Living by the Code

The mixed blessings of commercial gene testing

by Cushla McKinney

Imagine being able to send a sample of saliva off to a laboratory and (for a small fee) receiving a personalised assessment of your chances of developing a host of physical and mental illnesses, the medications which will be most effective in treating or preventing them, and the type of diet that you should follow to ensure optimal health. As an added bonus, you might be put in touch with a pharmaceutical company or private clinic that can provide the treatments you need.

How much happier and healthier you’d be if you could adjust your lifestyle to suit your particular genetic endowment! No more need to worry about which of those thousand pieces of advice out there to pay attention to, you’d just listen to relevant ones and ignore the rest. Because you’d know what diseases you are most likely to get, you’d be able to spot the earliest symptoms and tell your doctor exactly what was wrong, thus receiving prompt and appropriate treatment without time-consuming and unnecessary testing.

You’d save on insurance since you’d only need to buy cover for illnesses you are susceptible to, rather than take out blanket premiums ‘just in case’. Your family, too, would be far more healthy and well adjusted if you had this kind of information. You could get your kids tested at birth (or before), and know if they are at risk of developing addictions, eating disorders, antisocial behaviour, obesity, autism, and all of the other the things you, as a prospective parent might need to know.

Society as a whole would also benefit because government would be able to channel healthcare, education and early intervention programmes effectively and without the huge wastage of tax dollars that currently occurs. This may sound like the stuff of science fiction, but there are already companies out there promising to provide exactly this type of service.

Tests are available for a broad spectrum of developmental or medical illnesses; you can identify personal traits such as male baldness and sporting potential, or your susceptibility to diseases such as cancer, heart disease or schizophrenia. You can find out how well your body metabolises food, utilises nutrients and deals with toxins. You can even receive specific dietary supplements and advice based on your genetic profile. All these services are just an Internet search and a biological sample away. But be warned, you may find that what sounds like a utopian dream may in fact be a nightmare.

The first thing to consider is what the test results actually tell you. While some diseases, such as Huntington’s chorea, are caused by single-gene defects, the majority are the result of a complex combination of variations in a number of different genes and environmental factors, not all of which are known or fully understood.

Many of these tests and not diagnostic but predictive; while you may have some genetic predisposition to a particular illness, this does not mean that you will necessarily become sick. You might be told that you are at risk, but is this going to provide you with any more information than your GP can get from a detailed family history and physical exam? Do you even have all the information you need to interpret the results?

You may – for instance – be twice as likely to suffer a brain tumour than someone without the deleterious genetic variation (frequently referred to as relative risk), but this is meaningless unless you know the absolute risk of the disease. If your chances of developing a disease goes from 1:1000000 to 1:500000 there is little to worry about, but a change from a 1:10 to a 1:5 risk would be a cause for concern . And is this knowledge necessarily going to enable you to take proactive steps to prevent disease, or will you end up undergoing unnecessary testing or medical procedures in attempt to avoid an illness you might never have developed in the first place?

If I find out that I am at no genetic risk of developing heart disease, I might be tempted to decide that I don’t need to bother watching my weight, diet or fitness level. Alternatively, I could take a fatalistic view of a result showing genetic predisposition and decide that there is no point in bothering to try and change my lifestyle because I’m going to have a coronary anyway. Personally, I would probably interpret every instance or breathlessness or indigestion as symptoms of a heart attack, making a misery both of my own life and that of my GP. Doctors’ surgeries could well end up full of the ‘worried well’ demanding reassurance or prophylactic drugs they do not need, for illnesses they don’t yet (and may never) have.

Among the risks identified on the 23andMe consent form are the following:

  • You may learn information about yourself that you did not anticipate
  • The laboratory process may result in errors.
  • You should not change your health behaviours on the basis of this information.
  • Genetic research is not comprehensive. Future scientific research may change the interpretation of your DNA.
  • Genetic data you share with others could be used against your interests.
  • Taking these into consideration, the information gained from these tests is principally of use for genetic research rather than individual benefit. This is a legitimate goal, but needs to be clearly understood by those who pay for the services of such commercial enterprises. Another caveat is that it is the individual’s responsibility to ensure nobody else gains access to his or her account and password. Although the retail DNA test was voted Time’s Invention of the Year in 2008, that same year 23andMe was voted the biggest threat to genetic privacy in the Captain Cook Bio-piracy Awards.

    Even when the links between genetic variation and disease are reasonably direct, problems remain. One of the first genetic tests to become commercially available was for BRCA1 and BRCA2 mutations associated with breast and ovarian cancer. At first glance, knowing one’s BRCA status would seem to be beneficial from both a psychological and therapeutic standpoint. But this apparently straightforward case exemplifies many of the difficulties that can arise.

    For those who carry the deleterious mutation the risk of developing cancer by age 70 is highly variable, ranging from 35%-85% for breast, and 10%-46% for ovarian cancer. In the event of a positive gene test, there are a variety of preventative measures available, all of which carry risks of their own, and only prophylactic removal of breasts and/or ovaries is proven fully. This type of surgery is a drastic measure to take avoid *potentially* developing cancer, and one has to ask whether the benefit of knowing about having a mutation of unknown effect is worth the costs.

    These include psychological responses (anxiety, depression, perhaps even an anti-placebo effect), and the costs both to individual women and a struggling health system of widespread over-diagnosis and unnecessary treatment. Nor is a negative test any guarantee of safety, since there are other potentially cancerous BRCA mutations that this test does not pick up.[1] This is especially true for non-Caucasian women, since it (like most of the commercially available genetic tests) is based on the most common variations that lead to disease in Anglo-American or European populations. In other ethnic groups, different mutations may be clinically important but will go undetected by current tests, providing false reassurance.

    A final, important consideration is that in finding out one’s own genetic profile also provides information about other members of the family, information that they may not wish to know. To illustrate the problems this could arise, consider the mutation that causes Huntington’s Disease (HD) a late-onset disorder with no cure – the folksinger Woody Guthrie (pictured left) was one wellknown example of the condition.

    Take a purely hypothetical situation. Let’s imagine there is a history of this illness in my mother’s family, I would decide to find out if I carry the disease-causing version of the gene so I can decide whether to save for my retirement or spend my earnings on a round-the-world trip. My mother, however, doesn’t want to know if she will get Huntington’s. If my result is positive, this means my mother also has the mutation, a fact that will be difficult to hide from her. In exercising my right to know, I violate her right not to know, and the impact of this on our relationship needs to be weighed against the advantage of being able to plan for my future.

    Perhaps as a result, the uptake of predictive testing by those at risk of HD has been surprisingly low, ranging from less than 4% in Germany to 24% in the Netherlands. Although up to two thirds of potential HD carriers indicate an intention to take the test, the number who go on to provide blood samples after receiving genetic counselling declines dramatically. This seems to reflect the degree to which individuals feel they are able to cope with a bad result – although some felt that they had a moral obligation to be tested, so that their children could make informed reproductive choices.

    As things stand, the right not to know is now recognised in Article 5 (c) of the Universal Declaration on the Human Genome and Human Rights (1997), which states that: “The right of each individual to decide whether or not to be informed…should be respected”.

    Commercial genetic testing also raises issues regarding life and health insurance. Because insurance companies have the legal right to demand disclosure of the results of any genetic testing, they could potentially use commercially-generated data to ‘cherry-pick’ low-risk clients or refuse to provide cover for the very illness a person most wants insurance against.

    Ironically, however, concerns about easy availability of genetic information cut both ways. According to bio-ethicist Donald Evans, who has held discussions with New Zealand insurers, the insurance industry fears that people who find they are not genetically predisposed to disease of will cancel their policies, leaving the insurers carrying only higher risk individuals and potentially destroying the entire system. Similar fears in the UK have led to the British Insurance Association to impose a voluntary moratorium on the use of genetic tests for insurance purposes unless there is demonstrable evidence they are actuarially significant, and there are moves to negotiate a more formal agreement between the industry and Government.

    In New Zealand, the 2009 report by New Zealand’s Human Genome Research Project suggested an independent, non-statutory body to protect consumers should be established. It would be responsible for setting criteria for assessing the suitability of specific tests, evaluating and making recommendations about these tests, and monitoring and the use of genetic tests by the insurance industry. Although the primary focus of this report was on genetic diagnosis (such as screening for Huntington’s), this model could be expanded to include predictive testing.

    Another potential model for New Zealand legislators is the Genetic Information Non-Discrimination Act (GINA) that came into effect in the US in November. This makes it illegal for insurance companies to deny coverage or to charge a higher rate or premium to an otherwise healthy individual who is found to have a genetic predisposition to a disease or disorder.

    GINA also makes it illegal to use an employee’s genetic information when making employment decisions such as hiring, firing, promotions, or with respect to any other terms of employment. Although some workplace protection might be provided in New Zealand by human rights legislation (both the Human Rights Act 1993 and the New Zealand Bill of Rights Act 1990 prohibit discrimination on the grounds of disability), it is not clear whether the term ‘disability’ covers genetic predisposition to disease.

    The interpretation and explanation of the results of such tests, the implications of such knowledge, and the various management options can be provided by genetic counsellors. Unfortunately, there are currently fewer than 10 such specialists in New Zealand in the country, too few to meet current need let alone demands from those who purchase commercial tests, and such advice is not necessarily provided by the companies that market them. Increased investment in training genetic councillors and/or legislation requiring companies to provide these services need to be considered with some urgency as access to and affordability of genetic profiling increases.

    Although a variety of Government advisory bodies have made recommendations on the availability and regulation of genetic testing in New Zealand, these reports have concentrated on diagnostic tests offered through the public health system (and carried out by nationally-accredited laboratories). The UK has been wrestling with this issue for over a decade, and is several years ahead of us in developing legislation to regulate commercial testing.

    Although a 2002 report by the Human Genetics commission proposed prohibiting direct-to-consumer marketing, requiring tests to be nationally licensed, and available only after medical consultation, a House of Lords report released in July of this year favours a voluntary code of practice. Under this agreement, companies would provide information about laboratory standards, clinical validity and utility of the tests offered, and guidelines on appropriate pre- and post-test counselling. The change in approach probably reflects moves to develop international standards to evaluate all aspects of testing, and an expectation that consumer law (and market forces) will ‘punish’ corporations who fail to meet these benchmarks.

    In contrast, Article 12 of the 1997 Council of Europe Convention on Human Rights and Biomedicine specifically states that: “Tests which are predictive of genetic disease or which serve either to identify the subject as a carrier of a gene responsible for a disease or to detect a genetic predisposition or susceptibility to a disease [must be] subject to appropriate genetic counselling.”

    In 2008 an additional protocol was added to the Convention, Article (7) of which stipulates that any genetic test carried out for health purposes may only be performed under individualised medical supervision (Article 7). Despite this, a recently published study of companies advertising direct-to-consumer genetic testing also found that those offering ‘enhancement’ tests for multiple, low-risk variations were the least likely to require medical oversight, offer no counselling, and to provide misleading or irrelevant information about the genes being tested.

    In addition to the need for appropriate regulation and adequate counselling services to protect individuals and/or immediate family members, we need as a society to consider the wider implications of the information new genetic technologies can provide.

    How, for example, do we balance personal rights against collective benefit? Genetic information could remain private property, be made available to companies selling health services in a free market, or be used by scientists researching genetic disorders for the good of society. How much individual responsibility do we have for ensuring our own health?

    There is already debate about whether conditions impacted by ‘lifestyle choices’ such as smoking or weight related problems should be publicly funded. If I also have a genetic predisposition to heart disease, does this place an additional obligation on me to change my lifestyle? If I refuse to lose weight or stop smoking, should I then be liable for the resulting medical expenses because I did nothing to mitigate the contributing factors that were under my control?

    Alternatively, are people with ‘good’ genes who develop heart disease more responsible for their illness because it is the result of purely environmental and behavioural factors? What about the implications for crime and punishment? We know that if people with a particular form of the MAO gene are maltreated during childhood, they are more likely to develop antisocial behaviours than people with the alternative version of the gene. Should we conclude that these people are ‘born bad’ and that rehabilitation is pointless – or that they are less culpable for their crimes because they are not to blame for their genes (or their childhood)? Do we focus social support around such children to prevent them from being exposed to environmental factors that will send them off the rails, or work harder to ensure no children suffer abuse?

    Certainly there is a lot of useful and interesting information that can be gleaned from the types of tests offered by companies such 23andMe, and the potential for using individual genetic profiles to inform medical decision-making is an exciting development. Geneticists, ethicists and governmental advisory boards throughout Australasia, the USA and Europe all agree, however, that greater public understanding of the risks and benefits of genetic screening is crucial.

    Like any new technology, the consequences of its introduction need to be carefully considered from both an individual and a societal perspective. If Pandora had known what her box contained, both good bad, she might well still have opened it – but knowing all the trouble that would be released, would have probably have thought long and hard before doing so.


    [1] An analysis by US Preventative Services Task Force concluded that these tests were of little benefit for women who did not have an extensive family history of breast or ovarian cancer.

    [2] Initial caduceus image: U.S. Department of Energy Human Genome Program


    Dr. Cushla McKinney is a research scientist in the Biochemistry Department at Otago University, Dunedin.