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Rhys Lindmark: Hello, listeners, today I'm excited to chat with Alta Charo. Alta is a Professor Emerita of Law and Bioethics at the University of Wisconsin at Madison. She's been focused on bioethics for a few decades across government and academia and industry, and I learned about her through this Netflix documentary on CRISPR called Human Nature. Alta, thanks for being on the show, and welcome.

Alta Charo: It's my pleasure. Thank you.

Rhys: Yeah. Excited to dive in and really this Netflix documentary as I've been doing this biotech research and bioethics research. It's like, "Oh, there's Alta in this documentary, and she's saying really smart things. I want to learn from her." So that's kind of the goal for today. But before we dive specifically into some of my bioethics and biotech questions, Alta, can you share with us and the listeners, what does this through-line that ties all your work together, because you were a biologist and now a lawyer, and how do you think about that and that through-line?

Alta: I have a lifetime of trying to combine my interests in social justice and political movements with my interest in fundamental science. What I discovered in the world of bioethics was the ability to look for ways that socially responsible and individually ethical practice can act as a spur for innovation not as a hindrance but as a way to direct innovation so that it proceeds and also provides as many benefits as possible for people.

Rhys: Wow. Interesting.

Alta: So a luxury of a career.

Rhys: That's amazing. So, yeah, you have this interest in specific biology side and then you have this kind of social justice lens. It's interesting, as you say, that it's like you're kind of, and this is a vibe that I got from you as I read your stuff on the internet, is you are kind of more into this might be saying too much, but it feels like you're kind of an optimist or, "Hey, let's make this innovation good and have good things happen for humanity." Then you are, "Well, let's make sure we minimize the harms." It's kind of a blank statement, but is that true? How do you relate to that maximizing goods versus minimizing harms question?

Alta: I think when you're talking about novel experiences, whether it's science or otherwise, I think people do tend to break down along a spectrum. There are some people who are particularly risk-averse and they imagine all the ways it could go wrong and will be wary of moving forward unless they've nailed every possible downside and at the other end of the spectrum are people who simply don't look at any of the potential harms and just are full screen ahead of whatever happens. I like to think of myself as being slightly on the optimist end of that spectrum, but not irresponsibly so. I fundamentally believe that science and technology has and will continue to improve the quality of life on this planet for humans and ideally for every other living entity. I also think that you need responsible regulation in order to bring that about. That said, I also have probably as a result of my personal background of, you know, coming from immigrant families living in the United States. I do tend to have a healthy respect for individual choice and for serendipity as opposed to planning the future simply for me, it's about trying to create guardrails and then just see what happens.

Rhys: Yeah, I like that. It's almost kind of a not necessarily a market-based approach which like, look, we're going to constrain it a bit to a little bit of regulation and then kind of let the thousand flowers bloom and within this kind of set of constraints.

Alta: It is that and reasonable people can absolutely disagree about exactly how much planning and how much serendipity you want as you move forward in the future. These are perfectly legitimate political debates, and I just, I confess to a bias.

Rhys: Great. Great, great. It's good to know where you're at. I think I'm probably where you are too, which is maybe like six out of 10 on that spectrum where, you know, try to be optimistic, try to make good things happen and also you don't be dumb about it. But let's kind of talk more specifically about some of those new bioethical concerns. I want to kind of frame this for our listeners, but also for you. I guess for me, you know, I'm writing this book on What Information Wants and the history of genes kind of over four billion years going into environmental niches and replicating there. Then we have these memes that have done a similar thing with our memesphere, and they have created the tree of ideas and religions and companies and all that stuff. Now we're at this weird place where the humans we've learned the code of life, DNA, and we're starting to kind of rewrite it. So as I'm writing my book, I'm like, “Oh man, I need to know how like humans are going to affect the biosphere going forward.” So with that as a frame, how do you, Alta, think about in the next hundred years or 10 years or what have you, how humans will rewrite or affect the biosphere?

Alta: I think you have to start with recognizing that DNA in particular and genetics, in general, is only one of many influences on how we behave and how the biosphere develops. So I remember as a college student, listening to Richard Lewington, one of the great biologists of the 20th century, talking about how you can have exactly the same genes and then water them differently and here comes a field and it looks not only like the plants are growing to different heights, but almost as if they're different plants. So since about the 1960s or so or 1970s or so, we've become a little overly genetics-focused. So first and foremost, I think we need to recognize that there are some limits on what genetics can determine. I think you really should think about genes and as kind of limitations. From, let's say, the shortest versus the tallest version of this plant or the hardiest versus the most feeble. Then after that, everything else is going to determine where it falls. We're learning. We, I should say, not say we, because I'm not the one who's at the bench. But scientists are better understanding more and more the biological mechanism by which these other influences determine how genes will express themselves. So epigenetics is crucial in understanding how strongly a gene presents itself, right? We're also learning more and more about the interaction within humans of, for example, our microbiome within our gastrointestinal system. None of this even gets close to dealing with the purely psychological and anthropological aspects of this, which is whatever my inclinations are, what I choose to do with that, how strongly I resist or am inclined to follow those genetic predispositions is a matter of personal choice and of social environment and physical environment. So I think that we can have a tremendous effect on changing the parameters within which our biosphere develops. But I don't think that we can actually determine either our own body futures or the particular futures of other entities on the planet, I think there are some limits to our control.

Rhys: Cool. Yeah, that's interesting. I hear one thing, you're saying and I agree with it. I don't know that much about and I just started learning recently about all the cool things we could do with genetics today and the different sequencing and synthesis and stuff. So I'm probably a little bit over-indexed on like, "Oh, cool genes stuff right now." But as you say, and I totally agree with you, this kind of idea of the extended evolutionary synthesis where it's like, "Hey, it's not just genes, it's also epigenetics. It's also a kind of niche construction. It's also a kind of cultural evolution. It's some of these meta engineering of kind of embryology and how like the laws of physics kind of change, how genes can be actually like, move through time." I super agree with all those and I like the idea of limitations, not just a specific thing to happen.

Alta: Not a determination but a set of parameters or set of outside limits. Yes.

Rhys: Yeah, like that. So with that in mind, do you see us, you know if you imagine what humans are going to do with it? I mean, do you see us like there's just maybe a crazy vision here, which is like, "Oh, we're going to rewrite the whole biosphere in the different niches that will exist. We're going to do geoengineering to kind of change the environment. Do bioengineering to both change. There's going to be woolly mammoths all over the Earth now and then, you know, humans will live to infinity and we'll, we'll fix ourselves and the DNA that has existed for the last four billion years now will all be kind of optimized for humans instead." How much do you really believe that or how do you see that kind of rewriting of the biosphere? Is that going to happen or not?

Alta: Well, first, I think the answer is, who knows? I think those kinds of predictions are beyond our foreseeable future. So I think people can calm down a little bit if they're tremendously worried about this. But I do see a potential in our foreseeable future to use biology more and more where before we use mechanical engineering to change the way we build buildings to take advantage of the potential. For example, living skins on buildings that would react to sunlight and humidity in a way that regulates the ambient environment in the building without having to use the kind of power that now has contributed to things like global warming. I can imagine a world in which we can construct things like a runway in a military context. You construct a runway through biological mechanisms. You can bring in whatever you need to bring in, and then the runway can be recycled back into the Earth instead of having to build a concrete structure that lasts forever. So I think there are tremendous opportunities to begin to think of biology in the same way been used to thinking about metals and stone, right, as a building tool. I also think that we can look forward to an increased ability to maximize our wellness through these advances in biology to begin to regenerate organs or even in the future limbs that have been injured and to be able to extend the period of time in which we can function at a high level. On the other hand, I don't think we're likely to get to a point any time within what I think of as foreseeable future in which the actual timing of our deaths can be profoundly changed, adding a few decades, maybe, but adding more than that there, there are for the moment, strong suspicions that there are absolute limits on how long our cellular systems can continue to replenish and regenerate. What might happen a thousand or 2,000 or 10,000 or 100,000 years from now, I think it's almost— I don't want to say foolish because I love science fiction, but I think it is now entirely in the realm of science fiction because you need to assume so many things that have happened and ignore so many things that will probably happen in order to develop those scenarios.

Rhys: Yeah, totally. Yeah, I like and I agree with that pushback in general. Unlike your specifics there, the first one of mechanical engineering, but with biology makes me just think of, yeah, it's like a kind of a solar punk future or whatever. It's a beautiful thing where I'm imagining some of these, though these cool xenobots, where you can kind of create these little organisms. These, you know, artificially designed organisms that go in, they pick up plastic in the ocean. Then when after they've done their little job, they just die. Instead of being a big metal thing in the ocean, which kind of sucks or like ammonia. Pivot Bio is doing this thing where instead of us making ammonia through fossil fuels and things and injecting nitrogen into the ground, it's like they just kind of do some genetic engineering-ish things, like make these little microbes, and then the microbes just kind of die and it worked with the natural processes of the Earth, rather than this kind of very artificial concrete and metal thing. So I love that perspective. Do you think on the regeneration side, let's kind of dive in on that. Specifically, there's this, there are these induced pluripotent stem cells and they're kind of hip these days. But I know you've been like checking them out for a long time. When I say hip, there's Jeff Bezos adjacent company that's raised $3 billion and has a bunch of new people called Altos Labs, whose working on this and there are a bunch of other folks as well. Could you kind of explain both for me and the listeners, what are these iPSCs, these induced pluripotent stem cells, and what's kind of the promise or why are these people getting so much money to do this?

Alta: Well, to do that, it requires stepping back a moment and talking about what stem cells are. At the moment of fertilization, when an egg and sperm come together, you have the full set of chromosomes that are going to exist in all the cells of your body. But at the moment, they could divide and divide a divide into any number of cells. Each one is going to wind up having to have a different function. So how does the body know—how does each cell know whether it should become skin or bone? It is a process that we call differentiation, in which certain aspects of the genetic machinery of the cell is turned on or turned off and that's what allows them to develop from what you can think of as the trunk of the tree at the fertilized egg stage into branches and from branches into twigs, each one becoming more specialized. For a long time, the assumption had been that this could only go in one direction from unspecialized to increasingly specialized. Then, with the work-around embryonic stem cells, where you get the first stages of differentiation into, for example, the outside layer of cells versus the inside layer cells for an embryo. People began wondering, "Can you reverse the direction? Can you take something that's been partially specialized, like in an embryo, and reverted back to this form in which it could become anything?" That was the beginning of a whole series of experiments which led to what you're calling and what we call induced pluripotent stem cells. That is, you take a stem cell that is almost completely specialized and you try to reverse it so that you could then redirect it. Go from being a skin cell from like a buckle sample that you take from the inside of the mouth and revert it to a more primitive stage and then redirect it to differentiate into something else. Let's say, like muscle, and that offers the possibility that we could take cells from one part of your body and revert them, and then redifferentiate them into the cells that you need, let's say, after a cardiac arrest when you've lost heart muscle. Can we take cells from elsewhere and redirect them to now become the kind of lost tissue that you need? So that's the idea behind this.

Rhys: Yeah. Cool. That's an amazing explanation. I love the tree analogy. Then we have these stem cells. They grow up into these other things. It's like, wait a second, we can reverse that. Let's take this stem cell that's already the sort of thing that's going to suck it back into its original state, put in the heart, and then make it grow into heart tissue, a heart cell. So that makes some sense. I heard some of these ideas you're like, "Oh, that's like we can build a new retina or whatever or it's like, "Hey, let's going to take this, like build it in our brains or in our eyes or whatever. So the idea here that we'll just be able to any of—within our body that we're going to be able to take these stem cells, reverse them, and then when whenever something like gets too older or whatever. It's like, "Hey, just build a new one of those." Is that kind of the rough idea?

Alta: Yes, I suppose. Keep in mind that to take your example of the eye. It's not only the retina but there are portions of the brain that control how visual signals are processed and interpreted. There are other areas that are responsible for the way in which the light and the particular wavelengths that we associate with color are going to be made available for interpretation. So the visual system is not something that can be cured with only intervention on one spot. You need to look at the entire series of events in our bodies that must take place before you can interpret the signals that you've now made possible to enter into your eyes and into your brain. So, yes, the idea is that we would identify parts that need to be replaced or repaired, and in some cases, it won't be all you could try to use a redifferentiated cell to replace whatever was broken. But it's not going to be simple.

Rhys: Yeah, yeah. On that, I love that. That's a great—and there especially for me coming in for a little bit of an outsider view, it's like, "Oh, we just do this thing and boom, it works." And you're like, "Whoa, whoa, whoa, whoa, whoa, wait a second."  That makes me think about like a more general question from that, which is just like systems bio lens, which is, you know, we have to some extent, you know, I'm a computer science major and a computer science mindset of like, we're going to do this and do that, and we'll just all kind of be simple and work out. Then there's the system's bio lens, which says, "Hey if you try to do one thing within—like our bodies, are these amazing in the biosphere, amazing complex system and so how do we kind of understand the information flows and the energy flows and how everything relates to each other? Do you see that kind of like, do you take that—how does its systems bio lens help us determine, you know, what is going to happen with these biotech things? Or kind of is that a helpful lens that you kind of use to understand how this works?

Alta: I think it can be. I'm going to take an example from a slightly different area and has to just deal with general medical care. We take a lot of measurements. If you go to your physician, particularly as you get older, they're going to be looking at your blood pressure, they'll be looking at how your body responds to glucose, they'll be looking at your pulse and your respiration and your metabolic measures and there's a whole lot of individual numbers. There's a kind of idealized number that has been developed that's associated with being healthy. But a more, a kind of a more systemic approach is not to ask for each individual measure, is it off somehow, but to ask when you look at them all together, is the body functioning well because, in fact, one system can somehow adapt to another so that you develop a way in which the body can function? So you want to be looking at homeostasis, you want to be looking really at the range of ways in which the body can function well under all these different, slightly different measures. In some cases, a single measure may be so crucial that it when it's out of whack, nothing else works. In other cases, it may be when something's a little bit lower, a little bit high that there's a kind of correlative accommodation by a different system so that in the end, the body still functions. That kind of systemic approach, I think, is another reason why it's important to not get overly, narrowly focused on a single gene or a single measure, but to think more holistically about how things are interacting with one another.

Rhys: I love that and almost in some ways, it makes me think of your explanation for two things earlier. One of which is your kind of views on regulation to some extent, which is, "Hey, provide the rails and then allow for the experimentation what have you to exist." Then your second one was, "Hey, genes are actually these limitations." But then there are all kinds of stuff that expressed them and do all this different stuff them. Then now it's like, "Hey, our bodies have this set of, you know, limitations or whatever. Then there can be a lot of play in the homeostasis there." So it's like the constraints then breed the creativity afterward. So that was just a kind of a maybe a similar lens across all three. The thing that you just said there, though, which I think is interesting is thinking about this different—I want to talk about polygenic risk scores right now, which as far as I understand our way to kind of look at different embryos and say, "Hey, if you look across all genes, not just, you know, one gene for Down's syndrome or whatever. If you look across all genes and their kind of interaction, you can look at something like diabetes and kind of determine ones that are more, some things are more genetically predisposed. So you're going to kind of look across all these genes and say, "Oh, these ones for diabetes." If what you see is embryos, they will be better for diabetes versus these ones, or rather that you have less diabetes with these ones." Do you think— I guess, you know, the direct question here is if you were having a new kid these days or something or you were going to have one tomorrow, would you do some kind of polygenic risk score for your kids and choose between four embryos for the one that would be the most healthy? How do you think about that?

Alta: At this stage of the development of polygenic risk scores, I don't think I would. And it's because their validity has not yet been sufficiently tested, and knowing myself and many other people are like me if you give me that information, as much as I know that it's very tentative, I'm going to wind up focusing on it regardless and we see this all the time. You know, everything has kind of a human interpretation placed on it. And so in the law context, I'm a lawyer, you know, when a criminal trial, you do, you tell people that the fingerprints say this, but there's an interpretive aspect to it. But it's very hard for the jury to somehow put a discount factor on the confidence it places on the identification of the defendant based on that fingerprint because there's a human element of judgment going into whether or not it's close enough to be considered a match. I think that's true generally with a lot of these polygenic risk scores right now. What I would test for if I were having a child these days is for those things that we know are both highly penetrant and currently completely miserable and incurable. So my background is Ashkenazi Jewish, that's Eastern European Jewish, and I would absolutely go ahead and do the tests for those highly penetrant genetic mutations that cause Tay-Sachs disease. It's a miserable illness. It kills children very young, and we don't know how to tackle it yet. In other cases, highly penetrant things, but they don't appear until much later in life. That would be things like Huntington's disease is a closer call because in the 40 or 50 years from now, when it might present in my child, there may very well be treatments that have been developed. So there I would be a little less certain, and a lot depends on the social context. You're living in a world in which somebody who's got a limitation in sight or hearing or something else. But that is a world filled with accommodations so that they are still fully functional. Is one that feels very different than a world in which you're condemning somebody to a very limited life. So again, I think it's not just about the genes, it's about how you interact with the rest of the world.

Rhys: I love that. I love both those things that you said there. One is, and I kind of heard this pushback on polygenic risk scores from someone else, which is there's a—we focus on the data there. So even the fact that they exist, even if it doesn't have, and I know, as you said, there's kind of there's still unclear on various different things, and it's also unclear on more intense things like IQ or whatever. But even if you get a polygenic risk score that says your kid is going to be a little bit smarter or whatever. Us, human types, even if it actually has no impact, we're going to think, "Oh, now the rich kids all have this like +2 IQ boost." And it just, it has these weird—so I think bringing in the human element there is extremely important.

Alta: I also want to stop you before we go into the next question because I find myself very troubled when we talk about intelligence and IQ scores and being smarter because even before we get to whatever the genes appear to be coding for, we need to identify what we're looking for. I don't know anybody that's come up with a definition of intelligence that would allow us to then make some judgment about whether a particular genetic mutation or variant is going to lead more strongly or more weakly toward one of those outcomes. So I know that there's a tremendous fear about using biology to create a caste system. We already have a caste system. We have kids who are traumatized as very young children by physical violence, by lack of good nutrition, by exposure to toxic substances, and in many cases, those things will impair them for life and that is creating a biological caste system that has nothing to do with genetics. In fact, for many of the things that you might think, genetics can give you some information on, like if you've got a predisposition to obesity, I'm sure that they're going to find a whole variety of genetic mutations that predispose people to certain metabolic patterns. The answer to that, and I say this is somebody who suffers from obesity is in fact the stuff that everybody should do anyway, which is exercise and eating mostly unprocessed foods without adding a lot of sugar and salt and fat. So why do I need to have this polygenic score, which is already still not completely vetted when what I really need to do is what pretty much everybody has to do, right? Which is a more a public health approach as opposed to a kind of genetic and individualistic approach.

Rhys: No, I love that. I love. I mean, two of the things that you said there, I think, are great. One is this definition of intelligence and kind of what we're optimizing for. And it reminds me also of your accommodation piece, which is, yeah, if you say, OK, you know, today in the United States and I'm not blind, so I don't really know, but we're a lot better if we're kind of more disabled or blind folks than we were 100 or 200 years ago or 50 years ago. So, you know, when you think about how someone when they're growing up, you know, they fit into an environment. So if that environment is more kind of conducive to their reality, then OK, maybe it's like we don't have to do that. We don't have to. We're less, it's less desirable to do the gene thing and just create an environment that actually will allow them to succeed and thrive. So I love that perspective. I also love the perspective of hey, yeah, we got to make this, we—I do think we will as humans start to, we're going to start by, you know, picking off the worst diseases. Then over time, we're going to start to optimize for the good things, health, and whatever. But really, as we do all that, making sure we're extremely—that, we keep your point in mind to say, what are we optimizing for here? Is IQ really intelligence? Or do we want, what about emotional intelligence? What about this? What about that? What about the other thing? Yeah, do you see that? So I agree with all that in that progression from, like, you know, low hanging fruit at the beginning of like super intense diseases to kind of eventually maybe optimizing for not just reducing the bad, but also emphasizing the good. Do you see that progression happening with something like polygenic risk scores?

Alta: Again, I don't think that polygenic risk scores have been vetted enough. We haven't had time to test out whether or not their predictions pan out, let alone to measure how strong those predictions are in light of varying, contextual influences. But do I think in general that we can move from the single gene variant that is highly penetrant and causes something that is clearly unwanted like pain and suffering? To something that's a little more subtle, something that might be the result of a strong genetic predisposition, but also needs an environmental trigger. Yes, I do think we're going to move there and then the answer will be, do you worry about the genetics or do you worry about the environmental trigger or both, right? I think it's going to be a very, very long time before we are able to really see ourselves with tremendous numbers of genes affecting multiple sorts in multiple parts of the body function in light of all the other influences. That's a very complicated calculation, and the nature of human experimentation is that there are some things we won't do, even though it's the only way to live, the only way to learn them. So we won't take two twin children, identical twin children, and place them into two different boxes with different environments and very limited environments. So you can, this one gets x amount of sunshine that one gets x minus two degrees of sunshine. We can't do that, right? So we can't do the experiments that you'd need to do to really strip down to the particular influence of each individual variable. So we're dealing with what you'd call dirty data, noisy data when you're looking at real-world experience.

Rhys: Yup, I love all that and love the continued emphasis on that kind of complexity or system you—this all makes me think about this general question of playing God. You know, we've spent a lot of time kind of destroying the biosphere in many ways and then starting to shape it with the agricultural revolution and other things. Now we can obviously kind of start to create it, either with with with genetic engineering and other things. How do you see these narratives of religion versus synthetic biology in terms of playing God and how they will kind of cold interact in the next decade or two?

Alta: I do think that there are very different notions about what the phrase playing God means, depending upon your kind of, the kind of theological stance you're coming from and it may not be because you're religious, it's just kind of in the air. So for many people, playing God is about the idea that there's a deity that directs events and if we take control and direct events, we're taking over the role of the deity, right? That's the way the phrase tends to be used in the United States, and I think that accords with a number of different variations in Christianity where you have petitionary prayers, "God, please do this for me." Assumes that there is a deity that can actually intervene and determine outcomes. God's will is another kind of phrase you hear that suggests a kind of directive deity. There are other kinds of religions. I'm thinking now about Judaism and Islam, where you have a much different notion of God as maybe the initial force to creating a universe. But for example, in Judaism, you don't get petitionary prayers, you don't assume that God will do something. So here, playing God is to take control, is not playing God, it's actually playing human. You know, I remember many years ago I was on the National Bioethics Advisory Commission for President Clinton and we were doing a study on this new phenomenon called cloning. Remember Dolly the sheep that had been cloned in Scotland at the Roslin Institute? We had a panel of theologians speaking to us and after having heard from several of the Christian theologians, Rabbi Moshe Tendler got up and he kind of turned the conversation on its head. He said, “We view humans as guests in God's house.” Now, what is a good guest do? Guest doesn't wait for everything to be done. A guest gets up in the morning, makes the coffee, makes the orange juice, takes some control. However, he said the guest doesn't move the couch. So we wound up in a conversation about whether cloning was the same thing is getting orange juice or moving the couch, right?

Rhys: That's hilarious.

Alta: So there isn't an understanding that there may be some appropriate limits on human manipulation, often because we are not wise enough to really appreciate the implications of it. But it is still fundamentally a very different view. The second one and I apologize going on so long, but the second one comes from this very moving scene at the end of a novel called Mendel's Dwarf by an author named Simon Mawer. The protagonist is a hereditary dwarf. He is looking at several embryos in a petri dish. They had been fertilized with the egg from a woman who was of average height. He recognizes that some of these embryos represent a genetic profile that's going to lead to dwarfism, and others will lead to average height. He asks, "Should I pick?" Right. Should I select which is basically your question to me and he ruminates about this. He said, "You know. God rolls the dice." Because if you don't do anything, it's all just statistical chance, whether you're going to wind up with a child who's got dwarfism or a child who's going to be average height. So choosing is not playing God. Choosing is actually doing something different from what God would do because God simply rolls the dice. It was just a completely different way of thinking about these things, and what I find helpful is that it helps to change the, change the debate a little bit when people recognize that there are some assumptions that we're making that are not shared by everybody. And so you need to step back and say, "Oh, well, you don't share that assumption that how are we going to talk about this? What other bases can we use to discuss whether it's a good or bad thing to do?"

Rhys: Yeah, interesting. So if I understand that correctly, it is, you know, when we use the term "playing God" and so much of the stuff is like what I would call frame control where you're like you saying, "Oh, here's the frame that we're putting on this debate." What you're saying is, let's, whoa, let's evaluate the frame itself. As you said, God can mean different things to different people and you know, this kind of goal-directed God, the God's will. That's not the God that everybody imagines. So there's a different version of playing God, which is the God as God creates. We're all a guest in God's house, and we should kind of hang out and do things and, you know, make orange juice but we shouldn't move the furniture. Then another version of that is, “Hey, what we're choosing—like God is just a dice.” Not always. But you know, God is kind of dice roll. That's like choosing between these different genetic, you know, inheritances or what have you. What we're doing by inserting ourselves in is choosing not to roll the dice and instead choosing this other kind of path. Is that correct?

Alta: Yeah, absolutely.

Rhys: Yeah, interesting. So do you think—and I guess is the point here like or how do you? Mm-hmm. Do you see—how I say this? I guess there's this huge like taking a macro view, you know? You know, you know, religion has had so much influence on society for a long time. So it continues to have whatever 80% of the world is affiliated with the larger religion. Is there—I just see there is this and maybe just from the Christian point of view. But like this, how do you see this kind of narrative battle happening? Or I mean, there's like that question. There's another one, though, which is like, what if you were to like produce a narrative for synthetic biology? What would that narrative be? So those are two questions that I'm ruminating on. What do you think?

Alta: You know, I'm not really sure what it would mean to say this is a narrative for synthetic biology. I think, though, that we are beginning to face the capacity to make changes that are profound and whether it's based on religion or something else, there is a portion of our population globally and nationally that is more attached to the idea that whatever is was meant to be. That grace comes from adapting to what was meant to be and making the most of it and that it's character building and that, that is the way we live, the best life we can live. Then there's an entirely other world of people who think that nothing, in particular, was meant to be that we are the agents of our own futures and that it is not only a privilege but almost a duty to take as much control as possible to bring about as much good as possible. However, you define good, which people will also debate. These are two very different sensibilities. I don't think that we have to get everybody to agree. I do think we need to get people to recognize that when they're debating cloning or they're debating editing embryos, or they're debating genetically engineered foods that often they're not debating the technology, they're not even debating the product or the immediate social implications. What they're really debating is their underlying worldview. I just think it helps to clarify why we're disagreeing. You know, in the area of genetically engineered foods, for example, I've watched many times where people who are in the technical fields feel like if they could just explain more and more and more about why it's really perfectly safe, that the argument would be over. But in fact, I think from the other end, I think there's a worldview that has something to do with a notion about nature and its role and our obligation to respect nature as it exists. It also is, I think, a misperception of nature as static. But because of the way we debate things, people in that world feel like they need to engage on the battlefield of safety because it's the only one that's recognized. And so they make arguments about safety that may not be technically justifiable, but they're doing it because they can't figure out a way to articulate and use their other real concerns. And so the debate goes on and on and on because we never get anywhere instead of trying to figure out, well, so what would it mean to have a spiritual attachment to nature? Is it really that inconsistent with using modern genetics to achieve a fish that can grow more quickly and pollute less and feed the poor? Right? No, it would just change the way we talk to each other.

Rhys: Yeah, I think that's all incredibly smart in love at all. What I'm hearing there is, yeah, it's like there are two fundamental different worldviews. One of them is this kind of nature gives us the playfield and we need to adapt to it. The other is we are the agents and we should do what we can to change anything, you know? As you said, it's like the kind of talking past each other when these folks are like, "Oh, but it's super safe and it's super good, it's super, whatever and the other person's like. But it's still not just adapting to what we are given. So I think—

Alta: It also opens up the possibility of highlighting for people how often we are internally inconsistent. So I may have this notion about nature somehow purer and better and more righteous or godly or whatever word you want to use in my food. But I have absolutely no problem in altering nature when it comes to taking an antibiotic to cure a bacterial infection. I'm also pretty comfortable with the idea that we need to have another road over here because, you know, I need to get to work. So again, I think it helps people then step back and go, "Oh, hmmm." So maybe I have to decide when it is so important to leave nature untouched and let it develop as it would versus when I think it's OK to intervene. Well, now we've got a much different argument. Now we've got a discussion about appropriate levels of intervention. Yeah, we're talking about regulation, though. And that's my world, right? I'm a lawyer. I'm talking about regulation.

Rhys: If you change the conversation to be about regulation, amazing. No, I love that. I think that that's great. I just think it's a great reframe on it. I think that, as you said, I love this kind of relationship to, our relationship to nature. It's like, you know, how to think about that relationship and who knows what the correct level is and all that. So those are all juicy things. As we get into wrap mode. I want to ask a couple of more general questions or kind of wrap-up questions, one of which is what advice do you have for young people who want to work in bioethics or biotechnology?

Alta: Well, I think the most important thing is that you recognize that bioethics is an area of application, it's not really a discipline in itself. So I would say find out where you are most passionately interested, where you're fascinated, where you're emotionally moved. It could be philosophy. It could be political science, it could be basic biology, it could be law. Whatever it is, find the discipline that matters to you and become really good at it, really delve in and then apply it to these social questions that exist at the nexus of the life sciences and all these other social phenomena. That said, I would also counsel this. For those that go into the social science and humanities. It's very hard to do good bioethics if you don't understand facts. For that, you need to really make sure you understand something about science. You don't have to be a biologist, but you need to understand something about basic science. You also need to understand scientific method so that you can understand how to evaluate whether something's been proven or not. From the scientists' side, for those people that want to become bench biologists or chemists or physicists or whatever. These things, these areas of science do not develop in a social vacuum. So I think to those people, there's really an obligation to have at least some basic familiarity with the structure of government and about theories about the degrees of individual freedom and the role of government in guiding or constraining individuals. I think it's really helpful to understand the history of the different ways we've understood individual good and social good and harm. So I'd say get deep expertise in your expert, in your own particular discipline and then get an appreciation of all the others that surround it.

Rhys: That's amazing. That is amazing advice. I think, yeah, it's like kind of how to have an interdisciplinary career. It's like, OK, you go deep on one—it's the tea model. You know, you go deep on one thing and then white on the other. I just agree with you that and for me, kind of coming a little bit more from the philosophical or kind of historical lens here. Yeah, I felt like I need to really understand how does this induced pluripotent stem cell research actually works? What is actually happening with Sanger sequencing versus Next-Gen sequencing versus long-read sequencing? What's the, you know, so and you can learn it like you go to the interwebs and the internet's amazing. You go to Khan Academy and you go to YouTube and you go to Wikipedia and there are all these amazing resources. So I think that's a beautiful part about our modern-day is that you can actually go and learn either the scientific things or, as you said, kind of the history of the relationship between individual good and public good. So I love that.

Alta: You've reminded me of other thing that's super important in this world of a million different sources of information on the internet, and that is to learn how to differentiate between reliable and unreliable sources of information.

Rhys: Yeah, yeah. Yeah. Look for the people who, yeah, look for—yeah, there's lots of signals for that and get good at doing that. I agree. The final section here is a little underrated, overrated section. Or I just want to ask you about two little things. Then you just tell me which one do you think is overrated or underrated with, like a little tiny explanation why? So the first one is CRISPR. Do you think CRISPR is overrated or underrated?

Alta: Oh, no, I don't think it's overrated at all. I think we're only beginning to see its power. Now, we're also beginning to see many variations on it. It's editing of DNA versus editing of RNA. It's about editing of the DNA and RNA versus the editing of the epigenetic signals. It's, you know, and it's editing just for one trait versus many traits all at once. So we are at the very beginning of this incredibly exciting new tool that makes it easier and faster and cheaper to make these changes and then see what their implications are. So, no, I don't think that's overrated at all. It may get overtaken by some other technology, but I think it started us on a very exciting power.

Rhys: I love that. That's actually expected you to say the opposite of that, because CRISPR is just like so known by society or whatever. But even still, you know, it's still underrated because it's really impactful. So that's interesting. What do you think about the thing we chatted about earlier, the induced pluripotent stem cells? Is that overrated or underrated?

Alta: Well, I think those are linked to CRISPR, that is you're going to use CRISPR to edit the induced pluripotent stem cells, and that's going to be the vehicle for a variety of therapeutic interventions. In fact, right now, we've got clinical trials doing exactly that. Take cells from the body and get stem cells and then edit the stem cells and put them back. I think that over time, we may learn how to do that in the in vivo fashion. That is, instead of taking cells out of the body and manipulating them in a lab and putting them back in. I do think that at some point we will figure out how to do the kind of Dr. McCoy Beverly Crusher Star Trek approach, which is, you know, you press what actually in the original Star Trek was a was a saltshaker. You press the saltshaker, somebody's arm, and it would start an interior transformation that would repair damage. I do see that coming.

Rhys: Exciting. Well, Alta, thank you so much for your time and energy, and clarity today. I really appreciated it. Is there anything that you want to tell our listeners to go to, where to find you or where to find your work or anything like that?

Alta: I think that the most important thing is that people understand that there are some places they can go for good information. I will be involved with some of them, not all of them. There are so many people in this field, the National Academy of Sciences and Medicine, the, the American Academy of Arts and Sciences, the major journals like the New England Journal and JAMA and Lancet, and such. These are reputable places to go for information. The government websites like the NIH are very helpful with instructional materials. I would say, don't use Reddit. And I'd say use Wikipedia with a little bit of a check on yourself because Wikipedia is only as good as the information people load into it. So they're discriminating consumer of information. At some point you'll see me waving up at you from that website.

Rhys: That's great. Well, beautiful. Thank you so much, Alta, again. And thank you listeners for coming and enjoying the show. Goodbye, everybody.

Alta: Bye, thank you.