Knocked Up Podcast - We Can Make Eggs from Skin Cells?!
In this episode of Knocked Up, we unpack one of the newest breakthroughs in reproductive science.
In this episode of Knocked Up, Dr Raelia Lew and Jordi unpack one of the newest breakthroughs in reproductive science: the creation of human egg cells from skin cells. Dr Raelia explains how stem cells work, what makes egg cells unique, and why this research is both exciting and still far from clinical use. Together they explore the science behind the process, the ethical and safety hurdles that must be overcome, and what it could mean for people who can no longer produce eggs naturally. While the potential is extraordinary, Dr Raelia reminds listeners that proven options like egg freezing remain the safest and most effective way to preserve fertility today.
TRANSCRIPT
Jordi Morrison: Hello and welcome to Knocked Up, the podcast about fertility and women's health. You are joined, as always, by me, Jordi Morrison, and Dr. Raelia Lew, CREI Fertility Specialist. Welcome, Raelia.
Dr. Raelia Lew: Hey, Jordi.
Jordi Morrison: There was some big news recently, Raelia. The headline I saw was, Researchers produce human eggs from skin cells in scientific first. This sounds pretty exciting.
Dr. Raelia Lew: It does sound exciting. Like all exciting things, there's more to it than a headline.
Jordi Morrison: Can you explain to us in really simple terms what this new research has done, turning skin cells into eggs?
Dr. Raelia Lew: Sure. A good way to start is to consider that when we start ourselves in life as an embryo, we have to go on and make tissues of every organ system in the body. We need to make skin cells, egg cells, kidney cells, blood cells, nerve cells or neurons. And in order to be able to do this, we start off as stem cells. So stem cells means a cell that is what we call pluripotent, which means it can turn into lots of different types of cells. Cells in the body go through a process of what's called differentiation, meaning they gain characteristics specific to the cell type that they become. And for most cells, that is a one-way pathway. So once we differentiate into a kidney cell or into a liver cell or into a gut cell, we don't go back to being a stem cell.
And this is true for the way that eggs are made in human fetuses. Egg cells are created from embryonic stem cells when we are in utero. And after we've made all our eggs, we stop making them. We don't make any more for our reproductive lives. And that's one of the reasons that female infertility is serious and irreversible and associated with advancing age, as the eggs we have deplete and also become metabolically unable to make a baby due to the aging process. What scientists have tried to do is to use stem cells in the lab, potentially derived from embryos, or bone marrow cells, any kind of stem cell, and turn off their ability to make other cell types and turn on their ability to make eggs. We all have DNA in our chromosomes and every cell in the body that is euploid, meaning it's got two copies of each chromosome, has all the instruction manual to make every type of cell. So it's about turning genes on and off to make a certain type of cell from a stem cell.
Jordi Morrison: And how groundbreaking is this compared to what's come before?
Dr. Raelia Lew: Look, it's really interesting. We've always known that this is what happens. It's about really deciphering what happens in a cell to make it into an egg and then trying to turn those genes on to make that happen on purpose. And when we do it from a stem cell, that's understandable. A skin cell, which is a differentiated cell, to turn off the genes that made it differentiate into that type of cell and make it more like a stem cell again, and then turn on different genes to make it make an egg cell, and this is what has happened in this research. So it's a really cool concept. And you know, rather than just telling a stem cell how to make an egg, which is what happens in the body, so this doesn't ever happen in the body, this is totally what we call iatrogenic, or it's man-made, because this never happens in the body. A differentiated cell in the body doesn't go back to being a stem cell and then turn into something else. This is something that we've done in the lab by messing with these cells, in one of the more scientific terms, as scientists tend to do. It's a proof of concept. And this is potentially very exciting.
Jordi Morrison: What are the claims being made? And where might this take us?
Dr. Raelia Lew: So look, it's one of those areas that we do get very excited by the possibility and then we get reined back by the reality. The idea of turning a differentiated cell into a stem cell and then into another type of cell is super cool. However, as I mentioned, this is totally unnatural. And we don't know that the egg cells that look like eggs are going to behave normally, and certainly eggs are a very special type of cell and they have to make people. And we don't know that if they make a human baby that that's going to be a healthy baby. We can't assume that that's the case. It may be that if we make babies from cells made this way, they might have a shortened life expectancy. Maybe they'll be neurodevelopmentally compromised. Maybe they'll get cancer. We just don't know. It's certainly cool. It's a long way off being proven to be safe. And therefore, I would be very surprised if in the next 10 to 20 years, this actually is utilised in clinical practice.
Jordi Morrison: The article uses a term called mitomeiosis. We've spoken about meiosis before on the podcast. How does mitomeiosis compare to meiosis or any other procedures or approaches?
Dr. Raelia Lew: Again, it's not something that happens in nature. So usually egg cells are made from stem cells that become oocytes via a process of cell division. The oocyte then goes from being euploid, meaning it's got a copy of both parents' sets of genes, to being haploid, meaning it has only one copy of every gene so that the other half of the baby comes from the sperm. And that process of going from being a euploid egg cell to a haploid egg cell is called meiosis. Mitomeiosis is when you take a cell like a skin cell that has double the amount of DNA that an egg would give to a baby and then make that cell kick out half its DNA. So it's like activating meiosis in that cell. And again, it's not something that ever happens in biology. It's something that has been forced on the cell through laboratory experimentation.
Jordi Morrison: As with anything new, the researchers reported some challenges. Can you explain these to us?
Dr. Raelia Lew: I don't really fully understand myself all the technical hurdles that would be involved in this in a lab. It's not something a reproductive doctor would do. It's very much something that a cellular biologist would do. And the questions that I would have as a reproductive doctor are how do we know that this is going to make eggs that would be safe for a patient to make a baby. And that is what the whole world of reproductive medicine would be asking and what we would require for this to be utilized in clinical practice. First, it would need to be utilised in an animal model so that we could see that animals were potentially healthy. Usually, I know this sounds really unpleasant, but this is what we would need to see done. We would need to see it in an animal model that was similar to us, so potentially a primate animal model. And we'd need to watch them for the course of their life and observe if they had any increased risks developmentally, genetically, reproductively, in terms of diseases, in terms of their neurodevelopment, really everything about them. So you'd want to study several generations in an animal model before considering utilising this clinically in humans. And it might be that if you found some serious worries, then you'd never use it in humans.
Jordi Morrison: So you did mention animal trials. Are there any being done at the moment that we can learn from?
Dr. Raelia Lew: Again, it's not really something that I would know because I work clinically with proven methodologies in humans. But I can tell you as a medical director of an IVF unit, because I'm the medical director at Melbourne IVF, this is a long, long, long way away from being accepted in any form of clinical practice because we would be very reluctant to use such an experimental technique with the potential risks that it might result in to make actual babies. It would not be ethically permissible. The first rule of medical ethics is do no harm and we would not know that we were not doing harm and there's a great deal of potential to do harm.
Jordi Morrison: And I guess I wanted to talk about this. I chose this topic because I think we hear about these exciting developments and think, it's going to help me straight away or it's going to help me really soon. But you're saying 10, 20 years, so possibly not in our reproductive lifetime or in your career lifetime.
Dr. Raelia Lew: Oh, definitely, definitely not. I don't think it'll be in my career. I think it's good that the science is being done for sure. And I don't mean to be a naysayer, but most things in medicine take that amount of time in terms of adopting new techniques, technologies that are involved in creating human life, because we have a great sense of responsibility to not only our patients but to their children. And we can't accept science that isn't proven to be safe when we talk about creating babies.
Jordi Morrison: So when a new technology has been developed, what would you expect to be put in place before something novel went out to clinical use?
Dr. Raelia Lew: Well, we in Australia have a regulation of many things through the Therapeutic Goods Administration. In the US, it's the FDA. And rigorous scientific proof of safety needs to be a prerequisite for the adoption of any new technology in reproductive medicine when it comes to egg, sperm and embryo.
Jordi Morrison: One of the things that I read was that the embryos didn't progress and they think probably due to chromosomal abnormalities. This is a bit of a red flag. How big of a red flag would this be in your view?
Dr. Raelia Lew: Look, it's major because what they've done is made cells that look like eggs, but we don't know that they're normal. And the fact that they didn't progress means that they're... they definitely weren't normal, you know? And it's not surprising because it's really hard. I mean, sometimes in IVF, we walk a fine line because people may accuse us of playing God. And I think we can be really, I guess, hopeful and enthusiastic about progressing science. But we need to also be mindful that we have a great responsibility to our patients. I don't practice to get headlines. I practice to help people. And it's very important not to encourage false enthusiasm or false hope. And it's also important not to do harm to patients and not to do harm to children.
So everything we do in IVF is very cautious. We try and focus on patient safety. We don't do nearly as many double embryo transfers anymore. You know, when IVF was new and embryo success rates were very low because we weren't as good at making embryos as we are now in the lab and we weren't as good at freezing them. So if we didn't use them, we would lose them. Early IVF doctors used to put back multiple embryos and IVF became famous for twin pregnancies. And we have strived over the last 40 years to make incremental improvements. We've come a really long way and now we put one embryo back at a time as normal practice. And that's because, you know, our commitment is to safety. And the more double embryo transfers we do as IVF doctors, the more babies are admitted to intensive care for prematurity, because the more multiple pregnancies are made. And that is a serious consequence. So, you know, we take our responsibility very seriously to our patients and to the babies we create. And patients can be reassured that while we are enthusiastic about scientific endeavour and development, we're also very conservative and very focused on safety.
Jordi Morrison: On a positive note, this is exciting. Who would this potentially help in the future and what makes it so exciting?
Dr. Raelia Lew: What it gives the possibility of in theory is that if somebody doesn't have egg cells anymore, or they've had chemo, or maybe they were born with a genetic condition that they didn't make eggs, it might open the door, if we could make eggs from other cells, that they might still be able to become parents. And it would also, I guess, rock the boat of whether you could make an egg as well as a sperm from a male, from a genetic male. So there's lots of things that could be theoretically possible with this technology. As I said, I think it's a long way off and it may never result in the reality of what it's trying to achieve.
Jordi Morrison: So our listeners, what should they take away from this?
Dr. Raelia Lew: I think from a point of view of a female perspective, if you are young and you are not planning a family, there is proven safe possibility to freeze your eggs. And if you freeze your eggs, they retain their biological potential. And if you try to use them when you're older and the eggs no longer work, they give you your most realistic chance of having a baby. And I would encourage patients to consider their reproductive future in the context of existing proven, tested, safe technologies rather than hang their hopes on experimental potential future technologies that may never translate to clinical practice.
Jordi Morrison: And I think it's exciting that there's always development wherever it may take us.
Dr. Raelia Lew: That's right. We're exploring how the code of life works in cells, the DNA and the genes in the scientific world. And that can only help us understand ourselves better with potential offerings for the future within a safe ethical framework.
Jordi Morrison: Thank you, Raelia.
Dr. Raelia Lew: You're very welcome.
Jordi Morrison: To support Knocked Up, leave us a review or recommend to a friend. Join us on Instagram @knockeduppodcast and join Raelia @drraelialew. And email us your questions to podcast@womenshealthmelbourne.com.au.
Hosted by Dr Raelia Lew and Jordi Morrison
Dr Raelia Lew is a RANZCOG Board Certified CREI Fertility specialist, Gynaecologist and the Director of Women’s Health Melbourne.
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Have a question about women's health? Is there a specific topic you'd like us to cover? Email podcast@womenshealthmelbourne.com.au. We keep all requests anonymous.