Latest / From First Principles / The Race to the Double Helix — Watson, Crick, Franklin & the Real Story of DNA (EP. 19)

Transcript

The Race to the Double Helix — Watson, Crick, Franklin & the Real Story of DNA (EP. 19) · From First Principles

0:00
Ni hao, Internet.
0:01
This is your captain speaking, Lester Nare, joined as always by my co-host, our resident PhD, and number one Chamath Paliapathia cosplayer, Krishna Chowdhury.
0:13
My friend.
0:14
That's right.
0:15
I can't afford the sweaters that he wears.
0:18
The alpaca shipped from God knows where.
0:21
Yeah, yeah, yeah, yeah, yeah.
0:22
This is nylon shipped from TikTok shop.
0:25
You don't have the SPAC money.
0:27
No.
0:28
Maybe one day.
0:28
One day.
0:29
Maybe not via SPAC, but via science communication.
0:34
It is now.
0:35
We are in the holiday season.
0:37
So we are winding down for the year.
0:39
Big shout out to everyone who's joined the show.
0:42
We started less than six months ago.
0:44
Yeah.
0:45
The response has been incredible.
0:47
We're going to be wrapping up season one basically at the end of the year.
0:51
I think we've made the...
0:52
random executive decision to decide our seasons are just going to be every year.
0:57
And so we started only in halfway through this year.
1:00
Season one, a little truncated.
1:02
Yeah, no, it's good.
1:02
Pilot season.
1:03
No, the Gregorian calendar is a great calendar.
1:06
It's a great calendar.
1:07
So that's how we're going to do our seasons.
1:09
Yeah.
1:10
So this is the first of kind of our wrap-up of the year episodes.
1:14
Yes.
1:14
With holidays, with travel, all these things, with Mariah Carey being on the radio nonstop.
1:20
Yeah.
1:20
She's creeping up.
1:22
It's the holiday season.
1:25
So what we're going to do this episode is similar to what we've done when we did the Nobel Prizes.
1:30
Yes.
1:30
Which is we're going to do a single story, deep dive.
1:34
And what we're going to talk about in this episode is the discovery of DNA.
1:39
Yes.
1:40
And the reason why we're going to talk about the discovery of DNA is the unfortunate recent passing of one of the pioneers...
1:48
of the discovery of the double helix, which was James Watson, who recently passed away.
1:53
Yes.
1:54
And there's a lot of drama in this story.
1:59
This will be a complex episode.
2:01
We are really focused on science, experimental design, the concepts, thinking about things from first principles.
2:10
But this is one of the things I think we both do is it's a human story.
2:14
Yes.
2:15
Yes.
2:16
And it's a fascinating hand story.
2:17
And there's a lot of controversy...
2:21
associated with Mr. Watson.
2:24
And so we're not going to shy away from... No, not at all.
2:28
You know, talking about that in the context of what was one of the greatest... Discoveries.
2:35
Discoveries.
2:36
Of the 20th century.
2:37
Yeah.
2:37
Yeah.
2:38
Easy.
2:39
And as always, you guys know we're going to go deep.
2:42
It's going to be fun.
2:43
It's going to be lighthearted but serious.
2:45
We're going to learn something today.
2:47
This is from First Principles.
3:05
So James Watson, he recently passed away and colleagues and people in the field are wrestling with his legacy because he is a very controversial character.
3:20
He is clearly one of the greatest scientists of the 20th century.
3:26
Discovering the structure of DNA is...
3:30
an incredible achievement.
3:33
It is quite possibly, I would say in, in the world of biomolecular chemistry, it is the crown jewel of human achievement up till now is the discovery.
3:45
The DNA is this,
3:46
periodic, you know, double helix, twisted ladder, beautiful looking molecule that is ubiquitous in all of life from bacteria, archaea, fungi, plants, animals, all the way to us.
4:00
It's something that tells us that we're all connected, right?
4:04
Me and the plant and the bacteria, we all have the same lineage.
4:08
One of the definitive proofs of that is the fact that all of us use DNA as our information
4:16
Right.
4:17
It's the idea of this universal storage system.
4:20
Yeah.
4:21
Like everything that we classify as life uses the same Samsung hard drive.
4:28
Yeah.
4:29
Yeah.
4:29
Yeah.
4:30
Everyone uses like the same.
4:31
Yeah.
4:32
It's like a transistor in some sense.
4:34
Like it's everywhere.
4:37
Yeah.
4:37
It's everywhere.
4:38
And it's so good at what it does.
4:41
And one of the reasons why it's so good at what it does has to do with its structure.
4:45
At the end of the day, biology, I've told you, is just lock and key, right?
4:49
Right.
4:50
And the shape of these molecules has everything to do with what the thing is.
4:57
And DNA is one of these things that's just incredibly beautiful to look at, incredibly beautiful to think about.
5:04
beautiful to innovate on as a technology.
5:09
At the same time, James Watson is a very controversial figure.
5:14
He helped strengthen U.S. research.
5:17
He single-handedly did a lot for U.S. biomedical research, but at the same time, he was very controversial.
5:24
He said some really out-of-pocket things towards the later years of his life.
5:28
Sorry, I'm looking for my pocket, but it's kind of out right now.
5:31
Yeah, yeah.
5:34
Yeah, he was, dude, later on in the story, we're going to get into some of the stuff he said.
5:39
And they're like comical how bad they are as takes, right?
5:44
Look, as a member of the black community, it's exactly like the story of R. Kelly.
5:50
Yeah.
5:51
Great music.
5:52
But, man.
5:53
Man.
5:55
Really?
5:57
You can't.
5:57
It's tough.
5:58
Yeah.
5:58
It's tough.
5:59
It's tough.
5:59
But you got to celebrate the good with the bad, right?
6:02
And you got to know all of the nuances of the story to really appreciate it.
6:07
It's the human experience, right?
6:08
Yes, it is.
6:08
Yeah.
6:10
And I want to start by just talking about...
6:13
the historical landscape that sets up DNA as this molecule that everybody is going after, why it was such a big deal that we got this structure.
6:23
And then, and then we'll go into some of the future of, you know, after the 1950s, when this was discovered, what happened to the players.
6:31
Okay.
6:32
Okay.
6:32
So we're going to start actually all the way back in the 1800s with a man named Gregor Mendel, who,
6:38
Back then, you know, everyone knows about, like, inheritance, right?
6:43
Like, you get stuff from your parents, but nobody really knew how.
6:47
Gregor Mendel is this guy.
6:48
He's an Austrian monk, and he does experiments on pea plants.
6:54
And he starts noticing that, actually, when you do these quantitative experiments, you can—
7:01
really mathematically say how much of the next generation is going to get a certain trait from their parents.
7:08
He was doing very selective breeding where, for example, let's say a peapod had green, and then there was another pea plant that had yellow pods, right?
7:18
If you selectively breed them together, how many of the next generation are going to inherit the yellow versus the green?
7:24
How many of the next generation are going to inherit tall versus short?
7:29
Mm-hmm.
7:29
How many are going to do this or that, right?
7:32
And there was a mathematics to it.
7:35
There was an understanding that you could glean, which means that there's something.
7:39
It wasn't random.
7:41
It wasn't completely random.
7:43
There's some mechanism that's happening.
7:45
And this is before the whole mechanistic view about biology.
7:49
Got it.
7:49
Right?
7:50
Biology was still kind of a dark science of like things are just happening and we're trying to figure it out.
7:56
But here, this is one of these first clues that something as fundamental as inheritance was.
8:02
could be put into a mathematical language.
8:04
And if it's being put into a mathematical language, that means there must be some physical thingy that is going on.
8:10
That is facilitating the structure that allows you to make those, effectively, predictions.
8:15
Yes, exactly.
8:17
About what will happen based on initial conditions.
8:20
Exactly, yeah.
8:21
So it started out as a statistical abstraction that represented inheritance.
8:26
And pretty soon, people started asking, well, what is the thing?
8:30
What is the material?
8:32
that is conferring this inheritance right right so the prevailing view was that it's proteins okay everyone and and it kind of makes sense if you look back in the 1920s 1930s proteins have a really complicated structure there's 20 different amino acids that we had already kind of figured out from biochemical pathways
8:54
And the fact that there's 20 different amino acids, proteins already we know have so many different functions, right?
9:01
So it's like, it's kind of an obvious thing to say that, yeah, proteins are the thing that are conferring inheritance.
9:08
Right.
9:09
The idea is proteins are where a lot of – it's the workhorse.
9:13
Yes.
9:14
It's where a lot of stuff can happen.
9:15
Happen, yeah.
9:16
It happens.
9:17
Yes.
9:17
It can literally happen.
9:18
Yes, literally proteins are doing all these things.
9:22
They're incredibly diverse.
9:23
Right.
9:23
And given the diversity of life – It's just like, oh, it's another thing in the toolbox.
9:27
Yes, exactly.
9:28
Which is a fair...
9:30
Totally fair.
9:31
Totally fair.
9:31
Totally fair.
9:32
Right?
9:34
In 1869, actually, there was this guy, Friedrich Mischer, who identified something called nucleon, which is what we now call DNA.
9:44
He identified that inside the nucleus of cells, there were two different types of compounds.
9:49
There were proteins, and then there was this other thing that he said was nucleon.
9:53
But he was like, it's probably just like some structural thing.
9:56
He was like, nucleon.
9:58
Yeah, because it's in the nucleus.
10:01
So I'm going to call it nucleon.
10:02
And it was seen as a monotonous structural scaffold.
10:06
It's just like conferring structure into whatever is really important inside of the nucleus.
10:15
Then came Phoebus Levine from 1905 to 1930.
10:20
He was actually at the Rockefeller Institute, which is now called the Rockefeller University.
10:24
It's on the Upper East Side of Manhattan, endowed by the Rockefeller Foundation.
10:31
He discovered nucleotides.
10:34
Okay.
10:34
So he was going into this nucleon stuff, and he discovered that there's these things called nucleotides that really make up the structure of nucleon.
10:45
Okay.
10:45
And there's three different parts to a nucleotide.
10:48
There's some kind of sugar, which he identified as deoxyribose.
10:53
It's just a type of sugar.
10:54
It's like a carbohydrate.
10:56
Okay.
10:57
He also identified that there's a part of the molecule that's the phosphate, right?
11:02
And then if you actually look it up, there's another thing called the nitrogenous base.
11:07
There's something with nitrogen.
11:09
So there's three different parts to a nucleotide.
11:11
You have a base, you have a sugar, and you have a phosphate.
11:14
Exactly.
11:15
And these are the things that make up my nucleon.
11:19
Okay.
11:19
Okay?
11:21
That was sort of the prevailing thing.
11:23
There's four different types of nucleotides.
11:25
What he did notice was that there's four different types of bases in DNA.
11:31
Here we're actually showing five because RNA, which is another type of nucleon, has another type of nucleotide.
11:37
But notice the following, and this is going to be important later.
11:42
With those nitrogenous bases, which is part of the building block of this nucleon,
11:52
those are called the pyramidines.
11:54
Yes.
11:54
And then some of them have a double carbon ring.
11:57
They're a little bit bigger, right?
11:58
They've got a pentagon on a hexagon, whereas the other guys are just a bunch of hexagons, single hexagons.
12:04
Yes, yes, yes.
12:05
Right?
12:05
And he noticed that there's these four different types, and he had this thing called the tetranucleotide hypothesis, which is basically that all of DNA is just basically made up of
12:17
these four types of nucleic acids that are all coming for, and this, what you're seeing here, is the first ever proposed structure for DNA.
12:29
Okay.
12:30
He's like, these four different things, there's the A, there's the C, there's the T and the G, that's adenine, guanine, cytosine, and thymine.
12:38
Those things come together, and they create a structure called DNA, or nuclein at that point, and...
12:45
And this is what confers that structural scaffold into the nucleus.
12:50
So this is the very, very first proposed structure of DNA.
12:54
Okay.
12:55
Okay.
12:55
It's just like this box-like structure.
12:57
Yes.
12:58
With the four just in a little rectangle.
13:01
Yes.
13:02
Okay.
13:02
And he's like, this is what it is.
13:04
It clearly is not what it is.
13:06
It clearly is not what it is.
13:07
We know that now.
13:08
We know that now.
13:09
But back then, you can imagine, like, the tools that they have is not at all what the tools that we have, right?
13:14
There's no X-ray crystallography.
13:16
There's no genetic sequencing.
13:21
You're dealing with really crude tools compared to what we have today.
13:24
It's incredible that they were able to get to this intuition and this directionality of what was correct.
13:30
Right.
13:32
Details were a little fuzzy.
13:33
Yeah.
13:34
But it was directionally accurate and tactically wrong.
13:36
Yeah, yeah, yeah.
13:36
Tactically wrong.
13:38
But he had already figured out that there's four different types.
13:40
Right.
13:40
But because he had this hypothesis that, well, they're all just like conglomerated in this square shape, there's no real way for them to...
13:50
be complex they're just simple yeah and life is very complex so how do you how do you go from the simplicity of that structure and to all of the complicated kind of a little kind of yeah and so they're like okay okay so this is not this is not what it is right okay that makes sense then we get to a fisher so this is in liverpool university liverpool yeah shout out to all the scousers out there you never walk alone
14:13
Frederick Griffith.
14:14
Okay.
14:14
He's, he's at the Liverpool university and at the Liverpool medical institution.
14:19
Okay.
14:20
And he does a few experiments with bacteria and mice.
14:25
And this is what he's doing.
14:27
Back then, we knew that there were two types of bacteria of this particular strain called S. pneumoniae.
14:35
I think it's basically pneumonia.
14:38
Okay.
14:38
It's pneumonia that affects mice.
14:40
Okay.
14:41
Okay.
14:41
There's two types of these bacteria.
14:43
There's a smooth strain, which is the S. And then there's a rough strain, which is the R. Okay.
14:50
And we know that the smooth strain kills mice.
14:53
Okay.
14:54
But the rough strain does not.
14:56
Okay?
14:57
You can inject the rough strain into mice, they'll live.
14:59
The smooth strain into mice, they won't live.
15:02
Okay.
15:02
But here's the kicker.
15:03
Here's the genius of his experiment.
15:06
What Griffiths did was he said, okay, can I turn the rough strain into the smooth strain?
15:15
And you turn water into wine.
15:17
Yes.
15:17
In some sense.
15:18
Or the rice.
15:19
In some sense.
15:20
Here's what he's doing.
15:21
Like...
15:22
What he can do is, so if he puts the rough and the smooth strain together, and then he puts it in the mice, they die.
15:29
But that makes sense because you just put the smooth strain, the virulent form in the mice and they died.
15:34
Right.
15:34
What he does was he heat kills the smooth.
15:38
Heat kills?
15:39
Yeah.
15:40
So he gets a bunch of bacteria that are really bad that are going to kill the mice, and he heat kills them.
15:45
I don't know what that means.
15:47
Just heat it up.
15:48
So he literally turned the volume to 11 on the heat.
15:53
Yeah, he boiled them up.
15:54
Literally, just heat.
15:56
Yeah, just literally heated them up.
15:58
And then it inoculated kind of the fatal aspects of it.
16:01
Yes.
16:02
And now when he puts that into the mice, they still live.
16:06
They still live, right?
16:07
Because you've killed a bacteria.
16:08
I see.
16:08
That makes sense.
16:09
That makes sense.
16:09
But here's the thing.
16:10
This is the kicker.
16:11
He takes that heat-killed strain, that little sample that he has.
16:16
Let's say it's in a test tube.
16:18
He's put it into a really hot water bath.
16:21
It's killed all the bacteria.
16:22
And he mixes that with the non-viralant type.
16:26
And then he puts that mixture...
16:29
Into the mice.
16:30
So he's taking the thing that's bad.
16:32
He's boiled it.
16:33
He's boiled it.
16:33
And now he's done a little mix.
16:35
Mixing with the stuff that was fine.
16:37
That was fine.
16:38
And then he puts that mixture into the mice.
16:40
And the mice die.
16:41
Ah, so even when you boil, even when you heat, heat it up, boil it all up, and still mix, there's something there.
16:50
There's something there.
16:52
There's something there.
16:53
That's the thing.
16:54
That's the thing.
16:54
That's the thing.
16:55
There's something physically there.
16:56
Yeah.
16:58
That has transformed the non-viral form into the one that kills mice.
17:07
And it has nothing to do...
17:10
It's still present even after trying to have heated.
17:12
Yes.
17:13
Which the theory was that will kill any problematic things.
17:16
Yeah, that's why that control was very important, right?
17:19
Interesting.
17:19
The control of let's heat up my virulent form and then put that into the mice.
17:24
Right.
17:24
Right.
17:25
They don't die.
17:26
They don't die.
17:27
So I've killed a bacteria, but I've preserved something in that bacteria.
17:31
That is continuing to propagate.
17:32
That is continuing to propagate this ability to kill mice.
17:38
Yep.
17:38
Right?
17:38
This ability to be violent.
17:40
And that has gone and transformed the nice bacteria into the bad bacteria that...
17:46
And gone and done the experiment.
17:47
The point being there is something more fundamental than what we thought to be what is driving this process.
17:55
Yeah, it's not just the bacteria.
17:57
There's something inside the bacteria that is staying put, that is going inside the non-bad bacteria, the good one.
18:04
And replicating bad stuff.
18:05
Making them bad.
18:06
Bad.
18:07
And that's okay, right?
18:09
This is a very fundamental experiment.
18:10
It's very simple.
18:11
It's very simple.
18:12
But it shows you that there's a physical element to this idea of ability.
18:17
I want to just take a quick pause to point out how sometimes simple ability
18:24
or straightforward some of this early stage science sounds like.
18:29
Yeah.
18:30
But you actually need to be able to simplify before you can complexify, for lack of a better way to put it.
18:35
No, no, totally.
18:36
And with the tools that they had, this is already a huge leap, right?
18:41
Right.
18:41
This is showing that there is something there, that there's something physically there that is transforming the bacteria
18:48
to become something else.
18:50
Right.
18:50
Right?
18:50
The bacteria is going from a non-virulent form to a virulent form.
18:55
Right.
18:55
And it now has the ability to kill mice.
18:59
Right.
18:59
Even, yes, yes, yes.
19:01
Right?
19:02
This is pretty crazy.
19:03
No.
19:04
Already.
19:05
And this is in 1928.
19:06
Right?
19:08
So this is during, like, in the middle of the two wars in Liverpool that he's figured this out.
19:14
Liverpool!
19:15
Right?
19:15
Right.
19:17
People are trying to figure out what is that thing.
19:19
Which makes sense.
19:20
Now we've pointed out there's a mystery that is clearly identifiable and replicatable.
19:25
Yeah.
19:25
What is it?
19:26
What is it?
19:27
And now we get to the resolution of that with an experiment by Avery, McLeod, and McCarty in 1944.
19:34
Okay?
19:35
What they do is they systematically purify whatever the thing is.
19:40
that is doing this transformation.
19:43
And here's what they do.
19:44
They say, okay, there's possibilities, right?
19:46
It could be protein, it could be RNA, or it could be DNA.
19:50
What I'm going to do is I'm going to take that soup of heated up bad bacteria, and I'm going to treat it with something called trypsin, which basically cuts a bunch of protein,
20:04
and inoculates all the proteins.
20:06
It degrades all the proteins.
20:07
So the point is, if protein is the source, we're injecting a kill switch that kills the protein.
20:13
And so if the protein was the source...
20:18
It would not have...
20:18
The bacteria would not carry... Yeah.
20:21
Yeah.
20:21
And then mice would live.
20:23
Mice would live.
20:23
Right?
20:24
Yes.
20:25
They still die.
20:26
Kill switch was maybe a bad terminology to use when we had double kill going on.
20:31
However, the point is, trypsin killed the proteins.
20:34
Proteins no longer being problematic.
20:37
We put them to the new mice.
20:38
The new mice still die.
20:39
The new mice still die.
20:40
So it's not protein.
20:41
So it's not protein.
20:41
It's not protein.
20:42
Okay?
20:42
Then we do something called RNAs, which we know it's something that...
20:47
kills RNA.
20:48
It cuts RNA out.
20:49
Okay.
20:50
Same thing.
20:51
Nothing.
20:51
Then we do something called DNAs, which is something that cuts up DNA.
20:56
We know that.
20:57
Mm-hmm.
20:58
That's when the mice live.
21:00
Not to be confused with CRISPR, which also cuts up DNA.
21:02
Yes.
21:03
I mean, this was a very big precursor.
21:06
This is like, you know, 100 years ago.
21:09
It's a very specific CRISPR.
21:11
Understood.
21:12
Right?
21:12
But it is.
21:13
It's a scissor.
21:14
And what it's doing is it's cutting up DNA.
21:16
Well, and you cut up the DNA that would give the instructions to the bacteria to actually tell the bacteria how to infect the mice.
21:24
That's when we killed that ability.
21:28
Now we've found the building block.
21:30
Yes.
21:31
Now we've found the building block for the gene.
21:34
The idea of inheritance is something that is coming from DNA.
21:37
I actually want to take a quick step back and talk about this because at this time...
21:42
We did not understand how traits were passed generationally.
21:49
We knew that they were.
21:50
From Mendel.
21:51
Obviously.
21:51
And from all these.
21:52
I mean, obviously, like, I look like my parents.
21:54
You look like your parents.
21:55
So obviously there's something.
21:56
And then experimentally, we also proved it in a controlled context to know that there is this inheritance concept that...
22:04
of inheritance exists.
22:06
Yes, but what it is.
22:07
What actually makes up the fabric of that?
22:11
Yeah.
22:11
It's actually a really important point to know.
22:13
We actually didn't know that barely 100 years ago.
22:17
It is quite incredible, right?
22:18
100 years ago.
22:19
It is quite incredible to think about.
22:20
We didn't really know how I look like my dad.
22:25
Yeah.
22:25
Yeah.
22:25
Yeah, this is 1944.
22:27
That's crazy.
22:29
1944.
22:29
We didn't know if it was DNA or proteins or something else.
22:33
We figured out how to split the atom and create nukes.
22:35
Yeah.
22:36
But we still didn't know why I look like my dad.
22:38
Yeah.
22:39
I mean, that just goes to show you how complicated biology is, right?
22:43
And how hard it is to do experiments and really figure out what the hell is going on.
22:47
We talk about this often where you talk about like, oh, physics.
22:49
Yeah.
22:50
Yeah.
22:51
We've got that.
22:51
Biology.
22:53
Biology is tough, mate.
22:54
The variables are a little... Yeah, yeah, because every molecule is different.
22:58
Every individual is different.
23:00
You know, in physics, we have the nice pleasure of being like, that electron is the same as every other electron.
23:06
Electron in the universe.
23:07
In the universe.
23:08
We've never found one that's different, right?
23:10
So it is an incredible experiment that they did back in 1944, right?
23:15
Got it.
23:16
Okay.
23:16
At the same time in 1944, you've got...
23:21
Erwin Schrodinger's book called What is Life?
23:24
This is one of my favorite books of all time.
23:27
Okay.
23:28
It's on the FFP Readers bestseller list.
23:31
100%.
23:32
It's a very short book.
23:34
You can read it in about two hours.
23:37
Honestly, it's very short.
23:38
It's just a bunch of lectures that he gave at the Dublin College in Ireland.
23:44
But it is one of my favorite books of all time because it really shows how a physicist would approach this problem.
23:50
Okay.
23:51
Okay?
23:52
He was influenced by someone, by a bunch of physicists at the time, like Max Delbruck, who was a physicist.
24:00
that had gone to University of Göttingen, which we've talked about.
24:04
He was mentored by Lisa Meitner.
24:06
Yep.
24:06
And then he finally gets to Caltech.
24:09
And he shows that he really starts thinking about how hereditary material must be something that is solid.
24:16
It must be something that can resist temperature fluctuations.
24:21
Because of what we just talked about.
24:22
Yes.
24:22
And it must also be non-repetitive.
24:26
What does that mean?
24:27
Yeah.
24:27
If it's repetitive, if it's just a bunch of repetition, you can't store a lot of information there.
24:34
It's got to store a bunch of information, right?
24:38
It's got to be like, this is how you do this, and this is how you do that.
24:41
A recipe book is not repetitive.
24:43
Yeah, right, right.
24:45
Every page or every couple pages is a different... Is different, is a different recipe for all of the different things that I need in life, right?
24:52
This is quite nice, but it's a fundamental thing that you can even think about for a bit and be like, yeah, of course.
24:59
Okay, that makes sense.
25:00
Whatever the thing that is...
25:02
Giving you the information for inheritance has to be something that is not repetitive.
25:08
It's something that encodes a bunch of information, like a recipe book, right?
25:13
You can have multiple books.
25:15
Books are repetition, but within the context of a book, there's complexity within that object type.
25:22
Exactly.
25:23
Yeah, yeah, yeah.
25:24
And one of the key things that he says, it's a postulate that he puts, Erwin Schrödinger.
25:29
He says the gene is an aperiodic crystal.
25:33
What does he mean by that?
25:35
What he means is there's periodic crystals, right?
25:37
Diamond is a periodic crystal.
25:38
It's a bunch of carbon, carbon, carbon, carbon, carbon.
25:42
You can have salt, which is sodium chloride, sodium chloride, sodium chloride.
25:46
Not a lot of information there.
25:48
There's like two bits of information, which is you put the sodium here and the chlorine here, and then you repeat.
25:53
An aperiodic crystal is somewhere where the atomic arrangements are different.
25:59
And that difference tells you how to do whatever inheritance thing that you're doing.
26:05
So he was the first person to postulate that there's some kind of hereditary code script.
26:10
There's some aperiodic crystal inside of biology.
26:15
That is conferring information to the next generation.
26:19
And this is really important because this is cited by both Watson and Crick, who are the discoverers of the double helix.
26:27
They said this was a primary motivation for seeking the genetic structure.
26:31
What they wanted to do with their life was find this aperiodic crystal.
26:36
So just the idea here is that someone...
26:42
basically said it's a treasure map.
26:44
Yeah.
26:44
There's a treasure map, and this is what it looks like.
26:46
Right.
26:47
And this is this aperiodic crystal concept with a hereditary code script, which makes, you can intuit that logic.
26:55
Yeah.
26:56
From first principles, you can build it up and be like, okay, something that requires information capacity needs to be aperiodic.
27:03
It needs to not be the same everywhere, right?
27:06
Right.
27:06
Because your level of fidelity, if you just have two...
27:11
bits is very low as compared to 16 or 32 or 64.
27:15
Yeah.
27:16
And the order of those bits is what matters.
27:18
Is what matters.
27:18
Right?
27:18
You can't just be 0, 1, 0, 1, 0, 1, 0, 1.
27:20
Right.
27:21
It's got to be a different, and that sequence...
27:25
is what tells you what the information is.
27:27
Because DNA ultimately runs a variety of biological processes.
27:33
And so how are the instructions stored?
27:37
And you need basically a system of enough different component parts or variables to store that complexity.
27:46
Yeah.
27:46
And so we have the treasure map, and then with Watson and Crick we have the treasure hunters.
27:51
Yes, that's a very good way of putting it.
27:53
Yeah, they read this book and they're like, this is a treasure that I want to find.
27:58
Let's go find the gold of whatever.
28:00
What's that famous place where they had all the gold, the ancient place that back in the day... Yeah, I know what you're saying.
28:10
I saw National Treasure 2, one of my favorite movies.
28:13
The City of Gold, right?
28:15
It's the City of Gold.
28:16
Yeah, yeah, yeah.
28:17
The City of Gold.
28:18
They were looking... Because frankly...
28:21
The things we live, we'll get there.
28:22
City of gold.
28:24
So they're trying to find this thing.
28:26
They read this book.
28:26
It's an incredibly influential book for them.
28:29
Yes.
28:29
And they're like, we want to go find what this aperiodic crystal is and what does this crystal look like.
28:36
Right.
28:36
Okay.
28:38
This is around 1944.
28:40
So at this point, people are already trying to...
28:44
justify that DNA is really the thing that carries the genetic information.
28:50
Okay.
28:51
Erwin Chargaff, Chargaff, Erwin Chargaff at the University of Columbia in Manhattan.
28:57
I should say Columbia University.
28:59
Um,
29:00
He uses this technique of partition chromatography to look at what is the base composition of this DNA across species.
29:08
Okay.
29:08
Okay.
29:08
Because, you know, back then when Levine was trying to look at the base composition, he just said everything's the same, right?
29:18
There's an A, a C, a T, and a G, and they all just come together and it's all equal parts.
29:22
He didn't have the resolution.
29:24
Mm.
29:25
to figure out if there was more A or more T and so on and so forth, right?
29:29
Chargaff uses this new method called partition chromatography.
29:34
To quantify how much A is there in a species.
29:38
How much T is there.
29:39
How much G and how much C. As an analogy, you can say, oh, it's all soda.
29:44
But it's like, is it Coke?
29:46
Is it Sprite?
29:47
Yeah.
29:47
Is it Fanta?
29:48
Yeah.
29:48
And are they all in equal proportions?
29:50
Right.
29:50
Like, is there, what is the, is it Coke Zero?
29:53
Yeah.
29:53
Right.
29:53
Yeah.
29:53
Yeah.
29:54
Yeah.
29:54
Or Diet Coke?
29:55
What's the sugar volume?
29:56
I'm trying to identify, like, create an A or 4.
29:58
Well, there's only four different types of sodas.
30:00
So Coke, Sprite, Fanta, grape soda.
30:04
Yeah.
30:04
We'll say those four.
30:06
And those are the four, but Levine has said that they're all equal, and they're just creating the scaffold, right?
30:11
And Chargaff went out to say, okay, is this actually true?
30:15
And he actually dismantled that hypothesis by showing that there's species-specific variation, meaning...
30:22
Like the amount of A's and T's that I have is different from the amount that the cow has, is different from the amount that a pig has from a bird and so on and so forth.
30:32
And he came up with a rule that said there's actually a pairing ratio.
30:38
Okay.
30:39
The A and the T are always the same amount.
30:44
And the G and the C are always the same amount.
30:48
And if you look at that, this is an expert from his paper.
30:53
The source is actually, this is for humans, it actually comes from human semen.
30:58
Ah, we love it.
30:59
Yeah.
31:00
I mean, these guys, when you're doing science at the cutting edge, you got to get down under the weeds.
31:06
You got to go to the source.
31:07
Yeah.
31:07
And the advantage of human semen is like most of the stuff is DNA.
31:11
Yeah.
31:13
I get it.
31:14
You know, it's a good source.
31:15
Like with normal cells, there's so many proteins that like it's going to cloud whatever chromatography that you're doing.
31:23
With human semen, the sperm cell is like mostly just packaged DNA.
31:27
Mm-hmm.
31:28
And a tail.
31:29
So it's pure.
31:30
It's pure.
31:31
It's like...
31:31
It's sigma.
31:32
Yeah.
31:32
Pure alpha.
31:32
Yeah, exactly.
31:33
Exactly.
31:34
Like, the most of the stuff that's in there is like your DNA.
31:37
It's what you're looking for.
31:39
It's what you're looking for.
31:40
So he used that and he showed that...
31:42
I love that.
31:42
You know, with humans, the...
31:45
The A and T's were about 35%.
31:47
Yeah.
31:47
And the C and G's were the rest.
31:49
And then when he looked at, let's say, cows, he found a different ratio.
31:54
And with pigs, he found a different ratio.
31:56
But the ratios always came in these pairs.
31:59
So the point is A and C's, A and T's like to hang out.
32:04
And C's and G's like to hang out.
32:05
And that's true across species.
32:07
Across species.
32:08
The numbers could be different.
32:09
The proportion of it is a little different.
32:11
Yeah.
32:11
But in everything, the A and T's...
32:15
are hanging out and the season season which is like another level of
32:23
of fidelity.
32:24
Yes.
32:24
That we're going down.
32:25
Yes.
32:26
So we're getting clues into what DNA is, right?
32:29
Right.
32:29
We're getting slowly, we're honing down into this.
32:31
These are called Chargass rules, which is the A equals the T, the C equals the G, and they all add up to 100%.
32:38
Everything we have today is building off of the shoulders of the people who came before, who asked maybe simpler questions.
32:45
Yeah.
32:45
Yeah.
32:47
figured out the simpler question that allowed us to ask now more complex questions.
32:51
Yes.
32:52
Yes, exactly.
32:52
And we're kind of going through an example of that journey.
32:54
Yeah.
32:54
And I, I, that's why I love this story is like, it's really building up this, this,
33:01
you know, crown jewel, right?
33:02
It's not, it's not just randomly.
33:04
These guys came up with, they didn't walk into a cave and find it.
33:07
Yeah.
33:07
They had to be crafted.
33:09
There were, there were a bunch of people.
33:10
There was an entire community trying to figure this out.
33:13
Right.
33:14
And maybe these guys just got lucky.
33:15
Right.
33:16
You know, right.
33:17
Look, that happens.
33:18
It happens.
33:18
And now after all that, we get to the setting of the story.
33:23
After all that.
33:25
1951, England.
33:27
Oh, so what's great is we were in Liverpool.
33:31
Speaking of Scouts.
33:32
We were in Liverpool.
33:33
We were in Columbia.
33:35
We were in Rockefeller Institute in Manhattan.
33:40
And now we're finally getting to where the room where it happens.
33:44
The room where it happens.
33:45
There's two rooms where it happens, it turns out.
33:47
In the Cavendish Lab, which is the physics department of Cambridge University.
33:52
And King's College London.
33:53
I'm feeling a little Cavendish right now.
33:56
I don't know.
33:58
Yeah, but those are the two rooms where it happens, okay?
34:01
The Cavendish Lab, which is a storied lab.
34:05
It's where all sorts of stuff have happened, right?
34:10
J.D.
34:10
Thompson discovered the electron.
34:13
This is the crucible of experimental physics before America took over post-war, okay?
34:21
And this is actually one of the last big things that they did.
34:25
Tough.
34:26
But...
34:27
It's good.
34:28
They had a good run while they were at it.
34:30
And look, we appreciate the work that was done.
34:33
Oh, yeah.
34:34
Incredible work.
34:35
And one day when this podcast is big, I want to go there and record and show the room where it happens.
34:43
Because they still have the old Cavendish Lab there.
34:47
They have a new building now in Cambridge that is off campus that has all of the big facilities, obviously.
34:52
And Cavendish Lab in Cambridge, don't get me wrong.
34:54
Okay, Cavendish Lab in Cambridge is still one of the foremost institutions for experimental physics research, right?
35:01
But the old building, which is in the center of town, in like the old Gothic architecture, I mean, you can't beat that.
35:09
You can't beat it.
35:10
It's kind of like the Frisk Campus Center at Princeton, right?
35:13
Frisk Campus Center, there it says Palmer Physics Lab, and you've got –
35:19
You've got these statues of Benjamin Franklin and Joseph Henry, which are some of the founders of American physics.
35:26
You can't beat the building where Einstein had an office.
35:32
Now we've got Jadwin Hall, which is...
35:34
might i just say the most depressing piece of architecture on princeton campus built in the 1960s brutalist architecture i saw the brutalist it's a fine movie the architecture is absolute trash can i just say i it is when you look at it because there's a lot of beautiful amazing things to look at on princeton's campus yeah no and jack and hall is not one of them it's pretty depressing no it's it's awful
35:58
Yeah, but it does its job.
36:00
It does its job, and it's still pumping out amazing research.
36:03
Look, and Nobel Prize winners.
36:05
Yeah, yeah, all the time.
36:06
So anyways, let's get back to Cavendish Lab and King's College.
36:11
These are the two rooms where it happens, okay?
36:13
We're first actually going to run into Rosalind Franklin.
36:16
Okay.
36:17
Rosalind Franklin is this young PhD right out of Paris, who's a young PhD.
36:23
She joins John Randall's group at the MRC, which is the Medical Research Council, the biophysics unit at King's College.
36:32
Okay.
36:32
Okay.
36:33
And Randall writes to her and assigns her responsibility for the DNA project.
36:39
But he does not clearly inform the guy who he already has on staff, Maurice Wilkins, that he's doing this.
36:48
Oh.
36:48
So Maurice Wilkins...
36:51
thinks that Rosalind Franklin is joining as kind of a lab assistant.
36:56
Here we go.
36:57
But Randall has explicitly wrote in a letter to Rosalind Franklin that, no, you're going to have your own lab.
37:04
She's been doing a lot of X-ray crystallography, which we're going to get into, in Paris.
37:09
She's been actually investigating the structure of coal using X-rays and trying to figure out the crystalline properties of coal.
37:17
There's a miscommunication there happening from the head of the lab, John Randall, and that seeds years of personal tension between Maurice Wilkins and...
37:26
and Rosalind Franklin.
37:27
These are two players at King's College in London.
37:31
Maurice is like, I'm here.
37:33
Oh, you're bringing someone new?
37:34
They're my executive assistant.
37:36
They're going to help me take out the trash.
37:37
Yeah.
37:38
Give me coffee.
37:39
Yeah, yeah.
37:39
If I'm going to be like, I need this particular scan done, they're going to do it.
37:43
They're not really going to have...
37:45
the intellectual autonomy that is required for a true scientist.
37:49
Right, right.
37:50
They're not going to be smart enough and they're not going to have agency was Maurice's viewpoint.
37:53
Yeah.
37:54
But Randall was like, no, no, no, no, no.
37:56
Like, you're going to... You're at equal level.
38:00
Yeah, right.
38:01
But he didn't tell Maurice.
38:02
Oh, that's right.
38:04
You know?
38:04
And obviously that's going to cause issues.
38:07
100%.
38:08
Right?
38:08
Especially because, like, Rosalind Franklin is a woman.
38:10
So, like, it's like she's coming in.
38:13
At the time she's coming in, it's like, oh, this is my secretary.
38:16
Right?
38:17
This is actually in the same era, maybe a little bit earlier, as Mad Men, the TV show.
38:23
No, no, exactly.
38:25
Just in terms of context.
38:26
Yeah, it's the same dynamic, right?
38:28
There's a new person that comes in.
38:30
She's really good at what she does, but no one's taking her seriously, least of all Maurice Wilkins, because he didn't get the memo that this is someone that you need to take seriously as an equal.
38:40
Right.
38:40
Right.
38:41
Right.
38:41
Right.
38:42
So at the time, they both get into King's College.
38:46
Maurice Wilkins is already there.
38:48
He's established there.
38:50
Rosalind Franklin is a new researcher.
38:53
And they start researching DNA.
38:56
They get these samples from Rudolf Signer in Austria.
39:00
And this guy, Rudolf Signer, is...
39:04
An incredible DNA experimentalist.
39:08
And what he's really good at is getting pure samples of DNA.
39:13
Okay.
39:13
Okay.
39:14
And we've got pure samples of DNA that are coming in from this guy all the way from Austria.
39:20
Okay.
39:21
Right?
39:23
They're originally obtained by Wilkins, but now because Rosen and Franklin is kind of this equal player, she's getting samples too.
39:30
And these are very precious because it's really hard to extract DNA.
39:34
Signer's found some secret formula to do it.
39:38
He found the Krabby Patty secret formula.
39:39
Yeah, yeah, yeah.
39:40
And he's not telling anyone how he does it, but he's like, I'll give you my samples.
39:44
Just like, you know, cite me in your paper.
39:47
A little quid pro quo.
39:48
Yeah, yeah.
39:49
And then we'll do it.
39:51
So Rosalind Franklin, she's incredible at x-ray crystallography, which is taking pictures with x-rays.
39:56
Yes.
39:58
She builds her own camera apparatus, and she starts doing humidity-controlled photographs of DNA.
40:04
Okay.
40:05
And she actually starts creating the best pictures there are ever of DNA.
40:10
Morris, eat your heart out.
40:11
Yeah.
40:13
Rosalind Franklin is just incredible.
40:15
Her and her PhD student, Raymond Gosling, are just incredible at taking pictures of DNA.
40:20
Ryan Gosling, no relation?
40:22
No relation.
40:23
Oh, maybe.
40:24
I don't know.
40:24
But in this case, Raymond Gosling is learning from Rosalind Franklin.
40:28
So she has an underling, right?
40:31
And they're coming in and they're just crushing.
40:32
They're just crushing.
40:33
Crushing the high quality capture using x-ray crystallography of DNA.
40:38
And it's just like...
40:40
Yeah, and the personalities are crashing because Rosalind Franklin is very, you know, she's a woman in science.
40:45
And at the time, you got to be confrontational.
40:48
Yeah, you got to be tough.
40:49
You got to be tough.
40:50
You got to be tough.
40:50
Maurice Wilkins is this really shy guy, you know.
40:54
And so even personalities are crashing.
40:56
And he always got what he wanted in his life.
40:57
Yeah, yeah.
40:57
And now all of a sudden.
40:58
Because of being smart and all of a sudden this tough, you know, charismatic, you know, attitude.
41:02
He doesn't know what to do.
41:03
Exactly.
41:04
Yeah.
41:04
Okay, so that's the situation at King's College in London.
41:08
Understood.
41:08
Now let's go to Cambridge in the Cavendish lab.
41:11
Again, we're in 1951.
41:12
Mm-hmm.
41:14
These are happening simultaneously.
41:17
Simultaneously, James Watson moves there to Cavendish Lab.
41:21
He had just come out of a PhD in Chicago.
41:24
He had done a postdoc at Copenhagen.
41:26
And there in Cavendish Lab, he meets Francis Crick.
41:29
At the time, the Cavendish Lab, the director was Lawrence Bragg.
41:34
Lawrence Bragg is very famous for being the youngest Nobel Prize winner of all time in the sciences.
41:40
In the sciences.
41:41
In the sciences, right?
41:42
He won...
41:44
In 1915, at the age of 25, that's unreal.
41:49
Unreal.
41:49
Physics.
41:50
That's... Physics.
41:52
Yeah, this is a really, really interesting story, okay?
41:55
So he won it with his dad, William Bragg.
41:58
William Bragg and Lawrence Bragg won it together.
42:02
That's crazy.
42:03
Okay?
42:04
They're also the only...
42:04
They're the only LeBron, Bronny, James...
42:07
Yeah, to win at the same time.
42:09
Niels Bohr and Niels Bohr's son also won, but at separate.
42:12
At separate times.
42:13
At separate times.
42:14
That doesn't matter.
42:14
This is the same prize going to father and son duo.
42:17
We have a bunch of NBA players who have sons that play.
42:18
Yeah.
42:19
No one cares about that.
42:19
Yeah, yeah, yeah.
42:20
But you play on the same team at the same time?
42:23
Yeah.
42:24
So this is William and Lawrence Bragg.
42:26
That's cool.
42:27
They won for developing X-ray crystallography.
42:31
Basically, the idea of X-ray crystallography is you've got some crystal, let's say, which is a bunch of electron density maps, right?
42:38
You've got electron densities here and here and here where the atoms are.
42:42
An X-ray comes in.
42:43
Remember, the X-ray has a wavelength that is about the size of the atomic spacing, about one angstrom.
42:50
So what you can do is when the X-ray interacts with that crystal, it's going to constructively interfere and destructively interfere, meaning it's going to add up
42:59
and it's going to cancel out.
43:01
So at certain angles, it's going to add up, and you're going to get a bright spot.
43:05
At other angles, it's going to cancel out, and you're going to get nothing, right?
43:10
By looking at the angles...
43:13
Of where stuff adds up and where stuff cancels out.
43:18
You know, by looking at the angle, what I mean is you can rotate this crystal and keep shooting x-rays.
43:22
Right, right.
43:23
So I'm shooting a beam.
43:25
A beam.
43:25
Of x-rays.
43:26
Of x-rays.
43:27
At a crystal.
43:29
And then it's going to go through that crystal.
43:31
And on the other side.
43:33
I have a photographic plate.
43:34
I have something that I'm going to track.
43:36
And I can move the crystal around, and I'm going to get a different map based on how.
43:44
And that map allows me to actually then reconstruct what the crystal is, even though the map is like a 2D structure.
43:52
But because I rotate, and then I can reverse engineer.
43:55
Yeah, yeah, yeah.
43:57
In technical terms, you're getting a kind of Fourier transform in frequency space of like what frequencies at what angles are doing what.
44:05
And then from that, I can then back calculate.
44:08
Right.
44:08
Right.
44:09
And the funny thing about this, right?
44:12
You think Lawrence Bragg and William Bragg, father-son duo, sounds like Nepo baby.
44:17
Yeah.
44:17
Sounds like a Nepo baby, right?
44:20
Lawrence Bragg, who's the son, is actually the guy who came up with this technique.
44:25
No way.
44:26
Yeah.
44:27
His dad, William Bragg, was in charge of the lab at the time, and he set up the experimental apparatus.
44:33
But Lawrence Bragg is the guy who came up with the mathematics and the equations for it.
44:37
That's incredible.
44:38
And when his dad, William Bragg, reported their results at the meetings and in a paper, he gives credit to his unnamed son saying that this person...
44:51
My son came up with the equation, but the son is not a co-author on the paper.
44:57
And this is something that, like, Lawrence Bragg had to deal with for the rest of his life.
45:02
It was kind of like a trauma that he got from his dad.
45:04
No way, bro.
45:06
You're telling me.
45:07
Dude, it wasn't.
45:07
Yeah, dude, this is.
45:09
He's not a Nepo baby.
45:11
The dad is a Nepo dad.
45:13
You know who this is?
45:14
There's a viral story right now about Simon Cowell, the, like, judge from American Idol or whatever.
45:19
Yeah, yeah, yeah, of course.
45:20
he's come out in public in the last two weeks and said, my son is going to get none of my whatever, $500 million empire.
45:29
Zero.
45:30
All my money is going to go to charity, and he's going to have to figure it out.
45:34
And it's not quite the perfect analogy, but the dad basically took the son's work and was like, oh,
45:41
I guess I'm the only named person.
45:43
Yeah.
45:43
Oh, that's nice.
45:44
That's convenient.
45:45
Yeah.
45:45
I mean, I wouldn't say that because with the Simon thing, at least Simon is the guy who like did the thing.
45:52
The thing.
45:52
He did the thing.
45:53
This is Lawrence Bragg actually came up with x-ray crystallography.
45:57
His kids work.
45:57
He put it in the paper and said, ah.
46:00
My name's on it.
46:00
Yeah.
46:01
Yeah.
46:02
He wasn't even a co-author.
46:04
They both got the Nobel Prize.
46:06
But to be honest, only the son should have gotten the Nobel Prize.
46:10
The dad just had this name on the building.
46:12
Yeah.
46:13
He just had the facilities.
46:14
Yeah.
46:14
So he was a Nepo dad.
46:15
I don't think you have the facilities from that brother.
46:17
At this point, Lawrence Bragg is clearly extremely talented.
46:21
And at this point, he is the director of the Cavendish Lab for good reason.
46:25
At 25, he wins a Nobel Prize.
46:27
He's astute.
46:28
And he wants – he's been using the Cavendish Lab to create X-ray crystallography of a bunch of crystals.
46:37
They're just getting into biological compounds, creating protein crystals, and finding the structure of those.
46:44
He really wants this.
46:46
He really wants the DNA structure to be in England.
46:52
Okay?
46:52
Okay.
46:52
In Cavendish.
46:53
Okay?
46:54
Okay.
46:54
Okay.
46:55
I see what you're doing.
46:55
Right?
46:56
I see what you're doing.
46:57
And now, so he hires Francis Crick.
46:59
Francis Crick is a physicist.
47:01
And at the time, Francis Crick, he starts studying with a bunch of other colleagues at the time.
47:07
He starts studying just extra crystallography in general.
47:11
And he's asking, what would extra crystallography look like?
47:14
Yeah.
47:15
for different types of molecules.
47:17
Specifically, he's trying to ask, what would a helical molecule look like in an x-ray photograph?
47:23
Helical meaning helix?
47:24
Helix meaning a spiral.
47:26
A spiral molecule, I subject it to x-rays.
47:29
What is it going to look like?
47:31
He comes up with the Cochran Crick Vand theory with his two colleagues in 1952, and he publishes this paper.
47:38
And what it shows is that the scattering amplitude, like where the dark spots and the light spots should be, they should come up in X.
47:47
They should have these spots.
47:48
Mm-hmm.
47:49
And they should have the cross shape as a signature of a helix.
47:54
The angle of the cross tells you what the pitch of the angle is of that helix, right?
48:00
And things like that.
48:00
So they came up with a formula for if you're looking at a helix object.
48:05
Yeah.
48:06
And I have the photograph from the x-ray.
48:08
What would that tell me about the structure of the helical object?
48:11
Got it.
48:11
It's kind of like a dictionary or like a translation between a results list and what is the interpretable meaning of the raw results.
48:22
Exactly.
48:23
So Watson at this time moves there after a PhD in Chicago, postdoc in Copenhagen, and he strikes up an immediate friendship with Francis Crick.
48:33
They think very alike in terms of these words.
48:36
scientific problems.
48:38
They're very much alike, okay?
48:39
So they start working on the DNA structure with whatever information that they have.
48:43
We're going to need a photo like that on Princeton's campus in black and white.
48:46
Yeah.
48:47
In the whole... Easy.
48:48
We're going to need one of those.
48:50
Yeah, we're definitely going to need one.
48:52
Yeah.
48:53
So this is sort of setting up that situation, right?
48:58
Cavendish versus... Cavendish, you've got these theorists and these X-ray crystallographers that are trying to figure out what an X-ray crystall...
49:06
picture would look like and then in king's college london they're the guys that are actually taking the photos right right
49:12
Okay, so you have the people taking the pictures, and then you have the people creating the framework for the interpretation of the pictures.
49:19
Yes.
49:20
And they're both kind of cooking.
49:21
They're both kind of cooking, right?
49:23
At the same time.
49:23
Yes, and they're cooking at the same time, and they're kind of competing against each other.
49:26
Because they want to be, each one wants to be first.
49:29
For the whole thing.
49:29
They realize what this is.
49:32
Right, yeah.
49:33
Everyone knows what this is.
49:34
The treasure map was already created.
49:36
Yes.
49:36
They know that there's a city of gold.
49:38
Yes, yes, and they're trying to find it, right?
49:41
Franklin and Gosling.
49:43
Now we're back in King's College, London.
49:46
What they figure out is there's actually two different types of DNA in the sample that they got.
49:51
Okay.
49:52
Okay?
49:52
There's A-DNA and B-DNA.
49:55
And it has to do with two different types of humidity.
49:58
Okay?
50:00
Something that's super dehydrated is called A-DNA.
50:03
And that's what Rosalind Franklin was really after.
50:06
And then there's something that has a bunch of humidity, a bunch of water molecules there.
50:10
And that's the B-DNA.
50:11
Correct.
50:12
The way they're doing this is actually incredible.
50:14
They take single bits of DNA, like strings, okay?
50:18
And they pull these wires like spider webs.
50:24
And they put it in front of their x-ray machine.
50:27
And they take photographs with the x-ray machine.
50:30
And the exposures are something like 60 hours.
50:33
They're exposing this thing.
50:34
Because it's a tiny little thing, right?
50:36
So you need a really long time exposure to capture all of that information.
50:40
That makes sense.
50:41
Right?
50:42
So there's two different types of DNA that they're looking at.
50:46
Franklin is looking at both.
50:47
She gives an internal talk at King's, okay, explaining that there's these two different types.
50:53
The phosphates, the phosphate groups that I was talking about in those building blocks, those phosphates lie on the outside.
51:00
And there's some kind of helical structure that they've already found because phosphates.
51:05
They see these X's, right?
51:07
The stuff that Francis Crick was talking about.
51:09
They've already seen these X's.
51:10
So they're seeing a helical form.
51:15
Rosalind Franklin gives a seminar in King's College where she's talking about her work.
51:22
James Watson is in attendance in that seminar.
51:27
So the point is we have someone from this block and someone from that block.
51:31
They're both trying to be the best.
51:32
Yeah.
51:33
And then so Franklin on her block is like, I'm going to preach the gospel.
51:37
Yeah.
51:38
I'm going to do the actual experimental work.
51:40
And then Watson rolls up.
51:42
Watson rolls up.
51:43
He's in the back of the seminar.
51:44
He's kind of peeping game.
51:45
He's like, what's going on over here?
51:47
Yeah.
51:50
And he goes to the seminar.
51:51
Okay.
51:51
He's extremely excited.
51:52
He comes back to Cavendish.
51:54
Yeah.
51:54
He goes to Crick.
51:56
And he's like, this is all the stuff that they were talking about in the seminar.
51:59
He misremembers what happened in the seminar.
52:02
He didn't have a voice memo.
52:03
No, he didn't have the chemistry background, really.
52:07
Oh, to understand what was going on.
52:09
And internalize.
52:10
So he tells Francis Crick about all these things.
52:14
They get to working.
52:16
They create a model.
52:17
And at that time, Watson and Crick were really...
52:21
into making lego models these are like little stick figurine models of the they're like okay this is what the purine looks like it's a hexagon with these little sticks and the and the stick represents a hydrogen and the hexagon represents carbon ring and so on and so forth so they start creating this model and they think they have a model okay it's it's a triple helix there's three strands that are going out the phosphates are on the inside because he misremembers that but he's like really excited
52:49
He's like, oh, this might work So the Cavendish group Called the King's London The King's College group To come on down, get your car, come on down Check it out So Rosalind Franklin rolls up Demolishes them Okay In the presence of Lawrence Bragg Who's the director of Cavendish She's like, this is wrong This is wrong, this is wrong This is just stupid Laughter
53:19
Right.
53:19
And in Watson's garbled account, they've built this three-stranded helix and the data contradicts what the model they've built.
53:32
Cavendish is embarrassed.
53:35
Embarrassed?
53:35
Embarrassed.
53:36
Okay.
53:36
Lawrence Bragg is like, you need to stop.
53:40
This is in 1951.
53:41
You're making us look bad?
53:42
Yeah.
53:43
Yeah.
53:44
Stop it.
53:44
Stop it.
53:45
So Lawrence Bragg is like, this is, no.
53:48
This is not what we do in Cavendish.
53:50
Right.
53:51
One of the most, like, again, one of the most legendary.
53:54
Yeah.
53:54
This guy's a legend.
53:55
He won the Nobel Prize at 25.
53:57
He's telling you to stop.
53:58
He's in charge.
53:59
Stop.
54:00
They stop.
54:01
Okay?
54:01
They stop.
54:02
In 1951, they stop.
54:04
This is incredible.
54:05
It's actually incredible.
54:07
Then.
54:07
Okay.
54:09
The King's College group still keeps going on.
54:11
They still keep collecting data.
54:15
In 1953, early 1953, they get wind of a guy named Linus Pauling.
54:21
When you say they, who?
54:23
This is both King's College.
54:26
And Cavendish.
54:26
And Cavendish.
54:27
The Brits.
54:28
Okay, the Brits.
54:29
The Brits get wind of the Americans.
54:31
The Americans.
54:32
Okay.
54:33
Because Linus Pauling at Caltech.
54:37
Yeah.
54:37
Yeah.
54:38
has just discovered the structure of the alpha helix.
54:42
The alpha helix is a fundamental building block of proteins.
54:47
Okay.
54:48
There's a helical structure that almost a lot of proteins have this helical structure.
54:54
Okay.
54:54
That...
54:55
It's called a secondary structure that is used to build the tertiary big 3D structure.
55:02
Okay.
55:02
You build a bunch of these alpha helixes together and you make whatever protein you want.
55:08
It's a single Lego block that makes the thing you want to make of your Lego.
55:11
Exactly.
55:12
Exactly.
55:12
Right?
55:13
And Linus Powelling comes out with this manuscript of the alpha helix.
55:20
He's incredibly good at chemistry, trained under Neil's board.
55:25
Dangerous.
55:26
Dangerous.
55:26
Everyone's sweating over him.
55:30
And he comes out with this.
55:31
The Cavendish guys are like, wow, he just scooped us because they were working on the same thing.
55:36
Okay.
55:36
Okay.
55:37
Okay.
55:38
And at the same time, in 1953...
55:42
Linus Pauling comes out with his version of the DNA helix.
55:46
Okay.
55:47
It is the same triple helix.
55:48
Triple helix.
55:49
Very similar.
55:50
This three-stranded helical structure that Watson and Crick had done that was wrong.
55:55
Correct.
55:55
Right?
55:56
Because he has limited data.
55:57
He doesn't actually know the data.
55:59
Because he doesn't have the source.
56:00
Yeah.
56:01
He hasn't been to King's College.
56:03
If he was at that seminar, he's a chemist.
56:05
Yeah.
56:06
He would have figured it out.
56:07
So the point is that at King's, they were getting source data because of their expertise in being able to do the x-ray crystallography.
56:15
Exactly.
56:16
And so they had basically the best map for where the treasure is.
56:20
Yes.
56:21
And Watson and Craig only were able to get to it because they were local.
56:25
They were local.
56:26
Down the road, whatever, and were able to see it.
56:28
Now at Caltech, Pao Ling, he...
56:32
He is intuiting this without having a really good map.
56:36
No, no.
56:37
He's intuiting it from published data.
56:39
Right, right.
56:39
From stuff that's already out.
56:41
Right, right.
56:42
But this is a huge red flag for everyone in Great Britain.
56:47
Yeah, they're like freaking out.
56:47
It's like, oh, no, no, no, Linus Pauling is on it.
56:50
Yeah, the Americans are coming.
56:51
We got like a few months tops.
56:54
Right, right.
56:54
We're in the final lap of this race.
56:57
Okay?
56:57
No more pit stops.
56:59
This is it.
57:00
Whatever tires we have now, we need to get to the finish.
57:04
Because otherwise, Linus Pauling is like Max Verstappen.
57:09
Yeah, he's coming.
57:10
He's coming.
57:10
And if he figures it out, he's going to figure it out very soon.
57:14
This guy...
57:15
has the credentials, trained under Niels Bohr, knows quantum mechanics, like discovered the pi bond, which is like the way in which the quantum mechanics of how atoms bond to each other.
57:27
Like he's done incredible work, okay?
57:29
This guy is dangerous.
57:31
If he has a little bit more information, he's going to do it.
57:34
He's going to do it.
57:35
Okay.
57:36
So Watson actually gets wind of this manuscript because Linus Palin's son brought an early version of the manuscript to Cambridge.
57:47
I love 19 or mid 20th century.
57:51
Yeah, because there's no online, right?
57:53
It's not, it's not like just, it goes on nature website.
57:56
And then like, so, so physically Linus Pauling's son brought the manuscript to the Cavendish folks because he knew that they were working on it too.
58:05
And they, they might want to see it.
58:06
Right.
58:07
Watson looks at the manuscript and he's like, okay, this guy's clearly wrong because he's doing the same mistakes that I did.
58:12
But this guy's Linus Pyle.
58:14
Yeah.
58:14
Okay.
58:15
I am concerned.
58:16
Yeah.
58:16
Yeah.
58:17
So he goes to King's College.
58:19
Okay.
58:20
And he tries to show the manuscript to Rosalind Franklin and Maurice Wilkins.
58:25
He's like, guys, we need to set our differences aside.
58:27
Differences aside.
58:29
This is like in LA, it would be like two gangs in LA in different parts, right?
58:34
The blood and the curse being like, look, we have a bigger enemy right now.
58:37
Can we just have moratorium for a moment?
58:40
Yeah, like New York is coming up.
58:42
New York is coming.
58:43
Yeah.
58:44
50 just dropped Get Rich or Die Trying.
58:47
Yeah, it's going to be a problem.
58:49
It's going to be.
58:50
Yeah.
58:50
He's hooked up with Jimmy Iovine, Eminem, and Dr. Dre.
58:56
Yeah, exactly.
58:58
So this is when Watson goes to King's College.
59:00
Okay.
59:01
And he's like, look, we got a problem here.
59:03
Yeah, yeah, yeah.
59:04
He goes to Rosalind Franklin.
59:07
This is where things get sketchy.
59:08
Okay.
59:09
He goes to Rosalind Franklin's office.
59:11
She's not in there.
59:12
Okay.
59:14
I guess the door is open.
59:15
Okay.
59:16
This is where, you know, I don't know if the door is open or not.
59:20
Okay.
59:21
Okay.
59:22
He just goes in.
59:23
Rosen Franklin walks up on him in her office looking through her stuff.
59:30
Yeah.
59:30
No, no, no, no.
59:31
Never a good look.
59:33
No, no, no, no.
59:33
Okay.
59:34
Never a good look.
59:35
At this point, this is 1953.
59:38
Rosen Franklin has already had it with Maurice Wilkins.
59:42
because of the dynamic where they're just not getting along.
59:45
So, Rosen Franklin is about to leave in about six months to go to another university.
59:50
Right.
59:51
And the head of the group
59:55
has told Rosalind Franklin to give up all of the resources and all of the research that she's been doing on DNA to Maurice Wilkins, hand it over, right?
1:00:05
Because you're no longer going to be part of this group.
1:00:07
All of that is going to go to you.
1:00:10
Gosling, who is the PhD student, is also now going to go under Maurice Wilkins because he needs to finish his PhD.
1:00:16
Yes, he got to do what he got to do.
1:00:18
And in this whole time, Watson is in her lab just like...
1:00:23
Looking through her stuff.
1:00:23
Rifling through papers.
1:00:25
Right?
1:00:25
I mean, the guy is desperate.
1:00:27
I get it.
1:00:27
But my guy.
1:00:28
No, no.
1:00:29
That's like, what are you doing?
1:00:31
Okay.
1:00:32
Rosalind Franklin catches him.
1:00:33
It's like, what are you doing?
1:00:35
They have a little, you know, tiny argument.
1:00:38
Watson's like, well, I wanted to show you this paper from Linus Powling.
1:00:42
You know, we're on the same team.
1:00:44
Roland Franklin is not having it.
1:00:46
You were just in my office.
1:00:49
And now all of a sudden, like we're on the same.
1:00:51
No.
1:00:52
Okay.
1:00:52
Get the hell out of my office.
1:00:55
Okay.
1:00:56
He's like, fine, I'll go.
1:00:58
Down the hall, he goes to Maurice Wilkins' office.
1:01:01
Maurice Wilkins is in his office.
1:01:03
He goes to Maurice Wilkins.
1:01:04
He's like, maybe I can talk to this guy.
1:01:05
He's like, look, this is the manuscript, Linus Powling.
1:01:08
He's coming at it.
1:01:11
Wilkins has all of the data from Rosalind Franklin.
1:01:15
Right.
1:01:15
Right?
1:01:16
Because the transfer is happening.
1:01:17
Right.
1:01:18
And Wilkins shows him the famous photo 51.
1:01:21
Okay.
1:01:23
Okay.
1:01:23
This is the famous photo of BDNA.
1:01:26
This is an extremely famous photo of the X, the characteristic X that gets you the helix.
1:01:32
Yes.
1:01:33
It's so well done.
1:01:35
This is the photo that Ryan Gosling took at.
1:01:38
Not Ryan.
1:01:39
No, not Ryan.
1:01:40
What was his name?
1:01:41
Raymond.
1:01:41
Sorry.
1:01:41
Raymond Gosling.
1:01:42
I just screwed up on that.
1:01:43
This is the photo.
1:01:44
This is the photo that Raymond Gosling took.
1:01:46
Incredible detail.
1:01:48
Yeah.
1:01:48
Right.
1:01:49
The spots.
1:01:50
The you can tell the angle so you can tell the pitch of the helix.
1:01:53
Right.
1:01:54
You can tell that it's a helix because of the X.
1:01:56
The distance between the spots tells you how far apart each nucleotide is.
1:02:03
For people who are listening and not watching, I want to describe what we're seeing here.
1:02:06
So there's two photos next to each other.
1:02:09
There's sort of a black and white.
1:02:12
If you've ever looked at photos of people taking a picture of a Petri dish, like in any science context, that's what it looks like on the left, and then on the right is a 3D recreation of the structure.
1:02:21
Of what it would look like.
1:02:24
The point is there's a 2D black and white image.
1:02:27
Yes, and it's rich in information.
1:02:30
And you can derive the three-dimensional double helix from a variety of the angle.
1:02:39
The angle, the spacing of the dots.
1:02:41
All of these things in this black and white.
1:02:43
The fact that there's nothing in the middle means that one strand goes one way and the other strand goes the other way.
1:02:49
So it's anti-parallel.
1:02:51
Right?
1:02:52
There's so much information in this.
1:02:54
And Wilkins shows Watson this photograph.
1:02:57
Watson is immediately enamored.
1:02:59
He tries to memorize this photograph.
1:03:01
They were ops.
1:03:01
They were ops.
1:03:03
Kind of, because they were kind of competing with each other.
1:03:05
And then it came to a situation where the enemy of my enemy is my friend.
1:03:09
Yes.
1:03:10
Right?
1:03:10
Because Pao Ling showed up.
1:03:12
Yeah.
1:03:12
And we're like, at the end of the day, we're not going to let New York win.
1:03:15
The Americans.
1:03:16
We're not going to let Caltech win.
1:03:18
Right, right.
1:03:18
So in the rapper analogy, they already won.
1:03:21
With Alpha Helix.
1:03:22
Right.
1:03:24
So now Maurice is like, okay, let me show you what we got.
1:03:28
Here's what we got.
1:03:28
She's leaving anyway.
1:03:29
Yeah.
1:03:30
Yeah, exactly.
1:03:32
Exactly.
1:03:33
Let me show you what we got.
1:03:33
Okay.
1:03:35
Watson immediately heads back to Cambridge to tell Crick about this photo that he saw.
1:03:39
He saw it.
1:03:40
Right.
1:03:41
At the same time, Franklin publishes an internal report, which is something that institutions do where they talk about the research that they've done over the past year.
1:03:50
And it's an internal Medical Research Council report and King's College report that...
1:03:58
shows all of the, that shows this photograph along with a lot of the determination that Franklin has done on the photograph because she has the original, right?
1:04:07
She has that original print.
1:04:08
So she can measure the distance between those black spots and say that, okay, these things are 3.4 angstroms apart.
1:04:16
Each turn of the helix is 10 nucleotides, 34 angstroms.
1:04:21
And all of these little details.
1:04:23
This is a Medical Research Council report.
1:04:26
Crick gets...
1:04:28
wind of this and gets a copy of it.
1:04:30
Of course he does.
1:04:30
Okay.
1:04:32
All of this stuff is happening without Franklin knowing.
1:04:36
That's the key.
1:04:37
It's not with consent.
1:04:39
You're right.
1:04:39
Informed consent.
1:04:40
Right.
1:04:41
Right.
1:04:41
Okay.
1:04:42
And especially in this world at when the stakes are as high as they are.
1:04:47
It is a very meaningful...
1:04:47
They're working on DNA.
1:04:48
Yeah, this is a very meaningful...
1:04:49
They're working on the physical substrate of genetics.
1:04:53
I mean, obviously, they're working on a Nobel Prize level.
1:04:56
Everyone knows.
1:04:57
Everyone knows.
1:04:58
That this is what's happening.
1:04:59
The treasure map.
1:04:59
We know.
1:05:01
Right?
1:05:02
And so, Watson and Crick get to work.
1:05:04
They have all of this information.
1:05:06
Right.
1:05:07
They go up to Bragg, and they're like, look, Bragg...
1:05:11
Linus Powling is working on it.
1:05:13
We have all this information.
1:05:14
We need you to let us work on this again.
1:05:17
Because in 1951, he's like, stop embarrassing us.
1:05:20
Stop embarrassing us.
1:05:22
Bragg does not like Powling.
1:05:26
Ah.
1:05:28
Okay?
1:05:31
I love it.
1:05:32
It's such a human story.
1:05:33
Yeah, it's such a human story.
1:05:35
Bragg does not like Powling.
1:05:36
So he's on board.
1:05:37
Okay?
1:05:38
So he's like, do what you got to do.
1:05:40
Right, right, right.
1:05:41
Don't screw it up.
1:05:42
This time, do not embarrass me again.
1:05:45
I want this for Cavendish.
1:05:48
Okay?
1:05:48
Yeah.
1:05:49
This is ours.
1:05:50
Yeah.
1:05:50
You need to do it.
1:05:52
So, Watson and Crick go down to the machine shop.
1:05:55
They're like, boys, we're back in business.
1:05:57
I need you to make me little models of it so that we can tinker around.
1:06:02
They get these models of nucleotides, those base pairs that I was showing you earlier.
1:06:07
Yeah.
1:06:07
And they start trying to put them together in the way that they know now, right?
1:06:12
Things have to be anti-parallel.
1:06:14
The phosphates have to be on the outside.
1:06:16
The nitrogens and bases have to be on the inside.
1:06:18
It's still not quite working until their office mate, Jerry Donahue, looks at the bases that they're the Lego blocks that they're using to like do this.
1:06:28
And he's like, actually, you're doing it wrong.
1:06:33
Given the pH of the cell and the temperature of living organisms, the hydrogen there isn't actually going to be there.
1:06:41
It's going to be over here.
1:06:44
And Watson's like, oh, okay.
1:06:47
And then he goes back to the machine shop.
1:06:49
He's like, make me new ones.
1:06:50
And the new ones work out splendidly.
1:06:53
They fit like puzzle blocks.
1:06:56
Like that singular, subtle insight.
1:07:00
That subtle insight from his lab mate, Jerry Donahue, to turn from keto.
1:07:06
They exist in keto and amino forms and not in the enol form, meaning that the hydrogen was in the wrong place.
1:07:12
But now when the hydrogen is in the right place, the hydrogen of one is going to hydrogen bond with the nitrogen of the other or the oxygen of the other.
1:07:19
And you're going to create these weak bonds in the middle.
1:07:22
The other thing that was crazy was that when they –
1:07:26
had the A and the T and the G and the C, there was structural consistency because the A and the T is pairing two carbon rings with one carbon ring and two carbon rings with one carbon ring, meaning the distance between the backbones was going to be the same, right?
1:07:47
And there's a... You see?
1:07:50
You've got the C and the G. Yes.
1:07:52
Yes.
1:07:54
Those have three hydrogen bonds between them.
1:07:57
The A and the T have two.
1:07:59
In that case, that's a U, but same thing, right?
1:08:02
Yeah.
1:08:03
But notice that the distance between the phosphate backbone on the top and the bottom are the same.
1:08:09
So we're looking at an image where in the middle we have on the left the G and the C with three hydrogen bonds in the middle.
1:08:16
And on the right, the A and the...
1:08:19
I guess it's supposed to be a T?
1:08:20
Yeah, that's a U for the RNA, but it's the same structure.
1:08:23
It's a T with two hydrogen bonds.
1:08:26
And the point is, when you look at it at top to bottom, even though there's a difference in pair and number, the vertical distance is identical.
1:08:35
Yes.
1:08:36
Which means it can be a structure.
1:08:38
Which means it can be a structure.
1:08:39
It can be a Lego block where I can swap out A's and T's and A's and T's.
1:08:43
But the overall structure remains the same.
1:08:45
Yes.
1:08:46
So I've just created a code.
1:08:47
Yes.
1:08:48
Yes.
1:08:49
Where the Lego blocks themselves are different...
1:08:56
But when you extrapolate to the larger molecule, it fits and they're all the same, which means that whatever physics is happening here in this location, let's say there's more A's and less T's.
1:09:07
In that location, there's the other way around.
1:09:09
The physics is going to be the same.
1:09:10
The rope is going to look the same.
1:09:12
Yes.
1:09:13
Right?
1:09:13
Yes.
1:09:14
No.
1:09:14
The rope might be colored differently.
1:09:16
Right, right, right, right.
1:09:17
But the physics of the rope is going to be the same.
1:09:20
It's the aperiodic crystal that Schrodinger was talking about.
1:09:24
They finally now found the missing piece for what is required to actually create the physical structure of this aperiodic crystal.
1:09:33
Yes.
1:09:34
Which initially there was like, oh, it's a triple helix.
1:09:36
Because again, we have to remember there's no conception of this structure.
1:09:39
No, it's just all in the dark.
1:09:40
There's no concept of what the structure is.
1:09:44
Yeah, they're just trying to figure out what is going on.
1:09:46
They know that these are the building blocks, but they're like, does it go this way?
1:09:49
Does it go this way?
1:09:51
Are there three?
1:09:51
Are there five?
1:09:52
God.
1:09:53
And that one flip of the not eno form but the keto and amino form, that of the hydrogen, which creates the three and two pairing, which now is like that's how everything can now click together.
1:10:06
Yes.
1:10:06
And then this also explains chargas rules, right?
1:10:09
Yes.
1:10:09
Because now the A's and the T's are pairing and the C and the G's are pairing.
1:10:13
Because it's the two and the three hydrogen bonds as what creates – that's the reason why they're paired in that way.
1:10:19
Yes.
1:10:20
There's a physical understanding there, right?
1:10:23
And it's an incredible story, right?
1:10:26
That's good.
1:10:27
All of this stuff coming together because they hate the Caltech guy.
1:10:31
Look, I just want everyone to know California is still the best.
1:10:34
Yeah, yeah, yeah.
1:10:35
But like, they were scared.
1:10:37
They were scared.
1:10:38
And they were scared for a good reason because nothing's happened since.
1:10:42
So they were correct in their fear.
1:10:44
Dude, Linus Pauling was really scaring them.
1:10:47
So it's like, so now they finally figured this out.
1:10:51
April 1953.
1:10:52
Yes, okay.
1:10:53
Is when they decide, okay, we're going to publish this.
1:10:55
Okay.
1:10:56
Okay.
1:10:57
They have a triple publication.
1:10:58
Watson and Crick published their very famous molecular structure of nucleic acid, a structure for deoxyribonucleic acid.
1:11:07
It's just a two-page paper in nature.
1:11:10
No way.
1:11:11
It's a two-page paper in nature.
1:11:13
There's no experimental findings because they didn't do any experiments.
1:11:16
They just put it out.
1:11:16
They just put it out.
1:11:17
They're like, this is the structure.
1:11:18
They're going to work first.
1:11:19
Yeah.
1:11:19
Because we have to beat them.
1:11:21
So Wilkins, Stokes, and Wilson, they provided supporting evidence of the helical structure.
1:11:25
And then Franklin and Gosling Post had the third paper in the same issue, same issue of nature, back to back to back.
1:11:32
No way.
1:11:33
All three?
1:11:34
All three.
1:11:35
All three back to back to back had these papers, presented the empirical data with the famous photograph 51.
1:11:43
I'm going to need to get a copy of this April version.
1:11:45
Oh, I bet it's worth a lot of money.
1:11:47
I would love to have that on the wall.
1:11:50
Okay, so if you, audience, if you are currently in possession of the April 25, 1953 Nature triple publication of DNA –
1:12:01
please DM us.
1:12:03
Yeah.
1:12:03
If you know somebody that's in possession of that copy, please DM us.
1:12:08
Cause it will make a great addition as one of our first pieces on the wall.
1:12:13
We've now decided we're going to put,
1:12:15
The annals and history of science and great memorabilia on the walls behind us.
1:12:21
And this would be just absolutely incredible.
1:12:23
It's a single issue of nature that has all three of these publications.
1:12:26
That is so crazy.
1:12:27
Yeah.
1:12:28
That is so crazy.
1:12:29
They approached the editor of nature and they're like, this is... We got three things and they're these three.
1:12:36
And the editor of nature was like, yeah.
1:12:39
Obviously.
1:12:40
We got to put it together.
1:12:41
Yeah, we got to put it together.
1:12:42
And they put it back to back.
1:12:44
That's incredible.
1:12:45
Yeah.
1:12:45
This order, though, the fact that Watson and Crick were first, it sort of cemented that priority in the narrative, right?
1:12:52
Because there are the guys who came up with the structure.
1:12:55
Rosalind Franklin comes up with the empirical data that suggests that that structure is true.
1:13:00
But she didn't come up with the structure, technically.
1:13:02
Yeah, technically she did not come up with the structure.
1:13:04
She was incredibly close.
1:13:07
If you look at the laboratory notes, she has notes in her labs about how this has to be two strands.
1:13:13
They're anti-parallel.
1:13:14
All from her data.
1:13:15
Because she took the data.
1:13:16
And if Maurice didn't leak.
1:13:18
If Maurice didn't leak.
1:13:19
She could have had a little bit more time.
1:13:20
She would have had time.
1:13:21
And who knows?
1:13:21
Who knows?
1:13:22
Yeah.
1:13:23
But, you know, she was there.
1:13:27
She had the source.
1:13:27
She was there.
1:13:28
She was really the source.
1:13:29
Yeah.
1:13:29
And if you look at her notes, she didn't have the pairing, which was crucial.
1:13:33
That's the creepy.
1:13:34
That Donahue.
1:13:35
Yeah, yeah.
1:13:36
And she didn't have that guy who was like, no, it's not that form.
1:13:39
It's this other form, right?
1:13:40
And one of the other great things about Watson and Crick's paper is they say that it doesn't escape us that the replication mechanism is now obvious.
1:13:50
Because you've got a double helix.
1:13:53
You unzip.
1:13:54
Now there's a C here, you attach a G. If there's a T, you attach an A.
1:14:00
Because of the hydrogen bonding, which is unique, a 2 goes with a 2, a 3 goes with a 3, and the length constrains, the spacing of the ladder constrains that an A will not go with an A.
1:14:12
Even though an A and an A have...
1:14:14
two hydrogen bonds, it's going to be too wide for the latter.
1:14:19
That's a good point.
1:14:19
Right?
1:14:20
So it's obvious now, given the structure, how you would replicate this information, which was a huge deal.
1:14:27
Like, how can you have a molecule that does both, that stores and also is able to replicate really quickly?
1:14:33
Right.
1:14:33
Right.
1:14:34
Right?
1:14:34
Right.
1:14:36
It's an incredible story.
1:14:37
So now there's a shift in research.
1:14:39
Franklin, as I was saying, she moves to Birkbeck College, and she focuses on the tobacco mosaic virus.
1:14:45
She does incredible work on the tobacco mosaic virus with a colleague named Erin Klug.
1:14:50
Unfortunately, given that she was working with x-rays, it's...
1:14:54
Um, it's thought that the x-ray research actually contributed to ovarian cancer that she developed later on in life.
1:15:01
Not that much later.
1:15:02
She died actually in 1958 at the age of 37.
1:15:05
This is a photo of her when she was visiting California, um, in Yosemite.
1:15:10
And she had visited Berkeley to give some talks and UCLA to give some talks.
1:15:14
Um,
1:15:15
It's really unfortunate that she died so young at the age of 37.
1:15:19
Yeah, that's crazy.
1:15:20
And it was incandescently bright.
1:15:23
Yes, incredibly bright.
1:15:25
Incredibly bright.
1:15:27
And she figured out the structure of the tobacco mosaic virus.
1:15:30
Her colleague, Erin Klug, who was her subordinate at the time, went on to win the Nobel Prize for the tobacco mosaic virus.
1:15:37
So very, very likely that had she lived, she would have won the Nobel Prize.
1:15:41
Won the Nobel Prize.
1:15:42
for that as well um 1958 is when she dies four years later the nobel prize is awarded to james watson francis crick and maurice wilkins um obviously you can't give nobel prizes and actually john steinbeck won the literature prize there so he's he's in the in the group photo as well um obviously you can't give
1:16:06
the Nobel prize for posthumously, right.
1:16:10
And Rosalind Franklin was already four years passed away.
1:16:17
The problem is there is not a single mention of her in their Nobel lectures.
1:16:23
That's crazy.
1:16:23
That's crazy.
1:16:24
That's crazy.
1:16:25
Given, given photograph 51, like that is just insane.
1:16:29
Yeah.
1:16:29
You guys wouldn't have been, you would have been in the dark.
1:16:33
but for Maurice leaky ass.
1:16:36
Yeah.
1:16:36
Leaky Wilkins.
1:16:37
Leaky Wilkins giving you, for his own beef, that his personal attention is probably a non-zero driver opening the books up.
1:16:46
100%.
1:16:47
To a local competitor.
1:16:48
Yeah.
1:16:49
Right?
1:16:50
And so you can't not.
1:16:53
Yeah, you can't not say anything.
1:16:55
Nothing?
1:16:55
That's insane.
1:16:56
Nothing is crazy.
1:16:57
And Rosalind Franklin would have sort of,
1:17:00
gone under the radar.
1:17:02
But nowadays, whenever we think about DNA, I'll be honest, whenever people who know the story of DNA, if they know James Watson, they know Rosalind Franklin.
1:17:11
I mean, because of the resurgence of her persona and all of that happened because she was so wronged.
1:17:20
One, she was not given due credit in the Nobel lecture.
1:17:24
And then second, in 1968, James Watson publishes
1:17:29
The Double Helix, which is this book.
1:17:33
My dad bought this book.
1:17:34
It's in terrible condition because he bought this in the late 90s when he first came to America.
1:17:40
This is one of the first books that he bought, and he brought it all the way back to India, and we brought it back when we moved back.
1:17:46
The Double Helix was published in 1968.
1:17:48
It's a firsthand book.
1:17:53
memoir, first-person memoir about the scientific discovery.
1:17:57
It's unusual for its time because a lot of scientists didn't really talk about the human story.
1:18:01
But James Watson puts this out in print.
1:18:04
He wanted to get it published in the Harvard...
1:18:08
press.
1:18:09
But Francis Crick and Wilkins were like, no, we don't want that because they read copies of it.
1:18:16
And it was a lot of self-aggrandizing.
1:18:20
The other thing is he calls Rosie by her nickname.
1:18:24
He calls Rosalind Franklin by her nickname, Rosie, which at the time was actually a
1:18:30
No one said that to her face because she wasn't really a rosy personality, right?
1:18:36
As I was saying, she's a tough woman.
1:18:38
She's a woman in science and a man's field.
1:18:39
She's a tough woman.
1:18:41
So he's calling her rosy.
1:18:43
He's basically saying that Rosalind Franklin did not have the scientific expertise and the brain to figure it out on her own.
1:18:52
She didn't have the hutspa.
1:18:53
And yeah, and the men had to do it.
1:18:55
Yeah.
1:18:56
This creates a lot of tension among all of her colleagues.
1:19:00
And they're like, what are you talking about?
1:19:02
And then that's what starts this movement to be like, no, you're not going to get away with this.
1:19:06
We're going to start talking about Rosalind Franklin and her contributions.
1:19:10
Right?
1:19:13
That's so crazy given the context.
1:19:17
Because like...
1:19:19
Y'all were putting Legos together in the lab.
1:19:22
Yeah.
1:19:22
She was doing x-ray crystallography.
1:19:25
Yeah.
1:19:26
And actually got the key image that created the entire unlock for everything downstream.
1:19:33
Exactly.
1:19:34
And to not even just be able to...
1:19:36
Acknowledge?
1:19:37
Acknowledge that is weird, bro.
1:19:39
It's weird.
1:19:39
That's like weird.
1:19:40
It's really weird.
1:19:42
It's really, really weird.
1:19:43
It doesn't make your insight any less important.
1:19:46
No.
1:19:46
No.
1:19:47
Like, it didn't have to be anyway.
1:19:49
No.
1:19:49
Yeah.
1:19:51
That's crazy.
1:19:51
It's weird.
1:19:52
It's really weird.
1:19:54
James Watson goes on to be appointed the director of the Cold Spring Harbor National Lab.
1:19:58
This is a private, non-profit research institution.
1:20:01
It's kind of like the...
1:20:03
Institute for Advanced Study, but for biology and chemistry and biochemistry.
1:20:07
At the time, it was very small.
1:20:09
James Watson really transforms this into a research environment that is unparalleled.
1:20:15
And I will have to give him credit for that.
1:20:16
Cold Spring Harbor Lab today is one of the foremost great world institutions when it comes to cancer research, when it comes to genetic research.
1:20:28
They have eight Nobel Prizes to their name.
1:20:30
Oh.
1:20:30
For a single institution that is not a university.
1:20:32
That's not a university?
1:20:33
It's just like an institution.
1:20:35
It's pretty good.
1:20:36
BioArchive, which is the biology archive, is hosted by them.
1:20:41
Okay.
1:20:42
They discover telomeres, jumping genes, a bunch of other things.
1:20:46
Oh, we just talked about telomeres.
1:20:47
Yes.
1:20:48
In one of the two episodes ago.
1:20:49
Yeah, yeah.
1:20:50
So they've done a bunch of research, and James Watson was really one of the pioneer drivers of creating that institution.
1:20:56
So I have to give him credit for that.
1:20:58
Sure.
1:20:59
In 1990, he actually became head of the Human Genome Project before it was taken over by Francis Collins.
1:21:05
He left two years later because the NIH director at the time, Bernadine Healy...
1:21:11
was proposing acquiring patents on gene sequences, and he opposed any ownership of laws of nature.
1:21:19
So I have to give him credit for that too, because he said that genes are something that belong to humanity.
1:21:24
You can't patent something that is within me.
1:21:27
That sounds completely absurd.
1:21:29
So that's also really great.
1:21:32
In 1994, he goes back to Cold Spring Harbor, and that's where things get unhinged.
1:21:38
Starts getting old.
1:21:39
Maybe he starts thinking he's invincible.
1:21:41
Yeah.
1:21:42
We've seen that story before.
1:21:44
So in 2000, in Berkeley, Watson gives a lecture where he suggests there's a link between skin color and sex drive.
1:21:54
No way.
1:21:55
At Berkeley.
1:21:56
Berkeley.
1:21:57
Like of all institutions at Berkeley, you're going to say this shit?
1:22:01
I mean, Berkeley is like in the Oakland area of California, which is very diverse, very black.
1:22:09
Yeah.
1:22:09
And Berkeley is extremely liberal.
1:22:11
Yeah.
1:22:13
Like it's –
1:22:13
Because they have people around.
1:22:15
Anyway.
1:22:16
Yeah.
1:22:16
Yeah.
1:22:16
And he hypothesizes that dark skinned people have stronger libidos.
1:22:20
That's the dumbest thing.
1:22:21
And the lecture argues that like melanin, which is the thing that's giving us the brown and black color.
1:22:27
Yes.
1:22:28
That's somehow a derivative of a compound that boosts sex drive.
1:22:33
And then, quote, he says, that's why you have Latin lovers.
1:22:37
Yeah.
1:22:38
You've never heard of an English lover, only an English patient.
1:22:44
Bro, what are you doing?
1:22:46
I cannot cringe any hard.
1:22:48
That's pretty wild.
1:22:49
That's pretty wild.
1:22:50
And that's not even the start, dude.
1:22:51
Okay.
1:22:52
These are some other quotes from him.
1:22:54
Whenever you interview fat people, you feel bad because you know you're not going to hire them.
1:23:00
And then he doubles down later and he says that thin people are smarter.
1:23:05
Yeah.
1:23:06
What are you talking about?
1:23:08
Why is this consistent?
1:23:10
Anyway.
1:23:10
Yeah.
1:23:10
You know, earlier in the episode when I said like, you know, this guy's controversial.
1:23:15
Yeah.
1:23:16
It's more than controversial.
1:23:17
Yeah.
1:23:17
Right.
1:23:18
Yeah.
1:23:18
Like the behavior was not only problematic during the discovery.
1:23:24
Yeah.
1:23:24
Yeah.
1:23:24
During the discovery.
1:23:25
He's already like sketch.
1:23:27
Then afterwards trying to like rewrite history.
1:23:31
Yeah.
1:23:32
act also sketch also sketch and now you're just like just pointing fingers at everyone now he's just saying nonsense right and i just want to read you some of the other crazy stuff you said uh people say it would be terrible if we made all girls pretty i think it would be great bro i just just stop talking i just so at this point at this point cold spring harbor suspends any affiliation to him wait
1:23:58
Oh, yeah, he doesn't even leave the Indians alone.
1:24:01
So this is what he said about the Indians.
1:24:03
There's one more.
1:24:04
Yeah, there's one more.
1:24:05
I got to keep going.
1:24:05
So he doesn't leave the Indians alone.
1:24:08
He's like, Indians are servile because of selection under caste endogamy.
1:24:14
Caste endogamy meaning castes marry within castes in the Hindu tradition.
1:24:20
And because of that, we're servile.
1:24:22
Nothing to do with maybe the 200 years of colonialism that was subject to us by the British.
1:24:28
We'd love to never touch on that.
1:24:29
Yeah, yeah, yeah.
1:24:30
It doesn't matter.
1:24:31
And the other thing is, look, with the caste system, it's like he's only basically interacted with the top tier of caste, probably.
1:24:41
Because the way the caste system works is the lower caste haven't really had the kinds of opportunities that the higher caste have because of the messed up nature of the caste system.
1:24:49
Correct.
1:24:49
So...
1:24:50
The stereotype doesn't, the argument doesn't even make sense.
1:24:53
It makes sense.
1:24:54
100%.
1:24:55
Because he's interacting with the, you know, it's like at least be scientific in your bigotry.
1:25:01
Africans are less intelligent than Westerners.
1:25:04
Watson said his intention was to promote science, not racism, but some UK venues canceled his appearance.
1:25:11
Yeah.
1:25:11
He was going on a book tour and the UK canceled his appearances.
1:25:15
Um,
1:25:16
In 2007, the Cold Spring Harbor Laboratory suspended any affiliation.
1:25:22
Even though he was the father.
1:25:23
He basically created it.
1:25:26
I mean, he's doubling down on this stuff.
1:25:27
He's not even apologizing.
1:25:29
He's just saying that, no, this is how it is.
1:25:31
And there's this YouTube page called Web of Stories.
1:25:37
It's one of my favorite YouTube stories.
1:25:39
channels big plug for web of stories yeah it really is because what they do is they they have these long-winded interviews with the titans of science so they have james watson but they also have freeman dyson for example hans beta um
1:25:53
They also have Edward Teller.
1:25:56
Yeah.
1:25:56
And they're just – it's just stream of consciousness about their life.
1:25:59
Yeah.
1:25:59
Okay?
1:26:00
The ones from Hans Bethe and Edward Teller, I really enjoy.
1:26:03
They talk about their time in Manhattan Project and all of the physics that they did.
1:26:06
They talk about their experience with Niels Bohr and things like that.
1:26:11
Right.
1:26:11
So they also did James Watson because he is a titan of science, let's be honest.
1:26:15
The 20th century, he discovered DNA, the structure of DNA.
1:26:18
He got there in weird ways, but at the end of the day, he's the one who got there first.
1:26:22
He won.
1:26:22
Yeah, he won that race.
1:26:23
Max Verstappen, he might be a little bit of a dirty race, but he wins.
1:26:27
Yeah, he wins.
1:26:27
And so there was this one clip where he's asked about Rosalind Franklin.
1:26:33
The first thing he says was, I can't give...
1:26:36
I can't give a lecture anywhere without a few questions about Rosie.
1:26:39
It's like, yeah, no, because you stole her data.
1:26:44
Like, okay, so he's clearly already not in a good mood because the interviewer is asking him about Rosalind Franklin.
1:26:51
And he thinks that Rosalind Franklin doesn't deserve all of this attention.
1:26:55
And then the most unhinged thing was like, you know, Rosalind, she was a woman and she was also Jewish.
1:27:03
And they say that the woman brain...
1:27:07
does not think in 3d and neither does the Jewish brain.
1:27:10
The Jewish brain does not think in 3d crazy, bro.
1:27:13
What are you talking about?
1:27:15
He's saying this, right.
1:27:16
And then the interviewer is like, Oh, what about like Einstein?
1:27:20
Right?
1:27:20
Like I, I literally did like 40 mathematics.
1:27:24
Yeah.
1:27:25
And he's just like, yeah, well, yeah.
1:27:27
But he was a man.
1:27:28
He had a penis.
1:27:30
Dude, it's so insane the stuff that this guy is saying.
1:27:33
So really, I don't really have a good appreciation for how unhinged and problematic this guy was.
1:27:41
But I saw that video and I was like, oh my God.
1:27:43
Yeah, yeah, yeah, yeah.
1:27:45
Like, he's just saying this.
1:27:46
Like, it's everyone, it's fair game on everybody.
1:27:49
If you're a woman, if you're a person of color, if you're Jewish.
1:27:53
Like, it doesn't matter.
1:27:54
Like, unless you're Watson, you ain't shit.
1:27:58
Dude, it was insane.
1:28:00
I was watching these videos just going like, this is the guy who discovered the double helix that we celebrate.
1:28:08
And, you know, it really...
1:28:11
I don't even know what to think, right?
1:28:13
Because clearly he's a great...
1:28:17
scientist and he's a great uh thinker and he's a great manager of science but man oh man terrible human being terrible human being i gotta say like one of the worst i mean there was such a great opportunity to actually uplift rosalind in that context yeah like and and have this like the uk is better than you like you could have had a whole yeah
1:28:42
Like narrative and story around...
1:28:44
There could have been so many other ways to go about...
1:28:47
Right.
1:28:48
And handling that situation.
1:28:50
And what's interesting is when we were growing up and we heard the story about Watson and Crick, none of this stuff was really kind of like... No, dude.
1:28:58
I read the double helix.
1:28:59
I read this version, right?
1:29:00
And it just shows that he's like this brilliant guy.
1:29:03
Everyone else around him is dumb.
1:29:04
Yeah, yeah, yeah.
1:29:05
And like, you know, taking it at face value.
1:29:07
Yeah.
1:29:08
Which is why if you're going to...
1:29:10
Do anything.
1:29:11
Make sure you write your own biography.
1:29:14
Autobiography.
1:29:15
Because the world will make the story up of your life.
1:29:18
You either die a hero or you live long enough to see yourself become the villain.
1:29:24
Yeah.
1:29:24
Watson lived long enough.
1:29:25
Yeah.
1:29:26
To see himself become the villain.
1:29:28
But it's out of his own making.
1:29:30
Right.
1:29:30
He didn't have to say any of these things.
1:29:32
He could have just been a quiet old man.
1:29:34
The thing is, he didn't have to say any of it.
1:29:36
No, none of this.
1:29:39
This was so cool, though, because, like, again, this...
1:29:43
I know we kind of talk about it.
1:29:45
If you've reached this part of the episode...
1:29:50
In the comments, I want you to put Watson is not the guy.
1:29:55
Yeah.
1:29:55
Yeah, that's a good one.
1:29:56
Watson is not the guy.
1:29:58
That's how we'll know that people really enjoyed this journey.
1:30:02
I really enjoyed this journey.
1:30:03
Yeah.
1:30:04
Because DNA is one of these things that, again, we learn about in school.
1:30:07
We talk about.
1:30:08
It's Watson and Crick.
1:30:09
And it's like that's the only part of it.
1:30:11
Understanding this –
1:30:13
Cavendish versus Kings versus Caltech Caltech sort of like energy.
1:30:19
Uh, the, the starts and stops the actual fundamental science that led to the, like, how do we know?
1:30:26
Yeah.
1:30:27
Yeah.
1:30:28
How did we get there?
1:30:30
It was a triple helix at first.
1:30:32
Crazy.
1:30:33
Obviously dumb.
1:30:34
Yeah.
1:30:34
Now we're thinking about it.
1:30:37
Triple helix, you fucking idiot.
1:30:40
Asshole.
1:30:42
But really, from an image, from a 2D image of X-ray crystallography of...
1:30:49
like what the double being able to then extrapolate to the structure.
1:30:54
Yeah.
1:30:54
And shout out to Donahue who no one ever talks about.
1:30:58
No, but it's kind of like the last, the last little peg.
1:31:01
Yeah.
1:31:02
Peg in the, in the, in the structure to like get to the point of insight.
1:31:07
I think one of the most important things that I know as someone who works in tech startups and has been building teams for a long time is it's never about any individual.
1:31:17
Yeah.
1:31:18
It is always a team effort, whether that's one person gives 98% and another person gives 2% or 50-50 or there's 100 people or there's 1,000 people.
1:31:31
We are not sufficiently all-knowing as individuals.
1:31:36
Yeah.
1:31:37
And it requires collaboration.
1:31:39
Yeah, yeah.
1:31:39
It requires teamwork.
1:31:42
And just dogged commitment and unwillingness to give up.
1:31:48
Yeah.
1:31:48
To get to, like, these places.
1:31:50
Like, this is such a cool.
1:31:52
It's such a cool story.
1:31:53
It's such a cool story.
1:31:54
Yeah.
1:31:54
Because of the ending.
1:31:55
Science is not.
1:31:56
And these characters are so.
1:31:57
It's like Game of Thrones-y.
1:31:59
Yes, yes.
1:32:00
It is all science is a human story.
1:32:02
And we've talked about this before in a pod where it's like, even when you do a research paper, you're creating a narrative because raw data does not have a through line.
1:32:11
No.
1:32:12
That is, is digestible without, without,
1:32:16
framing and reference and context.
1:32:20
An unbelievable story.
1:32:21
Unfortunately, James Watson, again, as we mentioned at the beginning of the story, has recently passed away at age 97.
1:32:29
Clearly karma does not exist.
1:32:31
Yeah.
1:32:33
Because, you know, that's a whole thing.
1:32:34
Yeah, he lived till 97.
1:32:36
Rosalind Franklin only lived till 38.
1:32:38
And it's like, how does that work?
1:32:41
However, one of our best deep dives.
1:32:45
Yeah, I really enjoyed doing the research for this.
1:32:49
This was a good one.
1:32:51
We're in December now.
1:32:52
It's the holidays.
1:32:53
Yes.
1:32:54
As we get to the last episodes of season one, which will round us out for 2025, we are likely to do some probably best of episodes.
1:33:03
Maybe we'll do a little bit of a twist.
1:33:06
Had this idea of analyzing and breaking down the science of movies and TV.
1:33:12
Famous scenes we all know.
1:33:15
When Dr. Ian Malcolm talks about chaos theory.
1:33:19
Yeah.
1:33:20
And the amphibian DNA.
1:33:21
And you can just take some frog and mix it with... Yeah, yeah, yeah.
1:33:24
So the amber, or... We're not going to do Interstellar.
1:33:27
Everyone's already done that.
1:33:28
But we're going to try to do some concepts as we get into the holidays and it gets a little bit difficult for us to shoot to keep you guys tied over with the best content.
1:33:37
You guys are the best audience.
1:33:39
We're so grateful.
1:33:40
Thank you.
1:33:40
My name is Lester Nare.
1:33:42
As always, joined by...
1:33:43
our co-host and resident PhD, and the better brown person than Chamath, Krishna Chowdhury.
1:33:52
This is From First Principles.
1:33:54
We'll see you guys next week.
1:33:56
Peace.