 So good evening everybody. Welcome to the National Museum of Natural History and to tonight's program jointly sponsored by the NIH us and Johnson and Johnson. My name's Jonathan Coddington. I'm the associate director for science here at the Natural History Museum and just to give you a little bit of context this institution the Natural Museum of Natural History actually dates from the founding of a Smithsonian about 1846 So we're primarily a research institution like NIH. It's the largest Natural History Museum in the world and Also the most visited with about 8 million visitors. This is actually the capstone event to our genome exhibit which just closed last month and it's now opening in San Diego so about 3.8 million people saw that and The reason we're joined at the hip here is really because our of our interest in Informal science learning and getting the word out about the genomics revolution both at the level of human health and for us the genome of the rest of the animals on earth so That's what we do and I'll turn the program over to Sima Kumar who is from Johnson and Johnson and She'll do the rest of the introduction. Thank you. Good evening everybody. I'm Sima Kumar I am vice president for innovation global health and public policy communications at Johnson and Johnson and it's such a pleasure to welcome you all to this very special evening and To this closing ceremony of this wonderful exhibit that has been around here at this museum for about a year now cosponsored actually put together by the NIH the National Human Genome Research Institute and The Smithsonian Museum of Natural History We Johnson and Johnson just a couple of words about Johnson and Johnson were a broadly based health care company that does a variety of different Types of work that impacts the health of human beings all over the world We are in pharmaceuticals medical devices diagnostics as well as consumer health care and Most people know us as a baby powder and band-aids company But we are actually much much more than that we are that of course, but we're much more than that We're a scientific powerhouse We believe in the power of genomics to actually impact human health in a variety of different ways and so it was really a pleasure to be a Sponsor of this exhibit and also sponsored of today's events. We had some really stimulating discussions all the way To public health priorities today that we face With the outbreak of Ebola and how genomics is helping trace actually the the origin of the outbreak So it's been a wonderful day a wonderful evening and we're looking forward to actually our our next event And I just want to say on behalf of Johnson and Johnson that We also believe in public education Of science we believe in inspiring and engaging the public as well as the next generation of researchers and young scientists Into this field and so it was an honor for us to actually Be a sponsor of this and with that I Turned it over to dr. Eric Green who is the director of NHGRI Eric Thank You Seema. Thank You Jonathan. Let me add my own welcome to all of you to this last component of this Symposium that really is serving as a Celebration of the 14 month run of genome unlocking life's code here at the museum We bid it for well last month and watched it find its way to San Diego and several of us were at the opening of the exhibition As the first stop of a four to five year tour out in San Diego on Saturday evening This exhibition this entire program this entire collaboration really represents Very productive partnerships between a number of groups that includes the National Institute of Health in particular the National Human Genome Research Institute Which I have the pleasure of serving as the director the Smithsonian Institution in particular the National Museum of Natural History and Three years ago We got together without really knowing each other and I think have done a remarkable job in putting together not only an exhibition But a series of events and a series of public engagement activities That are really I think very much helping The public understand genomics and it also includes The partners that we've developed in terms of donors things like this just don't happen unless we are able to convince the private sector Such as Johnson and Johnson and other as well as a number of private citizens who are willing to Help support such an endeavor and working with our good friends of the foundation for NIH who raised the money on our side of The equation to make this a reality We've seen great things happen numbers of programs all year long while the exhibition was here And this is the final in this series of programs so needless to say we're immensely proud at the Accomplishment so far and the millions and millions of people that wandered through the exhibit and learned a lot about genomics and the number of people that came and really saw it and said wonderful things about it and And we had a great day today We learned a little bit about some ideas around genomic medicine and applications of genomics to medical care Especially looking towards the future and thinking about some of the aspects of genomics as it pertains to global health And then this final panel which I'm about to turn you over to Really is also going to continue this conversation of what the public is thinking about genomics and how it really is touching people's lives and It includes that I'm not going to introduce to people a member of our own Institute In bar B stickers it also includes a very good friend of ours of the Institute for many years Probably even decades day Valley, but I want to give a special thanks even before she's introduced formally to Carolyn hacks Who comes here at our invitation to to share with us her thoughts and some of her stories? And it was very very gracious of her to spend some time participating in this symposium, so I'm going to let the longer introduction be given by the moderator of tonight's session Rebecca Roberts who I now get to introduce And Rebecca is a program coordinator for Smithsonian associates another partner in these programs that we've been putting on Where she produces public programs on subjects as varied as ice cream scoops pirates and particle physics and now tonight genomics And for the past year she and her colleagues at the Smithsonian Associates have been collaborating with our Institute and also the National Museum of Natural History to create a whole series of these innovative programming all Around and meant to complement the genomics exhibition But before joining the Smithsonian, she was an award-winning science and technology journalist Now I'm just reading what my staff told me she traveled the world to interview Transgenic goats and hiking through Icelandic geysers and high heels, so I didn't make this up It's what's here, and I'm simply conveying that to you But here in Washington her hometown She serves as a substitute host for public radio programs like morning edition talk of the nation and the coach on andy show So I will turn this over to Rebecca also thank her for moderating this evening session And she will introduce the other members of the panel a bit more formally. Thank you very much It's a really great that you're here Having us here tonight. It is totally true about the goats And about the high heels on the geyser before we go any further. Let me just remind you please silence your cell phones You don't want to be that person. I was at a program recently where a guy's phone rang and his ringtone was the chicken dance So especially if you have something embarrassing like that going on, please turn them off now Let me introduce our panel starting from stage right Dr. Barbara Biesiker is the director of the Johns Hopkins University National Human Genome Institute Institute genetic counseling program and adjunct associate professor in health behavior and society The John Hopkins Bloomberg School of Public Health as well Dr. Biesiker is an associate investigator in the social and behavioral research branch of the National Human Genome Research Institute And head of the genetic services unit, and I'm afraid that's all the time we have this evening And in the middle here is Dr. David Valley He is the Henry J not professor and director of the McCusick Nathan's Institute of genetic medicine at the Johns Hopkins University School of Medicine He's also a professor of pediatrics ophthalmology and molecular biology and genetics Dr. Valley is also the founding director of the Johns Hopkins Center for inherited disease research And with a much easier title Carolyn Hacks is a writer and columnist for the Washington Post and author of the advice column Carolyn Hacks the column debuted in 1997. It's now syndicated on more than 200 newspapers Carolyn Hacks wants to scribe her column as intended from the start to be the kind of advice You'd get from a friend if that friend were relatively stable and brutally honest and had possibly gotten up on the wrong side of the Bad that year Welcome. Thank you so much for being here So let me just say that this panel grew out of the experience of having the exhibit up in this museum for 14 months And I hope you all did have the chance to see it before it went to San Diego Just from a visitor experience viewpoint. I was really impressed with that exhibit because when you're doing a whole Human genome exhibit. What do you show right? It's like well, let's have a model of the double helix and then you know I'm out. I'm done but that exhibit was incredibly smart about Rooting genomic research in the human story And so there was that great computer panel where you could sort of choose a hypothetical family who was facing a hypothetical Dilemma and see what happened when they made their hypothetical choices and That really brought some of these stories to life But what kept happening was people were saying Yeah, but what about in my family? My experience is slightly different. What if this happened? Bringing their own Family histories and their own priorities to the hypotheticals that were in the exhibit So that's what tonight is about tonight is the chance to talk about what about my situation And when you all reserve tonight, you were given the chance to submit questions We have lots which we are eager to start with but there are also going to be volunteers trolling the aisles Yes with index cards And so if you have questions, you would like added to the form We will get to as many of those as we can just write them down on the next card one of the volunteers will bring them up So let's get started. This is a question that was submitted by one of you and I'll just read the question then we'll sort of get everyone's reaction to it Discuss the difference between testing for a definitive result for untreatable disease Huntington's and the increased risk odds for treatable diseases such as breast cancer So I think there's two parts here the treatable untreatable part But also the definitive result versus increased risk So when people come and talk to us about genetic risk or the option for genetic testing They come usually based on their family history or something that's been brought to their attention that suggests that they're at increased risk And when we think about common disease like cardiovascular risk or cancer risk the testing that we can offer if it's indicated can help us Estimate the likelihood that they might develop that cancer in the future and then talk about prevention and Treatment options that may be available to them. That's very different then the definitive test that is in the question about whether or not you carry a single mutation for a Disorder like Huntington's which if you live long enough will inevitably declare itself And so there's no living at risk you either inherited the mutation or or you didn't so That's one of a choice that's much more about personal values and beliefs whether you want to know whether it's useful to you to know whether or not you inherited a gene mutation at risk for and one might argue that the risk estimate that you learn for cardiovascular risk or cancer risk is in many ways medical information because it can adjust your treatment and Least your screening activities that might result in early detection And so those are very different kinds of pieces of information and we might be more likely to persuade people if they're an increased risk to Use testing if it's going to help with screening Whereas in Huntington's we would all I think most of us agree that that's a very personal choice And we would want to help people make a good decision for themselves Caroline in terms of the Screening might make you change your life a little bit if you're at risk for something, but it also might be information you don't want It depends very much on your knowledge of yourself and it's asking a lot of people to Be able to say okay. I can predict how I will react to this information, but I think people Over the years. I've there are two kinds of people But there are there are the people who It's funny when we when we end up talking about infidelity of all things and you know I just saw somebody I just witnessed something do I tell and There are just over and over again in these situations There are the people who are just absolutely rabid tell they should know they need that information There are some people like oh gosh don't go in and blow up their lives That's the that's the schism. We're talking about here You know this camp gets tested this camp should not and the only to me the the thing to identify is Which do you know which camp you're in are you confident in that because I? Just I just think and I think you have to know be pretty confident in that before you make your decision And David, I think that the added question here about the increased risk question which sometimes you need to kind of know your statistics in order to understand what those tests actually well, I think one thing that's implicit in this question that I would just state is that as Genetics and genomics expands We will see a genetic component in all disease and so this scenario that we've laid out What do we how do we counsel people who are at risk for a specific disorder and a very black-and-white? Situation either they have it or they don't versus a group of people who? May because of certain genetic variants be at increased risk some modest increased risk That will be going on over and over again not just when you go see your friendly geneticists But as medicine advances it will be Part of going to see the doctor or even before you go to see the doctor I think helping people understand risk to get back to your specific question is Is challenging because I think people Incorporate into their understanding of risk not only the number but also the burden of the question Involved and I think probably we have all had families where you say You know your recurrence risk is very small. Let's say less than 1% And they may say I don't care how little I don't care if it's one in a million I don't I cannot bear to go through this again. Let's say if it's a parent, so we've had a child So we all Perceive risk differently I think it's the duty of the geneticist or the physician to help people understand the risk as accurately and as completely as possible and then We also need to in the case of being at risk. We need to give them Information consistent information clear information about what are their options of dealing with at risk and minimizing that risk and Increasing their odds for staying at a state of good health Let's put this in a specific instance because there is a question here What is some advice you can share about deciding whether to and when to get tested for the BRCA one or two gene? And what to do with the resulting information So staying with you David for a second First of all, where does that test fall on definitive answer versus increased risk? in the middle I Think I would also just parenthetically say one of the exciting things about being in Medicine and genetics at the current time is that our field is changing very very rapidly And so just in the last few years, I think we've seen Different ideas about how testing for breast cancer has evolved and so The sort of I think state of the art right now is to test Those individuals who by virtue of their family history are perceived to be at somewhat higher risk But we are now seeing other people begin to advocate Because the test our ability to interpret the test and because we understand that our knowledge has increased We're beginning to be at a situation where we can begin to contemplate Applying that test across the entire population of let's say age 30 now the answer Whether if you have a variant that we can interpret as being one of high risk It still isn't a hundred percent and there are things that one can do with that information to To bring your risk that to avoid let's say the the serious consequences of that So it's a very exciting time things are changing. I must say that I personally am attracted To the idea as we have learned more to really contemplating moving this to a population-wide test Right and so that because right now what we are doing is we're Identifying those families those individuals that are at risk by Picking those people whose relatives have had cancer and we should get to a stage where we don't that's not not the Entry point the entry point is we have this test. We know what it means We can give give you information about that and we know what to do about it So I guess in part one of the things you would want to know when you're making this decision is You're talking about the percentage of calculating risk But you also want to know the percentage of the effectiveness of the measures you take to prevent Absolutely, so that seems to be I mean that to me is more of an x-factor even than the likelihood of Getting the illnesses. Okay, because I can't do anything about I Want to know what I can control and if you can give me something high percentage to control I'm gonna be much more motivated to get tested even if I've got no family history So these are two very common mutations for hereditary breast and ovarian cancer and The screening is much better for breast cancer than it is for ovarian cancer So we can still screen for ovarian cancer And there's certainly surgeries that can be used to prevent or minimize the chance of getting ovarian cancer But people feel differently even about the things that you can do about both of those two cancers in this thick that are coincided with the same gene mutation Well this if we're talking about say that That test becoming something that you do after age whatever and it's a common test Regardless of family history that leads into a more general question which also comes from the audience How much testing should one get if there's no family history of genetic disease? Sort of goes back to Carolyn's point earlier, which is we're all very different in what information we want to know and For people who go to their positions if the physicians are familiar with new genetic testing Maybe the onset of genome sequencing they may have strong opinions about whether people with no history should avail themselves of these new tests Where they can learn potentially of variants and mutations that we understand pretty well But we wouldn't know to look for because it was no family history We don't really have an immediate precedent for that I think there'd have to be a lot of thought put into who would be available to counsel the people who find out there at increased risk These are not people who grew up in a family thinking that this is going to happen to them And some of the risk can be fairly startling if you look at the hereditary Cardiovascular disease mutations where people are at increased risk for sudden death That's a pretty dramatic piece of information to take on but think about it. We don't have counselors helping us Process our mortality. I mean, we're all we're all looking at this one and we've all had to process certain death and so what you're talking really is about putting a finer point on it and so You know, it's it's again It's it's how fine is this point going to be at the moment? It's it's varied for some illnesses It's a very fine point. We can give you certainty and with some of them It's we can give you percentages and again, you know, if you're gonna make me eat more broccoli I want to know it's gonna do something It will it will these are all fine shadings of processing what what could happen and it's really I mean to me It's how do you live with the weight of knowledge and how good is your? How good is your prevention information for me? I think that's wonderful because what you're doing is predicting the future I'm sort of talking about, you know moving into that and that's going to be sort of a graduation of now This being a sort of public consumer endeavor where you go to your physician And this is part of medical care and we get used to getting this information and it's routine And we don't specialize that we don't see a counselor about it. I think you're predicting exactly what's gonna happen I'd like to see us transition To get there because I think it's a little it's shifting the paradigm quite a lot and it takes people a while to kind of Get used to that but especially you got it and we're in the land of death this area I mean right Americans don't do death very well Which we don't talk about it. Well, we don't process it. Well, we certainly don't plan for it. Well and Medicaid it well so Maybe it's gonna maybe that future is coming in other societies and maybe we can peer in and say That makes sense. Well, I would come back to the Point that the field is changing or medicine is changing very very rapidly and so what? appears hopeless today, maybe May be more manageable five years from now. Let's say or ten years from now or it may not so it's I think what is going to be state-of-the-art today will not be state-of-the-art practice a few years from now and I think we're seeing that that sort of Transition in the breast cancer breast and ovarian cancer area right now, but there of course remain other disorders for which we're really Not able to budge the the needle at all Certainly I mean there's huge differences now and what all the information people have access to on the internet And we live in a very privileged part of the United States So people have a lot of access to information and come with very intelligent questions Taking control over the choices that they may face based on their family history. It's definitely I wouldn't say it's universal But we certainly see that in the clinic as well that the people come in some are extremely well informed Others are have worked hard at it, but still are have misinsert information and others are still pretty much They want to hear From the healthcare professional what what to do I can't count on Google You can look Along the veins of sort of increased public awareness Of course, there's been the ice bucket bucket challenge has you know flooded Facebook lately This question is with the overwhelming awareness of ALS actually before I ask this question Let me ask you what was your reaction to the challenge of someone who lived through watching your mom. It was it was so First of all, it was delightful I mean, I also saw the origin story which was so not delightful seeing this young person Afflicted was horrible but it's it's hard to describe the experience of being in a community where You're watching something terrible happen and there's nothing you can do about it. You're completely powerless and You know that the research has made progress, but we're still far from being I mean, there's really no treatment Even it's just it's just a death sentence and they send you home and they try to keep you comfortable and the families the patients are traumatized the families are traumatized and At the same time we're a very small community So we just can't make enough noise to make a difference and so this has been going just year after year after year we walk we we control we beg and We just make almost no dent and to see this thing just sort of come out of nowhere and just see this Millions just showering on your cause. I mean it was just my sister. We we have a family reunion on Cape Cod every year and my older sister Was sitting on her computer just playing the videos and she said she said I can't I Can't wrap my mind around this. I can't stop watching these and she was yeah, she was choked up And so it was just I just wanted to go around and say thank you Thank you everybody and of course that lasted about two weeks and then all the naysayers came in But I was just you know, thank you for Thank you, too because it kept it going even longer But it was just it was just it was a mind-blowing experience to take our our little Bit of health and to see just all this light and love coming to it was unbelievable The question specifically in David I think you're the best person to start with this is how do you think that changed the desire for more scientists to apply more clinical or translational research Well, it certainly I think raised the awareness in the research community and There is one of the paradoxes that we live with right now is that research funding from NIH and and the sources that we typically got research funded by in the past are having To tight tighten their belts and so people are looking for other sources of funding and so to see people so Involved in this and so enthusiastic about getting people Involved in the research was was very rewarding. I'm sure people came in that will come into the field and maybe somebody will come in with a really Good out good idea and good result this question I'll just read it. What are some current disparities in genetic research? Our advances being made more quickly within a certain subset of the human population due to population surveyed specifically in terms of certain Hard question We certainly would this allotted NIH when we do studies when we put out outreach to To groups in the area and put advertisements in the Washington Post The people who respond are largely well educated every sources and more often Caucasian In responding and so when we try to target specific populations of African-Americans or Hispanics We have to go out and into the community and do a much more involved targeted job to recruit people to our studies Obviously in rare disease and the patient populations that come into NIH rare disease does not discriminate And so we see much more diverse populations come into the clinical center and partake of research But it does take some sophistication or your physician being sophisticated to find out about studies at NIH and to make your way there And so all of us grapple with this on a day-to-day basis in the way We provide care and who has access to it in the way we do research and who answers our research surveys And we need we have a long way to go I think the thing that worries is probably more than anything is just the overall disparities in how medical Care is delivered in this country and people who don't have insurance don't receive the same care as people who do Well Here's an insurance question shouldn't Which is Shouldn't insurance companies pay for IVF and pre-implantation genetic diagnosis services for women who are carriers of fatal x-link disorders? They pay for IVF or infertile woman So now why not carriers of x-link diseases? Well, I I agree with a questioner I Mean this is a let me expand the question a little bit Although we are Being able to do we are currently able to do more and more sophisticated genetic testing Which yields precise and unambiguous in many instances yields precise and unambiguous diagnosis that allows us to counsel families and to treat patients in a much more informed way Getting those tests paid for It's still a challenge and people in the clinic. I mean in a typical working genetics clinic Part a substantial part of the time is spent trying to get reimbursement for those tests and Even though and I'm a way out of my depth here I'm not an economist, but even though it seems to me that one can argue that Over the long run if you invest up front and get good information in the long run it will Reduce the cost of let's say ensuring a particular patient or particular family Those arguments are still we're still having to rehash those arguments day after day after day and It would be in my view a great move forward if we could Get over this and do the testing that is medically indicated and Not have trained people spending time trying to figure out whether the test is going to be reimbursed or not When I think it's very tough question, which is if you are predisposed to certain quality of life altering conditions Would it be irresponsible to have children? It depends. I mean if do you Do you have the condition yourself? Or are you a carrier? You're in a you're in a strong position to decide if that is a lot if you look at your own life as worth living Given your health situation then I don't think it's irresponsible to Have children, but if you If you yourself don't have it then you have to think then you have to project that question Is this a life that I would want to live is this the life of people who have this condition want to live? I mean it again You're trying to decide the value of life, and I think any parent is doing that I mean you're when you decide to have children you're you are sort of You're conferring that yeah, I don't know you're you're playing God in a way You're deciding whether this you can be you can provide a good life, and I just think that that's it's the same question It's just more complicated and more fraught and probably when you don't want to talk about in public because you can You can have people take great exception to the way you look at it I think that's a really important point is that the personal part of that is to help people Make really good choices for themselves, but the what's hard about that question is that it implies that maybe we have a Responsibility to society not to bring people who are affected into this world And I think we don't have a lot of good open conversations about that in the United States. We really We really value our autonomy and our ability to make decisions for ourselves and very much the way that Carolyn Very nicely illustrated How we do it and we don't talk outside of our own personal bubble much about What we're doing and I think this is going to be something that we continue to need to talk about as a society on a large basis I can't imagine imposing restrictions on people's child-bearing decision This just seems to me the most personal and ultimate issue of controlling others, but I certainly do think Redistribution of resources and other social goods or something that I hope we get closer to in medicine as a whole Maybe not maybe preserving the Privacy of child-bearing decisions. I don't know. It's a hard question. I Think it's a I agree. It's a very difficult question And it's a and it can be approached at different levels You can approach it at a societal level and think about resources and so forth then you can approach it at the individual level and How how people see their the worth of their own lives and of course it's possible I would think to view that you your own life has a Real worth and you've made lots of contributions but you also decide that I'd rather not have my child have to deal with this I'd rather have them live life without having this problem and So from the point of view of a geneticist in the clinic. I think our job is to Inform people as clearly and has as accurately as we can so that they make those kinds of really Major decisions with a complete, you know with the state of art sort of knowledge set and And very often that means going over things more than one time and putting it in different terms even having different people pitch it so that The people who have to make the decision that is the parents or the or whatever make it with the state of the art information We talked about which is also the the parents I mean we're talking about the ability to project and also society to absorb but there's also is our you as a parent ready to take on Being the parent of somebody who might have these enormous needs And of course we're talking about all this and trying to calculate these decisions and then of course you can decide No, I won't do it. I will adopt for example get outside my gene pool Take on something that's you can end up with something even more complicated than the thing you were trying to avoid So it's amazing you really I mean no matter how we could we could talk this down to a To some sort of consensus. I'll just float that hypothetically because it's impossible But even then you're still there's still this leap But you just don't know And it occurs to me too. We've done a couple of studies over the years and of individuals affected with several different kinds of chronic genetic conditions and then their first-degree relatives or the parents perspective and parents and siblings rate their quality of life of their affected family member differently than the person who has affected themselves So even the people who live with it intimately and at first we always thought that the early study Trends were what we were going to see which is the people who are affected with the disease had higher ratings of their quality of Life than their parents because their parents are also very concerned and feel responsible for their kids But it didn't it didn't pan out that way in various conditions We found various different ratings and it became more upsetting when we saw people who are affected Rating their quality of life is lower than the people who love them and are close to them And so there's a lot of things we don't understand about what goes into how we make those assessments They're really important for us to understand Just the way that you've illustrated Let me remind you all there are people trolling the aisles with index cards if you have questions you would like to submit Way of a hand In terms of handling some of these issues that come up in what ways can a support group be good or bad for someone who has a High-risk factor or family member with the disease? I think it's But you may have a high-risk health issue, but it's a pretty low-risk venture to try out a support group often they're free and They are filled with people who probably have more experience just because you're seeking now generally the people there Have a base of knowledge about what you're dealing with and so even if you're unhappy with it You can talk to the Motten you're the leader of it and get other information to go somewhere else I mean it's one of those things where it's like what's the worst that can happen, you know You can you can have an accident on the way to the support group. I mean it's I Don't know but that's but I come to it with a with a bias toward Try the therapeutic approach and if it doesn't work, I don't think you've lost anything I mean some people might run out of there feeling like their hair is on fire, but that's not my experience personally So we deal with this daily and genetic counseling and I completely concur with Caroline I think there's not there isn't a group for everyone and sometimes you go and it Doesn't feel like people are talking about issues that are foremost in your mind or of concern or you somehow don't relate to the group There are other groups There are now online ways to reach out to people who are otherwise isolated who might write blogs who might Just make themselves available to have conversations with and you don't even have the messiness of having to meet people Personally, but you can share what you've learned about the condition or what you've learned in terms of coping I just think the internet has has just opened this up so widely We we definitely do not see people Feeling as isolated even if they're physically isolated Geographically isolated as we used to on a routine basis in the early days of providing genetic services I think it's tremendous and I mean it's funny I lived in Ann Arbor, Michigan ones where they have three support groups for Down syndrome And that was because they all had very different Goals and directions and one was for newborn parents and one was for sort of school-age parents And one was for adult parents because they were all dealing with very different things and they didn't like each other's groups But they worked really well because when your kid got older you went to the next one I think that I think there's a lot to be learned from from the support groups and very often Parents will say well you you told us this that and the other but what was really Really bothering me was how to cook the Pop-Tart the right way or some some little practical thing that a That people in the clinic don't doesn't come on our radar screen It turns out to be very useful information for the family and so I think that kind That kind of information is very useful on the other hand some people You know don't They find that they don't want to engage in support groups. They they they manage things in a different way, so I always try to Tell people that these opportunities are out there and increasingly they already know about it because of the internet But I also make it clear like you're not a bad person if you don't go join every support group for these things so Works for some people and not for others and from the general to the specific this question is How do I help my mother who's dealing with her mother my grandmother having dementia? It's heartbreaking all around and I don't live close enough to help I've recommended that she my mother get therapy for herself to know the fail Let's just say that's a great argument for a support group I mean there are a lot of people who don't want to get therapy that it feels like a It feels like it has a high barrier to entry although I would argue it does But I think to a lot of people it feels insurmountable where the support group barrier to entry is quite low And so somebody from afar can do the research and say here I've lined up respite care for you through this support organization, and you know You are going to this is where you would go for this meeting and obviously you You can only Point out where the water is to the horse, but it's something We're getting some really terrific questions in here This one, I really love can we open this up to the possibilities? What are the things you see 20 years from now that are awesome? Well, I think I Mean in case you can't tell I'm extremely enthusiastic about what genetics is going to do for medicine and So I think the sky is the limit for 20 years. I it's I wouldn't put any Limits on it, and I think there will be discoveries that We we can't anticipate right now And there are certainly things that we can do the things we can do in the lab right now that Two years ago, we barely even thought of this genetic or genomic engineering where we can create Much more accurate models of disease to study in the laboratory is something that's coming on like a tremendous Wave and has great opportunities So There's that sort of Eureka Results that will come along There will also be sort of the slow steady progress that is just going to take a lot of hard work and a lot of thought and And it's also going to take at some I think You know we're some of these problems some of the things we've discussed today are things like that They sound like there's some potential pitfalls And so one response to that is to say I can't I'm not going to do anything because I'm afraid of the pitfalls And another response to it is to say okay I'm going to learn as much as I can about this and then I'm going to take my best shot at it and May make some mistakes along the way. I may have to self may have to correct course periodically But I think we have to be willing to do that kind of slow steady progress and then also Embrace in and The sort of Eureka things that come along Caroline this question is for you what has been the most difficult health question you've answered in your column Can we go back can I think if we go back to that? That's absolutely Let me give our chance to answer the previous question about yeah, I think excitement. I think You know you can't be in genetics today, or if you are and you're not excited. That's really sad You should get another job because things are There's no more stimulating You know a scientific career to be in right now because things are I train graduate students and the curriculum We're teaching them this year doesn't resemble the one that we taught them last year and what they're seeing in the clinic and choices that people are being offered are more extensive and and differ and How you frame the choices for people so in 20 years the thing that I? I look forward to is the number of clinical trials that have just started up in rare diseases that I never Thought that I would live to see is tremendous their early phase trials and there's lots of bumps along the way But that's very very exciting things that I didn't think I'd ever see is potentially treatable maybe in 20 years. That's a lot of time to learn a lot about About treatment for things that we wouldn't have even had a dream about treating So that's very exciting and the other thing. I think we'll see is a movement from sort of Mendelian genetics one gene mutation for one disease or disease risk to The sort of cascade of multiple gene effects and hopefully Some input from understanding environmental insults that work together with the genes to cause people to tip over the threshold To have common disease Diabetes and cancer generally and heart disease. That's really complicated. It's hard to even think about how we're going to do that now But that's the direction things are going. That's it's a very very exciting So another thing that I should have mentioned is that I Agree 100% with what Barb said and but it's worth just Pointing out and I recently was asked to take stock. How many? Genes are there and our genome that when they have a particular variant can cause a disease or a clinical problem And it turns out the number that we currently know is still quite small a small fraction of the total and I think that we will see over the next few years because I think that the methods and the technology are now available and So I think this is a sort of you can bet on that kind of progress that we will in the relatively short time certainly within 20 years time be able to enumerate the contribution of every gene in our genome to human health and That knowledge which will be based in part on or in large part of the study of rare diseases involving those specific genes but also basic science and also large population studies will really bring a wealth of new knowledge into medicine and I think improve medicine and Make it a much more effective business In 20 years, it'll be on much more on prevention. I think I hope if we if we're not if we It'll be on prevention and treatment. He'll be on elder care But it won't be by us No, it's funny. I'm thinking of my questions that have a medical element to them and of course When it comes to me, it's always an emotional question. I mean, it's always an emotional problem Of course, I think one of the I didn't even answer it. I didn't answer it Because I didn't have an answer but it was it was a story of what serious illness can do to people It was a story of what our methods for dealing with Serious illness can do to people like our basically our health system and the expenses Basically, it was a it was a single mom and a daughter grown daughter. The mom was ill and needed constant care and so the daughter was and They didn't have money and so the daughter was working full-time to support both of them and also taking care of her mom full-time and She was writing to me just saying I see no hope Like I have no hope. I have no vacation. I have no savings. I have no life I have no friends and It just and I'm just looking at this I'm like I have no answer and I it was just I would say that is the hardest question I got on a topic of serious illness because I believe her I believe that this is You know, obviously we were we're talking about things like support groups and networks and online and sure I'm sure that whatever the mother had Had a community around it that Provided maybe respite care or something like that. But again, these are These are things that are available Somebody who's ill has doctors and doctors have access and so apparently those remedies had not been enough and Sometimes you're just stuck you're stuck for the basically the duration of this person's life And I at least that's what I was reading and it was it was it stayed with me. I probably got that six years ago Woody Guthrie and Lou Gehrig lived good lives in spite of ALS. Mozart died in his 30s Are we setting unreasonably high expectations? Waiting for someone else to answer Well, yes, but I just I think you have to look at the Again life involves suffering and I think we all have different thresholds but I think there are some basic thresholds for the amount of suffering we're willing to tolerate and and I think That's what most of this is about. It's like, okay, how can how can we minimize suffering? We can't eliminate it. And if you're asking to eliminate it, then you are being really unrealistic And in fact, you're denying yourself one of the great pleasures of life Which is seeing the comparison between your suffering and when you're not suffering and how can you enjoy this if you haven't had that? So I My my Puritan roots are showing But I do think that we will witness at times a level of suffering that that appears excessive and again this is totally subjective and it's it's it's based on Yours the society you grow up in I mean, I'm sure that our Our definition of unacceptable suffering is so much softer than one two hundred years ago And you know you keep going back and you just think of the amount of human suffering that led us to an industrialized society with With medicine and science in such a prominent role You know we're at a time where diseases aren't wiping out a Third of Europe so You know, I think we're realistic based on what we see around us and we Freak out accordingly Yeah, I don't think the objective here at least I would hope not is to somehow normalize the population I don't even know what that means Or how we would do it but difference is important in so many ways and teaches us so many things about About ourselves, but most many people with differences and there's a wide variety of them Don't feel that they suffer and many people with diseases that we consider as providers is pretty tough People live with with very high quality of life and when you interview them They often wouldn't change much about their life for exactly what you're saying is what they learn about suffering But there are plenty of things that we see in the genetics clinic where people suffer in ways that keep us awake at night Like your inquiry do that are just unimaginable and if we have a way to I mean All you have to do is spend any amount of time in a pediatric genetics clinic There are very sick children and children who die young and I don't think anybody wants to ever see that happen if that's Preventable, so I mean there are lines at which I think we can all as a society agree that we would like to do good With the things that we learn to I agree with those points. I mean I think that The people that were mentioned certainly did have productive lives and and I'm sure if they were here They would say that they enjoyed their lives whether they would choose to end to have the end point of their life the one that They were dealt with Is a different question I think and I Guess I Have the perhaps I have a luxury of being trained in pediatrics. There's as Barb mentioned There's just no question what our goal is which is to improve the quality of life of those patients Do dr. Beesiker or miss Hacks have some pertinent anecdotes relating to advising disclosing genetic information It's one of the most common questions we get in genetic counseling sessions, I think and it's one of my favorite because People often ask for advice and I ask them what they've been thinking and how they might do it in about half an hour Later they have this whole plan of what they're going to do and I haven't said anything and then they jump up and they hug me For my expertise and the truth is that they know what they're going to do It's a hard thing to do and it helps to have somebody to rehearse it with but most people have spent years thinking about how they're going to divulge something in their family to a sibling or a child and You know you can help them sort of Work through you know what the downsides are and what's holding them back and whether they this is the right time and why and what the setting might be but People do a very good job taking care of themselves and none of the rest of us know enough about their families To be able really to give them direct advice about that, but we can coach them to take good care of themselves Well, I just said don't without an invitation. I just think it's I again a real source of friction in Families and people who are close is when you cross that line between Your certainty that you needed to know and you project it as other another person's certainty That that person needs to know and I think that you have to be really really careful about How you use that information how you and again you have that conversation you have to know not just What you would want, but you have to understand your family member have to understand, you know To kinds of people which one which one is this and you also have to have a conversation to feel out The appropriateness of the conversation now Obviously if you have a child and you have something in your family, then you're gonna have to tell that child at some point Especially if again, you have their preventive measures You can do to preserve your health or if they need to know that they need to travel early and often, but you know, it's But with a peer, I think you have to be very careful not to over inform just because you wanted to know It's very hard in families where there are estranged family members or people who don't have much of a relationship and There's a risk identified for something like Regulatory cancer that people could be screened for It's it's understandable that they wouldn't want to contact people out of the blue and say oh by the way You're you may be at risk for this cancer very difficult thing to do But in many cases people often come to the decision that that's the right thing to do so that people are armed with Information that they can make their own personal choices about But that's not easy easy to do It's I would say it's surprising how different people view these issues differently and part of that difference Perhaps stems from lack of understanding, but then once you sort of done your very best to Bring their state of understanding to as an accurate level as possible They still have different views on what it means what they should do and and so it's very highly Individual and it also changes over time a person may have one to have a particular opinion at one point of time And then with the passage of time They have they see it in a different light so it's it's I think it's one one of the real fascinating parts about Doing this kind of work as to how how different people perceive it That's a good point too about the that you might change because I can think of you put yourself in the situation You say okay, would I want to know about the possibility of this illness at 22? I would probably say no, I don't want to know let me let me have this time And then now as I'm pushing 50 Now I'd want to know because there are certain things I'm going to want to get done You know it's and so that's very apt you have to think about the state of the people that you're talking to as well Anecdotally this is from an audience member who says I was a docent on the exhibit My experience the vast majority of visitors said they did not want to do testing of the docent group well over half That also might be I just think that's a fascinating issue when you get a room full of geneticists. That's a that's a fun fun conversation Despite the fact that I work on a genome sequencing study at the NIH where people are wildly enthusiastic to If I can grossly generalize to learn their results For a variety of different reasons. I don't have any interest in knowing my own genome sequence I never have as it veered it hasn't changed and it doesn't bother me that I do and it doesn't bother me that other people want to know I think you can be excited and interested in genomics and not necessarily Want to know everything? Is that on tape? Okay, you're on yeah, I'm not gonna add to that. Yeah I mean it I Haven't I certainly haven't done any of my own genetic testing, but I'm also You know It would be a curio for me now at this stage of my life It would be relevant perhaps to my kids, but I wouldn't do it without You know discussion with them. Well, that's that's that's an interesting point. We're talking about as As a theta complete when you know in something how do you say it? But but you can make an argument that even the decision to get tested is something that you have to think about in the context of The rest of your family, I mean because you might say I'm curious But then all of a sudden you're traded with this knowledge So you should almost ask whether they would want it They would want you to know I will say this I think one's Decisions will be different if it's sort of like a Just like well, would you would you want to have your genome sequenced for curiosity sake? Let's say that's one that's one level But if you're at risk or you're somebody in your family is at risk for a particular problem then you you know It's hard to really I think it's a different issue and what you think in a sort of non specific general way may be very different from what you Decide when you're under the gun basically For geneticists genetic information is Comprehensible for many lay people the results of genetic tests may be confusing even frightening The genetic tests become more common. Do you see the job of genetic counselor becoming more popular? Or should doctors be trained to perform the task of explaining the complicated results of a genetic test? Both Exactly that's exactly what I was thinking all of the above all of the above This is going to move out into mainstream medicine is already starting too So we got to get our primary care docs and we're comfortable with genetics and the studies even that have been Funded by our Institute have shown that primary care docs don't know a lot about genetics But I think we have to continue to try and help them And and the geneticists and genetic counselors will help with that transition It's going to be a mess for a while because there will be things that are hard to hard for the local docs to to interpret The genetic counselors are starting to think about workforce issues and different ways to train genetic counselors because we almost certainly Will need more of them. They may end up not looking exactly the same as they have for the past 35 40 years Because we have very small programs. We do very hands-on Training they're in the clinic at least a day a week all through their graduate education And it that makes it very time-intensive and so if we added a lot of Students it would put on most of the programs an undue burden for them to get clinical experience So we're starting to think about are there different ways to share what genetic counselors do and train people in different ways And it'll take some time to figure that out, but we're starting to look into it. It's been a fantastic career over the course of my career because things What we started with was pretty simple and we couldn't diagnose most of the people that we saw when we could it was a single gene mutation And it's gotten far more complicated So it's been stimulating and a way to sort of relearn as you go along you have to relearn your genetics the entire time It's been a very fun profession So I think it's a great thing for people to go into but I don't think it can stay the same In terms of training doctors are there specialties that are better out of than others? I'd like to weigh in on that In a general way the I think that Everyone who practices first of all genetics underlies all of medicine So whether you're a plastic surgeon or an internist or an obstetrician or psychiatrist or whatever you are as We go forward You're going to need to understand if you if your goal is to understand your patients Then you're going to need to understand genetics much more than days gone by so I think of genetics as something that should be Inculcated into the fiber of all physicians now that's going to take a while However Genetic counselors are fantastic They The reason being is that they have been they have training They understand the genetics, but they also have Training in areas about understanding people and how people make decisions and how people understand Information and good news and bad news and so forth and so on so at least at this stage of medicine boy, we need a lot more genetic counselors, I think and it also what I observe at our place is that Increasingly we are contacted with the Institute of genetic medicine are contacted to ask do we have a counselor that could come and work? Let's say a half a day a month in clinic X Because there's a few patients there that might need some genetic Counseling and so we always try to take advantage of that and what happens invariably 100% of the time is first of all The patients get better information That's number one number two while the counselors are sitting in the room waiting for the next patient. They educate the doctors and so it's a really potent educational activity and Usually two or three months down the road and they come back and they say we'd like that Could we increase that clinic that counselor in the clinic? A day a month and then it's a day a week and that sort of thing and so we As Barb indicated the train the number of counselors that are currently being trained I think are going to very shortly be or currently inadequate for the job at hand Now it comes comes to challenges you have to get reimbursement and and and all of those little mundane details about how to pay for them, but I Think they're incredibly valuable Somebody who loves the the science of genetics and how it works explaining it to other people and helping them make meaning out of it and Incorporating it into their lives. So it's a great combination of you know appreciation for a sort of basic science But what you care most about is how people process it and use it and apply it in their lives So most of our graduate students come into our program have strong background in molecular biology or genetics and also Psychology and we spend a lot of time I believe that actually it's harder to learn the counseling skills than it is the genetics if you already have a good Strong science background very hard to learn how to work with people and predict What they're going to need when they're making difficult decisions and live with difficult consequences. I live just last week a Student who's at the beginning of his his we have some boys in genetic counseling, although it's primarily women Of his second year he was presenting a case He saw over the summer where a father completely identified with him because he well He was assuming because he was the other male in the room And he had come in to find out if he was a BRCA to carrier because his mother was He was at 50% risk and he didn't want to be there. He hated physicians. He never wanted to go the clinic He was there because his wife told him he had to and he was learning about the chances that this could be passed on to his children And he just started to sob belly sob sob and sob and sob and he turns to the student who's not really in charge of the case And said if I had known this I never ever would have had these children to begin with and part of the students Reason for bringing up the case was how to take care of somebody who is regretting such a major life decision And part of my job is to help this student realize that what he regrets is that his children might be at risk He doesn't regret that he had his children So we have to learn how to be very sophisticated in hearing the meta message behind what people are saying He didn't mean literally he didn't Wish he had his children But he certainly didn't wish that he was in the situation that he had found himself in and that was even that was kind of hard for the Student to hear because the student helped so much Responsibility for the fact that this guy was sobbing and looking to him for comfort and he didn't know how to comfort him So this is part of the training is to deal with really difficult human emotions and difficult Situations and help him figure out if it was the best thing for him to go forward with testing What do you answer that question of what sort of person makes a good counselor? I Would say the ability to The ability to recognize in somebody else different ways of receiving news and I think I'd say In reading my mail over the years I found that the people who become most frustrated by others are the ones who see everything through their own framework They they understand they look at the world the world a certain way and just without even questioning it just assume others do the same and I think that's the person who won't make a good genetic counselor I mean, it's it's the one who can just step out of their own experience and and Be able to see that that every individual is going to have an individualized response to it and they've got to basically watch and You know take in the way the person is processing and then be with that person needs Really, it's almost the same thing that to make a really good parent. Actually, you know You've got to be the parent that your kids need not the one that you think is going to be the best parent, right? So for the genetic counselor, I would imagine with these incredibly difficult situations You've got to get over yourself enough to recognize what your Your patient to your client needs Will you do interviews for us? It's a great description So this is sort of the same question, but for you David you say that the field of medical genetics is changing rapidly What advice would you have for someone just beginning at their medical training training to work in a job? That doesn't really exist yet. Well I think that I mean, I I think the intersection of medicine and genetics is where it's happening right now and so if that is the kind of Area that is of interest to you then I would Get involved in it and go at it with a vengeance and learn as much as you can and on the one hand Be as good a doctor as you can be and on the other hand understand this and use it to give You know the most optimal care you can to your and informed care you can to your The people for whom you're responsible it seems like as Almost any job becomes more specialized ironically it means getting back to basics in terms of training Right. I mean it doesn't matter whether you're logging or vlogging or whatever you actually need to be a decent writer It doesn't matter if the genetic information is changing you need to be a good clinician and Right, but the originals I agree with that, but the original skills which is really Getting accumulating the information and accumulating it in a rigorous and thoughtful way It's just that now the information the quality of the information is Actually much better. That's not to say that the old information you still want that information But there's new opportunity for really high quality information and you want to get that information and make the best of it So There will be nothing I think in fact the contrary that will Replace I hope nothing that will ever replace a thoughtful and caring physician, it's just that To be a thoughtful and caring physician you're going to need this knowledge And bring it to bear on your patient's conditions When choosing a sperm or Ova donor how much screening is required How much screening is required as we move into this age of people choosing to have children on their own Back to what you mentioned earlier Carolyn about in your interest of avoiding your own genetics I don't know how much genetic information is available for donors So it depends on the center some of the centers do a lot of screening for Common mutations and that information available some of them take extensive medical histories and family histories on the donors Some of them do very little So it's a widely variable what information that you can get and it is one of the reasons that sometimes people go after identifying their own donors Because there are people they can sit down and talk to about their family history and their medical history and get that information I Know at our place. We do a much better job than we used to I think and in my earlier days, I had a child with PQU at our place and As we did the family history and so forth it turned out that there was a sperm donor and it the that had been set up at our clinic and what I discovered was as many this is decades ago, but what I discovered was that there was a woman that was sat at the desk and If you came in the office, you would say she was a secretary and She had a shoebox below her desk of index cards and she would look at the couple when they came in and then she'd go down under index cards and say this is a good one for you and the the the donor in this case was someone who had donated quite frequently and so and clearly was a carrier for PQU so I mean there's no way to know that ahead of time the Mistake if there was a mistake was to let you know to pick someone as the donor over and over again I Emphasize that was many many many years ago That's for the most part the cost of genome sequencing is no longer an issue or at least less of an issue And the evidence is already there that the benefit is immense and growing. What are the roadblocks preventing universal genome sequencing? I mean isn't the obstacle that some people don't want to know and is that a roadblock that we need to deal with? I mean, I think that's a that's a roadblock you leave in place Again unless unless preventive measures and treatments become so good that you can actually Act on the information, but even then I still think you can make it routine unless somebody checks the box It says yes, I think also despite the promise One thing that was illuminating for me. It's my husband and I a year ago visited the Sanger sequencing Center In the UK and they had done this fabulous thing So essentially everybody on this campus literally is working on sequencing in one shape or form But there's a small little sort of education Public Policy Center and they decided that it would be a really incredible Experience if they offered sequencing to everybody who worked there and they could go through the experience of having their genome sequence It was their choice. It was voluntary And then they would sit down together and talk about what it was like to get the results and many of the people we interviewed with when We were there had participated in this event and their overall conclusion was that it was absolutely the most boring information they'd ever done in their entire lives And that's because you know the amount of likelihood for any one individual to find out single gene mutations now at least the way it had been done for them That are useful to them is small for those people in which we find them. It's it can be very valuable information And so it's very hard to figure out when is the right time and when you know Are we really close to when it could be beneficial for people or are we still at a stage where we're mostly gonna get pretty boring information back And I don't think any of us has a really good crystal ball for that Yeah, I don't know when the time will be right but I do believe that we will see more and more of that and I think we have a lot left to learn if we if we could understand the Consequences of the sequence at every position in the genome right now We'd be doing it We have a lot left to learn and But Progress is moving at a reasonably rapid pace and its progress in many different areas It's not just the genome sequencing. It's hardcore biology Experimental biology of how to test and understand that information. It's how to keep track of this information how to go back and Reinterrogate the information because you think about it you do let's say you sequence someone's genome and you interpret it to the max today I can guarantee you that if you went back and reinterpreted it in a year from now There'd be stuff that you'd learn in the interim and and you would reinterpret it in a slightly More nuanced and more informed way and that's not the sort of standard way We do medical testing right now. We do a one-time kind of test and that's it so I Think I to me. I think that's the way we're going. It's just a question of how quickly we get there the other thing I would mention is that We're talking about doing genome sequencing to inform the health of the individual whose genome it is there's also an Activity that we really haven't mentioned yet, but what would be called what I might be called a preconceptual Genome testing let's say if not whole sequence a whole genome sequencing But preconceptual testing for carrier status for recessive very serious difficult to treat recessive disorders That have their onset in childhood and we can't do a good job at treating them And the way we discover couples that are at risk for those difficult Disorders is by them having a child with that difficult disorder now if we could And this is really I think much more in the future I mean in the in the present we could say just make a list and there are Groups that are already advocating this make a list of a number of disease gene that are very well worked out and the You get these diseases when your parents are asymptomatic carriers and they pass it on and you have a one-in-four risk for each pregnancy if we tested those parents preconceptually and Said we don't actually then require that they have a child with this disorder to know that they're at risk We say actually from the basis of the sequencing you're at risk for having your risk for having a child with this disorder is one in four and that information I Would think would have a substantial reduction would lead to a substantial reduction in those very thorny difficult to treat disorders This is essentially expanding the tastex the screening program to a larger number of difficult to treat disorders Do you think that Preneatal genetic diagnosis approaches an ethically sensitive line that approaches on eugenics How do we protect ourselves from assuming we know good and bad genes for example sickle trait protection from malaria? I would say that that kind of harkens back to Caroline's example earlier where if people are Affected or have had affected family members There are sort of impressions of what the condition the burden of the condition was Usually PGD is used in families where the parent is affected one of the parents is affected Doesn't want to pass on that condition to a child but wants to have a biological child And the thing I always I think PGD has offered options to families who didn't feel that they otherwise had options to have Biological children and so it could be seen as something that's been very important in people's lives But I always like to balance it with the fact that it is very expensive and it isn't always covered by insurance And so it is one of the areas where if you don't have money It is not available to you and I've had patients say very loudly to me Don't tell me that's a choice because for me it is absolutely not a choice And I think we need to always be keeping in mind when we herald up these new These new options that they're available for some people and PGD can be an incredible I've known people in Marfan families where parents are affected and they have biological children And they're selected not to have the gene for Marfan syndrome. So and there's many many many other examples Where they feel very happy to have biological children who were not affected Discuss the role of epigenetics in regards to various cancers Let's talk about epigenetics In in five words or less Well epigenetics is that Phenomenon where the expression of genes is regulated by modifications of the largely by modifications of the proteins coding the genes or modifications of the DNA that don't change the actual sequence and So just the way I like to think about it is that we all start life as a single cell and that single cell then must as The embryo develops must create a whole battery of cells some of which will be driven down the pathway of let's say being Heart muscle cells and some will be neurons and some will be blood cells They all have the same genetic information and yet once they've committed to being a heart cell when they divide They make two heart cells. They don't make a heart cell in a neuron or when neurons divide they make neurons so these are like modifications that are acquired as the individual develops that turn on certain sets of genes that makes certain cells do certain things and turn off other sets of genes so it's a Solution that Evolution has come up with for starting life as a single cell and ending up as a very complex Multicellular multi tissue Organism now Like every other biological process Epigenetics and the mechanisms by which those modifications are put in place Can sometimes go awry and when they go awry they usually lead to abnormalities of gene regulation and one area that that that we see medical consequences of that is in cancer I Think epigenetics has sort of been translated into the popular imagination as acquired traits that can then be passed on through your genetic Right, so the vast vast So the vast vast majority of epigenetic modifications are not passed on to the next generation Again think back to my example if if that happened You you couldn't really biology couldn't start with a single cell you have to have that Plasticity to make cells of many different kinds So if you think about it the way to do that is to erase all the epigenetics and then put it back again as the embryo develops Now it's an area of very intense interest right now because there are certain phenomenon that Suggest that sometimes the what what we call loosely the erasure of the epigenome and re-establishment of the epigenome may not occur 100% completely and some of the data that support that are these observations that have been in the epidemiology field for a long time that if you look at You can see transgenerational effects of let's say things like famines so a Group of people live through a famine They then two or three years later So that's not that the embryo experience the famine that just these people experience the famine Then they have children and then you look at the health outcomes of those children and you can see that there are certain conditions that are more that occur more frequently in such Children so it's hard to explain And we know it's not in the sequence per se so Then the question is is the epi are the epigenetic marks or the epigenome completely erased or are there some Parts of it that are not completely erased and that explains these phenomena And I would say that increasingly just in the last couple of I've been a person saying there's no evidence for that Are of no convincing evidence that but I must admit now I think there is some data that really looks pretty solid for that to me. I don't know what others Say, but that's what I think I Think we just have time for one final question here, and I'd like to hear from all of you on it Because I think you all have different takes the question is what are some tips regarding coping with uncertainty? Barbara let's start with you So I love this question one of my current research fascinations is perceptions of uncertainty We know a little bit from social science that our personalities have a lot to do with how we perceive and manage uncertainty There are people who are actually ambiguity averse So they they sort of stay away from Stay away from Things that have a lot of uncertainty. We also know that being an optimist Allows us to have greater tolerance for for uncertainty because we're more optimistic that the good will come of it on the other end And so it's a genetic counselor's job to get at Sort of how people manage and think about uncertainty and this has always been part of genetics from the very beginning We've often not been able to make a diagnosis or not been able to tell a family what the prognosis would be for their child or Even sometimes whether something's inherited in their family and and what the chances are it could happen again But it has never been more prevalent as it is today and certainly in genome sequencing So even when genome sequencing is done with very good indication for rare disease and can come up with a mutation that probably Explains the condition in a child It still has a lot of uncertain information that goes along with it And if there is another variant that's found that might be unrelated there's often uncertainty with that So we have to help prepare people for things that aren't necessarily related to why the test is done in the first place And our ability to interpret that information is wrought with uncertainty So the genetic counselors have to do a much better job at helping people really think through surprising information and information that may not come with a very full Explanation and so there's no magic answer to that, but I do think it's a responsibility the providers to help people sort through How they manage uncertainty in their lives in general one of my graduates to do and sort of said it clearly all of life is Uncertained so we we have to come up with our own models of how we manage that uncertainty But there are clearly some people for whom that really they really want to avoid uncertainty and in those cases It may be a good idea not to get themselves in a situation where there's a lot of it So I think That obviously to be alive is to deal with uncertainty because we all have uncertainties and different people respond to it in different ways The one the one thing that I usually say to patients where the where the uncertainty in the ambiguity comes down to some kind of medical issue is that I Think it's very helpful to let them know before whatever you're doing And it may be a whole genome sequence or it may be a simple blood test that you know Some of the information some the information may come back And I may be able to give you a very clear interpretation of the significance of this information nation or it may come back and And I won't be able to tell you with any certainty what it means That's that's something to be aware of before we do the test but when when they're when you accumulate the information and There's some degree of uncertainty in terms of its significance In a health matter what I like to say to the family is well, let's do what we can to deal with the To to eliminate as much of the uncertainty as possible and then we will in the end get down to some NIDIS of sort of Uncertainty that we can't reduce anymore, but at least let's ask ourselves Is there anything we could do to eliminate at least parts of it and that may be additional testing it may be tailored childhood education or Hearing test or it could be any number of things but rather than you know If it's something that we can actually do something about let's get that taken care of and then we'll deal with a fundamental core of uncertainty But I going back to your graduate student The all life is uncertain, you know, it's just I think that Really It's a it's a three-part process and I think the first one because I tend to be meaner is that you just have to poke through the idea that we are in control of anything and I just You just I have as I get old and cranky. I lose patience with people who think that they have a Say in what happens. I mean in what comes and certainly you can stockpile water in case your water goes out you know or something but but I Think it's you know the what was it the uncertainty a verse. What was it ambiguity a verse? Yes I mean I I call it controlling and and Stop it Because and again first is to tear down the illusion that you have say in many things You get to choose what you have for breakfast. Maybe but beyond that it's it's touch-and-go and then But then I think you also have to bring in of course once you've reduced all that to rubble Then you bring in the optimism you say okay now look at your history and look at the number of times that uncertainty like Your inability to control the outcome or your inability to foresee the outcome Actually resulted in something great that you never could have expected and that you never would have driven toward on Your own and I think when you start to understand that I Mean maybe I just live a particularly random and accidental life and that's entirely possible But when I do that exercise and I look back at all the things that I hold most dear almost all of them were the byproduct of Something going horribly wrong somewhere else and and at the time of course during that horrible wrong It seems like nothing good can will ever happen again But often again you find you find some of the best things when you get knocked off the road You find a beautiful path and so I think that's you know, that's part two and because I've Gone on too long in part two. I don't remember part three So but it's also I think That's right Not where you stole this part of the answer the small steps the things you can control because you can often do productive things and you can do calming things and I think usually the two of them are combined and If you can come up with a process that you can do and this could be anything this could be medical This could be preventive medicine. This could be figuring out treatment options This could have nothing to do with medicine. It could just simply be okay You know what I'm going to go back to a pencil and paper balancing my checkbook because then I don't lose sleep over money I mean it can be It can be as minor and as weird or as to anybody else completely ineffectual But if it comes you and if it feels like you're getting somewhere that isn't I find that actually is the most productive way to Deal with uncertainties like because I've got my little I can control this You know that what I have for breakfast and so I am going to you know, I'm gonna work the hell out of it I'm gonna do it great. I'm gonna rock breakfast. You know what I mean? And so that That becomes as this was sort of three parts of in in a way that's all of course going back to the first one I'm going back to my innate cruelty. It's really delusional basically you're constructing a delusion of Optimism and control but I'm fine with it It was a great three-part summary One of your parts I think was an important thing that I failed to highlight earlier which is in most of the families that we deal with even when we see Great sadness and suffering and we certainly see a lot of families who have Lost that we wish we could take away for them people are incredibly resilient and what we see more often is hope and Even in very serious diseases like Duchenne muscular dystrophy We've just finished a study that shows that parents who are enrolling their children in early phase trials can differentiate their expectation That their child is likely not to get better. These are early phase trials They're just really safety trials and they honor and they understand that but they still hope that their child will benefit And they can distinguish those two things and they sort of say We understand this leave us alone because we need our hope and it doesn't mean that we don't understand what a trial is about We've consented to it. We've signed on uncertainty often breeds unexpected wonderful things and the families we deal with tell us that Over and over again. This has been the hardest thing. I was ever dealt I wouldn't change anything for it and I'm a different person as a result of it and they mean it very Sincerely and I think we do need to remind all of us of that and you did that. Thank you That's a wonderful place to end Barbara B. Sicker David Valley and Carolyn Hacks. Thank you all so much Thank you all for your excellent excellent questions to close the program I'd like to invite Maria Friar the president of the foundation for the National Institutes of Health Well my goodness, I don't know about you, but it made me think a lot of and Ending with hope. I think that's absolutely fantastic I think we all a round of applause for Rebecca who did a fabulous To all our presenters Carolyn and David and Barbara Thank you a lot of good thinking and I still want that world 20 years from now when we can tackle all of these diseases I think it's going to be pretty awesome And frankly we've had an awesome audience and the questions have been truly remarkable and thought-provoking and thank you all for For being here. Thank you all. This has been a wonderful end of what is still continued journey to have this exhibit as you all know will go to different cities around the country and We are proud and pleased to continue this partnership with the museum the National Human Genome Research Institute the foundation for NIH and all of our sponsors and our funders So thank you all very much and we continue. This is a continuing exhibit We continue to raise funds to make sure that we have education and public programming around These different places of the exhibit. So thank you very much. Good night safe home