So my big question for you is how could studying human embryos in a dish help people who are dealing with infertility problems and miscarriages?

How would that kind of research help people like that?

I█m Insoo Hyun, a philosopher and bioethicist and director of life sciences at the Museum of Science Today, my guest is Magdalena Zernicka-Goetz She's a developmental and stem cell biologist at Caltech and the University of Cambridge.

We discuss her groundbreaking research on human embryos and human embryo models, which she uses to uncover the mysteries of pregnancy loss and infertility.

So, Magda, I'm so glad you joined us today.

You are a renowned developmental biologist and a stem cell biologist.

In your book, "The Dance of Life," you describe a scare that you had when you were pregnant with their second child.

Could you tell me what happened?

I didn't know I was pregnant with my second child for a while.

And then when I learned that I am pregnant, this was the fourth, nearly fourth month, of my pregnancy.

So I went through genetic testing called Chorionic Villus Sampling, CVS, this is when the doctor takes a few cells from the placenta and they take cells from the placenta to assess whether the baby's genetically normal, because placenta and the baby come from the same egg, from the same fertilized egg, from the same embryo.

And what have happened that they discovered that many cells, actually 25% of the cells that they tested had trisomy out of Chromosome 2, which is a huge chromosome, has many, many genes.

So there was a thought of concern.

Of course, I knew as embryologist that this is testing of the placenta and not the baby, but this is offered as a test of the genetic normality of the baby.

So this was gutting news, and this made me set up a new type of research in our lab in which we would create embryos that have some cells that are abnormal and some cells that are normal and that are mosaics.

And then we would be able to follow what happens to abnormal cells and whether they are destined to form placenta rather than baby to be.

That was our hypothesis.

So this inspiration for the study that you were describing came from your own experience?

100%.

That's amazing.

I think that in general, when I have a problem, a life problem or a scientific problem, I sort of tend to think about it quite a lot.

And I think this thinking led me to think that I should do something positive about the not-welcoming news.

And this was really to set up the system in the lab to address this question scientifically.

I was extremely lucky that I could do that.

And then what happened eventually in your pregnancy?

Did everything turn out okay?

Everything turned out okay.

So I waited for one more month to have another test that would directly test a genetic normality of the cells that came from Simon from my little baby.

And then they were normal.

And indeed, Simon was born very normal.

Is some of your motivation to study the human embryo, does it go beyond just wanting to understand human development and just that thirst for knowledge?

Or do you also hope to eventually use that knowledge to help patients, to help people with infertility problems?

Of course, this is just what is that mission, to help people.

And when I started to work on human embryos, that was around ten years ago.

This was with that aim of trying to solve the mystery of why so many pregnancies fail within these first few weeks of our life.

In fact, the first two weeks of our life are most fragile.

Many embryos fail before they are implanted, so until day seven, and another massive loss of embryos is at the time of implantation and soon after.

So really trying to find out what it is that our embryos find so difficult to get right at that stage.

Because some of those embryos might be genetically abnormal, and then we understand they are the embryos that will be by nature eliminated, but many of them are normal.

So to understand the reason behind it and to one day hopefully find a solution to prevent so many deaths would be my mission.

Do you have a general average statistic of how many embryos fail to implant or fail to go beyond the first two weeks?

About on average, how many are we talking here?

Around 60%.

60%.

So we often think about pregnancy losses when we talk about miscarriages, but actually they happen pretty regularly.

So if you think about pregnancy iceberg, only around 30% of embryos that are conceived are surviving to create a normal baby.

10% are lost due to miscarriage, which happened at later stages of development, and 60% are lost within the first two weeks of life.

I've heard you describe that process of trying to understand by looking at images or just sequences of still life, almost like trying to understand the game of basketball by looking at photographs of a game and trying to figure out what is going on in the game.

If all you have are photographs of the game is really hard to know what is important, what is not important about the game of basketball.

And similarly for embryo development, you just have these still images or still, you know, specimens, you can't see the process, you can't see what's actually happening from one stage to the other.

So I think that's why it might be so important to study specimens that are actually in culture that are going through those processes of development in real-time.

Yeah, that's absolutely correct.

So I think that if you have only snapshots of developing embryo, you do not understand what happens in between and therefore you cannot understand the mechanism development of how embryo develop.

You know, it develops, but you don't know how.

And understanding mechanism, as we say it scientifically, meaning understanding how embryo develop from one stage to another, how it reaches different milestones, is absolutely critical if we wish one day to understand what happens wrong when pregnancies fail.

So we often talk about the "black box" of development, actually not only in the case of human embryos, but also in mouse embryos, and this is particularly this moment of implantation development, because that was extremely difficult to culture embryos through this stage in a dish.

So until implantation, so the first seven days, embryo develop in a very simple medium.

We can culture it, we can manipulate it, we can observe it, mouse embryo and human embryos.

Of course, those donated for research by and parents that use IVF clinics and decide that they don't want to use these embryos for reproductive purposes, when they donated to research, we still can observe it at that stage.

But what happens next is enigmatic because embryo at that time have to be returned into the body of the mother for the process called implantation.

And since we cannot observe it, it is referred often as developmental "black box."

Until seven years ago that we published a paper that showed that we actually can culture human embryos for an extra few days in vitro.

So people have talked about the "black box" of human development.

Can you explain what that means?

What is this period we're talking about and why is it so hard to understand that?

So this period is the is the period of development where we cannot observe embryos directly.

So this is not the pre-implantation period, which is the first five, six days, when we can easily culture embryos in vitro in a dish.

Yeah, so obviously you can unite sperm and egg in a dish to study the first few days.

The first few days are sort of open for study.

Right.

But then embryo implant in the uterus of the mother, as this kind of invasion, and we were not for a long time able to mimic it in the lab.

And that's when major morphological changes to the embryo happen.

Embryos are entirely reorganized at the moment of implantation.

And at this period, women don't even know that this is happening.

Absolutely.

We don't even know we are pregnant at that stage.

And this is the stage when so many of our embryos are lost.

So, you know, when you think about that, how many pregnancy we might have lost without even knowing that.

So that's tragic.

Now, this is also going to be really relevant for couples who are trying to go through in vitro fertilization, right?

Because there, you unite, sperm and egg in a dish, and then you're going to transfer what look like pretty normal embryos into the womb hoping for implantation and pregnancy.

But from what you're saying, there's probably a very high likelihood that none of these will actually implant and go on.

Yes.

So at the moment, what happens is that there is particular criteria for choosing which embryos should be implanted into the body of the mother.

They're not perfect.

And therefore, some of those embryos that will be chosen to be implanted, to be transferred to the body of the mother, will not survive.

So one of my missions is to identify and characterize precisely the criteria that have to be taken into account in IVF clinics, which embryos should be transferred into the body of the mother.

Let me back up a little bit and ask you — So to study human embryos in the lab, where do you get those human embryos?

How do you get them and how long do you normally study them in the lab?

The embryos that we use for human embryo experiments in the lab are donated by parents, but not directly to me, but through IVF clinics with which we collaborate.

So we have lots of IVF clinics who are our collaborators.

And I am extremely grateful to them because they are incredible in making time and putting effort, in preparing consents with the consent forms, with the parents to donate those embryos for our research.

When we receive them in the lab they are often at the blastocyst stage.

This is the moment when an embryo would like to implant.

So we developed, several years ago, a method that allow us to culture human embryos, beyond implantation, in the lab.

Yeah.

So this was like the major — That was a very famous paper.

So this is 2016 you published this paper.

So we published in 2016, our first embryo culture experiment was actually 2014, but at the time I was moving the lab at the University of Cambridge, I was, but I was moving from from Gurdon Institute to University of Cambridge, So we actually couldn't do many of this experiment because the license that I had for this work was in one institution, I was moving to another.

So the publication of this work was actually a delight, and many experiments could then be repeated too, for me to get the confidence that I really can do it, to be able to report it to to the public.

But it was incredible.

And the first embryo I still remember so vividly when when we had this first human embryo cultured beyond blastocyst stage, it's the first time when embryos grow.

So you can see them not just dividing into smaller and smaller cells, (They get larger.)

you see them for the first time expanding.

They're still pretty small at that stage.

But you're right, they're getting larger than the egg size, right?

That's right.

That's right.

So that was quite a remarkable experiment because I remember when I read it, I thought, boy, I have to change what I would tell my students.

Because I would tell my students IVF clinic embryos, in vitro fertilization clinic embryos, Either you have to use them, implant them, or freeze them, because I assumed, many other people assumed, that you need it to be within the uterus for it to develop any further for what your study showed was that it actually attaches to a dish and goes much further than we would expect on its own.

And that was really quite amazing, that it kind of had the capacity to develop further without being in a maternal body.

And you got it all the way up to day 13.

In fact, you had to stop the experiment at that time because by law in the UK you cannot go beyond 14 consecutive days in culture.

So we're actually standing right here at the border of Boston and Cambridge.

This is the line that divides the two cities and it runs right through the Museum of Science here.

I always think that it's so fun to be at this point where you're crossing from one side to the other.

You're crossing from Boston into Cambridge, but there's another boundary, another border in developmental biology that's been very important.

The 14-day mark.

Can you say what is important about the 14-day mark?

What do people think is happening in the human embryo at that point?

Day 13 to day 14.

So, yes, as you know, this is a very important boundary in human embryo development.

That's the time when the primitive streak structure forms.

It's the time when embryo initiate the process that we refer to as gastrulation.

So this is the process when STEM cells that are set aside until day 14 initiate the action to build the body.

So that's the moment when we don't just accumulate cells to build the future body, but we start the building process.

What was the record before you hit 13?

Like how long did people actually get to?

All of the cultures of human embryos stopped at day 6/7.

That's the time when embryos are at so-called blastocyst stage.

They look like a ball of cells with a tiny little mass inside.

And this was the limit of the culture.

Sometimes people would culture those blastocysts a little bit longer, but not in a way that will allow embryo to grow.

Mm hmm.

So this was the first time.

First time we were able to take it further to day 8 and 9 to 10 then 11.

And we stopped just around day 12 when we started to see that embryo, that the media that we developed — media, meaning the environment for the embryo to develop properly — was maybe, you know, our limitation at day 11 slash 12.

What can you learn up to day 13?

So so you went from 7 kind of the previous milestone, 7, to day 13.

What did you learn about that little area?

So, a lot.

So it took us years to understand the first seven days.

So from the time when the first human egg was fertilized to until a few years ago, we were still studying the first days of our lives in humans.

In mouse, there are many laboratories, including ours, that studied this stage of development.

And still we have many questions.

For example, how an embryo know what time is it.

And they have to measure time somehow because they have to reach certain decisions at certain stages of their lives.

So there is no clock.

So that is an example of an open question, you know, to identify this sort of time and the mechanism of it.

So we obviously there's still many, many questions not addressed until day 7.

But we don't know, well, we hardly know anything beyond day 7.

So many things we learned.

We learned how cells divide and communicate with each other chemically, mechanically, how they exchange signals, what are those signals.

We know that in the mouse that a specific group of cells formed soon after an embryo implants.

It's a migratory group of cells, they become specified in one region.

Still, we don't know exactly how.

And then this group of cells migrate together to protect the adjacent cells from undertaking process of gastrulation, in primitive strict formation that we talk about.

In the future, this part of the embryo will be the head.

So we were able to identify this group of unique group of cells in human embryo too.

So that's another example.

But essentially we are still discovering many, many things.

That's a lot to discover in that period.

That's really the time when the foundation for the future body is built.

Where the cells have to change their state of potency.

When they have to make certain decisions that we can't even dream about because we don't know what they are.

So we are still we are still in the process of discovery of what happens at this stage.

There's been a lot of discussion about this 14-day limit, 14-day rule.

It comes from, most famously, the Warnock Report in the UK.

This is the early '80s.

and it eventually became law in the UK in 1990.

And, you know, this has got a long history.

People are now thinking maybe it's time to rethink that mark.

So my big question for you is: How could studying human embryos in a dish help people who are dealing with infertility problems and miscarriage?

How would that kind of research help people like that?

So any research on human embryos within the first week, second or third week of our life will help to understand why so many pregnancies fail and will help people with infertility problems.

Absolutely.

And we know that infertility problems are incredibly difficult emotionally.

So this type of research is the only way.

And human embryo models created from stem cells, that I hope we can talk at one point about, are really aiming to address this issue.

Why it is and how we can fix it.

What can we do about that problem?

So I believe any permission for culturing human embryos that otherwise would have been discarded — so these are not embryos created for research — they are so-called samples.

Right, they come from fertility clinics and actually it's when the couple, or the person for whom they're made decides that they want to throw them away, they're approached by somebody who asks, can you maybe instead of throwing them away, donate them for scientific research, here is the kind of work that we would do and what we will learn.

So that's where they come from.

They come people who would have otherwise thrown them way.

That's very important to remember.

So many people think that maybe those embryos are created for research and actually they don't.

They are not created for research, they are given for research because otherwise they would have been discarded.

Yes.

So I think that instead of discarding those embryos, if we can use them, either for generating human embryonic stem cells that we can use in the research to understand also the process of and not only infertility problems, but also the process of regeneration, are very influential.

I wanted to ask you that question.

I know that it's very close to your interests and your way of thinking is very broad in the context of human embryo development.

Not everyone has such a broad view as you do.

So what do you think?

How long should we be able to culture human embryos?

As you know now, we can do it until day 14.

Where would you put that boundary?

Yeah, I think, to put my answer into some context, I want to refer a little bit back to the Warnock Report that gave rise to the UK law, law in other countries and guidelines everywhere else.

When in-vitro fertilization was first developed in the late '70s, there was a really important question before all members of society, which is: Now that we can unite sperm and egg in a dish, basically have fertilization outside the body, which we never were able to do before.

Now the question is, what should we be able to do with these embryos?

Obviously we want to use them for reproductive purposes.

There are all kinds of questions from the Warnock Report, very interesting at that time that we think are maybe a little bit quaint questions, but questions like, "Does the couple have to be married to have IVF?"

You know, "Can can a single person have IVF?"

So those are questions that we're dealing with.

But then there was the further question of now, do they all have to go back into a womb for a pregnancy and reproduction, or can researchers use them to study human development, because there's no other way to get this information.

So that was a big topic of discussion for the committees back in the day.

And they decided, they made the first big decision.

The first big decision was, yes, you can use them for research that was a momentous declaration.

You can use them for research.

If they were donated by a couple.

Then the question was how long can you study them?

And they had to come to a decision because Mary Warnock and others on the committee believe that they could not get it through Parliament unless they came up with some kind of deadline.

It was not politically very expedient for them just to say: as long as people want.

So they had to put a line.

They thought two weeks was good because maybe you can learn everything you wanted to learn within two weeks.

It's easy to mark off two weeks on your lab calendar.

It seems like a pretty reasonable place to stop because, as you said, that's the first time at which we have another major developmental milestone, gastrulation, the beginning of the primitive streak.

So it seemed like a sensible place to stop.

That of course didn't make everybody happy because there are some people who believe, clearly, that life begins at conception.

So any embryo research, any use of an embryo besides reproduction, is wrong.

There are others on the other very other end of the extreme that thinks, no, it's not a real person until it's independent of the mother, or has self-consciousness, which happens year 3 or 4, or that it has sentience, which maybe happens at week 24/23.

So there is a big range of people's beliefs.

So what the Warnock Committee was trying to do is capture as many people kind of in the middle as possible with this compromise of 14 days.

Here we are today now wondering, well, should we move the line again?

And I think really that the issue is, is there a good argument that can be made for why interrogating that period is important for human health and of benefit to society?

Because now the technologically we can get to that point, we may have to recalibrate that negotiation.

So there's an enormous range that people believe the embryo has full moral status from day 0, day 1, to all the way to after it's been born.

In order to capture the most people in the middle, I think the committee and the policy is to try to come to a compromise of how can we have some scientific exploration reasonably while also protecting people against this idea that we're going to go too far with this research.

So I think it really has to do with what could be learned from the research, is that important, and can we still have some assurance for society that there is a stopping point that's reasonable?

My view is that once we are out of that "black box" of human development, maybe after day 28, there's no reason to continue to culture the embryo, to learn from it, because there are other ways to get information that you may need.

So I think that the natural stopping point now, given the technology, will be to aim for about day 28 or so, but I wouldn't really go much further than that.

I was wondering, though, when you did the experiment that got up to day 13, it probably then requires other systems or other kinds of technology to enable the embryo to go, right?

Because of course, you started day 13 because of the law and all of your values, but you really cannot expect it to keep going on and on, right?

So it probably needs some other kind of support to even go past day 14.

So far, the cultural system that we have for culturing mouse embryos in vitro also has its limitation.

So we can control mouse embryos in vitro until day 9, maybe 10, maybe 11, but at that stage it starts to rely on placenta, which has to be provided by interactions, the interactions of the embryo with the body of the mother.

So we don't have that, even for mouse embryos, that are much simpler.

So I believe that the culture system that we did establish several years ago for culturing human embryos through the implantation stages in the lab will allow us to culture it maybe until this day 12, 13, but maybe not much further.

One would have to enrich the culture system massively to be able to feed very quickly-growing embryo at that stage.

It still doesn't look like an embryo as we think of all the embryos, as we have photographs of them, but it's growing very quickly.

So, yes, the culture system.

So what I've heard about when Baroness Warnock and Anne McLaren, a colleague of mine, were at the time discussing where we should put the stopping point, is that they actually believed that nobody would be able to go until they 14.

Because obviously the first six weeks of our life is very easy to maintain in vitro, but not beyond.

Yeah, in my view the 14-day rule is very symbolic, but it actually didn't do much work in research, oversight and regulation because technologically you couldn't break the rule.

There's another approach, though, that you can use to try to study the "black box" of human development, besides using natural embryos or embryos from IVF clinics.

These are called embryo models, now, you've doing some really exciting work in that area.

Tell me about some of your latest work in embryo modeling.

So when we cultured the first mouse and then human embryo in the lab beyond blastocyst stage, so through the implantation until this early post-implantation stages of development, we were able to identify exact interactions that happened between different types of stem cells that are in play at that time.

Three different types.

And how they not only talk to each other chemically through exchanges of the signals, but also mechanically.

So this really was the stepping stone in my life.

I realized that these interactions should be possible to recapitulate with stem cells, with embryonic stem cells or stem cells for those two extra embryonic tissues that are really guiding forces for embryonic stem cells of what to do.

So that's when we started to make first embryo models.

This was actually 2014, so 9 years ago, we first made those models for mouse embryos.

And each year, actually nearly each year, we make them more complex, more accurate by adding different types of stem cells.

So not using just one type of stem cells, adding two actually different type of stem cells altogether, three stem cells and merging them together.

So really it's a model because you're taking stem cells, you putting them together and then they're sort of self-organizing, they're forming what looks like an embryo or could be.

They form structures that look extremely similar to embryos, they're not real embryos, but they look very similar to embryo.

And this allows us to make save a lot of very important discoveries that we would find very difficult to make in real embryos.

For example, we learn how cells recognize who is who, how they sense that I am this type of cell and I have to be here and the other one will come and we'll take another role.

So we talk about that, the self-organization process.

So those models are extremely useful.

We also can take stem cells and do genetic modifications in them that will change the expression levels of certain genes and find out how this affects the whole apparatus of development.

Again, something that would be very difficult to do on the embryos and we can now do it because we can change one component and not two others, or we can change the gene in one of these extra embryonic tissues and see how it will impact the embryo.

So what we did over these last nearly 10 years is to perfect those models to make them more integrated.

So these are mouse embryo models.

Mouse embryo models.

So now we also do human embryo models.

So you use human stem cells to make the human embryo models.

So human embryo models, we make them from different type of human stem cells.

We actually do we use human embryonic stem cells, but we program them by modifying them through generating induction expression of specific factors that will make them differentiate in desirable directions.

So we take three type of stem cells like that, one is we call it white type that, that kind of naive human stem cell, embryonic stem cells.

And then those two other type of stem cells that we genetically modified and we put them together to create very faithful reproduction, but not identical.

Yeah.

Of the human embryo.

So then that means, to this point, these are the most complex human embryo models in existence.

They're really quite amazing.

Can you use these models to to help patients and doctors and scientists understand some of the developmental disorders and the causes of miscarriage that so many people are affected by?

Absolutely.

That's the aim for those models.

So we know that some pregnancies are failing because one part of the embryo might develop genetic abnormalities.

So we can now actually test whether this is the case and maybe in the future.

That's the aim.

I can't promise it, but that's the aim to see how we would be able to prevent it.

What's fascinating also about this area of work is the 14-day rule doesn't for the International Society for STEM Cell Research, for example, apply for an embryo model.

So you can actually study much later stages of development using their real models that you can't do using IVF-derived or natural embryos.

I'm very pleased that you bring this point because this there is some confusion, and I'm often asked how long could we culture those human embryo models in the lab?

There's a lot of confusion about it.

And people say, well, does the day 12, sorry, 14, day 12 in California, apply?

And I am often trying to explain that actually there are models, not real embryos.

So the timeline is anyway different.

Right?

And because they're models, we should not think of them as we think about real embryos.

Well, none of these models are viable.

And it's not like they could become a baby.

They would never be able to.

Some of them are missing some components, some cell types.

Absolutely.

And also, even if they have these three components, the three tissues that we will bring together to create the embryo, these embryos at this stage of development, they cannot be returned back to the mother, so they will never be implanted back.

So they are just really model of the post-implantation stages of development, those stages that you call the developmental "black box."

That's amazing.

So just an amazing tool to to interrogate that black box of human development.

At some point, though, do you think you would have to compare the embryo models to IVF-derived models to really make sure that they are doing what you think they're supposed to be doing?

Very important.

Just to understand that what we are studying does reflect reality.

So often we look at the models, Carnegie's collection of embryos that were collected in the '60s, and so we look them at them and try to identify exactly the same stages of development.

But also luckily, or, you know, my design in our lab, we also have access to real human embryos.

So we are able to culture them in parallel and make these comparisons all the time.

And I think only because we have that possibility of comparing them with real human embryos, we are able to make a great progress in this.

Yes.

So my view, because earlier you asked me where do I sit on the 14-day rule, I think that the rise of embryo models, human embryo models really changes the discourse in very important ways that was not present when the first rule was first established back in the early '80s.

And that is we have embryo models.

Now it may be possible, it may be justified to let some people explore a little bit past day 14 in the natural embryo to gather data that will be extremely important to validate the embryo models, because you really want to make sure that the models are accurate.

But once you have that data it may overall in the long run, require less use of human embryos because you can study embryo models to interrogate disease, to interrogate, you know, the causes of deformations and other ailments.

That's why I think I'm open to the idea of going to day 28, because you get all that data you need to then propel forward the embryo model.

I feel that can do just so much great work for society, scientific benefit, and the rest of society.

Of course, people are very worried about a slippery slope.

Where does it end?

You know, where do people stop once you allow them to go past day 14 with the natural embryo?

I think the natural stopping point is 28 because at that point you have all the data you need to validate the embryo models and to understand human development in that "black box" period.

There are some people who are wonder, though, you know, the technologies that enable both the embryo models to go on and on and that enable the natural embryo to go past day 14, people may be worried that that kind of gets us on the road to like an artificial womb kind of environment.

Do you think that that's really a danger?

I'm sure that there are a lot of science fiction people who are really worried about that.

Yeah, I think external womb was a science fiction concept, at least it does sound to me like that.

When we think about what we can do to develop, to support embryo development in culture for longer, particularly for those embryo models that we were discussing, to really make them teaching us about the stages of development, that we can not get access to, then yes those artificial platforms some people will call artificial wombs.

I wouldn't call them this way, and I imagine that they might not have to be as sophisticated as we think.

Yeah.

Most of the growth at that stage is dependent on nutritions that have to be provided to the embryo.

And this is a very important point.

So both in the embryo work, embryo model work and in organoid field work, we have a big obstacle.

It is to feed these organoids these sort of synthetic organs or embryoids in a proper way that they can develop.

This is still not achieved.

And that's why many organoids at early stages of their life, they look, they can develop better because the nutrition can reach the core of the structure, but not at later stages.

So this sort of organoids and embryoids community have the same problem to solve, and I don't call it artificial womb for organoids either, but rather the platform that we developed years ago for implantation to develop equivalent platforms for embryos and organs that are in more advanced stages of growth.

Yeah so essentially then you're saying the systems that help support embryo research and embryo models are not equal to what would be necessary to support external pregnancy.

Like, you know, gestation outside the womb, that's a wholly other different.

more complicated thing.

So this is really not a slippery slope toward that, it's really just to enable the research questions that you are pursuing.

You often talk about biology and science as a type of dance, and you've also explained that sometimes cells almost like dance together and coordinate.

That's a wonderful image.

What do you hope eventually throughout your career to really — I mean, you've done so much already — What are you hoping to sort of establish and what's the next dance you want to interrogate?

Oh, there's so many different types of dance that are absolutely fascinating for me.

So these interactions between cells, when they build the embryo, I call it in my mind dancing, because the cells have to exchange.

I mean, they communicate with one another.

They shape each other, they influence each other.

I think this is what happened real partnership in, for example, dance, but it also happens throughout "Oh, like you and I now work together to achieve something that is very important for us and hopefully important for many, many people."

I think cells try to do the same.

They are not aware of it, but they do that.

I really love the metaphor of the dance because actually in my area of bioethics, sometimes you do have to do a dance between these grand ethical principles you may have and everyday experience and you have to dance between the two and negotiate.

Or the 14-day limit that's been around for over 40 years okay, but isn't it time to negotiate and dance in order to move to move to another stage?

So cells are dancing and negotiating with each other too.

Of course, they are not, you know, plotting, I guess, but they have to negotiate many hard decisions.

And for me to be able to work out those decisions to the extent that we can mimic them perfectly and create perfect models, which sort of we are on a journey for, it's already very exciting.

Now, I never — you know, I have dreams.

Of course I do have dreams like all of us have dreams.

But I also leave a lot in my life for being influenced by what happened today.

So, you know, some of the things that I do today I would have not predicted 5 years ago, meaning some of the specific.

I think many people.

wouldn't have predicted it 5 years ago.

That's how rapidly you're moving forward.

Magdalena, it was just wonderful to have you today.

And I just so enjoyed our conversation.

Thank you so much for sharing your insights with us.

Thank you.

Thank you, you too.

This was really a pleasure and thank you so much.