the gun." So what can be done? Everyone seems to agree that the labs involved should be vetted for basic quality controls and confidentiality procedures. Even some of the firms themselves accept that. Martin of Sciona says: "Right from the start we called for regulation." But some scientists also want to introduce laws that ensure tests do what they are claimed to do, and that they are not being mis-sold. The only safeguards at present are the ethics of biotech firms' chief executives. And companies are not benevolent providers of medical care - they're in business to generate profits for their shareholders. Wallace wants the tests themselves to be licensed, like drugs and medical devices. She says: "We'd like a proper regulator - an Ofgene with teeth." Webb has previously suggested that the existing Medical Devices Agency might be a suitable regulatory authority in Britain, if one is needed. Another option would be to return control of genetic testing to the medical profession, banning companies from providing tests unless requested by a doctor. Companies say this is a step too far towards medical paternalism, and argue that people have the right to obtain genetic information about themselves. But Wallace disagrees: "We need to ensure proper consultations through GPs to ensure that people understand the implications of taking a test," she says. Some firms argue that by selling the tests through pharmacists and complementary therapists, customers are indeed getting guidance from healthcare professionals. But at the conference last week, a spokesman for the British Consumer's Association, which has been lobbying for better regulation in this area, pointed out that some complementary therapists have few qualifications. You can call yourself a "registered nutritional therapist", for example, after a four-day course. And should pharmacists be seen as guardians of evidence-based medicine when these days they stock their shelves with magnetic bracelets and homeopathic remedies? At the least, a voluntary code of practice is on the cards, backed up by the threat of legislation if the industry fails to fall into line. Of course in some respects, the gene genie is out of the bottle. The Internet is making a nonsense of the notion of national control. Those who favour regulation aren't swayed by this argument, however. After all, just because you can buy Viagra over the Internet, we don't shut down the Medicines Control Agency. "We want to set standards we feel are appropriate for the UK," says Webb. "The Internet means that national boundaries are less significant, and we can't control what happens in other countries," he concedes. "But we can put forward our recommendations so at least people are aware of the issues. If there's no code at all, anything could happen."