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Speaker 1: For all of medical history, we've tried to persuade sick cells to behave better What if instead we just swap them out? If you have Parkinson's disease, should we give you another pill or should we grow brand new neurons from your own skin cells? Just imagine medicine a century from now. Will people look back and wonder why we spend so much effort trying to coax damaged cells into functioning instead of just replacing them. And what does this have to do with sending one's own cells into space or rescuing animals on the very brink of extinction. Today we talk with stem cell biologist Gene Loring about some very exciting future possibilities. Welcome to Innercosmos with me, David Eagleman. I'm a neuroscientist at Stanford and in these episodes we sail deeply into the cosmos of our thirty trillion cells to uncover some of the most surprising aspects of our lives. So what is synthetic biology? That kind of sells like maybe it means creating artificial life from scratch, but that's not really what it's about. A better way to think about synthetic biology is this biology has become an engineering discipline. For the entirety of history, biology has been observational. We caught sight of cells like bacteria and eventually neurons, and eventually we started studying proteins and then genes, and with centuries of labor, we've managed to figure out a whole lot about how these systems work, just like astronomers learned about the motions of the planet. But just over the past few decades, and in some cases over the past few years, we've developed tools that allow us to intervene directly. We can now edit DNA such that we can rewrite genomes, we can design proteins that have never existed on our planet before. We can program immune cells to do things.
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Speaker 2: Like hunt cancer.
00:02:25
Speaker 1: And what this has all led to is a different angle on the whole field, where instead of us just asking how biology works, we're now asking how biology can be redesigned, so that shift from observing things to engineering them. That is what synthetic biology is all about. And today's guest Gene Loring, works squarely in that world. She is a stem cell biologist and a developmental neurobiologist, and a geneticist and an entrepreneur and one of the pis of regenerative medicine. We'll get into what all that means in a moment, but before we jump into the conversation, there are two concepts that I want to make sure to set the table with. The first is stem cells. Every cell in your body contains essentially the same DNA. So when you look at two very different cells, like a skin cell on your arm and a neuron in your brain, the difference between them isn't about the genetic code itself, It's about which parts of that code are being used. So think about this like a cookbook. You and I have the same cookbook on our kitchen shelves, but you cook the pasta recipe out of it and I cook the Brussels sprout recipe. The information in the book is the same for both of us, but we get very different results out of it depending on which pages were consulting. Okay, so back to cells. Cell start off the same, meaning you could flip to any pages of the cookbook, and then during development, your different cells gradually specialize. Some become muscle and others liver and others retina and others, dopamine, neurons, deep inside the brain. As they specialize, they become increasingly committed to a particular identity. So stem cells mark the beginning of that developmental journey. A stem cell hasn't yet committed to becoming one particular cell type, so they retain this ability to grow up into any different type they want. Now, just about twenty years ago, biology experienced one of its great revolutions. There was a Japanese scientist named Shinya Yamanaka who discovered that by introducing just four proteins known as transcription factors. Now we call those proteins the Amanaka factors, you can persuade an ordinary adult cell, like a skin cell from your elbow, to travel backward along its developmental path. So you take the skin cell, you introduce these four transcription factors, and instead of remaining a skin cell, it essentially forgets what it was. It becomes what we call an induced pluripotent stem cell. Induced means you pushed it to get there, and pluripotent is just a fancy word that means it has the potential to become almost any cell type in the body. It has a plurality of potentials. Pluripotent, so a tiny piece of your skin can be transformed into cells that could later become heart cells, or liver or retina or dopamine neurons or whatever. Now, when I sit on airplanes and I chat with people, I have found that made Most people in the world haven't really.
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Speaker 2: Heard of this.
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Speaker 1: But what I want to say is that this discovery has fundamentally changed medicine and will continue to make it more and more unrecognizable.
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Speaker 2: Because now if you need.
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Speaker 1: Some sort of cells for a patient, instead of trying to get donor tissue or stem cells from an embryo, which is how it used to get done, you can start with the patient's own cells. You rewind them back to the beginning, and you nudge them to grow up however you want them to, and then you stick them back in the body.
00:06:35
Speaker 2: And that leads to.
00:06:36
Speaker 1: The larger story that we are exploring today. Historically, medicine has tried to influence cells that are already there. If some neurons are malfunctioning, we give drugs to try to change their chemistry. If immune cells are overactive, we try to squish them down. If blood pressure is too high, we alter the signaling pathways. In other words, we've mostly been practicing chemistry, but now we are looking at something very different, regenerative medicine. This means, rather than trying to persuade damaged cells to behave differently, what if we simply replace them. If you've got neurons that have died in some area of the brain, can you just make new ones and pop them in more generally all around the body. Can you restore tissue instead of merely treating symptoms. So it's less like trying to repair a broken part with duct tape, but instead saying, hey, I'm just going to grow the new part and stick it right in there. So this idea of cell replacement as medicine, this is still in its infancy, but this might ultimately become one of the defining medical revolutions of the coming decades. And today we're going to hear from one of the pioneers here, Jean Lorang, who has spent her career helping bring that future into reality. And as you're going to hear the implications stretch way beyond treating patients to things like the rescuing of endangered species. But I'm getting ahead of myself, so let's go to my talk with Gene Loring. I interviewed her on stage at the sin Bio Beta conference hosted by John Cumbers. This is a conference that brings together scientists and entrepreneurs and investors who are all exploring this fast moving frontier of synthetic biology. Here's my interview with Gene Louring. Gene you said at the intersection of developmental neuroscience, regenerative medicine and genomics, and Parkinson's disease, and more recently space science and conservation biology. So just to get us started and warmed up, just make sure we all understand what is a stem cell and what is an induced poor important stem cell.
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Speaker 3: Yeah, yeah, I'm trying not to use any acadyms. So a stem cell is any cell that can give rise to more copies of itself and it can then go on to become at least two different cell types. So we have stem cells in our body and our livers, especially in our bone marrow. Bone marrow has really great stone cells, but induced pluripotent stem cells are something entirely different. They only live in culture dishes, they are done in our bodies, and they are made from little bits of our tissue, either our blood or our skin and they are subjected to this process called reprogramming, which makes them pluripote, means that they can make any cell type in the body.
00:09:36
Speaker 2: So imagine, I mean, just this is where you start.
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Speaker 3: You could have your own cells in a culture dish that could be in every cell.
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Speaker 2: Type in the body that's yours. It has the same DNA as you.
00:09:48
Speaker 1: And why was the invention of high PSC such a scientific earthquake?
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Speaker 3: It just changed everything because before that we were working with embryonic stem cells, which made a lot of people uncomfortable. But also they didn't come from actual people. They came from embryos that were discarded in IVF clinics. And so the great thing about IPS cells is that we can know somebody's whole, whole medical history and then make cells from them with all that history behind it.
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Speaker 2: So now we have cells in a dish that have a medical history.
00:10:20
Speaker 1: So when you take a skin cell and you chemically rewind it all the way back to a pluripotent cell, what is actually happening inside the cell?
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Speaker 2: Yeah?
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Speaker 3: So I think you've heard about epigenetics while so essentially what it does is that it erases the reprogramming, erases the marks in the genome that make us sell a particular cell type. It doesn't change the DNA. So your skin cell has like some kind of pattern of DNA and mesylation.
00:10:48
Speaker 2: Reprogramming sort of gets rid of most.
00:10:52
Speaker 3: Of that at least, and then eventually that cell can no longer remember chemically, remember that it was a skin cell.
00:11:00
Speaker 1: And so you have described stem cells as being wonky.
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Speaker 2: Yeah, what did you mean by that? Yeah, So here's the problem.
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Speaker 3: So this is all the good stuff about stem cells, and then the bad thing is that they go on dividing forever. So the are two qualities of pluripotent stem cells and a culture dish.
00:11:15
Speaker 2: They will divide forever.
00:11:17
Speaker 3: They are the only cells that we culture that aren't cancer cells that have that property, and that's really important to note because they're unique in the universe. And because of that, every time they divide, and every time any cell divides, they acquire some mutations in the gene. There's not quite perfectly redone, so they accumulate maybe eight or ten mutations, which is no big deal because we have three billion base pairs, but every once in a while, the mutations occur in genes that are involved in cancer, like ONCA genes or the you know, like P fifty three, which is a protector of the genome. And when that happens, you start this process of essentially evolution in a culture dish. So the cells that do better are the ones that have those mutations. They're more cancer like, they're actually have the same qualities as cancer cells, and they survive better, they divide faster, and if you keep those cells growing for a long period of time, all of your cells will have those mutations.
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Speaker 2: So that's what I mean about being lucky.
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Speaker 3: And if you didn't look for them, you wouldn't know because the cells don't look any different.
00:12:24
Speaker 1: And so what are the implications for centerative medicine here, because we'll get to this in a minute about putting these cells back in the humans. But the bar is very high for this. So what does this mean that you've got this little Darwinian ecosystem in the petri dish.
00:12:39
Speaker 2: Well, it's it's like all evolution.
00:12:43
Speaker 3: I think you can't control it, but you can identify it. And if you look at your cells frequently, and we do whole genome sequencing to just to find out what happened, then it's no problem. And if they do acquire mutations, we throw them out. So it's a fail fast strategy. So that means we let them grow for a little while. If that culture dish has mutations arising in it, it gets tossed and there's always another one that hasn't done that.
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Speaker 2: And so this is like quality control. It is living sremely. It is really important.
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Speaker 1: Yeah, exactly, and so you use machine learning for that. Just give us a sense of how that works.
00:13:21
Speaker 3: Yeah, So the way that we've designed this trial, which we'll talk a little bit more about, is that we have some quality control what they're called release criteria. So we sequence the cells that we're making into neurons three times during the manufacturing when we first get them from a person. That's a reference. After we make ips cells out of those cells, that shows us what has changed, and then just before the cells are transplanted to people whatever has changed between those two stages. So we have algorithms that allow us to find out what mutations occurred and also which mutation and whether thoseations or are of concern because there are databases the tally which ones you should worry about? Now, does that eliminate all chance of those cells becoming cancerous. No, it doesn't, but it reduces the risk really considerably. And I was going to mention the phenotype of the cell as well. So to show that a cell's plury potent, one way you can do it is to do messenger RNA do transcriptone analysis. Because each cell type has a particular pattern of gene expression. So we developed a tool that in which you can use gene expression profiling of a cell culture you have in your lab, and then you can take those cells and like differentiate them into everything that they can possibly make, and then you get feedback from that, you do another gene expression profile, and then each one that's successful.
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Speaker 2: Falls into a particular category.
00:14:52
Speaker 3: So this is an asset called plury test and it is used by a lot of researchers. We published a long time ago, but it is still an acceptable way of you knowing that your cells are pluripotent just based on their gene expression profiling.
00:15:05
Speaker 2: It's machine learning.
00:15:07
Speaker 3: You just gather a lot of reference samples and then have you tested against a lot of other samples. And that's it's very very simple. It's not AI, it's machine learning. And then we have a second test, which we call neui tests. It's really essentially the same.
00:15:20
Speaker 1: But we.
00:15:22
Speaker 3: Profile the cells at the stage before they're going to be transplanted into somebody, and that allows us to know exactly the right stage at wish to transplant them. And that information is based on real information we get from animal models that when we put the cells into an animal model of the disease, then we get a result. The cells survive, the animal recovers, and we use that information to feedback to find out what kind of gene expression profile we want in those cells that we're going to put in humans.
00:15:51
Speaker 2: Cool.
00:15:52
Speaker 1: So this changes biology from just being an observational science being more like a predictive engineering discipline.
00:15:57
Speaker 2: Yeah, very cool.
00:15:58
Speaker 1: Okay, so now let's go to what you do with this, Because when people started looking at these induced pluripotent stem cells, they you know, they were very interested in what was going on alow, but your interest has always been how do we get this into humans?
00:16:12
Speaker 2: Right?
00:16:13
Speaker 1: So, in Parkinson's disease, you have the destruction of a little tiny nucleus called the substantial niagra, which has neurons in it that spit out dopamine to the rest of the system. So, first of all, why are those cells so crucial.
00:16:27
Speaker 3: So there are cells that control sort of fine movements. You know the problems with people with Parkin's disease. There are a lot of motor deficits. Sometimes they freeze, sometimes they have a tremor. But by the time people are actually diagnosed with Parkins disease, they've already lost half of their dopamin neurons that are in the substantialiagra. And so our goal is to replace those neurons and restore the function so that people can recover or at least be don't not progress any further progress of neurodegenitive disease. So if we can arrest it, that's great. If we can reverse it, that's even greater.
00:17:21
Speaker 1: So when did you first realize that neuron replacement therapy might be feasible.
00:17:27
Speaker 2: Well, I have some historical help.
00:17:31
Speaker 3: Back in the nineteen eighties and nineteen nineties, there were some very brave researchers in the US and mostly in Sweden who took little bits of fetal tissue aboorded fetus. There's a part of the brain of an aboarded fetus at particular stage six weeks old. You can cut it out and you can put it into a syringe and inject into people's brains. That's what they did, which seemed very crazy at the time. It's probably still crazy, but the fact was that some people who got those fetal cell transplants recovered from Barkins's disease, I mean completely recovered. It was really it was just like a miracle, but it was a rare miracle. So the reason we picked Parkins diseases was that we knew that if we got the right cells into the brain, we might.
00:18:19
Speaker 2: Be able to have that happen every time.
00:18:22
Speaker 3: And induced puripotent stem cells gave us the opportunity to make cells that what might function just as well.
00:18:30
Speaker 1: So now, when people started thinking about this, it's fair to say that everyone else thinking about it was thinking about using allergenic approaches, meaning you take a donor cells and you distribute those among patients. But you started thinking about what if you could do this autologously, meaning use people's own cells in their own brain stem.
00:18:51
Speaker 2: So, yeah, well that makes.
00:18:52
Speaker 3: Logical sense, right if if you had a choice of using of having your own cells replaced your own cells, you would not have to be on the suppressed. Your cells should recognize the environment, they should thrive so people didn't think that was possible. But because we had such a strong genomics background, we figured out ways to qualify individual cells from individual patients.
00:19:17
Speaker 1: I just want to get that street though. Why did people think that was possible? Why did they think that doing this other method was better?
00:19:23
Speaker 2: I think it was sort of like I think.
00:19:25
Speaker 3: I mean, we had a unique combination in my lab. We had a lot of people in new stem cell biology and a lot of people are new genomics. So we talked to each other, and so it just made sense that we could do it. And then we had lots of reasons to do it, because you don't want to men to suppress people. If you don't have to, it's dangerous. In another one of the trials that was using allergenic that is, not unmatched cells, one of the patients died from an infection. So using atolog of cells means that we don't have to worry about things like that, and so in theory, those cells could still be in the person twenty or forty years later because they're their own cells.
00:20:05
Speaker 1: So walk us through the actual pipeline. So patient comes in with Parkinson's disease, how do you go from taking some skin cells all the way to having neurons that you put in their brain.
00:20:15
Speaker 3: Yeah, so it's more straightforward than sounds. These cells are very good at making neurons. There are lots of ways that people have established them making different neurons from pluryponent stem cells, lots of history. So we take a skin biopsy, you grow out the fiberglasts which are the dermal layer, and then those are exposed to what we call the Yamanaka factors transcription factors that transform those cells into induced pluriponent stem cells. And then of course we put them all through the rigorous testing and then we have as efficient as possible a method to go from undifferentiated cells to cells that are poised to become dopamine neurons. We haven't done it yet, so we need to. We had to identify that percise stage, and we did it by gene expression profile, and we identified it by that. And when you have the cells at that stage, at least in anal models which we had, that's the only thing went to go on. Those cells would thrive and they would reverse the symptoms of the disease. So we then those cells are then put into person's brain, so it takes the whole process. I mean it takes a while. For the first part reprogramming, you just need to make a little bit of a bank of cells. We don't need very many cells. This is one of the really important things. But about neural about replacing neurons, is that we only put around five to ten million cells inject them.
00:21:40
Speaker 2: That's not very much.
00:21:42
Speaker 3: People who are working on heart disease, for example, are talking about using billions of heart cells in order to restore hearts that are damaged by heart attacks.
00:21:51
Speaker 2: So this is like in a culture dish.
00:21:54
Speaker 3: If you looked at that many cells and a culture dish, it would be like a culture dish that big, and it'll only be one it's enough cells to treat a person. So it's not it takes a while because the steps take a while. But from the time that the cells are plury potent to the time they're staged in order to be put into a person is about twenty to twenty four days, so that's not very long, and we can make them in advance. That's a really great thing about the FDA, in their wisdom, allows us to make the cells that collect the fireroblasts, make the IPS cells ahead of starting the clinical trial. So that's what we did. In this case, you get id approval. We had all the cells already before we got the approval, so that made it really fast from then on.
00:22:43
Speaker 1: So historically medicine has said, look, let's target existing cells and try to influence them with some sort of drug. This is a very different kind of thing. This is replacing the cells entirely. Do you see this as a totally new chapter of medicine. And if so, what are the diseases, let's say, neurodegenerat diseases that are next, and which ones are really hard?
00:23:07
Speaker 2: So I think the hard ones.
00:23:09
Speaker 3: I mean the brain is actually a really great place to place cells because they don't Neurons and other glial cells, for example, support our cells of the brain. They don't leave the brain, you don't have to go search for them later. They don't travel throughout the body like if you were using a cart therapy. It goes into your bloodstream and it goes everywhere, even into your brain as a method. So we're so brain disease is really, I think a really kind of easy target in that way.
00:23:38
Speaker 2: The hard part of the target is.
00:23:39
Speaker 3: That we have to have we actually have to inject the cells into the brain, and that's neurosurgery. The diseases that I think are could be handled by not so much celler replacement. It is actually celler replacement, but a little more subtle than that. Or Alzheimer's disease and stroke, maybe multiple scroves. Those are all cases in which there's the cells are not working correctly. And one of the things I wanted to mention about the brain in general is how the neurons don't divide, but they keep making a synapsis over and over and over again. And David is one of the ex world's experts on what we call neuronal plasticity, So do.
00:24:18
Speaker 2: You want to explain that.
00:24:20
Speaker 1: Yeah, neural plasticity is just that, you know, you've got these eighty six billion neurons and your whole life, they're all moving around and sort of crawling and trying out different connections. Each one has about ten thousand connections with its neighbors, and it's sussing out those connections and unplugging and seeking somewhere else. So it's very weird to think about this crawling around process that's happening in your head, and that's not to mention the eighty six billion glial cells and everything else going on in there. But yes, your whole life, cradle to grave, your brain is reconfiguring. Every piece of experience, every memory that you have is represented by a change in the structure of the brain.
00:25:00
Speaker 2: Yeah.
00:25:01
Speaker 3: So that I think opens up the whole idea of once you place a neuron in the right place, then it will make connections in the right places, and it will adjust those connections. They'll become stronger, just like they are when during neural development. So these are not inert cells. They're actually quite plastic.
00:25:20
Speaker 1: Excellent, Okay, I want to make sure we have enough time. Tell us about the frozen zoo in San Diego.
00:25:26
Speaker 2: What is that? Okay?
00:25:27
Speaker 3: So my roots are employee potent stem cells. That's what I know most about. So I started working with the San Diego Safari Park quite a long time ago. They have a frozen zoo in which they have about about I think it's something like two thousand different species frozen in liquid nitrogen, which is where we store cells. It started in nineteen seventy five and it was made essentially to try to rescue the animals or try to save bits of the animal of animals that died in the zoo or even in the wild and interesting lay. The cells they decided to use starting in nineteen seventy five were dermal fibroblasts, so they have this huge bank of dermal fibroblasts. And a friend and I realized that we could maybe make IPS cells from one of the animals that's in the frozen zoo, and we picked one that is right on the brink of becoming extinct. It's the northern white rhino. And remarkably, a post doc in my lab was able to take the cells from the frozen zoo, thaw them out, and figure out how to reprogram them so we can make IPS cells.
00:26:33
Speaker 2: And one of the things that was so.
00:26:35
Speaker 3: Remarkable to me was to look at the IPS cells from an animal that had died ten years ago and we'd made them into heart cells in a dish, and we had in the dish those cells were beating, and so it really felt like that light that that animal had come back to life. What we want to do is to be able to make oocytes, eggs and sperm perhaps and then generate new animals.
00:26:59
Speaker 2: And that's that's not the same as.
00:27:01
Speaker 3: The extinction and the extinction it's it is a rescue of animals that are still alive or have cells in that bank, in the frozen bank. So the animals could all be gone in the wild, but if their their cells have been frozen in that bank, we might be able to bring them back.
00:27:18
Speaker 1: And I know that you make a good distinction between the extinction, which is usually using ancient DNA, versus this kind of rescue, which is using frozen cells. What did it feel like to you when when your post doc first made I p.
00:27:37
Speaker 2: Yes, ips cell. I knew she was. I mean, that's a that's a great thing about running a lab.
00:27:42
Speaker 3: You know, go try that and then I come back to me when you've done it, and it was yeah. I was thought, oh my god, it was so easy. In retrospect, she tried a lot of things. You know, it's trial and error when you are doing something completely new. But it turned out that the human yamanok effect reprogrammed the rhino. That's not true of other animals. We picked the rhino of all animals, and it worked. But if we picked a different animal, it wouldn't have because the factors are a little different different species.
00:28:12
Speaker 2: So rhinos turned out to be really easy.
00:28:15
Speaker 1: But in fact, one of the challenges you have is that you can make gamme meats in mice, but in rhinos. It hasn't succeeded yet. But you feel that's just a matter of tweaking.
00:28:24
Speaker 3: I think it's just a matter of tweaking because almost everything we've ever done started in a mouse. It was like the mouse paved the way, and then the methods are developed in the mouse. The methods have to be changed, sometimes modified, but that doesn't mean it's impossible. So when we have that basis, we have a hope that we can do it with any animal species.
00:28:44
Speaker 1: So in the future, if we freeze cells of all the animals that are around now, you think this technique could address sis if somebody.
00:28:51
Speaker 2: Wanted to do it, Absolutely yes.
00:28:53
Speaker 1: And somebody you know has human cells frozen at the San Diego Frozen Zoo.
00:29:00
Speaker 2: Yeah, I represent the human race in the Santiago.
00:29:04
Speaker 3: That was from years ago, you withdrew, Yeah, yeah, I made my own IPS cell. I mean, we made my own IPS cells back in two thousand and nine.
00:29:13
Speaker 2: We've been using them sort of as.
00:29:14
Speaker 3: Our standard for mucking around with things, and they're pretty good.
00:29:19
Speaker 2: Actually, they're pretty talented. We have to wrap it.
00:29:22
Speaker 1: I just wanted to ask you one last question, which is fifty years from now, when we look back on modern medicine, what do you think we're going to find shocking.
00:29:29
Speaker 3: I think this is going to be one of the options for diseases that we can't touch now at all. It would be cell replacement, and I think that there will be animals roaming the earth that didn't have a chance before.
00:29:41
Speaker 1: Thank you so much, Gene, and thanks for your work. That was my interview with Gene Loring. One of the things I find really exciting about what she and many of her colleagues are doing is that it's not just about stem cells. Stem cells are the enabling technology, but the deeper story is a change in how we think about medicine itself. As I said at the beginning, for most of medical history, we've treated disease by just trying to influence the cells that are already there. We've looked for molecules that crank one pathway up and squish another pathway down. We look for things that you can swallow or inject that suppress inflammation, or activate receptors, or block enzymes or produce more neurotransmitter or whatever. But fundamentally, we've always been trying to persuade tissues to behave a little better by changing their chemical environment, and that, by the way, has been tremendously successful. We've essentially tripled our life expectancy that way. But what's known as regenerative medicine proposes something fundamentally different. Suppose the problem isn't that the cells are behaving incorrectly. Suppose the problem is that the cells are gone. And if that's true, the answer is not going to be another drug. Maybe the answer is just to swap in some new cells. This is a conceptual leap from putting the duct tape on the broken parts to manufacturing replacement parts. Now, Parkinson's disease is an especially compelling place to start, because the disease destroys a specific population of dopamine producing neurons. If you replace those neurons successfully, you've addressed the problem at its source. But of course you can hear Gene already thinking beyond Parkinson's to stroke, to multiple sclerosis, to Alzheimer's disease, and eventually lots of other conditions in which cells have died or are no longer functioning now. It goes without saying that none of this is simple. As you heard Gene allude to, growing cells is really hard and subtle, and ensuring their genetically stable is difficult, and delivering them into the brain requires neurosurgery. And every new technology brings ethical questions hand in hand with the technical ones. But I want to note that's true of every major revolution in medicine. Antibiotics once sounded impossible, organ transplantation sounded reckless, gene therapy spent decades struggling before finally starting to fulfill its promise. Medicine advances because people are willing to imagine totally new ways of approaching disease. And there's another aspect of Gene's work that are found so cool. The same technology that can restore neurons in people with Parkinson's disease is also being used to preserve endangered species. The very same cellular reprogramming can help rescue the northern white rhinoceros and presumably eventually lots of other animals whose populations have dwindled. It's sort of rare that one scientific idea stretches from treating a human brain to helping preserve biodiversity only at the beginning of this story, and if history is any guide, future generations are going to look back on this moment in time, this first quarter of the twenty first century, as the moment that medicine began evolving from the science of influencing cells into the science of building them. Go to eagleman dot com slash podcast for more information and to find further reading. Join the weekly discussions on my substack and check out Subscribe to Inner Cosmos on YouTube for videos of each episode and to leave comments Until next time. I'm Dave Eagleman and this is Inner Cosmos.
Speaker 1: For all of medical history, we've tried to persuade sick cells to behave better What if instead we just swap them out? If you have Parkinson's disease, should we give you another pill or should we grow brand new neurons from your own skin cells? Just imagine medicine a century from now. Will people look back and wonder why we spend so much effort trying to coax damaged cells into functioning instead of just replacing them. And what does this have to do with sending one's own cells into space or rescuing animals on the very brink of extinction. Today we talk with stem cell biologist Gene Loring about some very exciting future possibilities. Welcome to Innercosmos with me, David Eagleman. I'm a neuroscientist at Stanford and in these episodes we sail deeply into the cosmos of our thirty trillion cells to uncover some of the most surprising aspects of our lives. So what is synthetic biology? That kind of sells like maybe it means creating artificial life from scratch, but that's not really what it's about. A better way to think about synthetic biology is this biology has become an engineering discipline. For the entirety of history, biology has been observational. We caught sight of cells like bacteria and eventually neurons, and eventually we started studying proteins and then genes, and with centuries of labor, we've managed to figure out a whole lot about how these systems work, just like astronomers learned about the motions of the planet. But just over the past few decades, and in some cases over the past few years, we've developed tools that allow us to intervene directly. We can now edit DNA such that we can rewrite genomes, we can design proteins that have never existed on our planet before. We can program immune cells to do things.
00:02:23
Speaker 2: Like hunt cancer.
00:02:25
Speaker 1: And what this has all led to is a different angle on the whole field, where instead of us just asking how biology works, we're now asking how biology can be redesigned, so that shift from observing things to engineering them. That is what synthetic biology is all about. And today's guest Gene Loring, works squarely in that world. She is a stem cell biologist and a developmental neurobiologist, and a geneticist and an entrepreneur and one of the pis of regenerative medicine. We'll get into what all that means in a moment, but before we jump into the conversation, there are two concepts that I want to make sure to set the table with. The first is stem cells. Every cell in your body contains essentially the same DNA. So when you look at two very different cells, like a skin cell on your arm and a neuron in your brain, the difference between them isn't about the genetic code itself, It's about which parts of that code are being used. So think about this like a cookbook. You and I have the same cookbook on our kitchen shelves, but you cook the pasta recipe out of it and I cook the Brussels sprout recipe. The information in the book is the same for both of us, but we get very different results out of it depending on which pages were consulting. Okay, so back to cells. Cell start off the same, meaning you could flip to any pages of the cookbook, and then during development, your different cells gradually specialize. Some become muscle and others liver and others retina and others, dopamine, neurons, deep inside the brain. As they specialize, they become increasingly committed to a particular identity. So stem cells mark the beginning of that developmental journey. A stem cell hasn't yet committed to becoming one particular cell type, so they retain this ability to grow up into any different type they want. Now, just about twenty years ago, biology experienced one of its great revolutions. There was a Japanese scientist named Shinya Yamanaka who discovered that by introducing just four proteins known as transcription factors. Now we call those proteins the Amanaka factors, you can persuade an ordinary adult cell, like a skin cell from your elbow, to travel backward along its developmental path. So you take the skin cell, you introduce these four transcription factors, and instead of remaining a skin cell, it essentially forgets what it was. It becomes what we call an induced pluripotent stem cell. Induced means you pushed it to get there, and pluripotent is just a fancy word that means it has the potential to become almost any cell type in the body. It has a plurality of potentials. Pluripotent, so a tiny piece of your skin can be transformed into cells that could later become heart cells, or liver or retina or dopamine neurons or whatever. Now, when I sit on airplanes and I chat with people, I have found that made Most people in the world haven't really.
00:06:02
Speaker 2: Heard of this.
00:06:03
Speaker 1: But what I want to say is that this discovery has fundamentally changed medicine and will continue to make it more and more unrecognizable.
00:06:13
Speaker 2: Because now if you need.
00:06:15
Speaker 1: Some sort of cells for a patient, instead of trying to get donor tissue or stem cells from an embryo, which is how it used to get done, you can start with the patient's own cells. You rewind them back to the beginning, and you nudge them to grow up however you want them to, and then you stick them back in the body.
00:06:35
Speaker 2: And that leads to.
00:06:36
Speaker 1: The larger story that we are exploring today. Historically, medicine has tried to influence cells that are already there. If some neurons are malfunctioning, we give drugs to try to change their chemistry. If immune cells are overactive, we try to squish them down. If blood pressure is too high, we alter the signaling pathways. In other words, we've mostly been practicing chemistry, but now we are looking at something very different, regenerative medicine. This means, rather than trying to persuade damaged cells to behave differently, what if we simply replace them. If you've got neurons that have died in some area of the brain, can you just make new ones and pop them in more generally all around the body. Can you restore tissue instead of merely treating symptoms. So it's less like trying to repair a broken part with duct tape, but instead saying, hey, I'm just going to grow the new part and stick it right in there. So this idea of cell replacement as medicine, this is still in its infancy, but this might ultimately become one of the defining medical revolutions of the coming decades. And today we're going to hear from one of the pioneers here, Jean Lorang, who has spent her career helping bring that future into reality. And as you're going to hear the implications stretch way beyond treating patients to things like the rescuing of endangered species. But I'm getting ahead of myself, so let's go to my talk with Gene Loring. I interviewed her on stage at the sin Bio Beta conference hosted by John Cumbers. This is a conference that brings together scientists and entrepreneurs and investors who are all exploring this fast moving frontier of synthetic biology. Here's my interview with Gene Louring. Gene you said at the intersection of developmental neuroscience, regenerative medicine and genomics, and Parkinson's disease, and more recently space science and conservation biology. So just to get us started and warmed up, just make sure we all understand what is a stem cell and what is an induced poor important stem cell.
00:08:54
Speaker 3: Yeah, yeah, I'm trying not to use any acadyms. So a stem cell is any cell that can give rise to more copies of itself and it can then go on to become at least two different cell types. So we have stem cells in our body and our livers, especially in our bone marrow. Bone marrow has really great stone cells, but induced pluripotent stem cells are something entirely different. They only live in culture dishes, they are done in our bodies, and they are made from little bits of our tissue, either our blood or our skin and they are subjected to this process called reprogramming, which makes them pluripote, means that they can make any cell type in the body.
00:09:36
Speaker 2: So imagine, I mean, just this is where you start.
00:09:39
Speaker 3: You could have your own cells in a culture dish that could be in every cell.
00:09:43
Speaker 2: Type in the body that's yours. It has the same DNA as you.
00:09:48
Speaker 1: And why was the invention of high PSC such a scientific earthquake?
00:09:53
Speaker 3: It just changed everything because before that we were working with embryonic stem cells, which made a lot of people uncomfortable. But also they didn't come from actual people. They came from embryos that were discarded in IVF clinics. And so the great thing about IPS cells is that we can know somebody's whole, whole medical history and then make cells from them with all that history behind it.
00:10:17
Speaker 2: So now we have cells in a dish that have a medical history.
00:10:20
Speaker 1: So when you take a skin cell and you chemically rewind it all the way back to a pluripotent cell, what is actually happening inside the cell?
00:10:28
Speaker 2: Yeah?
00:10:29
Speaker 3: So I think you've heard about epigenetics while so essentially what it does is that it erases the reprogramming, erases the marks in the genome that make us sell a particular cell type. It doesn't change the DNA. So your skin cell has like some kind of pattern of DNA and mesylation.
00:10:48
Speaker 2: Reprogramming sort of gets rid of most.
00:10:52
Speaker 3: Of that at least, and then eventually that cell can no longer remember chemically, remember that it was a skin cell.
00:11:00
Speaker 1: And so you have described stem cells as being wonky.
00:11:04
Speaker 2: Yeah, what did you mean by that? Yeah, So here's the problem.
00:11:07
Speaker 3: So this is all the good stuff about stem cells, and then the bad thing is that they go on dividing forever. So the are two qualities of pluripotent stem cells and a culture dish.
00:11:15
Speaker 2: They will divide forever.
00:11:17
Speaker 3: They are the only cells that we culture that aren't cancer cells that have that property, and that's really important to note because they're unique in the universe. And because of that, every time they divide, and every time any cell divides, they acquire some mutations in the gene. There's not quite perfectly redone, so they accumulate maybe eight or ten mutations, which is no big deal because we have three billion base pairs, but every once in a while, the mutations occur in genes that are involved in cancer, like ONCA genes or the you know, like P fifty three, which is a protector of the genome. And when that happens, you start this process of essentially evolution in a culture dish. So the cells that do better are the ones that have those mutations. They're more cancer like, they're actually have the same qualities as cancer cells, and they survive better, they divide faster, and if you keep those cells growing for a long period of time, all of your cells will have those mutations.
00:12:17
Speaker 2: So that's what I mean about being lucky.
00:12:20
Speaker 3: And if you didn't look for them, you wouldn't know because the cells don't look any different.
00:12:24
Speaker 1: And so what are the implications for centerative medicine here, because we'll get to this in a minute about putting these cells back in the humans. But the bar is very high for this. So what does this mean that you've got this little Darwinian ecosystem in the petri dish.
00:12:39
Speaker 2: Well, it's it's like all evolution.
00:12:43
Speaker 3: I think you can't control it, but you can identify it. And if you look at your cells frequently, and we do whole genome sequencing to just to find out what happened, then it's no problem. And if they do acquire mutations, we throw them out. So it's a fail fast strategy. So that means we let them grow for a little while. If that culture dish has mutations arising in it, it gets tossed and there's always another one that hasn't done that.
00:13:12
Speaker 2: And so this is like quality control. It is living sremely. It is really important.
00:13:16
Speaker 1: Yeah, exactly, and so you use machine learning for that. Just give us a sense of how that works.
00:13:21
Speaker 3: Yeah, So the way that we've designed this trial, which we'll talk a little bit more about, is that we have some quality control what they're called release criteria. So we sequence the cells that we're making into neurons three times during the manufacturing when we first get them from a person. That's a reference. After we make ips cells out of those cells, that shows us what has changed, and then just before the cells are transplanted to people whatever has changed between those two stages. So we have algorithms that allow us to find out what mutations occurred and also which mutation and whether thoseations or are of concern because there are databases the tally which ones you should worry about? Now, does that eliminate all chance of those cells becoming cancerous. No, it doesn't, but it reduces the risk really considerably. And I was going to mention the phenotype of the cell as well. So to show that a cell's plury potent, one way you can do it is to do messenger RNA do transcriptone analysis. Because each cell type has a particular pattern of gene expression. So we developed a tool that in which you can use gene expression profiling of a cell culture you have in your lab, and then you can take those cells and like differentiate them into everything that they can possibly make, and then you get feedback from that, you do another gene expression profile, and then each one that's successful.
00:14:50
Speaker 2: Falls into a particular category.
00:14:52
Speaker 3: So this is an asset called plury test and it is used by a lot of researchers. We published a long time ago, but it is still an acceptable way of you knowing that your cells are pluripotent just based on their gene expression profiling.
00:15:05
Speaker 2: It's machine learning.
00:15:07
Speaker 3: You just gather a lot of reference samples and then have you tested against a lot of other samples. And that's it's very very simple. It's not AI, it's machine learning. And then we have a second test, which we call neui tests. It's really essentially the same.
00:15:20
Speaker 1: But we.
00:15:22
Speaker 3: Profile the cells at the stage before they're going to be transplanted into somebody, and that allows us to know exactly the right stage at wish to transplant them. And that information is based on real information we get from animal models that when we put the cells into an animal model of the disease, then we get a result. The cells survive, the animal recovers, and we use that information to feedback to find out what kind of gene expression profile we want in those cells that we're going to put in humans.
00:15:51
Speaker 2: Cool.
00:15:52
Speaker 1: So this changes biology from just being an observational science being more like a predictive engineering discipline.
00:15:57
Speaker 2: Yeah, very cool.
00:15:58
Speaker 1: Okay, so now let's go to what you do with this, Because when people started looking at these induced pluripotent stem cells, they you know, they were very interested in what was going on alow, but your interest has always been how do we get this into humans?
00:16:12
Speaker 2: Right?
00:16:13
Speaker 1: So, in Parkinson's disease, you have the destruction of a little tiny nucleus called the substantial niagra, which has neurons in it that spit out dopamine to the rest of the system. So, first of all, why are those cells so crucial.
00:16:27
Speaker 3: So there are cells that control sort of fine movements. You know the problems with people with Parkin's disease. There are a lot of motor deficits. Sometimes they freeze, sometimes they have a tremor. But by the time people are actually diagnosed with Parkins disease, they've already lost half of their dopamin neurons that are in the substantialiagra. And so our goal is to replace those neurons and restore the function so that people can recover or at least be don't not progress any further progress of neurodegenitive disease. So if we can arrest it, that's great. If we can reverse it, that's even greater.
00:17:21
Speaker 1: So when did you first realize that neuron replacement therapy might be feasible.
00:17:27
Speaker 2: Well, I have some historical help.
00:17:31
Speaker 3: Back in the nineteen eighties and nineteen nineties, there were some very brave researchers in the US and mostly in Sweden who took little bits of fetal tissue aboorded fetus. There's a part of the brain of an aboarded fetus at particular stage six weeks old. You can cut it out and you can put it into a syringe and inject into people's brains. That's what they did, which seemed very crazy at the time. It's probably still crazy, but the fact was that some people who got those fetal cell transplants recovered from Barkins's disease, I mean completely recovered. It was really it was just like a miracle, but it was a rare miracle. So the reason we picked Parkins diseases was that we knew that if we got the right cells into the brain, we might.
00:18:19
Speaker 2: Be able to have that happen every time.
00:18:22
Speaker 3: And induced puripotent stem cells gave us the opportunity to make cells that what might function just as well.
00:18:30
Speaker 1: So now, when people started thinking about this, it's fair to say that everyone else thinking about it was thinking about using allergenic approaches, meaning you take a donor cells and you distribute those among patients. But you started thinking about what if you could do this autologously, meaning use people's own cells in their own brain stem.
00:18:51
Speaker 2: So, yeah, well that makes.
00:18:52
Speaker 3: Logical sense, right if if you had a choice of using of having your own cells replaced your own cells, you would not have to be on the suppressed. Your cells should recognize the environment, they should thrive so people didn't think that was possible. But because we had such a strong genomics background, we figured out ways to qualify individual cells from individual patients.
00:19:17
Speaker 1: I just want to get that street though. Why did people think that was possible? Why did they think that doing this other method was better?
00:19:23
Speaker 2: I think it was sort of like I think.
00:19:25
Speaker 3: I mean, we had a unique combination in my lab. We had a lot of people in new stem cell biology and a lot of people are new genomics. So we talked to each other, and so it just made sense that we could do it. And then we had lots of reasons to do it, because you don't want to men to suppress people. If you don't have to, it's dangerous. In another one of the trials that was using allergenic that is, not unmatched cells, one of the patients died from an infection. So using atolog of cells means that we don't have to worry about things like that, and so in theory, those cells could still be in the person twenty or forty years later because they're their own cells.
00:20:05
Speaker 1: So walk us through the actual pipeline. So patient comes in with Parkinson's disease, how do you go from taking some skin cells all the way to having neurons that you put in their brain.
00:20:15
Speaker 3: Yeah, so it's more straightforward than sounds. These cells are very good at making neurons. There are lots of ways that people have established them making different neurons from pluryponent stem cells, lots of history. So we take a skin biopsy, you grow out the fiberglasts which are the dermal layer, and then those are exposed to what we call the Yamanaka factors transcription factors that transform those cells into induced pluriponent stem cells. And then of course we put them all through the rigorous testing and then we have as efficient as possible a method to go from undifferentiated cells to cells that are poised to become dopamine neurons. We haven't done it yet, so we need to. We had to identify that percise stage, and we did it by gene expression profile, and we identified it by that. And when you have the cells at that stage, at least in anal models which we had, that's the only thing went to go on. Those cells would thrive and they would reverse the symptoms of the disease. So we then those cells are then put into person's brain, so it takes the whole process. I mean it takes a while. For the first part reprogramming, you just need to make a little bit of a bank of cells. We don't need very many cells. This is one of the really important things. But about neural about replacing neurons, is that we only put around five to ten million cells inject them.
00:21:40
Speaker 2: That's not very much.
00:21:42
Speaker 3: People who are working on heart disease, for example, are talking about using billions of heart cells in order to restore hearts that are damaged by heart attacks.
00:21:51
Speaker 2: So this is like in a culture dish.
00:21:54
Speaker 3: If you looked at that many cells and a culture dish, it would be like a culture dish that big, and it'll only be one it's enough cells to treat a person. So it's not it takes a while because the steps take a while. But from the time that the cells are plury potent to the time they're staged in order to be put into a person is about twenty to twenty four days, so that's not very long, and we can make them in advance. That's a really great thing about the FDA, in their wisdom, allows us to make the cells that collect the fireroblasts, make the IPS cells ahead of starting the clinical trial. So that's what we did. In this case, you get id approval. We had all the cells already before we got the approval, so that made it really fast from then on.
00:22:43
Speaker 1: So historically medicine has said, look, let's target existing cells and try to influence them with some sort of drug. This is a very different kind of thing. This is replacing the cells entirely. Do you see this as a totally new chapter of medicine. And if so, what are the diseases, let's say, neurodegenerat diseases that are next, and which ones are really hard?
00:23:07
Speaker 2: So I think the hard ones.
00:23:09
Speaker 3: I mean the brain is actually a really great place to place cells because they don't Neurons and other glial cells, for example, support our cells of the brain. They don't leave the brain, you don't have to go search for them later. They don't travel throughout the body like if you were using a cart therapy. It goes into your bloodstream and it goes everywhere, even into your brain as a method. So we're so brain disease is really, I think a really kind of easy target in that way.
00:23:38
Speaker 2: The hard part of the target is.
00:23:39
Speaker 3: That we have to have we actually have to inject the cells into the brain, and that's neurosurgery. The diseases that I think are could be handled by not so much celler replacement. It is actually celler replacement, but a little more subtle than that. Or Alzheimer's disease and stroke, maybe multiple scroves. Those are all cases in which there's the cells are not working correctly. And one of the things I wanted to mention about the brain in general is how the neurons don't divide, but they keep making a synapsis over and over and over again. And David is one of the ex world's experts on what we call neuronal plasticity, So do.
00:24:18
Speaker 2: You want to explain that.
00:24:20
Speaker 1: Yeah, neural plasticity is just that, you know, you've got these eighty six billion neurons and your whole life, they're all moving around and sort of crawling and trying out different connections. Each one has about ten thousand connections with its neighbors, and it's sussing out those connections and unplugging and seeking somewhere else. So it's very weird to think about this crawling around process that's happening in your head, and that's not to mention the eighty six billion glial cells and everything else going on in there. But yes, your whole life, cradle to grave, your brain is reconfiguring. Every piece of experience, every memory that you have is represented by a change in the structure of the brain.
00:25:00
Speaker 2: Yeah.
00:25:01
Speaker 3: So that I think opens up the whole idea of once you place a neuron in the right place, then it will make connections in the right places, and it will adjust those connections. They'll become stronger, just like they are when during neural development. So these are not inert cells. They're actually quite plastic.
00:25:20
Speaker 1: Excellent, Okay, I want to make sure we have enough time. Tell us about the frozen zoo in San Diego.
00:25:26
Speaker 2: What is that? Okay?
00:25:27
Speaker 3: So my roots are employee potent stem cells. That's what I know most about. So I started working with the San Diego Safari Park quite a long time ago. They have a frozen zoo in which they have about about I think it's something like two thousand different species frozen in liquid nitrogen, which is where we store cells. It started in nineteen seventy five and it was made essentially to try to rescue the animals or try to save bits of the animal of animals that died in the zoo or even in the wild and interesting lay. The cells they decided to use starting in nineteen seventy five were dermal fibroblasts, so they have this huge bank of dermal fibroblasts. And a friend and I realized that we could maybe make IPS cells from one of the animals that's in the frozen zoo, and we picked one that is right on the brink of becoming extinct. It's the northern white rhino. And remarkably, a post doc in my lab was able to take the cells from the frozen zoo, thaw them out, and figure out how to reprogram them so we can make IPS cells.
00:26:33
Speaker 2: And one of the things that was so.
00:26:35
Speaker 3: Remarkable to me was to look at the IPS cells from an animal that had died ten years ago and we'd made them into heart cells in a dish, and we had in the dish those cells were beating, and so it really felt like that light that that animal had come back to life. What we want to do is to be able to make oocytes, eggs and sperm perhaps and then generate new animals.
00:26:59
Speaker 2: And that's that's not the same as.
00:27:01
Speaker 3: The extinction and the extinction it's it is a rescue of animals that are still alive or have cells in that bank, in the frozen bank. So the animals could all be gone in the wild, but if their their cells have been frozen in that bank, we might be able to bring them back.
00:27:18
Speaker 1: And I know that you make a good distinction between the extinction, which is usually using ancient DNA, versus this kind of rescue, which is using frozen cells. What did it feel like to you when when your post doc first made I p.
00:27:37
Speaker 2: Yes, ips cell. I knew she was. I mean, that's a that's a great thing about running a lab.
00:27:42
Speaker 3: You know, go try that and then I come back to me when you've done it, and it was yeah. I was thought, oh my god, it was so easy. In retrospect, she tried a lot of things. You know, it's trial and error when you are doing something completely new. But it turned out that the human yamanok effect reprogrammed the rhino. That's not true of other animals. We picked the rhino of all animals, and it worked. But if we picked a different animal, it wouldn't have because the factors are a little different different species.
00:28:12
Speaker 2: So rhinos turned out to be really easy.
00:28:15
Speaker 1: But in fact, one of the challenges you have is that you can make gamme meats in mice, but in rhinos. It hasn't succeeded yet. But you feel that's just a matter of tweaking.
00:28:24
Speaker 3: I think it's just a matter of tweaking because almost everything we've ever done started in a mouse. It was like the mouse paved the way, and then the methods are developed in the mouse. The methods have to be changed, sometimes modified, but that doesn't mean it's impossible. So when we have that basis, we have a hope that we can do it with any animal species.
00:28:44
Speaker 1: So in the future, if we freeze cells of all the animals that are around now, you think this technique could address sis if somebody.
00:28:51
Speaker 2: Wanted to do it, Absolutely yes.
00:28:53
Speaker 1: And somebody you know has human cells frozen at the San Diego Frozen Zoo.
00:29:00
Speaker 2: Yeah, I represent the human race in the Santiago.
00:29:04
Speaker 3: That was from years ago, you withdrew, Yeah, yeah, I made my own IPS cell. I mean, we made my own IPS cells back in two thousand and nine.
00:29:13
Speaker 2: We've been using them sort of as.
00:29:14
Speaker 3: Our standard for mucking around with things, and they're pretty good.
00:29:19
Speaker 2: Actually, they're pretty talented. We have to wrap it.
00:29:22
Speaker 1: I just wanted to ask you one last question, which is fifty years from now, when we look back on modern medicine, what do you think we're going to find shocking.
00:29:29
Speaker 3: I think this is going to be one of the options for diseases that we can't touch now at all. It would be cell replacement, and I think that there will be animals roaming the earth that didn't have a chance before.
00:29:41
Speaker 1: Thank you so much, Gene, and thanks for your work. That was my interview with Gene Loring. One of the things I find really exciting about what she and many of her colleagues are doing is that it's not just about stem cells. Stem cells are the enabling technology, but the deeper story is a change in how we think about medicine itself. As I said at the beginning, for most of medical history, we've treated disease by just trying to influence the cells that are already there. We've looked for molecules that crank one pathway up and squish another pathway down. We look for things that you can swallow or inject that suppress inflammation, or activate receptors, or block enzymes or produce more neurotransmitter or whatever. But fundamentally, we've always been trying to persuade tissues to behave a little better by changing their chemical environment, and that, by the way, has been tremendously successful. We've essentially tripled our life expectancy that way. But what's known as regenerative medicine proposes something fundamentally different. Suppose the problem isn't that the cells are behaving incorrectly. Suppose the problem is that the cells are gone. And if that's true, the answer is not going to be another drug. Maybe the answer is just to swap in some new cells. This is a conceptual leap from putting the duct tape on the broken parts to manufacturing replacement parts. Now, Parkinson's disease is an especially compelling place to start, because the disease destroys a specific population of dopamine producing neurons. If you replace those neurons successfully, you've addressed the problem at its source. But of course you can hear Gene already thinking beyond Parkinson's to stroke, to multiple sclerosis, to Alzheimer's disease, and eventually lots of other conditions in which cells have died or are no longer functioning now. It goes without saying that none of this is simple. As you heard Gene allude to, growing cells is really hard and subtle, and ensuring their genetically stable is difficult, and delivering them into the brain requires neurosurgery. And every new technology brings ethical questions hand in hand with the technical ones. But I want to note that's true of every major revolution in medicine. Antibiotics once sounded impossible, organ transplantation sounded reckless, gene therapy spent decades struggling before finally starting to fulfill its promise. Medicine advances because people are willing to imagine totally new ways of approaching disease. And there's another aspect of Gene's work that are found so cool. The same technology that can restore neurons in people with Parkinson's disease is also being used to preserve endangered species. The very same cellular reprogramming can help rescue the northern white rhinoceros and presumably eventually lots of other animals whose populations have dwindled. It's sort of rare that one scientific idea stretches from treating a human brain to helping preserve biodiversity only at the beginning of this story, and if history is any guide, future generations are going to look back on this moment in time, this first quarter of the twenty first century, as the moment that medicine began evolving from the science of influencing cells into the science of building them. Go to eagleman dot com slash podcast for more information and to find further reading. Join the weekly discussions on my substack and check out Subscribe to Inner Cosmos on YouTube for videos of each episode and to leave comments Until next time. I'm Dave Eagleman and this is Inner Cosmos.
