The ready availability of genetic testing has created a contradictory set of challenges.
(Disclosure/reminder: Im Chief Medical Officer of DNAnexus, a genetic data management company.)
On the one hand, there are data suggesting that some patients dont modify their behavior even after genetic testing indicates they might be at increased risk for a condition, such as lung cancer or skin cancer, a risk that could be mitigated through deliberate behavior change. (I recommend this 2016 Atlantic piece on the subject, by law and policy professor Timothy Caulfield, for his wise emphasis on social context, though Im less persuaded by the published meta-analysis that motivated the commentary.)
But Ive been at least as struck by what seems in many ways to the be opposite problem: the use of specious genetic tests to motivate behavior change, such as the use of genetically informed diets or genetically informed exercise programs (or both), solutions an increasing number of consumer genetics companies seem to promote.
Although a robust scientific link between the genetic results and the indicated intervention is generally lacking, many individualswhether patients or elite athletesseem to find the idea that their recommendations are based on cutting-edge genetic science compelling. In a very real sense, this is genetics as placebo.
Credit: Twenty20
There are many examples demonstrating the impact of placebo on athletic performance, for example, in both trained (see here, here, here) and untrained (here) athletes. Its not a stretch to imagine that athletes who believe genetics can offer them a distinct advantage might perform better if they believe their training program is driven by genetics.
Its also entirely believable that patients with a particular faith in geneticsfor example, those who have self-selected by seeking out such testingmight be more likely to adhere to a wellness regimen represented as the customized output of genetic evaluation.
This phenomenon seems like an expression of what medical anthropologist (and one of my favorite undergraduate instructors) Arthur Kleinman called the Explanatory Model. The basic idea is that different people have different views of illness and disease, and the physician or healer needs to understand and acknowledge the patients model to optimize the therapeutic relationship.
Consider NIH director Francis Collins, for instance. After genetic testing suggested he was at increased risk for diabetes, he immediately altered his diet and exercise regimenpresumably because he strongly connected with the idea of genetic risk. Collins reaction isnt unique; Ive encountered a number of individuals whove apparently been motivated to change their lifestyle after getting curiosity-driven genetic testing.
The thing is, from a medical perspective, the logic is lacking, or at least soft; most people would presumably benefit from a healthier lifestyle, whether genetic testing reveals a particular predisposition or not. Collins, a physician-scientist, shouldnt have needed genetic testing to motivate lifestyle changes. Yet apparently, it took genetic testing because that deeply resonated with his explanatory model of illness.
As an aside, its important to recognize that patients are not the only ones who may find themselves beguiled by the charms of genetic data. A recent, powerful Stat article described a dubious genetic test used to help doctors select the optimal opioid for patients; the reporter, Charles Piller, memorably captures how the analysis was perceived by an enthusiastic physician:
Tests of how his patients would respond to particular drugs validate his clinical judgment most of the time, [the physician] said. When they dont, he ignores the results.
This seems like another version of genetics as placebomaking the doctor feel better about his diagnosisrather than genetics as discriminating science.
Ive also seen a similar phenomenon in biopharma companies that aspire to use biomarkers (not necessarily genetic) to guide decision-making during early drug development. Ive been surprised by how often biomarkers or other early signals are embraced when seem to support the decision the team wants to make (generally advancing a drug), but ignored or rationalized away when they go in the wrong direction. Of course context is always important in interpreting specific results, but its striking how early signals can be selectively employed in drug development decisions to inject the imprimatur of science into a confusing and often highly political process.
Returning our focus to patients, some might ask, whats so wrong about using genetic testing to motivate behavior change in those who are susceptiblewho in essence advertise their susceptibility by seeking out genetic testing? If the testing is legitimateas presumably Collins wasthen perhaps it will provide the motivation needed to pursue a healthy lifestyle. And even if the relationship between testing and therapeutic recommendation is scientifically dubious, it might still motivate the recipient to eat healthier, exercise more or perform at a higher level. It would be ironic, certainly, if the primary benefit of many genetic tests proves to be behavioral, but whats the harm, especially if its paid for by consumers?
The problem is that even if there are short-term successes, they may come at the unacceptable cost of eroding trust in the underlying science, a consequence that might ultimately undermine what genetics could one day deliver.
My fear is that validated genetics gets overwhelmed by hucksterism, and patients who might benefit from genetics will get turned off, and reject critically important advice. Just as unsupported belief in the science could lead to overly enthusiastic adoption today (such as using genetics to guide diet), its not hard to envision this ending badly, besmirching the reputation of genetics and leading to the concerning possibility that down the line, expectations of disappointment might dissuade potential users of genetic testing in the future.
But inevitably, Im more optimistic than concerned.
First, I hope is that even in a sea of unsupported wellness claims (eat this, not that; train this way, not that), it will still be possible to discern legitimate medical advice (take extreme measures to avoid the sun and see your dermatologist frequently if you carry particular mutations predisposing to melanoma, say) that could save someones life. Ideally, this rigorous vetting will come from the community itself, as it has in a number of other examples cardiologist and former FDA Chief Health Informatics Officer Taha Kass-Hout frequently cites.
Second, I hope that responsible, critical scientists continue to pursue links between genetics and behavior, including diet, exercise and human performance (the pioneering work of Stanford cardiologist Euan Ashley falls squarely into the last category, for examplealso discussed on this recent Tech Tonics podcast).
Thirdmuch as I argued in the New York Times when the human genome was first sequenced, nearly two decades agoI suspect the rigorous pursuit of genetics will perhaps paradoxically reveal the limits of reductionism, highlight that genetics is not everything and emphasize the need for more integrative approaches to vexing population health problems.
Or, as Dennis Ausiello, Joseph Martin and I put it in 2000, in the American Journal of Medicine,
As Goldstein and Brown recently noted, paraphrasing Magritte, a gene sequence is not a drug, and although the development of rational therapy for a disease may require an understanding of its molecular basis, the path from mechanistic understanding to clinical treatment is often difficult to define and hard to predict. Proteins often behave differently in test tubes than in cells, and cells behave differently in culture than as part of a vital organism. Finally, a patients experience of disease reflects more than simply an underlying biologic defect. It is, to quote Eric Cassell, a process inextricably bound up with the unfolding story of this particular patient. Thus, the critical question we are now struggling with as physicians and physician-scientists is how to avail ourselves of the advances in molecular biology without losing sight of our primary goalthe care and treatment of our patients.
Clearly, this struggle continues.
See original here:
Precision Credulity: How Specious Genetic Tests Might Motivate Real Behavior Change - American Enterprise Institute