Death by Design: Where Parallel Worlds Meet
- Description
- Reviews
- Citation
- Cataloging
- Transcript
If you are not affiliated with a college or university, and are interested in watching this film, please register as an individual and login to rent this film. Already registered? Login to rent this film. This film is also available on our home streaming platform, OVID.tv.
There exists a world where death creates life, where suicides without sadness occur billions of times an hour, where every individual does exactly what is required by the society as a whole. It is a world of highly sophisticated communication, of vast depth and endless mystery. It is utterly alien, yet it is also, in every moment, creating us all. Death by Design is a guided tour of the invisible world of our cells, told through a collage of metaphors. State-of-the-art micro-cinematography is playfully intercut with parallel images from life at the human scale: a hundred lighted violins, imploding buildings, pieces of film on the cutting room floor. Our scientist-guides include two Nobel prizewinners, Rita Levi-Montalcini and Robert Horvitz.
“It stimulates both curiosity, illuminates the world of cells with great charm and unpretentious artistry, and explains its biologic wonders with poetic clarity.” —NATURE
“Intelligent and imaginative. . .inventively choreographed images. . .surprising, revealing metaphors for what the program rightly boasts is "a cast of billions”. —NEW YORK TIMES
“One of the ten best films of the year.” —FILM COMMENT MAGAZINE
"Sounds and images of rigorous beauty, captivating interviews, audacious and masterful editing. . .a superb film. “ —LE MONDE (France)
“Without lab coats or jargon, an American filmmaker and a French scientist renew the science film. Eureka!” —TELERAMA (France)
"This enthralling film. . .should be shown by every biology teacher in Britain.” —TIMES OF LONDON
Citation
Main credits
Laurent, Emmanuel (film producer)
Friedman, Peter (film director)
Friedman, Peter (film producer)
Friedman, Peter (screenwriter)
Friedman, Peter (editor of moving image work)
Brunet, Jean-François (film director)
Brunet, Jean-François (screenwriter)
Brunet, Jean-François (editor of moving image work)
Jörg, Danielle (interviewer)
Chimini, Giovanna (interviewer)
Other credits
Microcinematography, Gerard Evan [and 12 others].
Distributor subjects
No distributor subjects provided.Keywords
[00:00:20.01]
(upbeat instrumental music)
[00:00:33.04]
- Ladies and gentlemen,
[00:00:34.05]
I'm sure you'd all like to know something
[00:00:36.02]
about the new entertainment
miracle programmed cell death?
[00:00:41.09]
Well, the best way I
can describe it to you,
[00:00:44.08]
is to tell you that it makes the screen
[00:00:47.07]
absolutely real and alive.
[00:00:51.06]
Of course, these illustrations
are only a pale suggestion
[00:00:54.05]
of the real thing.
[00:00:55.06]
It can't be described,
[00:00:56.08]
it's got to be seen and experienced.
[00:01:01.06]
I tell you from its
size and its appearance,
[00:01:04.02]
there's some form of life in it.
[00:01:07.04]
What do you want?
[00:01:08.04]
What are you doing?
[00:01:09.06]
Let me see you as you really are.
[00:01:13.03]
(upbeat instrumental music)
[00:01:55.08]
- Well, a cell I guess
you would define it as the
[00:02:00.06]
ultimate unit of life,
[00:02:01.09]
in the sense that anything that's alive
[00:02:03.05]
is either a cell or it's made up of cells.
[00:02:15.06]
(singing in foreign language)
[00:02:43.05]
- What's a cell?
[00:02:45.08]
I think I would start
with Van Leeuwenhoek,
[00:02:48.03]
who in 15 something made
the first microscope
[00:02:53.02]
and using it, he looked at onion skins,
[00:02:57.07]
and he found that the onion skin
[00:03:01.00]
was broken up into square bits.
[00:03:05.05]
And these looked like the
cells that monks live in,
[00:03:08.03]
and so he called them cells.
[00:03:10.09]
(gentle instrumental music)
[00:03:18.07]
And that's what most
plants cells look like,
[00:03:20.04]
squares with walls between them.
[00:03:24.00]
Animal cells don't look like that.
[00:03:27.04]
They're round, and they don't have walls.
[00:03:31.06]
They have very, very thin partitions
[00:03:33.09]
that are more like soap balls.
[00:03:39.03]
What do cells do?
[00:03:44.08]
They talk to each other.
[00:03:46.07]
They help each other live,
they kill each other,
[00:03:50.01]
they regenerate themselves.
[00:03:56.04]
- [Raff] They move around,
they eat other cells,
[00:03:59.08]
they do everything an animal can do.
[00:04:06.06]
- [Polly] And those cells
come together as communities
[00:04:09.09]
and those communities we
call animals and plants.
[00:04:16.02]
(gentle instrumental music)
[00:04:50.06]
(speaking in foreign language)
[00:05:13.06]
(gentle instrumental music)
[00:05:17.08]
- [Raff] I think that's a useful way of
[00:05:18.08]
viewing an animal or a plant
[00:05:20.09]
that it is a community of cells
[00:05:22.09]
that have to interact and obey the rules
[00:05:26.01]
that a community of
individuals would have to.
[00:05:32.01]
(gentle instrumental music)
[00:05:37.01]
But in addition, the cells have to become
[00:05:39.07]
different kinds of cells, a muscle cell,
[00:05:41.09]
a nerve cell, a red blood cell, and so on.
[00:05:45.00]
(gentle instrumental music)
[00:05:53.02]
- [Male Cast] Every man
has a job to perform.
[00:05:59.06]
(upbeat instrumental music)
[00:06:10.03]
- In addition, if we simply
made a mass of cells,
[00:06:13.03]
a big blob of nerve cells,
muscle cells, intestinal cells,
[00:06:17.07]
and so on, we would hardly be people.
[00:06:27.04]
All of those cells must get
together at the proper place,
[00:06:31.00]
and in fact, at the proper time,
[00:06:33.00]
in order to form the structures
[00:06:34.06]
that we know to be organisms.
[00:06:36.09]
(gentle instrumental music)
[00:06:53.09]
(speaking in foreign language)
[00:07:04.02]
(gentle instrumental music)
[00:07:12.09]
(speaking in foreign language)
[00:07:37.06]
(gentle instrumental music)
[00:07:41.02]
- For a unicellular organism to evolve
[00:07:43.09]
into a multicellular organism
[00:07:45.04]
is enormously complex process.
[00:07:48.03]
And in fact, if you look
at the fossil record,
[00:07:50.06]
it took some three billion years
[00:07:52.09]
after the first appearance
of unicellular organisms
[00:07:55.06]
to the first multicellular organism.
[00:07:57.02]
So this took an enormously long time.
[00:08:00.02]
And when you think about
what would be necessary,
[00:08:02.03]
it's not surprising.
[00:08:04.00]
(gentle instrumental music)
[00:08:14.04]
Before a collection of cells
is useful as an organism,
[00:08:17.01]
where they will actually work together
[00:08:18.08]
for the benefit of a single organism,
[00:08:21.03]
then the behavior of every
cell has to be controlled.
[00:08:30.07]
You needed to have complex
mechanisms in place
[00:08:35.01]
to control the behavior of
every cell in that animal,
[00:08:39.06]
so that it's an advantage
[00:08:41.01]
to the collection of cells as a whole.
[00:08:53.06]
Now, it's clear that they've evolved
[00:08:55.05]
from the social interactions
that unicellular organisms use.
[00:09:00.02]
Because single celled animals,
[00:09:02.02]
not infrequently are social
[00:09:04.08]
to the extent that they
interact with their neighbors
[00:09:08.01]
for the purpose of sexual
reproduction, for example.
[00:09:11.07]
♪ In the winter let me
bring the spring to you ♪
[00:09:16.05]
- [Raff] There's a lot
of social interactions
[00:09:17.07]
between unicellular organisms,
[00:09:19.07]
probably many more than we understand now.
[00:09:27.06]
(gentle instrumental music)
[00:11:11.09]
- Okay cells in our bodies
are not isolated entities,
[00:11:16.02]
they have to know about each other,
[00:11:20.02]
and they have to talk to each other.
[00:11:23.00]
(gentle instrumental music)
[00:11:41.03]
(conversing in foreign language)
[00:12:03.08]
- And they do that in
many complicated ways,
[00:12:05.08]
but in general, they send
signals to one another,
[00:12:17.07]
hundreds, thousands of different signals,
[00:12:21.08]
each one telling the cell
[00:12:23.06]
to do something slightly different.
[00:12:34.05]
The behavior of an
individual cell in an animal
[00:12:38.04]
is coordinated by
signals from other cells.
[00:12:41.04]
So, cells don't do anything
[00:12:43.06]
unless they're signaled
to do it, it seems.
[00:12:47.06]
(gentle instrumental music)
[00:12:55.06]
People are constantly being
bombarded with signals
[00:12:59.09]
and behaving according to these signals.
[00:13:02.00]
Every time you drive your car,
[00:13:03.05]
you're tuning into signals of all kinds
[00:13:07.04]
horns, eye contact,
traffic lights, and so on.
[00:13:14.08]
You're tuning into all kinds of sounds
[00:13:17.02]
and very subtle visual
differences are cueing you.
[00:13:25.02]
In an organism such as ourselves,
[00:13:27.06]
cells obey these signals
in exactly the same way.
[00:13:34.01]
(loud drum banging)
[00:13:52.01]
Hundreds and hundreds of different signals
[00:13:53.07]
have been defined.
[00:13:55.09]
Some of them are proteins,
[00:13:57.01]
some of them are small molecules.
[00:13:58.09]
Some of them are gases even.
[00:14:08.09]
They're saying move or don't move,
[00:14:12.08]
or grow or don't grow or
divide or don't divide,
[00:14:15.07]
or release this molecule
that you've been storing,
[00:14:19.06]
that kind of thing.
[00:14:21.08]
(loud drum banging)
[00:14:46.04]
- Sometimes, you may wanna get a behavior
[00:14:50.09]
from a whole group of individuals.
[00:14:53.04]
And at other times you may
wanna get that behavior
[00:14:55.05]
from some small portion of
that group of individuals.
[00:14:59.08]
For example, if I want both
my sheepdogs to lay down,
[00:15:03.01]
I say "lay down", and they both go down.
[00:15:06.01]
If I only want Annie to lay down,
[00:15:08.01]
I put my hand up, and Annie goes down,
[00:15:09.09]
but Poppie keeps going.
[00:15:12.06]
If I say "viens", Annie comes,
[00:15:15.09]
if I say "come", both of them come, right.
[00:15:19.04]
Now the immune system does the same thing.
[00:15:21.07]
Sometimes it wants to signal
[00:15:23.05]
all of the white blood cells to grow
[00:15:26.09]
and uses certain hormones,
[00:15:28.09]
to which all of those
white blood cells respond.
[00:15:31.08]
Sometimes, it only wants
the killer cells to grow,
[00:15:35.04]
so it uses a different signal,
[00:15:37.03]
and only the killer cells grow.
[00:15:39.01]
- And those are considered
to be social controls
[00:15:42.00]
to ensure that a cell only divides
[00:15:45.01]
when new cells are needed.
[00:15:47.07]
(gentle instrumental music)
[00:16:38.05]
Any one cell is listening
to hundreds of signals
[00:16:43.03]
at any one time.
[00:16:48.05]
And has to integrate all those signals
[00:16:51.00]
and decide to do something
[00:16:53.03]
like to move or not move,
[00:16:56.06]
or divide, or not divide.
[00:17:16.06]
For example, if you were hearing
[00:17:20.02]
the voices of many people
telling you what to do,
[00:17:22.07]
you're in a situation,
[00:17:23.05]
you're in a room and the room's on fire,
[00:17:25.05]
and somebody is saying go to the window
[00:17:27.09]
and somebody else is
saying go to the door,
[00:17:28.08]
and the other one's saying
turn off the light, you know,
[00:17:30.06]
put blankets under the door cracks,
[00:17:32.04]
all those things are
happening all at once,
[00:17:33.09]
people screaming at you,
[00:17:36.00]
the thing you don't wanna
do is to be paralyzed,
[00:17:38.07]
you need to integrate all these things
[00:17:40.04]
and make a decision and run for the door
[00:17:42.03]
or run for the window or do something.
[00:17:44.06]
And so a cell is integrating
all these signals
[00:17:46.09]
all of the time,
[00:17:48.02]
and making these all or none decisions,
[00:17:51.02]
move, divide, stay where you
are, becomes something else.
[00:17:58.04]
And these are very
complex integration events
[00:18:01.02]
that are happening inside the cell.
[00:18:02.07]
And we don't understand if a cell does it.
[00:18:10.08]
How do we know that cells
receive all these signals,
[00:18:13.09]
and they regulate all these activities?
[00:18:16.03]
Well, one way you know
is if you take a cell
[00:18:18.08]
and put it alone in a culture dish,
[00:18:21.07]
and remove all the
signals, it doesn't divide,
[00:18:25.00]
it doesn't move.
[00:18:25.09]
In fact, it doesn't survive.
[00:18:28.06]
And it turns out that
for cells to stay alive,
[00:18:31.06]
they need signals from other cells
[00:18:34.01]
to tell them to stay alive.
[00:18:35.09]
And if they don't get those signals,
[00:18:38.00]
then they kill themselves.
[00:18:41.05]
(loud gong banging)
[00:19:00.01]
- [Polly] It's happening all the time.
[00:19:02.06]
I mean, cells are dying
in us all the time.
[00:19:09.04]
- During the course of an hour,
[00:19:11.08]
billions of your cells will die,
[00:19:13.09]
by programmed cell death,
they'll commit suicide.
[00:19:17.02]
(gentle instrumental music)
[00:19:32.02]
The cells are programmed to
die automatically, it seems
[00:19:36.09]
that the only reason
it's not killing itself,
[00:19:39.01]
the only reason any cell
in your body is alive,
[00:19:41.05]
the only reason is that other cells
[00:19:43.05]
are constantly telling
it don't kill yourself.
[00:19:47.02]
(upbeat instrumental music)
[00:20:04.03]
(speaking in foreign language)
[00:20:44.06]
- [Horvitz] I think
the analogies are fair,
[00:20:46.07]
and I think they're useful
[00:20:48.07]
because they allow us to
think in a familiar way.
[00:20:52.06]
So by suicide, we mean there's
an act of participation
[00:20:57.02]
on the part of the cell that's dying.
[00:21:06.03]
(speaking in foreign language)
[00:21:31.06]
- So this is an intrinsic
cell intrinsic program.
[00:21:35.09]
It can be activated by
signals from other cells,
[00:21:39.04]
so the cell's happily living,
moving, doing its thing,
[00:21:42.09]
it can receive signals that
tell it to commit suicide
[00:21:46.07]
and it will do this program.
[00:21:48.08]
- These cells are not killed.
[00:21:52.03]
They're told to die.
[00:21:54.03]
(upbeat instrumental music)
[00:22:07.02]
(speaking in foreign language)
[00:22:27.02]
(upbeat instrumental music)
[00:22:55.08]
- So this is a coordinated program,
[00:22:58.05]
just like the cell division program
[00:23:01.03]
is a coordinated set of events
[00:23:04.02]
that divides the cell in two,
[00:23:06.01]
this is a coordinated set of events,
[00:23:08.06]
that kills the cell in a very neat way.
[00:23:11.08]
And the cell goes through
this little dance,
[00:23:14.06]
where its surface boils,
[00:23:17.04]
then it shrinks and condenses
and stops moving all together.
[00:23:28.08]
- The first step is basically kill,
[00:23:32.02]
take a happy, healthy
cell and make it dead.
[00:23:38.09]
The second step involves
engulfing that dying cell corpse.
[00:23:47.03]
And so there's a neighboring
cell that swallows
[00:23:50.08]
the dying cell, we'll call
that step, step of engulfment.
[00:23:57.00]
And then the third step
that destroys the evidence.
[00:24:01.04]
So we'll call here, destroy,
[00:24:04.07]
and that leaves you
with nothing at the end.
[00:24:12.05]
- It's a very important process,
[00:24:14.03]
because if the cell died
in a messy sort of way
[00:24:17.05]
and spilled all of its
guts all over the place,
[00:24:20.00]
that induces an inflammatory response,
[00:24:22.00]
and that would be very
dangerous for the animal.
[00:24:24.00]
So this is a program
to kill a cell neatly.
[00:24:27.09]
It's remarkable that you
take this complex structure
[00:24:30.06]
and it's got in an hour or so.
[00:24:34.03]
(gentle instrumental music)
[00:25:21.06]
This death program is enormously useful
[00:25:25.07]
because you do need to
get rid of a lot of cells
[00:25:28.05]
to build the normal animal.
[00:25:33.06]
- For example, look at our hands or feet,
[00:25:36.00]
which are a little harder
to display at the moment,
[00:25:38.02]
and what you see are fingers and toes
[00:25:40.01]
and they're separated from each other.
[00:25:42.03]
But if you looked at a developing
human being in the womb,
[00:25:46.04]
what you would see is the fingers
[00:25:47.08]
and toes are not separated,
[00:25:49.09]
but rather they're connected by webbing.
[00:26:00.00]
- What happens is the
cells in between die,
[00:26:03.03]
and so the cells that
are left are the ones
[00:26:05.00]
that go and make the fingers.
[00:26:07.02]
- The duck's foot is wet,
[00:26:08.03]
that's important for a duck
[00:26:09.03]
it swims and it uses
its web foot as a pedal.
[00:26:19.05]
The chicken foot developmentally
[00:26:22.00]
undergoes program cell death,
the duck foot does not.
[00:26:30.09]
So we are more like chickens than ducks.
[00:26:35.06]
- We haven't the vaguest idea
of how that is controlled,
[00:26:38.08]
so that cells die between the digits
[00:26:40.09]
and not where the digits should be.
[00:26:42.07]
But that's a fact,
[00:26:44.00]
the reason you have digits
[00:26:45.01]
is because cell death sculpts them.
[00:26:48.06]
(gentle instrumental music)
[00:27:26.04]
(upbeat instrumental music)
[00:27:56.02]
Another dramatic example
is in the metamorphosis
[00:27:58.05]
of a tadpole, into a frog.
[00:28:05.07]
That is signaled by a
hormone, thyroid hormone,
[00:28:09.00]
whose levels increase dramatically
[00:28:10.09]
at the time of metamorphosis,
[00:28:12.03]
and that effectively turns
this tadpole into a frog.
[00:28:16.00]
Now in that process, the tail
of the tadpole disappears.
[00:28:23.04]
And it turns out the thyroid hormone
[00:28:25.05]
signals the cells in
the tail of the tadpole,
[00:28:28.08]
to commit suicide,
[00:28:29.07]
time to go, program cell death.
[00:28:32.02]
In other parts of the tadpole,
[00:28:33.09]
the thyroid hormone
induces the cells to divide
[00:28:36.08]
or to change and do
some other kind of cell.
[00:28:39.02]
But in the tail,
[00:28:40.01]
it induces cells to
activate this death program
[00:28:43.01]
and kill themselves.
[00:28:45.04]
(upbeat instrumental music)
[00:29:00.00]
- There are many other examples
[00:29:02.05]
of the way in which cell death affects us.
[00:29:06.00]
In the development of our brains,
[00:29:08.04]
again, in the embryo,
[00:29:10.01]
as a fetus in the womb, as fetuses,
[00:29:13.02]
as many as 80 or 90% of the
nerve cells that are made died.
[00:29:20.06]
- It's thought that the reason you do that
[00:29:22.08]
is that it allows you to match
the number of nerve cells
[00:29:26.09]
to the number of target cells
that they have to contact.
[00:29:30.03]
So if you had to get the
numbers exactly right,
[00:29:32.09]
10,000 cells here and 10,000 cells there,
[00:29:35.09]
this would be extremely
difficult to do in development
[00:29:38.02]
and in evolution,
[00:29:39.04]
but by over producing these cells,
[00:29:41.08]
and having the ones that make
contact appropriately survive
[00:29:45.02]
and all the others you kill,
[00:29:48.02]
you would enormously speed up
[00:29:49.06]
both evolution and development.
[00:29:54.00]
- [Horvitz] You know, here
you are making an animal
[00:29:55.08]
from a single cell,
[00:29:58.00]
and you would think again,
[00:29:59.03]
that process should be efficient
[00:30:01.02]
and make the cells that you need
[00:30:02.06]
and that would make the organism.
[00:30:09.02]
But instead what happens in
the development of every animal
[00:30:12.05]
is more cells are made that are needed
[00:30:14.08]
and those cells die.
[00:30:18.06]
So, a normal aspect of the
program of animal development
[00:30:24.00]
is cell death, therefore
programmed cell death.
[00:30:30.09]
(speaking in foreign language)
[00:31:12.01]
- All organisms develop
from a single cell.
[00:31:15.03]
And what happens is that cell divides
[00:31:17.06]
and makes two and then those two divide
[00:31:20.07]
each of them to make a total of four
[00:31:23.09]
that goes on and on and on.
[00:31:27.03]
And that's the basic problem
[00:31:28.09]
that developmental biologists
are trying to solve.
[00:31:31.05]
How does this happen?
[00:31:32.09]
And this problem has been
very difficult to approach
[00:31:36.00]
in complicated organisms like ourselves.
[00:31:39.05]
We, for example, probably
have on the order
[00:31:42.06]
of 10 to the 13th,
[00:31:45.00]
that is, one followed
by 13 zeros of cells.
[00:31:54.08]
If you look in the microscopic
roundworm that we study,
[00:31:59.00]
what we see is that there
are 959 cells, count them,
[00:32:05.06]
we have one, two, three, four, up to 959,
[00:32:09.01]
in this individual, in this
individual, in this individual,
[00:32:12.05]
and in fact by starting
with the single celled egg,
[00:32:15.05]
and all of us start
from single celled eggs,
[00:32:19.00]
if one looks at this worm,
[00:32:21.07]
it's possible to simply look at that egg
[00:32:25.02]
going from one cell to
two and then two to four,
[00:32:29.06]
and trace the entire pattern of divisions
[00:32:33.03]
that generates all of those 959 cells.
[00:32:39.02]
That is not possible in an animal
[00:32:41.04]
that has millions or trillions
[00:32:44.04]
or trillions of trillions of cells.
[00:32:52.02]
So this is a room in which
we are studying the worms
[00:32:56.00]
in a variety of ways and also grow them.
[00:32:57.06]
If we come in here,
[00:32:59.04]
we can see for example, on this slide,
[00:33:02.00]
here are worms growing in flasks,
[00:33:04.09]
and they're eating bacteria.
[00:33:08.01]
And we grow them both like that,
[00:33:10.02]
and also on the small petri dishes.
[00:33:13.05]
And just to give you an idea
[00:33:14.09]
of the small size of these worms,
[00:33:16.07]
one of these petri dishes can hold
[00:33:18.08]
10,000 individual animals.
[00:33:22.05]
These animals grow,
[00:33:24.03]
they take from generation to generation,
[00:33:26.07]
they take three days.
[00:33:28.05]
So one animal can have
[00:33:30.01]
maybe three to 400
offspring in three days,
[00:33:32.06]
each of which can then
have another three to 400
[00:33:35.09]
in another three days.
[00:33:37.05]
So in one week from one animal,
[00:33:39.03]
we can get 10,000
animals on a petri plate.
[00:33:44.06]
We probably have oh, I don't know,
[00:33:48.01]
I would say we have maybe on
the order of a billion worms.
[00:33:55.06]
Probably more than a billion worms,
[00:34:00.05]
we probably have between a
billion and a trillion worms
[00:34:03.00]
between 10 to the nine and 10 to the 12
[00:34:06.04]
would be the estimate of
the number of worms we have
[00:34:08.05]
but not all of them are crawling around
[00:34:09.09]
some are frozen and asleep.
[00:34:14.02]
(gentle instrumental music)
[00:35:58.09]
One way in which this
animal has been analyzed
[00:36:01.06]
is to look at the highest
microscopic resolution possible
[00:36:05.07]
at individual cells and
within individual cells.
[00:36:11.00]
And what's done is to take the worm
[00:36:13.00]
which is essentially shaped like a sausage
[00:36:15.05]
and cut it the same way
one was slice a sausage,
[00:36:18.03]
from nose to tail.
[00:36:20.02]
Making about 20,000 different slices
[00:36:23.00]
in this tiny one millimeter worm.
[00:36:34.01]
What this has allowed,
[00:36:35.05]
is a complete reconstruction
[00:36:38.00]
of the anatomy of the animal
with every single cell
[00:36:40.09]
and connections amongst the cells.
[00:36:43.09]
(gentle instrumental music)
[00:37:04.03]
When that was done,
[00:37:05.09]
what was found was that
more cells were made
[00:37:09.00]
than the 959.
[00:37:10.06]
To be precise, 131 more cells were made,
[00:37:14.09]
but those cells are not
present in the adult,
[00:37:17.05]
they're not present, because they undergo
[00:37:20.02]
programmed cell death.
[00:37:23.03]
Cell death is a cell fate.
[00:37:26.04]
Some cells live and
turn into muscle cells,
[00:37:29.01]
other cells live and turn into nerve cells
[00:37:31.02]
and other cells die.
[00:37:38.02]
Okay, so one question to be considered,
[00:37:41.00]
is why cells are made and destroyed
[00:37:44.04]
instead of simply not made?
[00:37:46.05]
And the answer to this,
[00:37:48.00]
like the answer to many
why questions in biology
[00:37:51.08]
is that's what's happened.
[00:37:56.08]
Because the way in which
our development works,
[00:38:02.02]
is based upon a history.
[00:38:06.01]
It's based upon evolution.
[00:38:12.01]
It's not that somebody designed
[00:38:13.08]
the best way to make a human being,
[00:38:15.09]
but rather that human beings
evolved over many, many years,
[00:38:20.02]
from creatures that were, in
fact very different from us.
[00:38:29.01]
And each step in this
evolution is a small step.
[00:38:32.02]
So that basically what evolution is,
[00:38:34.06]
is a tinkering.
[00:38:39.02]
A modifying of what has come before.
[00:38:48.00]
And so one never goes back
to the beginning and says,
[00:38:49.07]
is this an efficient process?
[00:38:50.08]
Maybe we can do it a better way,
[00:38:52.02]
'cause that's not how it can happen.
[00:38:55.04]
But instead, what has happened
[00:38:57.03]
is that one builds step by step,
[00:39:02.06]
going this way, and that
[00:39:05.09]
and this way, and that.
[00:39:10.08]
And what you end up with is the
organisms that we see today.
[00:39:16.08]
(gentle instrumental music)
[00:39:38.01]
- It's counterintuitive, that
there would be all this waste
[00:39:41.09]
that you would produce millions of animals
[00:39:44.06]
so that only a few thousand would survive,
[00:39:47.00]
or you'd produce billions of spermatozoa
[00:39:49.05]
so that only one will fertilize the egg.
[00:39:53.00]
And the same way,
[00:39:54.07]
the fact that you produce
[00:39:55.09]
so many cells during development that die
[00:39:58.02]
and never serve a useful
function in the animal.
[00:40:02.03]
It's counterintuitive that
there'd be this waste,
[00:40:04.03]
but it turns out that over and over again,
[00:40:06.09]
biologists have learned that
this is how biology works.
[00:40:10.08]
And in order to get a
few things that work,
[00:40:13.09]
the most efficient way of doing
[00:40:15.01]
is produce thousands and
pick the few that work.
[00:40:36.08]
This is how biology works.
[00:40:39.01]
And in order to get a
few things that work,
[00:40:42.01]
the most efficient way of doing
[00:40:43.03]
is produce thousands and
pick the few that work.
[00:40:47.07]
(speaking in foreign language)
[00:41:42.05]
(gentle instrumental music)
[00:42:06.07]
- In this slime mold,
[00:42:08.09]
the individual cells live
as free living Amoeba
[00:42:11.09]
crawling along in the forest floor.
[00:42:14.02]
But when conditions deteriorate,
[00:42:18.07]
then they do this remarkable social thing.
[00:42:23.02]
(gentle instrumental music)
[00:42:35.08]
These amoebae come together
to form a multicellular slug,
[00:42:40.00]
this worm like structure that crawls along
[00:42:42.07]
to try to find a better environment.
[00:42:47.03]
(gentle instrumental music)
[00:43:19.07]
And then the worm changes into
a small plant like structure,
[00:43:24.06]
which now creates these very
hardy cells called spores.
[00:43:37.07]
So cell death is involved
in this unusual life cycle,
[00:43:42.03]
when the slug stops migrating
[00:43:45.01]
and forms this little plant like structure
[00:43:47.07]
called a fruiting body,
[00:43:49.03]
it forms a stock and the stock is formed
[00:43:52.04]
from the corpses of dead cells.
[00:43:57.00]
The cells die in this altruistic way
[00:43:59.08]
to get the spores off the ground.
[00:44:03.02]
(gentle instrumental music)
[00:44:09.04]
And when conditions get better,
[00:44:11.06]
these spores now germinate
[00:44:14.02]
to give rise to free living Amoeba again.
[00:44:32.08]
(speaking in foreign language)
[00:45:05.06]
- If you look in a mature human being,
[00:45:08.02]
you look in the immune system,
[00:45:10.01]
you find that as many as 95%
[00:45:13.02]
of certain kinds of blood
cells that are made die, okay,
[00:45:17.07]
massive cell death.
[00:45:19.05]
And if that cell death didn't occur,
[00:45:22.03]
our immune systems
basically would go haywire.
[00:45:25.05]
(speaking in foreign language)
[00:45:46.02]
- The immune system has to
be prepared for everything.
[00:45:49.08]
And the way it does that
[00:45:50.06]
is it generates zillions
of these white blood cells.
[00:45:56.07]
And they're generated in
an organ called the thymus.
[00:46:01.01]
These cells are amazing,
[00:46:03.02]
they're the world's best micro surgeons.
[00:46:08.02]
They can kill one virus infected cell
[00:46:10.00]
among a whole skinful of healthy cells
[00:46:12.03]
and stop the infection.
[00:46:15.05]
These millions and millions
of white blood cells
[00:46:17.04]
are randomly generated
[00:46:19.04]
each one able to see something different.
[00:46:25.00]
There're cells in there
able to recognize anything.
[00:46:33.00]
Now out of all these cells,
[00:46:33.09]
there's gonna be some that
recognize you yourself,
[00:46:37.07]
your kidneys, your skin, your heart,
[00:46:41.00]
and that's very dangerous.
[00:46:44.08]
If you didn't do something
about them, they'd kill you.
[00:46:49.02]
(gentle instrumental music)
[00:47:00.06]
All those little micro
surgeons going around,
[00:47:02.06]
you'd die pretty quick.
[00:47:06.05]
You wanna get rid of those cells.
[00:47:09.04]
So there's a point in their
development, in the thymus
[00:47:12.01]
where any cell which can
react against your own body
[00:47:17.01]
is told to commit suicide.
[00:47:20.08]
(gentle instrumental music)
[00:47:37.04]
So most of the killer cells,
[00:47:39.03]
most of the armies of
killer cells commit suicide.
[00:47:47.02]
But a small portion stick around
[00:47:50.08]
and they start circulating around the body
[00:47:52.08]
looking for danger.
[00:47:58.09]
- [Horvitz] So we need
to generate a vast array
[00:48:02.05]
of random types of cells.
[00:48:05.09]
And we need to destroy the ones
[00:48:08.01]
that are gonna destroy us if
we don't get to them first.
[00:48:16.02]
Like any aspect of basic biology,
[00:48:20.07]
cell death can go wrong
and lead to disease.
[00:48:25.05]
(cross talking)
[00:48:29.02]
(speaking in foreign language)
[00:48:32.00]
(conversing in foreign language)
[00:48:45.02]
(speaking in foreign language)
[00:50:21.06]
- HIV infects lymphocytes
[00:50:26.00]
in very small numbers it would seem,
[00:50:28.04]
and it's also clear that
that results in the death
[00:50:31.05]
of an important class of lymphocytes
[00:50:33.09]
which makes the individual now susceptible
[00:50:36.00]
to many infections that they otherwise
[00:50:37.05]
wouldn't be susceptible to.
[00:50:39.01]
But how this virus kills the
cell remains controversial.
[00:50:42.05]
One favorite hypothesis
[00:50:45.00]
is that it induces the cell to
undergo programmed cell death
[00:50:48.00]
in some way.
[00:50:49.04]
In fact, many cells that die
[00:50:52.00]
seem to die even though they're
not infected with the virus
[00:50:56.04]
and they seem to die by
programmed cell death
[00:50:58.06]
at least that's one current view.
[00:51:00.04]
How that happens remains unknown.
[00:51:03.04]
But programmed cell death,
when the answer is known
[00:51:05.09]
and the dust clears,
[00:51:07.09]
programmed cell death will be
[00:51:08.09]
an important part of the answer.
[00:51:10.02]
I think most people
would think that's true.
[00:51:14.02]
So it's really only been
in the last few years
[00:51:17.08]
that cell death has
moved into center stage
[00:51:20.05]
where it's now recognized
[00:51:22.02]
that this is a fundamental
feature of animal cells
[00:51:25.08]
and of animals
[00:51:26.06]
and probably also of plants
[00:51:28.01]
although there's been much
less study of it there.
[00:51:30.09]
So it is remarkable
[00:51:33.02]
that something so fundamental
[00:51:35.05]
has been ignored for so long.
[00:51:38.07]
(speaking in foreign language)
[00:53:23.03]
(gentle instrumental music)
[00:53:57.09]
- Yes, I think that when
you're dealing with death,
[00:53:59.06]
whether it be a cell or an organism,
[00:54:01.04]
it's just, you know,
[00:54:02.05]
it's kind of reminding
you of your own mortality.
[00:54:05.03]
This is the great human problem
[00:54:06.07]
is coming to grips with your own death.
[00:54:09.07]
I think there probably was something
[00:54:11.03]
about that psychological explanation.
[00:54:24.01]
It certainly requires some explanation
[00:54:26.00]
because, you know, there
were voices out there
[00:54:28.05]
for many, many years saying,
[00:54:29.09]
hey, cell death, very
important, pay attention,
[00:54:32.06]
and no one was paying attention
[00:54:34.04]
other than these few people
[00:54:36.00]
who were out there in the
wilderness working on cell death.
[00:54:42.03]
Even Rita if you look at the history,
[00:54:46.08]
she saw cell death very early.
[00:54:48.07]
She wasn't the earliest,
[00:54:49.06]
but she did see it early.
[00:54:51.09]
And her most important contribution
[00:54:53.09]
was the discovery of nerve growth factor
[00:54:56.00]
this factor that is a signal
[00:54:58.05]
that is required for
developing neurons we now know
[00:55:01.06]
of some kinds to survive.
[00:55:03.08]
But the connection between
nerve growth factor
[00:55:07.02]
and cell death was made many years
[00:55:10.03]
after she had first found cell death
[00:55:12.05]
in the nervous system in her
own studies, it's remarkable.
[00:55:17.01]
(gentle instrumental music)
[00:56:36.09]
(speaking in foreign language)
[00:57:22.09]
(speaking in foreign language continues)
[00:58:41.00]
(gentle instrumental music)
[00:58:56.09]
(speaking in foreign language continues)
[01:00:05.02]
(gentle instrumental music)
[01:00:20.02]
(speaking in foreign language)
[01:00:48.07]
(speaking in foreign language)
[01:01:06.07]
- She simply took from a photo
[01:01:08.05]
this is a photo which she enlarged.
[01:01:10.06]
So she interpreted something
which is true, real.
[01:01:17.02]
(speaking in foreign language)
[01:01:44.02]
(speaking in foreign language)
[01:02:34.03]
- I didn't see my sister.
[01:02:41.03]
(speaking in foreign language)
[01:02:50.04]
(gentle instrumental music)
[01:03:13.04]
- In Britain, there is
a disdain for science,
[01:03:18.01]
they group, they put
science and technology
[01:03:20.03]
together into the same basket.
[01:03:21.09]
And it is kind of menial, it you know,
[01:03:24.06]
if you are trying to
understand how something works,
[01:03:27.08]
it's like being a plumber, right?
[01:03:30.06]
The real essence of being
an advanced human being
[01:03:36.08]
is to listen to music, or to go to a play,
[01:03:41.02]
or to think about philosophical issues,
[01:03:45.00]
it's on a different plane.
[01:03:46.04]
And that means that the politicians,
[01:03:48.07]
the captains of industry,
[01:03:49.08]
all these people are
scientifically illiterate.
[01:03:52.09]
They are making all these decisions
[01:03:55.00]
on which our lives depend
[01:03:56.08]
on whether we should use
nuclear power or not.
[01:04:00.03]
You know, what the levels
of pollution are acceptable
[01:04:03.01]
and all these decisions
[01:04:04.02]
which depend on understanding the science.
[01:04:06.07]
They know no science,
[01:04:07.09]
not only do they not know any science,
[01:04:09.03]
they don't want to know any science.
[01:04:11.04]
They would consider it demeaning,
[01:04:13.04]
somehow polluting their ethereal spirit.
[01:04:18.04]
Isn't that depressing?
[01:04:19.02]
That is depressing.
[01:04:22.04]
Feynman, Richard Feynman
made this point explicitly
[01:04:25.08]
when he says, you know,
because I understand this rose,
[01:04:30.03]
you know, I understand
that it's made of cells
[01:04:33.00]
and I understand how the pigment is made,
[01:04:33.08]
and I understand why I
see it as red, you know,
[01:04:36.01]
I understand the physics
of the light reflection
[01:04:38.09]
and so on and so forth,
[01:04:41.01]
in no way decreases my ability
[01:04:43.06]
to appreciate the beauty of the rose.
[01:04:45.00]
In fact, it increases my ability
[01:04:47.04]
to appreciate the rose
[01:04:48.08]
because I see so much more in that rose.
[01:04:56.09]
(gentle instrumental music)
[01:05:07.05]
(gentle sheep bleating)
[01:05:15.09]
- Annie go away!
[01:05:16.09]
Poppie come by!
[01:05:19.05]
Poppie lay down, good girl!
[01:05:23.05]
Annie, round-a-by, Annie round-a-by
[01:05:41.05]
Biology is all around us
and so we don't see it.
[01:05:47.01]
It's like the one thing
[01:05:48.08]
the fish swimming in a sea don't see,
[01:05:51.03]
is the water they're swimming in.
[01:05:55.03]
We're swimming in biology,
[01:05:58.05]
and so we don't see it,
[01:06:02.01]
that will do.
[01:06:39.09]
(gentle instrumental music)
[01:09:44.04]
♪ In the winter let me
bring the spring to you ♪
[01:09:48.02]
♪ Let me feel that I
mean everything to you ♪
[01:09:52.00]
♪ Love's old song will be new ♪
[01:09:57.08]
♪ In the shadows, when I
come and sing to you dear ♪
[01:10:04.05]
♪ In the shadows, when
I come and sing to you ♪