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PROFESSOR: All right.

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It's 11:05.

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OK, let's get started.

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Last day we talked about
protein structure.

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00:00:28,930 --> 00:00:33,220
We talked about composition,
which is the primary structure

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of proteins, and that's the
instant R group sequence, as

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you go down the backbone.

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The secondary structure proteins
is all about packing,

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00:00:42,500 --> 00:00:45,070
and we saw that there were three
different structures,

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00:00:45,070 --> 00:00:48,190
the alpha helix, the
beta pleated sheet,

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00:00:48,190 --> 00:00:49,380
and the random coil.

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00:00:49,380 --> 00:00:52,480
And the gambit here is to
maximize hydrogen bonding.

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00:00:52,480 --> 00:00:56,440
And why you choose alpha, beta,
or random coil depends

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00:00:56,440 --> 00:00:59,790
upon the instant R group
sequence, which is why in some

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00:00:59,790 --> 00:01:01,260
instances, you can't
form the coil.

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00:01:01,260 --> 00:01:03,450
Because the R groups
won't allow it.

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00:01:03,450 --> 00:01:07,280
And then lastly, we talked about
tertiary structure, and

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00:01:07,280 --> 00:01:10,080
that's conformation, and that
talks about our group

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00:01:10,080 --> 00:01:14,390
interactions, and ultimately
explains protein folding.

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00:01:14,390 --> 00:01:17,040
Today I want to talk about
denaturing of proteins, which

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00:01:17,040 --> 00:01:21,610
is disruption of secondary
and tertiary structures.

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But before we do so, I
wanted to show you.

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00:01:24,360 --> 00:01:27,440
I found another movie reference
to chemistry.

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00:01:27,440 --> 00:01:29,585
This comes from 1957,
and the movie

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00:01:29,585 --> 00:01:30,990
is called Silk Stockings.

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00:01:30,990 --> 00:01:33,770
It's based on an old
Cole Porter play.

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00:01:33,770 --> 00:01:36,950
And this stars Cyd Charisse
and Fred Astaire, who were

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00:01:36,950 --> 00:01:38,680
both fantastic dancers.

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00:01:38,680 --> 00:01:40,360
And I want you to see
in this film clip

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how she carries herself.

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00:01:41,900 --> 00:01:43,140
And she actually sings this.

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00:01:43,140 --> 00:01:44,600
She didn't have somebody
dub it over.

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00:01:44,600 --> 00:01:45,510
So the singing is OK.

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00:01:45,510 --> 00:01:48,610
It's not great, but you've
got to see her posture.

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00:01:48,610 --> 00:01:49,840
She's so graceful.

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00:01:49,840 --> 00:01:52,320
And Fred Astaire is a terrific
dancer, but he doesn't dance

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00:01:52,320 --> 00:01:53,300
in this sequence.

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00:01:53,300 --> 00:01:56,120
And last thing you need to
know here is, this is set

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00:01:56,120 --> 00:01:57,510
during the Cold War.

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00:01:57,510 --> 00:02:00,920
So she's playing Ninotchka
Yoschenka, a good Ukrainian

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name, and she's a Soviet
representative.

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00:02:03,810 --> 00:02:06,450
And she's fighting with
Fred Astaire, who

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00:02:06,450 --> 00:02:09,950
is an American agent.

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00:02:09,950 --> 00:02:12,620
And they're talking about the
differences between the Soviet

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and the American systems. So
that's the background.

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It's 1957.

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I guess we better get
some volume up here

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so we can hear it.

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And she will explain to you--
and remember, just

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00:02:23,050 --> 00:02:26,740
parenthetically, that my
particular interest in

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00:02:26,740 --> 00:02:29,150
chemistry is, of course,
electrochemistry, which is the

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highest form of chemistry.

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Now she'll explain it to you.

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[BEGIN FILM PLAYBACK]

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-If you studied, Kamachev,
you would know what

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I am talking about.

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-Who's Kamachev?

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-He was one of our greatest
scientists.

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He has proved beyond any
question that physical

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attraction is purely
electrochemical.

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-You don't say.

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-Kamachev has proven it!

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-For 30 years, he worked.

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-I happen to have worked on the
same subject for about the

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same amount of time, and I have
very good reasons for

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believing otherwise.

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-Facts are facts

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[SINGING]

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-When the electromagnetic
of the he-male meets the

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electromagnetic of the female,
if right away, she should say,

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this is the male, it's a
chemical reaction, that's all.

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And though you Fascists may
answer with kisses, the same

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00:03:16,560 --> 00:03:20,970
applies when your Mr. And Mrs.
Hey-diddle-diddle with

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middle-class kisses, it's a
chemical reaction, that's all.

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Say in love, with you, I fall.

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And in love, with me,
you also fall.

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Though the uninstructed faction
calls it mutual

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attraction, it's a chemical
reaction, that's all.

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[END SINGING]

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-You don't believe
in Kamachev?

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-No, ma'am.

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[END FILM PLAYBACK]

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PROFESSOR: See the posture?

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It's just unbelievable.

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Fantastic.

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00:03:54,860 --> 00:03:55,130
OK.

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00:03:55,130 --> 00:03:57,920
So let's talk about denaturing
of proteins.

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So we want to talk about how
we can alter the structure.

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00:04:02,550 --> 00:04:06,640
And we do so by invasive
means.

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00:04:06,640 --> 00:04:08,130
So let's get to the
next slide.

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00:04:08,130 --> 00:04:09,760
So here's the tertiary
structure, and I

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00:04:09,760 --> 00:04:11,150
can point to that.

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00:04:11,150 --> 00:04:14,720
The first thing I wanted to draw
attention to, is we can

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00:04:14,720 --> 00:04:17,480
disrupt that structure by
change in temperature.

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00:04:17,480 --> 00:04:22,560
So temperature is the first
agent that we can use in

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disrupting, or denaturing,
protein.

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00:04:26,220 --> 00:04:30,040
And the whole idea here
is to break bonds.

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00:04:30,040 --> 00:04:33,295
But we're only going to break
secondary or tertiary bonds.

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00:04:33,295 --> 00:04:35,330
We're not going to do anything
to the backbone.

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00:04:35,330 --> 00:04:40,400
And a good example is what
happens when we fry an egg.

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00:04:40,400 --> 00:04:42,560
The egg has protein in it.

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00:04:42,560 --> 00:04:43,910
One of them is ovalbumin.

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00:04:43,910 --> 00:04:47,510
It's about 90% water,
about 10% protein.

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And its native state, its
natural state, conformation is

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00:04:51,095 --> 00:04:52,500
a tight ball.

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00:04:52,500 --> 00:04:56,710
And the diameter of that ball is
small enough that uncooked

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00:04:56,710 --> 00:04:59,060
egg is transparent
to visible light.

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00:04:59,060 --> 00:05:01,620
Egg white is transparent to
visible light in its natural

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00:05:01,620 --> 00:05:05,340
form, but when we heat beyond
the denaturing temperature,

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00:05:05,340 --> 00:05:09,210
that changes the bonds in
here, and it unpacks.

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00:05:09,210 --> 00:05:11,760
And when it unpacks,
two things happen.

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00:05:11,760 --> 00:05:15,090
First of all, the length scale
changes to be great enough

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that it scatters light.

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00:05:16,530 --> 00:05:18,440
So now the egg white
appears white.

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00:05:18,440 --> 00:05:22,220
And secondly, those various
chains entangle, and that

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00:05:22,220 --> 00:05:24,450
gives it its rubbery
character.

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00:05:24,450 --> 00:05:29,200
So all of that is happening as
a result of the increase in

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temperature.

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00:05:30,350 --> 00:05:36,610
So second way that we can
operate, is to change pH.

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00:05:36,610 --> 00:05:40,120
And what that does, is it
changes hydrogen bonding and

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00:05:40,120 --> 00:05:41,190
electrostatic interactions.

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00:05:41,190 --> 00:05:44,040
Now I draw your attention
to zone two here.

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00:05:44,040 --> 00:05:48,490
In zone two, imagine if we take
that proverbial drink of

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00:05:48,490 --> 00:05:52,190
cola, and now the pH in here
goes way, way down.

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00:05:52,190 --> 00:05:56,090
You can see this N has got a
hydrogen bond over to here.

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Now, if there's a proton excess,
the proton can cap,

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00:05:59,140 --> 00:06:01,270
because this is a proton
attachment site.

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00:06:01,270 --> 00:06:05,590
If the proton caps this
carboxyl, then this hydrogen

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00:06:05,590 --> 00:06:08,750
bond is broken, and now
this thing can unfurl.

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00:06:08,750 --> 00:06:11,620
Over here, you see, this is an
electrostatic attraction.

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00:06:11,620 --> 00:06:15,550
Again, the carboxyl could be
kept by a proton, and now the

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00:06:15,550 --> 00:06:19,650
plus minus electrostatic
attraction is lost. So by

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00:06:19,650 --> 00:06:22,900
change of pH, we could denature
what we see here.

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So there's a good example.

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And in fact, I think
we do this.

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We pickle our foods.

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00:06:28,390 --> 00:06:31,590
And then this one I have,
because of my interest in high

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00:06:31,590 --> 00:06:34,220
temperature electrochemical
processing of metals, I've

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00:06:34,220 --> 00:06:35,600
been to Norway many times.

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And this is a food that they
will never let me eat, because

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they're afraid if I ever
taste this, I'll

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00:06:40,570 --> 00:06:41,690
never return to Norway.

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00:06:41,690 --> 00:06:45,400
But this is lutefisk, which
literally means lye fish.

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00:06:45,400 --> 00:06:47,020
And lye has high pH.

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And this is an example of
denaturing protein by going to

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very, very high pH.

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And then you soak it and draw
back out and so on.

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00:06:55,070 --> 00:06:57,790
So there's a good
example of food.

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00:06:57,790 --> 00:07:01,730
Now the third one I want to
talk about is oxidizing

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00:07:01,730 --> 00:07:04,450
reducing agents to denature
proteins.

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00:07:15,050 --> 00:07:20,760
And what they do, they can
either create or destroy the

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00:07:20,760 --> 00:07:24,640
sulfide linkages, the
sulfur-sulfur linkages.

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00:07:24,640 --> 00:07:27,720
So for example, you see at
position number one.

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00:07:27,720 --> 00:07:30,310
Position number one, we
can use oxidizing

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00:07:30,310 --> 00:07:31,440
and reducing agents.

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00:07:31,440 --> 00:07:34,790
And a good example, that
comes from hair.

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00:07:34,790 --> 00:07:36,123
So first of all, I want
to talk to you.

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Hair is protein.

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00:07:37,410 --> 00:07:42,270
And this first example is just,
how protein can, one

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00:07:42,270 --> 00:07:44,980
strand can bond to the other
by hydrogen bonding.

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00:07:44,980 --> 00:07:48,195
So up here you have one strand
and a second strand, and there

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00:07:48,195 --> 00:07:50,230
are hydrogen bonds
in your hair.

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00:07:50,230 --> 00:07:54,680
Now, what you do when you want
to change your hair by blow

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00:07:54,680 --> 00:07:57,020
drying is first you
wet the hair.

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00:07:57,020 --> 00:07:59,820
And the water goes in and
interrupts these hydrogen

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00:07:59,820 --> 00:08:01,540
bonds between strands.

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00:08:01,540 --> 00:08:05,460
So now each of these cross-links
that want to form

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00:08:05,460 --> 00:08:08,220
instead terminate with
a water molecule.

176
00:08:08,220 --> 00:08:11,450
And now with the water
molecules, now you can move

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00:08:11,450 --> 00:08:15,340
the hair one strand versus the
other, hold it in place, blow

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00:08:15,340 --> 00:08:19,630
dry, get rid of the water, and
form new hydrogen bonds.

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00:08:19,630 --> 00:08:23,700
So what, on the basis of what
I've just told you, how can

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00:08:23,700 --> 00:08:25,430
you account for a
bad hair day?

181
00:08:25,430 --> 00:08:27,290
What is a bad hair day?

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00:08:27,290 --> 00:08:30,880
A bad hair day is a day in
which it's rather humid.

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00:08:30,880 --> 00:08:35,120
And so water can get in from the
atmosphere and interrupt

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00:08:35,120 --> 00:08:38,460
these bonds, and then the hair
will relax, and go back to a

185
00:08:38,460 --> 00:08:41,790
native state that is unfavorable
vis-a-vis what you

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00:08:41,790 --> 00:08:44,840
tried to achieve with the blow
dryer in the mirror.

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00:08:44,840 --> 00:08:46,710
So you want to combat this.

188
00:08:46,710 --> 00:08:47,590
So what do you do?

189
00:08:47,590 --> 00:08:49,900
Well, you bring out
covalent bonds.

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00:08:49,900 --> 00:08:53,710
So here's two strains of hair,
and there are disulfide

191
00:08:53,710 --> 00:08:55,990
linkages between the
strands of hair.

192
00:08:55,990 --> 00:09:00,730
So now with a reducing agent,
reducing agent is going to be

193
00:09:00,730 --> 00:09:02,460
a proton donor.

194
00:09:02,460 --> 00:09:08,340
And can you see, these disulfide
linkages are capped

195
00:09:08,340 --> 00:09:10,940
with hydrogen, and now
they're terminated.

196
00:09:10,940 --> 00:09:14,380
And so now the two strands of
hair are free to move relative

197
00:09:14,380 --> 00:09:15,640
to one another.

198
00:09:15,640 --> 00:09:18,500
And now when you're at the
beauty parlor or the

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00:09:18,500 --> 00:09:22,700
hairdresser, now you can take
this hair, for example, and

200
00:09:22,700 --> 00:09:25,150
wrap it around--

201
00:09:25,150 --> 00:09:26,280
what do you call this thing?

202
00:09:26,280 --> 00:09:28,530
It's a mandrel in the
metallurgical word.

203
00:09:28,530 --> 00:09:29,680
What do you call this thing?

204
00:09:29,680 --> 00:09:30,890
Curling iron or something?

205
00:09:30,890 --> 00:09:31,110
Yeah.

206
00:09:31,110 --> 00:09:31,430
OK.

207
00:09:31,430 --> 00:09:32,740
So here you are.

208
00:09:32,740 --> 00:09:33,510
You wrap this around--

209
00:09:33,510 --> 00:09:34,520
I know what it does.

210
00:09:34,520 --> 00:09:35,800
I don't know the terms,
all right.

211
00:09:35,800 --> 00:09:39,090
So now you see, we've got the
hair now wrapped around in

212
00:09:39,090 --> 00:09:41,710
this fashion, and now we
use an oxidizing agent.

213
00:09:41,710 --> 00:09:43,830
The oxidizing agent
is peroxide here.

214
00:09:43,830 --> 00:09:46,130
You know the derogatory
term, peroxide blonde.

215
00:09:46,130 --> 00:09:47,290
There it is, right here.

216
00:09:47,290 --> 00:09:49,610
So the peroxide goes
in, and now it

217
00:09:49,610 --> 00:09:51,880
removes these hydrogens.

218
00:09:51,880 --> 00:09:55,100
The peroxide takes the hydrogens
away and reforms the

219
00:09:55,100 --> 00:09:57,590
disulfide linkages, but
now the hair is

220
00:09:57,590 --> 00:09:59,350
in this curled state.

221
00:09:59,350 --> 00:10:01,400
You know, you might
have the opposite.

222
00:10:01,400 --> 00:10:04,190
Maybe in your native state, your
hair, because of the way

223
00:10:04,190 --> 00:10:07,350
the R groups are formed along
the length of your hair, you

224
00:10:07,350 --> 00:10:09,910
know, it's always, the ones with
the curly hair want the

225
00:10:09,910 --> 00:10:11,660
straight hair, the ones with
the straight hair want the

226
00:10:11,660 --> 00:10:12,230
curly hair.

227
00:10:12,230 --> 00:10:14,290
And so, you know, maybe you
could be running this sequence

228
00:10:14,290 --> 00:10:14,890
in reverse.

229
00:10:14,890 --> 00:10:17,870
But in this case, somebody
obviously wants curly hair.

230
00:10:17,870 --> 00:10:20,290
Now they form the disulfide
linkages.

231
00:10:20,290 --> 00:10:22,680
So this is the object,
here, of denaturing.

232
00:10:22,680 --> 00:10:25,770
So now when we go over to here,
we have a disulfide

233
00:10:25,770 --> 00:10:29,410
linkage, which is forcing
this run of the random

234
00:10:29,410 --> 00:10:30,960
coil to stay straight.

235
00:10:30,960 --> 00:10:36,660
But if we get, in this case, the
oxidizing, the reducing,

236
00:10:36,660 --> 00:10:39,390
and what will happen is that
we will break this.

237
00:10:39,390 --> 00:10:46,340
So the reducing agents will
destroy disulfide linkages,

238
00:10:46,340 --> 00:10:50,830
and the oxidizing agents will
create disulfide linkages, and

239
00:10:50,830 --> 00:10:56,940
thereby we can distort the
natural form of the protein.

240
00:10:56,940 --> 00:10:58,290
And here's a fourth example.

241
00:10:58,290 --> 00:11:01,260
There are many others, but I'll
just give you four here.

242
00:11:01,260 --> 00:11:02,990
In the fourth one, we
can use detergents.

243
00:11:06,880 --> 00:11:12,060
And last day, I showed
you the example of

244
00:11:12,060 --> 00:11:14,270
how to do your laundry.

245
00:11:14,270 --> 00:11:18,800
And so you've got this long
aliphatic tail and the

246
00:11:18,800 --> 00:11:23,330
hydrophobic head, and you can
imagine if you take such

247
00:11:23,330 --> 00:11:27,660
species and you've got this
hydrophobic pocket, the

248
00:11:27,660 --> 00:11:32,460
species will operate in such a
way as to pull these non-polar

249
00:11:32,460 --> 00:11:34,730
entities out, and
then destabilize

250
00:11:34,730 --> 00:11:36,290
this hydrophobic pocket.

251
00:11:36,290 --> 00:11:40,190
So depending on what the nature
is of the protein,

252
00:11:40,190 --> 00:11:46,300
these various chemical and
thermal actions can lead to

253
00:11:46,300 --> 00:11:46,860
denaturing.

254
00:11:46,860 --> 00:11:53,870
So this destabilizes hydrophobic
pockets.

255
00:11:59,180 --> 00:12:00,250
All right.

256
00:12:00,250 --> 00:12:02,150
So that's pretty good.

257
00:12:02,150 --> 00:12:03,390
All right.

258
00:12:03,390 --> 00:12:05,880
Well, I think this is where I
want to leave it with the

259
00:12:05,880 --> 00:12:07,500
treatment of proteins.

260
00:12:07,500 --> 00:12:11,790
And I want to move on to
a second biomolecule,

261
00:12:11,790 --> 00:12:13,790
and that's the lipid.

262
00:12:13,790 --> 00:12:15,240
We'll say a few words
about lipids.

263
00:12:15,240 --> 00:12:18,200
Lipids are not classified
on the basis of their

264
00:12:18,200 --> 00:12:20,660
composition, but rather
by their properties.

265
00:12:20,660 --> 00:12:25,970
So they are defined
their properties,

266
00:12:25,970 --> 00:12:27,480
which is kind of unusual.

267
00:12:27,480 --> 00:12:30,330
Normally we define things in
terms of their chemical

268
00:12:30,330 --> 00:12:31,210
compositions.

269
00:12:31,210 --> 00:12:33,975
And in particular, they're
soluble in

270
00:12:33,975 --> 00:12:35,225
solvents of low polarity.

271
00:12:40,620 --> 00:12:44,930
Some of the books say nonpolar
solvents, but even something

272
00:12:44,930 --> 00:12:48,580
that's polar but only mildly so
will work, in solvents of

273
00:12:48,580 --> 00:12:51,240
low polarity.

274
00:12:51,240 --> 00:12:52,320
So that's the example.

275
00:12:52,320 --> 00:12:55,300
They're insoluble in water,
they're oily to the touch.

276
00:12:55,300 --> 00:13:01,840
And this includes things
like fats, oils,

277
00:13:01,840 --> 00:13:02,790
these are all lipids.

278
00:13:02,790 --> 00:13:09,710
Cholesterol, hormones.

279
00:13:09,710 --> 00:13:13,430
These are all members
of the lipid class.

280
00:13:13,430 --> 00:13:17,410
And so let's look at
some examples.

281
00:13:17,410 --> 00:13:19,190
We've got some slides.

282
00:13:19,190 --> 00:13:22,100
So if you start over here with
the glycerol, this is a

283
00:13:22,100 --> 00:13:23,590
trialcohol.

284
00:13:23,590 --> 00:13:24,900
And you can see the OH.

285
00:13:24,900 --> 00:13:27,170
We're going to drop the H's, and
we're going to put these

286
00:13:27,170 --> 00:13:30,290
long aliphatic chains on.

287
00:13:30,290 --> 00:13:32,635
There's 14 carbons here,
plus the two, so

288
00:13:32,635 --> 00:13:34,380
it's 16 carbons long.

289
00:13:34,380 --> 00:13:37,620
And this also is seven
plus seven, and

290
00:13:37,620 --> 00:13:39,340
then the two carbons.

291
00:13:39,340 --> 00:13:42,420
And the difference here is that
in this case, it's all

292
00:13:42,420 --> 00:13:43,430
straight chain.

293
00:13:43,430 --> 00:13:46,830
In this case, we go for seven,
then we put in a double bond.

294
00:13:46,830 --> 00:13:49,220
And by doing so, when we get
to the double bond, that

295
00:13:49,220 --> 00:13:53,560
forces everything to go into
planar 120 degree arrangement.

296
00:13:53,560 --> 00:13:56,030
So you go for seven however
you want, and then there's

297
00:13:56,030 --> 00:13:59,030
this rigid 120 degree placement,
and then you go for

298
00:13:59,030 --> 00:14:00,370
seven however you want.

299
00:14:00,370 --> 00:14:04,140
Well, clearly, the one in the
middle is going to pack better

300
00:14:04,140 --> 00:14:05,270
than the one on the left.

301
00:14:05,270 --> 00:14:08,850
And so even though they have
seemingly the same chemical

302
00:14:08,850 --> 00:14:11,430
composition, the one in
the middle is a solid.

303
00:14:11,430 --> 00:14:12,050
It's a fat.

304
00:14:12,050 --> 00:14:14,790
The one on the right is a
liquid, because it doesn't

305
00:14:14,790 --> 00:14:15,480
pack well enough.

306
00:14:15,480 --> 00:14:17,250
The bonds aren't
strong enough.

307
00:14:17,250 --> 00:14:19,110
So these are both examples.

308
00:14:19,110 --> 00:14:21,150
And this is called
a palmitic acid.

309
00:14:21,150 --> 00:14:23,510
And you can see here
oxygen acting as a

310
00:14:23,510 --> 00:14:25,330
bridge, as an ester.

311
00:14:25,330 --> 00:14:29,710
So oxygen, over and over again,
acting in this way to

312
00:14:29,710 --> 00:14:35,930
give us the ability to make
these other longer structures.

313
00:14:35,930 --> 00:14:38,840
Now we can replace that oxygen
bridge with a dibridge.

314
00:14:38,840 --> 00:14:41,380
So instead of having just an
oxygen here, we're going to

315
00:14:41,380 --> 00:14:42,660
put a phosphate.

316
00:14:42,660 --> 00:14:46,720
So with the phosphate, we've got
a phosphodiester linkage.

317
00:14:46,720 --> 00:14:50,030
There's one ester, there's
a second ester.

318
00:14:50,030 --> 00:14:51,310
And why we doing this?

319
00:14:51,310 --> 00:14:53,720
Because nature wants to
get the spacing right.

320
00:14:53,720 --> 00:14:55,900
And remember what I just said,
because by the end, you're

321
00:14:55,900 --> 00:14:58,460
going to see that spacing
is everything.

322
00:14:58,460 --> 00:15:02,110
So we can use this, and we can
even lose that oxygen, and put

323
00:15:02,110 --> 00:15:03,350
something else here.

324
00:15:03,350 --> 00:15:04,090
So here's a--

325
00:15:04,090 --> 00:15:06,060
I'm not expecting you to
know these by heart.

326
00:15:06,060 --> 00:15:09,740
I would give you the structure
and tell you what it is, tell

327
00:15:09,740 --> 00:15:11,890
you its name, and then we
can go on from here.

328
00:15:11,890 --> 00:15:13,090
So what do you see here?

329
00:15:13,090 --> 00:15:15,340
Well, this is called
a phosphatide.

330
00:15:15,340 --> 00:15:18,580
And this one is a
phosphatidylethanolamine,

331
00:15:18,580 --> 00:15:20,720
because there's the
amine here.

332
00:15:20,720 --> 00:15:22,140
And look at this thing.

333
00:15:22,140 --> 00:15:23,600
Well, you've got a
phosphate in the

334
00:15:23,600 --> 00:15:24,690
center that's the bridge.

335
00:15:24,690 --> 00:15:27,310
This is the glycerol,
the three carbons.

336
00:15:27,310 --> 00:15:29,430
In its most primitive
form, we could just

337
00:15:29,430 --> 00:15:30,900
have hydroxyls here.

338
00:15:30,900 --> 00:15:33,380
This is the fatty acid
off the one end.

339
00:15:33,380 --> 00:15:35,990
Long chains here,
not to scale.

340
00:15:35,990 --> 00:15:38,590
So these things should be
way, way over to here.

341
00:15:38,590 --> 00:15:40,480
And over here, we have
an ethanol amine.

342
00:15:40,480 --> 00:15:42,540
But look more closely.

343
00:15:42,540 --> 00:15:45,220
Well, this is a hydrophilic
head, this is

344
00:15:45,220 --> 00:15:47,020
twin hydrophobic tails.

345
00:15:47,020 --> 00:15:48,520
Look, this is just
hydrocarbon.

346
00:15:48,520 --> 00:15:50,220
It's not soluble in water.

347
00:15:50,220 --> 00:15:52,250
So now you've got this
amphipathic molecule.

348
00:15:52,250 --> 00:15:54,250
It looks like a detergent,
doesn't it?

349
00:15:54,250 --> 00:15:58,160
This long, hydrophobic tail
could stab the grease, and

350
00:15:58,160 --> 00:16:00,330
this hydrophilic head can
bond to the water.

351
00:16:00,330 --> 00:16:03,760
And now if we shake things up,
we'll release the grease

352
00:16:03,760 --> 00:16:06,320
that's binding the soil
to your T-shirt.

353
00:16:06,320 --> 00:16:09,170
Got the phosphate bridge here,
and look even more closely.

354
00:16:09,170 --> 00:16:11,420
There's a minus, and
there's a plus!

355
00:16:11,420 --> 00:16:15,210
This is zitterionic, on top
of everything else.

356
00:16:15,210 --> 00:16:18,160
So this can function as
a zwitterion, too.

357
00:16:18,160 --> 00:16:20,300
And everything we learned about
zwitterionic chemistry

358
00:16:20,300 --> 00:16:23,540
and buffering, this
thing can do.

359
00:16:23,540 --> 00:16:25,290
That's cool.

360
00:16:25,290 --> 00:16:25,580
All right.

361
00:16:25,580 --> 00:16:28,120
So now I want to show what
happens when I take a whole

362
00:16:28,120 --> 00:16:29,330
bunch of those.

363
00:16:29,330 --> 00:16:29,640
All right?

364
00:16:29,640 --> 00:16:30,370
So let's go back.

365
00:16:30,370 --> 00:16:33,830
I want to keep this one up, and
I want to want to do is

366
00:16:33,830 --> 00:16:37,810
take a whole bunch of those,
and show how lipids can

367
00:16:37,810 --> 00:16:41,110
actually operate in order
to build complex

368
00:16:41,110 --> 00:16:42,150
structures for us.

369
00:16:42,150 --> 00:16:43,440
So what I'm going to
do, is I want to

370
00:16:43,440 --> 00:16:45,100
represent that molecule.

371
00:16:45,100 --> 00:16:47,600
So here's the hydrophilic
head.

372
00:16:47,600 --> 00:16:49,420
That's the amine, right?

373
00:16:49,420 --> 00:16:52,470
And then we've got twin
hydrophobic tails.

374
00:16:52,470 --> 00:16:55,970
And that's your carbon
sp3 chains.

375
00:16:55,970 --> 00:16:57,540
And I don't want to write
that so much.

376
00:16:57,540 --> 00:17:03,400
So I'm just going to simplify
that as simply hydrophilic

377
00:17:03,400 --> 00:17:05,640
head and hydrophobic
twin tails.

378
00:17:05,640 --> 00:17:07,640
So this now represents
the twin tails.

379
00:17:07,640 --> 00:17:10,550
Now if I put a whole bunch
of these in water,

380
00:17:10,550 --> 00:17:11,660
what's going to happen?

381
00:17:11,660 --> 00:17:14,600
First of all, this
is hydrophilic.

382
00:17:14,600 --> 00:17:18,320
And what if I were to just
pour this into a beaker?

383
00:17:18,320 --> 00:17:20,660
What do you think would happen
if I introduced this into a

384
00:17:20,660 --> 00:17:21,900
beaker of water?

385
00:17:21,900 --> 00:17:24,860
Well, this is hydrophobic,
this is hydrophilic.

386
00:17:24,860 --> 00:17:27,070
Can you imagine that they
would all sort of

387
00:17:27,070 --> 00:17:28,060
line up like this?

388
00:17:28,060 --> 00:17:33,970
We're trying to stick
the hydrophobic

389
00:17:33,970 --> 00:17:35,870
tails up into the air.

390
00:17:35,870 --> 00:17:37,350
Because they don't want
to be down in here.

391
00:17:37,350 --> 00:17:38,720
This is hydrophobic.

392
00:17:38,720 --> 00:17:39,910
Doesn't want to be here.

393
00:17:39,910 --> 00:17:42,470
So now suppose I put a whole
bunch of these in water.

394
00:17:42,470 --> 00:17:44,500
More than four, right?

395
00:17:44,500 --> 00:17:46,220
With only four, that's
the best can do.

396
00:17:46,220 --> 00:17:48,860
What if I put some molar?

397
00:17:48,860 --> 00:17:50,790
So then what it does, is
it forms a pocket.

398
00:17:50,790 --> 00:17:52,290
It's going to do this.

399
00:17:52,290 --> 00:17:55,560
All the heads are going to find
each other, and all of

400
00:17:55,560 --> 00:17:57,620
the tails are going to
find each other.

401
00:17:57,620 --> 00:18:00,760
Because now they're going to
form a hydrophobic pocket.

402
00:18:00,760 --> 00:18:05,120
So they'll do it this way,
because they can-- can you see

403
00:18:05,120 --> 00:18:10,580
how the heads can sort of make
a wall against the water?

404
00:18:10,580 --> 00:18:13,455
And you go on and on and on, not
to scale, and then finally

405
00:18:13,455 --> 00:18:15,370
you have some end
effects here.

406
00:18:18,560 --> 00:18:20,250
So what have I formed here?

407
00:18:20,250 --> 00:18:24,590
I've got something, first of
all, I've got a lipid layer

408
00:18:24,590 --> 00:18:26,240
here, and a lipid layer here.

409
00:18:26,240 --> 00:18:29,210
So together, I have
a lipid bilayer.

410
00:18:33,360 --> 00:18:35,407
In here, there's a pocket.

411
00:18:47,100 --> 00:18:50,490
And now, what I can do with
this whole thing, is I can

412
00:18:50,490 --> 00:18:53,000
build a cell wall with this.

413
00:18:53,000 --> 00:18:54,800
I've got a cell wall.

414
00:18:54,800 --> 00:18:57,990
I've got an outside
and an inside.

415
00:18:57,990 --> 00:19:02,050
So what happens is, when we put
all these things together,

416
00:19:02,050 --> 00:19:04,720
because of the clustering
of the hydrophobic and

417
00:19:04,720 --> 00:19:07,835
hydrophilic, we say this thing
is endowed with the property

418
00:19:07,835 --> 00:19:09,085
of self-assembly.

419
00:19:13,020 --> 00:19:18,010
Very hot topic in material
science.

420
00:19:18,010 --> 00:19:20,860
And that leads to cellular
structure, and I think we've

421
00:19:20,860 --> 00:19:23,150
got a nice cartoon here.

422
00:19:23,150 --> 00:19:25,650
So this is taken from
one of the readings.

423
00:19:25,650 --> 00:19:29,420
So you can see this with
the plurality of these.

424
00:19:29,420 --> 00:19:32,570
They're actually showing
the twin tails.

425
00:19:32,570 --> 00:19:34,960
Now, this was taken
from another text.

426
00:19:34,960 --> 00:19:40,040
I like this one, because it
shows the hydrophilic top,

427
00:19:40,040 --> 00:19:43,470
hydrophilic bottom, and the
hydrophobic interior.

428
00:19:43,470 --> 00:19:45,920
And then this thing is called
an integral protein.

429
00:19:45,920 --> 00:19:46,510
Why?

430
00:19:46,510 --> 00:19:49,560
Because it's integrated
into the cell wall.

431
00:19:49,560 --> 00:19:52,330
And let's think about this
protein for a second.

432
00:19:52,330 --> 00:19:55,680
What must be the nature of the
R groups in this vicinity of

433
00:19:55,680 --> 00:19:58,430
the protein, that it
sits where it does?

434
00:19:58,430 --> 00:20:01,810
The R groups around here must
be dominantly hydrophilic,

435
00:20:01,810 --> 00:20:05,170
otherwise it would get dumped
out of that zone.

436
00:20:05,170 --> 00:20:08,450
And in here, it must be
dominantly hydrophobic, so

437
00:20:08,450 --> 00:20:12,050
that it feels at home with all
of these hydrophobic tails.

438
00:20:12,050 --> 00:20:14,300
And over here, it must
be hydrophilic.

439
00:20:14,300 --> 00:20:15,860
Now imagine what happens.

440
00:20:15,860 --> 00:20:18,090
I'm going to go back to that
drink of Coca Cola.

441
00:20:18,090 --> 00:20:19,500
Forgive me, no brand names.

442
00:20:19,500 --> 00:20:20,100
Cola.

443
00:20:20,100 --> 00:20:25,370
And now the this zone here gets
flooded with protons,

444
00:20:25,370 --> 00:20:26,910
because the pH is dropping.

445
00:20:26,910 --> 00:20:29,940
So that could cause
conformational changes,

446
00:20:29,940 --> 00:20:34,480
because pH changes the
conformation of the protein,

447
00:20:34,480 --> 00:20:37,540
and it could cause this
thing to change shape.

448
00:20:37,540 --> 00:20:41,230
It could unfold, or it might
unfold in such a way as to

449
00:20:41,230 --> 00:20:44,880
open a channel down
the center here.

450
00:20:44,880 --> 00:20:49,220
And so in response to a change
in pH here, we open up a

451
00:20:49,220 --> 00:20:53,900
channel, which means this is
acting as a chemical gate.

452
00:20:53,900 --> 00:20:56,970
This is how things
are animated!

453
00:20:56,970 --> 00:20:58,980
It responds.

454
00:20:58,980 --> 00:21:02,290
And then once the proton
concentration has been

455
00:21:02,290 --> 00:21:06,440
depleted and you're back to a
more neutral pH, then this

456
00:21:06,440 --> 00:21:08,840
thing changes back to its
old confirmation,

457
00:21:08,840 --> 00:21:10,920
and the gate closes.

458
00:21:10,920 --> 00:21:12,310
It's that simple!

459
00:21:12,310 --> 00:21:15,980
The secondary bonding
explains animation.

460
00:21:15,980 --> 00:21:16,830
That's what's happening.

461
00:21:16,830 --> 00:21:18,310
And there's one other
cool thing.

462
00:21:18,310 --> 00:21:18,970
Look at this.

463
00:21:18,970 --> 00:21:21,500
If they all have the
same head, They're

464
00:21:21,500 --> 00:21:22,750
going to close pack!

465
00:21:27,100 --> 00:21:28,610
It's fantastic.

466
00:21:28,610 --> 00:21:29,630
Everything.

467
00:21:29,630 --> 00:21:32,090
Everything you need to
know, 3.091 here.

468
00:21:32,090 --> 00:21:32,430
All right.

469
00:21:32,430 --> 00:21:36,240
So what is the key
to animation?

470
00:21:36,240 --> 00:21:38,520
The key to animation
is self-assembly.

471
00:21:38,520 --> 00:21:40,850
And why do we have
self-assembly?

472
00:21:40,850 --> 00:21:43,360
Because we have these molecules
with the hydrophilic

473
00:21:43,360 --> 00:21:45,320
head and the hydrophobic tail.

474
00:21:45,320 --> 00:21:47,070
These molecules are called
amphipathic.

475
00:21:56,580 --> 00:21:56,910
OK.

476
00:21:56,910 --> 00:21:59,790
So this has hydrophobic and
hydrophilic components.

477
00:21:59,790 --> 00:22:03,820
So if you take amphipathy, you
end up with self-assembly.

478
00:22:03,820 --> 00:22:05,660
That's the key.

479
00:22:05,660 --> 00:22:06,910
All right, good.

480
00:22:09,910 --> 00:22:10,190
All right.

481
00:22:10,190 --> 00:22:12,640
I think that's all I want
to say about lipids.

482
00:22:12,640 --> 00:22:14,630
That's all you need to know
about lipids, is lipids will

483
00:22:14,630 --> 00:22:15,910
give you cellular structure.

484
00:22:15,910 --> 00:22:17,870
Now we've got a little bit of
time left, and we're going to

485
00:22:17,870 --> 00:22:19,880
talk about nucleic acids.

486
00:22:26,160 --> 00:22:28,170
So what do I want to say
about nucleic acids?

487
00:22:28,170 --> 00:22:30,950
Nucleic acids carry
information.

488
00:22:30,950 --> 00:22:33,850
They carry information that
directs metabolic activity,

489
00:22:33,850 --> 00:22:36,120
including replication.

490
00:22:36,120 --> 00:22:39,490
And something can be animated,
but it doesn't count as a life

491
00:22:39,490 --> 00:22:41,730
form unless it replicates.

492
00:22:41,730 --> 00:22:46,890
That's the characteristic of
life forms. So nucleic acids

493
00:22:46,890 --> 00:23:00,540
carry information that directs
metabolic activity, including

494
00:23:00,540 --> 00:23:01,790
replication.

495
00:23:11,950 --> 00:23:14,430
So these are macromolecules.

496
00:23:14,430 --> 00:23:16,020
Not polymers, but
macromolecules.

497
00:23:19,406 --> 00:23:22,500
We'll take a look in a moment
at their structure.

498
00:23:22,500 --> 00:23:26,810
They're macromolecules, and the
basic structural unit is

499
00:23:26,810 --> 00:23:28,060
called a nucleotide.

500
00:23:37,230 --> 00:23:40,140
And it's got three
building blocks.

501
00:23:40,140 --> 00:23:44,520
Every nucleotide has three
building blocks.

502
00:23:44,520 --> 00:23:46,880
See, what we're doing right
now, is we're really tying

503
00:23:46,880 --> 00:23:50,270
together all of that chemistry
you've been learning the

504
00:23:50,270 --> 00:23:52,750
entire semester.

505
00:23:52,750 --> 00:23:55,330
And it's fun to see it
actually go to use.

506
00:23:55,330 --> 00:23:57,260
So what are the three
building blocks?

507
00:23:57,260 --> 00:23:59,460
Every nucleotide has a sugar.

508
00:23:59,460 --> 00:24:02,810
And we didn't study
carbohydrates, but I'll just

509
00:24:02,810 --> 00:24:04,480
show you the structure
the sugar.

510
00:24:04,480 --> 00:24:05,790
It's got an amine.

511
00:24:05,790 --> 00:24:06,570
You know what that is.

512
00:24:06,570 --> 00:24:09,360
That's the NH something group.

513
00:24:09,360 --> 00:24:10,610
And it's got a phosphate.

514
00:24:13,350 --> 00:24:16,720
So the nucleotide has those
three components,

515
00:24:16,720 --> 00:24:17,860
So let's take a look
at the sugar.

516
00:24:17,860 --> 00:24:23,480
There's really two types of
sugars found in amino acids.

517
00:24:23,480 --> 00:24:25,400
There's the ribose--

518
00:24:25,400 --> 00:24:27,240
and the only reason I'm showing
you this, is so that

519
00:24:27,240 --> 00:24:29,180
you'll understand
the terminology.

520
00:24:29,180 --> 00:24:30,430
There's the deoxyribose.

521
00:24:33,200 --> 00:24:39,910
So if you look here, the sugar
on the left has this five-fold

522
00:24:39,910 --> 00:24:41,880
symmetry, the five-fold ring.

523
00:24:41,880 --> 00:24:44,830
And there's hydroxyls at the
number one position, number

524
00:24:44,830 --> 00:24:46,810
two position, number
three position.

525
00:24:46,810 --> 00:24:50,060
The deoxyribose is missing
the hydroxyl at

526
00:24:50,060 --> 00:24:51,520
the number two position.

527
00:24:51,520 --> 00:24:52,710
That's the difference.

528
00:24:52,710 --> 00:24:55,150
The reason I'm showing you
this, is this is called

529
00:24:55,150 --> 00:24:59,170
deoxyribose, and ultimately
this is the D in DNA.

530
00:24:59,170 --> 00:25:02,850
So you'll be able to at least
hold your own with your course

531
00:25:02,850 --> 00:25:05,160
seven major friends,
if you have any

532
00:25:05,160 --> 00:25:06,150
friends in course seven.

533
00:25:06,150 --> 00:25:09,870
And you can say, I know
what the D is.

534
00:25:09,870 --> 00:25:11,100
It's deoxyribose.

535
00:25:11,100 --> 00:25:11,790
OK.

536
00:25:11,790 --> 00:25:13,900
So then the amines.

537
00:25:13,900 --> 00:25:19,320
The amines we've got, there's
five of these.

538
00:25:19,320 --> 00:25:25,000
And they split for
RNA and DNA.

539
00:25:25,000 --> 00:25:26,250
And they're shown here.

540
00:25:28,880 --> 00:25:30,140
So it's interesting.

541
00:25:30,140 --> 00:25:33,530
There's two of them that are
called purines, because

542
00:25:33,530 --> 00:25:35,920
they've got this
ring structure.

543
00:25:35,920 --> 00:25:38,270
And then the six fold, and
then the five fold.

544
00:25:38,270 --> 00:25:42,050
So these are the purines, and
then the pyrimidines have just

545
00:25:42,050 --> 00:25:43,210
the six fold structure.

546
00:25:43,210 --> 00:25:44,410
There are three of those.

547
00:25:44,410 --> 00:25:47,290
So A, G, C, U, and T.

548
00:25:47,290 --> 00:25:49,840
Those are the five different
amino acids.

549
00:25:49,840 --> 00:25:55,620
And the difference is that in
DNA, you only have A, G, C and

550
00:25:55,620 --> 00:25:59,730
T, whereas in RNA, you
have A, G, C, and U.

551
00:25:59,730 --> 00:26:00,670
This is the chemistry.

552
00:26:00,670 --> 00:26:03,430
If you take 7012, you'll figure
out how all of this

553
00:26:03,430 --> 00:26:04,310
other stuff goes.

554
00:26:04,310 --> 00:26:05,820
And this thing here
is phosphate.

555
00:26:05,820 --> 00:26:07,300
And why is phosphate present?

556
00:26:07,300 --> 00:26:11,570
Because it's acting as the
bridge and a spacer.

557
00:26:14,480 --> 00:26:18,230
So let's take a look
at the structure.

558
00:26:21,090 --> 00:26:21,430
OK.

559
00:26:21,430 --> 00:26:23,320
There's more of the amines
in nucleic acid.

560
00:26:23,320 --> 00:26:24,760
So this is what it looks like.

561
00:26:24,760 --> 00:26:27,960
So you have a backbone that
consists of sugar phosphate,

562
00:26:27,960 --> 00:26:30,630
sugar phosphate, sugar
phosphate, shown here.

563
00:26:30,630 --> 00:26:33,710
So in this case, you've
got the deoxyribose.

564
00:26:33,710 --> 00:26:36,250
So there's the sugar, there's
the five-fold symmetry.

565
00:26:36,250 --> 00:26:39,350
Then the spacer, the phosphate,
then the sugar, and

566
00:26:39,350 --> 00:26:41,260
then the spacer,
the phosphate.

567
00:26:41,260 --> 00:26:46,140
And you can see that the sugars
are acting as hangers

568
00:26:46,140 --> 00:26:48,310
for these amine groups.

569
00:26:48,310 --> 00:26:50,700
And they're called bases,
because in fact they act as

570
00:26:50,700 --> 00:26:51,760
Bronsted bases.

571
00:26:51,760 --> 00:26:55,300
They're proton acceptors, and in
the early days of molecular

572
00:26:55,300 --> 00:26:59,090
biology, people determine the
chemical composition by wet

573
00:26:59,090 --> 00:27:00,930
assay, and these
were determined

574
00:27:00,930 --> 00:27:03,340
to be Bronsted bases.

575
00:27:03,340 --> 00:27:06,960
And so to this day, people refer
to them as base pairs,

576
00:27:06,960 --> 00:27:08,880
et cetera, et cetera, even
though now we know they're

577
00:27:08,880 --> 00:27:10,100
amines, et cetera.

578
00:27:10,100 --> 00:27:12,150
So this is the structure
going up.

579
00:27:12,150 --> 00:27:14,750
And you see, at one end, you've
got the three, and

580
00:27:14,750 --> 00:27:15,705
going up to the five.

581
00:27:15,705 --> 00:27:18,800
The three is, you have the
carboxylic acid end, and at

582
00:27:18,800 --> 00:27:21,650
the other end you have
the amino end.

583
00:27:21,650 --> 00:27:21,970
OK.

584
00:27:21,970 --> 00:27:24,270
So there the structure.

585
00:27:24,270 --> 00:27:25,950
And you have a choice here.

586
00:27:25,950 --> 00:27:29,230
So again, the sugar hanger,
the phosphate spacer, the

587
00:27:29,230 --> 00:27:31,070
sugar hanger, the phosphate
spacer.

588
00:27:31,070 --> 00:27:34,580
And you have a choice of
one of these four.

589
00:27:34,580 --> 00:27:38,440
Any one of these four is what's
found in a DNA strand,

590
00:27:38,440 --> 00:27:40,055
as you go up the strand.

591
00:27:46,120 --> 00:27:48,440
Now, how is information
encoded?

592
00:27:51,170 --> 00:27:53,540
Well, the information
is encoded--

593
00:27:53,540 --> 00:27:55,490
first of all, we have
to recognize what

594
00:27:55,490 --> 00:27:56,810
the structure is.

595
00:27:56,810 --> 00:28:00,450
Know that the structure, turns
out that it forms a double

596
00:28:00,450 --> 00:28:06,020
helix, which is the first
secondary structure, right?

597
00:28:06,020 --> 00:28:09,370
It doesn't have. The primary
structure is this instant A,

598
00:28:09,370 --> 00:28:12,380
C, G, T sequence all along.

599
00:28:12,380 --> 00:28:14,760
And then the secondary structure
is, in order to

600
00:28:14,760 --> 00:28:18,960
maximize hydrogen bonds, this
forms a double helix with a

601
00:28:18,960 --> 00:28:22,310
second chain.

602
00:28:22,310 --> 00:28:26,940
And furthermore, the pairing
is such that A always pairs

603
00:28:26,940 --> 00:28:30,460
with T, because they have two
hydrogen bonding sites between

604
00:28:30,460 --> 00:28:34,280
them, whereas C pairs with G,
because they have three

605
00:28:34,280 --> 00:28:36,780
hydrogen bonding sites
between them.

606
00:28:36,780 --> 00:28:38,580
And furthermore, look
at the spacing here.

607
00:28:38,580 --> 00:28:41,420
This always just stuns me.

608
00:28:41,420 --> 00:28:43,990
If you look down the center
of the strand--

609
00:28:43,990 --> 00:28:47,970
so I've got two strands
of nucleic acid.

610
00:28:47,970 --> 00:28:53,590
The center to center spacing is
1.085 nanometers between A

611
00:28:53,590 --> 00:28:58,380
and T, and it's 1.085 nanometers
to four significant

612
00:28:58,380 --> 00:29:01,170
figures between C and G.

613
00:29:01,170 --> 00:29:05,450
And you might say, well, is it
possible that I could take two

614
00:29:05,450 --> 00:29:09,810
of these hydrogen bond sites and
line them up to two of the

615
00:29:09,810 --> 00:29:11,550
three hydrogen bond sites?

616
00:29:11,550 --> 00:29:14,690
And the answer is no, because
the spacing is wrong.

617
00:29:14,690 --> 00:29:17,830
You can't, these two are far
enough apart that they won't

618
00:29:17,830 --> 00:29:18,450
line up here.

619
00:29:18,450 --> 00:29:23,561
So it's guaranteed that it's
always A to T, C to G.

620
00:29:23,561 --> 00:29:24,140
All right.

621
00:29:24,140 --> 00:29:25,960
So now you see the
double strand.

622
00:29:25,960 --> 00:29:27,600
You have one strand moving up.

623
00:29:27,600 --> 00:29:31,230
You see the pentagon is pointing
up, and here you see

624
00:29:31,230 --> 00:29:33,590
the pentagon is pointing
down, and we have the

625
00:29:33,590 --> 00:29:34,870
base pairs in between.

626
00:29:34,870 --> 00:29:38,960
C pairs to G, and
T pairs to A.

627
00:29:38,960 --> 00:29:42,730
And down here is the basic end,
the acidic end, the basic

628
00:29:42,730 --> 00:29:44,060
end, the acidic end.

629
00:29:44,060 --> 00:29:46,800
And so the secondary structure
is the double helix.

630
00:29:46,800 --> 00:29:47,750
Why?

631
00:29:47,750 --> 00:29:51,580
To maximize hydrogen bonds in
between, and then to keep

632
00:29:51,580 --> 00:29:53,130
maximizing hydrogen bonds.

633
00:29:53,130 --> 00:29:55,530
Hydrogen bonds between
the galleries.

634
00:29:55,530 --> 00:29:57,378
Maximize, maximize, maximize.

635
00:30:00,310 --> 00:30:04,815
So there's what they call the
base pairs, and et cetera, et

636
00:30:04,815 --> 00:30:05,950
cetera, et cetera.

637
00:30:05,950 --> 00:30:09,270
This distance is all prescribed
by the fact that we

638
00:30:09,270 --> 00:30:11,150
have the phosphate present.

639
00:30:11,150 --> 00:30:11,420
OK.

640
00:30:11,420 --> 00:30:12,990
Now where's the information
here?

641
00:30:12,990 --> 00:30:15,880
I said this encodes metabolic
information.

642
00:30:15,880 --> 00:30:20,000
Well, suppose I want to direct
protein synthesis.

643
00:30:20,000 --> 00:30:23,140
I want to put amino acids
in a sequence.

644
00:30:23,140 --> 00:30:24,950
So I have to be able to call.

645
00:30:24,950 --> 00:30:27,535
You know, I'm sitting here as
nature, and I'm saying, I want

646
00:30:27,535 --> 00:30:28,680
to make this protein.

647
00:30:28,680 --> 00:30:32,470
So I need this amino acid, and
then I need this amino acid,

648
00:30:32,470 --> 00:30:34,030
and then maybe that amino acid,

649
00:30:34,030 --> 00:30:35,780
and put them in sequence.

650
00:30:35,780 --> 00:30:39,520
So I need 20 different
words to call 20

651
00:30:39,520 --> 00:30:40,540
different amino acids.

652
00:30:40,540 --> 00:30:47,160
Well clearly, clearly if I have
just A, C, G, and T--

653
00:30:47,160 --> 00:30:54,340
so if I have one-letter
words, it won't work.

654
00:30:54,340 --> 00:30:56,550
Because I need to call out 20.

655
00:30:56,550 --> 00:31:00,260
I need 20 amino acids.

656
00:31:00,260 --> 00:31:01,680
So how am I going
to get to 20?

657
00:31:01,680 --> 00:31:02,840
I don't have 20 of these.

658
00:31:02,840 --> 00:31:05,510
I'm only using, there's
only four of these.

659
00:31:05,510 --> 00:31:06,150
So I say, oh.

660
00:31:06,150 --> 00:31:07,020
I know what to do.

661
00:31:07,020 --> 00:31:10,380
I can use this idea.

662
00:31:10,380 --> 00:31:15,940
The number of words will equal
the number of letters that I

663
00:31:15,940 --> 00:31:19,100
have in my alphabet, raised
to the power, number

664
00:31:19,100 --> 00:31:24,800
of letters per word.

665
00:31:24,800 --> 00:31:25,510
OK?

666
00:31:25,510 --> 00:31:28,320
So if I use this idea,
then I can say--

667
00:31:28,320 --> 00:31:30,570
what if I have two-letter
words?

668
00:31:30,570 --> 00:31:36,920
So in other words, to call out
an amino acid, I have to take

669
00:31:36,920 --> 00:31:40,690
two base pairs in sequence.

670
00:31:40,690 --> 00:31:42,200
That means I'll have--

671
00:31:42,200 --> 00:31:43,800
there's only four letters.

672
00:31:43,800 --> 00:31:47,080
But if I have two letters per
word, that's 16, which is

673
00:31:47,080 --> 00:31:50,980
still less than 20, and that's
no good, because I

674
00:31:50,980 --> 00:31:52,190
can only call 16.

675
00:31:52,190 --> 00:31:53,770
So what does nature do?

676
00:31:53,770 --> 00:31:56,500
What if I had three-letter
words?

677
00:31:56,500 --> 00:32:01,140
Three-letter words, then, is a
64, which is greater than 20,

678
00:32:01,140 --> 00:32:02,710
and that works.

679
00:32:02,710 --> 00:32:07,550
So now I've got, in point
of fact, 61 of these

680
00:32:07,550 --> 00:32:11,180
three-letter words.

681
00:32:11,180 --> 00:32:13,700
So I go down the sequence.

682
00:32:13,700 --> 00:32:16,290
First base pair, second base
pair, third base pair.

683
00:32:16,290 --> 00:32:19,210
That triad represents
one amino acid.

684
00:32:19,210 --> 00:32:24,930
I've got 61 to call out 20, And
I've got three left over.

685
00:32:24,930 --> 00:32:25,960
For what?

686
00:32:25,960 --> 00:32:27,640
Well, let's think about this.

687
00:32:27,640 --> 00:32:29,730
See this?

688
00:32:29,730 --> 00:32:35,960
How do you know to read this,
defined by their properties?

689
00:32:35,960 --> 00:32:39,120
You know to read from
left to right.

690
00:32:39,120 --> 00:32:44,070
You know that there's a space
here between words.

691
00:32:44,070 --> 00:32:48,900
So if I just give you
this strand of

692
00:32:48,900 --> 00:32:53,600
DNA, where do I begin?

693
00:32:53,600 --> 00:32:55,730
Do I take these three, or
do I start counting

694
00:32:55,730 --> 00:32:56,650
from here or here?

695
00:32:56,650 --> 00:33:00,280
So built into this, it tells you
to read either from left

696
00:33:00,280 --> 00:33:02,100
to right, or right to left.

697
00:33:02,100 --> 00:33:04,090
It tells you where to
start, and it tells

698
00:33:04,090 --> 00:33:06,340
you where to stop.

699
00:33:06,340 --> 00:33:08,730
These three-letter words, by
the way, are called codons.

700
00:33:15,900 --> 00:33:18,670
So we've got sixty-one to call
out 20 amino acids, which

701
00:33:18,670 --> 00:33:21,500
means, some amino acids have
more than one name.

702
00:33:21,500 --> 00:33:23,820
There's one of them that has
six different names.

703
00:33:23,820 --> 00:33:26,010
There's six different codons
that can call it

704
00:33:26,010 --> 00:33:26,950
a given amino acid.

705
00:33:26,950 --> 00:33:28,530
For some of them it's only
one, for some it's

706
00:33:28,530 --> 00:33:29,950
two, three, et cetera.

707
00:33:29,950 --> 00:33:30,240
OK.

708
00:33:30,240 --> 00:33:32,150
So that's the information.

709
00:33:32,150 --> 00:33:32,310
Look!

710
00:33:32,310 --> 00:33:32,710
Here it is!

711
00:33:32,710 --> 00:33:33,470
There's the information!

712
00:33:33,470 --> 00:33:34,470
It's all in there.

713
00:33:34,470 --> 00:33:38,610
Just hydrogen bonds like this,
hydrogen bonds like this.

714
00:33:38,610 --> 00:33:41,720
It's all bonding.

715
00:33:41,720 --> 00:33:42,690
So here's the codon.

716
00:33:42,690 --> 00:33:45,060
So somewhere here, see, we take
this, this, and this.

717
00:33:45,060 --> 00:33:48,920
This triad represents one
piece of information.

718
00:33:48,920 --> 00:33:49,200
All right.

719
00:33:49,200 --> 00:33:50,770
So let's go back and look
at some of the history.

720
00:33:50,770 --> 00:33:52,190
Who got us to this point?

721
00:33:52,190 --> 00:33:54,260
This is fresh!

722
00:33:54,260 --> 00:33:56,640
A lot of this happened
in my lifetime.

723
00:33:56,640 --> 00:33:56,880
All right.

724
00:33:56,880 --> 00:33:57,810
So Oswald Avery--

725
00:33:57,810 --> 00:33:59,060
this is before my lifetime.

726
00:34:02,370 --> 00:34:07,040
He was working at the
Rochester Institute.

727
00:34:07,040 --> 00:34:08,380
And he was the first
person-- he was

728
00:34:08,380 --> 00:34:10,070
born in Halifax, actually.

729
00:34:10,070 --> 00:34:13,360
And he worked professionally
here in the United States.

730
00:34:13,360 --> 00:34:16,760
And he was the first person to
recognize that nucleic acids

731
00:34:16,760 --> 00:34:19,970
store and transmit genetic
information.

732
00:34:19,970 --> 00:34:22,960
Up until the 1940s, people
thought nucleic acids--

733
00:34:22,960 --> 00:34:25,580
are you ready for this?--
are too complicated.

734
00:34:25,580 --> 00:34:28,160
Their structure was too
complex to contain

735
00:34:28,160 --> 00:34:29,490
information.

736
00:34:29,490 --> 00:34:32,550
It's precisely the complexity
that gives us the abundance of

737
00:34:32,550 --> 00:34:33,460
information!

738
00:34:33,460 --> 00:34:37,820
The prevailing belief was that
proteins contained the genetic

739
00:34:37,820 --> 00:34:38,380
information.

740
00:34:38,380 --> 00:34:40,390
But people couldn't figure
out how to make it work.

741
00:34:40,390 --> 00:34:47,880
So he was the first to make the
argument that the nucleic

742
00:34:47,880 --> 00:34:50,920
acids have the information.

743
00:34:50,920 --> 00:34:53,480
And then the second giant
is Erwin Chargaff.

744
00:34:53,480 --> 00:34:57,350
Erwin Chargaff worked at
Columbia in New York, and

745
00:34:57,350 --> 00:34:59,760
hospitals in the vicinity.

746
00:34:59,760 --> 00:35:03,090
And he was a painstaking
analytical chemist. He did all

747
00:35:03,090 --> 00:35:05,490
of this work by analytical
chemistry, and he gave us

748
00:35:05,490 --> 00:35:08,360
Chargaff's Rules, 1949.

749
00:35:08,360 --> 00:35:12,820
And he said that in any
biological system, the

750
00:35:12,820 --> 00:35:14,920
concentration of a--

751
00:35:14,920 --> 00:35:17,010
remember, they didn't know
the structure of DNA yet.

752
00:35:17,010 --> 00:35:19,800
I'm going to lead up to how we
get to the structure of DNA.

753
00:35:19,800 --> 00:35:22,410
So we're going back, this is
like a flashback in a movie.

754
00:35:22,410 --> 00:35:24,480
Now we're going back to see
how we got to the double

755
00:35:24,480 --> 00:35:25,820
helix, all right?

756
00:35:25,820 --> 00:35:29,070
People knew that the
concentration of A in any

757
00:35:29,070 --> 00:35:32,520
nucleic acid was equal to
the concentration of T.

758
00:35:32,520 --> 00:35:35,100
They knew that there were sugar
present, they knew there

759
00:35:35,100 --> 00:35:36,980
were amines present,
and they knew there

760
00:35:36,980 --> 00:35:38,860
were phosphates present.

761
00:35:38,860 --> 00:35:41,390
That's all they knew, based
on chemical analysis.

762
00:35:41,390 --> 00:35:45,770
And now he tells us that, of the
amines, concentration of A

763
00:35:45,770 --> 00:35:49,930
always equals concentration of
T, concentration of G always

764
00:35:49,930 --> 00:35:52,150
equals concentration of C.

765
00:35:52,150 --> 00:35:55,510
And then the sum of
concentration A plus G is the

766
00:35:55,510 --> 00:35:56,910
sum of C plus T.

767
00:35:56,910 --> 00:35:59,290
That's Chargaff's rule.

768
00:35:59,290 --> 00:36:02,020
And so here we are,
Homo sapiens.

769
00:36:02,020 --> 00:36:04,940
31, 31, 19, 19, a little bit of

770
00:36:04,940 --> 00:36:06,600
statistical error, et cetera.

771
00:36:06,600 --> 00:36:07,490
But look!

772
00:36:07,490 --> 00:36:09,020
Corn!

773
00:36:09,020 --> 00:36:09,980
Yes!

774
00:36:09,980 --> 00:36:13,580
Corn reproduces using
this same code.

775
00:36:13,580 --> 00:36:18,180
All living organisms on this
planet use the same code.

776
00:36:18,180 --> 00:36:19,280
Which makes sense!

777
00:36:19,280 --> 00:36:22,920
If I eat corn, and I'm going to
get nutrition from it, and

778
00:36:22,920 --> 00:36:27,410
it's going to help me build
cells, and regenerate my body,

779
00:36:27,410 --> 00:36:32,030
and get energy from it, it has
to be made of this same stuff,

780
00:36:32,030 --> 00:36:34,580
otherwise my body can't
recognize it!

781
00:36:34,580 --> 00:36:37,870
Because I'm a biological
machine.

782
00:36:37,870 --> 00:36:40,850
This is not a fireplace
in here, right?

783
00:36:40,850 --> 00:36:42,630
If it's a fireplace, you
can drink something

784
00:36:42,630 --> 00:36:43,790
combustible and boom!

785
00:36:43,790 --> 00:36:45,000
You've got energy.

786
00:36:45,000 --> 00:36:47,950
But we can't derive energy from
something combustible.

787
00:36:47,950 --> 00:36:51,160
We can only derive energy from
something like this.

788
00:36:51,160 --> 00:36:54,280
So, you know, when you think
you're really hot stuff, your

789
00:36:54,280 --> 00:36:58,390
DNA is not that different from
that of an ear of corn.

790
00:36:58,390 --> 00:37:01,480
So a little bit of humility
might be in order.

791
00:37:01,480 --> 00:37:01,900
All right.

792
00:37:01,900 --> 00:37:03,420
And then the last person
we want to talk

793
00:37:03,420 --> 00:37:05,730
about is Rosalind Franklin.

794
00:37:05,730 --> 00:37:09,100
Rosalind Franklin worked at the
King's College in London,

795
00:37:09,100 --> 00:37:11,870
and her specialty was
x-ray diffraction.

796
00:37:11,870 --> 00:37:15,490
And she made painstaking
experiments where she could

797
00:37:15,490 --> 00:37:21,040
take a strand of DNA with a
stainless steel needle and

798
00:37:21,040 --> 00:37:24,330
pull it out of an aqueous
solution, and hold it in a

799
00:37:24,330 --> 00:37:28,140
chamber where the chamber was
humidified so that the DNA

800
00:37:28,140 --> 00:37:29,550
didn't dry out.

801
00:37:29,550 --> 00:37:33,200
And while it was humidified in
this chamber, take an x-ray

802
00:37:33,200 --> 00:37:36,800
diffraction exposure for hours,
because all of the

803
00:37:36,800 --> 00:37:38,890
recording was done by film.

804
00:37:38,890 --> 00:37:41,470
By halide photography,
and you had to have

805
00:37:41,470 --> 00:37:43,950
long exposure time.

806
00:37:43,950 --> 00:37:46,860
This is one of the most famous
images of the 20 century.

807
00:37:46,860 --> 00:37:52,510
This is the image of
the DNA from calf

808
00:37:52,510 --> 00:37:54,660
thymus, the beta structure.

809
00:37:54,660 --> 00:37:56,490
And this is a Laue pattern.

810
00:37:56,490 --> 00:38:00,240
So the symmetry of this pattern
is reflective of the

811
00:38:00,240 --> 00:38:06,740
symmetry in the DNA structure,
which people don't know yet.

812
00:38:06,740 --> 00:38:09,640
And what you see is
five positions.

813
00:38:09,640 --> 00:38:12,290
One, two, three, four, five.

814
00:38:12,290 --> 00:38:13,540
Four is missing.

815
00:38:13,540 --> 00:38:16,760
There's no reflection there.

816
00:38:16,760 --> 00:38:20,110
But it's where you would expect
a position to be.

817
00:38:20,110 --> 00:38:22,110
So it's sort of Bragg-like,
isn't it?

818
00:38:22,110 --> 00:38:24,450
Not all of the lines
are reflecting.

819
00:38:24,450 --> 00:38:28,170
On the basis of this image,
this is what we learned.

820
00:38:28,170 --> 00:38:35,400
We learned, first of all, that
the Laue pattern is indicative

821
00:38:35,400 --> 00:38:36,750
of a double helix.

822
00:38:40,300 --> 00:38:41,850
Based on X pattern.

823
00:38:41,850 --> 00:38:43,840
Remember, they had no computers
in those days!

824
00:38:43,840 --> 00:38:45,700
All they had was a
pencil and paper.

825
00:38:45,700 --> 00:38:48,590
So to do the Fourier transform,
and go back out of

826
00:38:48,590 --> 00:38:52,040
K-space, and discern what
the pattern is--

827
00:38:52,040 --> 00:38:54,110
you know, today it's trivial!

828
00:38:54,110 --> 00:38:56,560
They did this all longhand.

829
00:38:56,560 --> 00:38:58,640
Number two.

830
00:38:58,640 --> 00:39:02,270
On the basis of that pattern,
you learn that it's 3.4

831
00:39:02,270 --> 00:39:05,615
angstroms between nucleotides
along the backbone.

832
00:39:15,020 --> 00:39:16,630
We don't know what
the backbone is!

833
00:39:16,630 --> 00:39:18,150
We just know that there's
sugar, there's

834
00:39:18,150 --> 00:39:19,230
amine, there's phosphate.

835
00:39:19,230 --> 00:39:20,610
There's different ways
of putting this

836
00:39:20,610 --> 00:39:22,990
together to make a chain.

837
00:39:22,990 --> 00:39:26,300
And the third thing that you
learn, because the strong,

838
00:39:26,300 --> 00:39:29,060
clear lines indicate
that the heaviest

839
00:39:29,060 --> 00:39:36,910
elements must lie outboard.

840
00:39:40,670 --> 00:39:41,630
What does that mean?

841
00:39:41,630 --> 00:39:46,440
If you've got a double helix,
based on the first finding,

842
00:39:46,440 --> 00:39:48,490
what's the heaviest element?

843
00:39:48,490 --> 00:39:50,650
Phosphorus.

844
00:39:50,650 --> 00:39:53,400
Because otherwise you've got
carbon, oxygen, nitrogen.

845
00:39:53,400 --> 00:39:55,810
Nitrogen is atomic mass 14.

846
00:39:55,810 --> 00:39:57,940
Phosphorus is atomic mass 30.

847
00:39:57,940 --> 00:39:59,950
So it must be outboard.

848
00:39:59,950 --> 00:40:02,770
Otherwise, if it were inboard,
there would be other elements

849
00:40:02,770 --> 00:40:05,560
farther out, and you wouldn't
get the clear lines.

850
00:40:05,560 --> 00:40:07,500
Because the heavy elements are
the ones that give the

851
00:40:07,500 --> 00:40:10,020
reflection, and if the heavy
elements are obscured by

852
00:40:10,020 --> 00:40:12,270
lighter elements that are
shielding them, you get a

853
00:40:12,270 --> 00:40:13,300
lousy reflections.

854
00:40:13,300 --> 00:40:15,596
Blunted reflections,
blurry reflections.

855
00:40:15,596 --> 00:40:24,290
So all of that comes out
of her findings.

856
00:40:24,290 --> 00:40:28,530
So what happens next?

857
00:40:28,530 --> 00:40:32,250
So there's the 3.4, and 10,
and et cetera, et cetera.

858
00:40:32,250 --> 00:40:34,820
All of that happens based
on the pattern that

859
00:40:34,820 --> 00:40:36,070
I just showed you.

860
00:40:36,070 --> 00:40:41,210
So I'm going to read to you what
happens in those days,

861
00:40:41,210 --> 00:40:46,750
back in the 1950s.

862
00:40:46,750 --> 00:40:48,030
There was intense competition.

863
00:40:48,030 --> 00:40:52,470
You know, Linus Pauling had
proposed a triple helix, and

864
00:40:52,470 --> 00:40:55,410
people in the UK were working
hard on it, and so on.

865
00:40:55,410 --> 00:40:56,950
A lot of competition.

866
00:40:56,950 --> 00:41:02,210
So what happens is that Watson
goes down to King's College in

867
00:41:02,210 --> 00:41:06,970
London, and he meets Rosalind
Franklin in the hallway, and

868
00:41:06,970 --> 00:41:08,100
they get into a big argument.

869
00:41:08,100 --> 00:41:12,220
And she really chews him him
out, and he goes running away.

870
00:41:12,220 --> 00:41:13,430
She was very tough.

871
00:41:13,430 --> 00:41:17,550
And so he goes to Maurice
Wilkins, who was her boss.

872
00:41:17,550 --> 00:41:20,580
And I'm reading, now, from
Freeman Judson's book.

873
00:41:20,580 --> 00:41:22,560
"Wilkins told Watson as they
went down the hall that

874
00:41:22,560 --> 00:41:25,710
Franklin had found that DNA
fibers, when kept wet, yielded

875
00:41:25,710 --> 00:41:28,540
a different x-ray pattern,
suggesting a second structure.

876
00:41:28,540 --> 00:41:30,940
Fourteen months after the King's
colloquium, despite

877
00:41:30,940 --> 00:41:33,590
repeated correspondence and
conversations, visits, meals

878
00:41:33,590 --> 00:41:36,030
together between Wilkins,
Watson, and Crick, the

879
00:41:36,030 --> 00:41:38,400
possibility of a second
structure was news to Watson,

880
00:41:38,400 --> 00:41:39,340
he wrote."

881
00:41:39,340 --> 00:41:43,320
Now, this is quoting
from Watson's own

882
00:41:43,320 --> 00:41:45,270
book, The Double Helix.

883
00:41:45,270 --> 00:41:48,770
'When I asked what the pattern
was like, Maurice went into

884
00:41:48,770 --> 00:41:51,370
the adjacent room to pick up a
print of the new form they

885
00:41:51,370 --> 00:41:53,130
called the beta structure.

886
00:41:53,130 --> 00:41:56,400
The instant I saw the picture,
my mouth fell open, and my

887
00:41:56,400 --> 00:41:57,920
pulse began to raise.

888
00:41:57,920 --> 00:42:00,470
The pattern was unbelievably
simpler than those obtained

889
00:42:00,470 --> 00:42:02,410
previously, the a-form.

890
00:42:02,410 --> 00:42:05,280
Moreover, the black cross of
reflections which dominated

891
00:42:05,280 --> 00:42:09,670
the picture could arise only
from a helical structure.

892
00:42:09,670 --> 00:42:12,000
With the a-form, the argument
for a helix was never

893
00:42:12,000 --> 00:42:12,650
straightforward.

894
00:42:12,650 --> 00:42:15,650
With the b-form, however, mere
inspection of its x-ray

895
00:42:15,650 --> 00:42:16,740
picture gave"--

896
00:42:16,740 --> 00:42:20,810
listen to this-- "several of the
vital helical parameters."

897
00:42:20,810 --> 00:42:21,860
I'm going to come
back to that.

898
00:42:21,860 --> 00:42:24,540
"The picture that Wilkins showed
Watson was Rosalind

899
00:42:24,540 --> 00:42:27,330
Franklin's, without
her approval."

900
00:42:27,330 --> 00:42:31,590
So then Watson goes on the train
back to Cambridge, and

901
00:42:31,590 --> 00:42:36,090
sits down with Crick, and in
no time, they've put the

902
00:42:36,090 --> 00:42:36,860
structure together.

903
00:42:36,860 --> 00:42:38,000
And this is a famous picture.

904
00:42:38,000 --> 00:42:38,620
This is Crick.

905
00:42:38,620 --> 00:42:40,490
This is Watson.

906
00:42:40,490 --> 00:42:42,230
And I don't know if you
can see really well.

907
00:42:42,230 --> 00:42:44,570
These are lab clamps
that they're using.

908
00:42:44,570 --> 00:42:45,710
This is a lab stand.

909
00:42:45,710 --> 00:42:50,380
They're using lab clamps to put
the structure together.

910
00:42:50,380 --> 00:42:51,556
So here's the paper.

911
00:42:51,556 --> 00:42:53,380
The paper as it comes
out, Molecular

912
00:42:53,380 --> 00:42:55,120
Structure of Nucleic Acids.

913
00:42:55,120 --> 00:42:57,620
And this was the first
image of DNA.

914
00:42:57,620 --> 00:43:02,360
And I submit to you that if
the earth were to end in a

915
00:43:02,360 --> 00:43:05,860
giant explosion, and we were to
only send two images in a

916
00:43:05,860 --> 00:43:09,890
spaceship out to let some other
race discover what we're

917
00:43:09,890 --> 00:43:12,320
all about, it would be
this image, and the

918
00:43:12,320 --> 00:43:13,560
image of the atom.

919
00:43:13,560 --> 00:43:15,162
That's all you need.

920
00:43:15,162 --> 00:43:18,260
Because you have the simple
atom, and you've got this, and

921
00:43:18,260 --> 00:43:21,070
everything else is just
detail in between.

922
00:43:21,070 --> 00:43:23,140
So there's the first image.

923
00:43:23,140 --> 00:43:23,620
All right.

924
00:43:23,620 --> 00:43:25,800
"We wish to suggest a structure
for the salt of

925
00:43:25,800 --> 00:43:28,140
deoxyribonucleic acid.

926
00:43:28,140 --> 00:43:30,560
The structure has novel
features which have

927
00:43:30,560 --> 00:43:33,020
considerable biological
interest. The structure for

928
00:43:33,020 --> 00:43:36,660
nucleic acid has already been
proposed by Pauling and Corey.

929
00:43:36,660 --> 00:43:39,000
They kindly made their
manuscript available to us in

930
00:43:39,000 --> 00:43:39,810
advance."

931
00:43:39,810 --> 00:43:42,720
These guys never made their
manuscripts available to Corey

932
00:43:42,720 --> 00:43:45,240
and Pauling.

933
00:43:45,240 --> 00:43:47,610
"Their model consists of three
intertwined chains with the

934
00:43:47,610 --> 00:43:51,080
phosphates near the fiber axis
and the bases on the outside."

935
00:43:51,080 --> 00:43:55,360
See, they got the
positions wrong.

936
00:43:55,360 --> 00:43:57,450
"Without acidic--" da, da,
da, da, da, and so on.

937
00:43:57,450 --> 00:43:59,170
Whatever.

938
00:43:59,170 --> 00:44:00,080
Now here's--

939
00:44:00,080 --> 00:44:02,550
remember, I've quoted
from Watson's book.

940
00:44:02,550 --> 00:44:06,240
"The previously published x-ray
data on deoxyribonucleic

941
00:44:06,240 --> 00:44:08,280
acid are insufficient for
a rigorous test of our

942
00:44:08,280 --> 00:44:09,830
structure."

943
00:44:09,830 --> 00:44:10,600
Really?

944
00:44:10,600 --> 00:44:13,490
"So far as we can tell, it is
roughly compatible with the

945
00:44:13,490 --> 00:44:16,290
experimental data, but it must
be regarded as unproved until

946
00:44:16,290 --> 00:44:18,590
it's been checked against some
more exact results."

947
00:44:18,590 --> 00:44:21,570
Remember, he's writing this
after having seen Rosalind

948
00:44:21,570 --> 00:44:23,980
Franklin's x-ray pattern.

949
00:44:23,980 --> 00:44:26,110
"Some of these are given in the
following communications."

950
00:44:26,110 --> 00:44:28,670
Yeah, the next paper is Rosalind
Franklin's paper.

951
00:44:28,670 --> 00:44:31,930
"We were not aware of the
details of the results

952
00:44:31,930 --> 00:44:34,930
presented there when we devised
our structure,--"

953
00:44:34,930 --> 00:44:36,800
That's a lie.

954
00:44:36,800 --> 00:44:39,690
"--which rests mainly, though
not entirely, on published

955
00:44:39,690 --> 00:44:42,670
experimental data and
stereochemical arguments."

956
00:44:42,670 --> 00:44:45,190
You know what? once I've given
you the data, and you know

957
00:44:45,190 --> 00:44:48,300
what the structure is, you can
give me a very, very strong

958
00:44:48,300 --> 00:44:49,810
stereochemical argument.

959
00:44:49,810 --> 00:44:51,390
But that's hindsight.

960
00:44:51,390 --> 00:44:54,890
If you don't know what the
structure is, you have no idea

961
00:44:54,890 --> 00:44:56,950
what the stereochemical
arguments are, because you can

962
00:44:56,950 --> 00:44:58,590
justify anything.

963
00:44:58,590 --> 00:45:02,000
So this is just absolute lies.

964
00:45:02,000 --> 00:45:02,900
Who are the authors?

965
00:45:02,900 --> 00:45:06,150
Watson and Crick, even though
it's based on data that was

966
00:45:06,150 --> 00:45:07,880
taken from other people.

967
00:45:07,880 --> 00:45:08,470
So here they are.

968
00:45:08,470 --> 00:45:09,550
This is the acknowledgments.

969
00:45:09,550 --> 00:45:11,350
We're indebted to--
blah, blah, blah.

970
00:45:11,350 --> 00:45:14,990
The experimental results in
ideas of Wilkins, Rosalind

971
00:45:14,990 --> 00:45:17,620
Franklin, and their coworkers
at King's College.

972
00:45:17,620 --> 00:45:20,870
And one of us, Jim Watson, he
was the American, and I think

973
00:45:20,870 --> 00:45:23,760
there's an irony here, was aided
by a fellowship from the

974
00:45:23,760 --> 00:45:26,200
National Foundation for
Infantile Paralysis.

975
00:45:26,200 --> 00:45:28,340
And I think there's a joke
there, if you know anything

976
00:45:28,340 --> 00:45:30,540
about Jim Watson.

977
00:45:30,540 --> 00:45:33,230
And now contrast
that with this.

978
00:45:33,230 --> 00:45:35,990
This is the publication
of the human genome.

979
00:45:35,990 --> 00:45:37,790
And look at all the
names here.

980
00:45:37,790 --> 00:45:41,110
Everybody who was involved in
the enterprise was named.

981
00:45:41,110 --> 00:45:42,080
This is not the paper.

982
00:45:42,080 --> 00:45:44,190
This is just the names
of the authors.

983
00:45:47,300 --> 00:45:50,120
Now, to be literate, there's
this one phrase.

984
00:45:50,120 --> 00:45:52,210
Typical British understatement.

985
00:45:52,210 --> 00:45:55,330
Remember, this was about
the structure of DNA.

986
00:45:55,330 --> 00:45:56,580
But there's this passage.

987
00:45:56,580 --> 00:45:58,100
It has not escaped our notice.

988
00:45:58,100 --> 00:46:00,930
This is the litotes.

989
00:46:00,930 --> 00:46:02,160
Understatement, right?

990
00:46:02,160 --> 00:46:04,810
"It has not escaped our notice
that the specific pairing we

991
00:46:04,810 --> 00:46:08,890
have postulated immediately
suggests a possible copying

992
00:46:08,890 --> 00:46:11,490
mechanism for the genetic
material."

993
00:46:11,490 --> 00:46:15,780
That is the understatement
all time.

994
00:46:15,780 --> 00:46:18,620
We've got the structure of DNA,
and parenthetically, I

995
00:46:18,620 --> 00:46:22,500
think this is how you direct
replication in all living

996
00:46:22,500 --> 00:46:24,910
creatures, by the way.

997
00:46:24,910 --> 00:46:27,380
So when this paper
was published.

998
00:46:27,380 --> 00:46:30,150
and they rolled out
the human genome

999
00:46:30,150 --> 00:46:33,630
as a sort of a literary--

1000
00:46:33,630 --> 00:46:34,880
what's the word--

1001
00:46:37,580 --> 00:46:38,670
allusion, thank you.

1002
00:46:38,670 --> 00:46:41,690
The literary allusion was--
there's a passage in this

1003
00:46:41,690 --> 00:46:44,930
paper that at one point begins
"It has not escaped our

1004
00:46:44,930 --> 00:46:46,300
noticed," da, da, da, da.

1005
00:46:46,300 --> 00:46:50,160
So if you're ever with some
Course 7 people, and you want

1006
00:46:50,160 --> 00:46:52,420
to really get under their skin,
you know, you could be

1007
00:46:52,420 --> 00:46:54,280
at a party or something, and
finally, you say you know,

1008
00:46:54,280 --> 00:46:55,680
it's not escaped my notice.

1009
00:46:55,680 --> 00:46:58,870
And they know what
you're saying.

1010
00:46:58,870 --> 00:47:01,345
It'll make you less popular
then you are now.

1011
00:47:04,630 --> 00:47:05,660
So let's fast forward.

1012
00:47:05,660 --> 00:47:08,200
This is Stockholm, December
10, 1962,

1013
00:47:08,200 --> 00:47:09,750
the Nobel Prize ceremony.

1014
00:47:09,750 --> 00:47:12,110
Here is the King of Sweden.

1015
00:47:12,110 --> 00:47:14,610
This is Francis Crick.

1016
00:47:14,610 --> 00:47:15,860
This is James Watson.

1017
00:47:15,860 --> 00:47:17,040
This is Maurice Wilkins.

1018
00:47:17,040 --> 00:47:19,420
No Rosalind Franklin.

1019
00:47:19,420 --> 00:47:23,540
This is Kendrew, and I'm
drawing a blank.

1020
00:47:23,540 --> 00:47:26,290
These two guys were getting the
Nobel Prize in Chemistry

1021
00:47:26,290 --> 00:47:28,730
for hemoglobin structure.

1022
00:47:28,730 --> 00:47:31,580
This, if you look carefully, is
John Steinbeck, getting the

1023
00:47:31,580 --> 00:47:32,830
Nobel Prize in Literature.

1024
00:47:35,600 --> 00:47:39,550
Over in Oslo is Linus Pauling,
getting his second Nobel

1025
00:47:39,550 --> 00:47:40,930
Prize, but for peace.

1026
00:47:40,930 --> 00:47:43,450
So ironically, he's getting
his Nobel Prize.

1027
00:47:43,450 --> 00:47:46,270
They're getting the Nobel Prize
not in Chemistry, not in

1028
00:47:46,270 --> 00:47:48,340
Physics, but in Medicine.

1029
00:47:48,340 --> 00:47:50,370
You know, what's medicine?

1030
00:47:50,370 --> 00:47:52,520
I mean it's not really
a science.

1031
00:47:52,520 --> 00:47:53,830
But anyway.

1032
00:47:53,830 --> 00:47:54,620
Here it is.

1033
00:47:54,620 --> 00:47:57,100
It's worthy of a Nobel Prize.

1034
00:47:57,100 --> 00:47:59,470
So what really happened here?

1035
00:47:59,470 --> 00:48:00,460
What really happened?

1036
00:48:00,460 --> 00:48:03,230
Why was there no Rosalind
Franklin?

1037
00:48:03,230 --> 00:48:05,320
She was marginalized
as a woman.

1038
00:48:05,320 --> 00:48:07,670
She was mistreated
by these men.

1039
00:48:07,670 --> 00:48:09,230
It was 1955.

1040
00:48:09,230 --> 00:48:10,400
You realize in the 1950s--

1041
00:48:10,400 --> 00:48:13,500
and I'm not talking about the
England of Charles Dickens.

1042
00:48:13,500 --> 00:48:16,260
I'm talking about the England
after World War II.

1043
00:48:16,260 --> 00:48:18,840
Women were not allowed
in the common room.

1044
00:48:18,840 --> 00:48:20,940
And the common room
is where everybody

1045
00:48:20,940 --> 00:48:22,400
congregates at 4:00 p.m.

1046
00:48:22,400 --> 00:48:24,350
to drink coffee and
exchange ideas.

1047
00:48:24,350 --> 00:48:26,650
So she couldn't go into the
common room and so on.

1048
00:48:26,650 --> 00:48:31,670
And it was just a terrible,
terrible story of misuse, of

1049
00:48:31,670 --> 00:48:34,490
information, lack of
attribution, and so on.

1050
00:48:34,490 --> 00:48:37,450
If this story were unfolded
today, I guarantee you these

1051
00:48:37,450 --> 00:48:40,260
guys would not be getting a
prize, and in fact, the

1052
00:48:40,260 --> 00:48:44,120
publication would probably be
rescinded on the grounds of

1053
00:48:44,120 --> 00:48:48,450
its fraudulent claims, that
they were unaware of the

1054
00:48:48,450 --> 00:48:50,480
previous information.

1055
00:48:50,480 --> 00:48:53,220
So after the paper was
published, she was so

1056
00:48:53,220 --> 00:48:56,100
brokenhearted that she resigned
her position at

1057
00:48:56,100 --> 00:49:00,800
King's College, and took a job
at another college in London.

1058
00:49:00,800 --> 00:49:03,630
Her terms of severance included
her signing a

1059
00:49:03,630 --> 00:49:09,040
document in which she agreed to
abandon all future work in

1060
00:49:09,040 --> 00:49:10,290
biochemistry.

1061
00:49:12,060 --> 00:49:14,650
I mean, imagine that you leave
your job, and they tell you

1062
00:49:14,650 --> 00:49:15,590
what you cannot do!

1063
00:49:15,590 --> 00:49:19,440
I mean, obviously, if you were
privy to intellectual property

1064
00:49:19,440 --> 00:49:21,880
and so on, you're bound
by confidentiality.

1065
00:49:21,880 --> 00:49:25,450
But no one can tell you, you
can't go to work for somebody!

1066
00:49:25,450 --> 00:49:30,650
And so she changed fields, and
made seminal discoveries in

1067
00:49:30,650 --> 00:49:35,390
two other fields outside
of the DNA work.

1068
00:49:35,390 --> 00:49:37,080
So why isn't she here?

1069
00:49:37,080 --> 00:49:41,070
She died of cancer in
1958, very young.

1070
00:49:41,070 --> 00:49:44,460
And you can't get the Nobel
Prize posthumously.

1071
00:49:44,460 --> 00:49:48,530
So some people are quite
outraged by this story.

1072
00:49:48,530 --> 00:49:52,820
But there's a symbolism
here to have Wilkins.

1073
00:49:52,820 --> 00:49:54,580
It's basically saying that
you two guys are not

1074
00:49:54,580 --> 00:49:55,450
the authors of this.

1075
00:49:55,450 --> 00:49:58,190
And so some people say that
Wilkins is standing in for

1076
00:49:58,190 --> 00:50:01,370
Rosalind Franklin, and the
Nobel committee at least

1077
00:50:01,370 --> 00:50:02,490
acknowledged that.

1078
00:50:02,490 --> 00:50:03,630
So what's the message here?

1079
00:50:03,630 --> 00:50:08,220
The message here is, I hope
nobody in 3.091 is ever

1080
00:50:08,220 --> 00:50:10,400
embroiled in a controversy
like this.

1081
00:50:10,400 --> 00:50:14,150
We have to acknowledge
our collaborators.

1082
00:50:14,150 --> 00:50:17,390
All of us are here because
somebody helped us.

1083
00:50:17,390 --> 00:50:18,830
Don't go away.

1084
00:50:18,830 --> 00:50:20,060
You haven't been
dismissed yet.

1085
00:50:20,060 --> 00:50:20,970
This is important.

1086
00:50:20,970 --> 00:50:21,950
What I'm telling
you is far more

1087
00:50:21,950 --> 00:50:24,700
important than that structure.

1088
00:50:24,700 --> 00:50:26,150
I'm telling you how to
stay out of jail.

1089
00:50:29,250 --> 00:50:32,680
See, here, you know, 50 years
ago, you cheat and steal, you

1090
00:50:32,680 --> 00:50:33,700
get a Nobel Prize.

1091
00:50:33,700 --> 00:50:36,020
Today you go to jail.

1092
00:50:36,020 --> 00:50:37,470
It is a Nobel Prize
in Medicine,

1093
00:50:37,470 --> 00:50:39,840
of course, but anyway.

1094
00:50:39,840 --> 00:50:42,750
So this is a book, if you're
interested in Rosalind

1095
00:50:42,750 --> 00:50:45,710
Franklin's story, it's
fantastic reading.

1096
00:50:45,710 --> 00:50:46,960
Real page-turner.

1097
00:50:46,960 --> 00:50:48,360
This is James Watson's book.

1098
00:50:48,360 --> 00:50:51,050
If you read this, you know,
have your you-know-what

1099
00:50:51,050 --> 00:50:53,620
sensors on all the time.

1100
00:50:53,620 --> 00:50:55,240
And here's a picture of
Rosalind Franklin

1101
00:50:55,240 --> 00:50:56,870
on vacation in France.

1102
00:50:56,870 --> 00:50:59,070
And we'll leave with The Twist
by Hank Ballard, who was

1103
00:50:59,070 --> 00:51:01,150
another person who
was marginalized,

1104
00:51:01,150 --> 00:51:02,520
because he was black!

1105
00:51:02,520 --> 00:51:05,740
And so you couldn't listen to
this music, and so there was a

1106
00:51:05,740 --> 00:51:06,500
cover made.

1107
00:51:06,500 --> 00:51:09,520
The version of The Twist that
you have heard is probably by

1108
00:51:09,520 --> 00:51:10,200
Chubby Checker.

1109
00:51:10,200 --> 00:51:12,320
This is the original one
by Hank Ballard.

1110
00:51:12,320 --> 00:51:13,620
It's gritty.

1111
00:51:13,620 --> 00:51:14,530
It's very gritty.

1112
00:51:14,530 --> 00:51:15,900
All right.

1113
00:51:15,900 --> 00:51:17,320
Treat each other well.

1114
00:51:17,320 --> 00:51:18,950
Get out of here.