Restoring sight to blind kids, making babies without a womb, and challenging the benefits of clinical trials

This episode delves into pioneering medical research on restoring sight to congenitally blind children, growing babies outside the human body (ectogenesis), and reevaluating the assumed benefits of clinical trial participation for cancer patients.

1. Recent meta-analyses suggest that cancer clinical trials may not provide a survival benefit, contradicting previous assumptions.
2. Project Prakash has successfully restored sight to over 500 children, offering them significant life improvements despite some persistent visual deficits.
3. The discussion on ectogenesis explores its potential to revolutionize human reproduction by removing physical pregnancy burdens and addressing gender inequalities.
4. Technological advances in artificial wombs and embryology hint at a future where full ectogenesis might be feasible, raising profound ethical questions.
5. The episode emphasizes the importance of nuanced communication and ethical considerations in medical research and its public perception.

1: Challenging Cancer Trial Benefits

This segment revisits the presumed benefits of participating in cancer clinical trials, suggesting that survival advantages might be overstated. Jennifer Couzin-Frankel: "We need to be cautious promoting trial participation as a definitive survival advantage without solid evidence."

2: Vision Restoration in Congenitally Blind Children

Explores the transformative impact of sight restoration surgeries conducted by Project Prakash and discusses the ongoing challenges these children face post-surgery. Lucas Vogelsang: "Restoring sight is just the beginning; we're learning how these children adapt and the unique challenges they face."

3: The Future of Reproduction - Ectogenesis

Angela Sainy and Claire Horne discuss the cutting-edge concept of ectogenesis, its potential societal impacts, and the ethical considerations it entails. Claire Horne: "Ectogenesis could drastically alter our approach to reproduction, offering new freedoms but also new challenges."

1. Stay Informed: Keep up-to-date with the latest research to understand the actual benefits and risks of medical innovations.
2. Participate Ethically: If considering participation in clinical trials, ensure informed consent and understand the scope and purpose of the study.
3. Support Innovation: Advocate for and support research projects like Project Prakash that offer both humanitarian aid and scientific insight.
4. Engage in Dialogue: Discuss and debate the implications of technologies like ectogenesis to prepare ethically for their potential integration into society.
5. Promote Accessibility: Encourage initiatives that make advanced medical treatments and technologies accessible to underserved populations.

Studying color vision in with children who gain sight later in life, joining a cancer trial doesn’t improve survival odds, and the first in our books series this year

First on this week’s show, Staff Writer Jennifer Couzin-Frankel joins host Sarah Crespi to discuss the pros and cons of participating in clinical trials. Her story challenges the common thinking that participating in a trial is beneficial—even in the placebo group—for cancer patients.

Next, Lukas Vogelsang, a postdoctoral fellow in the department of brain and cognitive sciences at the Massachusetts Institute of Technology, talks about research into color vision with “late-sighted” kids. Studying children who were born blind and then later gained vision gave researchers new insights into how vision develops in babies and may even help train computers to see better.

Last up on the show is the first in our series of books podcasts on a future to look forward to. Books host Angela Saini talks with author Claire Horn, a researcher based at Dalhousie University’s Health Justice Institute. They discuss the implications of growing babies from fertilized egg to newborn infant—completely outside the body—and Horn’s book Eve: The Disobedient Future of Birth.

People

Jennifer Couzin-Frankel, Lucas Vogelsang, Claire Horne, Angela Sainy

Companies

Project Prakash

Books

"The Disobedient Future of Birth"

Guest Name(s):

Jennifer Couzin-Frankel, Lucas Vogelsang, Claire Horne

Content Warnings:

None

Sarah Crespi
This podcast is supported by the Icon School of Medicine at Mount Sinai, one of America's leading research medical schools. Icon Mount Sinai is the academic arm of the eight hospital Mount Sinai health System in New York City. It's consistently among the top recipients of NIH funding. Researchers at Icon Mount Sinai have made breakthrough discoveries in many fields vital to advancing the health of patients, including cancer, Covid and long Covid, cardiology, neuroscience, and artificial intelligence. The Icahn School of Medicine at Mount Sinai, we find a way.

This is the science podcast for May 31, 2024. I'm Sarah Crespi. First up, staff writer Jennifer Cousin Frankel joins me to discuss how though it's commonly been thought that participating in a trial is beneficial for cancer patients, even if they're in the placebo group, new studies are calling this benefit into question.

Next, we have researcher Lucas Vogelsang. He did research with late sighted kids. These are children born blind that later gained vision. Last up on the show is the first in our series of books, podcasts on a future to look forward to books, host Angela Sainy talks with author Claire Horne about the implications of growing babies completely outside the body, and they discuss Claire Horne's book, the disobedient future of birth.

Is being in a clinical trial good for you? When it comes to trials for cancer treatments, it's been widely thought that participation in trials is beneficial to patients, even if they're in the placebo group. This week in science, staff reporter Jennifer Cousin Frankel wrote about recent studies that suggest this might not be the case. Hi, Jennifer. So glad to have you back.

Jennifer Cousin Frankel
Thanks.

Jennifer Couzin-Frankel
Glad to be here.

Jennifer Cousin Frankel
Yeah.

Sarah Crespi
So why do people think that being in a trial for a drug, you know, that's not even necessarily proven effective yet, would be good for cancer patients?

Jennifer Couzin-Frankel
So there are a number of reasons to think that there are advantages to trials, and there probably are advantages, but the reasons have been, first of all, when you are in a trial, regardless of what group you're assigned to and whether you're getting the experimental therapy, you are often getting treatment or getting care and monitoring at a top cancer center by top doctors. You also have care that's very standardized. There's less likely to be disparities in care because everybody in a trial is getting the same care. They're typically asked the same questions about how they're feeling. They have the same monitoring, and that's part of the point of a trial, of course. And so if you're in a trial, you have access to that standardization, which has also been thought to potentially be a benefit. And then, of course, there's a separate point, which is that trials are often testing an experimental treatment. And if the experimental treatment is better than the standard of care, you have access to that, too, although you may not get assigned to that group.

Sarah Crespi
So the new study out this month suggests something different.

Jennifer Couzin-Frankel
This new meta analysis, which was published in Jama, was looking at one particular benefit, which is survival. They weren't looking at anything else because they had access to the survival information. And the question was pretty simple. It was basically, if you participate in a trial, if you sign up for a cancer trial, regardless of what group you're in in that trial, are you more likely to survive longer than if you are not in a trial? And typically, what they were able to do in this study was to focus on research that was comparing patients who were getting the same treatment, whether inside or outside a trial, because that does happen. It may sound a little strange, but that does happen not so infrequently. Things can be prescribed off label outside of trial, or there might just be things that someone wants to test in a trial, even if they're already practiced to a degree in oncology. One example of a trial that was part of this larger analysis was of men with prostate cancer who were getting radiation treatment. And the trial was saying, is there a benefit to giving them a certain pattern of radiation treatment versus not. And the study that looked at this compared those people to people not in a trial who were getting radiation treatment or not. So the idea is, does the mere act of being in a trial help you survive longer?

Sarah Crespi
They didn't find a survivorship benefit.

Jennifer Couzin-Frankel
Yeah. So what's interesting is that they looked at these 39 studies, which were basically comparing trial participants with non participants. It's almost like a nesting doll set, because within those studies, there were often multiple other studies. It's a little confusing, but basically, some of the comparisons that had been already published did say there was a benefit. They said, we looked and we did find a survival benefit to being in a trial. What this group did was they tried to look really deeply at each of those comparisons and found there were often confounding factors or certain biases that could tilt the outcome in favor of a trial. So one example, very simple example, is that clinical trials in general often exclude people who have a whole bunch of other health conditions. So if you're a cancer patient and you also have serious heart disease, you might not be eligible for a trial of an experimental treatment. But you may also be more likely, unfortunately, to not survive as long and so if you have people like that not in a trial, they may not survive as long, but that's not because they're not in the trial. It's just because they have these other health conditions. So this study was trying to look for all these different other factors that could kind of tilt the playing field, and they were trying to level it out to really compare trial participation versus.

Sarah Crespi
Not when they took all these confounders out, they started to see a decreased effect.

Jennifer Couzin-Frankel
They didn't find a survival benefit, right? Yeah, they couldn't say there weren't other benefits. And there may be other benefits, but they did not see a survival benefit to being in a trial for cancer.

Sarah Crespi
Did they separate out the potential benefit of the placebo group versus the potential benefit of being in the experimental treatment arm?

Jennifer Couzin-Frankel
Yeah, that's a really interesting question. So the new study which just came out this week, was not designed to do that, but the same group had another research paper that came out in April that was looking at that question. It was a different study, but they essentially were looking at a number of trials that were testing treatments for certain types of solid tumors in cancer and looking at exactly that question. Do you have a benefit? So again, a survival benefit if you're assigned to get the treatment versus the placebo? They did find a small survival benefit of about five weeks. Now, again, that's like average across all these trials. And they also, not too surprisingly, found higher risks for getting the investigational therapy because those may have more toxicities, more side effects, more risks, et cetera. So in that study, there was a small survival benefit that was real. It was statistically significant.

But you want to weigh that against the downsides, too. That may come.

Sarah Crespi
Yeah. So I don't want to kind of keep pushing on this. Like, is there a benefit to cancer trials? Because obviously there's a benefit to cancer treatment trials. But, you know, what about non survival benefits? So, for example, like, you're saying they might see more people, they might see their doctor more regularly, that kind of thing.

Jennifer Couzin-Frankel
You know, it's important to note that there could definitely be other benefits for patients in trials, and some of them may be really intangible. Maybe you are more hopeful if you're in a trial or you feel like you're getting more care. It could really depend. I mean, you may feel it the other way around, too. I don't know that it's universal in one direction or the other. It could be that you're getting additional monitoring that could help you, but I think we need to be really careful in how we frame trials, because if we're saying that they give patients a health benefit, it's important to have data to support that.

Sarah Crespi
Right. You know, as you write in your story, if people walk around with the idea that just the pure fact of being in a trial could help you as a cancer patient, maybe survive longer, if that's used as an inducement to get patients into the study, that could be a problem.

Jennifer Couzin-Frankel
Yeah. I mean, I think it's really important to be upfront with people who could enroll in a trial about why they might want to enroll, what the benefits are, what the value is, and what the trial isn't designed to do for them as well.

Sarah Crespi
Yeah. Is there a worry then that these findings, which are pretty prominent in JAMA, is there a worry that they could make people less likely to participate or that doctors might discourage cancer patients from taking part in trials?

Jennifer Couzin-Frankel
I don't know that there's so much a worry about doctors discouraging cancer patients from participating. And there have been other studies, actually, that have found this as well, that have looked for survival benefits from trials in cancer and haven't found them. The research is uneven. So this isn't the first study to describe this. I think the concern is more about how we communicate trials to patients, and we don't want people to sign up not understanding what they're getting. So, yeah, I mean, I guess it depends how it's sold. There could be a concern that fewer people are signing up, but you don't want people signing up unless they want to sign up and are informed. Right. So.

Sarah Crespi
Yes, exactly.

Jennifer Couzin-Frankel
And you know, this is all, it's such a huge and heterogeneous area. We're talking about vastly different trials for vastly different cancers of vastly different treatments. There's a lot going on here and it's really hard to generalize as well.

Sarah Crespi
It kind of sounds like people are making the case. Well, you're getting so, so care when you go to the cancer clinic, but if you're in a trial, let me tell you, we're going to give you the best cancer treatment care. I mean, that just, it just sounds a little bit odd. I feel like.

Jennifer Couzin-Frankel
Yeah. And I think that that is sometimes the message, and it may be the message of, again, it's like the being in a trial part of it. You're going to some top, top hospital. Of course, you may have to travel 2 hours to get there instead of 15 minutes to your local hospital, which could be a real burden. But I think that's an argument that some people make, or that is almost implicit. And this paper is saying the care people are getting outside of trials is good care. And I think also sometimes cancer, people with cancer may feel if they cannot access a trial or don't have a trial nearby, that can be very disheartening or worrying to them, like, I need to be in a trial, or they're.

Sarah Crespi
Excluded for various reasons.

Jennifer Couzin-Frankel
Yeah, yeah. And I think it's important, you know, one message of this, too, is that that's okay. Like, it's, you're not necessarily at a huge disadvantage. Now, of course, there can be advantages to trials, but it's not like there are advantages for every single person with cancer.

Sarah Crespi
Now, should we talk about clinical trials that don't involve cancer treatment? Is there a similar story there?

Jennifer Couzin-Frankel
I didn't do as much research on that for this story.

This same group has looked at neurological trials, like, for Alzheimer's disease, Parkinson's disease, ALS, and they did a similar study to one that I'm writing about now, where they were looking at, if you get assigned to the treatment group, the experimental therapy group, is there a benefit versus the placebo group? And basically they found no benefit. It wasn't bad. It was just kind of a wash. So that, again, I think, showcases the idea that you're not necessarily worse off if you're not getting the experimental therapy.

Sarah Crespi
We should just remind people that, of course, it may not benefit anyone individual specifically to be involved in a clinical trial, but it does benefit everybody. For clinical trials to go forward and to help refine and discover new treatments.

Jennifer Couzin-Frankel
Yeah, I mean, I think what's important to remember is that the point of a trial is not to provide someone with medical care. It's to test a new treatment. And the people who are volunteering for these trials are doing so in part out of the goodness of their heart, because they want to help science, and that's really, really valuable. And, of course, a lot of them are also hoping that they will get something out of it as well, and they may. But the overarching purpose of the trials in cancer is to give us better cancer treatments, and trials have certainly done that.

Sarah Crespi
Yeah. All right. Thanks so much, Jennifer.

Jennifer Couzin-Frankel
Thank you.

Sarah Crespi
Jennifer. Cousin Frankel is a staff reporter for science. You can find a link to the story we discussed@science.org. podcast. Up next, my chat with Lucas Vogelsang about restoring vision to born blind people and what it can tell us about how sight develops in babies.

This week's episode is brought to you in part by the Eppendorf and Science Prize for Neurobiology.

Are you or one of your colleagues doing great neuroscience? If so, then we encourage you to apply for the prestigious Eppendorf and science Prize for neurobiology, an international prize which honors young scientists for outstanding neurobiological research based on methods of molecular cellular systems or organismic biology.

Submissions are due June 15. Visit science.org eppendorf to apply today.

All right, so say you're out in the forest and the sun is starting to set. It's getting darker. Your eyes are adjusting.

It takes a while. And once we acclimate, the trees look black and white, or like grayscale. That's the rods in our eyes kicking in, giving the cones a little break.

Despite the lack of the hallmark green in the leaves all around us, they still look like leaves to us. No green, no brown cues. We still can tell a leaf or a log is a leaf or a log. But as Lucas Vogelsang and colleagues report in science, this isn't always the case for those who gain vision later in life. Hi, Lucas. Welcome to the science Podcast.

Lucas Vogelsang
Well, thank you so much for the invitation. It's a great honor to speak with you today.

Sarah Crespi
This is a really unique study population. It's one of the first things I noticed. These people got vision later in life, so they were late sighted, as you call them in the paper. Can you talk more about this group that you worked with and about Project Prakash?

Lucas Vogelsang
These experiments took place as part of Project Prakash. Project Prakash is an initiative. It's located in Delhi in India, and it was founded by professor Pawan Sinha, who is at MIT in the US.

The humanitarian goal of Project Prakash is to provide treatably blind children around northern India with free site restoring surgeries. So typically for the removal of congenital cataracts. And the scientific mission is to then study the children's visual development after their site onset. I would say that these two missions have really been quite successful. So through the project, site was initiated in more than 500 children. And even though most of these children have been blind for many, many years, something like ten years, 20 years after the surgeries, many visual skills can still be acquired, at the very least partially. So this is a quite magical transformation that these children undergo. But there are some deficits that do remain in some cases. And this paper is kind of one of these cases.

Sarah Crespi
The participants, they have no vision when they're born. They are able to see after the surgery, and they can see color right away. But the changes I alluded to in the intro, you know, when objects have different coloration because the light changes or it's dark out. The people who gain vision late in life, they run into problems with these changes in color. Can you talk a little bit about that?

Lucas Vogelsang
We conducted an experiment that is pointing this out. These patients that we were talking about, they were presented with grayscale images, and they were asked to name the objects that were presented in these images. And then later they were presented with the same objects, but in full color, and they were again asked to name these objects. We also had non prakash control participants that were matched in terms of age or the visual acuity. And what we find is normally sighted controls. They almost show no difference in recognition performance on grayscale versus color images. But the Prakash children, they do show such a difference. So for them, when color information is removed, their recognition performance really drops.

Sarah Crespi
So it would be really difficult to watch a black and white movie, for example.

Lucas Vogelsang
That's right. They seem to have great difficulty with that. This pointed us to a hypothesis that would explain essentially these two experimental findings. So, first, why do Prakash children have these difficulties? And second, why do we not have these difficulties? Why are we so good and have this resilience to color shifts or removal?

Sarah Crespi
You look to the way babies actually learn to see or how they develop vision. How does that fit in with what's happening with these project Prakash patients?

Lucas Vogelsang
So, typically developing newborns, they start seeing the world with very immature retinas. The cone photoreceptors in the retina, they're extremely limited, and therefore the color vision is, is initially very poor. It's not exactly black and white, but it's really poor. And it then gets better over the first months or years of life. Now, for the Prakash children that are born blind and treated later on, this is different because even while they are blind, so, say, in the first years of their life, the processes that lead to the maturation of the retina, they appear to continue. So this means that once the vision of these children is restored, the child begins seeing the world with very mature retinas. So we have these late sighted individuals. They were blind for 1020 years. And when they were tested just two days after the surgery to differentiate between slightly colored and gray scale circles, they were just as good as normally developed adults.

Sarah Crespi
Wow.

Lucas Vogelsang
So they really start essentially with perfect color vision.

Sarah Crespi
That actually might be underlying their problem with object identification because color vision came as soon as they had vision.

Lucas Vogelsang
That's right. So intuitively, one might think, well, that's so great for the Prakash children is that their color vision is so good. That's such a nice thing, they can see all of these beautiful colors. But what we hypothesize is that this is really too much too soon, because this can induce the system to develop this over reliance on colors. So normally sighted children wouldn't have this because they start out with these color degraded inputs. And so this period might actually be crucial to help the visual system to emphasize more robust representations, more perhaps the luminance or the shape. And the Prakash children, they might really rely on very specific color cues to then learn how to identify objects.

Sarah Crespi
Obviously, we're not going to deprive babies of color to test this out. Instead, you trained a computer on different sets of visual stimuli that kind of emulated these different scenarios.

Lucas Vogelsang
We use deep convolutional neural networks that we trained on image classification. So these networks, they are by no means perfect models of the biological system, but they do serve some purpose as a model system. And we trained these networks in different ways. The key finding is really that if we train a network using only full color images, so roughly akin to the Prakash experience, then this network is good with full color images, but it really doesn't generalize to anything else. It performs fully with grayscale images, with color manipulated images of any sort. But when we train a network in a developmentally inspired, or how we say, biomimetic way, that is initially on color degraded, later on full color images, then the network performs well with grayscale images, also with full color images, and with all sorts of color manipulated images.

Sarah Crespi
So it sounds like you kind of have an application built in right now. This could really help computer vision get better by making it more like the way humans develop their vision.

Lucas Vogelsang
That's right. This is one of the potential implications of the study.

Sarah Crespi
And what about the implications for people, people who are recently sighted or have other stuff going on? Could this insight help them in some way?

Lucas Vogelsang
I think this is the most exciting potential implication, because it really suggests an opportunity for rehabilitation or intervention in these Prakash patients. Because if the hypothesis is true, then it would seem that the Prakash children would benefit from perhaps a kind of training program, say, with virtual reality that essentially reduces the intensity of, say, colors, initially at least, so that it could mimic the experience of a newborn more and to allow for the emergence of these more robust and perhaps luminance based representations. And I think this possibility is really intriguing because it could, in a quite realistic way, further brighten the prospects of these children.

Sarah Crespi
Do we know if other senses, like the sense of smell or hearing, also kind of go through this staged development where we're only perceiving a portion of what's available at an early age.

Lucas Vogelsang
This seems to be the case. So we are examining whether there could be a broader developmental phenomenon. And actually we have in the past also obtained similar results in the domain of visual acuity. So the initially blurry vision of a newborn being beneficial in helping to focus on the big picture, essentially, and also beyond vision, we have found an interesting case in prenatal hearing. So when you're born, your auditory machinery is actually quite good, but the transition from poor to rich might happen prenatally, because if your fetus in the womb, then you already experience some of the auditory sickness from the outside, but you only hear these kind of muffled sounds. This could be useful in that the fetus is forced, in a sense, to focus on the lower frequencies and to develop some extended temporal integration to make use of these information in the lower frequency. So this theory could potentially be a very broad theory of how perceptual development happens or why even it happens.

Sarah Crespi
I think I saw this in your paper, that vision we talked about starting with rods, first blurry, it's low color, and then you start to improve your acuity and your color perception. But that finalization, that, like peak performance, actually is quite a few years out of infancy. I was really surprised by that. How old are we when we have all our visual systems working?

Lucas Vogelsang
That's a good question, and I think that this might even differ. So, for instance, between color vision and visual acuity, under the impression that visual acuity takes even a little longer to finalize. But it's true that both of these, it does take time. And I think we're a bit different from some other species where it's more you're born and you have your ability. So we seem to have this really long period of these initial degradations or limitations as one could otherwise think about this.

Sarah Crespi
We have really good vision, so maybe we just need all that time to get everything working right.

Lucas Vogelsang
So that is one way of thinking about this. The other way of thinking about this is that theoretically, maybe it's possible that it could be faster, but maybe we just don't need it so early in life because we are very well protected, say, by our parents or so. And there might be these benefits of having these initial degradations early on, so that we have, for instance, this big picture vision and these generalization benefits. So it could be that because we are anyway so well protected, we don't need it immediately, and then later on we can have the full proficiency, but we can also derive the benefits of this initially degraded state.

Sarah Crespi
I guess it's going to be pretty variable. What happens with the project Prakash patients. If you've had congenital cataracts for ten or 20 years, will you ever have pretty proficient vision or will it always have some deficits?

Lucas Vogelsang
What's for sure is that the journey from pre to post surgery is really a remarkable one. So their vision really improves, their quality of life really improves. But there are these specific deficits, like, for instance, for the generalization to grayscale images, but they are also a bit more general deficits that usually are to some extent around. So at least as of now, the Prakash children, they don't reach the level of vision that perhaps you or I have. But it's still so much better than what they had before. And hopefully, through things like these interventions, we could push this even further so that they would get even closer, maybe to the normal visual experience one day, hopefully.

Sarah Crespi
Tell me a little bit about how this collaboration came together. This is kind of a big project across multiple continents.

Lucas Vogelsang
There are so many people involved to make any of this work. There is the outreach team of project Prakash to identify the children that are potentially, treatably blind. Then there is the medical team. There is a surgeon performing these site inducing surgeries. Then there is the science team in India that is running the experiments, and then the science team in the US, for instance, designing the experiments or running the computational simulations or the conceptualization. So it's really a remarkable collaboration. Fun fact to add here. Some people of the author list are in India, some in the US. Some are experimentalists, some are computationalists, some medical doctors. Also, some authors of the paper are in their twenties. And then there is our co author, Doctor Sydney diamond, who is now 98 years old.

Sarah Crespi
Wow.

Lucas Vogelsang
And one of the most active researchers ever, perhaps. So. He retired as a neurologist, and he then joined the lab at MIT quite a while ago. And he's still coming to the lab every day, perhaps being really the fittest of all of us.

It's amazing that inspiring the rest of the team. So I think these personal and human factors behind the work, they really further add to all of these things happening.

Sarah Crespi
Thank you so much for talking with me today, Lucas.

Lucas Vogelsang
Well, thanks again for inviting me. It was great.

Sarah Crespi
Lucas Vogelsang is a postdoctoral fellow in the department of brain and cognitive Sciences at MIT. You can find a link to the paper we discussed@science.org. podcast stay tuned for the first in our six part series on books looking to an optimistic future. This month, host Angela Sainy talks with legal scholar Claire Horne about the prospect of babies being born outside the womb.

Angela Sainy
Hello, Im journalist and author Angela Sainy. And as Sarah says, this segment is all about books. Every month, I interview authors on a particular theme. In previous years, weve looked at race, gender, and food and agriculture. This year, the theme is a future to look forward to, optimistic visions of a world at a time when things can feel pretty bleak. To kick things off, Im joined by Claire Horn, a researcher based at Dalhousie Universitys Health Law Institute in Nova Scotia, Canada.

Shes the author of the disobedient Future of Birth. This book explores the possibility of ectogenesis, birth outside a human body. Now, in science fiction, of course, we often serve these dystopian visions in which humans are taken out of the process of having babies gestated and raised by machines, often with disturbing consequences.

But in this book, Horn asks if breakthroughs in reproductive technologies in the future, just like the ones we've seen in the past, could actually benefit humanity in unexplored ways. Clare, this book covers a lot of ground in terms of the history as well as the ethics of reproduction. But just to start, when did physicians first begin to intervene technologically to keep premature babies alive? How early can a baby be born today and still have a chance of survival and good health?

Jennifer Cousin Frankel
Sure. So that's a big question. I'll take the first part to begin with. So physicians really started to look at treating premature babies as a kind of separate medical subject to ailing babies in general in the late 18 hundreds. And that's when we saw the development of the first incubators. And today, it's generally treated as quite an agreed upon fact that caring for babies that are struggling is a positive thing. But at the time, this was very much contested. So the way that physicians actually drummed up support for incubator technology was by taking them on tours of world's fairs across Europe, replete with live infants inside, which generated a lot of excitement from the public at the time. In terms of where we're at today, generally, there's a chance of survival for extremely preterm babies born at around 23 to 24 weeks, although this very significantly globally and depending on the region as well as the expertise that is available.

Angela Sainy
And so when did the idea of an artificial womb first appear on the medical radar? Because that's another leap way ahead of this idea of incubators.

Jennifer Cousin Frankel
Absolutely. Where we are now is that there's contemporary research that's oriented towards allowing part of gestation to continue outside the body and what makes the technologies that they're working on somewhat different than what we've seen before is that while existing forms of neonatal technology are really designed to treat the complications of babies being born too soon, these technologies are really intended to prevent those complications from arising to begin with, by extending the period of gestation and treating the extremely premature baby as though it had not yet been born. So that's a really significant kind of leap. However, one of the things that I include in Eve is around the medical discussion of incubators when they were first introduced. Because, in fact, in medical journals at the time, including the British Medical Journal in the Lancet, you had some physicians that were boasting that had actually already become possible to replicate part of gestation outside the body. In fact, there was one article where a physician noted that the incubator was a more attractive option than the uterus.

Angela Sainy
Wow.

Jennifer Cousin Frankel
Yeah, exactly. It's quite remarkable. And this was also contested. There were physicians that were saying, you know, these incubators are for infants that are no more than around a week premature, and this will never happen. But I included that because while some of the technologies that we're seeing today are indeed futuristic in some ways, these are also discussions that we've been having for actually a really long time.

Angela Sainy
And as you explain in your book ectogenesis. So the idea of reproduction entirely outside the human body, so not involving any human whatsoever, would mean two separate medical technologies essentially meeting in the middle, the growth of human embryos in the laboratory, and then on the other end, artificial wombs. How close are we to that possibility?

Jennifer Cousin Frankel
So, in terms of the contemporary science, you know, I already mentioned the work that's being done towards allowing part of gestation to continue outside the body as a form of total life support for extremely preterm babies. And I don't speak for any of these scientific researchers. That's really important to note, however, where we're kind of at with that is that there's been really promising animal trials. At least one of those groups is hoping to move to preclinical and clinical trials with humans within the next few years. And the FDA actually convened an advisory committee in the fall of 2023 to start looking at what would be required to make that move at the other end of gestation. In embryology, we've also seen some really interesting developments there, including, most recently, two research teams were actually able to grow mice from embryos into fetuses with fully formed organs using a mechanical, artificial womb. So these things are on the horizon. But one of the questions that I raise in Eve is there's some pretty significant scientific barriers to allowing those two areas of research to meet in the middle, including just practically talking about these new neonatal technologies. There could very likely be a certain threshold below which the extremely preterm baby simply could not be connected to, to the technology. And there's also some pretty significant ethical questions to be asked as to whether we would ever allow research towards full ectogenesis to occur.

Angela Sainy
So just on a theoretical level now, because this podcast series about futures to look forward to and just looking way into the future, then you do explore the positive political and social possibilities created by taking humans further out of the reproductive process, including this feminist dream that women might no longer be disproportionately burdened by pregnancy and childbirth. You know, that we wouldn't have to bear the weight of that anymore. Where did that idea first emerge, and is it still a feminist ideal?

Jennifer Cousin Frankel
It is. And what I found really interesting about that kind of threat of thought is that we see some of that discussion actually first emerging in the 1920s, when the word ectogenesis was first coined, but it's really made famous by Shulamuth firestone. In the 1970s, she wrote a manifesto in which she declared something to the effect of pregnancy is barbaric. She said, I think her phrasing was birth hurts and it isn't good for you. And essentially, the argument that she was making was pregnancy and birth can have all of these emotional and physical and social consequences that do disproportionately fall on women. She also felt that that sort of disproportionate division of reproductive labor led to a disproportionate division of care laboratory. And she argued that if feminist researchers were leading the research agenda, we would have achieved an alternative to pregnancy already. And I really take those threads of argument as a really powerful political provocation. The central argument that I make in Eve is that technology in and of itself cannot solve social problems. And these are equated to social problems, including a continued lack of research investment in health issues that primarily impact women, including understanding and addressing the causes of complications in pregnancy and birth, and also a lack of progress in terms of addressing social policies that equate to an inequitable distribution of care, labor as well.

Angela Sainy
But this idea that women could be taken out of this equation, and it is a very radical one, do you think that still survives in feminist thinking now? Are there still calls today for a redistribution of labor when it comes to reproduction? I'm just thinking here of the fact that fatherhood has changed so dramatically. Could this be the next, theoretically, the next stage of that evolution in the way that we think about childbirth and pregnancy and childcare?

Jennifer Cousin Frankel
Writing Eve, and also researching Eve, I've really been inspired by the reproductive justice movement, which is a movement that was founded by black feminist activists in the 1990s and fights for the aims of equally accessing the right to have a pregnancy, the right to end a pregnancy, and the right to raise one's children in a safe and healthy environment. And reproductive justice is also powerful because it's intertwined with other progressive social justice movements, including environmental justice and gender justice. And so one of the things that I come to an Eve because I want to be hopeful about the future. And one of the things that I come to in the book is that the preconditions for the kind of future where ectogenesis could be used to benefit all pregnant people could be used as this kind of further tool in allowing people to build families on their own terms, is the realization of the aims of reproductive justice and other progressive social movements.

Angela Sainy
Now, coincidentally, you were pregnant while you were writing this book. What was that experience like for you? Did it change how you approached the subject?

Jennifer Cousin Frankel
It was really interesting because my research on artificial wombs very much predated writing the book. It certainly gave this particular intimacy both to the subject matter of the book and the experience of writing it, because I was writing about creature birth while my baby was in the very early stages of development, and I was writing about what it actually means to experience a pregnancy throughout, one of the things that I kept thinking about is this very relational experience of growing a baby. And those are the sort of intangible things that I think can't fully be replicated.

Angela Sainy
I'm a mother myself, and I did feel, when I was reading your book, of course, there are so many risks associated with pregnancy, and it's not an enjoyable experience for everyone, but I did feel like it was an enjoyable experience for me. So there is, you know, there's a range of opinions.

Jennifer Cousin Frankel
Absolutely. In the course of writing this book, I've had the chance to have many conversations with people about ectogenesis. And something that I have found really interesting is that I've had as many discussions with people who say, that sounds incredible. I would have loved to have access to that, as people who say, that sounds horrifying. And I think how we feel about it, it's really shaped by our own personal experiences of pregnancy, of pregnancy, loss of birth, as well as our identities and our communities.

Angela Sainy
Yeah. And this does raise these kind of legal issues, the rights of the parent, the rights of the child, bioethics, you are a legal scholar. What do you feel are the most pressing issues that need to be addressed by the scientific community now in advance of these kind of technologies becoming available?

Jennifer Cousin Frankel
I mean, there's a number of issues that I explore in Eve. Three big ones include, when we're talking about the contemporary technologies that are in development, the first patient of those technologies is actually the pregnant person. So a really key thing is establishing really clear guidelines for consent for these technologies to be trialed. I also write about issues of the impact of this technology in the context of quite significant globalized and racialized health inequality among pregnant people and preterm babies. And then there's also a whole chapter in the book that is about the impact of the artificial womb in the context of really serious attacks on reproductive and human rights.

Angela Sainy
And on that question, actually, you also touch on that more politically frightening prospect, that in nations or states in which abortion is banned or people are deemed unfit to be parents, that if a technology like ectogenesis were available, might the state use it as a means of removing those fetuses, gestating them separately? I mean, it's so dystopian, this idea.

Jennifer Cousin Frankel
It is. I'll break that into kind of two responses, because to the first point, what I was really horrified by when I was researching for Eve and also for my PhD before that, was that there was this massive body of literature from mostly male bioethicists and conservative legal commentators, where they were effectively arguing that if we had artificial womb technology, we should require pregnant people to have unwanted fetuses transferred into this technology rather than seeking termination. And I did look at the construction of abortion law in this book. And what I really found was that in places where abortion is protected in law, as this limited right to bodily autonomy or privacy, that is always weighed against a purported state interest in the life of the fetus. That's where you see technologies that are intended to support the lives of wanted, extremely preterm babies, potentially mobilized by anti abortion lobbyists as yet another tool to try to undermine access to abortion. And that's in contrast to jurisdictions like Canada, where abortion is decriminalized through a pregnancy and treat it as a matter of health care. And I think that really speaks to the need to much more robust articulations of the abortion right in law as a human right and as healthcare.

Angela Sainy
Yeah, I mean, as you show, this is often about social and political context, and that's often, you know, how technologies play out. And it's interesting, you've written that when incubators were first introduced in hospitals, people did find them strange. And the same with IVF that was considered, this idea of test tube babies was considered very strange. Yet both technologies are now very normal and relatively uncontroversial. Could the same happen here then, in the distant future, could we see the idea of babies being born outside the womb as a completely normal thing?

Jennifer Cousin Frankel
That's such an interesting question. I mean, the central kind of thread of eve is that technologies are often heralded as this kind of world changing thing. Right. When incubators were introduced, contemporary newspapers were already calling it an artificial foster mother, and people believed that it had become possible to grow babies like flowers in a greenhouse. And with IVF, we saw all of these media articles referring to test tube babies. And was this the future? And so I think what, what is very interesting about that is that there tends to be this kind of immediate reaction to the development of technologies. And yet it is indeed the case that the use of technologies and their impact is shaped by our social circumstances. So perhaps in the, in the far distant future, we could see the same thing happen.

Angela Sainy
And so just finally, then, having researched this topic on balance, because this series is about a future to look forward to, how do you feel about the prospect of artificial wombs? Do you believe this is a technology which, as you write, might change humanity for the better?

Jennifer Cousin Frankel
After all, I think that we do have a future to look forward to, and it's because of progressive social movements. And I think that if we see social progress continue to move in that direction, then I think we could build a world where ectogenesis could be also used to progressive feminist ends.

Angela Sainy
Wonderful. Claire Horne, thank you so much.

Jennifer Cousin Frankel
Thank you.

Angela Sainy
And thanks also to all of you for listening. Next month, I'll be interviewing Rachel O'Dwyer about her book, the Future of money in the age of the platform. See you then.

Sarah Crespi
That was Angela Sainy and Claire Horne. You can find a link to the books list for the whole year, all six books@science.org. podcast and that concludes this edition of the Science Podcast. If you have any comments or suggestions, write to us@sciencepodcast.org to find us on a podcasting app, search for Science magazine, or you can listen on our website, science.org podcast. This show was edited by me, Sarah Crespi, and Kevin McLean. We also had production help from Megan Tuck at Prodigy. Special thanks to Angela for her intriguing interview about the future of reproductive technologies. Jeffrey Cook composed the music on behalf of science and his publisher, Aaa's. Thanks for joining us.