Embryonic stem cells | Cells | MCAT | Khan Academy

Summary

This script explores the journey of a fertilized egg, or zygote, through the stages of early embryonic development. It explains how the zygote becomes a diploid cell with full DNA complement, undergoes mitosis to form a morula, and then differentiates into the trophoblast and embryoblast, leading to the formation of a blastocyst. The focus then shifts to embryonic stem cells within the inner cell mass, highlighting their potential to develop into any cell type and the ethical debates surrounding their use, especially in contrast with the destruction of embryos in in-vitro fertilization processes.

Takeaways

• 🌟 The script discusses the process of fertilization where a sperm cell meets an egg cell, leading to the formation of a zygote.
• 🧬 After fertilization, the zygote, which is haploid, becomes diploid, containing the full set of DNA (2N) necessary for a human cell.
• 💧 The zygote undergoes mitosis without significant growth in size, leading to the formation of a multicellular structure known as the morula.
• 🌱 The morula differentiates into an outer layer called the trophoblast and an inner cell mass known as the embryoblast, which will develop into the organism.
• 🌀 The embryoblast is also referred to as the inner cell mass and is composed of embryonic stem cells, which have the potential to become any cell type in the body.
• 👶 The trophoblast will eventually develop into the placenta, serving as the interface for nutrient and waste exchange between the fetus and the mother.
• 🔬 The debate around embryonic stem cells centers on their potential to cure diseases and the ethical concerns of destroying embryos for research purposes.
• 🤔 The script highlights the difference between embryonic stem cells and somatic (adult) stem cells, with the former being more 'plastic' or versatile in their potential cell types.
• 🧪 The term 'blastomere' is introduced for the individual cells resulting from the early mitotic divisions of the zygote.
• 🌐 The script points out the ethical inconsistency in the public debate, noting that in-vitro fertilization also results in the destruction of embryos, similar to stem cell research.
• 🔍 The potential of embryonic stem cells to repair damaged tissues or grow new organs is a significant area of scientific research with both promise and controversy.

Q & A

What is the initial result of the fertilization of a sperm and an egg?

The initial result of the fertilization of a sperm and an egg is the formation of a zygote, which is a diploid cell with a full complement of DNA (2N).

What happens to the zygote immediately after fertilization?

Immediately after fertilization, the zygote undergoes cleavage through mitosis, which results in a series of cell divisions without a significant increase in size, leading to the formation of a morula.

What is the term used to describe the early stage of cell division in the developing embryo?

The term used to describe the early stage of cell division in the developing embryo is 'morula,' which is named for its resemblance to a mulberry.

What differentiates the cells of the morula into two distinct types?

The cells of the morula differentiate into two distinct types: the trophoblast, which are the outer cells, and the embryoblast, which are the inner cells.

What is the term for the fluid-filled space that forms between the trophoblast and the embryoblast?

The fluid-filled space that forms between the trophoblast and the embryoblast is called the blastocoel.

What is the term used to describe the stage of development after the morula, where cells have differentiated into trophoblast and embryoblast?

The term used to describe this stage of development is 'blastocyst.'

What is the potential role of embryonic stem cells in medical treatments?

Embryonic stem cells have the potential to differentiate into any cell type in the body, which could be used for repairing damaged tissues, treating diseases, and potentially growing new organs for transplants.

What ethical debate is associated with the use of embryonic stem cells?

The ethical debate revolves around the destruction of the embryo to extract embryonic stem cells, as the embryo has the potential to develop into a human being.

What is the difference between embryonic stem cells and somatic (adult) stem cells?

Embryonic stem cells have the potential to differentiate into any cell type in the body, whereas somatic (adult) stem cells are more limited in their potential and can only form certain types of cells.

How does the process of in-vitro fertilization relate to the ethical debate on embryonic stem cells?

In-vitro fertilization also results in the creation of multiple embryos, many of which are not used and can be destroyed, highlighting a similar ethical issue regarding the destruction of embryos.

What is the term used for the individual cells resulting from the early divisions of a zygote?

The individual cells resulting from the early divisions of a zygote are called blastomeres.

Outlines

00:00

🌱 Zygote Formation and Early Development

This paragraph discusses the process following meiosis, where two haploid gametes, a sperm and an egg, combine to form a diploid zygote. The zygote, now with a full set of DNA, undergoes mitosis, leading to the formation of a morula, a solid mass of cells. The morula then differentiates into the trophoblast and the embryoblast, with fluid filling the gap between them, forming the blastocoel and eventually the blastocyst. The focus is on the development of the fertilized egg into an organism, highlighting the initial stages of cell division and differentiation.

05:01

🔬 Embryonic Stem Cells and Their Potential

The second paragraph delves into the significance of the inner cell mass of the blastocyst, which consists of embryonic stem cells. These cells have the remarkable plasticity to differentiate into any cell type in the body, offering potential therapeutic applications such as repairing damaged tissue or growing replacement organs. The paragraph also touches on the ethical debate surrounding embryonic stem cell research due to the destruction of the embryo, which has the potential to become a human being, and contrasts this with the use of somatic or adult stem cells that are more limited in their potential.

10:04

🤔 Ethical Debates and Somatic Stem Cells

This paragraph examines the ethical considerations of embryonic stem cell research, particularly the destruction of embryos to extract these cells. It raises the question of why embryonic stem cells are distinct from somatic or adult stem cells, which are present in the body and help in tissue repair but lack the same plasticity. The discussion highlights the potential of making somatic cells more plastic and the implications that could have on the need for embryonic stem cells, as well as the ethical landscape of such advancements.

15:05

🧪 In-Vitro Fertilization and Embryo Destruction

The final paragraph presents an argument about the equivalence of embryo destruction in both embryonic stem cell research and in-vitro fertilization (IVF) processes. It explains that during IVF, multiple embryos are created, and only a select few are implanted, with the remainder often being discarded or destroyed. The paragraph suggests that if one opposes embryonic stem cell research on the grounds of embryo destruction, they should also oppose IVF for the same reason. It concludes by emphasizing the importance of understanding the science behind these processes to engage in informed debate.

Keywords

💡Meiosis

Meiosis is a type of cell division that results in four daughter cells, each with half the number of chromosomes of the parent cell. It is crucial for sexual reproduction, as it produces the haploid gametes (sperm and egg) necessary for fertilization. In the video, meiosis is mentioned as the process that leads to the formation of gametes, each with half the DNA content, setting the stage for the creation of a zygote upon fertilization.

💡Gametes

Gametes are the reproductive cells (sperm and egg) that fuse during fertilization to form a zygote. They are haploid, meaning they contain half the number of chromosomes of a diploid cell. In the script, the focus is on the sperm and egg as the two gametes that combine to initiate the development of a new organism.

💡Fertilization

Fertilization is the process where a sperm cell penetrates and fuses with an egg cell, leading to the formation of a zygote. This event marks the beginning of development of a new organism. In the video, fertilization is described as the moment when the sperm and egg combine, creating a diploid zygote with a full set of chromosomes.

💡Zygote

A zygote is the initial cell formed when two gametes (sperm and egg) fuse during fertilization. It is diploid, containing a full set of chromosomes. The script explains that the zygote is the starting point of development into a new organism, undergoing mitosis to form multiple cells.

💡Mitosis

Mitosis is a type of cell division that results in two daughter cells, each with the same number of chromosomes as the parent cell. It is essential for growth and repair in multicellular organisms. The video describes mitosis as the mechanism by which the zygote divides to form a multicellular structure known as the morula.

💡Morula

The morula is an early stage of embryonic development characterized by a solid ball of cells resembling a mulberry. It is formed through several rounds of mitosis following fertilization. The script uses the term to describe the stage where the zygote has divided multiple times to form a cluster of cells.

💡Trophoblast

The trophoblast is the outer layer of cells in the blastocyst that will eventually develop into the placenta. It plays a critical role in nutrient exchange between the mother and the developing embryo. In the script, the trophoblast is highlighted as the outer cells that differentiate from the morula and contribute to the formation of the placenta.

💡Embryoblast

The embryoblast, also known as the inner cell mass, is the group of cells within the blastocyst that will develop into the embryo. It is composed of pluripotent stem cells capable of differentiating into various cell types. The video emphasizes the importance of the embryoblast as the precursor to the organism's body.

💡Blastocyst

A blastocyst is an early stage in embryonic development where the morula undergoes further differentiation to form an inner cell mass (embryoblast) and an outer membrane (trophoblast), with a fluid-filled cavity called the blastocoel. The script explains that the blastocyst is the stage where the differentiation into trophoblast and embryoblast occurs.

💡Embryonic Stem Cells

Embryonic stem cells are pluripotent cells derived from the inner cell mass of the blastocyst. They have the potential to differentiate into any cell type in the body, making them a subject of significant research and ethical debate. The video discusses the potential therapeutic uses of embryonic stem cells and the ethical considerations surrounding their extraction.

💡Plasticity

Plasticity, in the context of stem cells, refers to their ability to differentiate into various types of cells. The term is used metaphorically to describe the 'moldable' nature of these cells, which can adapt and change into different cell lineages. The script mentions plasticity to illustrate the versatility of embryonic stem cells and their potential in regenerative medicine.

💡Somatic Stem Cells

Somatic or adult stem cells are found in various tissues of the body and are responsible for the growth and repair of those tissues. Unlike embryonic stem cells, they are multipotent, meaning they can only differentiate into a limited number of cell types related to their tissue of origin. The video contrasts somatic stem cells with embryonic stem cells to highlight the unique properties and potential of the latter.

💡In-Vitro Fertilization (IVF)

In-vitro fertilization is a medical procedure where eggs are fertilized by sperm outside the body, in a laboratory setting. The resulting embryos can be cultured and then implanted into the uterus. The script discusses IVF as a process that also involves the creation and potential destruction of embryos, drawing a parallel to the ethical considerations of embryonic stem cell research.

Highlights

The process of fertilization where a sperm meets an egg is described, leading to the formation of a zygote.

A zygote is a diploid cell resulting from the fusion of two haploid gametes, containing the full DNA complement.

Cleavage of the zygote through mitosis results in a mass of cells known as the morula, resembling a mulberry.

Differentiation of the morula into the trophoblast and the embryoblast, with the latter being the precursor to the organism.

The formation of the blastocoel, a fluid-filled cavity, and the resulting structure known as the blastocyst.

The blastocyst stage is a critical point of differentiation in mammalian development, including humans.

The trophoblast cells will eventually develop into the placenta, providing a crucial interface for the developing fetus.

Embryonic stem cells within the embryoblast have the potential to become any cell type in the body, known as pluripotency.

The concept of cell plasticity, where embryonic stem cells can adapt to their environment and transform into needed cell types.

Potential therapeutic applications of embryonic stem cells, including repairing damaged nerve cells and curing paralysis.

The ethical debate surrounding embryonic stem cell research due to the destruction of embryos with potential human life.

Differentiation between embryonic stem cells and somatic or adult stem cells, with the latter being less pluripotent.

The process of in-vitro fertilization and its connection to embryonic stem cell research, both involving embryo destruction.

The potential equivalence in ethical considerations between embryonic stem cell research and in-vitro fertilization practices.

The scientific basis for engaging in debates about stem cell research, rooted in the understanding of meiosis and fertilization.

Transcripts

Where we left off after the meiosis videos is that we had

two gametes.

We had a sperm and an egg.

Let me draw the sperm.

So you had the sperm and then you had an egg.

Maybe I'll do the egg in a different color.

That's the egg, and we all know how this story goes.

The sperm fertilizes the egg.

And a whole cascade of events start occurring.

The walls of the egg then become impervious to other

sperm so that only one sperm can get in, but that's not the

focus of this video.

The focus of this video is how this fertilized egg develops

once it has become a zygote.

So after it's fertilized, you remember from the meiosis

videos that each of these were haploid, or that they had--

oh, I added an extra i there-- that they had half the

contingency of the DNA.

As soon as the sperm fertilizes this egg, now, all

of a sudden, you have a diploid zygote.

Let me do that.

So now let me pick a nice color.

So now you're going to have a diploid zygote that's going to

have a 2N complement of the DNA material or kind of the

full complement of what a normal cell in our human body

would have. So this is diploid, and it's a zygote,

which is just a fancy way of saying the fertilized egg.

And it's now ready to essentially

turn into an organism.

So immediately after fertilization, this zygote

starts experiencing cleavage.

It's experiencing mitosis, that's the mechanism, but it

doesn't increase a lot in size.

So this one right here will then turn into-- it'll just

split up via mitosis into two like that.

And, of course, these are each 2N, and then those are going

to split into four like that.

And each of these have the same exact genetic complement

as that first zygote, and it keeps splitting.

And this mass of cells, we can start calling it, this right

here, this is referred to as the morula.

And actually, it comes from the word for mulberry because

it looks like a mulberry.

So actually, let me just kind of simplify things a little

bit because we don't have to start here.

So we start with a zygote.

This is a fertilized egg.

It just starts duplicating via mitosis, and you end up with a

ball of cells.

It's often going to be a power of two, because these cells,

at least in the initial stages are all duplicating all at

once, and then you have this morula.

Now, once the morula gets to about 16 cells or so-- and

we're talking about four or five days.

This isn't an exact process-- they started differentiating a

little bit, where the outer cells-- and this kind of turns

into a sphere.

Let me make it a little bit more sphere like.

So it starts differentiating between-- let me make some

outer cells.

This would be a cross-section of it.

It's really going to look more like a sphere.

That's the outer cells and then you have your inner cells

on the inside.

These outer cells are called the trophoblasts.

Let me do it in a different color.

Let me scroll over.

I don't want to go there.

And then the inner cells, and this is kind of the crux of

what this video is all about-- let me scroll

down a little bit.

The inner cells-- pick a suitable color.

The inner cells right there are called the embryoblast.

And then what's going to happen is some fluid's going

to start filling in some of this gap between the

embryoblast and the trophoblast, so you're going

to start having some fluid that comes in there, and so

the morula will eventually look like this, where the

trophoblast, or the outer membrane, is kind of this huge

sphere of cells.

And this is all happening as they keep replicating.

Mitosis is the mechanism, so now my trophoblast is going to

look like that, and then my embryoblast is going

to look like this.

Sometimes the embryoblast-- so this is the embryoblast.

Sometimes it's also called the inner cell mass, so let me

write that.

And this is what's going to turn into the organism.

And so, just so you know a couple of the labels that are

involved here, if we're dealing with a mammalian

organism, and we are mammals, we call this thing that the

morula turned into is a zygote, then a morula, then

the cells of the morula started to differentiate into

the trophoblast, or kind of the outside cells, and then

the embryoblast. And then you have this space that forms

here, and this is just fluid, and it's called the

blastocoel.

A very non-intuitive spelling of the coel part of

blastocoel.

But once this is formed, this is called a blastocyst. That's

the entire thing right here.

Let me scroll down a little bit.

This whole thing is called the blastocyst, and this is the

case in humans.

Now, it can be a very confusing topic, because a lot

of times in a lot of books on biology, you'll say, hey, you

go from the morula to the blastula or the

blastosphere stage.

Let me write those words down.

So sometimes you'll say morula,

and you go to blastula.

Sometimes it's called the blastosphere.

And I want to make it very clear that these are

essentially the same stages in development.

These are just for-- you know, in a lot of books, they'll

start talking about frogs or tadpoles or things like that,

and this applies to them.

While we're talking about mammals, especially the ones

that are closely related to us, the stage is the

blastocyst stage, and the real differentiator is when people

talk about just blastula and blastospheres.

There isn't necessarily this differentiation between these

outermost cells and these embryonic, or this

embryoblast, or this inner cell mass here.

But since the focus of this video is humans, and really

that's where I wanted to start from, because that's what we

are and that's what's interesting, we're going to

focus on the blastocyst.

Now, everything I've talked about in this video, it was

really to get to this point, because what we have here,

these little green cells that I drew right here in the

blastocysts, this inner cell mass, this is what will turn

into the organism.

And you say, OK, Sal, if that's the organism, what's

all of these purple cells out here?

This trophoblast out there?

That is going to turn into the placenta, and I'll do a future

video where in a human, it'll turn into a placenta.

So let me write that down.

It'll turn into the placenta.

And I'll do a whole future video about I guess how babies

are born, and I actually learned a ton about that this

past year because a baby was born in our house.

But the placenta is really kind of what the embryo

develops inside of, and it's the interface, especially in

humans and in mammals, between the developing fetus and its

mother, so it kind of is the exchange mechanism that

separates their two systems, but allows the necessary

functions to go on between them.

But that's not the focus of this video.

The focus of this video is the fact that these cells, which

at this point are-- they've differentiated themselves away

from the placenta cells, but they still haven't decided

what they're going to become.

Maybe this cell and its descendants eventually start

becoming part of the nervous system, while these cells

right here might become muscle tissue, while these cells

right here might become the liver.

These cells right here are called embryonic stem cells,

and probably the first time in this video you're hearing a

term that you might recognize.

So if I were to just take one of these cells, and actually,

just to introduce you to another term, you know, we

have this zygote.

As soon as it starts dividing, each of these cells are called

a blastomere.

And you're probably wondering, Sal, why does this word blast

keep appearing in this kind of embryology video, these

development videos?

And that comes from the Greek for spore: blastos.

So the organism is beginning to spore out or grow.

I won't go into the word origins of it, but that's

where it comes from and that's why everything has

this blast in it.

So these are blastomeres.

So when I talk what embryonic stem cells, I'm talking about

the individual blastomeres inside of this embryoblast or

inside of this inner cell mass.

These words are actually unusually fun to say.

So each of these is an embryonic stem cell.

Let me write this down in a vibrant color.

So each of these right here are embryonic stem cells, and

I wanted to get to this.

And the reason why these are interesting, and I think you

already know, is that there's a huge debate around these.

One, these have the potential to turn into anything, that

they have this plasticity.

That's another word that you might hear.

Let me write that down, too: plasticity.

And the word essentially comes from, you know, like a plastic

can turn into anything else.

When we say that something has plasticity, we're talking

about its potential to turn into a lot

of different things.

So the theory is, and there's already some trials that seem

to substantiate this, especially in some lower

organisms, that, look, if you have some damage at some point

in your body-- let me draw a nerve cell.

Let me say I have a-- I won't go into the actual mechanics

of a nerve cell, but let's say that we have some damage at

some point on a nerve cell right there, and because of

that, someone is paralyzed or there's some nerve

dysfunction.

We're dealing with multiple sclerosis or who knows what.

The idea is, look, we have these cell here that could

turn into anything, and we're just really understanding how

it knows what to turn into.

It really has to look at its environment and say, hey, what

are the guys around me doing, and maybe that's what helps

dictate what it does.

But the idea is you take these things that could turn to

anything and you put them where the damage is, you layer

them where the damage is, and then they can turn into the

cell that they need to turn into.

So in this case, they would turn into nerve cells.

They would turn to nerve cells and repair the damage and

maybe cure the paralysis for that individual.

So it's a huge, exciting area of research, and you could

even, in theory, grow new organs.

If someone needs a kidney transplant or a heart

transplant, maybe in the future, we could take a colony

of these embryonic stem cells.

Maybe we can put them in some type of other creature, or who

knows what, and we can turn it into a replacement heart or a

replacement kidney.

So there's a huge amount of excitement about

what these can do.

I mean, they could cure a lot of formerly uncurable diseases

or provide hope for a lot of patients who

might otherwise die.

But obviously, there's a debate here.

And the debate all revolves around the issue of if you

were to go in here and try to extract one of these cells,

you're going to kill this embryo.

You're going to kill this developing embryo, and that

developing embryo had the potential to

become a human being.

It's a potential that obviously has to be in the

right environment, and it has to have a willing mother and

all of the rest, but it does have the potential.

And so for those, especially, I think, in the pro-life camp,

who say, hey, anything that has a potential to be a human

being, that is life and it should not be killed.

So people on that side of the camp, they're against the

destroying of this embryo.

I'm not making this video to take either side to that

argument, but it's a potential to turn to a human being.

It's a potential, right?

So obviously, there's a huge amount of debate, but now, now

you know in this video what people are talking about when

they say embryonic stem cells.

And obviously, the next question is, hey, well, why

don't they just call them stem cells as opposed to embryonic

stem cells?

And that's because in all of our bodies, you do have what

are called somatic stem cells.

Let me write that down.

Somatic or adults stem cells.

And we all have them.

They're in our bone marrow to help produce red blood cells,

other parts of our body, but the problem with somatic stem

cells is they're not as plastic, which means that they

can't form any type of cell in the human body.

There's an area of research where people are actually

maybe trying to make them more plastic, and if they are able

to take these somatic stem cells and make them more

plastic, it might maybe kill the need to have these

embryonic stem cells, although maybe if they do this too

good, maybe these will have the potential to turn into

human beings as well, so that could

become a debatable issue.

But right now, this isn't an area of debate because, left

to their own devices, a somatic stem cell or an adult

stem cell won't turn into a human being, while an

embryonic one, if it is implanted in a willing mother,

then, of course, it will turn into a human being.

And I want to make one side note here, because I don't

want to take any sides on the debate of-- well, I mean,

facts are facts.

This does have the potential to turn into a human being,

but it also has the potential to save millions of lives.

Both of those statements are facts, and then you can decide

on your own which side of that argument you'd like to or what

side of that balance you would like to kind of

put your own opinion.

But there's one thing I want to talk about that in the

public debate is never brought up.

So you have this notion of when you-- to get an embryonic

stem cell line, and when I say a stem cell line, I mean you

take a couple of stem cells, or let's say you take one stem

cell, and then you put it in a Petri dish, and then you allow

it to just duplicate.

So this one turns into two, those two turn to four.

Then someone could take one of these and then put it in their

own Petri dish.

These are a stem cell line.

They all came from one unique embryonic stem cell or what

initially was a blastomere.

So that's what they call a stem cell line.

So the debate obviously is when you start an embryonic

stem cell line, you are destroying an embryo.

But I want to make the point here that embryos are being

destroyed in other processes, and namely, in-vitro

fertilization.

And maybe this'll be my next video: fertilization.

And this is just the notion that they take a set of eggs

out of a mother.

It's usually a couple that's having trouble having a child,

and they take a bunch of eggs out of the mother.

So let's say they take maybe 10 to 30

eggs out of the mother.

They actually perform a surgery, take them out of the

ovaries of the mother, and then they fertilize them with

semen, either it might come from the father or a sperm

donor, so then all of these becomes zygotes once they're

fertilized with semen.

So these all become zygotes, and then they allow them to

develop, and they usually allow them to develop to the

blastocyst stage.

So eventually all of these turn into blastocysts.

They have a blastocoel in the center, which is

this area of fluid.

They have, of course, the embryo, the inner cell mass in

them, and what they do is they look at the ones that they

deem are healthier or maybe the ones that are at least

just not unhealthy, and they'll take a couple of these

and they'll implant these into the mother, so all of this is

occurring in a Petri dish.

So maybe these four look good, so they're going to take these

four, and they're going to implant these into a mother,

and if all goes well, maybe one of these will turn into--

will give the couple a child.

So this one will develop and maybe the other ones won't.

But if you've seen John & Kate Plus 8, you know that many

times they implant a lot of them in there, just to

increase the probability that you get at least one child.

But every now and then, they implant seven or eight, and

then you end up with eight kids.

And that's why in-vitro fertilization often results in

kind of these multiple births, or reality

television shows on cable.

But what do they do with all of these other perfectly--

well, I won't say perfectly viable, but these are embryos.

They may or may not be perfectly viable, but you have

these embryos that have the potential, just like this one

right here.

These all have the potential to turn into a human being.

But most fertility clinics, roughly half of them, they

either throw these away, they destroy them, they

allow them to die.

A lot of these are frozen, but just the process of freezing

them kills them and then bonding them kills them again,

so most of these, the process of in-vitro fertilization, for

every one child that has the potential to develop into a

full-fledged human being, you're actually destroying

tens of very viable embryos.

So at least my take on it is if you're against-- and I

generally don't want to take a side on this, but if you are

against research that involves embryonic stem cells because

of the destruction of embryos, on that same, I guess,

philosophical ground, you should also be against

in-vitro fertilization because both of these involve the

destruction of zygotes.

I think-- well, I won't talk more about this, because I

really don't want to take sides, but I want to show that

there is kind of an equivalence here that's

completely lost in this debate on whether embryonic stem

cells should be used because they have a destruction of

embryos, because you're destroying just as many

embryos in this-- well, I won't say just as many, but

you are destroying embryos.

There's hundreds of thousands of embryos that get destroyed

and get frozen and obviously destroyed in that process as

well through this in-vitro fertilization process.

So anyway, now hopefully you have the tools to kind of

engage in the debate around stem cells, and you see that

it all comes from what we learned about meiosis.

They produce these gametes.

The male gamete fertilizes a female gamete.

The zygote happens or gets created and starts splitting

up the morula, and then it keeps splitting and it

differentiates into the blastocyst, and then this is

where the stem cells are.

So you already know enough science to engage in kind of a

very heated debate.