Now, the narrative of “Let’s see what’s in your DNA” is virtually irresistible. If you say to someone, “Would you like to know what’s in your DNA, or what’s in your baby’s DNA, that might be useful in saving your life in the future,” who’s going to say no to that? But the reality is a little more complicated.
We’re really trying to figure out how best to interpret genetic information, determine what might be useful for a patient, and then return that information back to the patient so they can use it in their own care.
I’m Lisa Girard, director of scientific communications at the Broad Institute, and you’re listening to BioLogic, the logic behind the science: conversations with Broad researchers exploring what they do and why they do it.
In this episode, we’re exploring questions about best practices for returning genetic information to patients in a way that will optimally impact their health. In order to develop these protocols, researchers are modeling a time in which genome sequencing is accessible and widely used in healthcare.
What do patients really want to know about their genomes? How do people tend to act on such knowledge? What are the benefits and the risks? And what kind of privacy are you entitled to when it comes to your DNA? The answers have medical, economic, and societal consequences for the future.
Robert and Heidi are pursuing many of these questions. Heidi is an institute member at Broad, associate professor at Harvard Medical School, and director of the Laboratory for Molecular Medicine at Partners Healthcare Personalized Medicine. Robert is an associate member at the Broad Institute, professor at Brigham and Women’s Hospital and Harvard Medical School, and director of the Genomes to People Research Program.
But let’s take a step back for a moment, before we talk about the future. What do we already know about how genetic information influences patients?
There’s been a lot of fear for many years, even decades, that returning genetic information is going to somehow create devastating or catastrophic psychological reactions.
And it turns out that among people who elect to learn genetic results, who really want to know this information, there’s very little in the way of disastrous psychological consequence.
Now we don’t want to be cavalier about that — it certainly is possible for people to learn information that’s upsetting, learn information that has to be handled gingerly, learn information that applies to them or their family members or their children that can be distressing, but the kind of widespread fear of genetic information that characterized the field perhaps fifteen years ago has simply not turned out to be widespread. And so that’s, that’s a huge relief.
There’s been a great deal of concern that people would misuse information that they received from direct-to-consumer genetic testing. An example of misusing information might be that you have some sort of false reassurance, what I call “reaching for the jelly doughnut,” you know, you learn that your diabetes risk is fairly low on a genetic basis so you don’t mind gaining weight, and of course that would be the wrong way to approach risk of diabetes. So there was a lot of concern that people would now be falsely reassured by genetic information and would not take care of themselves. And that really hasn’t turned out to be the case, either, when we’ve actually collected data on these behaviors.
Both programs are rooted in the assumption that genome sequencing will, at some point in the future, be entered into everyone’s medical records as a routine part of healthcare. Clinicians need to develop the best protocols to do so in a safe and controlled manner — and the first step is to collect data on what works and what doesn’t, for both adults and children.
In MedSeq, adults receive information about genomic sequencing and are offered the option to enroll in the program. Heidi tells us more.
We really look at the outcomes of those patients, their experiences in receiving or not receiving genetic information, how that information is used in their care, do we diagnose disorders they were unaware of — all of those different things so we can really understand how to bring genetics into routine care.
And, in particular, we’re studying two different physician populations, both primary care physicians as well as cardiologists, neither of whom necessarily have deep training in genetics. And so part of this study is really, “Can we bring genetic and genomic information into the practice of medicine in places where there’s not sophisticated genetics training up front?”
BabySeq is a little different, and in some ways, a little trickier. Parents receive information about genome sequencing for their child, and make the decision to enroll or not while their infant is still in the hospital.
We’re asking who elects to receive this information, why do they elect to receive it, how do they understand it, what do they do with it, and what does it trigger in terms of medical next steps, medical outcomes — either in terms of finding a diagnosis, in terms of distracting from a diagnosis, in terms of providing secondary or unanticipated information that then must be pursued — and how do families and doctors adjust to all this. We’re really creating a sort of process-oriented exploration of how you use sequencing in very early childhood.
One of the differences between MedSeq and BabySeq is that in MedSeq we really sought to return anything in their genomes that we felt could be relevant or interesting to their health. In BabySeq we are much more strict about what we return to patients. We are largely focused on the return of information related to pediatric diseases, where they onset before adulthood, or disease risk where the babies may have some sort of intervention in childhood to prevent disease in adulthood. So there largely has to be some sort of what we call “actionability,” or way we might change the care of the patient during childhood, in order to justify returning that information at a stage in their life where they’re not able to make the decisions themselves and are, of course, relying on their parents to make decisions for them.
If information from genome sequencing is not interpreted or conveyed appropriately, the data can be used in ways that negatively impact the patient. Robert explained some of the health-information risks involved in genetic testing, and the potential problems that he and Heidi are trying to mitigate.
Remember, any kind of test, even a genetic test for a monogenic condition, is going to have true positives, meaning the variant is correctly detected and results eventually in the disease, and is going to have false positives — which, by this I mean, you could have a false variant. Or, more likely, you detect the correct variant but because of low penetrance, the individual never develops the disease.
For example, I think we generally agree at this moment in time that in families that have heritable conditions, such as breast and ovarian cancer from the BRCA mutations, that disclosing this information to people who want it, and to people who will consider taking precautionary surgical interventions, can save their lives.
The trouble is that we don’t know for so many other genetic conditions whether the kinds of interventions are feasible, whether people will do them, and whether they really will save lives.
If we are not careful, we throw out a whole lot of risk information, even for monogenic conditions, that results in downstream medical costs, downstream medical interventions — and it is actually possible that we could do more harm than good. And this is why it’s so critically important to run very rigorous, empirical clinical trials to better understand the clinical utility of providing unanticipated genetic information.
And these concerns aren’t limited to the doctor’s office. Genetic sequencing is a fraught topic on the political and societal stage, as well. Heidi and Robert broke down some of the other factors that today’s patients have to contend with, for both themselves and their children.
One of the challenges that we’ve identified in running the BabySeq study is the actual enrollment process. Really, only about six percent of families enroll in the study. And some of the families are rightly concerned that genetic information about risk for their newborns could go into the baby’s medical record and put them at risk for discrimination later in their lives.
They are concerned about privacy breaches, they’re concerned about stigma, they’re concerned about discrimination of various types, from employer discrimination to insurance discrimination, both health insurance and other types of insurance.
I think that parents are making that decision based on what they know now, in this year 2017, and some of them are extremely aware that anything could change between now and the time their newborn babies reach adulthood, at least 18 years from now. And so that is another reason why they are so hesitant.
This is a very confusing climate, I think, for individuals who are considering clinical genetic testing — much less research genetic testing — because the kind of protections that we have been all hoping will be in place, and will be reassuring, are really under attack right now.
There are some legal protections currently in place intended to protect against discrimination based on genetic information. But they’re not exhaustive, and the future of these protections may be in jeopardy. One of these foundational laws is called the Genetic Information Nondiscrimination Act, often called GINA, which was passed in 2008.
It protected very clearly against employer discrimination and health insurance discrimination on the basis of family history and genetic testing.
However, it does not prevent discrimination for life insurance or long-term disability insurance.
GINA was then buttressed by the Affordable Care Act in 2010, which, among other things, prevents discrimination due to pre-existing conditions. Heidi explained how these two pieces of legislation work together.
If you have identified a genetic risk for an individual for some disease, that may lead you to do much more sophisticated diagnostic tests to identify the earliest stages, and most subtle findings, that might relate to your actual risk. In doing those studies, prompted by a genetic result, you may diagnose the patient much, much earlier with this disease risk.
Now, the good thing about that is it allows you to intervene at the earliest stages of the disease, and that can often prevent, you know, more serious disease development later down the road.
However, the downside in terms of the health insurance situation is that the moment you actually diagnose a patient with disease, now they’re in a situation where they essentially have a pre-existing condition. So GINA no longer applies in that case, because we’re not talking about genetic risk — we’re talking about actual disease that’s been detected at a very early stage, prompted by the genetic information.
Once they have actual evidence of disease, if there is not a healthcare clause that prevents discrimination based on pre-existing conditions, then those individuals would be at risk for losing their health insurance, or not being able to get insurance, or being given a very high premium because of their pre-existing condition. And that is why maintenance of the Affordable Care Act is really critical in the context of genetic testing and the information that we identify and return to patients.
In spite of the hurdles, healthcare is slowly pivoting from population-based medicine to personalized medicine. Data from genetic testing can point out potential risk factors for disease, empower patients to take a more active role in their healthcare, and help refine diagnoses, all of which could lead to better health outcomes.
Heidi and Robert, and their colleagues, continue to advocate for protections against genetic discrimination, and to hammer out the best ways forward in an uncertain future. You can read more about their work, including the MedSeq and BabySeq projects, and find other episodes of BioLogic, at broadinstitute.org.
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For the Broad, I’m Lisa Girard. Thanks for listening!