Two opinion pieces appear in this week's Nature (here and here) on the problems facing the direct-to-consumer genetic testing industry. These are companies, such as 23andMe, deCodeMe, or DNA Direct, that sell estimates of the likelihood of a consumer having a genetic disease or trait. Obviously, what is on offer, and what people mainly want to know about, is what to be afraid they might get. Fear for sale is not too far off the mark for this industry.
The industry has been growing fast, as more and more genes 'for' traits and diseases are published, but legal and scientific questions about what these companies have to offer abound.
The burgeoning, but virtually unregulated, direct-to-consumer (DTC) genetic-testing industry faces some serious changes in the United States. In a series of hearings last month, the US Food and Drug Administration (FDA) hinted that it will impose new regulations on companies selling such tests. The agency has also sent letters to test makers, as well as to one maker of the gene chips on which many such tests rely, saying that the firms are not in compliance with its rules.
In addition, the Government Accountability Office (GAO) last month unveiled the findings of its year-long investigation into the scientific validity, safety and utility of the gene tests used by the industry. The report called some of the tests misleading, pointing out inconsistencies in the results they provided, as well as some companies' shady marketing practices.Not all companies have been found to have shady marketing practices, or to intentionally mislead, but many of the other issues pertain to all of these companies because they pertain to both the science and the product they sell. Indeed, it can be argued that the probabilistic nature of these tests means that they all mislead, even if unintentionally, especially as so few people have a good sense of what probability means.
Genetic-testing services are proliferating fast. In 1993, tests were available for about 100 diseases. By 2009, the number was almost 1,900. Some forms of testing are major advances in the diagnosis of certain conditions, such as Rett syndrome and types of brittle bone disease. The clinical utility of others — such as the high-throughput genotyping that is widely offered by companies that sell tests directly to consumers — is debatable.The problems with these companies are multiple, some having to do with the marketing of tests, and some with the quality of the testing and the test results themselves.
According to the FDA, these companies are performing medical tests and marketing medical devices without a license, and this needs to be corrected. There's no doubt that's how many people view these tests, and how they interpret the results. As such, the FDA believes it should regulate these companies as it regulates any company selling medical devices or medical tests. The FDA has recently brought this to the attention of many of these companies -- here is the letter sent to 23andMe on this subject in June, e.g..
But, many observers believe that the way the testing is done also needs to be regulated to standardize DNA sequencing results, for example, and otherwise assure that results are valid. So, that's also something that's under consideration. According to the Nature piece, less than 1% of DTC genetic testing is regulated in the UK, and the proportion is low in the US as well.
While regulatory and legal issues are real and must be thrashed out, a deeper and thornier issue has to do with the science -- the actual causal connections (if and where they exist) between DNA sequence differences and a particular disease or other trait, and the assumption that we have accurate knowledge of those connections, which is usually far from the case.
If you send your DNA to 3 of these companies, you'll get not only risk estimates for 3 different sets of diseases and traits, but estimates you're given for the same diseases can differ. Yet isn't there just one truth out there? The problem arises because the study results these companies are basing their estimates on can vary considerably, depending on who's included in the study, how the trait is defined and so forth, and which results the company chooses to use to calculate their own estimates will determine the estimated risks they send to you. Further, there are often in fact no correct answers when it comes to complex diseases -- your risk of type 2 diabetes, or heart disease or stroke is genetic and environmental, and your particular genetic component is unique to you, and exposure patterns are always changing, which all means it can't be necessarily be accurately predicted from a pool of other people's genes.
Different genes and different alleles contribute to risk in different populations, and in every individual. And, risk of complex diseases is due to the contribution of more genes than have yet been identified, or even that will ever be identified for you. Even if all the genes that contribute to risk of type 2 diabetes could be identified for your neighbor, or even your parents!, the list won't be the same for you.
And this is before we even begin to consider the environmental contribution to your risk of disease, and this can be very elusive. One example is risk of breast cancer in women with BRCA1 or 2 mutations -- mutations which confer some of the highest risk of cancer known. Risk is very different depending on whether a woman was born before 1940 or after, because of changes in exposure to environmental risk factors. And, we can't predict future environmental risk factors, so it's impossible to know what gene by environment risk will be going forward, which is what these companies in effect are doing. Yet recent history very, very clearly shows that secular trends in risk, which must be due to lifestyle exposure differences, frequently make huge differences in risk.
Most results of DTC genotype testing amount in some way to fear for sale. That may not be the companies' intent, but it's not unfair to describe them in this way, because it's increasingly unlikely, as more data accumulate, that anyone will be given a no-worry clean bill of genetic health. Everyone is at risk for something! Especially if the criteria for expressing risk are not particularly major or definitive.
And, as we've said, the risks they are selling are mainly pretty elusive. But when it comes to real and substantial risk, we've already got a system, called genetic counseling, for estimating risk for hundreds of known single gene disorders. These are genes for which risk and predictability are extremely high, and that are primarily pediatric disorders like Tay Sachs or cystic fibrosis, though Huntington's, which strikes in adulthood, is another example. Prediction of these disorders has long been done by genetic counselors, who are trained to predict risk (which, with these disorders, is fairly simple to do, as they generally follow Mendelian rules of inheritance) and to inform and counsel people about their risk. They work in closely integrated ways with clinics, physicians, and medical schools. Counselors are professionals who are tested, regulated, and must keep up their license with regular education. So, where risk is actually definable, we've got no need for DTC testing.
If genetics was still in the business of finding genes that follow Mendelian rules, they'd just be added to the list of traits that genetic counselors understand and counsel about. But, largely driven by the profit motive it must be said, the genes these days being identified 'for' complex diseases by and large have individually small effects, effect estimates vary considerably by study, and they are simply not now, or probably never will be useful for accurately predicting your risk of complex disease.
So, how the DTC genetic testing industry does its testing is one question, and the FDA is trying to decide how to regulate this. Whether the industry has anything of real value to sell you is another question entirely. That's the rub.