Designer Genes

00:00:22 recording in progress good afternoon on behalf of edinburgh session director of helix the helix center i welcome you to the first of our season this second zoom year in our covert period we have gone ahead this year and

00:00:54 scheduled some marvelous programs that i just want to mention to you so you can mark them down in february february 26th we'll be having one on kinetic economics which will discuss what how we are affected in an international global trade world that when goods can't move march 12th will have a program on psychedelics april 30th on metaphysics

00:01:26 and may 4th on flourishing versus languishing so just consider us on those dates and for today we're very happy to have you join us for designer jeans as in g-e-n-e-s and we have a wonderful group who are going to be with us today and um let me introduce a few of you we're having a little bit

00:01:58 of problem with with the zoom but some you may hear phoning in and some are present henry greeley is the edelman johnson professor of law at the genetic center at the center for law and biosciences at stanford he specializes in ethical legal and social issues arising from the biosciences and you can read online all of his incredible distinguished accomplishments

00:02:32 robert klitzman we are hoping will be able to join us he's professor of psychiatry at the college of physicians and surgeons and the joseph mayellman school of public health and the director of the online and in-person bioethics masters and certificate program at columbia university fraud rabitski here she is is a full professor at the bioethics program at the school of public health

00:03:04 university of montreal and senior lecturer on global health and social medicine at harvard medical school her research covers a variety of topics such as public funding of introvert ivf the use of surplus frozen embryos posthumous reproduction pre-implantation genetic diagnosis and many other related focuses and nathaniel comfort is here as professor of history of

00:03:36 medicine at johns hopkins his interest lies in the history of genetics eugenics genomics and biomedicine as well as bioethics and you can read of his other accomplishments and publications on the website so i welcome you all we've we've had a little bit of zoom entanglement and so we hope the difficulties are over and from here on in it will be very compelling

00:04:06 so jerry horowitz who is the co-director of the helix center will now moderate thank you jerry and jerry is from columbia university professor of psychiatry thank you beverly this is very exciting made even more exciting by the late uh appearance of two of our esteemed panelists this is great thank thank you to miguel and to alex for getting this all done just at the last moment anyway i i'm

00:04:36 eager to let the panelists begin their conversation um on today's topic i want to point out that questions can be submitted on zoom and also um through youtube that will be collected by our administrator alex and he will read them out or read out a selection of them at the end of our conversation and so just bear in mind that they will be collated and referred to later anyway with no further ado hank greeley

00:05:07 in advance agreed to sort of start things off and give us a sort of an overview of this topic and then we'll see how the conversation proceeds from there hank okay well thank you happy to be here wherever here is in cyberspace uh it was almost exactly three years ago three years and a week ago when i was shocked one sunday evening by an email from a friend the title of which was crispr babies he was reporting on

00:05:38 the then leaked report that a giant chinese scientist named who john cue or something close to that had announced the birth of twin girls whose embryos had been edited using a process called crispr clustered regularly interspaced short palindromic repeats which is a real good reason to use the acronym and just call it crispr and had been born that year this caused a huge uproar

00:06:09 ultimately i think uh dr hu expected to be hailed as a hero ended up getting denounced as a villain and ultimately sentenced to three years in prison in china but that's the that's the most recent of many interesting things that have gone on with human reproduction at the intersection of human reproduction and genetics we can go back 50 years or so to when we started doing prenatal genetic testing through a process called amniocentesis

00:06:40 after the birth of louise roberts the the first ivf baby we started having more possibilities and we can go back 30 years to the birth of the first child who was born after a procedure called pre-implantation genetic diagnosis where embryos created through ivf so outside the woman's body are genetically tested that child is 31 years old i had the good fortune of talking to the

00:07:11 reproductive endocrinologist who was involved in her birth and he's so proud of the fact that she's now a scientist i keep telling him it didn't have anything to do with him or his genes and he just smiles and now things have gotten more complicated we have embryo selection through pgd we have fetal selection through prenatal diagnosis we have embryo selection through pre-implantation genetic diagnosis which i'm just going to call pgd and starting three years ago we have embryo editing

00:07:42 through crispr editing of embryos with at least three cases doctor hood did at least dr who's work led to the birth of at least three babies before he was stopped and ultimately imprisoned these options are continuing they're growing they're new possibilities like mitochondrial replacement therapy and there are new possibilities coming from the genetics world including some new efforts to try to figure out more meaning from genes particularly a process that is quite controversial a

00:08:12 procedure that's quite controversial called probabilistic risk scores so all of these are going on the one thing that i think is clear is that at least in places and for people with access to good health care modern health care and money to pay for it genetics is playing an increasing role in how we're having our babies so i think between prenatal diagnosis

00:08:44 pre-implantation genetic diagnosis and embryo editing those are the three main steps that we need to think about in conjunction with how much or how little we know about what the dna sequences actually mean and i'll stop there excellent thank you hank i think you've raised so many interesting and i i would dare say these are all touching on our sort of uh ethical sense each one of them i wonder if we could uh and i also just i just

00:09:16 want to add very quickly i'm always i want to try to keep you honest in this sense i've always load the expression you know these are complex moral issues because i find that sort of as a hand-waving gesture i'd like to get down more into nitty-gritty of how they are morally complex so i invite any of the rest of the panelists to start in with any one of these topics and let's see how far we can go with it yeah so uh first of all thank you again to the organizers for planning this and it's great to see my colleagues and have a chance to interact with them this afternoon on this very important topic

00:09:47 so i'm honored to be here and thank you again and hank thank you for laying out uh some of the background in the issues uh i think there's a few uh things i should say one is just as a little bit of background uh so we don't demonize the technology entirely the ability to edit genes i should say does offer potential benefits for living people in other words that we there are now clinical trials being done of gene therapies and my scientists friends who were uh work on this are uh

00:10:20 emphasized that uh we don't wanna uh shut down all research using this crispr technology that hank so eloquently presented but it's important that is in other words for instance for alzheimer's disease for people who are already born with alzheimer's they have the genes that they're going to have there are the potentials to use crispr these so-called sort of genetic scissors to cut out bad genes for instance and so there's a potential to use this for disease that could benefit large numbers

00:10:50 of people also for improving food improving crops livestock making food that's resistant to pests for instance so just as a background um uh i think it's important to mention that the area i think where we're all concerned of course is using these technologies to alter future human beings that is to uh take when uh uh sperm meets egg and forms an embryo and eventually would form uh two cells and fourth and eight and eventually become one of us uh when

00:11:21 it's still at the one embryo stage we can go into hank was saying and alter the genes uh and uh this is what dr her uh did uh and i think uh as hank and my fellow panelists know uh the problem is it's not quite ready for prime time in addition to all the other ethical problems so and answer your question there's a lot of risks involved basically uh is number one so doctor who apparently took out more dna than he wanted to uh and so there are so-called off-target effects i may want to just take out this

00:11:53 much dna and end up taking that much also genes probably have multiple functions in the body so one gene he actually wanted to disable the so-called ccr5 gene that would allow hiv to get into cells so he disabled that gene but by disabling that gene uh the child has a higher risk of having other viruses uh influenza virus west nile virus getting into cells uh and uh in

00:12:25 addition uh uh he took out too much and genes made that one gene may do other things as well that we're not even aware of yet so there's a lot of risks involved uh and a problem is that uh we may we now live in a globalized world and so even though there have been attempts in the u.s and in western europe to come up with guidelines by the national academy of sciences and the uh royal academy of science the royal scientific society association in

00:12:55 great britain it's not clear what kind of enforcement ability if any or what kind of power such guidelines put out by such international organizations will have clearly we need to try to have such uh uh guidelines but uh the un of course doesn't do is very important doesn't manage to prevent all the wars that go on and so the possibility of a rogue sign just like doctor who uh in

00:13:25 fill in the blank of whatever country outside western europe you want to think of russia north korea might go ahead and use this so there are questions about uh international uh um uh oversight and ability to sort of control what's going on and then and lastly i'll just make uh the point that as uh hank really mentioned uh with uh pre-implantation genetic diagnosis uh we in the u.s have a basically unregulated assisted reproductive technology industry it's a multi-billion

00:13:56 dollar industry that uh allows many people to have children who are infertile but these technologies are being used to for instance give people just a boy child if they want a boy child or uh we're now being able to prevent the breast cancer mutation other mutations that we know about from being transmitted to future generations uh but this is a technology that wealthy people can use but not poor people so there are questions of justice that we're uh

00:14:27 beginning and will begin to see diseases like breast cancer increasingly become diseases of the poor because wealthy people as we go into the future will be able to afford to prevent such diseases from being transmitted that those genes so just to highlight some of the sort of ethical complexities involved sort of drilling down a little bit so i think it's great to have this discussion because i think awareness public awareness of these issues is really crucial right bardeet you had something to say yeah because the points i wanted to make

00:14:58 uh follow uh beautifully from exactly the points robert just made which are that regardless of which technology we're using regardless of whether we're editing embryos in vitro or selecting embryos in vitro or selecting against certain fetuses through prenatal testing um i think that one of the key ethical challenges is why are we doing that what is it that we're keeping and what is it that we're rejecting from the human gene pool

00:15:31 uh or what kinds of individuals we would like to welcome into our future society and uh what kind of individuals were practically avoiding having so i want to uh offer my comments through a critique of the title of this event designer genes because i get phone calls from journalists every week uh to talk about these technologies to talk about the ethical and social dimensions of these technologies and what do they all want to talk about

00:16:03 designer babies yeah i don't like designers in any field of life uh but when you take the concept of designer and attach it to the baby i think this is dangerous because i think it gets a lot of public attention and a lot of our social discourse and social debate that we should have urgently into the wrong direction uh what do i mean everybody's scared of having um so here's what's going on in the media right in the public

00:16:33 imagination we're gonna have super intelligent babies we're going to have tall babies we're going to have blue eyes and blond hair which always take offense because you know me why nobody wants to have um we're scared of enhancement we're scared of sort of selecting traits of future people in areas that have nothing to do with all the good stuff robert talked about which is avoiding disease and preventing

00:17:03 suffering and preventing early death we're afraid of going in the direction of sort of designing human beings but i think it's misguided to dedicate so much attention to it because we scientifically still don't know how to do that those traits that everybody's so worried about intelligence height sexual orientation uh they're controlled by many genes they're controlled by interactions between genes and they're controlled by the interactions between our genomes and the environment through epigenetics and

00:17:33 other processes even if we wanted to create a beautiful basketball player we don't know how to do that at the same time we're spending so much energy discussing this instead of discussing the really urgent question which is within the um the area of medical uses what is justified so all these um declarations and policy statements that robert just mentioned tell us that if we ever move forward responsibly with crispr that hank explained we should

00:18:06 only do it for serious genetic diseases and nobody to date has defined what is a serious genetic disease and i want the public conversation to be on that because that is the question we're facing right now he gave the twins resistance to the hiv virus is that serious enough to justify putting them at risk another russian scientist now wants to edit out the gene that causes hereditary deafness is that serious enough how do

00:18:39 we understand as a society what is a serious disease that we all agree we'd rather not see in our children we haven't actually had the deep conversation on that and that conversation is urgent whereas those designer genes uh are definitely not urgent because we don't know how to do it now and potentially we'll never know how to do it so these are my two cents well you know you might be unhappy to understand that an alternative title for our talk today was going to be cosmetic uh

00:19:10 genetics uh yeah i know it's a pl it was intended to be a slightly polemical title to gather in the both the serious part of this problem that you're highlighting really perfectly well and the fact that some of it gets appropriated for other uses um nathaniel i wonder if you have any comments on that or you want what did you want to add sure thank you first uh hello to everyone it's wonderful to be here um and actually i can follow on uh vardit's

00:19:41 really thoughtful uh commentary with a with a couple of things bringing a little bit of a historical perspective to to the conversation um i completely agree um with the all the remarks so far that uh crispr has many important uh medical medical applications and has already had some some real medical benefits it became almost almost overnight it became a standard workhorse laboratory technique you know just basic research

00:20:13 everybody was doing it it's cheap it's easy so yeah we need to be sure to differentiate between the um the the really kind of work a day use of of crispr just in doing it all kinds of biomedical laboratory research and these kinds of sci-fi scenarios and and um and and huge ethical issues uh that are raised with things like um prenatal genetic diagnosis and so forth um

00:20:43 i guess i would say two things uh in response to uh varnite one is the um she's absolutely right of course that we have no idea how to um how to create uh how to design a smarter baby or a taller baby or even uh estimates now range about out of sort of 20 to 25 000 human genes um

00:21:14 the current estimates i've seen are that about on the order of a thousand of those genes one in you know about one in 20 genes uh influences intelligence somehow uh it's not clear that the separation of genes and environment is actually how biology works and so there's a risk one of the risks that i see looking at this in a long-term historical point

00:21:44 of view over a couple of centuries is the is the public effects of um the the social importance of of these anxieties that we're talking about the fact that we cannot do it but people believe that we can um has that has social and ethical ramifications itself right and um so these are questions of um accurate science communication of myth busting you know and and de-sensationalizing

00:22:18 the uh the science where we can um the i guess the other thing i could say right right now in the immediate response is um that the i agree uh that that we should be the the important aspects of um if we're going to edit embryos we should be thinking about what diseases we can address profitably

00:22:48 you know most and and let's face it most of those diseases if we're talking about um embryos and uh and future human beings as hank started us with you know most of those can be effectively and easily prevented with a prenatal genetic diagnosis and uh and abortion right and so in most cases it's probably not going to be practical to go in and just you know oh i love this embryo all of it it's got

00:23:20 all the right genes except for that one snip that i want to fix it's not uh it doesn't it doesn't work like that um the other thing is but the the line i think you know most people many people anyway are uncomfortable with the idea of enhancement but the uh and and our fa and most people are in favor of the idea of using the techniques to prevent disease but the problem is the line between therapy and enhancement is really blurry

00:23:53 um i like to use the example of of human growth hormone right which can be used therapeutically if uh if someone is considered to be a extremely short stature now one has to note that in some cases uh conditions like achondroplasia uh chondroplastic dwarfism uh can like like deafness may

00:24:26 be actually a desirable trait in in certain communities so we have to keep that in mind but if you are thinking of a child as you know sort of pathologically short okay you can say that's a therapeutic application of human growth hormone then what if the child is is you know quite below normal in the normal range but the very bottom end well you could say there are you know there there are social costs to that and i would like to give my baby uh

00:24:57 you know every advantage to succeed every chance to succeed uh so i'd like to to be you know normal headache or tire taller or her and you know then you're in gray area that's a it's a different kind of therapy surely right not so much medical as psychological and social and you know so where exactly how much is too much growth hormone is are you then gonna say to the to the parent whose child is uh is gonna be abnormal height that i wanna give my child every advantage and you

00:25:28 know um uh like um julian savolieski says the you know appropriative beneficence we have a responsibility to provide our children with the best genetic environments that we can where do you draw that line how much growth hormone where does the growth hormone become go from therapeutic to enhanced to enhancement so these are so the fuzzy lines between some of these categories is also where some of the big

00:26:00 ethical issues um really you know that's really where the the rubber meets the road and we're going to have to have i think really serious conversations to hash these things out pretty much on a case-by-case basis in many cases so i'd like to pick up on a couple of things from both vardid and nathaniel um bardic said something that i say all the time even though i'm about to criticize it which is we need to decide we need to figure out we need to do this we need to

00:26:30 do that but of course we also have to ask who is the we is that we individual parents and if it's individual parents is it individual parents of normal height or is it individual parents where both parents have achondroplasia and are very are little people is it individual parents with good hearing or is it individual parents who are deaf and if it's not individual parents but it's society as a whole how do we do that vard it's actually i mean i think you're absolutely right that this issue of

00:27:01 serious disease versus non-serious disease on the one hand or big risk versus acceptable risk unacceptable versus acceptable risk just as nathaniel is right that the line between enhancement and treatment gets very blurry by the way on the height issue the current medical standard is two standard deviations below the mean so basically if you're in the lowest five perce five percentile of height you can get treated with human growth hormone regardless of whether we know

00:27:32 why you're so short but that's obviously not a really compelling number they picked it because five is a nice number right so we do see places that have tried to do go in a more organized way the uk has a very complex system of regulation involving something called the human fertilization and embryology authority the hfea because nothing in this discourse can avoid acronyms everything's acronyms here

00:28:03 and the hfea actually decides what diseases you can do pre-implantation genetic diagnosis for and which diseases you can't and if you can't if they decide you can't what happens in many cases at least to parents with enough money is they come to the u.s to get it done because the u.s has heard it said has no regulation on what can be done it's a matter of choice between the individual ivf clinic and the parents the parents with money at least and so you know mardi i think is is

00:28:35 rightly focusing on what both varda and nathaniel are talking about treatment versus enhancement in the us now there is no such enforceable line and if you can find a clinic that is willing to do something that's enhancing now granted there's very little we can do and almost nothing legitimately that we can do with respect to intelligence or sports ability or music ability or math ability or all those we probably can figure out light eyes versus dark ice and light hair versus dark hair

00:29:06 but which versions of light hair or dark hair or light eyes or dark eyes we can't figure out in the u.s all you need is parents money and a clinic that's willing to try and that's i think something the u.s at a social and governmental level needs to address i can pick up on a few things from there i'm sorry okay so he got her hand up first actually okay i love how this conversation is flowing so directly following up on hank's last

00:29:38 words who the we is is obviously the question um so we decided we and my research team decided to gather one possible group of we we gathered experts from various disciplines and also people who live with genetic conditions and we ask them to discuss what serious is to them and we discovered something very interesting at the level of the individual conversation conversations for example

00:30:10 that patients or parents are having with clinicians about prenatal testing about what justifies going through ivf in order to do in order to test embryos people resist hard definitions they want the understanding of sirius to remain something very personal very subjective uh because you know we have different uh we come with different stories to the to these decisions um for example if

00:30:40 several women in the family died of breast cancer having an embryo with increased risk of this disease even though it's later in life even though it's just a risk uh you know you have resistance to that because you're traumatized by what you've lived whereas for another person who's not familiar with the disease oh it's just risk it's not necessarily that this child will have it and in any case it's going to be much later in life so you know it's just not that threatening so the understanding of what is serious

00:31:12 is contextualized is cultural is personal subjective and people want it to remain that way they don't want the government to tell them that this does not deserve to be screened because some you know political body decided it's not serious enough however there's another context where we have to make decisions as a society what will be allowed or banned what will be offered to patients or not mentioned what will be funded or people will have

00:31:43 to pay out of pocket these are decisions we make as a society and for these decisions we must come to an agreement even on questions that are so complicated that maybe at some level they should be left to individual decision making so i just want to add that layer of layer of complexity to our conversation i can just add a few points and again great conversation so in answer to vardy's earlier comments about why such attention to iq and for which diseases um uh first of

00:32:14 all it was quite interesting that the national academy of science with the royal society addressed this issue of which diseases uh they thought once uh crispr for embryos is safe enough it should be used and they actually came up with several categories so they tried to define this but i think the ways they did it themselves raised questions so they said uh well if both parents or one of the parents has both genes that are autosomal dominant

00:32:46 as they say for serious condition like huntington's disease so if someone had both parents with huntington's disease which is a fatal disease that for which there's a very predictive gene they thought that uh and uh for for in that situation uh it would be permissible they thought that if uh both parents were uh quote homozygous for a recessive disease so both parents had sickle cell disease or both parents had cystic fibrosis then it would be acceptable the problem is and they gave another example

00:33:18 as well which is if both parents were homozygous for different diseases that were autosomal dominant so both parents had genes for uh early onset alzheimer's the problem is though that if both parents these are extremely extremely rare conditions but i think the reason they were putting them forward is because there's a certain technological imperative so i think it's not only the media and the public that's interested in how do we enhance children like uh how do we increase iq but i might i'm concerned that scientists themselves or

00:33:50 that there are some scientists and researchers at least who feel we have this technology let's use it this is what we've done in the past we have technology and so let's go ahead and use it so for instance with those cases if both parents have huntington's disease they're probably not going to raise the kids well which has raised another question they probably won't live to reproductive age if they have huntington's from both their parents uh same if they have both parents have sickle cell again it may be hard for them to reach reproductive age so these

00:34:20 are very hypothetical situations but the fact that they were put forth by the national academy of science and the raw society i think shows that there's pressure to leave the door open for scientific research in this area and i think that raises ethical questions itself i'll just say a few of the things which is one is uh who the we is at least the united states uh the example here i think is that we is who's gonna pay for it right so in this country i think uh the art the assisted reproductive

00:34:51 technology industry as i mentioned is seen as the wild west uh because it's paid for mostly out of pocket so if you can afford to uh uh uh you know pay to have the breast cancer mutation look for in your embryos and those embryos that have it screened out you get to do it and again this raises questions of justice etc uh similarly there are other uh uh in in western europe a pgd is banned in some countries or it's very limited which cases can be uh covered because the

00:35:22 national health insurance is covering it and so they have more of a say i think in what ends up happening uh so uh again just a couple of other thoughts to throw in the conversation uh i i think again the the the the fact that the uh in this country the assisted reproductive technology is monitored by the american society for reproductive medicine which is a guild uh of those doctors uh they come up they have an ethics committee they come up with guidelines they're not always followed one problem in the u.s is that

00:35:53 if we did have guidelines and regulations there's concern among many researchers that the issues would be taken over by the religious right and by pro-lifers so they may say for instance you can't do any pgd or they may get involved in other ways in preventing either infertile people from uh accessing these treatments or from pgd being used for getting rid of uh diseases someone has huntington's disease and they want to screen out the embryos there may be legitimate uses of

00:36:24 pgd which may they then be shut down as well so we're living in a precarious political time in some ways for the the political body of our country to take these issues on one quick note on what robert just said in the u.s you also have the issue of is it a federal question or is this state by state question and this kind of regulation typically is state by state imagine you could probably construct a constitutional federal statute though it might be a bit

00:36:55 of a stretch i think you'd have to use the interstate commerce clause but if you think of 50 states each with their own different regulatory schemes and the likelihood that mississippi or south dakota would have a different scheme from new york or california it gets gets very complicated very fast just quickly we already have that with the problem of gestational surrogacy so people quote renting wounds as it said uh california has a large industry new york just voted to do our governor

00:37:26 cuomo the late governor for the our recent governor former governor of hobo recently uh put it in place but it varies too state by state by state in all kinds of ways that lead to complexities people having children born in other states etc i think you've certainly been declared politically dead not legally dead right sorry about that i wonder if you would we would all agree and please don't if you don't uh that in many of these instances there's a a bit of an arbitrary there needs to be a certain amount of

00:37:56 arbitrariness and where the cutoff may be maybe you kind of returned it over and over again and um i think that doesn't necessarily mean certain bodies shouldn't try to create a cut off but that perhaps it should be something that's open to revision over time what have you i don't know what you all think about that if that's true or not i'm willing to jump in i mean i i think this follows from nathaniel was saying that often in medicine we think of

00:38:27 diagnostic categories as being very clear but in fact to a certain degree we construct these notions uh what is serious disease uh even what are the boundaries of disease one is someone uh everyone faces some anxiety and depression at some point in their life but one is someone quote unquote clinically depressed or need treatment for anxiety etc and so uh nature is complicated but we try to apply these rigid categories and in some ways uh it may not always be

00:38:57 possible to do so it was raised that in the case of the babies in china that he got involved with that of course it was an attempt to prevent hiv infectivity in those children but many of the critics said well there's uh triple antiretroviral therapies and this is not a death sentence as it had been many many years ago i wonder if the response would have been different if hiv was still the sort of fatal illness it was you know 25 years ago

00:39:29 um i think it's fascinating to see how the ethical discussion reflection and even guidelines and recommendations change over time exactly gerald in response to what you said we learn more about the technologies our social perceptions of what justifies certain interventions changes for example because we didn't have a treatment and now we do or because we realize that something is actually more detrimental than we thought um and it's

00:39:59 just an opportunity to kind of plug in another you know more general point which is that the bioethical conversations that we're having sometimes the public expects us as bioethicists to make arguments come up with a position tell everybody what to do you know whether it's individual patients or governments and be done with it but we roll with the punches and the punches again can be um the evolution of science and what we know

00:40:30 uh the accumulation of data and the evolution of social values and norms look at the end-of-life debates uh that uh all countries are going through over the past decades and how we change legislation as our social values change um so i think when it comes to these uh questions that are inherently societal what the next generation is going to look like is of course a personal question what child am i going to raise but it's inherently a social question of the face of future society

00:41:02 we have to also be responsive to the science and to where social values are at at a given time and when i look at just the last six years of declarations and statements on crispr you see that evolution happening right before your eyes in 2015 there was an international summit and the general vibe was definitely no not ready dangerous stay away only four or five years later the the you know the the last thing off the press is talking about a responsible

00:41:34 translational pathway all of a sudden it's kind of obvious that we're going to translate this into the clinic but how do we do it responsibly um so we're seeing this evolution before our eyes and what i'm struggling with because i do a lot of media is how to explain to the public that the fact bioethics you know shifts and changes and devolves is not because we're unreliable or capricious or we don't know what we're talking about it's because we're taking into account all these changing factors

00:42:06 of course during covid it was the big challenge one day public health tells you masks the next day tells you you know we saw recommendations change and we saw the bioethical debate change because we learned more about the virus and it's the same in this arena we learn more about genetics the public becomes better informed and educated the conversation changes the bio ethics uh evolves and it's not easy to explain the sort of um the backstory of how our

00:42:36 conversations leading to all these international guidelines and statements how these are happening and what they're informed by it's a very complex process but i think it's critically important that the public understands why we're sometimes shifting our positions towards more permissive or less permissive so two things from what verdict just said and one has to do with the role of bioethicists some people look to bioethics for advice some people hate bioethicists because they view them as

00:43:06 acting like black robed judges who say this is good no you go to hell in fact i think you get three bioethicists talking about any issue and you end up with five different positions so the we in bioethics is not a unified we as well but with respect to gene human germline genome editing which is the fancy term for what her did so it's editing human genes in a way that can be passed on to future generations that's why it's

00:43:37 different from just using gene therapy on me to fix the disease i've got unless it gets into my sperm and at this point two thirty year old kids ago and a vasectomy even then it wouldn't matter for me but unless it gets into somebody's sperm or eggs it's not going to affect it's not going to change the genes of the next generation so it's the germline the eggs and sperm that make it that have raised this issue i was part of some of those groups in 2015.

00:44:09 everybody agreed then that this was not ready for prime time because it was not proven safe and effective and that we haven't really talked about of all the ethical issues i think the least controversial and the most important is it's unethical to do something that's unreasonably unsafe or to sell people something that's unreasonably ineffective safety and efficacy we think of as fda and not really ethical but they're they're powerful powerful ethical issues

00:44:41 and back in 2015 everybody agreed that this wasn't safe and effective hadn't been shown safe and effective some people said if it is unsafe and effective there may be some times in which it could be used and that's where robert's point about the particular diseases that this commission picked out they were picking those up because those were things that pre-implantation genetic diagnosis couldn't fix but maybe this could so some people say if it's safe and effective there are some ethical uses

00:45:11 other people say even if it's safe and effective we should never use it because the germline is a line we shouldn't cross messing with our future generations is something we shouldn't do that distinction remains but it's become a little more exacerbated i think the latest commission and the idea that we're moving to how to do it responsibly those are the people who say if it's proven safe and effective but it hasn't yet been proven safe and effective here are some ways it could be used there's still the whole there's a large

00:45:42 set of people in bioethics and otherwise who say it should never be used at all for any reason so the i think the the discussion has evolved but what was a more obscure and more nascent division six years ago is becoming a little clearer now between those who say never and those who say well maybe under some circumstances but right now everybody almost everybody says it's not proven safe and effective

00:46:13 it's not ready for prime time you shouldn't try to make babies in something that's this in a manner that is this risky i would just say i'm sorry robert i think nathaniel had a point you wanted to make oh i was just going to say that the points that hank just made are super important i'm really glad you you raised them so so clearly and articulately um i would say that it's important to remember that safety and efficacy aren't the only two ethical

00:46:43 issues that are involved here and i think sometimes in discussing these issues with people members of the scientific community um the ethical discussions sort of end there once it's safe and effective then you know then it's out of our hands you guys deal with it and there are there are other important ethical questions to keep in mind while we're thinking about safety and efficacy as well um for example consensus you know what

00:47:14 what is there you know how do we decide that if there's a social consensus that this kind of thing should be allowed the fda ultimately is supposed to go supposed to go on along by the will of the the people we have to we're going to have to reconcile with this right um and um that raises the the question that actually comes back to some of uh variety's comments on the last comments which is um we're we've been raising a

00:47:45 number of issues around the issue of of informed consent right um and we haven't i don't think we've used that phrase yet but we've all been talking about it and uh what counts as informed when we're talking about technologies that are so you know so new so powerful and so complex right um is really difficult to to identify we have we take informed consent as kind of this

00:48:17 gold standard of ethical uh ethical behavior and what does it mean to be informed you know if you do a uh if you if you take a 23andme test they um they can send you back there's a there's a a a set of snips that apparently are correlated with an increase in 7.7 iq points right and um

00:48:47 i don't know the name of the gene maybe some of you you do uh but there's um but but this is what people are told and then as as i'm sure everybody in on the panel is well aware people mistake probability for certainty right people don't understand probability uh you've got a polygenic score that says you're you know um 80 less likely to finish college than

00:49:19 someone with you know a higher polygenic score people think oh my god my kid's going to be going to be done i'm going to drop out of high school what do i do it's probably going to be more inclined toward criminal behavior and and drug use and all sorts of bad things that correlate with low you know lower educational attainment or years in school so there's some really important issues here you know around the question of informed consent and the informed part

00:49:50 what what counts as informed when we're talking about genetics and these complex behavioral traits not now i'm going beyond at the moment you know uh some relatively simple cases like alzheimer's disease or even cystic fibrosis and thinking more about say mental traits um uh schizophrenia or or or mental retardation or depression things that are extremely complicated biology uh biologically as as we've said

00:50:22 um people will be told that you can you know you can get people to tell you that that they can give you the genetic answer to your likelihood for schizophrenia and no matter how often they say this is just a probability people think oh my god you know my child's going to be schizophrenic so we have to there's some really important issues here with the question questions surrounding informing the public people can't make

00:50:54 good decisions we need to let people make their own decisions we can't we're obviously not going back to a state run eugenics program but any kind of um you know liberal sort of program of allowing individuals to make these kinds of decisions hinges upon being actually informed and what that means is far from clear when we're talking about complex traits i'm sorry robert i think had a question first yeah just a few thoughts uh i'm on i'm

00:51:25 from my phone cause i think the the link didn't work for my computer so it's it's hard to raise hands exactly but um a few thoughts so one is i think uh just to get back to the issue of risk uh the problem is that uh risks themselves are not always clear we're talking about potential future risks and so in we need to weigh not just the benefits of using the technology what the risks will be and as mentioned some of the reports that have come out have said you know when it's safe enough safe enough is not a black and white line

00:51:57 uh to know uh that the procedure is safe enough may mean following people for a generation or two in other words if we create a child using this technology we want to see that there are not adverse uh effects on that child and perhaps that child's child for instance uh and uh i think there are even in other kinds of research the fda has gotten to controversy sometimes in terms of deciding when the benefits are sufficiently uh uh uh uh you know out

00:52:27 are sufficiently outweigh the risks whatever they are so even there there's some subjectivity involved the issue with genes is important because i think as nathaniel was saying we still don't know a lot about genes or rather there's still a lot we don't know uh so even with iq for instance as mentioned my understanding is from scientists i trust that uh among the however many uh there have been hundreds certainly of genes looked at for iq uh the one that's been most powerful i've heard gives you so just one extra point on your iq test

00:52:59 so again many many genes involved and another problem is there's a sociologist whose work i admire pierre conrad who wrote a paper called why has the gene for alcoholism been discovered five times it turns out that five times the new york times reported the gene for alcoholism has been discovered uh and only of course to have it reported somewhere buried in later pages uh several months or years later that in fact that was not replicated so there's a

00:53:30 long history of claims for genes being associated with traits and diseases that are not replicated because if we look at a group of hundred people who have a disease and a group of hundred people who don't we look at literally millions of genes we're going to find some genes that are present in the one group but not the other and some researchers may say well that's the cause when it's not in terms of informed consent i think it gets even trickier when we're talking about designing future people uh

00:54:01 obviously they can't consent so there have been cases some apocryphal some reported where deaf parents for instance have said i want to use pgd pre-implantation genetic diagnosis to have a deaf child or dwarf parents have said i want to create a dwarf child because we feel these are not disabilities and we feel that this is the child we want and again there too obviously the child can't decide for him or herself the child's not yet been born um which i think raises the stakes even more because there may be doctors who say yes

00:54:32 i'm willing to do pgd for that purpose the parents may want it the child obviously is not there to say no we also have so-called savior siblings where we have a child or a parent who has a terrible disease uh and needs uh bone uh bone marrow transplants for instance so we can through pgd create a child's will be a match to create uh sufficient uh bone marrow to serve as a donor obviously that child doesn't have a say in it so i think we need to be extra

00:55:03 careful and i think that's an important role for bioethicists uh to play lastly just to put on the table i think one of the concerns that hasn't been mentioned is eugenics or it's been mentioned a little bit but you know when we've tried in the past historically uh to alter the genes of our society it's led to disastrous results obviously with the nazis uh and eugenics actually started in the united states in the 1920s uh there were efforts as waves of immigrants came from southern europe eastern europe uh there were eugenics fairs in the midwest to

00:55:35 give awards not just to the biggest pumpkin and the best pig but the best genealogy uh mean read you know wasp genealogy i think again culturally these are uh i think forming a background of why there's such interest in improving genes and why we need to be careful vardy um taking the conversation first of all to another level higher level of complexity on one hand and on another hand from the science fiction to the here and now so we talked about what if

00:56:06 someday we can use crispr safely and effectively and combine that capacity with uses that are socially very controversial what are we going to do then but there's something that we can already do now and actually some private companies are beginning to sell it uh to prospective parents and that scares people like hank and myself very much and that relates to the use of the well-established technology of screening embryos in vitro before deciding which one to implant

00:56:37 not to look at one gene that causes a disease but rather to look at multiple genes that increase uh in to various degrees the risks of the more prevalent diseases heart disease uh diabetes diseases that you know pop at a population level we're really trying to tackle as a public health issue now if you have imagine that you have 10 embryos in vitro and as parents you know that there's a genetic disease that is

00:57:08 very serious running in your family and the result of this test is here are the four five embryos that will be sick as children you know they they carry the gene and the other ones will not suffer from this disease now you choose you know it's a sort of a simple decision because you tested from the beginning to screen against that gene right now imagine that for each of those ten embryos you get a map that tells you

00:57:39 for heart disease the risk will be at this percentage for these kinds of issues but so that's a little higher over the general population but for diabetes you're actually going to get for the same embryos lower than the general population now let's look at a variety of you know 10 other diseases and for each one you're going to get a different risk score but also with different nuances within that risk score no embryo of the 10 will be perfect or clean or free of risks

00:58:10 because we all including us on the screen we all carry problematic genes um and so what are we going to do with the reproductive decision making when each time we screen embryos we face what hang called at one point an avalanche of information that is extremely complicated multi-dimensional and we don't have an obvious choice because one of those embryos is perfect they all carry some problem

00:58:41 uh so we're we're really scared of such a future because on one hand we always say oh more information is better but at some point more information will might actually become a disaster how do we identify that point i think it's important for people to appreciate that what you're referring to vardeed is that there are certain diseases and many of the more common chronic diseases many of them very serious have a they're polygenic there's there's not one or two genes that are associated with that condition

00:59:13 uh there was a seminal paper about schizophrenia some eight years ago that said they located at least 108 genes that were associated with some risk of schizophrenia and they were still trying to work out now to what degree these various and numerous genes have to interact with one another or be exposed to certain environmental circumstances that would raise the risk of schizophrenia in that in that individual on the other hand without doubt many of those uh 108 genes and there probably are more

00:59:44 may confer some increased fitness they have a there there are qualities among those genes that are all over the gene pool or for all of us and uh which are probably good for us so right it's it's much more complex the question then would be how do we educate people or who would be the who would be responsible for educating the public so that they would understand this or be able to make better decisions or not be offered the option to be to make the decision

01:00:18 hank you're muted you're good first time this week wow that's pretty good it's saturday i made it almost through the week without uh messing up my muting so two things um one on this issue of the riskiness of particular genetic variations and i'm i'm really glad that verdi brought up the prs this polygenic risk score point there are some things traits or diseases where it is really where a particular genetic

01:00:48 variation is really really powerful so if you've got more than 40 cag repeats on your huntington and jane the only way you're not going to die of huntington's disease is to die first from something else and then every other disease trait condition etc seems to have some genetic influence but it's really complicated and so you got if you did say whole genome sequencing you could look at 6000 or 10 000 different genes that are associated with particular rare diseases where special

01:01:20 variations cause the disease with a high degree of confidence either 100 or something like brca1 or 2 mutations which increase a woman's risk of breast cancer to about 80 percent increase the ovarian cancer risk from 1 to 30 which in some ways is more significant even though we think of it as a breast cancer gene and then you've got these statistical things looking at variations not even in individual genes or sequences but at variations in markers a million markers across the genome

01:01:52 and coming up with this very controversy and sticking machine learning algorithms or artificial intelligence on them and coming up with these numbers that are very scientifically uncertain but are being sold to prospective parents already so you've got the the known high risk for some things genes which may also have unknown benefits as well and then you've got this machine learning algorithm constructed

01:02:23 gamish of a whole bunch of different markers that's an important distinction to keep in mind particularly since we're seeing the commercialization of the latter one i think way too prematurely but then the second thing i wanted to say is to go back to robert and the consent of the embryo obviously right on the other hand i can't remember the consent form i signed saying yeah i'd like to be born and by the way i'd like to be born to this couple in columbus ohio et cetera et cetera

01:02:53 you know i'm a parent um they're 30 and 33 so we've survived not only childhood but teenagers i've survived they've survived we do all sorts of things without our kids consent it's our job you know you don't say well here are the advantages and disadvantages of you going to bed right now and i want to make sure you fully understand them before you make the decision say it's your bedtime and what i swore i would never do before i had kids was do what my parents did and of course i

01:03:24 broke this oath why after 17 different why's because i say so you know at some point parents do those things i do agree that the fact that the embryo can't consent makes it a higher raises the the issues more highly but at some point that's what parents not only do but that's our job in some sense and trying to mold these babies these embryos fetuses and babies

01:03:54 into good happy loving people i do think though the deafness example in particular is really interesting i have mixed feelings about whether a deaf couple should be able to choose a deaf embryo as opposed an embryo that would grow up to be deaf as opposed to embryos that wouldn't i have no mixed feelings about whether a deaf couple should be able to you know artificially deafen a child that's been born with hearing

01:04:26 i'm not entirely sure that it's a defense that i have a defensible line there between birth after birth and before birth in the second case you call child protective services and the police in the first case it feels different to me but i'm not sure how i come out on it robert yeah i know you wanted to make a comment even before uh hank's comments so uh go take it we'll take it away yeah so i think that children are entitled to an open future as it's been

01:04:57 said uh so we don't want to be making it's one thing to say this is your bedtime you have to go to bed why because it's your bedtime and you have to go to bed it's another thing to biologically sort of constrict an otherwise open future that a child would have within the range of open futures that are available to children so i think if we don't want to forcibly impose risks on children uh when we otherwise don't need to and i think that's sort of the spirit in which

01:05:28 i think that uh we need to be careful about and i should say some of this can be addressed through research to see children who were selected to be so-called savior siblings how do they feel about it we don't know do they feel i feel great i was created to be able to manufacture bone marrow for my sibling or my parent or they may feel what a pain in their butt i mean i were pain in the hip i'm being you know having a needle shoved in my hip every a few months to extract bone marrow so again i think empirical data can help somewhat

01:06:00 think about some of these issues i wanted to come back to the issue with understanding genetics also though because i think one uh one problem is that as hank said uh commercialization is playing a huge role in this space and as far deep mentioned with companies that are selling uh sort of polygenic risk score tests of parents and to physicians uh there's a lot of money to be made here but or companies are making a lot of money and so they're often i think the ones pushing the agenda even when it may not be in

01:06:31 the consumer the patient the prospective parents best interest and this affects uh not only uh prospective parents and patients but providers too so there are tests being sold to psychiatrists now and psychiatrists are buying them genetic tests to predict the risk of someone being schizophrenic and the report comes back and it's also available to consumers as well they can have this test that you have an increased or decreased risk or increased or normal risk of schizophrenia and what increased means is that your

01:07:02 risk goes from one percent if it doubles to two percent which means that whereas normally the average population risk is say one percent of schizophrenia if you test positive for this gene it doubles to two percent well people may just see you have twice the risk of schizophrenia and get scared uh seeing the so-called relative risk without understanding that the absolute risk means that the the chance goes from one percent to two percent that is as there's a otherwise a 99 chance you won't have

01:07:32 schizophrenia to a 98 chance you won't have schizophrenia so i think we need to educate the public about statistics about math about science in general not just regarding this but overall and i think this is an area that has also not gotten as much attention as it should and that i think would help us be able to deal with this in other areas where questions of our use of technology comes up nathaniel yeah following up on on robert's comments on

01:08:03 i wanted to raise the question of the ethical issues surrounding the free market um the you know our we have a very largely fair uh attitude toward economics in this country and there's um and as we're as someone said earlier there's uh that's basically an unregulated market for for pgd and there's also an unregulated market for genetic testing for um for for genetic entertainment for you

01:08:36 know spitting in a tube and getting a report for uh for for you know just about any trait you can that you can name uh or or behavior you can get someone to tell you you know give you one of those risk scores right and um there's so there's a whole lot to be said about about that maybe i'll come back to that later say that for for later in the conversation but i did want to raise the question of uh of the

01:09:07 the ethical issues surrounding the free market where a lot of decisions are made that we would oftentimes put under the heading of informed consent that are in fact strongly affected by things that we know have big psychological uh exert large psychological pressure like advertising and and peer pressure and so forth where um so if you're marketed you know a a test that you know promises

01:09:39 to tell you what your your iq is going to be what your children or diseases are going to be what what so forth and so on there's not really much you know there are only very broad outlines uh you know guidelines about what can be said uh and what can't and i'm not an economist so i mostly want to raise the question and uh see if if the rest of you had thoughts on the on the marketing aspects of the new genetic technologies

01:10:09 verdit you want to respond to that yes so uh one technology that we haven't talked about so much yet and is actually one of the fastest spreading technologies with millions and millions of women around the world using it even though it's only been around for about a decade is a new way of testing fetuses during the pregnancy but early on and without invading the the uterus and causing a risk of miscarriage just by a simple blood test of the pregnant woman and this is a technology that we call

01:10:40 non-invasive prenatal testing another acronym hank and ipt um and the reason i want to bring it up is that my my research group has done a lot of thinking about the ethical and social dimensions of this technology and we've been talking to pregnant women to families and especially to families raising children with trisomy 21 or down syndrome because this is one of the main conditions that this technology targets and what we're hearing is that sometimes

01:11:11 um you know nathaniel talked now about uh unconscious uh mechanisms how we respond to the societal pressures economic pressures but some people are telling us that they're very conscious of these pressures for example they say i would love to welcome into our family a child with down syndrome but society will not provide me with the support mechanisms that i need what happens to my child when i'm too old to take care of him or her i don't want the child to become a burden

01:11:43 on their siblings we won't have enough financial support so sometimes the same pressures that nathaniel mentions are very explicit in people's decisions about terminating certain pregnancies not because they think that the condition in itself is as we said very serious or the quality of life will be so terrible that they don't think it's a life worth living but because they feel society would either not support their decision or that they would be judged and criticized um so when we say informed consent what about

01:12:14 free consent when are we actually free to make these decisions knowing that we live in a society that would support us and our child uh because it's a society that has diversity that appreciates diversity that has a high degree of tolerance towards difference or are all these technologies gradually closing up what we consider to be acceptable so that only you know savalesco's best children uh deserve to be born and the others you

01:12:46 know will be uh parents will be judged for even having them and the last point i want to make today is a story um a nurse once came to me after a talk that i gave about this technology about nipt and said you know i'm coming back from uh from a shift now and we were in the er a couple arrived arrived with a very very young child uh suffering from a disease and the first thing i heard the doctor tell them is you didn't test what did the doctor mean didn't you test

01:13:17 this uh fetus before it was born to find out that it had this disease and therefore terminate what was implicit in the question why am i even seeing this child this child shouldn't be here so the first reaction the parents get when they rush to the hospital with a sick child is your child shouldn't even be here we have technologies in place to screen out this child before birth why are you creating a burden on me and on society and that's my last word of caution because all these technologies can push us into that

01:13:48 corner and that's my greatest fear bank i think you had a comment also yes and i'm actually not muted so really three quick things first i think nathaniel's question about the role of the free market is a very important one and particularly the role of the free market and a an increasingly constitutionally protected world of advertising where the supreme court has held more and more

01:14:19 so-called commercial speech is actually protected by the constitution we are one of only two countries in the world that allows advertising of prescription drugs i don't know why new zealand does it but i think i know why we do it because it makes a lot of people including a lot of media outlets a lot of money and it sells things and i think i i think the problem of consent is not just a problem of advertising but the two exacerbate each other second the disability points and

01:14:50 inverted i'm glad that you you just talked about it at some length to me they're the hardest issues in this whole area you know there's one set that gets a fair amount of attention because it's kind of you know titillating or exciting and and that should the deaf parents be able to have deaf kids or should a quadriplasic parents be able to have little people children it's it's significant i don't want to dismiss the importance of that but it's relatively minor in terms of the percentage of the population involved

01:15:21 there are a lot of disabilities out there and i had us i was on a panel once with a stanford graduate a woman with something called spinal muscular atrophy genetic disease it comes in a variety of different degrees of seriousness some are fatal early hers had her in a wheelchair from about 18 on and we were talking about this stuff in a panel and she said well what you people are saying is i should never have been born and i sure as hell didn't want to say yes that's what we're saying

01:15:53 so of course i sort of intentionally um sidestepped and said well no what what people on that side are saying is that you should have been born but without your disease and she being a very smart person immediately said well without my disease i would not have been me i don't know where we go with that i mean that's sort of the if on the one hand i don't see any problem with preventing the birth of children who have just really inevitable nasty awful

01:16:26 diseases tay sachs disease or lesh nihan where children are intellectually disabled and at the age two they start chewing on their on their hands and feet and disfigure themselves these are terrible things but when you get into the the grayer area i can see why parents wouldn't want to have a child with sma but should we stop them from doing that because of the people who have sma or wouldn't want to have a child with down syndrome should we stop them from

01:16:57 doing that because of the people who have children with down syndrome or the people who have down syndrome and not just the psychological effect on them of knowing the world thinks i shouldn't have been born but the shortage the debt the the diminution of research funding going into the area physicians specializing in their treatment social support for their condition all of those are real problems that the ability to avoid the birth of people with certain disabilities brings to the people who've already been born or will

01:17:28 in the future be born with those disabilities and then finally earlier this week on wednesday we saw pretty much the heard pretty much the death knell for roe v wade sounded at the u.s supreme court the only question i think at this point is when in june they come out with the decision it will eliminate roe entirely or just say well right now we're just saying up to 15 weeks you can ban it after 15 weeks and we'll

01:18:00 deal with the others later i think there's a really interesting question about how the death of roe v wade is going to affect the assisted reproduction field industry whichever you prefer and the use of genetics and the possible uses of genetics afterwards so there's a big one to throw on the table

01:18:30 or a comment he wanted to make and i want to let him do that and then we could open up the floor to some questions right just a few quick comments interestingly in terms of uh the pro-life movement and the religious right when pgd was developed that is screening embryos those clinicians were concerned that the religious right might shut them down and in fact what happened is that people on the right uh felt gee if i can afford to have a better child i should have the right to do so so what's interesting is

01:19:02 that a certain libertarian attitude prevailed that has allowed some of the things that we're actually concerned about uh as well as potentially some benefits beneficial things like pgd out there so i think uh it's hard to break what's going to happen though i certainly worry a lot about the future of roe v wade as hank was just saying just on nipt the sort of uh way of uh looking at the genes of the fetus just by taking blood from the mother's arm one uh issue that come up

01:19:33 comes up with that which is what vardy was talking about a few minutes ago that has a lot of uh uh folks i know concerned is that those tests often give the results of say 70 different diseases and the actual sort of validity of those tests for all 70 diseases has not been determined so patients again are coming in with these reports look at all uh the diseases the 70 diseases that the test showed that i have and they say to their uh their ob gyn what do i do with this information and often uh doctors themselves are not

01:20:05 sure uh you know should i abort the fetus or not given it that it has a say you know 30 or 40 percent chance of having whatever the disease is because these are not always predictive tests unlike in the case of downs where we're much more able to predict it so again a lot of confusing issues i would just say with the free market question that nathaniel raised uh we have a free market but we also have an fda and we do have concerns about protecting consumers protecting patients protecting their rights as well and i think for those who are not familiar with bioethics this is a lot of what

01:20:35 bioethics is is often trying away conflicting principles and conflicting issues well this has been a very stimulating talk so far i hate to jump in um but we do have some questions i think beverly do you want to start with a question yes for all these considerations it seems the genie is really out of the bottle though and it's going to affect family psychology sociology theology etc and one sort of

01:21:06 non-sci-fi horror as you could imagine a child saying mommy why didn't you take the gene out for my adhd i mean they're going to be so many different kinds of reverberations about what one didn't do even from the child's point of view as well as what one did do so we're in for quite a ride but thank you you you are all just marvelous i really appreciate the thoughtfulness and consideration

01:21:37 great thank you beverly all right alex i think you have to thank you so alex you want to um start to read some of these questions and see what the panelists have to say in response uh yeah and um everyone watching on zoom and youtube on zoom we could write in questions on the bottom panel so you see a button says q a and then on youtube just you could write it in the comments so from al danieli on youtube um they're wondering i mean given everything you talked about do you think

01:22:08 there's anything you could add when you look at trauma so any given the intergenerational effects of pdsd via epigenetics so do you think there's any comments you could add given that frame i know you've talked about every other possible disease or what have you that could occur so anything to add there i would just say that for most psychiatric can you hear me uh for most psychiatric conditions uh uh the genetics are much more complicated and the gene environment

01:22:40 interactions are much more complicated uh so it's easier to find genes for cancer say than it is for most psychiatric conditions including ptsd so i think we're just uh the genetics of that i think are far away from our understanding at the moment and i'd add i think the questioner may have also been interested in the epigenetics which is not so much the sequence itself but the way the sequence gets expressed because of things that are above the the sequence that determine when it

01:23:12 gets when certain genes get used or not the existence and extent of inherited epigenetic markers in humans is very unclear and very controversial it's not and it would really be very hard to test for example the extent to which epigenetic markers may have some role in children of somebody with ptsd having issues one thing that is quite clear though is we pass on things to our kids in lots of ways that don't have anything to do with

01:23:43 our genes and a parent with ptsd or a parent with a mental illness or a parent with a physical disability is changing those conditions are going to affect how the kid grows up in a sense this goes back to robert's argument about an open future our our characteristics as parents to some extent and where we're born and what country and what socioeconomic status and so on these all close in our children's futures and affect our

01:24:13 children's futures in ways that are usually much more important except for the few and really unfortunate outliers who get some really nasty early onset genetic disease these are much more important than what genes we pass on i think also we might have another panel some years hence to discuss the ethical uh contra uh uh confusion sewn by epigenetic manipulation uh that that technology is not really here yet but it's coming

01:24:46 okay thank you yale for that question next we have carol gerson who has a comment then a question so the comment goes i once asked the fertility doctor to whom do you say no and his answer was pretty much no one and then her question based on how she wrote in the q a part i assume this is her question um well suppose one is not a consequentialist who is primarily concerned about unintended negative consequences of unregulated gene editing

01:25:16 how does the panel think about arguments from thinkers like michael sandell or william may that gene editing encourages us to use values appropriate for evaluating manufactured things to pearson's and that this undermines the basis for human dignity and equality etc um i think this throws us back to a distinction that hank put on the table between those who think that gene editing is inherently a bad idea for a variety of reasons but it's not

01:25:48 about the safety or the efficacy it's just that as a species we should not start to meddle and mess up at the level of designing our own dna here i finally did work the work design into a comment we should not try to intentionally design our dna either because you take a theological position that we shouldn't play god or because you think that it would never be safe enough or because you think deontologically there are certain things humans should not do because it violates

01:26:18 human dignity those people have already made up their mind right so to them it's not about where is the science going what is the condition that we're targeting what about off targets when will we be ready for first in human clinical trials to them you know the decision has been made but i think if i look at you know the community of thinkers that's a minority and the majority of bioethical thinking is about those questions that i just mentioned where is the science how do we define safety and efficacy and

01:26:51 especially what genes do we want to target once it is safe enough um so you know that that minority that sees this as inherently uh uh something that should be banned there's no conversation there right it's not about anything that's going to change it's just an in-principle position um that that shuts down the conversation about the i technology just add i agree with what varde said uh uh hank early on mentioned

01:27:22 uh mitochondria replacement therapy which is that a small amount of human genes are not in the so-called nucleus of the cell but in mitochondria and uh scientists have developed ways of uh using another woman's uh uh sort of mitochondria so to speak through mitochondria replacement therapy and this is altering the genes arguably of a future child to prevent terrible diseases and i think that there is some

01:27:52 distinction morally between using these technologies to prevent terrible diseases versus adding some iq points or some of the other milder conditions that we're talking about i think that distinction uh is something that a lot of people find helpful so going back to the argument that sandel and may made and that was referred to in the question um you know i think sandel makes that argument as well as it can be made i don't personally find it very compelling or convincing

01:28:23 in two ways one i look at people who were born as a result of in vitro fertilization the same arguments about viewing children as a commodity as a manufacturer as a product were made 40 years ago with respect to ivf i typically in the seminar undergrad seminar i do these days i have usually at least one or two people who are ivf kids they don't seem different they don't seem unloved they don't seem viewed as a manufacturer as an

01:28:53 it's actually an empirical statement about how people are going to react to these sorts of technologies that i think that we have no evidence to believe it's that the technologies are changing the way people look at their children viewing them as less gifts and more products to be perfectly designed and you know return to return to manufacturer if you know to get your money back if it didn't work out right the other side of it is you know parents have kids for all sorts of different

01:29:24 reasons parents have kids because they need somebody to work on the farm parents have get used to and in some societies still do parents have kids to provide for them when they're old and infirm if there's no social security parents have kids because it seemed like a good idea at the time parents have kids without even intending to have kids there are all sorts of reasons parents have kids whether this argument's saying parents will view and treat their children differently as a result of this i haven't seen any evidence for it i

01:29:55 don't find it compelling great alex the next question uh thank you carol and i just want to add my parents had me just so i could open up pdfs for them i'm kidding they know how to do that uh i know i believe that okay so thank you carol then we have anonymous sorry hold on we have an anonymous questioner on zoom and they asked is it even feasible to test the efficacy and safety of germline editing in an ethical manner

01:30:29 so let me take that on i i wrote a book about the crisper babies called crisper people that came out this past february and there's a whole chapter devoted to if you did want to try to prove it was safe and effective how would you go about it and you would go about it i think using the sort of things that the fda normally wants but put a particular focus and and more than usual requirement for proof given that you're dealing with the birth of infants who haven't been able to consent one thing you would do is

01:31:00 non-human animal studies and you need more than mice and rats for this i think you've got to use non-human primates certainly monkeys follow them for a couple of generations look to see is and use large numbers hundreds because if you're looking for say a five percent problem you're not going to see it if you only use 10 and you may not see it if you use 20. so do germline editing in a couple hundred rhesus attacks

01:31:31 and see what the results are in terms of the health of the babies as well as the efficacy of the actual editing do human embryo studies where you modify the embryos and then you watch to see watch them as long as you are allowed to up to 14 days under current guidelines maybe longer in the future depends on part also how much jurisdiction you're in and see if they look normal if they act the way the same way that normal human embryos act but then at some point you've got to hold your breath cross your fingers

01:32:02 throw salt over your shoulder you know launch prayers do whatever else you do and go to first assuming everything all that work all that preclinical work says we don't see any real big issues here you have to try it in humans and you try it in a small number of humans who are very carefully studied and typically i think you would try it in the humans for whom the need seems most strong and see what happens will you wait for 70 years no how long will you wait that's a good

01:32:33 question it could well be that every baby born from ivf will drop dead at age 44 because louise is now 43. no reason to think that they will but we can't know until we wait it out nobody's going to wait that long but yes i think there are ways to try to try to not prove safety not prove not prove unacceptable risk proving a negative is always problematic but there are ways to try to get some more confidence that this could be done in a relatively safe way bearing in mind

01:33:06 that safety is always a relative term hank wouldn't you agree that those guidelines are not much different than the ones you might rely on for just drug development yeah no that's right although a problem with this is it is not entirely clear whether or not those fda rules apply to this kind of work the fda has taken the position that it does going back to the early cloning hysteria

01:33:36 i took the position in 1980 i'm sorry in 2000 that cloning would be a cloned human embryo would be a drug or biological product subject to fda jurisdiction that's never been tested in court i think they probably should win on that but i can certainly imagine a federal judge saying wait you're telling me that a human embryo is a drug get out of there where does it say that in the 1938 federal food drug and cosmetic act

01:34:06 robert it's not clear that that legally fda would have that power i think it should and i hope it does and i agree with everything hank said but answer the question i would also add it's not clear that there's enough benefit to justify the risk yet uh in other words for what medical condition would we even do the things that hank rightly says would need to be done and i think that as i mentioned the report from the national academy of science saying well if both parents had

01:34:36 huntington's disease that that it's not clear that that ever happens in the west uh and so uh again it's good to keep an open mind but uh i think we need to be careful that we don't rush into this for the wrong reasons which is capitalism sort of pushing us there i was gonna think we should move on to the next question because we have a quite a number of questions i think alex am i right now let's have two more so let me let me follow up on robert i think

01:35:07 one plausible example of a need would be a couple where both members have cystic fibrosis the life expectancy for cystic fibrosis used to be under 10 it's now people in their 40s every decade it seems to get a decade longer which is a nice thing it's still not a good disease you don't want to have it it's a real problem to deal with and life expectancy is shorter and morbidity is higher but people live into their 20s 30s and 40s and some of them are going to be

01:35:38 healthy enough that they want to have kids and i think it's not irrational to uh unrealistic to think that two people with cf will meet bond and decide they want to marry and have kids together or not have kids together um they would say the only way we can have a child that would not have cystic fibrosis is to use genome editing so i would just say i don't know of any documented cases of people of a couple where both have

01:36:08 cystic fibrosis wanting children maybe it's out there but ivf docs i've talked to say this is a hypothetical yes uh no known case to have happened thus far uh not a good disease but if people uh have if treatments are getting better for cf there are people who if someone's making it to 50 60 with cf uh do we need to be getting rid of the disease this gets back to the issue if it's uh not that bad that people are making it to 16

01:36:38 want to have kids uh along the way uh should we be getting rid of it so again who makes that decision the parents or the governments right or the bioethicists yeah i'm just saying we need to think about our efforts right you know the relative risks and benefits and what would the benefits be alex next question um yeah so thank you anonymous uh viewer uh this is from charles murkowski and he asked what's the current

01:37:08 understanding of als genetically um i could just add as an addendum to that i i know pathologically it has to do with um ubiquination problems so ubiquinated proteins not being properly disposed of in the cells and then the buildup of that leads to um cell death so anyone want to add on to that i know a little bit about this if somebody knows a lot about it i would be happy to defer but i think it's like a lot of diseases a few cases are powerfully caused by a

01:37:39 known genetic variation in this case it's a mutation in a gene called sod two sodium oxidase dismutase or something might be sod one i forget whether it's sod one or sod two and that makes up one or two percent of patients with als there are a whole bunch of other genetic variations that increase your risk of als but not enormously and then there are a whole bunch of patients with als who have no genetic no known genetic predisposition at all

01:38:11 almost every disease almost every common disease seems to fall into that pattern alzheimer's there are some genetic mutations that give you a 100 chance of early onset alzheimer's it's about one person and a thousand carries them there's a genetic variation that 20 of the population carries that doubles your risk of alzheimer's but most people with alzheimer's don't have either of those risk factors so als is partially heavily genetic with the sod 1 gene partially weekly genetic with a bunch of other genes and as far as we can tell

01:38:42 partially not genetic at all and and we're going to see that we are seeing that more and more with disease alex you want to get to the last question for us um let's see on youtube okay yeah this is the last uh question on zoom anonymous viewer asks uh how common is finding a doubling of maternal a paternal dna when companies like 23 and me do testing do you mean a false paternity is that

01:39:15 uh the person further wrote i asked because i was found to be a half sibling to my sister and brother although the most likely explanation is a different bio father i've read that a doubling of one's parents dna is another explanation i've not heard of it i mean 23 and me as i understand it usually if they say you're only a half sibling of someone you thought was your sibling that the vast majority of those cases are due to so-called quote false paternity that is that there

01:39:48 are surprising number of people i've heard reports a good one percent of the population uh they find that the person they thought was their father was not their father i should ed i wrote a book design called designing babies how technology's changing the ways we create children uh and in that i looked at people who were created through sperm donation or egg donation and the vast majority of those people were never told by their parents they were created by sperm or egg donation most men don't want to say i was infertile i was impotent

01:40:20 women also are afraid to say we created using someone else's egg their parents are afraid the child will love them less so that's turned out not to be the case and so people are not told and are now finding out through 23 and me uh that in fact uh they were not uh from the genes of one of their parents but rather there was an egg or sperm donor used in some way i think that's the most likely bardeed i think you had also kind of commented

01:40:51 yeah it would be inappropriate to finish this uh pandas interesting conversation without noting the dangers of going through direct to consumer testing without understanding the potential things you might learn people think of it as fun you know somebody will tell me how fast i metabolize caffeine or that i'm you know i have five percent indigenous that i didn't know about oh that's curious that's fun but they don't realize that sometimes the results come with uh disaster with information that

01:41:23 can be disastrous for family relationships for their psychology for their identity so this is an interesting opportunity to mention a book that hank edited that just came out i received it just received it in the mail oh it's hard to see it's called consumer genetic technologies ethical and legal considerations and in it is a chapter a fascinating chapter about a family that went through this fun testing and found out that they have a half sister they never knew about and it turns out their their mother was raped

01:41:55 as a young woman had a child and gave up this child for adoption and then decades later the story emerges and throws the entire family dynamics into havoc and exposes a secret that the mother kept her whole life so just this fascinating fascinating example of things that can come up um unintended um uh people don't think about this in advance they just send out their dna and think this will be fun so a big you know red flag and a warning to

01:42:28 all of us before we just use this testing for fun to think through all the things that might happen i i feel the need to give a disclaimer i was one of four co-editors on that book along with nita farahani glenn cohen and carmel shakkar and i was clearly the one who did the least work so it's it's a good book probably because i did so little work on it and has a lot of chapters from great people including i think uh pardon

01:42:58 ah bravo now anyone have any uh other sort of last comments they want to add yeah i just want to get uh vicky madden's comment on youtube just so she knows just a comment she just noted that um when i think during one of the question answer responses um she noted that the issues raised about privilege already visible they moved from an affluent area to a more socially mixed area and they they experienced an increase in

01:43:28 people with down syndrome and other conditions and they sort of related that to affluent couples not having as many kids as the less affluent couples so just want to thank vicky for that comment i would just say it's affluent couples are more able to afford these technologies i mean ivf is expensive insurance covers very little of it uh and i think that's that's a major problem or the justice issues or the injustice issues and the fact that the gap these technologies are being used so

01:43:59 far at least in the us in ways that i think unfortunately increase the gaps between the haves and have-nots hank so i it feels like we're getting toward the end um and maybe it each of us could take a shot at something we think is really important that hasn't been discussed and i'm preemptively going to do that because i'm on a i've got a i'm on a hobby horse right now i think that our species has many characteristics but one of the

01:44:29 strongest is we do not lack for self-esteem uh we are very species-centric and we are paying way too much attention in my mind to the effects of these technologies when they're used for human reproduction which i think is going to lag in part because they're not going to be that useful and in part because we won't take lots of risks you know we don't want to take a lot of risks with babies but with non-humans we have the other 99.99999 a couple more nines percent of

01:45:02 the species on this planet we have the ability to make vast changes in the biosphere we're doing it already we've been doing it for a long time the tools allow us to do it better we are much less concerned about the risks of deformities or stillbirths in cattle than we are in babies we're still less concerned about it in mosquitoes and we're not concerned about it at all in bacteria we are going to remake the biosphere

01:45:33 very quickly using these tools and our regulatory mechanisms stick that's where i think we should be spending more attention um and less of this on us you know the biosphere is not just about us even though we like to think it is nathaniel i think that's my sermon for the end nathaniel um yeah first of all just thank you hank for for that comment we didn't get at all into things like

01:46:05 gene drives and uh and environmental engineering which maybe it could be a topic for a future conversation like this um i guess um if i were going to make two if i two quick closing points just to raise a couple of issues that we didn't get to very much in this conversation that i think really are important for um for the for the uh for everyone to consider who's thinking about genetic technologies um

01:46:36 one is we've talked a lot about genetic engineering um and we also mentioned it briefly at the beginning of polygenic scores polygenic risk scores or polygenic indexes and i think genetic prediction is going to be just as important if not more important as far as having an impact on the everyday person's life and genetic engineering and so and

01:47:08 there are a lot of really thorny hairy uh ethical issues tied up with predicting traits especially complex behavioral traits um before they happen and and you know the notion is well we could provide the uh a better environment or we could you know do things that would mitigate any kind of uh condition whether it's you know mental retardation or schizophrenia or you know a lower predicted school behavior so so i would

01:47:41 just urge people to to pay attention to things to these ideas of genetic prediction as they come out through um you know direct-to-consumer uh marketing and and so forth these are really important and tied with that uh we never really to uh talk today much about about race and i think there are some important racial issues tied up in uh a lot of these questions

01:48:12 for example and some of them are hidden uh it's not that obvious for example the uh the the biobanks where the sequence is um that people are using to do the big genome-wide association studies calculate polygenic scores and make all these predictions whether it's disease or behavior or intellectual you know capacity or whatever um it's still the case that the overwhelming majority of the sequence

01:48:42 that's being used is uh in comes from people of european descent and so we have no idea what the effects are well you know what what such a score would mean to someone of of hispanic or or you know with immediate african ancestors or or asian we have very very little data on this and so um that's i i know some people who are

01:49:12 trying to uh who are trying to address that and that's important and uh getting a more diverse um uh data set more diverse data sets to work with but the flip side of that is that that can can reify those um bile you know those supposed racial boundaries and uh and and make and make race racial differences seem more biological than they are so

01:49:44 um so there are some complex and and often hidden uh racial issues involved with this that i think are worth uh worth bearing in mind great anyone else i i would avoid her i'm happy to say something too uh sure uh so i would say uh and i agree with everything that's been said i think a major issue is education need for public education uh about a lot of these issues and i think the point about race is extremely

01:50:14 important one problem i know i'm at columbia and we are one of the centers that are involved in the all of us project to try to do whole genome sequencing on a diverse group of people and it's been very hard to get people from certain ethnic and racial groups who've experienced terrible discrimination in the health care system to want to give their dna to be studied uh and uh we need to uh definitely have a more diverse uh set of

01:50:45 people uh whose dna we can examine to see what genes are put them at risk of disease but at the same time we need to educate and work with these groups and i think that uh the scientific community has been trying i think can try harder but has not done a very good job i think there's a lot of understandable suspicion and wariness as i said given past abuses and discrimination i think that's something we need to work on uh nathaniel's point about the genetic prediction uh here too i think uh i agree and i think at some

01:51:17 point in the near future maybe 10 years from now when we all go to see our doctor our complete genome will be on in the medical record uh and doctors will be able to say you have genes associated with say increased risks of alzheimer's disease and there are major questions that we've not discussed but as suggested might be great for a future discussion on uh do people want that information how will they understand that especially when again these are uh uh are not highly predictive genes in other words your risk of alzheimer's may go up

01:51:50 three times from say five percent to fifteen percent depending on your age or fifteen percent to forty five percent so these are partial numbers and we're not good uh at thinking about this or brains or did not evolve think about these kinds of complex numbers and lastly i would just say these are global phenomena and so the question of who's going to decide it may be researchers and patients in a country that is not one in which we are now sitting uh as mentioned earlier it was in china that the first uh uh uh

01:52:21 crispr uh first use of crispr in human embryos occurred uh it was then decided okay you can do crispr on embryos but don't plant them into the womb and then in china again uh embryos were implanted into the womb so it may be in a country that is not one of ours uh where this moves forward i think that's important to be aware of and to try to think about ways to encourage as much cooperation with the kinds of guidelines that have come out and the kinds of ethical concerns that we've been talking about today

01:52:55 thank you hank for inviting us to give sort of a concluding word um we talked about plants and animals and adults but i think where bioethics is most concerned is in the area of reproduction right what children these technologies allow us to have the cont the level of control that we can have over future children and my last thought is this we tend to think of having children as a profoundly personal choice we need in light of these technologies

01:53:25 to be acutely aware of how our personal choices accumulate at a population level to create the society of the future and if all of our choices start excluding certain individuals in a way that as a society we have less uh tolerance for diversity and for differences i think we're paying a terrible price um you know as a species uh for allowing these decisions to occur

01:53:57 in the privacy of you know people's uh you know own personal um reflections without engaging with the societal implications so invite all of us to take this into account when we uh you know have these very very private conversations uh with ourselves with our partners with our family and friends um about what what it is that our personal decisions uh imply uh for the future of humanity great

01:54:28 well i want to just tell everyone here how thrilled i am with how wonderful this conversation has been and how enlightening and i actually personally feel that to whatever degree there are and there must be open issues i think in many instances we outlined the sorts of issues that should be open for discussion uh politically with one's doctor with one's conscience and i think it's fascinating to reflect that so far from uh these sorts of technologies robbing us of human dignity um actually dialogues

01:55:01 like this i actually think enhance when they're as as well thought out as these were today they really enhance our human dignity i think having the opportunity to have these conversations is uh uh it's incredible so i want to thank you all again and uh look forward to uh our audience coming back to see us uh for our next talk thank you everybody thank you thank you fellow panelists it was fun great bye-bye

01:56:44 you