 Welcome, everybody, and thank you for turning out this evening. This is Conversations About Ethics, and I am Ruth Bergren, Director of the Center for Medical Humanities and Ethics here at the UT Health Science Center. This is actually the 11th event that we've had for Conversations About Ethics. It's a series that explores ethical dilemmas that occur throughout the human life cycle. And we usually have two presentations annually, and oftentimes we select a theme for both of the presentations in any given year. We are partnering with the Ecumenical Center for Religion and Health, and together our center and the Ecumenical Center receive generous support from Methodist Health Care Ministries. So would anyone who is actually representing Methodist or Ecumenical Center please stand and be recognized? If they're not here, we will nevertheless thank them for their efforts. Thank you. Thank you, Methodist and Ecumenical Center, without whom we would not be having this event. I especially want to mention the names of the Methodist Health Care Ministries CEO Kevin Moriarty, who's also a board member at the Center for Humanities and Ethics, and the Ecumenical Center's dynamic and successful Executive Director, Mary Beth Fisk. There are some special guests here that you might notice, and these are the promising young scientists of the Velcro Academy. So I want to say welcome to you. They are here at the UT Health Science Center learning to conduct biomedical research under the direction of doctors Irene Chapa and Sophie Pina. So don't be surprised if some of these Velcro scholars are responsible for some of the discoveries of tomorrow. OK, now to the very, very exciting housekeeping parts. First, Dr. Amy McGuire and the Planning Committee have no financial relationships that are conflicts of interest to disclose, either in the planning or implementation. Those of you who are seeking continuing education credit, please be sure to sign in and record your attendance, and you will then subsequently receive further instructions by email. Please watch that email. If you don't respond to it and fill it out, you will not wind up getting the credit that you deserve. Those seeking continuing nursing education will receive a link to an online evaluation tool within one week. And then for CEU credit, please fill out the survey provided at the sign in and return it to the CEU desk before you leave, and you'll get a certificate at that time. We have lots of volunteers at the tables in the back who can clarify any questions you might have about some of these details. But to all of you, we really do appreciate your feedback. And we, in fact, need your thoughtful evaluation of this evening's program to allow us to plan subsequent programs that will be for professional education continuing credit. You can either fill out the email evaluation form that will send you after the presentation or use the QR code that you will find on the back of the program and use your smartphone. Tonight's presentation is titled Before Birth and Throughout Life, Ethical Considerations in Genomic Sequencing, and will be presented by Dr. Amy McGuire. She is an attorney bioethicist. How about that, Belcher scholars? Did you know there was an attorney bioethicist? And she is from the Baylor College of Medicine. At this time, I'd like to ask our ethicist from the Center for Humanities and Ethics, Dr. Jason Morrow, to introduce our speaker. Thank you, Ruth, and thanks to all of you for being here tonight. Our topic is an especially relevant one. Powerful new knowledge about the human genome is ushering in an era of personalized medicine. Researchers are answering questions that seemed out of reach even just a decade ago. Their findings are becoming a common part of patient care. It's critical that we understand not only the science of these breakthroughs, but also the legal, the ethical, and the social implications. Many health care providers feel unprepared to handle the challenges that come with an era of genomic medicine. Researchers, too, are wrestling with how to advance genomic research while protecting participants in the face of unknown risks. In a moment, Dr. Amy McGuire will help us consider some of the ethical dilemmas posed by genomic medicine and research. But first, let me tell you just a little bit about her. Dr. McGuire is the Leon Jaworski Professor of Biomedical Ethics and the Director for the Center for Medical Ethics and Health Policy at Baylor College of Medicine. Her research interests include ethical and policy issues in genomics and human genetics with a particular focus on clinical integration of emerging technologies. Her research and writings have been published in prestigious journals, including the New England Journal of Medicine, Journal of the American Medical Association, and Science on multiple occasions. She is a member of the National Advisory Council for Human Genome Research at the NIH. Her current research is funded by the NIH's National Human Genome Research Institute and the Baylor College of Medicine Health Policy Institute. She received her Bachelors of Arts from the University of Pennsylvania and her Juris Doctorate from the University of Houston, receiving summa cum laude honors at both, and her PhD with distinction from the Institute for Medical Humanities at the University of Texas Medical Branch in Galveston. Now, this is where I met Amy in graduate school at UTMB. Her intellectual acumen and her passion for learning is matched only by her passion for teaching, her wit, and her charm. She is at once a persuasive advocate, an educational innovator, a world class researcher, and a devoted mother. She is someone you want on your team. And we're so glad she accepted our invitation to join us in this stimulating conversation, addressing one of the most challenging sets of ethical issues in our time. Help me welcome Dr. Amy McGuire. Wow, thank you, Jason. If I ever run for office, I know who to call. Thank you all very, very much for coming today. And I want to especially thank Ruth and Jason for inviting me. It's very nice to come out and see our neighbors in San Antonio. It's a song. Yeah, this song. OK, so I'm really excited to be here today to talk to you about some of the ethical considerations and genome sequencing throughout the entire lifespan. So let me just start. I have two computers here because we had a little bit of technological difficulty. So bear with me. But let me just start by asking you guys a question. How many of you have seen the movie Gattica? OK, a handful of you. So Gattica was a film, was filmed in 1997. And in this movie, Ethan Hawth plays a character who lives in a world where everybody is sequenced at birth. And their genome sequence predetermines who they can marry, what job they can have, and what their social status is within the society. So I'm going to play you for a second just a little clip from Gattica so you can get a sense of what this world is like. I was conceived in the Riviera, not the French Riviera, the Detroit variety. They used to say that a child conceived in love has a greater chance of happiness. They don't say that anymore. I'll never understand what possessed my mother to put her faith in God's hands rather than those of her local geneticist. 10 fingers, 10 toes, that's all that used to matter, not now. Now only seconds old, the exact time and cause of my death was already known. Neurological condition, 60% probability. Manic depression, 42% probability. Attention deficit disorder, 89% probability. Heart disorder, 99% probability. Early fatal potential. Life expectancy, 30.2 years. So in 1997, this was science fiction. But what I'm here to tell you today is that this very futuristic vision of reality is now upon us. So what is genome sequencing? Many people have referred to your genome as the book of life or the blueprint of your biological self. So your genome is made up of all the genes in your body. There are 3 billion base pairs or letters across your genome. And those letters code for proteins that basically are the instructions for your body, for the traits that you have, your hair color, your eye color, and all of your bodily functions. Sometimes across those letters, there's a change or a duplication or a deletion in those letters. It might be in a single letter. It might be in a group of letters. And many of those changes don't mean anything. They're essentially harmless. Some of them code for things that make us different from one another. And other of those changes can lead to problems like future disease or current disease. So the traditional way that we used to tell whether somebody had a mutation or a change in their genome that would contribute to disease is that we would basically do targeted testing of individual mutations that we were looking for. So if you had a disease like Huntington's disease or certain kinds of cancer and there was a genetic mutation that put your child at risk of having that disease or whatever, you could do a targeted test looking for that mutation and you, who have the disease and your child to see if they have the mutation. And that would tell you their risk of getting the disease in the future. So up in the right hand corner here is just sort of a very traditional pedigree of how we would do targeted genetic testing of single gene disorders. But now with through technology over the last decade, we've been able to actually look across your entire genome, all three billion base pairs, and see what changes occur across your genome. And then to interrogate those changes and filter through them to identify which of those have significance from a clinical perspective and which of them don't. And there's still a lot we don't know about which have clinical significance and which don't. But that's essentially how this works. This year over one million people are estimated to have their genome sequenced across the globe. That is fairly remarkable given the fact that the reference human genome was sequenced in 2003. It took 13 years and over three billion dollars to sequence the reference human genome. It was a massive international collaboration and effort. The technology has advanced so rapidly since 2003 that by 2007 we were able to sequence the first individual human genome. And that took about a cost about a million dollars and took about a month to sequence the first individual human genome. Now the cost has dropped so dramatically and the sequencing speed has increased so dramatically that we're able to sequence its estimated a million people just this year across the globe. That's pretty remarkable if you think about technological advance. Many people envision a world in the not so distant future when everyone will be sequenced potentially at birth similar to the movie Garga. So these are some quotes from, the first one is from the NIH director Francis Collins back in 2009. We said whether you like it or not, a complete sequencing of newborns is not far away. Alan Gutmacker who's the director of the National Institute for Child Health and Development is quoted as saying one can imagine the day that 99% of newborns will have their genome sequenced immediately at birth. And there are many ways in which people envision us using sharing and playing with our genomic information. So many people think we will be sharing genomic information on Facebook that that will be routine. We'll be social networking on the basis of our genomic information. And we'll be using it to find our perfect mate. So this is already an advertisement for discovering the magic of chemistry with genetic matchmaking. So you can send in your genetic sample, they can do an analyze it and try to match you with somebody who is compatible at the biological level and potentially that might make for a better partner. Already we're using genome sequencing, not only to diagnose disease and such, but also to try to avoid having pregnancies in children who have devastating genetic diseases. So we now can do non-invasive prenatal genomic screening. We've always for a very long time done prenatal genetic testing. That's been common. But now we can do non-invasive testing. So when a mother is early in her pregnancy, we can take her blood and because maternal blood has fetal cells in it, we can separate out the fetal cells, we can sequence the fetal cells and we can get the genome sequence of the fetus. And based on that genome sequence, we can tell whether the fetus is at risk of having very severe genetic anomalies. We can do pre-implantation genetic screening or genomic screening. This is when you need to have in vitro fertilization and you have an egg and a sperm outside of the body. You're going to fertilize them in a Petri dish. You can take one cell from the fertilized embryo and you can do genome sequencing until the entire genome of the embryo and you can then select which embryos to implant into a woman based on the genetic makeup of that embryo. And this is typically used to avoid very severe genetic anomalies, but you can imagine it being used for other types of genomic enhancement. Some people even talk about designer babies. And this is real, this is in the news now. So a very well-known commercial genetic testing company, 23andMe, this is a company where you can send them a saliva sample and they'll do a SNP array which is looking across many, many points across your genome, not doing a whole genome analysis, but looking at many points across your genome. And they'll tell you about different risk factors that you may have for different diseases or traits based on your genetic information. They have a software algorithm called the inheritance calculator. And this is kind of a fun little tool from a marketing perspective. And what they do with this is you can send in your saliva sample and your partner can send in their saliva sample and they'll match them up and they'll say, well, based on your DNA, you guys are at X% chance of having a child with blonde hair, blue eyes, freckles and a low risk of Alzheimer's disease and breast cancer based on the newest and greatest scientific evidence that we have around those diseases. So 23andMe recently, just this past year, got a patent on their inheritance calculator and one of the big things in the media was how they were gonna use this and market it. And one of the concerns was, and one of the potential, I guess, commercial bill aspects of this was, to sell it to fertility clinics. So if you need to go in and have a sperm donor or an egg donor to help you conceive a child, instead of flipping through the big book where you're looking through baby pictures and some medical history to figure out who your perfect biological mate might be, you could send in your DNA sample, they could analyze your DNA, they could also analyze the DNA of all of the donors and potentially match you with somebody who increases your risk of having a child with blonde hair, blue eyes, freckles and a low risk of Alzheimer's disease. So if you were given the opportunity, would you have your genome sequenced? Would you use genomic sequencing to help you have a child with a low risk of disease or to have a child with certain biological traits? If yes, why, and if not, why not? So these are really important questions to begin to consider. So clearly there are some examples where having genomic information could be very beneficial and maybe even lifesaving. So just by way of example, I wanna introduce you to the Beery twins. This is Noah and Alexis Beery. They were born in 1996. And at age two, they were both diagnosed with cerebral palsy. Their medical conditions continued to get worse. Alexis's was worse than Noah's, but they were both deteriorating pretty rapidly. And their mother was a very, very active parent, very active participant in her children's medical care. And so she was constantly reading up in the medical journals on new articles. And she came across an article that talked about a disease that's not cerebral palsy. It's called doporesponsive dystonia. And it mimics cerebral palsy, but it has a couple of distinguishing characteristics. And one of those characteristics is that for kids with doporesponsive dystonia, their symptoms tend to progress throughout the day. And she was noticing that that was true of her own children. And so she consulted with her children's pediatricians and they decided together to start the kids on a low dose of Aldopa, which created a dramatic improvement in the kid's health. So within a couple weeks, Alexis who could barely stand up without falling down for more than five minutes was now able to get in a car and put on her own seatbelt. And within a few months, the kids were able to start playing sports and music and participate in the daily activities of a young child. And they pretty much lived a very healthy, normal childhood until they were about 13 years of age. And then their disease started to regress again, their medical condition. And Alexis started having difficulty breathing, significant difficulty breathing. NOAA was also deteriorating and was struggling with tremors when they were 13. And they started again going back into the pattern of going to see doctors, getting all kinds of testing done, all kinds of workup done. There were no answers and it was very frustrating. Well in 2009, Alexis and NOAA's father got a job at Life Technologies, which is one of the biggest genome sequencing companies. And in 2010, he decided, do you know what, let me see if I can get my kid's genome sequenced and if it will give us any new information about their disease. So he had their genome sequenced. It was actually done at Baylor College of Medicine where I work. And the researchers at Baylor actually found a gene mutation that both of the twins had inherited from both of their parents. And this mutation, because of its function, led them to believe that not only did the twins have a problem with dopamine production, but they also had a problem with the production of serotonin. So in addition to keeping them on low doses of L-dopa, they added sort of a very basic supplement that helped with their serotonin production. And within three weeks, Alexis was off the nebulizer. Within a couple months, she was running track in high school. So these kids are now 18 years of age. They look perfectly normal and healthy. This is a picture of them. They go around talking about sort of their very painful diagnostic odyssey that they were pretty much on for their entire childhood. And how whole genome sequencing literally saved their lives. So this is a tremendous story, right? I mean, this is great. This is a great success story. Unfortunately, this is extremely rare these days. So the ability for genome sequencing, this is the goal. This is the vision. This is sort of what we all are hoping for is that we'll be able to sequence individuals. We'll be able to identify and diagnose very rare genetic conditions and we'll be able to know based on that diagnosis and the pathway that's involved in the mutation that we find that we can change their treatment and we can improve health. And that's what we're all hoping for. And there have been a handful of cases, usually very highly publicized, where that has actually been the case. There have been a much larger number of cases where it doesn't actually lead to improved treatment because we don't know what to do yet or we don't know enough about the disease, but it still helps families tremendously in ending a very painful diagnostic odyssey. So this is a picture of a six-year-old Bertrand Might. You might recognize him because there was a recent New Yorker article on him a couple of weeks ago with this picture. But shortly after Bertrand was born in 2009, his parents knew that something was wrong with him. And for the first several years of his life, he underwent numerous medical tests, including genetic tests, but nobody could figure out what was going on with him. So in 2010, his parents connected with scientists at Duke University and they decided to do whole exome sequencing on him. And whole exome sequencing is sequencing all of the coding genes in the genome. It's significantly cheaper than whole genome sequencing. And so they decided to do that on him. And what they found was that he had a very rare mutation in the NGLY1 gene. It had been seen only a couple of times and been reported only a couple of times. But this, they thought, contributed to and was the cause of his medical condition. So it turns out that this is an extremely rare genetic change, but it helped explain his medical condition. And knowing this information, his parents were able to use social media and social networking to connect with several other families across the globe who also helped children who had this very rare mutation and were going through the same painful, isolated diagnostic odyssey that the mites were going through. So although there's not yet any known treatment or cure for the disease that Bertrand is suffering from, in the New Yorker article that was published a couple weeks ago, his parents described what a tremendous comfort it was to them to first get some answer to what was wrong with their child, and then to connect with others who were going through the same thing that they were going through. This is the much more similar to the typical case that we see in the genetics lab where I am, and I think in most clinical genetics labs. So at Baylor, we have one of the largest clinical genomics labs where we do whole exome sequencing. We're processing a couple of hundred samples a month. Most of them are pediatric cases and most of them involve kids who have very rare undiagnosed genetic disorders. And what we're finding is that in about 26% of the cases we're actually able to identify a genetic mutation that's causative for the child's condition. So 26% of the cases, for some of you that might sound pretty low, like gosh, only 26% of the cases. But for others, and particularly for these families who have spent years getting medical tests and diagnostic workups, having an answer is a tremendous relief and a tremendous benefit. So genome sequencing can be used beneficially, not just to diagnose disorders that are undiagnosed, genetic disorders that are undiagnosed. It can also be used in some cases to predict future risk of disease. So many of you probably have heard of Angelina Jolie's recent brave decision to have a mastectomy, as this news article calls it. So Angelina Jolie's mother died of breast cancer in her 50s and she had the BRCA1 gene mutation. BRCA1 gene mutation has been shown to be associated with breast cancer and it significantly increases somebody's lifetime risk of getting breast cancer. And so Angelina was tested herself and she did carry the BRCA1 gene mutation. And so she decided that to lower her risk of getting breast cancer, she would have a prophylactic preventative double mastectomy. So if you discovered that you had the BRCA gene mutation, would you make the same decision as Angelina Jolie and have a double mastectomy prophylactically? Again, some of the questions that I think are worth considering. So while there are several examples like this, that where there are clear disease associations when you find a genetic mutation. As I mentioned earlier, the vast majority of genomic variation between individuals has much less direct relationship with disease or behavior. So despite what popular media suggests, there is no single gene that determines your IQ. Sorry. There also is no single gene that determines your religiosity. And as good of it as an excuse it may be, infidelity is still much more about what you take out of your genes than what's in your genes. So I would like to suggest that the biggest threat to the field of genomics is not technological. We've overcome that barrier. And it has nothing to do with bioinformatics, but despite the fact that there is a lot of discussion about this bioinformatics bottleneck that we're currently in. It is the seductive tendency that we have to simplify the complex relationship between our genes and our environment, and to reduce the mysterious nature of the human spirit to our genetic makeup. Your genome is the genetic blueprint of your biological self, but how much does it or will you let it determine who you are? And I think that is the critical question. Because when we have the tendency to reduce our biological makeup or our genetics, and we have the tendency to let it determine who we are as people, it has severe social consequences. We only have to look back less than 100 years to see how this plays out, right? So concerns about genomic determinism or reducing genetics down to who we are is deeply rooted in historical misuse of genetics to advance the social and political agenda of the eugenics movement. So when you guys think about eugenics, who do you think about? What comes to mind first? Adolf Hitler, Nazis, right? One thing that I was really fascinated to find out when I started looking into this is actually Adolf Hitler in the entire sort of philosophy behind the eugenics movement in Nazi Germany was very much informed by what was going on in the United States. So this is just one of many, many, many quotes that Adolf Hitler has, where he says, I have studied with great interest the laws of several American states concerning prevention of reproduction by people whose progeny would in all probability be of no value or be injurious to the racial stock. So in the early 1900s, we had a very strong legal and social culture of eugenics in the United States. These are several laws that were on the books until the mid 1900s in the United States that allowed for the forced sterilization of individuals that we as a society felt were unjust to reproduce, that were unfit to reproduce, I'm sorry. Usually these were people who were institutionalized, who were potentially mentally ill, who were criminals in the criminal justice system, and there were others. There's a very famous 1927 United States Supreme Court case, right? So this was a case that was brought all the way up to the United States Supreme Court. And the case involved a woman who was institutionalized. She had mental disabilities and her mother had been institutionalized for mental disabilities as had her grandmother. So she was the third generation of women who had been institutionalized. And the state of Virginia was trying to sterilize her against her will under the state law that allowed for that. And so a lawsuit was brought on her behalf challenging the constitutionality of the Virginia state law. And in a very famous case that went to the United States Supreme Court, our United States Supreme Court upheld Virginia state law and said that it was constitutional for the states to sterilize individuals against their will. And Supreme Court Justice Oliver Wendell Holmes was quoted as saying, it is better for all the world if instead of waiting to execute to generate offspring for crime or to let them starve for their imbecility, society can prevent those who are manifestly unfit from continuing their kind. And he goes on referring to the woman who had brought the lawsuit or the lawsuit had been brought on behalf of and says three generations of imbeciles are enough. Stocking, right? I mean, this is in the United States in 1927. Eugenics was also deeply embedded in our social culture in the United States. So these are really interesting photos that I think have been archived at Cold Spring Harbor Laboratories in New York from the 1920s and 1930s. And these are from the Kansas State Fair. And at the Kansas State Fair in the 1920s, they had exhibits such as the Eugenics and Health exhibit. They had the better baby contest where you could enter your baby and they would evaluate them based on how much they were of the pure Anglo-American race and you would get, you would win if your baby was deemed to be, I guess, pure. And they had the Fitter Family exhibit where individuals would enter their entire family and they would get evaluated based on those same criteria. So again, shocking. So let's fast forward 70 years past World War II. And here we are today. We've discovered the structure of DNA. We've sequenced the entire human genome. There's been tremendous technological advances and it has made it feasible and affordable to sequence a million individuals just this year. Now what do we do with that? So we're at that time now in history and what are we gonna do with that information and what are we gonna do with that ability? I was recently given the opportunity to have my genome sequenced. So you can tell from my job that this is something that I think a lot about. I have funding to research. So these issues were not new to me. But it wasn't until I was faced with the decision about whether or not I wanted to have my own genome sequenced that these issues really became real for me. So perhaps it's because I live in both worlds, right? I work very closely with scientists and I see the excitement around these technological advances. I see the possibilities of what we can do with genome sequencing. And at the same time, I'm always attuned to the potential dangers of doing things just because we can do them without carefully paying attention to the downstream implications of our actions. So perhaps because I straddle these both worlds when this decision was presented to me, this opportunity was presented to me, I was tremendously ambivalent. Now anybody who knows me knows that I don't like ambivalence. I am not one to live in a world of ambivalence. I tend to be a planner. I have very low tolerance for indecision. And so I'm not very good with ambivalence. But we all know that the world is not so black and white. So ironically, I had been thinking a lot about the issue of ambivalence and I had decided that I was going to spend a little bit more of my life trying to explore some of its various shades of gray when this decision was presented to me. And to me, this decision was a very murky, uncomfortable shade of gray. So the sequencing that I was being offered was part of a very small research project that was being done at Baylor by some of my colleagues. And I didn't have a huge window of time to decide whether I wanted to allow them to take my blood and do the sequencing. So what I decided at the time is that I was gonna let them take my blood and I was gonna let them use it for research purposes. But I told my colleagues that I needed a little bit more time to think about whether I actually wanted the results back from the sequencing. And they agreed to that. So honestly, I didn't really think much more about it while the sequencing was being done until about six months ago when I got a phone call from my colleague who was running the study. And he said, well, we finished the sequencing and we have your results. Do you wanna set up an appointment to come meet with me and go over them? And so then I started to think about it a little bit. And then I began sort of this process of what I thought would be a pretty straightforward decision analysis that would move me from my place of ambivalence to a place of informed choice. And that's what I do a lot of my work in is moving people from ambivalence to informed decision making and informed choice. But what I thought was gonna be a pretty straightforward decision analysis actually over the last six months has morphed into a much deeper journey of self-reflection. And at that root of that journey of self-reflection for me was really coming face to face with my own genomic vulnerability. So I have a family history of neurodegenerative disease. My grandfather who mostly, I mostly remember him as a smart, funny World War II veteran. He taught high school math and wrote textbooks and he would tell the same joke over and over again as if it was for the first time. And he was diagnosed in his 70s with Alzheimer's disease. I watched throughout my high school and college years as this disease hijacked first his brain and then eventually his personality. And I remember thinking to myself as a healthy, invincible 20-year-old, man I hope that never happens to me because it was really tough. My mother who's one of the strongest, most amazing women I know was diagnosed in her 50s with Parkinson's disease. We now know a lot more about Parkinson's disease partly in thanks to the advocacy of people like Michael J. Fox and Sergey Brin who's the founder of Google and Michael J. Fox of course has Parkinson's disease. Sergey Brin's mother has Parkinson's disease and he found out that he has a genetic mutation that puts him at increased risk of Parkinson's disease. And so they've both invested quite a lot of money and raised quite a lot of money to study not just the genetic contributions to Parkinson's disease but also environmental contributions to Parkinson's disease. And what we know right now in terms of the science is that for most cases of Parkinson's there are some exceptions. If you have genetic mutations and genes that have been shown to be associated with Parkinson's it puts you at increased risk of getting the disease. It doesn't mean you're gonna get the disease and if you don't have that mutation it doesn't mean you're not gonna get the disease. It just tells you that you're at increased risk. So when I first considered this I thought, well, knowledge is good. Why wouldn't I wanna know about my genetic risk of disease? Now of course I know when I study all of the ethical concerns, the social concerns about getting genomic information and about genetic testing. So everybody that I talk to when I talk to them about genetic testing they're concerned mostly about privacy. They're concerned about discrimination and that makes a lot of sense to me. I've done most of my research in the area of genomic privacy. I know that your genome is unique to you and that I know that you can identify somebody just based on their genomic information. So our privacy is compromised whenever we have genomic information out there and whenever we get it done it's out there. It goes in your medical record. It goes on, I personally believe it's very difficult to keep any information private these days. I also know that there is some risk of genetic discrimination. So in 2008 we passed a federal law called the Genetic Information Non-Discrimination Act. This was after years and years of lobbying by many groups that we needed a federal law to protect against genetic discrimination. And this law does protect against genetic discrimination in the area of health insurance and in the area of employment. Now we can talk about this law in great detail about what it actually does now that we have the Affordable Care Act and how it interacts with the American with Disabilities Act but there are some major areas that this law does not cover and that people still worry about and what you typically hear them talk about is concerns in long-term care disability and life insurance because those are not covered under GINA and they're not really covered under any law. So you can still discriminate against people based on genetic information in those domains. But ironically when I was thinking through my decision about whether or not to have my genome sequenced I wasn't that concerned about my privacy and I wasn't that concerned about genetic discrimination. I also wasn't so worried that I was gonna freak out if I got this information. So this is another thing we hear a lot of people talk about is the psychosocial or the psychological response of having this information. It's gonna overload us, we're gonna freak out, we're gonna find out that we're at risk for something like Alzheimer's disease and we're gonna get depressed and suicidal and anxious and we're not gonna be able to function. Well I know that that's a possibility but I also know that we're pretty resilient and we're pretty adaptable as human beings and there have been a few studies that have been done looking at people who have had genetic testing even at people who are at risk of things like Alzheimer's disease and these studies have shown that people don't actually really freak out. They don't get really depressed or really anxious at least over the long term. Now I'm sure there are exceptions to this and the research isn't perfect and we're continuing to do studies in many, many different populations about the psychological response but that was not my main concern when I was thinking through whether or not I wanted to get my genome sequenced. But I was concerned a little bit about my response to the genetic information in a much, much more subtle way and this reminded me of Jim Watson. So up here you see Jim Watson in the yellow suit. Jim Watson of course was the co-discoverer of the structure of DNA back in the 1953 I think and he's shaking hands and receiving a hard drive with his entire genome sequence on it from Jonathan Rothberg who is the head of 454 Life Sciences. Jim Watson was one of the first of two humans to have their genome sequence back in 2007. It was sequenced by 454 Life Sciences and analyzed at Baylor so I was involved in this project. So Jim Watson of course had 60 years ago showed that genetics is the basis of inheritance and so it was really only fitting that he would kind of be the first person to get his genome sequence and when he had his genome sequence what he told us is I want all my information and I wanna put it all on the internet except for my APOE gene status. So the APOE gene has been shown to be associated with risk of Alzheimer's disease and Dr. Watson's I think mother or grandmother had Alzheimer's disease and he did not want to know if he had the APOE gene risk for Alzheimer's disease. So I think what his major concern was with regard to getting this information was not that he was gonna freak out or get overly anxious or depressed but rather that he was gonna then mistake at his age of I think at the time he was in his late 70s that he would mistake every single senior moment he had for the early signs of dementia. Now Dr. Watson knows probably better than anybody else that having an increased risk for Alzheimer's disease based on your APOE gene status does not mean you're gonna get Alzheimer's disease but he also recognized the very slippery way that our human intellect attributes meaning to things and an effort to corroborate whatever story we have created about who we are and what will become of us. And this I would suggest is really the deep seated danger of genetic determinism. The sort of subtle ways in which we interpret the information and we make meaning of it about who we are and what's gonna become of us. So for example, if you get your child's sequence and they find out that they have a gene mutation that has been shown to be associated with fast muscle twitch and quick running, speed running. Is it gonna influence whether you invest your money in soccer lessons or piano lessons based on that outcome? That's what this company is trying to suggest that you should do. You can send us a live a sample of your child and they will test them and they'll tell you whether they were born to run or not. I would argue that's fairly dangerous. I think the ways in which genetic determinism seep into our interpretation of genetic information are again really subtle but definitely there. So this is a story and I think it's a good example. It's a reporter, a journalist who had done genetic analysis on herself and her daughter through 23andMe when 23andMe was still allowed to do that. Now they've been at least temporarily shut down by the FDA but this is her reporting on getting the results back from her daughter's sequence. She says later that week I get an email addressed to my daughter whom I had just tucked in for the night. Her 23andMe results are ready and I approached them with an even greater ravenousness than my own results. At first glance, everything looks great and there it is, screaming out at me from my computer screen. My daughter who is learning to read and tie her shoes has two copies of the APOE4 variant, the strongest genetic risk factor for Alzheimer's. According to her 23andMe results, she has a 55% chance of contracting the disease between the ages of 65 and 79. This is like a three or four year old. My husband who is out of town on business texts that he will call me at 8.30. Everything okay he adds, all good I write back except our daughter is going to get Alzheimer's. So this I'm sure had some journalistic sort of lenience to it but I think this is very much the way in which we tend to think. Not so unlike myself where I like to do the black and the white and not so much pay attention to the shades of gray because they're much harder. I'm gonna end by just saying that I think one of the biggest things we need to think about as we move into this era of genome sequencing and the affordability and feasibility of doing it at a very, very large scale is what meaning we make individually and collectively of the genomic information that we get back. Our genetic, our genome is the genetic blueprint of our biological self but it does not define who we are. Great questions. So there are a group of Mendelian genetic disorders that you might have a causative gene, right? So you know that if you have the gene you will get the disorder. It is, there are not many of those. For the vast, vast, vast majority of things it is so much more complex than your genetics and there is a whole field of epigenetics that is emerging that's looking at what is the relationship between one gene and five other genes, between your genes and your metabolites and your proteins, between your genes, metabolites, proteins and the environment and it is so, so, so complex that I would say no. I think 55% chance that she cited is actually among the highest that you'll see in these kinds of disorders. I'm sorry, I couldn't understand that. Say it again. Reductionist. So I couldn't agree more and if I didn't get across that that was my point, that is my point and maybe you articulated it better than me but the point is that it isn't deterministic and our tendency to try to make it deterministic is the problem. The science is not there and I would argue it's never gonna get there because it's not, that's not, genetics is just one small piece of a very, very large puzzle for most disorders. So the idea of thinking that having a genetic mutation will cause some of these common and complex disorders is misleading, it's wrong. I think people know that but I still think that there's a tendency to try to reduce it in our own minds and the subtle ways in which we respond to that socially I think can be very dangerous. Right, so and I would say that a large burden falls on not just the scientists but also the media and communicating the limitations of the science. Those sort of time magazine covers that I showed about the IQ gene and the religiosity gene and the infidelity gene, those are fairly old time magazine covers and I'm happy to say that more recent time magazine covers are starting to show things like why your genetics is not your destiny and talking about the complex field of epigenetics and things like that and we have had some of that in the media which I think is a great step forward in terms of improving understanding. Yeah, so the FDA it's a very complicated story but the FDA has been thinking about regulating in the space for several years now and they've been in communication and negotiation for those who didn't hear the question it was how did the FDA shut down 23andMe? They've been in communication and conversations with companies like 23andMe trying to figure out how they can best regulate at least the health claims that are being made by these companies based on their genetic analysis and to make a very long story short there were certain things that the FDA said that 23andMe needed to do that weren't done and so they issued them a cease and desist kind of letter. I don't think it's the end of the story I think 23andMe is still talking to them and negotiating with them and the FDA is also looking into how it's going to regulate in other areas of this not just commercial genetic testing but also research projects that involve this type of genetic testing and that sort of thing. Yeah, so good question. So the question was in countries where it's preferred to have male children will they start using pre-implantation genetic diagnosis to try to select for male embryos, yeah? So this has been a very hotly debated topic. There are some cases where you can use pre-implantation genetic diagnosis to do sex selection but some states in the United States have outlawed it and there's a very big sort of ethical debate about whether we should be going down that route or not and whether that should be allowed from a legal perspective or not but I certainly think it's one possibility and something that people worry about and think about. Where am I with my own decision? I haven't decided yet, honestly. I'm still living in ambivalence. I'm really glad that I kind of had the impetus to think about this carefully because I think about it at sort of this level on a daily basis in my work and it brought me to this level and it's been a really interesting journey but I still haven't decided. Does it really? So I mean it's a really good question. I'm not sure how much I've thought about it. Obviously my own personal example is with neurodegenerative disease which is very much related to personality and the brain and some of the intimate ways in which we think about ourselves. So I'm not sure if I've really thought about that. Clearly, you know, having heightened awareness about, you know, abnormal skin, things on your skin if you're at heightened risk for melanoma would be a good thing and maybe even being at heightened awareness for some of the things associated with these neurodegenerative diseases would be a good thing. So I'm not saying it's not necessarily a good thing. I think where we get in trouble is where we start treating people differently, thinking about people differently, treating ourselves differently based on an overinterpretation of what that means. So I guess what's been really challenging and interesting for me is that I know that if whatever my genetic results are, it doesn't mean I am or I'm not gonna get a disease, but I don't know if I know that. You know what I mean? There's a difference and I think that's hard and so I think sort of until I feel like I know that and I'm like solid in that, then I think it's for me individually, it's a really challenging thing to do. Yeah. Yes. So this is a really complicated question because at one level it goes, so let me just say Gina's a really interesting law, right? Because people, I mean there was strong advocacy for Gina. As in any law, it was somewhat of a compromise. I think there are some people on certain sides of the fence who would argue, well why are we protecting just genetic information? We should protect any health information and then other people on the other side of the fence saying why are we just protecting in these certain areas? We should protect in all areas. So one of the major problems is that Gina kind of puts a band-aid on the underlying problem which is that our insurance industries function, particularly life insurance disability and long-term care as a market economy. I mean they're making risk assessments all the time. When you go to get life insurance, if you've smoked a cigarette or a cigar in the last, you know, however long they're detecting it and it's gonna increase your premiums, I mean that's how they do business. So we would have to fundamentally change the business model of how we do business. Now one of the things that the Affordable Care Act is kind of does that a little bit for health insurance and that's why I said the Affordable Care Act in some ways sort of is much broader than what Gina was doing for health insurance. But you're absolutely right that in those areas of insurance and I don't mean to downplay what an issue that is because for a lot of people that is a huge issue. So we have some data that helps inform this. One is we just did a really interesting survey. It was kind of a quick and dirty survey, sort of national survey and most people, I think 70% of those who we surveyed had no idea what Gina was compared to 1% who had no idea what the Affordable Care Act was and like 30% who had no idea what HIPAA was. So it's not a very well-known law. So I'm not sure people really know that it protects them or what it protects or what it doesn't protect. When we actually told them about what Gina was about a third of them felt better. They felt a little bit more comfortable with their privacy and their protections and about a third of them felt much worse. Like, oh now I'm really worried about like those other stuff that it's not covering kind of thing. We also know that since Gina was passed there haven't been a significant increase in the documented cases of discrimination in health insurance or employment but also not in life insurance, disability or long-term care. So you can interpret that in different ways. It could be that, well, maybe there's sort of this symbolic importance of Gina which is that we're not gonna tolerate as a society discrimination on the basis of genetic information and so the other insurance companies aren't doing it. Another sort of read of it is it just doesn't make sense for them because what we were talking about before what we know about genetics is not that informative for them to make decisions about whether they're gonna cover somebody or not. So I think we still have to wait to see how it plays out in terms of what is the risk to any identified population whether they actually are being discriminated against or not. Gina was in very much a law to address public concerns about discrimination. It wasn't actually dealing with addressing a huge number of cases of discrimination that were being filed. There was some anecdotal evidence of discrimination but not actual cases that we had as evidence. So just from a practical perspective, I think we need to wait and see whether this is a real issue. From an ethical perspective, I think if we wanna sit back in our armchair it is an issue and it really comes back down to the underlying way in which our insurance industry operates. Do we think that people have a basic right to life insurance? We have a hard enough time agreeing that they have a basic right to certain types of health insurance. I'm not sure we're gonna get there on life insurance or disability but it's gonna require that sort of value assessment on a societal level, I think for us to really make significant changes. Sure. Yeah, so I think that's a much larger issue than genetic discrimination in those domains. I think irrespective of whether companies actually start making coverage decisions based on genetic information, that's an issue of how the industry itself runs and whether we should continue to let it self-regulate and make individual risk decisions or whether we should do a more sort of governmental regulatory approach and have risk sharing across the industry. I can tell, I haven't been terribly involved in the legislative process with regards to this, I've kind of been an outsider looking in, not gonna be an easy solution but I think certainly it's worth talking about and thinking about from a societal and ethical perspective. Yes. So this has again been a very, very, very hotly debated topic. All of the professional consensus guidelines over the years have said you should not test children for genetic conditions that are adult onset, right? So if there's something that is not gonna, there's nothing you can do about it in childhood, it's not gonna manifest if it manifests at all until adulthood, you shouldn't test them because you should wait until they turn 18, allow them to make their own autonomous decision about whether they want the result or not and whether they want the testing done or not and then allow them to get the testing. The debate has been that there have been several groups that have argued that when it comes to genomic sequencing that there are other considerations that need to be weighed against the future autonomy of the child. So for example, you might be doing genomic testing on a child for one reason and there's an incidental finding related to an adult onset condition that you weren't anticipating, right? And there's no way for the parents to know that they're at risk for that because they don't know that they should get tested but telling them that their child has it gives them information about themselves. So how much should you take into account the potential benefit to the parents or other relatives as it sort of weighs against the future autonomy of the child, people talk about this about giving the child the right to an open future, the right to make decisions on their own behalf. So there's intense debate right now about how those things weigh out. And I think part of it depends on the context in which you're doing the testing or getting the result. So it's one thing to make an informed decision about whether to order a test. It's another thing once you've ordered the test about what decision you make about returning particular types of results if you have that in your hands. I also have written a lot about and thought a lot about what position that puts the physician in who has the information with regard to their own professional integrity if they decide then not to communicate that information to the family. And does that put them in a sort of ethical bind that is really not appropriate? So, yeah. Well, and that's another huge complicating factor is that once the lab delivers the test to the physician it's in the medical record and then you can't really control access to it. So, yes, that's a big issue that has been ongoing. Yeah. You got it right, why? Oh, yeah. That's true. I don't know. Do we have time? I know we're over time. I'm one of our students. So do I think ambivalence around genetics? Say that one more time. I'm sorry. So I think, so the question was is the ambivalence around, socially ambivalence around genetics more attributed to lack of education or things like the FDA not doing more to regulate, is that? Okay. So I think education, public education and professional education is a huge issue that I think we're just starting to hit the tip of the iceberg in terms of really being able to address. I think still, you know, overall health literacy is really low. Genetic literacy is super low. It is really complicated. I know a lot about genetics and I still don't know a lot about genetics. I mean, it's a really complicated concept. But I think the education piece also goes back to what I was saying before about knowing it and really knowing it and what meaning we make out of it versus knowing sort of intellectually what it means, if you can make that distinction. The regulatory process, the FDA, there's several regulatory agencies dealing with this and it's really complicated. They're all trying to deal with it, but there is no easy solution. And, you know, we've been doing a lot of research in terms of regulation of this and I can tell you that it's not easy. There's a lot of things to take into consideration. It doesn't, genomics challenges in many, many ways, standard frameworks that we have for assessing validity, utility, things that we have typical evidentiary standards for that it just, it's hard to do. It's hard to do a prospective randomized control trial about the clinical utility of whole genome sequencing when you're getting tons of incidental findings that you don't know you're gonna find, find out about and it's predictive information about future risk of disease. They're really, really, it's really hard to do. So it's not an easy, easy, and so I would say both.