[00:00:20.01]
(upbeat instrumental music)

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- 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?

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Well, the best way I
can describe it to you,

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is to tell you that it makes the screen

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absolutely real and alive.

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Of course, these illustrations
are only a pale suggestion

[00:00:54.05]
of the real thing.

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It can't be described,

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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.

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What do you want?

[00:01:08.04]
What are you doing?

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Let me see you as you really are.

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(upbeat instrumental music)

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- Well, a cell I guess
you would define it as the

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ultimate unit of life,

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in the sense that anything that's alive

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is either a cell or it's made up of cells.

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(singing in foreign language)

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- What's a cell?

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I think I would start
with Van Leeuwenhoek,

[00:02:48.03]
who in 15 something made
the first microscope

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and using it, he looked at onion skins,

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and he found that the onion skin

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was broken up into square bits.

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And these looked like the
cells that monks live in,

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and so he called them cells.

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(gentle instrumental music)

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And that's what most
plants cells look like,

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squares with walls between them.

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Animal cells don't look like that.

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They're round, and they don't have walls.

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They have very, very thin partitions

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that are more like soap balls.

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What do cells do?

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They talk to each other.

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They help each other live,
they kill each other,

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they regenerate themselves.

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- [Raff] They move around,
they eat other cells,

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they do everything an animal can do.

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- [Polly] And those cells
come together as communities

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and those communities we
call animals and plants.

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(gentle instrumental music)

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(speaking in foreign language)

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(gentle instrumental music)

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- [Raff] I think that's a useful way of

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viewing an animal or a plant

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that it is a community of cells

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that have to interact and obey the rules

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that a community of
individuals would have to.

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(gentle instrumental music)

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But in addition, the cells have to become

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different kinds of cells, a muscle cell,

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a nerve cell, a red blood cell, and so on.

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(gentle instrumental music)

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- [Male Cast] Every man
has a job to perform.

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(upbeat instrumental music)

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- In addition, if we simply
made a mass of cells,

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a big blob of nerve cells,
muscle cells, intestinal cells,

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and so on, we would hardly be people.

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All of those cells must get
together at the proper place,

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and in fact, at the proper time,

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in order to form the structures

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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)

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(speaking in foreign language)

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(gentle instrumental music)

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- For a unicellular organism to evolve

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into a multicellular organism

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is enormously complex process.

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And in fact, if you look
at the fossil record,

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it took some three billion years

[00:07:52.09]
after the first appearance
of unicellular organisms

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to the first multicellular organism.

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So this took an enormously long time.

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And when you think about
what would be necessary,

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it's not surprising.

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(gentle instrumental music)

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Before a collection of cells
is useful as an organism,

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where they will actually work together

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for the benefit of a single organism,

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then the behavior of every
cell has to be controlled.

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You needed to have complex
mechanisms in place

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to control the behavior of
every cell in that animal,

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so that it's an advantage

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to the collection of cells as a whole.

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Now, it's clear that they've evolved

[00:08:55.05]
from the social interactions
that unicellular organisms use.

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Because single celled animals,

[00:09:02.02]
not infrequently are social

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to the extent that they
interact with their neighbors

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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

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between unicellular organisms,

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probably many more than we understand now.

[00:09:27.06]
(gentle instrumental music)

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- Okay cells in our bodies
are not isolated entities,

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they have to know about each other,

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and they have to talk to each other.

[00:11:23.00]
(gentle instrumental music)

[00:11:41.03]
(conversing in foreign language)

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- And they do that in
many complicated ways,

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but in general, they send
signals to one another,

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hundreds, thousands of different signals,

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each one telling the cell

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to do something slightly different.

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The behavior of an
individual cell in an animal

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is coordinated by
signals from other cells.

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So, cells don't do anything

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unless they're signaled
to do it, it seems.

[00:12:47.06]
(gentle instrumental music)

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People are constantly being
bombarded with signals

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and behaving according to these signals.

[00:13:02.00]
Every time you drive your car,

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you're tuning into signals of all kinds

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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.

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In an organism such as ourselves,

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cells obey these signals
in exactly the same way.

[00:13:34.01]
(loud drum banging)

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Hundreds and hundreds of different signals

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have been defined.

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Some of them are proteins,

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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.

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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,

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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.

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- 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

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at any one time.

[00:16:48.05]
And has to integrate all those signals

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and decide to do something

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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 ♪