TRANSPERS collaborator Amy McGuire, JD, PhD, Leon Jaworski Professor of Biomedical Ethics and Director of the Center for Medical Ethics and Health Policy at the Baylor College of Medicine, provides a cautionary framework for genomic sequencing that takes into account its personal, social and policy consequences.
[bioscience imagery, music, woman vocalizing. Onscreen titles: TEDMED Talks, TEDMED]
If you could take a test today that told you your chances of getting cancer or of developing a disease like Alzheimer’s disease that you can’t do anything about, would you take that test? If you are a physician would you recommend that test for your patients? What if your child had their genome sequenced, and you discovered that they had a genetic predisposition to, say, sudden cardiac death? Would you let them play Little League baseball or high school basketball? These are no longer hypothetical questions, and the ability to routinely sequence humans is no longer science fiction. It is estimated that by the end of this year more than one million people will have had their genome sequenced. Many envision a world in the not-so-distant future where we will all be sequenced, potentially at birth; where we will all have access to predictive information that suggests diseases we might get and how we might die; where we will be sharing our genomic information on social media and using it to find our perfect mate. Genome sequencing has propelled biomedical research, and we now have many examples we’re having genomic information is beneficial, even life-saving. Thousands of patients are benefitting right now from genome sequencing. For many of them, we are able to understand the genetic cause of their disease and for some having that information has even led to more effective medical treatments. There are also examples of gene mutations that have been shown to meaningfully predict your future disease risk. So, for example, as Angelina Jolie discovered, having the BRCA gene mutation can significantly increase your risk of breast or ovarian cancer. And many people with that gene mutation may decide to do what Miss Jolie did and prophylactically have their breasts removed but one person’s transparency may be too much information for another. Many people assume that under all circumstances more information is better, but there may be times or places or people for whom it isn’t wise or compassionate or even appropriate for us to burden ourselves with every possible scrap of predictive information, especially if we treat our genome as if it were a guaranteed lockdown forecast. Now, you all know this already, but I think it’s worth stating the obvious. Our genome sequence is not an infallible prophecy of our future. The vast majority of diseases, traits, and behaviors are complex and multifactorial. They can’t be reduced to a single gene or even to genetics alone, and despite what popular media suggests, there is no single gene that determines your IQ or your religiosity. And as good of an excuse as it might be, infidelity is still more about what we take out of these jeans than what is in them. I believe that genetic determinism is the biggest threat to the responsible integration of genomics. Too often we are seduced by the tendency to simplify the very complex relationship between our genes and our environment and to reduce the mysterious nature of the human spirit to our genetic makeup. Our genome sequence is the genetic blueprint of our biological self, but how much does it—or will we let it—define who we are? I recently had the opportunity to have my own genome sequenced for free as part of a colleague’s research study. Much to my surprise I was tremendously ambivalent about whether or not I wanted to go through with it. Now, as part of my research I study people like me who are offered to have their genome sequenced. We have one study where we’re recruiting individuals who have a compelling medical reason to be sequenced, and in that study what we’re finding so far is that about 97% of the people who we have recruited to participate have agreed to participate. In another study where we’re recruiting individuals who don’t have as compelling a medical reason to be sequenced, only about 51% of those who we approach agree to participate, and of the 49% who have declined participation, there’s really two reasons why they decide they don’t want to have their genome sequenced. First they’re concerned that having access to predictive information might stress them out or make them anxious, and second, they worry about their genetic privacy and the potential for others to be able to access their genetic information and use it to discriminate against them. Now, I only had a small window of opportunity to decide if I was going to participate in my colleague’s research study. I personally am a huge proponent of research, and I also understand the social benefits of studying many different people’s genomes, so I let my colleagues take my blood and sequence my DNA and use it for their research, but with the understanding that I needed a lot more time to think about whether or not I actually wanted to know the results. And so began what I thought at the time would be a pretty straightforward decision analysis to move me from my position of ambivalence to an informed choice. But over the past couple months that decision analysis has really morphed into a much deeper journey of self-reflection, and at the root of that journey has been me coming face-to-face with my own genomic vulnerability. I have a family history of neurodegenerative disease. My grandfather who I fondly remember as a funny, smart, World War II veteran, he taught high school math, he wrote textbooks, and he used to tell the same jokes over and over again as if it was for the first time. He was diagnosed in his 70s with Alzheimer’s disease. Now, I remember spending my high school and college years watching as this devastating disease hijacked first his memory and eventually his entire personality, and I just remember thinking to myself as a young, invincible 20-year-old, man, I hope I never get like that. My mom who is still one of the most amazing women I know was diagnosed in her early 50s with Parkinson’s disease, and so one of the first things that I thought about when I thought about getting my genome sequenced was, okay, all of the sequencing is good for discovery, and it may benefit others, but what about me? Now, I may benefit from the information especially if it leads to early detection or better prevention, but how was I going to feel if I found out that I had a genetic risk of getting Parkinson’s disease or Alzheimer’s disease? What if they found something I didn’t even know that I was at increased risk for, like cancer or diabetes? How would that make me feel? How would it make my family feel? Would my mom feel guilty? Would my husband look at me and instead of seeing me see the potential burden that I might become for him in the future? There’s a lot of research going on right now to study how people actually do respond to genetic information, whether it stresses them out and makes them anxious or whether it has the opposite effect and actually empowers them and motivates them to do all the things that we all know we should be doing anyways but we don’t, like exercise more, eat healthier, get regular check-ups. Early studies confirm what we know from decades of human psychology research. First, it is really hard to get people to change their behaviors for the long term, and second, we are pretty terrible at forecasting how we’re going to respond psychologically to upsetting events or bad news. The good news is that we tend to be incredibly adaptable, and so we don’t usually get debilitatingly depressed or anxious even when faced with upsetting genetic information. But I wasn’t so worried about severe depression or anxiety. I was much more concerned about the very subtle ways that having access to genomic information might affect me and those around me. Now, I am acutely aware of the fact that in the vast majority of cases even if you have a gene mutation that shows that you’re at increased risk for Parkinson’s disease or Alzheimer’s disease, for example, it doesn’t necessarily mean that you’re going to get that disease. And conversely, even if you don’t have that gene mutation it doesn’t necessarily mean that you’re not gonna get the disease. But knowing this in your head and knowing this in your heart are two very different things. I also wondered whether other people might be able to access my information and use it to discriminate against me, but I trusted my colleagues to keep my information confidential, and I personally think that the risks to my privacy are very small. In fact I am much more concerned about the privacy of my credit card information, which I have voluntarily agreed to share on way too many websites, but still I couldn’t help but wonder would other people who I don’t even know be able to see my genetic information? And would they use it to make assumptions about who I am and what will become of me? Or would they resist this temptation towards genetic determinism and understand that for the vast majority of diseases, traits, and behaviors our genome sequence is not a crystal ball? Although they are available I still have not received the results of my genome sequence. Perhaps I never will. But if I have a compelling reason to I hope that I remember who I am and that I never let that information define for me the limits of what I can expect of myself and of this extraordinary life that I was given. And as the next million people get sequenced I hope that we as a community remember who we are, that we use the information to improve health and to better understand our individual and collective biological inheritance, that we use it to connect to one another rather than to create an even larger divide between us and them. I am optimistic because although I think it is easier to reduce this complicated, mysterious, beautiful thing that some people refer to as the human spirit to a string of letters, I believe that there is an entire generation waking up to the reality of who we really are and that we are all connected. We are so much more than our string of A’s, C’s, T’s, and G’s. We’re the stories that we tell about ourselves. We’re our emotions and our lived and shared experiences. Genome sequencing is a wonderful tool to help us better understand our genetic makeup but there is no genome for the human spirit. There is no us versus them. We are all expansive and connected at all levels, even at the genomic level. In a sense that is our social inheritance, and it is up to us right now to decide that it is that rather than the fallacy of genetic determinism that gets passed on to future generations. Thank you.
[Onscreen titles: TEDMED, TEDMED Talks]