 We welcome you to Conversations About Ethics. Today's workshop and keynote speaker represent the 12th installment of Conversations About Ethics in the series, which explores ethical dilemmas that influence both health care delivery throughout the life cycle. The conversation about ethics is presented twice a year by the Ecumenical Center and the Center for Medical Ethics and Humanities with the generous support of the Methodist Health Care Ministries. We'd like to ask if there's anyone here with the Methodist Health Care Ministries to please stand. We'd like to recognize and thank you for sponsoring this evening's event. A special recognition and thank you goes out to their CEO, Mr. Kevin Moriarty, who has made possible, along with his board of directors, the funding to bring this to you this evening. Is there anyone from the Methodist Health Care Ministries here with us this evening? They may be joining us a little later. Dr. Ruth Bergren, my colleague, is the director of the Center of Medical Ethics and Humanities and regrets that she's not able to be here this evening. And she's actually on a global health work in Haiti at this particular time. And so she sends her best as well. I'd also like to say hello to Principal Delia McLaren and her students from the Young Women's Leadership Academy. This all-girl college preparatory school focuses on science, math, and technology fields where women are often underrepresented. And we're so very pleased to have them with us here tonight. Do we have some folks from the academy here tonight? I believe we have two representatives and the others are stuck in traffic, but they'll be here momentarily. Before we get started, I have a few housekeeping details to go over. Dr. James Evans and the planning committee for this lecture have disclosed no relevant financial relationships with any commercial interests related to the planning or implementation of this activity. 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Tonight's presentation is entitled Genomic Medicine. What do you know about your genome? At this time, I'd like to recognize to the podium Dr. Jason Morrill who will introduce our speaker for this evening, Dr. James Evans. Dr. Morrill. Thank you, Mary Beth and to everybody who made the time to be here tonight. Tonight's topic represents some of the most challenging issues of 21st century medicine and technology. 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. Laboratory and computational discoveries are changing how medicine is practiced and understood. It's critical that we understand not only the science of these breakthroughs but also the legal, ethical and social implications in our culture. And it is critical that those who understand the technology communicate the purposes and implications of this technology to the public. Consider how patients and families are increasingly making decisions about health conditions not just months away but decades away. Who will be the messengers and interpreters of the information that people and families receive? Who will guide the families and their decisions? How will we train physicians and other clinicians to communicate information and guide decisions usefully, compassionately, and according to sound ethical standards? How will genetic information be protected? How will we balance the privacy rights of patients with the operative needs of insurance companies and employers? What role should the government play in regulating access to private information? And what other possible personal or informational risks lay ahead? To what extent is the pursuit of genomic mapping in medicine a shared social enterprise? Is genomic medicine a technological fancy, perhaps a privilege of those who can afford to participate? Or is genomic medicine the foundation of what will become a core practice and an essential right in our systems of health care? In a moment, Dr. James Evans will describe how genomic advances are affecting the practice of medicine and what they mean for your health and perhaps his insights will gesture towards answers to these difficult questions. First, let me tell you just a little bit about him. Dr. Evans is funny. I noticed that just a moment ago when meeting him. He is also the Bryson Distinguished Professor of Genetics and Medicine at the University of North Carolina School of Medicine. He evaluates and counsels patients with a variety of genetic conditions. He directs the Bryson Center for Human Genetics and seeks to integrate basic science investigation with clinical care. He is also the editor-in-chief of the prestigious journal Genetics in Medicine. His major research interest is how best to use powerful new DNA sequencing methods to diagnose genetic disorders ranging from cancer to heart conditions, developmental abnormalities, and neurologic diseases. Dr. Evans has extensive experience in the realm of policy regarding genetic issues. He has testified before Congress and presented to the United States Presidential Commission on Bioethics. He was also written up in the New York Times for his work teaching the nation's judges what they need to know about genetics. It is my privilege to welcome our most distinguished professor, Dr. James Evans. Thank you. I really appreciate it. It's a thrill to be here. I think that the work that this center does is very important because if we ignore the ethical implications of the science and the technology that are really changing our world, we're not going to be able to use those technologies and that knowledge to benefit. And in fact, it can cause harm. So what I want to ultimately talk to you about is how genomics is being used in medicine and some of the challenges that are being presented now and are on the horizon in the relatively near future. But I think it is probably instructive to back up and talk about a little bit of history first. And I think it's especially instructive to look at how technologies that have changed our world were first perceived when they were discovered. So this is the very first x-ray that was ever taken. That's William Rentkin's wife's hand. And you can see here her wedding ring. And it did not take incredible insight to recognize how this technology would be used in medicine. And in fact, the world literally beat a path to the door of the Rentkins. And within months, this technology was being used for obvious applications in medicine. But another technology that affects our lives every second since from our birth to our death did not have such a clear trajectory and that's electricity. Electricity was known by the ancient, the Greeks described it, for example. But as late as the late 18th century, Benjamin Franklin, who was very well known as a scientist before he was known as a statesman, made the comment that electricity is a fascinating phenomenon, but it will never be of any practical use, which is quite a remarkable statement given that it influences us every second. So I think genomics is more along the lines of the x-ray than it is electricity, but I'm sure there are surprises in store for what it can do for us. Certainly there will be ethical challenges in store for us. Also with new technologies, we have those who misuse it intentionally through either greed or perhaps not intentionally just through ignorance and seek to capitalize on the general ignorance about science and technology that exists in our society, something that has gotten even greater as we have advanced in our ability to understand the world in a scientific view. So understanding genetics has actually been something that has been a relatively recent phenomenon. It wasn't too long ago, really at the turn of the last century, that the only way to grapple with the phenomenon of heredity was through philosophy or poetry, for example. Thomas Hardy, one of the great English poets, wrote a poem that really encapsulates the mystery of heredity, and he wrote this before Mendel's Laws were rediscovered right around 1900. I haven't been able to find the actual date, but it's a beautiful poem. It says, I am the family face, flesh perishes I live on, projecting trait and trace through time to time's anon and leaping from place to place over oblivion. The year's aired feature that can in curve and voice and eye despise the human span of endurance, that is I, the eternal thing in man that heeds no call to die. It's a beautiful distillation of the mystery of genetics, right? The fact that something transcends generation to generation and retains its fundamental information and properties, but at that time, no one had the faintest idea. Well, there was one person who had the faintest idea, and that was Gregor Mendel, but nobody paid attention to him. So flash forward 50 years, and on a Saturday afternoon in February, February 28th, 1953, these two guys, Watson and Crick, walked into the Eagle Pub in Cambridge, England, and announced, we've discovered the secret of life. And for once, a boast made in a pub was actually true. They had, right? And they had done it using data that Rosalind Franklin had generated, unbeknownst to her, to the time of her death, probably from a genetic condition that caused her to have an incredible predisposition to breast and ovarian cancer. But how did we get from Thomas Hardy to Watson and Crick, right? Well, we got there to the application of science. And my, oh, there it is. And I think it's really important before we explore the current landscape of genomics to just think for a minute and explore science itself, because we live in a society where science and technology dominate every facet of our life. And yet, we also live in that same society in which most individuals don't really know what science is. And even more to our detriment, our decision makers rarely have a good grasp of science. And this is a big problem, right? And I think that we need to all work to try to ameliorate that deficit. Science is an intellectual toolkit. That's all it is. It's a process that we've developed for better understanding the world and in hopes of controlling the world. It is based on these basic tenets. You all learned in elementary school of observation, hypothesis, generation of the hypothesis, measurement, prediction, experiment. And then critically, it's an iterative process, a reapplication of those types of approaches in order to come closer and closer to an underlying truth. And it has a long history. Roger Bacon, for example, this gentleman named Edward Grossateste, was one of the first people to advocate what is probably the most critical aspect of the scientific method, which is experiment. But it hasn't been very long. It's only been a few hundred years that experiment has been recognized as an important facet. Science is an intensely practical endeavor. It really demands nothing more than predictable results. It's not a belief system. And it's achieved a remarkable measure of control over the world. We're in a room that is climate controlled with the flick of a switch we can cause lights to come on. And the fruits of science are technology, but they're not the same thing. Technology and science have an interesting and a synergistic relationship, but they're very much not the same thing. Science is the process that often leads to better technology, which in turn propels our understanding and advances in science. And really importantly, of course, it's necessarily tentative. We can never ever be absolutely certain in science. We are always open to revision if it's justified by data. And the trajectory, therefore, isn't smooth because we do a lot of iterations in our attempts to understand the world. And that means that the history of our efforts are stuttering, they're full of blind alleys and U-turns, but in the end, they've been shown to be remarkably successful. Mendel was not absolutely right. And we have come up with exceptions to Mendel's laws. Likewise, Newton described the world to a very close approximation, but Einstein was able to describe it better. In the end, though, we have made a lot of progress and we've achieved tremendous success in controlling our world. And this has philosophical implications in addition to technical implications. The very fact that science is so successful says something about it. It says that it is a way of glimpsing and underlying reality. There's an old saying, I'm not sure how old it is actually, that there are no pure social constructionists at 30,000 feet. In other words, the fact that most of you are willing to get on an airplane is a very strong testament to the fact that you trust science to glimpse the underlying reality of the universe and act on it. You would probably not trust an airplane that was built on principles other than scientific principles. There's an important corollary to this and that is that common sense is not necessarily a good guide to underlying reality. And I remind myself of this every time I look at a sunrise or sunset. It's very difficult to look at a sunrise and really internalize the reality that the sun isn't moving, that we are actually spinning at 1,000 miles an hour on a tangential route and that's just appearing to make the sunrise. So science can also be seen as a way to short circuit being misguided by our inappropriate and our incorrect intuitions. So flash forward another 50 years from 1953 to 2003 and by that time the human genome had been sequenced. And our ability to grapple with the human genome is limited by one major thing and that is it's really, really big. And I know that doesn't come as a surprise to any of you but it bears thinking about just for a minute to try to get your head around just how big the human genome is. This is about one millionth of the human genome. And if I showed a slide like that every second we would still be here in 12 and a half days taking absolutely no breaks and I would have only gotten through the haploid component of your genome. That is the part that your mom or your dad gave to you. Now the genome is filled with fragments of genes and throughout that genome are polymorphisms where you differ about every thousand bases, every thousand rungs on the DNA ladder. I've been told that it's humorous to own one DNA tie that's kind of pathetic to own as many as I do but I wore this one in celebration of being here tonight. So about one out of every thousand rungs on your DNA ladder differs from the person sitting next to you and many of those are frankly meaningless. They don't affect your health, they don't affect traits, they don't affect anything. Some of those however do influence traits like what color eyes you have, they're few things as genetic as what color eyes you have. Some of them influence medically important characteristics and occasionally there are mutations, there are serious changes in your DNA code that results in a dramatic influence on your health. So the question is we've got this ability now to dissect and define your genome, what do we do with that? What's the potential for benefit there? Any time a new technology is rolled out you hear the criticism sometimes very justifiably that if you've got a hammer everything looks like a nail and sure enough we've been using this technology to just bash the heck out of every genome we can find and there's a role for that because we find out a lot when we do that but as a physician what I wanna know is how can this technology be used for bettering people's lives and I'm especially interested in how that can be used in sick people and how that can be used in healthy people. So what are the right nails for the use of this very powerful instrument? Well in sick people it's pretty clear that it is going to be an effective diagnostic tool for those conditions that have a major very prominent genetic etiology. So take this woman who's 47 years old and she has a sudden cardiac arrest she's fortunately resuscitated successfully but in EKG what's noted is that she has a syndrome called long QT syndrome in which individuals have a very high risk of sudden death it's a very grim disorder. It's treatable if you know about it you can really make huge inroads in decreasing an individual's susceptibility to sudden death if you know about it there are pharmacologic approaches that are very successful you can use implantable defibrillators et cetera. The problem is up until a few years ago we couldn't know what mutation was responsible for somebody's long QT syndrome in the majority of cases because there are many genes that are implicated and which gene is implicated as a cause for an individual's long QT syndrome has a lot to do with the successful treatment of it but now with massively parallel sequencing we're able to detect mutations and by so doing we can guide a patient's treatment and just as importantly to most of these people we can guide evaluation of family members to figure out who's at risk and who isn't who needs to go on these agents who might need an implantable defibrillator and who can rest easy that they are not at a high risk for sudden death. Now sometimes you hit a home run when you apply this technology and you not only make a diagnosis that matters in treatment but you make a diagnosis that really changes somebody's life and for the rest of my life whenever I give a presentation I'm gonna show this slide, all right cause this is one of the best cases I've ever had as a researcher and a physician and I don't wanna imply that this is the norm for the application of genome sequencing but it is the potential at times to achieve results like this. So we had a 36 year old woman who was diagnosed when she was six years old with hereditary spastic paraplegia. Within a year or two she had such spasms of her legs and basically loss of control of her legs that she couldn't walk and needed two crutches or if she was going very far a wheelchair. And that's her when she came to her first appointment. She also in addition to this disability had painful episodes of spastic contractions of her legs multiple times a day they were very painful and very disruptive to her life. We entered her in the study that we're doing in which we use whole exome sequencing which is a kind of a little brother of whole genome sequencing in which you sequence all of an individual's expressed regions or their genes. And what we found was a mutation in the GTP cyclohydrolase one gene which had been previously described to be associated with a condition called DOPA responsive dystonia and of course what caught our eye was this DOPA responsive aspect of the name of that disease. DOPA is a very routinely given drug it's you all know people on DOPA because it's the first line of treatment for Parkinson's disease millions of people are on it. It's a very safe drug so we called up her neurologist and we said why don't you try DOPA and she was very excited to do so and she walked back in six weeks and had left her crutches at home. I felt like a faith healer it was unbelievable. And maybe the best part or probably the second best part about this was it also vindicated my career and my daughter's eyes because Cosmo picked this up right and there's the story about bad girl sex and am I normal down there and it picked this up as a mystery diagnosis and as I said my daughter was fine finally understood why I went into medicine. So this technology will be useful in those people who have difficult to diagnose diseases that are primarily genetic in their etiology but if you really wanna make an impact on health you need to start with healthy people because it's a whole lot better to prevent disease than to cure it even when you can do that later on. The problem is that there are challenges to applying technologies and knowledge to healthy people. This is the world's happiest colonoscopy patient that's Katie Couric and she's got a lot of reasons for promoting colon cancer screening because her husband Jay Monahan died at the age of 42 because he had a dramatic predisposition to colorectal cancer. He had a Lynch syndrome. The problem is though that we have to think hard before we start inflicting our technologies on healthy people in part because they have less to gain than sick people. When a sick person comes to me in clinic there's an understanding that I may not be able to help them that most people understand that medicine can hurt them as well but when you start out healthy you kinda only have a downward course as your only option. In addition, when you try to implement public health measures you have a different relationship between the provider and the recipient. Patients come to us but healthy people don't come to us. We go to healthy people and say you should have colonoscopies, you should have pap smears, you should have mammograms. So we have to be careful about that. The individual isn't seeking us out. In addition, the benefits are less obvious. Great news, you didn't get sick. That's not very dramatic to tell somebody and the downsides are easy to see and every intervention we have ever come up with in medicine has potential downsides. In addition, the applications are implemented and mass. We do them in everybody and the problem with that is that everybody has to say including people who have an agenda and including people who are simply wrong. Does anybody know who this is? This is Jenny McCarthy who's done a lot of damage in her advocacy against vaccines. I can think of actually no greater single advance in the history of medicine than vaccines and discouraging people from vaccination I think is a big problem. So because of all of these things, policy issues are orders of magnitude more difficult when you start with a healthy population. And I think the lesson is that the ratio of benefit to harm has to be very high before you start implementing such things. But I think there are opportunities for the general public, the general population to benefit from these technologies. And the one that I'm most interested in, this is me as an infant with one of my DNA ties. I think of in terms of newborn screening for adults. Newborn screening has been a singular success in the realm of genetics as a public health intervention. The diseases that are screened for are not common but they are so bad and they are so preventable, right? If you pick the right ones to screen for that it still makes sense to test everybody. Well it so happens that roughly 1% of us in the general US population harbors a mutation that leads to a very high risk of a preventable disease and a good example of that is Lynch syndrome. Lynch syndrome results from mutations in one of four genes and if one has such a mutation one is at a very high risk for colorectal cancer. And the way we diagnose it now is just a little too late. We wait for people to tell us that a bunch of members of their families had colon cancer and maybe died or we let them get colon cancer and look at their tumor and say hey this might be Lynch syndrome. Not a great way to diagnose this, right? Well massively parallel sequencing now offers a technology by which we could screen carefully selected genes that when mutated cause a high predisposition to a preventable disorder and inform people before they get sick so they can take preventive action. It's not all about cancer, BRCA 1 and 2 are examples of this but also there are genes that when mutated cause a very high risk of vascular catastrophe et cetera things that if you know about them you can intervene. And as I said about 1% of us carry such mutations and we can find those now with massively parallel sequencing and indeed we have an effort at UNC in which we're piloting this type of approach. But when we start thinking about especially taking healthy people and looking at their genome it kind of pays to ask what's in your genome that you wanna know or don't wanna know. So let me ask you a question and get a show of hands. Here is a short list of a few really bad genetic diseases. I mean the very existence of these diseases presents profound challenges to philosophers and theologians and ethicists but I won't go there. But there are forms of Alzheimer's disease that strike at very young ages that if you have a mutation in one of a handful of genes will essentially guarantee you're gonna get Alzheimer's disease. Same with a disease that's grimly but accurately named fatal familial insomnia. If you carry a mutation so just think about yourself for a minute in your life that essentially guarantees that you will develop a severe and untreatable neurological disorder in the next 10 years, do you wanna know? So who here would say yes, I wanna know. Okay, we've got a roughly half I'd say maybe a third. Who here feels like no, I don't wanna know. So not quite as many but a substantial number. Who here doesn't know? So I think that the doesn't know is probably the quote right answer in the sense that we know from Huntington's disease where I actually have data that although many people espouse an interest in this when push comes to shove, fewer than one out of five people actually elect to know which I think says something about how powerful and how useful denial is in our lives. And I'm not saying that in a pejorative way. I think denial is very useful if we really got up every morning and internalized the fact that we're gonna die and all our friends and loved ones are gonna die, we might not get out of bed, right? But the point is that your genome has value heterogeneity. That is you see the same information perhaps in very different terms from somebody else and we have to navigate that. That's a challenge to our new ability to define and dissect one's genome. There are a lot of other challenges that we have to come to. One that frustrates me is exaggerated expectations and claims. You hear oftentimes that soon everyone will have their genome sequenced and I don't really buy that. It's typically predicated on low cost, right? It's gonna be really cheap. The problem with that is, it reminds me of a really well-known personal finance aphorism that an elephant for a nickel is only a bargain if you have a nickel and you need an elephant, right? And I don't think whole genome sequencing is really an elephant that most of us need even if it's virtually free. Moreover, low cost upfront is an illusion in medicine, all right? Misapplication of medical tests is very, very expensive. And not only in terms of cost, but in terms of morbidity and mortality to individuals. And the most recent example of that probably is the premature implementation of massive PSA screening. Probably not a great idea upon collecting the requisite data. This costs a lot in terms of dollars as well. And I would add that patients and healthcare systems aren't well-served when we seek information that we really don't understand and we're not sure how to use. I think we have to be careful about what information we seek in medicine. It's not only needless, but it begs for misinterpretation and overinterpretation. Medicine has a lot of hubris associated with it and it's very, very tempting when you have a result in hand to think you know what's going on. And what I would plead for is the need to establish evidence that we really do know what's going on before we implement such things outside of a research setting. And we have to be guided by evidence. And when we ignore the need for evidence, it's a real problem in medicine because the stakes are very high. A great example of this is hormone replacement therapy. There was a time not too long ago when every post-menopausal woman, it was recommended that she go on hormone replacement therapy. And it's not that that can't be useful. There's a role for HRT, but it's clearly not something that we should be doing in a reflexive manner to everyone because we cause excess mortality. We cause heart attacks, we cause breast cancer, et cetera. Again, I'm not saying it can't have a role. It can, but it should be an individual decision. And the most grim reminder of this to me is something that we did when I was an intern on a routine basis. When a patient came in with a heart attack, we would put all of those patients on a lidocaine drip, the same stuff you get at the dentist to deaden you up. And the reasoning was really seemed almost unassailable. This is a PVC, a premature ventricular contraction. We know that people who have just had a heart attack have a lot of these. And we know that we can suppress these by giving lidocaine. And we know if you have a lot of these, you're at an increased risk for death from a dysrhythmia. So why the heck wouldn't you give lidocaine? So we gave lidocaine to everybody. And then when the studies were done, it was found that we were actually increasing mortality. So what I wanna get at with that anecdote is that all of the reasoning in the world is not good enough to implement things when the stakes are as high as they are in medicine. We have to see evidence of benefit. And there are a slew of other examples like this. The medical literature is littered with the bodies of hypotheses that seemed great, but were implemented before proper evidence was accrued. So what we've now seen, of course, with the rise of this technology is, we've seen the rise of a variety of claims of commercial offerings for DTC that is direct to consumer genomics. So I wanna just explore for a minute what kinds of information you can get from such things. For example, your ancestry, common disease risks and reproductive guidance. It reminds me a little bit of the quote by Andy Warhol that buying is more American than thinking, right? And I think there's some truth to that. Now, ancestry is a fairly harmless pursuit, right? So I have no problems at all with companies selling kits to look at your ancestry. I would tell you that it's probably not gonna give a lot of you surprises. But we're narcissistic, right? We really like looking at ourselves. And I spent $95 several years ago to find out my ancestry. So I got my mitochondrial haplotype and my y-chromosome haplotype. And it turns out that my ancestors are from Europe. I mean, who'd have thought that, right? I got that result. I was not $95, I never looked at it again. It was pretty obvious. I could have just used a mirror. So I would just, you know, it's interesting. I'm not trying to dissuade anybody from getting that, but you also might wanna think about whether you probably know the answer already. Common disease risk assessment I think is more problematic. That has been a hope of genomics for years now that we would be able to impact common diseases through analysis of one's risk. And the problem is that common diseases have many causes and genetics is only one, right? We've got exercise and hypertension and smoking for heart disease and diet. So this place is an inherent limit on how useful any genetic analysis is ultimately gonna be for telling you something useful about your risk of heart disease. And what I think is even more profound is the conflation of absolute risk and relative risk. I know what you're gonna die of, okay? You're gonna die like I am of cancer or heart disease. Now, a few of you will get lucky and like get shot or something. But to a first approximation, we're gonna die of common diseases, right? So the question is what does it really mean to parse our relative risk? If I tell you you're at a 0.8 relative risk because of your genetics for heart disease, you still may very well die of heart disease. In fact, it happens every day. So what I would caution you about is that it's hard to get useful information out of adjusting risks for things that you're no matter what gonna be at high risk for. And we're all gonna benefit from the same interventions like these really difficult things to do, like eating right and exercising, et cetera. Another challenge of implementing this technology in my mind is the role of the market. Now don't get me wrong, I think that the market can be a very useful thing. I mean, we would not have these great smartphones which I love, I'm like sutured to this thing, all right? And we wouldn't have that without the market. But in medicine, I think it's problematic to rely on the market to propel the uptake of a complex medical test. It's often marketed with unrealistic claims or as entertainment. My friend Peter Byers coined the term Narcissism, right? Which I think is pretty good. And the fact is that genetic analysis is a complex medical test. It does the power to hurt, to help, and to confuse. I don't think aggressive marketing is the way we want technologies to gain a foothold in medical care. I think that harnessing the market for the developments and innovation with regard to technologies is great. But as far as implementation, I think there are major problems with that. And I would also remind you that we all have a shared stake in using medical tests correctly. The libertarian argument does not hold much water in the realm of healthcare because even Bill Gates, I guarantee you, has health insurance, okay? We all are in a shared environment. So when you use a medical test improperly or I use a medical test improperly, it impinges on all of our pocket books. Now you can't talk about genetics very long, especially the ethics associated with it, without thinking about reproduction. Because really, reproduction is all about genetics, right? And this caught my eye. It was in the New York Times a number of years ago. And it was about an ad that had been placed in Ivy League alumni newsletters. They didn't take out an ad in my alumni newsletter, the University of Kansas, go figure. But what they wanted was this couple offered, they said, we want an egg donor. We want her to have SAT scores of over 1400. We want her to be five, 10 or taller. And we want her to be athletic. And we will give $50,000 to the winner, right? To the egg donor that we pick. And I think most of us feel a little uncomfortable about this and it's sometimes a little bit hard to figure out why we feel uncomfortable. I think part of it is the illusion that we really have that much control over our progeny. I think any of you who are parents know that in the end we probably don't. But I think it also is instructed to reformulate this ad. Because how do you feel about it if instead of saying this, it just said, let me go back. If it said, we want these traits, but we'll just reimburse expenses. We won't give 50,000. That might be a little more palatable. But what you don't see is you don't see this. And I'm not sure the world needs a lot more tall jocks that are good at standardized tests. But I can tell you if I can bequeath, I say that as a short non-jock. But if I could bequeath one thing to my children, it wouldn't be those things. It would be probably a positive attitude towards life. Now, I know that's harder to quantify, et cetera, but you can actually, you can quantitate those things. And if I were trying to select a sperm donor or an egg donor, I would be interested in those types of things. But what this gets to is the fact that we are inching closer towards designer babies. This is a patent that was taken out by 23andMe, the major direct-to-consumer genomics company. They were very quiet about it, okay? But this patent was granted last year by the USPTO. And it's a method. It's a very nebulous thing. They can't do this yet, but they wanted to get, they wanted to stake it out. And it's a method for asking people what traits they want in a child and then delivering a high probability of that type of child. Now, I think most people would not check the box. I want a high probability of colorectal cancer in my offspring, right? But what they also included were things like, okay, I want a child with blue eyes who can taste bitter or can't taste bitter, who is a likely sprinter or a likely endurance athlete, right? And it's hard to think at first why we are made uncomfortable by that. And I would warrant that most of us are made a bit uncomfortable. I mean, after all, we do try to optimize our progeny. We go to all kinds of lengths to optimize our progeny, so how is this different? And I struggled with that until I read in the Dalai Lama's book, The Universe in a Single Atom, he puts his finger, I think, on why we're uncomfortable. He says that thus society will find itself translating in inequity of circumstances that is relative wealth into an inequity of nature through enhanced intelligence strength and other faculties acquired through birth. In other words, we can at least kid ourselves that we are living in a society where everybody has an equal chance. And we know that's not true, but it's kinda true to an extent. But if we lock in those advantages biologically, we are no longer, we can't even pretend we live in that kind of society. And traits do have a genetic component. None of you are shocked or probably made to feel uncomfortable by the fact that height and weight and blood pressure have a genetic component. But it is also the case that things like personality traits are vocational interests as adolescents and things like religiosity, which not surprisingly tracks with traditionalism have a genetic component. So a better understanding of these things not only holds out the fear of a dystopia, like design or babies, but it also holds out the hope that we could use such knowledge for human betterment. So if we could understand bad behaviors better, this would be a good thing, all right? Diabetes and cancer are very costly, but just in terms of money, substance abuse, which is really a behavioral problem, costs more than those two things combined. And as a general physician for 30 years, I'll tell you that I don't think there is another set of diseases that causes more just absolute human suffering than psychiatric disorders. So if we can understand these things better, maybe we could intervene, maybe we could ameliorate some suffering. Well, we know that 50% of the Earth's population has inherited a distinct genetic factor that predisposes to a proclivity for engaging and risky behavior. It's the Y chromosome, right? It cuts across all demographics, all borders, all time. Although you do find women who do this, most of the idiots who do this kind of thing are men, right? And that is, I warrant, and there will be arguments with this, but that it has some biological basis. And if we could understand those things better, we could approach perhaps substance abuse and addiction more effectively. Now, in a study that sought to understand more about the interplay of genetics and environment, a real landmark project was done by Caspi who followed over 1,000 children for 26, until they were 26 years of age, and they assessed the genotype of an important gene that controls a variety of neurotransmitter levels called MAOA, as well as their exposure to maltreatment growing up. And those with both a low MAOA polymorphism and who were maltreated had very distinctly elevated outcomes for things like conduct disorder, 10-fold increase in violent crime, 85% of males with a low MAOA genotype who were also severely maltreated developed some sort of antisocial behavior. So you can say then that in this context of maltreatment, the low MAOA polymorphism increases susceptibility to the ill effects of such maltreatment, or you can flip it around and say that, gosh, a high MAOA genotype protects against such an outcome with maltreatment. And one of the things I love about genetics, unlike most medical specialties other than, for example, psychiatry or neurology, is that it forces you to grapple with some fundamental philosophical issues. And one of those is, for example, free will. We know that our behavior is influenced by genetics. What does that say about free will? What does it say about the judicial system in which we hold people accountable for their behaviors? And it's not that I'm advocating that violent criminals be given a pass. We unfortunately are unable to correct that and such people do need to be quarantined from the rest of society. But I think it is a fair question to ask how much choice they had. Is free will an illusion or is it real? There's a large body of philosophical thought that holds that free will is actually a very, very good illusion. And there's some very interesting evidence to suggest that may be the case. So the question is, as we understand this better, largely through genetics and neurochemistry, are we gonna someday be able to detect violence alleles and do something about them, to correct them, right? What about preemptive correction of such things, like the movie Minority Report? Now on one hand, we already treat violent individuals with nonspecific court-mandated psychotropic drug. So we already kinda do this in an extraordinarily blunt and not real effective way. A better understanding of such things could perhaps help us more effectively treat such people. But of course, people are probably squirming a little, as I say this, because it could also lead to a real dystopia, right? I don't really wanna live in a society where we're casually altering people's brain chemistry because we have a hunch that maybe they're gonna do something bad, right? That's pretty scary. And there's the unintended consequences. Every time we do something in science and technology, there are usually things we didn't anticipate, including things like stigmatization of people who are now labeled as perhaps potentially violent. So science is not gonna solve these dilemmas, right? We're not gonna come to resolution of these ethical dilemmas through science, but I can tell you this, we're gonna need a scientifically literate populace and scientifically literate leaders if we're gonna successfully navigate these challenges. And that's a problem, right? Because again, we live in a society where most people don't really know what science is. They run from it, they're turned off by it at young ages. Half the population, women, are discouraged in very overt ways from pursuing science all too often. And the problem with that is when we misunderstand and when we misapply science, the consequences are formidable, right? They're formidable in fairly trivial ways by people buying electric corsets, right? But they are formidable in absolutely existential terms when we misunderstand some issues that put our entire planet and our entire species at peril. So what we need to do is we need to work on creating a scientifically literate society. And I think there's actually one educational reform that could go a long way towards helping with that. And that is some type of statistical literacy. My kids went to a very good public school, all right? Junior or middle school and high school. And yet, while they had to take trigonometry and pre-calculus, they never had to take a course in statistics. And I can tell you, I haven't taken a lot of mathematics that I don't use my integral calculus very often, right? But everybody can use statistical reasoning. Whether you're staying at home and taking care of kids and shopping and trying to get the right product, whether you're going out in the weather and you have to understand what a 30% chance of rain means, which depressingly a lot of people don't when it's tested. Our policymakers need to understand something about statistical significance. And when coincidence is just coincidence, right? And why a rare event doesn't necessarily should be generalized. The press isn't very good at getting these things across. And there's this idea that statistics are boring and dry and yet we have an entire city, not that far from here, that's based on probability, basically based on misunderstanding probability, right? On the part of the consumers. So it doesn't have to be boring. Science needs to be taught in a way that its actual relevance to one's life is made manifest. And I would also add, as somebody who is passionate about science, that we need to emphasize the beauty of two. Because I will tell you, as most of you I think appreciate, but much of the population doesn't, that an understanding of science is an unbelievable boon to our appreciation of the beauty of the universe. From understanding how mountains arose, understanding that these stars, that the light that's impinging on your retina is literally millions of years old, right? It does nothing but enhance the beauty. I bristle at the idea that enhanced understanding somehow makes art dry or makes beauty less manifest. I don't think that's true. So I wanna finish up by addressing the elephant in the room. You can't really talk about science and technology and all without discussing at some point, if you're honest, science and religion. And it is the fact that a scientific worldview is not inherently inconsistent with the belief in the existence of a God. And when I say it's a fact, I mean it's empirically evident. There are scientists, very good scientists who are able to reconcile a belief in a supernatural God, right, with their scientific endeavors. Religion's persistence I would add is insured by the inherent limits on our own understanding and on our drive to understand. We're never gonna be satisfied with an incomplete description of our universe and yet we're never gonna have a complete description of our universe for a reason I will say in a minute. On the other hand, the uncomfortable thing for many people is that there's no question that religion is constrained by science. I'm sorry but the earth is not 6,000 years old. It's 4 billion years old and there's plenty of evidence to support that and we can't cling to religious views that are manifestly false. But scientific understanding itself is also constrained and we can't think of science as an absolute antidote to all ignorance in the world. And the reason I show my dogs, this is Sparky and this is the auxiliary backup dog, Lily, is no matter how hard I try, I would never be able to teach Sparky integral calculus. It is just beyond his brain, right? And there is every reason to realize that our brains have limits too. We are not up to the job of omniscience. We are limited by our biological resources. We will never completely understand the world. There will always be room to wonder and to invoke religion and supernatural explanations. I love what Ken Jennings said when the IBM computer beat, just crushed everyone, right? At Jeopardy. He wrote on his final Jeopardy thing, I for one welcome our new computer overlords, right? Because it is interesting to think that while we are limited in our ability, could we build machines that could build further machines that ultimately are not limited in an attempt to understand the universe? But we're left with a paradox, right? Science can demonstrate our need for emotional warmth and connection. It can explain through neurobiology, through evolutionary biology, why we need those things and it may even be able to inform how to achieve those things in the best way possible. But it can't fulfill that need alone. Science, science will inform that quest but will not solve that quest for us. And for that we need one another. I want to end this with just a few other random challenges that I will not offer the answers to, okay? One is concerns about genetic discrimination. This remains a concern. Gina, the Genetic Information Non-Discrimination Act is wonderful and it has helped me in my practice because I can assure patients that they're not gonna lose their health insurance because they're gonna get a genetic test. Unfortunately, we have no protections against long-term care insurance, life insurance, disability insurance and that's a problem. And I think we need some kind of protection although it's a thorny issue because we already do discriminate say with life insurance because I need to pay more than a woman of my age because it's more likely that I will die and that's fair, right? So I mean some discrimination in life insurance is probably reasonable but it is disturbing that people can be born through obviously no fault of their own with the mutation that obviates their ability to get long-term care insurance or disability insurance. I thought allealism was kind of, I threw that in there thinking, yeah, that's possible. And then I saw this quote by the co-founder of 23andMe in the Washington Post who said, we envision a new type of community where people will come together around specific genotypes. Now that's a little scary, right? I understand that it'd be good if people with disease mutations could come together and promote research and that's probably what she meant. I don't mean to pick on her but we have to be careful about coming together around specific genotypes. The human beings have done that in the past, right? In my own state of North Carolina with mandated sterilization in Europe in the 1930s, right? Gene patenting was largely alleviated by the Supreme Court in June of 2013 when they ruled that human genes are not eligible for patent protection and that's wonderful, okay, that's great. But we still have some problems. That's not the case in Canada, for example. There is a new case that hopefully will achieve the same result. It achieved the opposite result in Australia where patents still exist. But the problem is that people are keeping some labs, are keeping the data secret that they generate on patients. And I can tell you as a medical geneticist that we need to share these data or we're never gonna figure out how to interpret people's genetic tests. So I think this is a problem. Privacy issues are huge. Your genome is a digital archive of information. That is not a metaphor. It is an actual digital store of information. And we are really good at storing, disseminating and hacking digital information. In this paper, they used public databases to look at DNA sequences and in 20% of the time, they were able to find a name, address, and phone number just from the DNA sequence and then going online. You can imagine a prosecutor's eyes lighting up that a blood spot might show not only a DNA genotype but could show a telephone number and an address. The problem is they also had an 18% false positive rate which is wholly unacceptable in the criminal justice system, right? So we're gonna have to grapple with those. I love this quote from the co-founder of Sun Microsystem, Scott McNeely. He said, privacy is dead, deal with it, right? And I think he's right. I think privacy is dead. We're not gonna put that genie back in the bottle. What we need to do is we need to deal with it. We need to figure out how to set up policies and structures that penalize people for the improper use and encourage the proper use of all the data that are out there. How many of you have a grocery store card that gets you a break when you buy groceries, right? Probably everybody in the room. And when you do that, you're making a deal, right? They get to know everything about what you buy and you get a break on dog food, right? I do the same thing. I think it's worth it. But they know a lot about you by what you buy. They know who you're gonna vote for in the next election. When decode, one of the direct-to-consumer companies went bankrupt, one of the envisioned solutions in the bankruptcy court was that the data that they had accrued over several years would become the property of a venture capital firm in Cambridge, Massachusetts. Probably not what the people who spit into those tubes and sent it off to the company really were counting on. So we're gonna have to grapple with who will control, have access to this information and how we ensure that it's used predominantly for good. And I will end with a cartoon from Hilary Price, Rimes with Orange, about the dangers of genetic engineering. Create a dog that's scared of cars that's clean enough to enter bars who never would a cat mistreat whose breath's forever minty sweet. But first, before we splice a gene, let's think about the unforeseen. Our good intent to hybridize can engineer a bad surprise. A dog who might be quick to judge or God forbid who holds a grudge, who leaves behind its role traditional and offers only love conditional. So I will stop there and I think we got some time for questions. So if you can go to the microphones, right, because otherwise they're recording it and it'll be a big blank. Yes. Hey. Jim, come and play. That's it, go on. I noticed that you didn't use one term, you skirted around the phrase sometimes, but the term eugenics. Yeah. And could you comment on, did you intentionally disregard that or? No, not really. I think that I alluded, right, when I talked about coming together around specific genotypes. Genetics has been, it's not one of those fields where there's just the potential and the hypothetical chance of misuse. It has been misused. It has been horribly misused. If you look at Nazi Germany, if you look at our own country, the eugenics movement was very strong. And I think that that came from several things, including hubris, we thought we knew more than we did. But what I would emphasize, too, is it came from a lack of understanding of genetic principles and a lack of evidence that what was being done was actually going to benefit. So I think that, again, that eugenics is both a strong argument for the work of a center like this. And it's a strong argument for our policy leaders and our population to have a thorough understanding of science because most of eugenics was just bad science in addition to being horrific from an ethical standpoint.