Transcript: CRISPR Babies – Episode #1

let’s begin to move into the topic of today’s discussion which is these CRISPR babies that recently generators for babies designer babies and so this touches on your interest in in genomics it does and so let’s get a little background about this let’s talk a little about CRISPR first and I have to say first of all this these babies aren’t in some sense surprised we’ve been talking quite a lot but when this was gonna happen absolutely not anticipating it for several years there’s a theory which is you know in technology anything is possible eventually happen and so you can’t be surprised by yes but but give a little background about what you know about this particular case and what happened the Filioque gene editing yeah so recently I’d say what five years ago big breakthrough in gene editing technology something called CRISPR I think you actually deserve credit for making Michigan State institutionally aware of CRISPR running some big meetings on it helping set up a gene editing lab here so you’re probably actually in a sense know more about CRISPR than I do but you could just say we now have the ability to very selectively edit a genome with relatively low whether it’s exactly zero or not low off target mistaken edit rate and so there are now many possible applications one of the applications is if you’re going through in vitro fertilization you have an embryo you might edit the genome of that embryo and you could edit it edit the genome in a way making a change that isn’t present in the mother or the father so a de novo change in the child that makes it inevitably very different genetically very different from the parents and so what was done in this first experiment was they actually because many embryos had been edited before and testing had been done to see how effective the edit was this is the first time the Edit the embryo was implanted and actually became in this case twin baby girls and so this has caused enormous controversy yes it was announced at a meeting on Gina you know editing in Taiwan yep it’s it from Kong Hong Kong Hong Kong and it’s interesting because I guess they were I saw an article MIT Technology Review seems like there’s her signals early on this might be happening but the reporter at MIT Technology Review who whom I actually know he broke this story through some actual gumshoe reporting he was he was kind of aware of stuff like this was going on and he found the record online record of the experiment at this hospital website so he broke he actually broke the story so give us a little background what was edited and what was the researchers trying to accomplish right so this researcher is very interesting guy his background is actually in physics and he did his postdoc at a very famous lab at Stanford who’s run by another physics guy who went into genomics in molecular biology so he’s a little bit he’s a little bit of an outsider to the mainstream genomics world he’s actually more kind of a bioengineer kind of physic he has that kind of physicist view of things that like oh great thing let’s do it so this guy who’s a professor at a university in China he ran this experiment where he recruited couples to be part of the experiment they gave them free IVF and his goal I think all along was to produce the first gene edited baby and the Edit that he made was an edit to a particular gene ccr5 that actually if it’s done correctly and it’s not clear it was actually done correctly and these two that it actually worked properly in these two girls gives you resistance for a against HIV and there’s actually about I think I think that percentage might be 10% in Europe there’s something recession some percentage of the European population actually has this mutation and is very resistant to HIV the father of this girl of the girls is a is HIV positive and was very I guess according to the what was said extremely traumatized by becoming HIV positive and so he had a very strong desire that his daughters would be HIV resistant now a lot of what’s reported in the press doesn’t take into all the information that we know because this guy that the researchers named huh he gave a talk at this meeting in Hong Kong and he went over what he his description of the experiment and what had been done and a lot of the facts that now again he might have been lying but if he was telling the truth about what he did those are important facts which are seldom reported by the press ok so one of the things he said was both parents are highly educated and they by the time this this process takes time because you have to go through the IVF process and collect the embryos and then do the editing and then sequence the embryos to make sure the off targets aren’t there and then communicate with the parents there’s a lot of time over which she was communicating with these parents and so he claimed that they had a good understanding of the science and the technology behind all this and what he told them at this point when the embryos had been edited was we found what might be an off target in one of the embryos but when you’re sequencing an embryo you’re only taking I think in his case he they just took one sell off the embryo and so it’s a kind of noisy method of how many cells are there 50 to 100 tipica and so they take as few as possible because you don’t want to damage the embryo so they took one cell off and they they sequence and he said he said to the parents we found some evidence of an off target we’re not sure it could be an error in just the sequencing we won’t know until the kid is actually born whether that is really an oft argumentation and he said that the parents were offered the choice of using to complete the IVF cycle either the edited pair or some other unedited embryos there were unedited embryos that came from this mother and father and they had the option of using those so at that moment it was parental choice to implant and the editing of embryos is not controversial generally so sign that scientifically has been done many places around the world so the key decision here was actually made by the parents not by the researcher if they parents had just said okay let’s stop let’s just use the unedited embryo so you could finish the pregnancy no you would have never heard about this this was just being one of dozens of you know kind of well okay they’re testing the CRISPR technology it works we checked the embryo so they the parents went ahead and had the kid and and it turns out the off-target isn’t really there it was actually an artifact of the sequencing and so that aspect of it I have not seen reported anywhere so it kind of changes the tenor of the whole thing nothing’s been really interesting to watch the response to this because it’s been uproar than the scientific community and the researchers been denounced as having done something unethical and I like I think their enormous number of complexities here but I have to say I think the scientific position may not be tenable actually the idea that you should be allowed to edit an embryo but somehow moral to implant–
the embryo yeah as if this embryo somehow needs to be obligatory destroyed if you’re a Catholic I mean what’s totally legal in most of you I think all the United States to go in abort something that looks like a actually looks like a baby’s not a bundle of soccer ball of 50 cells but a baby or what people think you know some people would call a baby you’re allowed to abort that how can there be moral equivalency between the question of oh I want to make one tiny change to the genome of this embryo or implant or not implant this embryo those decisions seem very minor to me compared to the decisions made every day by you know potential mothers about abortion right so so I think people are not people are just doing what they’re kind of so the thing they’re accustomed to they don’t question the new thing they question a lot in this context I think it’s very common but one interesting issue is gonna be how this will evolve as this practice probably becomes more common and whether people’s attitudes will change yeah there’s a Pew survey actually a couple years ago about attitudes towards gene editing it turns out the US public’s Morla split right down the middle yeah um as to whether they would support editing to it bring about exactly what they did in this case which is disease resistance yeah people more religious were more opposed people knew more about CRISPR were more supportive right but it seems like it’s an issue that at the very same conference in Hong Kong the Dean of Harvard Medical School who’s himself I think a stem cell or anyway some kind of molecular biology researcher he gave a talk and he was on a panel in 2050 Kien that set forth a bunch of guidelines for when CRISPR could be used in a clinical setting and 2015 was far enough away that they could be rational from as opposed to what people are doing now of talking about what happened so he gave his talk and he actually just said well these are the things that we thought in 2015 would have to be in place before we could do it and frankly we’re pretty close you know we’re pretty sure that it works well we’re pretty it’s effective it’s safe we can carefully monitor what’s going on we can we can make sure the page the the parents understand and give you know informed consent so he actually said something which was quite supportive not of this particular researcher huh who everybody says is a villain now but but but of the general trend he was quite supportive and then it was announced I think it was revealed like that Harvard is all some Harvard researchers are doing like CRISPR on sperm right now so it’s gonna happen there’s no question it’s gonna happen yeah it’s interesting you know a lot of our kind of casual conversations are where you know again the cats out of the bag yeah people gonna do this we’re thinking is gonna be Russia is gonna be China right and those seem to be the two leading case right it’s funny because the Chinese scientists who are all sort of cowardly conformists they were the most vociferous in denouncing her when this happened and the most supportive guys were the Dean of Harvard Medical School and George Church who’s also at Harvard medical scan from yeah Georgia says him over this yeah so it’s kind of funny and the most amusing thing is if you go on YouTube when you watch the video of this guy had a video all set up of just an interview of him in his own lab talking about what had been done that he peep himself put on YouTube like when the story broke and you read there like there must be like 5,000 comments on YouTube under this video and every comment from a Chinese person is is all is sort of like I am a life scientist and has disgraced that has shamed the Chinese people and and he should never have done this because well international people don’t like it and so is the last part key to that comment yeah it is it is it’s all about like oh well with the international community thinks this is bad this is you know anyway but then they’re all the other this is a YouTube right so then there are thousands of comments by people mostly Americans European saying hey it’s awesome man technology is gonna happen you know what are you coming down on this guy so hard you know so it’s kind of amazing the dichotomy of those comments yeah but in the u.s. pressed of course the Chinese or they don’t have morals like we do and they’re all for they’re gonna edit all their babies and you know but it’s people should just look at this Pew survey of a marriage yes right whereas ends like half of them said if they thought that this was was acceptable yeah so in judging this in the same survey people were very resistant to things like editing to increase intelligence and we’re gonna get in this too because this is actually something I think that you’ve written about that you are supportive of right Wow okay about that okay we’ll be careful I think but see is this gene in particular right yes is it has other effects yes and this gene looks like it’s also involved in contextual memory at least in mice yes and when you even heterozygotes where one copy of the gene is disabled one is as normal those mice look like they have better memories than regular mice do yeah and the question is how will this work out in these children it’s quite possible that these edits may give some cognitive enhancement yep and these children may have any thoughts about that well so I’m pretty sure the parents didn’t do it for cognitive enhancement I think this story about the the father being really traumatized about by accident to becoming HIV positive and wanting his kids to be resistant I probably is it has the ring of truth to me and it didn’t seem like the parents were trying to enhance this is a weird way to enhance the intelligence of your kids the effect is not that big but whether we’ll see people making active edits to accomplish goals which are not related to disease yeah we might eventually see that I think the biggest barrier which people do not understand so people are very focused on CRISPR the technology how well can we edit are there off target edits made the thing people don’t understand is that the more informatica problem of actually figuring out what pieces of the genome are affecting which traits and in what way that’s a huge machine learning AI problem that’s that’s what I work on and that is not a solved problem so we don’t actually if you gave me today a super crisper you know a vector that could edit 1000 places in the genome instantaneously with no error okay we wouldn’t know how to use it because we actually do not know the specific edits that we want to make and so so people misunderstand what is the gap that the barrier that needs to be crossed before all the nightmare scenarios of you know blondes six-foot-five super genius decathletes babies can be produced we haven’t solved the problem yet extra well I mean I want to say that I think part of the story is that this is new technology yeah but let’s be honest people are already in the process of trying to produce blonde six-foot-tall babies by simply having Scandinavians be it perhaps the largest firms you’re right that’s what am argument which is people get upset about CRISPR yeah already making choice about their genome yeah already seeking out particular kinds of mates this is only advancing techno it’s only using a very different technology yeah the fact is these kind of decisions are being made by absolutely most women all the time yeah or men and men actually if they’re looking for a you know some an egg donor egg donation in the u.s. is somewhat I don’t know if it’s regulated but statistics are gathered and so for example there’s a famous plot that was I think I put it on my blog a few years ago but it was gathered by the data was gathered by researchers on the horizontal axis is the SAT score of the egg donor and then the vertical axis is the price paid by the parents for the egg and it’s it’s it’s like this so yes people are already doing this kind of thing and when a bit height is actually a similar for height yeah if you look at the ads like for if you if you go to like the the crimson or the Yale Daily here whatever it is the ad will usually say like we want a smart Yale student who’s also an athlete you know to donate eggs and we’ll pay well you know what hey there’s a famous toast I think maybe 10 or 15 years ago via a woman who was I mean I think a six foot tall athlete and her eggs you sell her eggs for like fifty thousand there he goes yes so just to say I think you know the free market man yeah it’s interesting I think I think these things people get I’ve gotten used to it right so they don’t say anything about it yeah but I personally don’t see any principle difference between people making these kind of choices I wasn’t principled I agree I totally agree with you I know some of the people who were the early pioneers in IVF IVF itself which is now 30 plus 40 years old I think the you can go back and read what were the reactions what did the New York Times say what did bioethicists say when the first test-tube I remember this being on TV I was like we’re eating dinner would you know Dan Rather was on TV a 78 yeah with my yeah I was a little kid it’s like dad test-tube babies and so I remember how freaked out people were then now you might be surprised that a million test-tube babies are born each year in many European countries 5%
of all births are through IVF in Denmark it’s 10% in Japan it’s 5% and it’s just a consequence of women having more professional more career options and you know tending to have the kids later and then there’s maybe a fertility issue and so they go through IV yeah but what was reviled and thought to be a milestone in you know Mangala talk yeah evil progress of science cold technology now has become a way to produce you know 5% or 10% of all babies in France or in Denmark so it’s interesting in my state Massachusetts I think right around the turn of this millennium became the first state where for women over 30 had children than women under exactly it and that’s kind of driving this I think all young women should be told that fertility decline in women happens between the ages of 30 and 40 or almost everybody and if you’re lucky it’s in your late 30s and if you’re unlucky it’s in your early 30s and so there are many women who wow you you still pretty young now you’re looking and you’re looking for a husband and you’ve got a great career going you know you’re a lawyer we’ve already had fertility Klein you just don’t know it right so I think we all had friends were exactly come an issue yep but you’re involved in start-up actually that’s I’m involved in I’m a founder of a startup that does advanced genetic testing of embryos okay and how does that work well it’s very similar to the Mengele story I’m just kidding so it’s standard practice now to let the embryo grow to fifty or hundred cells and then you can take a few cells off for genotyping and then they freeze it they actually freeze it in liquid nitrogen and the freezing doesn’t see it freezing and thawing doesn’t seem to harm the embryo and so there are a lot of women who actually advised if their high-powered career women to freeze embryos so that they can use them later that little sample that’s taken off now the DNA from those few cells can be amplified and we can get a full relatively inexpensively we can get a full kind of 23andme level genotype for each of embryos and then you can predict certain things like disease risks so you can you can you can detect mutations that are dangerous and you can also predict polygenic disease risk so for example the probability that someone gets breast cancer or the probability that someone has heart disease is actually controlled by many genes but we are the machine learning is getting good enough that we can from this measurement of the genome actually make meaningful predictions about whether a particular embryo is going to be an outlier for a particular health risk and so if you have multiple embryos and you’re only going to use may one or two of these multiple embryos you can now make a more informed decision then you could just year or two ago and it’s it’s known that taking these cells off of the embryo has no negative health effects so it’s no detectable ones yet so so far there have been no statistically significant results shown about the viability of the embryo post biopsy it could turn out there’s some slight effect from the biopsy but so far it’s not been detected there’s no negative effects to the freezing long term actually the freezing thing is actually positive possibly for reasons that embryos that are they look okay but there’s some problem with the way that they’re developing those when they thaw out are not viable and the ones that thaw are able to go through the thawing process are viable and so the actual success rates of frozen thawed embryos is actually significantly higher then yeah then just fresh yeah that’s like almost like an evolutionary test it is it is exactly what it is it’s a filter for fitness but it doesn’t it doesn’t actually death I mean it doesn’t actually impact most of the embryos at all so and so where do you see the story going I mean we’ve read this far these babies are now born yeah these and there was there’s another pregnant woman – I’m pretty sure or so I know what’s your expectation for the next year – well I think the bigger story is actually selection not editing for the reason that I stated which is that we don’t really even if I gave you a super CRISPR we don’t know what to add this moment in our scientific knowledge we don’t know exactly what edits we would make the predictors rely on correlations if you’re going to edit stuff you have to know about causation and so you can know ahead of time that okay this distribution of genes in this trial in this embryo predisposes it to has a higher probability of having breast cancer but you don’t know how to change the genome necessarily – to make it resistant to breast cancer so that’s science I think is going to take at least another five or ten years if not more to develop before we can go hog wild on today go hog wild on editing because you’d need to know what to edit however the the the the the strength of these predictors is increasing very rapidly because machine learning just needs data and there’s there’s more and more data and so the number of traits that we can predict from genome alone is going up and up and up and we don’t really even need to fully predict the trait we just need to figure out who’s an outlier so if I’m just trying to warn you about hey embryo four may have much worse health much you know decrease the longship expected longevity than the other ones maybe you should use one of the other ones that kind of differentiation is already possible and it’ll just get better and better so how much does this process process cost now by your startup I think the price so I’m not involved in the day-to-day of the startup I’m one of the founders but I’m on the board of directors but I’m not really directly involved so I might say something that’s wrong but I think the pricing is four hundred dollars in embryo for the advanced testing it’s very unique it’s very affordable how’s that compared to the price of the IVF I think in ivf cycle it really depends on where you do it like if you do it in Korea or Taiwan it’s actually pretty inexpensive it could be like a few thousand dollars for an IVF cycle I think but in the u.s. maybe it’s more like ten five $10,000 but it’s a it’s a it’s a per bation – it’s a small correction to the overall cost that’d be fab okay so let’s let’s let’s just cut it there and until the next time fabulous all right