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42 - Insights from a Futurist: Genetic Engineering, An Interview with Jamie Metzl

42-metzl

Preimplantation genetic testing has opened up a world of helping families have successful pregnancies. But when does the testing and selection of embryos go too far? In this episode of Inside Reproductive Health, Griffin talks to Dr. Jamie Metzl, author of Hacking Darwin: Genetic Engineering and the Future of Humanity. They discuss the implications of advanced technologies such as the future of embryo screening and gene-editing. More importantly, Dr. Metzl discusses the significance of understanding the coming technologies and how those in the fertility field can help prepare their patients and the rest of the world for these changes.

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Welcome to Inside Reproductive Health, the shoptalk of the fertility field. Here, you'll hear authentic and unscripted conversations about practice management, patient relations, and business development from the most forward-thinking experts in our field.

Wall Street and Silicon Valley both want your patients, but there is a plan if you're willing to take action. Visit fertilitybridge.com to learn about the first piece of building a Fertility Marketing System--The Goal and Competitive Diagnostic. Now, here's the founder of Fertility Bridge and the host of Inside Reproductive Health, Griffin Jones.

GRIFFIN JONES: Today on Inside Reproductive Health, I'm joined by Jamie Metzl. Jamie is a leading futurist and geopolitical expert and science fiction novelist, as well as a senior fellow of the Atlantic Council. He was recently appointed to the WHO’s expert advisory committee on human genome editing and he has served in the US National Security Council, the State Department, and Senate Foreign Relations Committee, as well as having studied with the United Nations in Cambodia and has written on the Cambodian genocide. He has written books such as The Depths of the Sea, which is a historical novel and The Genesis Code and The Eternal Sonata, which are science fiction thrillers. His latest book is Hacking Darwin: Genetic Engineering and the Future of Humanity. That's the reason why he's on the show today. He has a few other less impressive credentials such a PhD from Oxford and a JD from Harvard Law. I'm very excited to have them on the show. Jamie, welcome to Inside Reproductive Health.

DR. JAMIE METZL: Thanks so much, Griff. I'm thrilled to be here with you.

JONES: You're on the show because Serena Chen is a mutual friend of ours. She's always trying to get me to do something, to read stuff. And she said, “You have to have my friend Jamie on the show!” And I said, “Ok, sure, he’s probably an interesting guy.” And I think you and I had corresponded before MRS. And then I’m at MRS--Midwest Reproductive Symposium--and I didn't go to your talk because I was probably doing something really important, like talking with a client about Google AdWords or something. And everyone comes out of the talk and says, you could hear a pin drop in there. And they gave me a copy of your book, and you had later sent me a copy of your book, but that's what everyone wanted to talk about for the rest of the conference. And I thought, “Oh, I should really see what this guy is talking about.” So I’ve read through most of your book. What I can tell is that you really have a vocation for that.

METZL: I'm really passionate about it. So first, thanks for the kind words. Even though you have finagled an extra free copy of Hacking Darwin, and I'm thrilled for you to have it. And I'm just incredibly passionate about what the implications are of this incredible genetics revolution that we, and we I don’t just mean people in the field of fertility, or medicine, or science--we humans are passing through, we're really, these revolutionary genetic technologies. They're not just going to change healthcare as we transition from generalized to precision to predictive healthcare and health and life, and they're certainly going to change the entire field of assisted reproduction, which is already starting to happen. But in the longer term with this, we will have significant implications for even our evolutionary trajectory as a species, whether it's here on Earth or as a spacefaring species, which we will have to be over time because this planet isn't lasting forever. So I’m incredibly passionate about it. I do a lot of speaking to medical groups and science groups. And so that's why I'm very happy to be here speaking with you.

JONES: I'm glad that it's you as well because you approach this from a very tempered angle, a very considered angle, and it's not someone who only stands to gain financially by pushing some version of genome editing. It's not someone that trying to rouse the masses in hysteria for some sort of political concern. You pretty much from the beginning of the book, lay out this is where we're going and here are some of the really great things that can happen, here's some of the really bad things that could happen. And you revisit both sides pretty frequently throughout the book.

METZL: That's really important because if anybody is saying, for any technology, it's all good, it's all upside, nobody is going to trust you and no one should trust you because every technology has an upside and a downside and people are conscious of that with AI. But even things like the plow, the wheel, they have an upside and a downside. So if we are one thing to have a meaningful conversation about these technologies and how they should best be used to optimize the good stuff and minimize the bad stuff, we just have to be honest about, here are the potential ways we’ll benefit, and here are the potential dangers. And then we need to bring people into an inclusive, not just a conversation, but a process of figuring out how do we optimize the good and minimize the bad. And that’s what I’ve tried to do in the book.

JONES: I think that you said something along the lines of--having the balance humility with hubris. But you said something along the lines of, if humility not hubris has been our guiding principle as a race, we would look very different from who we look today. Can you talk a little bit about that?

METZL: Yeah. I mean we are these crazy monkeys and somebody had an idea to first, whatever, one of us to climb down from the trees, and if somebody was always the first person to do all these crazy, crazy things that we've done, and every time there's been some new technology that could be used for something, whether it's hunting or showing other people or whatever, we've done it. And we are this--and that's why our species has been so distinguished from better and for worse from every other species on Earth. And that's until we can't pretend that we now have this Promethean new set of technologies, and certainly genetic technologies are foremost among them--the genetics, AI, robotics, all these things. We just can't assume that we are a different species than we are. We are this hubristic species and there are just so many of us trying so many different things that we just have to assume that we are going to very aggressively use this and every other technology, and that's the starting place. And then we have to ask ourselves, if that's the case, what do we do about it?

JONES: That’s a decision that you lay out for us in the beginning saying that will be the most important and consequential decision we individually and collectively will ask over the coming years. How we answer it will determine who and what we are, where we live and can live, and what is possible for us as people and as the species. So we don't have a couple hundred page book, we have maybe an hour podcast, but if you were to lay out the decision as it is--as you describe it in the book from a bird's-eye view, first talking about the technology that we have to screen, now with IVF and then ultimately to genome sequencing to gene editing to epigenetics. What is the decision that you're laying out for us here?

METZL: It's a process of decisions and so part of it--and I’ll just jump over this very quickly--part of it deals with how we think about the application of genetic technologies in medicine. I talked about this transition to precision, also known as personalized healthcare, and so that's certainly something that is coming. But in the context of ART, we have some really big decisions in front of us. So, the first one is how we think about the role of IVF and embryo screening, not just for the higher risk pregnancies as is currently the case, but for everybody. And it's my contention that we're going to move from conception through sex, primarily, we’re going to move toward more and more people procreating and through IVF and embryo screaming. And the reason that we're going to do that is when you take conception outside of the human body, you then have the ability, as all of your listeners know, to apply science to the pre-implanted embryo in ways that weren't possible before. And so in the first phase, that will be through enhanced embryo screening and certainly will continue to screen for the single gene mutation and chromosomal disorders that are now primarily what we screen for. But as we continuously and continually unlock the secret of complex genetics, we're going to be able to screen for a lot more, certainly health-related, but also life, traits, things like, if we choose to, height, genetic component of IQ, genetic component of personality stuff--really personal stuff. So that's Phase 1 and Phase 2 is using induced pluripotent stem cell technology to dramatically increase the number of eggs available in the IVF and embryo screening process. And that is a technology that, as your listeners know, is advancing very rapidly in animal models, not yet applied to humans, but I think it’s pretty likely that in some number of decades, we're going to be able to generate large numbers of human eggs and that really opens up the mathematics of embryo selection because if you're selecting from among about 15 pre-implanted embryos, you don't have that many options, but bump that number up to 10,000, we have a lot of options. And then finally, is another frontier that--again, we've already crossed this line--it is of the gene editing of pre-implanted human embryos. As your listeners know, last year the world's first two CRISPR babies were born in China. This year, it's very likely that a third baby was probably already born in China and those numbers are going to go up and so we're individually and collectively going to have to ask ourselves questions at each level: What do we want for ourselves? What are we comfortable with for ourselves? For our communities? For our country? And then for the world? Because this really--when somebody in some other country makes a germline or heritable change to a pre-implanted embryo that’s taken to term, that our kids could procreate with their kids and so, very quickly, if we don't have global rules and a global standard, this could get very complicated.

JONES: When you were talking about Phase 1 in the book--and you do a good job. Throughout the book, I'm reading and I have a question in my head, and I say, what about this? And for most of them you answer them later on in the book, but when you start off talking about this phase one, as you describe it here on the show, moving toward more screening, optimal embryos, using PGT as we have it now, and probably some better variations of it. And you paint a picture of an REI as a coffee barista--and the listeners should read that chapter because I laughed at that and thought that's not too far from where we're going as far as a practice setups are. But as far as the ethical concern, you're laying out the ethical concern, and woman goes and she has a few options for things like screening for down syndrome among her embryos, she freezes her embryos, she comes back much later and she's got more options. She comes back many years later and has even more and that part I thought--this is child's play, Metzl. I haven't heard the ethical dilemma for most people yet because most people, I think, are still feeling like this is--what's the difference if I had eight embryos and I have the option to pick which one is going to be the most successful. They're still all of my embryos, all of my partner--from my partner's gametes as well, they’re genetically us, that still falls within what, I guess anecdotally perceived, what most people would consider natural. And I don't want to skip over Phase 2 because there's so many implications there, but I really see in Phase 3 just so many options that as the technology progresses, I think there's so many different possible outcomes to weigh against each other and that's where a lot of the dilemma comes out. Do you think I'm being too remiss over Phase 1?

METZL: Yes, I do.

JONES: Or do you think Phase 2 is where most people will--

METZL: No. No, I think that every one of those phases will be unbelievably complicated because even if it's phase one--let's say you have 10 fertilized eggs, zygotes, you're having to select among them. Yes, people will understand, “Well, I don't want to make a selection of an embryo is likely to die. The child is likely to have some terrible deadly mendelian genetic disorder.” I think most people will eventually become comfortable with that outcome. But we're going to have a lot more information of what we are selecting. Will people be comfortable if others are selecting the kid with the highest genetic component of IQ? Let’s say it’s a mixed-race couple and they tell the doctor we want to have the lightest skin child, the darkest skin child, we want to have a child who's more outgoing, or more introverted, or deaf. I mean there are all kinds of possibilities that it's not just motherhood and apple pie, it’s actually pretty complicated. And that's why there are countries in the world like Germany where there are pretty significant restrictions just on embryo screening because they feel that embryo screening is--and it's technically the case--it’s a form of eugenics. And I, myself, am the child of a refugee from Nazism. So when we're doing eugenics, even though we need, maybe, eugenics to promote health, we just need to be very mindful. We need to recognize that there are a lot of really important ethical issues that we can't skate over. And that's just magnified when if we are able to use IPS technology, IPSC technology to have 10,000 eggs. I mean, that's really able to do a lot--you're able to push the human development process. And then with genome editing, then that adds a whole new angle of what are the different kinds of traits and attributes that we will be able to engineer going forward? So all of it is tricky and I think that it would not be in our interest to underplay the significance of the ethical issues from the start.

JONES: I definitely see your point of all of the controversy that can come in from Phase 1. Probably the reason why I made that assumption is because I just concluded as an inevitability, and of course, I could be wrong, history will play out. But I just look at the way Gen Z and Millennials make demographic decisions, the way they make political decisions, the way they talk, and there's so much to argue for what we now might consider ancillary traits or as things that could be elective, like musical talent, or height, or athleticism, where I just see the argument that someone could make of I had a really rough childhood. I wasn't athletic, I was bullied because of that. There was so much that I couldn't participate in and that led to depression and addiction, and just--I hear a very similar narrative already among Millennials and Gen Z that I could just see this leading to the public acceptance. So I’m sort of concluding it as an inevitability. You point out the controversy, which I think means it not inevitability, but do you still see the more widespread acceptance of it?

METZL: I, for sure, agree. I think that it is inevitable, the only thing I'm saying is we shouldn't pretend that it's not incredibly complex, not just from an ethical perspective, but just for a human resilience perspective. I mean, we are human, humans, our diversity--it's not some little add-on, it’s our core survival strategy as a species. And so let's just say that we have widespread acceptance and everybody ends up wanting to have a tall kid with an outgoing personality and a high genetic component of IQ. If we could get all of those things, that may help us in some ways, but it could reduce, potentially, the overall diversity, and therefore, resilience of our population as a whole. And even if we did things like selecting out recessive carriers of potentially deadly mendelian genetic disorders--which is kind of just, that's kind of like most basic intervention that most people will probably want--even that comes with the risk. And we all know that being a recessive carrier of the Sickle Cell mutation actually can concur some additional resistance to Malaria. But how many other recessive traits do we have--genetic disease states do we that could protect us against future pathogens or threats that we haven't yet faced. And we have no way of knowing that. But, all in all, I do think that this future is inevitable for our species and the question to us is, how do we want it to play out? And how can we intervene to make sure it plays out in a way that is most helpful to each and all of us?

JONES: That example of the potential adaptation to Malaria, for example, by being Sickle Cell Anemic is a good segue into Phase 2 implications and disruption, the possible controversy, because in the book, as I am reading it, I'm developing this notion--perhaps it’s not fully thought out yet--but it's essentially that by the current science is really able to plow through a controversy, it sometimes solves what had been controversial prior. An example of that to me is embryonic stem cells. That part of the controversy of stem cells, among many others, was that they came from embryos and now having the ability to revert almost any cell to a stem cell, eliminates that--I suppose, just puts that particular concern out of consideration. So could you talk a little bit about that? About what concerns that we might have had going into Phase 2 regarding stem cells or ability to to reprogram them, re-edit them, I should say?

METZL: Right.

JONES: And what that means going forward?

METZL: Yeah. Yeah, well, certainly embryonic stem cells and induced pluripotent stem cells are extremely similar, but they're not always completely identical. And so there will be differences in different jurisdictions around the world in how comfortable people and societies are in using those embryonic stem cells. So certainly, that issue has not been overcome, but there are other avenues for accessing or even generating stem cells. And so, but yes, in terms of the big picture point, that's exactly right. In the world of science, and the world of policy, and the world of culture are all changing and they’re changing in a very dynamic and interactive way. And so what we need to be doing is talking honestly about the issues in the context and recognize that that context changes. But the core point and the reason why embryonic stem cells were so sensitive and are still so sensitive politically and otherwise is that this represents--and depending on your politics--at least the potential for human life. And because of everything that we're talking about deals with human life and the future of human life, we just need to make sure that we're being extremely thoughtful and extremely respectful and also extremely inclusive because these are, as we've seen with stem cells, that we've seen in the abortion debate, these are very, very sensitive issues and we don't want to turn the future of reproduction into another battleground like GMOs and abortions have become.

JONES: Which could easily happen and that doesn't even consider some of the implications in the field. Which you give--one of the examples that you mentioned, if you add the ability to turn skin cells into egg cell for example, instead of just retrieving a dozen eggs. Instead of a woman having 3-400 eggs in her lifetime, you could have more than that in a single retrieval or whatever would replace the retrieval in this sense. You've mentioned same-sex male couples, for example, being able to create egg cells from skin cells, which means that both partners could both be biological parents of the child. And this one little application essentially wipes out almost everything that we have for donor egg today.

METZL: Yeah. So insofar as mice are examples for human potential, we already have two different labs in China that have bred one female mouse with another female mouse and they had their own mouse pumps and those mouse pups were able to procreate. There is another lab that bred a male mouse with another male mouse and they had pups. Those above were not able to procreate. And so, basically what we're seeing here is the malleability of biology and insofar as this transitions into humans, which over time I think it very likely will, just a lot of our assumptions about how the world works, how biology works, will be challenged and that's going to be very difficult for people. It’s just a whole new set of assumptions that are different from the assumptions we have had and now have.

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JONES: Your cautionary tale towards Phase 1 and 2 and my cavalier attitude, at least towards the beginning, is notwithstanding. Let's move on that the juicy stuff--Phase 3.

METZL: Yes, so Phase 3, again, it's gene-editing pre-implanted human embryos. If, you know, two years ago, if you had asked most experts in this field when we want to see the first gene-edited baby, maybe people would have said 7 years, 8 years, 10 years, but it was 2018-- October 2018--when those first two little girls were born in China. So we have entered the era of genome-edited humans and the numbers are going to go up. It'll be a little in the beginning--it may be a few a year, I would guess, but then at some point--and that point to be five years from now, it could be 10 years from now, but it's certainly not 20 years from now--those numbers are going to start going up significantly. And again, it's really challenging stuff and we need to start thinking about it and preparing for it. And so when there is a dominant genetic disorder or it could be a small number of embryos generated through the IVF process and all of those, all the available embryos will have some kind of terrible, it maybe deadly, genetic disorder, people are going to want to have this kind of embryonic “surgery.” And it's very, very hard for society to say that they shouldn't have it because the alternative is to it is actually pretty terrible. So that’s the world that we’re heading into and, again, the goal is how can we do this in a way that is as inclusive, as thoughtful, as respectful as it possibly can be.

JONES: Can you talk a little bit about that case in October 2018 in China because, if I recall correctly, you did not feel that that was ethical. You felt it essentially amounted to human experimenting--if I'm not putting words into your mouth.

METZL: Yeah, no one hundred percent right. He Jiankui, the Chinese biophysicist who did this, in my view, was a villain--and I called him a villain at my World Science Festival event here in New York with Jennifer Doudna--or a monster or whatever. This was human experimentation and he lied in his IRV application. He was extremely secretive, didn't collaborate, lied to the parent, the consents were, in my view, fraudulent consents. So it was just terrible and the intervention wasn't particularly successful. And the intervention that he was trying to do, it turned out we had the potential to even--if successful--shorten the lives of these girls. And then finally, it was so unethical because the first step toward in applying gene-editing to human embryo in the best case scenario would have been something very collaborative, very well thought through, addressing a specific target that would have otherwise caused a harm, where as in this case, it was trying to create a mutation on the CCR5 gene to create an enhancement which in this case, would have been increased resistance to HIV. Yes. It was just really, in my view, absolutely terrible in every way, but somebody was going to be the first. And He Jiankui, as far as we know, was the first. More are coming.

JONES: So the recklessness and human experimentation are 1 concern, and they’re likely very tied into the concern of eugenics. But I do see eugenics is a particularly distinct concern. And you answer once you get to the chapter on ethics which is chapter 7, I believe, but in the beginning, I am thinking, the concern about eugenics and why it has gone down in history as being so morally repugnant to me has so much to do with essentially, an authoritarian administration of forcing certain people to breed and forced restriction of other people that can't--through sterilization or even in some cases, euthanasia of small children, at some of its worst applications. So I always saw this concern of eugenics as being one that was authoritarian, either by mandate or restriction, whereas the ability now, perhaps the idealist promise of this in the future, is that, well, we can make everybody equal now. Now, we're not just saying that short people can't breed and tall people have to breed in this way, we can make everyone have whatever advantage that is important to them. So can you talk about how this concern of eugenics will be different from what we saw in the past?

METZL: Well, first let me just correct a little bit your interpretation of the past. So the real originators of eugenics weren't the Nazis. It was the Democratic American System that were really the pioneers of eugenics and, as a matter of fact, the Nazis learned from and looked at US State Eugenics laws when they were developing their frameworks. And then they took that too far greater level with the death camps and the people like Dr. Mengele came out of the eugenics movement, which is essentially a subset of science and medicine in Germany, very much connected to the United States. The difference here though is that while the eugenic model, at least in Nazi Germany was the top down, authoritarian dictas. Here, I think that some of the biggest--there maybe countries that will practice eugenics, I mean you could imagine a country like North Korea deciding you wanted to genetically engineer its population for one reason or another could, you know, over time, that will be possible--but the real drivers in most parts of the world are going to be parents. And who are going to be, in many cases, demanding interventions that have the potential to provide benefit to their kids. And then the question is how do we think about that? Because you know, I certainly support a woman’s reproductive rights. I mean, no human should have unlimited rights to do kind of “crazy things” to their own embryos. And so we, as a society, are going to have to decide what we think--as a national society, as a global society--what we think is okay and what we think is not okay. And certainly, people don't have the right to do harmful experimentation on their own embryos, even if they want to. We put people in jail for doing things like that. And so we're going to have to have restrictions. But you’re absolutely right. It's in most cases, it's not going to be the authoritarian state, it's going to be demanding parents wanting to confer benefits on their kids.

JONES: And I’m not sure if this is your quote or someone else's, but at one point in the book, you said, “Renegade scientists and to totalitarian loonies are not the folks most likely to abuse genetic engineering. You and I are. Not because we're bad, but because we want to do good.”

METZL: Yes. And we want to do good for our kids. And the problem is there's a little bit of a conflict between even individual desire to do what parents may seem it may feel like is good for their kids and a societal interest in maintaining the diversity of the population. And so that's going to be very, very difficult to negotiate.

JONES: Especially if you could use the first, meaning that the parental interest for the child, to argue--or maybe use the second to argue the first. Can people essentially say, “Well, we want to edit our child to be a different ethnicity than we are because we want to have a certain level of inclusion in our family” or--

METZL: Or maybe a different color. Yeah.

JONES: Yeah, and so just looking at the palette of especially Millennials and GenZ and how they frame political priorities now, that could be very difficult when those two especially go against one another.

METZL: Yeah, absolutely. And because these issues are so complicated is why now, we need to be laying a foundation of public education, of engagement, of inclusiveness, so that when we when these issues become more and more pressing, as they will become, we’ll at least have a foundation of readiness. Maybe we can use that as an opportunity to pivot to your primary audience of the people--the reproductive endocrinologists and the people in the fertility industry because those people are really at the point of the spear where these technologies, where the rubber is going to hit the road of kind of big ideas, basic science, and real-world applications. And that's why that whole ART community needs to be much more educated about these bigger picture issues, about the ethics issues. Already many people have dealt with patients, clients, whatever you want to call them, who come in and say, “Well, I want to have a boy” and in some places that’s legal, or maybe a girl, and in some places that’s legal and some places, it's not. Now there are fertility clinics that are letting people choose eye color and there’s going to be more and more of that. And the ART and REI doctors are going to need to be much more aware of the issue. That's why I particularly enjoy speaking to a lot of medical groups, I love speaking to the MRS Convention--a lot of doctors are reading my book so they can have a little bit of preparedness to have the conversations that are going to become broader than just the more narrowly defined issues of fertility and avoiding single gene mutation and chromosomal disorders which are now the kind of the mainstay of what ART docs are doing.

JONES: That community, by the way, I've forgot about them as we're getting so engrossed in this conversation.

METZL: Yeah!

JONES: It’s so broad and overreaching. And to your point, as this conversation that were getting into is broader than many of the applications that they have today, at what point does REI just become so little of a part of it to perhaps, relatively nothing to do with what we’re talking about?

METZL: Well, REI and ART, it's going to be critically important for a very, very, very long time because these applications of genetic technologies to the experience of childbirth, somebody is going to have to do it. And it's going to have to be these doctors and the community. Having said that, this industry is going to need to change because if IVF, embryo screening, and ultimately, genome-editing of pre implanted embryos becomes more and more mainstream, as I believe it will, somebody's going to have to do it. And that means that this whole community that is built around this set of assumptions about how many people are going through IVF, how many kids are born through ART, if that number starts to explode, then we’re going to need to think about ways of automating systems so that there's a lot less done by hand and more by machines. We're going to need to think about who are other kinds of professionals who we can bring into this process and how we can make sure there's adequate training. But we don't yet have an infrastructure that could support. Right now, we're a little less than 2% of kids born in the US are born through IVF. In Japan, it's about 5%. In Norway and Denmark, it’s about 10%. So if we went to Norway and Denmark levels here in the United States, the REI community would be overwhelmed and I think that's where we're going. We need to start building that infrastructure and certainly, there's a human capabilities part of that and there's an automation part of that. When I go and visit ART/REI clinics, you can just see there's a lot of mom-and-pop stuff that’s happening where the technology isn't really changed. I know I believe you’ve had David Sable on your show, who’s very thoughtful about automation. There's a lot that’s happening with companies like TMRW that are working on robotic egg and embryo preservation that just a higher level than the standard operating system of what kind of looks like a keg in the back of some of fertility clinics where the samples are stored. So this industry is going to have to change and that's going to have to change pretty rapidly. But better, there should be planning that goes into that process now, then scrambling if we don't prepare and that comes upon us later.

JONES: Yeah, they already are overwhelmed. And this gives a whole new impetus to access to care. I have clients that have seven week waiting lists. There’s only 1100 board-certified REIs in the United States and we already see a number of people that can’t afford care--part of the reason is by how it’s paid, but the other part is that the demand for fertility treatment is multiples higher than the supply of providers and infrastructure to provide for them. And you make the case in the book that essentially, it will be considered negligent to have children not using Assisted Reproductive Technology.

METZL: Or parents not using it. So it’s certainly in the future. Like, right now, when you see a kid with Down Syndrome, I think we all feel--I mean, they are wonderful kids--but you would wish a kid didn't have Down Syndrome, I wish the kid didn't have it because it's very difficult! But when you see a kid with Polio, you think, well wait a second, kids aren't supposed to have Polio. What went wrong? Why does this kid have Polio? And so we're going to change the way we think about many genetic disorders from some visitation of fate to some decision that somebody made in the system, or the decision among parents about how to go through the process of reproduction, or from the society about what services would be covered. So all of that is is coming and it's going to change our culture. But in order to be ready for it, certainly the whole suite of services that the REIs and ART practitioners are providing, it needs to be much higher throughput and less expensive. And I think those are both good things. We should want those things as people who care about providing the best service to our to our patients. But to make sure that there's not a quality drop, we're going to need to think differently about how this whole industry operates.

JONES: It really circles back to the conversation with David Sable as well because if it weren’t for entities incentivised by really bringing solutions to scale and using the market to reward them for that, it's hard to see how anything gets more cost effective or less costly if supply is to provide treatment, it grows incrementally at best and demand for services grows exponentially as you and others have outlined.

METZL: Yep. That's exactly right. And that's what we need to start preparing for and other models will be built in other countries. And so if there is too big of a problem here, then lots of people will start--who can--will go to other countries and this we now live in a global marketplace where there's a competition, not just of ideas, but of ways of societal and professional organization. And so this is coming. And the question for all of us and certainly for the REI docs and the ART industry as a whole is do you want to be facilitating this new phase, in not just this part of medicine and health care, but in our societal development, to make sure that it happens in the way that benefits the most people? Or do you want to be defending this old system that will increasingly become out of date? I think that the former is a much better place to be.

JONES: You’ve waxed philosophical and given us a lot of data throughout the episode, but Jamie, how would you want to conclude with your vision for the society and how ART can play a positive role and what our listeners should start taking into consideration now?

METZ: Really great question. So, I'll do big picture and then small picture. Big picture: this future is coming. Our genetically engineered future is coming. It's got some really incredible upsides and some real dangers. And we all--and especially those of us like the listeners to your podcast who are more aware of what's happening--we all need to play a role in doing what we can to optimize the good stuff and minimize the bad stuff. And that can happen on the individual level, in terms of professional organizations, but also in terms of getting our government involved. We have elected officials who don't know much about science, but they have to. And so we need to be part of that education process. And for the REI professional, the ART professionals, as I said before, they--I’ll say you--are all really at the pointy edge of the spear. And you are the ones who need to understand what's happening, and be able to educate your patients. And there's been some real progress, there’s some wonderful websites that provide educational material. Who is going to go beyond that? We have to keep building on that strong base. So certainly one of the reasons why I wrote the book is so that all kinds of people, including professional like your your listeners, to have a one-stop-shop place they can go and learn what they need to know to join the conversation. Once you have this background, we all have an obligation to engage others, to educate others, because our world is changing so rapidly and as you said in your earlier question, if the world is changing quicker than people are prepared for, it gives people a lot of anxiety. And in an issue like this, that could be incredibly dangerous and destructive and because we don't want that, everyone not only is, but has to see themselves as a stakeholder in building the kind of future we'd all like to live in.

JONES: I know we said we were concluding, but I'm really curious because we talked pretty little about this in the field, basically conversations that I hear both in talks and in side casual conversations, when you speak to REIs, to lab directors, to ACLDs, how familiar are they, generally, with what you’re talking about? I imagine they are curious, but what’s the baseline level of interest and background knowledge?

METZL: So all the people you've mentioned,they’re are all domain experts. I would say I speak to a lot of domain experts whether it's the doctors--I spoke to 300 of the top scientists at Lawrence Livermore National Laboratory at the guest of their director--but most of the people, 98% of everyone in these fields, they are quite rightly focusing on solving the problem right in front of them. And so these bigger, more philosophical issues are often further away and that's what I'm trying to impress upon people, is that this, what seems like an abstract philosophical sci-fi future, is actually coming so much sooner than we all think or are prepared for. So the kind of big picture--or the little picture understanding is extremely high. Big picture awareness is relatively low and that's what I've been trying to change through the book and the outreach around it.

JONES: Dr. Metzl, thank you for coming on after my razzing of your very prestigious alma maters and getting background knowledge, and the data, and bringing this to the forefront of our field. Jamie, I would love to have you back on Inside Reproductive Health. Thanks for coming to the show.

METZL: My great pleasure!

You’ve been listening to the Inside Reproductive Health Podcast with Griffin Jones. If you're ready to take action to make sure that your practice drives beyond the revolutionary changes that are happening in our field and in society, visit fertiltybridge.com to begin the first piece of the Fertility Marketing System, the Goal and Competitive Diagnostic. Thank you for listening to Inside Reproductive Health.