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

Hosted by Lester Nare and Krishna Choudhary, this single-story deep dive tells the full story of how humanity uncovered the structure of DNA — and the human tensions that shaped it. From Mendel’s pea-plant mathematics to Rosalind Franklin’s groundbreaking x-ray crystallography, from Cavendish–King’s College rivalries to the famous Photo 51, this episode follows the scientific and ethical arc behind one of the most important discoveries in modern biology. Summary Before DNA — Mendel’s inheritance laws, Miescher’s nuclein, Levene’s early models, and why scientists initially believed proteins carried heredity. The turning point — Griffith’s transformation experiment and the Avery–MacLeod–McCarty proof that DNA is the genetic material. The physics connection — Schrödinger’s What Is Life? and the idea of an “aperiodic crystal” inspiring Watson, Crick, and a generation of physicists to enter biology. Two labs, one race — Cavendish vs. King’s College, Wilkins vs. Franklin, and the clash of personalities, methods, and interpretations. Photo 51 — Franklin and Gosling’s pivotal diffraction image revealing the helical structure of DNA. The model — base pairing, antiparallel strands, and why the double helix immediately explained replication. Recognition & legacy — the 1953 Nature papers, the 1962 Nobel Prize, Franklin’s omission, and Watson’s later controversies reshaping his legacy. Show Notes Mendel (1866) — Pea Plant Genetics Griffith (1928) — Transformation Avery–MacLeod–McCarty (1944) Schrödinger — What Is Life? Franklin’s Photo 51 Watson & Crick (1953)

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Lester Nare?

  Ni hao, internet. This is your captain speaking, Lester Nare, joined as always by my co-host, our resident PhD and number one Chamath Poliopetia cosplayer, Krishna Choudhary. My friend.

• 0:14Krishna Choudhary?

  That's right. I can't afford the sweaters that he wears.

• 0:18Lester Nare?

  The alpaca shipped from god knows where.

• 0:21Krishna Choudhary?

  Yeah, yeah, yeah, yeah. This is nylon shipped from TikTok shop.

• 0:25Lester Nare?

  You don't have the SPAC money.

• 0:27Krishna Choudhary?

  No. Maybe one day.

• 0:28Lester Nare?

  One day. Maybe not via SPAC, but via science communication.

• 0:32Krishna Choudhary?

  Yeah.

• 0:34Lester Nare?

  It is now, we are in the holiday season, so we are winding down for the year. A big shout out to everyone who's joined the show. We started less than six months ago.

• 0:44Krishna Choudhary?

  Yeah.

• 0:45Lester Nare?

  The response has been incredible. We're going to be wrapping up season one basically at the end of the year. I think we've made the random executive decision to decide our seasons are just going to be every year.

• 0:56Krishna Choudhary?

  Yeah.

• 0:57Lester Nare?

  And so we started only halfway through this year, so season one, a little truncated.

• 1:02Krishna Choudhary?

  Yeah, no, it's good season. No, the Gregorian calendar is a great calendar.

• 1:06Lester Nare?

  It's a great calendar. So that's how we're going to do our seasons.

• 1:09Krishna Choudhary?

  Yeah.

• 1:10Lester Nare?

  So this is the first of kind of our wrap up of the year episodes.

• 1:14Krishna Choudhary?

  Yes.

• 1:14Lester Nare?

  With holidays, with travel, all these things, with Mariah Carey being on the radio nonstop.

• 1:20Krishna Choudhary?

  Yeah. She's creeping up.

• 1:22Lester Nare?

  It's the holiday season. So what we're going to do this episode is similar to what we've done when we did the Nobel Prizes.

• 1:30Krishna Choudhary?

  Yes.

• 1:30Lester Nare?

  Which is we're going to do a single story, deep dive, and what we're going to talk about in this episode is the discovery of DNA.

• 1:38Krishna Choudhary?

  Yes.

• 1:39Lester Nare?

  And the reason why we're going to talk about the discovery of DNA is the unfortunate recent passing of one of the pioneers of the discovery of the double helix, which was James Watson, who recently passed away.

• 1:53Krishna Choudhary?

  Yes.

• 1:54Lester Nare?

  And there's a lot of drama in this story. This will be a complex episode. We are really focused on science.

• 2:05Lester Nare?

  Experimental design, the concepts, thinking about things from from first principles. But this is, one of the things I think we both do is it's a human story.

• 2:14Krishna Choudhary?

  Yes, and it's a fascinating human story.

• 2:17Lester Nare?

  And there's a lot of controversy associated with Mr. Watson. And so we're not going to shy away from.

• 2:27Krishna Choudhary?

  No, not at all.

• 2:28Lester Nare?

  You know, talking about that in the context of what was one of the greatest.

• 2:34Krishna Choudhary?

  Discoveries of the 20th century.

• 2:37Lester Nare?

  Yeah, yeah.

• 2:38Krishna Choudhary?

  Easy.

• 2:39Lester Nare?

  And as always, you guys know, we're going to go deep. It's going to be fun. It's going to be lighthearted, but serious. We're going to learn something today. This is from first principles.

• 3:05Krishna Choudhary?

  So James Watson.

• 3:07Lester Nare?

  Yes.

• 3:07Krishna Choudhary?

  He recently passed away and colleagues and people in the field are wrestling with his legacy because he is a very controversial character. Okay. He is clearly one of the greatest scientists of the 20th century. Right. Discovering the structure of DNA is an incredible achievement. 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 that DNA is this periodic, you know, double helix, twisted ladder, beautiful looking molecule that is

• 3:53Krishna Choudhary?

  ubiquitous in all of life, from bacteria, archaea, fungi, plants, animals, all the way to us. It's it's something that tells us that we're all connected. Right. Me and the plant and the bacteria, we all have the same lineage. One of the one of the definitive proofs of that is the fact that all of us use DNA as our information molecule. Right.

• 4:17Lester Nare?

  It's it's the idea of this universal storage system.

• 4:20Krishna Choudhary?

  Yeah.

• 4:21Lester Nare?

  Like everything that we classify as life.

• 4:25Lester Nare?

  Uses the same Samsung hard drive.

• 4:28Krishna Choudhary?

  Yeah, yeah, yeah. Everyone uses like the same. Yeah, it's like a transistor.

• 4:33Lester Nare?

  Yeah.

• 4:33Krishna Choudhary?

  In some sense, like it's, it's everywhere.

• 4:37Lester Nare?

  It's everywhere.

• 4:38Krishna Choudhary?

  And it's so good at what it does. And one of the reasons why it's so good at what it does has to do with its structure. At the end of the day, biology, I've told you, is just lock and key, right?

• 4:49Lester Nare?

  Right.

• 4:49Krishna Choudhary?

  And, and the, the shape of these molecules has everything to do with what the thing is. And DNA is one of these things that's just incredibly beautiful to look at, incredibly beautiful to think about, beautiful to innovate on as a technology. At the same time, James Watson is a very controversial figure. He helped strengthen US research. Like, he, he single-handedly did a lot for US biomedical research, but at the same time, um, he was very controversial. He said some really out of pocket things towards the later years of his life.

• 5:28Lester Nare?

  Sorry, I'm looking for my pocket. But it's kind of out right now.

• 5:31Krishna Choudhary?

  Yeah.

• 5:34Krishna Choudhary?

  Yeah, he was, he, dude, uh, uh, later on in the story, we're gonna get into some of the stuff he said, and they're like comical how bad they are as takes, right?

• 5:44Lester Nare?

  Look, as, as a member of the black community, it's exactly like the story of R. Kelly.

• 5:50Krishna Choudhary?

  Yeah.

• 5:51Lester Nare?

  Great music.

• 5:52Krishna Choudhary?

  But man.

• 5:53Lester Nare?

  Man.

• 5:54Krishna Choudhary?

  You really?

• 5:56Lester Nare?

  Yeah, this, you can't, it's tough.

• 5:58Krishna Choudhary?

  Yeah, it's tough. It's tough, but you gotta celebrate the good with the bad, right? And you gotta know all of the nuances of the story to really appreciate it.

• 6:06Lester Nare?

  It's the human, it's the human experience.

• 6:07Krishna Choudhary?

  Yes, it is. Yeah. Um, and I want to start by just talking about the historical landscape that sets up DNA.

• 6:16Lester Nare?

  Yeah.

• 6:16Krishna Choudhary?

  As this molecule that everybody is going after.

• 6:19Lester Nare?

  Mm-hmm.

• 6:20Krishna Choudhary?

  Why it was such a big deal that we got this structure. 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. Okay?

• 6:32Lester Nare?

  Okay.

• 6:32Krishna Choudhary?

  So we're gonna start actually all the way back in the 1800s with a man named Gregor Mendel. Back then, you know, everyone knows about like inheritance, right? Like, you get stuff from your parents, but nobody really knew how. Gregor Mendel is this guy. He's an Austrian monk. And he does experiments on pea plants. And he starts noticing that actually, when you do these quantitative experiments, you can really mathematically say how much of the next generation is gonna get a certain trait from their parents. He was doing very selective breeding, where for example, let's say a pea pod had green,

• 7:13Krishna Choudhary?

  and then there was another pea plant that had yellow pods, right? If you selectively breed them together, how many of the next generation are gonna inherit the yellow versus the green? How many of the next generation are gonna inherit tall versus short? How many are gonna do this or that, right? And there was a mathematics to it. There was an understanding that you could glean, which means that there's

• 7:39Lester Nare?

  It wasn't random.

• 7:40Krishna Choudhary?

  It wasn't, it wasn't completely random. There's some mechanism that's happening. And this is before the whole mechanistic view about biology.

• 7:49Lester Nare?

  Got it.

• 7:49Krishna Choudhary?

  Right? Biology was still kind of a dark science of like, things are just happening and we're trying to figure it out. But here, this is one of these first clues that something as fundamental as inheritance could be put into a mathematical language. And if it's being put into a mathematical language, that means there must be some like physical thingy that is, that is, that is going on.

• 8:10Lester Nare?

  That is facilitating the structure that allows you to make those effectively predictions.

• 8:15Krishna Choudhary?

  Yes, exactly.

• 8:16Lester Nare?

  About, about what will happen based on initial condition.

• 8:20Krishna Choudhary?

  Exactly, yeah. So it started out as a statistical abstraction that represented inheritance. And pretty soon, people started asking, well, what is the thing? What is the material that is conferring this inheritance?

• 8:35Lester Nare?

  Right.

• 8:35Krishna Choudhary?

  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. And the fact that there's 20 different amino acids, proteins already, we know have so many different functions, right? So it's like, it's kind of an obvious thing to say that, yeah, proteins are the thing that are conferring inheritance. The idea is, you know, proteins are where a lot of, it's the workhorse. Yes. It's where a lot of stuff can happen. Happen, yeah. It happens, not can, literally happens.

• 9:19Krishna Choudhary?

  Yes, literally, proteins are doing all these things. They're incredibly diverse. Right. And given the diversity of life. It's just like, oh, it's another thing in the toolbox. Yes, exactly. Which is a fair. Totally fair. Totally fair. Totally fair, right? In the, in 1869, actually, there was this guy Friedrich Miescher, who identified something called nuclein, which is what we now call DNA. He identified that inside the nucleus of cells, there were two different types of compounds. There were proteins, and then there was this other thing that he, he said was nuclein, but he was like, it's probably just like some structural thing. He was like, you, nuclein. Yeah, yeah, because it's in the nucleus. So, so I'm gonna call it nuclein.

• 10:02Krishna Choudhary?

  And, and it was seen as a monotonous structural scaffold. Okay. Right? It's, it's just like conferring structure into whatever is really important inside of, inside of the nucleus, right? And then came Phoebus Levine, and from 1905 to 1930, he was actually at the Rockefeller Institute, which is now called the Rockefeller University. It's on the Upper East Side of Manhattan. Yes. Endowed by the Rockefeller Foundation. Yes. He discovered nucleotides, okay? So he, he was, he was going into this nuclein stuff, and he discovered that there's these things called nucleotides that really make up. That, that's the structure. The, the structure of nuclein. Okay.

• 10:45Krishna Choudhary?

  And there's three different parts to a nucleotide. There's some kind of sugar, which he identified as deoxyribose, it's just a type of sugar. It's like a carbohydrate. He also identified that there's, there's a part of the molecule that's the phosphate, right? And then if you, if, if you actually look it up, there's, there's another thing called the nitrogenous base. There's something with nitrogen. So there's three different parts. Yes. To a nucleotide. You have a base, you have a sugar, you have a phosphate. Exactly. And these are the things that make up my nuclein. Okay. Okay? That's, that was sort of the prevailing thing. There's four different types of nucleotides.

• 11:25Krishna Choudhary?

  What he did notice was that there's four different types of bases in DNA. Here, we're actually showing five because RNA, which is another type of nuclein, has another type of nucleotide. But notice the following, and this is going to be important later. With those nitrogenous bases, which is part of the building block of this new clan, some of them have a single carbon ring. Those are called the pyramides.

• 11:54Lester Nare?

  Yes.

• 11:54Krishna Choudhary?

  And then some of them have a double carbon ring. They're a little bit bigger, right? They've got a pentagon on a hexagon, whereas the other guys are just a bunch of hexagons. Single hexagons.

• 12:04Lester Nare?

  Yes, yes, yes.

• 12:05Krishna Choudhary?

  And, and he noticed that there's these four different types. And he had this thing called the tetra nucleotide hypothesis, which is basically that all of DNA is just basically made up of 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.

• 12:29Lester Nare?

  Okay.

• 12:29Krishna Choudhary?

  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. Those things come together and they create a structure called DNA or a nuclein at that point. And this is what confers that structural scaffold.

• 12:49Lester Nare?

  Right.

• 12:49Krishna Choudhary?

  Into the nucleus.

• 12:50Lester Nare?

  Right.

• 12:50Krishna Choudhary?

  So this is the very, very first proposed structure of DNA.

• 12:54Lester Nare?

  Okay.

• 12:54Krishna Choudhary?

  Okay, it's just like this box-like structure.

• 12:57Lester Nare?

  Yes.

• 12:58Krishna Choudhary?

  With, with the four just in a little rectangle.

• 13:01Lester Nare?

  Yes.

• 13:01Krishna Choudhary?

  Okay, and he's like, this is what it is.

• 13:04Lester Nare?

  It clearly is not what it is.

• 13:05Krishna Choudhary?

  It clearly is not what it is. We know that.

• 13:07Lester Nare?

  We know that now.

• 13:08Krishna Choudhary?

  We know that now, but back then, back then, you can imagine like the tools that they have is not at all what the tools that we have, right? There's no X-ray crystallography. There's no genetic sequencing. There's, you're dealing with really crude tools compared to what we have today.

• 13:24Lester Nare?

  It's incredible that they were able to make, to get to this intuition and this directionality of what was correct. Details were a little fuzzy.

• 13:33Krishna Choudhary?

  Yeah.

• 13:34Lester Nare?

  But it was directionally accurate and tactically wrong.

• 13:36Krishna Choudhary?

  Yeah, yeah, yeah, tactically wrong, but but he had already figured out that there's four different types.

• 13:40Lester Nare?

  Right.

• 13:40Krishna Choudhary?

  But because he had this hypothesis that, well, they're all just like conglomerated in the square shape, there's no, there's no real way for them to be complex. They're just simple.

• 13:52Lester Nare?

  Yeah.

• 13:52Krishna Choudhary?

  And life is very complex.

• 13:54Lester Nare?

  So how do you, how do you go from the simplicity of that structure and

• 13:57Krishna Choudhary?

  To all of the complicated.

• 13:58Lester Nare?

  Kind of a little kind of.

• 13:59Krishna Choudhary?

  Yeah, and so they're like, okay, okay, so this is not, this is not what it is, right?

• 14:04Lester Nare?

  Okay, that makes sense.

• 14:04Krishna Choudhary?

  Then we get to a Fisher. So this is in Liverpool University.

• 14:08Lester Nare?

  Liverpool.

• 14:09Krishna Choudhary?

  Yeah.

• 14:09Lester Nare?

  Shout out to all the Scousers out there. You never walk alone.

• 14:13Krishna Choudhary?

  Frederick Griffith, okay, he's, he's at the Liverpool University and at the Liverpool Medical Institution.

• 14:19Lester Nare?

  Okay.

• 14:20Krishna Choudhary?

  And he does a few experiments with bacteria and mice. And this is what he's doing. Back then, we, we knew that there were two types of bacteria of this particular strain called S pneumonae. I think it's basically pneumonia. Okay, it's pneumonia that affects mice.

• 14:40Lester Nare?

  Okay.

• 14:41Krishna Choudhary?

  Okay, there's two types of these bacteria. There's a smooth strain, which is the S, and then there's a rough strain, which is the R.

• 14:49Lester Nare?

  Okay.

• 14:50Krishna Choudhary?

  And we know that the smooth strain kills mice.

• 14:53Lester Nare?

  Okay.

• 14:54Krishna Choudhary?

  But the rough strain does not. Okay, you can inject the rough strain into mice, they'll live. The smooth strain into mice, they won't live.

• 15:01Lester Nare?

  Okay.

• 15:02Krishna Choudhary?

  But here's the kicker, here's the, the genius of his, his experiment. What Griffiths did was he said, okay, can I turn the rough strain into the smooth strain?

• 15:15Lester Nare?

  And you turn water into wine.

• 15:17Krishna Choudhary?

  Yes, in some sense. In some sense, here, here's what he's doing, like. What he can do is, so if he puts the rough and the smooth strain together, and then he puts it in a mice, they die. But that makes sense because you just put the smooth strain, the virulent form, into the mice and they died.

• 15:34Lester Nare?

  Right.

• 15:34Krishna Choudhary?

  What he does was he, he, he kills the smooth.

• 15:38Lester Nare?

  Heat kills?

• 15:39Krishna Choudhary?

  Yeah, so he, he, he gets a bunch of bacteria that are really bad, that are gonna kill the mice, and he heat kills them.

• 15:45Lester Nare?

  I don't know what that means.

• 15:46Krishna Choudhary?

  Uh, just heat it up.

• 15:47Lester Nare?

  He, so, so he, he literally turned, turned the volume to 11.

• 15:52Krishna Choudhary?

  Yeah.

• 15:53Lester Nare?

  On the heat.

• 15:53Krishna Choudhary?

  Yeah, he boiled them up.

• 15:54Lester Nare?

  Literally, literally just heat.

• 15:56Krishna Choudhary?

  Yeah, just literally heated them up.

• 15:58Lester Nare?

  And then inoculated kind of the, the fatal aspects of it.

• 16:01Krishna Choudhary?

  Yes, and now when he puts that into the mice, they still live. They still live, right? Because you've killed the bacteria.

• 16:08Lester Nare?

  I see.

• 16:08Krishna Choudhary?

  That makes sense.

• 16:09Lester Nare?

  That makes sense.

• 16:09Krishna Choudhary?

  But here's the thing, this is the kicker. He takes that heat killed strain, that little sample that he has, uh, it's a, you know, let's say it's in a test tube. He's, he's put it into a really hot water bath, it's killed all the bacteria, and he mixes that with the non-virulent type. And then he puts that mixture into the mice.

• 16:30Lester Nare?

  So he's taken the thing that's bad, he's boiled it.

• 16:33Krishna Choudhary?

  He's boiled it.

• 16:33Lester Nare?

  And now he's done a little mix.

• 16:35Krishna Choudhary?

  Mixing with the stuff that was fine.

• 16:37Lester Nare?

  That was fine.

• 16:38Krishna Choudhary?

  And then he puts that mixture into the mice, and the mice die.

• 16:41Lester Nare?

  Ah, so even when you boil, even when you heat,

• 16:46Lester Nare?

  you heat it up, boil it all off, and still mix, there's something.

• 16:50Krishna Choudhary?

  There's something there, there's something there, that's the thing.

• 16:54Lester Nare?

  That's the thing.

• 16:54Krishna Choudhary?

  That's the thing, there's something physically there, the, that, that has transformed.

• 17:01Lester Nare?

  Right.

• 17:02Krishna Choudhary?

  The non-virulent form into the one that kills mice.

• 17:07Lester Nare?

  And it has nothing, and it has nothing to do, like, it, it's still present even after trying to have heated.

• 17:12Krishna Choudhary?

  Yes.

• 17:13Lester Nare?

  Which the theory was that will kill any problematic.

• 17:16Krishna Choudhary?

  Yeah, that, that's why that control was very important, right? The control of, let's heat up my, um, virulent form, and then put that into the mice.

• 17:24Lester Nare?

  Right.

• 17:25Krishna Choudhary?

  They don't die.

• 17:26Lester Nare?

  They don't die.

• 17:26Krishna Choudhary?

  So, so I've killed the bacteria, but I've preserved something in that bacteria.

• 17:31Lester Nare?

  That is continuing to propagate.

• 17:32Krishna Choudhary?

  That is continuing to propagate this ability to kill mice.

• 17:37Lester Nare?

  Yep.

• 17:38Krishna Choudhary?

  Right? That this ability to be violent, and that has gone and transformed the nice bacteria.

• 17:43Lester Nare?

  Right.

• 17:44Krishna Choudhary?

  Into the bad bacteria. And gone and done the experiment.

• 17:47Lester Nare?

  The point being, there is something more fundamental than what we thought to be what is driving this process.

• 17:55Krishna Choudhary?

  Yeah, it's not just the bacteria. There's something inside the bacteria that is staying put.

• 18:00Lester Nare?

  Right.

• 18:00Krishna Choudhary?

  That is going inside the, the, the non-bad bacteria, the good one.

• 18:04Lester Nare?

  And replicating bad stuff.

• 18:06Krishna Choudhary?

  Bad.

• 18:07Lester Nare?

  And it, that's okay.

• 18:08Krishna Choudhary?

  Right?

• 18:09Lester Nare?

  Yeah.

• 18:09Krishna Choudhary?

  This is a very fundamental experiment. It's very simple. It's very simple, but it shows you that there's a physical element to this idea of ability.

• 18:17Lester Nare?

  I want to just take a quick pause to point out like how sometimes simple or straightforward some of this early stage science sounds like.

• 18:29Krishna Choudhary?

  Yeah.

• 18:30Lester Nare?

  But you actually need to be able to simplify before you can complexify.

• 18:34Krishna Choudhary?

  Yeah.

• 18:34Lester Nare?

  For lack of a better way to put it.

• 18:35Krishna Choudhary?

  No, no, totally. And with the, with the tools that they had, this is already a huge leap, right?

• 18:40Lester Nare?

  Right.

• 18:41Krishna Choudhary?

  This is showing that there is something there, that there's something physically there that is transforming the bacteria to become something else.

• 18:50Lester Nare?

  Right.

• 18:50Krishna Choudhary?

  Right? The, the bacteria is going from a non-virulent form.

• 18:53Lester Nare?

  Right.

• 18:54Krishna Choudhary?

  To a virulent form.

• 18:55Lester Nare?

  Right.

• 18:55Krishna Choudhary?

  And it's now has the ability to kill mice.

• 18:59Lester Nare?

  Right. Even, even, yes, yes, yes.

• 19:01Krishna Choudhary?

  Right? This is, this is, this is pretty crazy.

• 19:03Lester Nare?

  No.

• 19:03Krishna Choudhary?

  Already.

• 19:04Lester Nare?

  And it, it is.

• 19:05Krishna Choudhary?

  And this is in 1928, right? So this is during, like, in, in the middle of the two wars.

• 19:11Lester Nare?

  Right, right.

• 19:12Krishna Choudhary?

  In Liverpool, that, that he's figured this out.

• 19:14Lester Nare?

  Liverpool.

• 19:15Krishna Choudhary?

  Right? People are trying to figure out what is that thing?

• 19:19Lester Nare?

  Which makes sense. Now that we, now we've pointed out like, there's a mystery that is clearly identifiable and replicatable.

• 19:25Krishna Choudhary?

  Yeah.

• 19:25Lester Nare?

  What is it?

• 19:26Krishna Choudhary?

  What is it? And now we get to the resolution of that with an experiment by Avery McLod and McCarty in 1944. Okay? What they do is they systematically purify whatever the thing is that is doing this transformation. And here's what they do. They say, okay, there's, there's possibilities, right? It could be protein. It could be RNA, or it could be DNA. What I'm gonna do is I'm gonna take that soup of heated up bad bacteria.

• 19:56Lester Nare?

  Right.

• 19:57Krishna Choudhary?

  And I'm gonna treat it with something called Tripsin, which basically cuts a bunch of protein. And inoculates all the proteins. It degrades all the proteins.

• 20:07Lester Nare?

  So the point is, if it's, if protein is the source, we're injecting a kill switch that kills the protein. And so if the protein was the source,

• 20:17Lester Nare?

  it would not have the bacteria would not carry.

• 20:20Krishna Choudhary?

  Yeah, yeah, and then and then mice would live.

• 20:22Lester Nare?

  My mice would live.

• 20:23Krishna Choudhary?

  Right?

• 20:24Lester Nare?

  Yes.

• 20:24Krishna Choudhary?

  Um, they still die.

• 20:26Lester Nare?

  Kill switch was maybe a bad terminology to use when we have double kill going on. However, the point is, trips in, kill the proteins, proteins no longer being problematic. We put into the new mice, the new mice still die.

• 20:39Krishna Choudhary?

  The new mice still die.

• 20:40Lester Nare?

  So it's not.

• 20:40Krishna Choudhary?

  So it's not proteins.

• 20:41Lester Nare?

  It's not protein.

• 20:42Krishna Choudhary?

  Okay, then we do something called RNase, which we know it's something that

• 20:47Krishna Choudhary?

  kills RNA, it cuts RNA out.

• 20:49Lester Nare?

  Yeah, okay.

• 20:50Krishna Choudhary?

  Same thing.

• 20:51Lester Nare?

  Nothing.

• 20:51Krishna Choudhary?

  Then we do something called DNase, which is something that cuts up DNA. We know that. That's when the mice live.

• 21:00Lester Nare?

  Not to be confused with CRISPR, which also cuts up DNA.

• 21:02Krishna Choudhary?

  Yes, I mean, this was, this was, this was a very big precursor of this is, this is like, you know, a hundred years ago, it's a very specific CRISPR.

• 21:11Lester Nare?

  Understood.

• 21:12Krishna Choudhary?

  Right? But it is, it's, it's a scissor. And what it's doing is it's cutting up DNA. Well, well, and you cut up the DNA that are give the instructions to the bacteria to actually tell the bacteria how to infect the mice.

• 21:24Lester Nare?

  That's when it.

• 21:25Krishna Choudhary?

  That's when, that's, that's when we killed that ability.

• 21:28Lester Nare?

  Now we've found the building block.

• 21:30Krishna Choudhary?

  Yes, now we've found the building block for the gene. The idea of inheritance is something that is coming from DNA.

• 21:37Lester Nare?

  I actually want to take a quick step back and talk about this because at this time, we did not understand how traits were passed.

• 21:47Krishna Choudhary?

  No.

• 21:48Lester Nare?

  Generationally.

• 21:49Krishna Choudhary?

  We knew that they were from Mendel.

• 21:51Lester Nare?

  Obviously.

• 21:51Krishna Choudhary?

  And from all these, I mean, obviously, like, I look like my parents, you look like your parents. So obviously, there's something.

• 21:56Lester Nare?

  And then experimentally, we also proved it in a controlled context to know that there, there is this inheritance concept.

• 22:04Lester Nare?

  Of inheritance exists.

• 22:06Krishna Choudhary?

  Yes, but what it is.

• 22:07Lester Nare?

  What is like, what actually makes up the fabric of that?

• 22:11Krishna Choudhary?

  Yeah.

• 22:11Lester Nare?

  It's actually a really important point to like, we actually didn't know that barely a hundred years ago.

• 22:16Krishna Choudhary?

  It is, it is quite incredible, right?

• 22:18Lester Nare?

  Years ago.

• 22:19Krishna Choudhary?

  It is quite incredible to think about.

• 22:21Lester Nare?

  Know how my dad, I look like my dad.

• 22:25Krishna Choudhary?

  Yeah, yeah, this is 1944.

• 22:27Lester Nare?

  That's crazy.

• 22:28Krishna Choudhary?

  1944, we didn't know if it was DNA or proteins or something else.

• 22:32Lester Nare?

  We, we figured out how to split the atom and create nukes.

• 22:35Krishna Choudhary?

  Yeah.

• 22:36Lester Nare?

  But we still didn't know why I look like my dad.

• 22:38Krishna Choudhary?

  Yeah, I mean, that just goes to show you how complicated biology is, right? And how hard it is to do experiments and really figure out what the hell is going on.

• 22:47Lester Nare?

  We talk about this often, where you talk about like, oh, physics.

• 22:50Krishna Choudhary?

  Yeah.

• 22:50Lester Nare?

  We've got that biology.

• 22:53Krishna Choudhary?

  Biology is tough, man.

• 22:54Lester Nare?

  The variables are a little.

• 22:55Krishna Choudhary?

  Yeah, yeah, because every, every molecule is different, every, every individual is different. You know, in physics, we have the, we have the nice pleasure of being like, that electron is the same as every other electron.

• 23:06Lester Nare?

  In the universe.

• 23:07Krishna Choudhary?

  In the universe, we've never found one that's different, right? So, um, it, it is an incredible experiment that they did back in 1944, right?

• 23:16Lester Nare?

  Got it, okay.

• 23:16Krishna Choudhary?

  At the same time in 1944, you've got Erwin Schrodinger's book called What Is Life? This is one of my favorite books of all time, okay?

• 23:28Lester Nare?

  It's on the FFP readers, uh, uh, bestsellers.

• 23:30Krishna Choudhary?

  100%. It's, it's a very short book. You, you can read it in about, you can read it in about two hours, honestly. It's very short, it's just a bunch of lectures that he gave at the Dublin College in Ireland. But it is one of my favorite books of all time because it really shows how a physicist would approach this problem.

• 23:50Lester Nare?

  Okay.

• 23:50Krishna Choudhary?

  Okay, he was, he was influenced by someone, but by a bunch of physicists at the time, like Max Delbruck, who was a physicist that had gone to University of Gottingen, which we've talked about. He was mentored by Lisa Meitner.

• 24:06Lester Nare?

  Yep.

• 24:06Krishna Choudhary?

  And, um, then he finally gets to Caltech and he shows that, he really starts thinking about how hereditary material must be something that is solid, it must be something that can resist temperature fluctuations and.

• 24:21Lester Nare?

  Because of what we just talked about.

• 24:22Krishna Choudhary?

  Yes, and it must also be non repetitive. What does that mean?

• 24:27Lester Nare?

  Yeah.

• 24:27Krishna Choudhary?

  If it's repetitive, if it's just a bunch of repetition, you can't store a lot of information there.

• 24:34Lester Nare?

  Ah.

• 24:35Krishna Choudhary?

  It's gotta store a bunch of information, right? It's gotta be like, this is how you do this and this is how you do that. A recipe book is not repetitive.

• 24:43Lester Nare?

  Yeah, right, right. Every, every page or every couple of pages is a different.

• 24:47Krishna Choudhary?

  Is different, is a different recipe for all of the different things that I need in life.

• 24:51Lester Nare?

  Mm hmm.

• 24:51Krishna Choudhary?

  Right? This is a, it's, it's, it's quite nice, but it's, it's, it's a fundamental thing that you can even think about for a bit and be like, yeah, of course.

• 24:59Lester Nare?

  Okay, that makes sense.

• 25:00Krishna Choudhary?

  Whatever the thing that is giving you the information for inheritance has to be something that is not repetitive. It's something that encodes a bunch of information, like a recipe book.

• 25:11Lester Nare?

  Mm hmm.

• 25:11Krishna Choudhary?

  Right? So.

• 25:13Lester Nare?

  Cause you could say, you can have multiple books. Books are repetition, but within the context of a book.

• 25:18Krishna Choudhary?

  Yeah.

• 25:19Lester Nare?

  There's complexity within that.

• 25:20Krishna Choudhary?

  Yeah.

• 25:21Lester Nare?

  That like object type.

• 25:22Krishna Choudhary?

  Exactly. Yeah, yeah, yeah. And one of the key things that he says, it's a postulate that he, that he puts, Erwin Schrödinger. He says, "The gene is an aperiodic crystal." What does he mean by that? What he means is there's periodic crystals, right? Diamond is a periodic crystal. It's a bunch of carbon, carbon, carbon, carbon, carbon, right? You can have salt, which is sodium chloride, sodium chloride, sodium chloride. Not a lot of information there. There's like two bits of information, which is you put the sodium here and the chlorine here and then you repeat. An aperiodic crystal is somewhere where the atomic arrangements are different.

• 25:58Lester Nare?

  Mm hmm.

• 25:58Krishna Choudhary?

  Right? And that difference tells you how to do whatever inheritance thing that you're doing.

• 26:04Lester Nare?

  Right.

• 26:04Krishna Choudhary?

  Right? So he was the first person to postulate that there's some kind of hereditary code script. There's some aperiodic crystal inside of biology that is conferring information to the next generation.

• 26:19Lester Nare?

  Mm hmm.

• 26:19Krishna Choudhary?

  And this is really important because this is cited by both Watson and Crick, who are the, who are the discoverers of the double helix.

• 26:26Lester Nare?

  Right.

• 26:27Krishna Choudhary?

  They said, "This was a primary motivation for seeking the genetic structure. What they wanted to do with their life was find this aperiodic crystal."

• 26:36Lester Nare?

  So, so just the idea here is that someone.

• 26:42Lester Nare?

  Basically said, it's a treasure map.

• 26:43Krishna Choudhary?

  Yeah, there's a treasure map and this is what it looks like.

• 26:46Lester Nare?

  Right. And this is this a periodic crystal concept.

• 26:49Krishna Choudhary?

  Yeah.

• 26:50Lester Nare?

  With a hereditary code script, which makes you can intuit that logic.

• 26:55Krishna Choudhary?

  Yeah, you can, you can, from first principles, you can build it up and be like, okay, something that requires information capacity.

• 27:01Lester Nare?

  Right.

• 27:02Krishna Choudhary?

  Needs to be a periodic and needs to not be the same everywhere. Right?

• 27:06Lester Nare?

  Right. Because your, your level of fidelity, if you just have two bits.

• 27:11Krishna Choudhary?

  Yeah.

• 27:12Lester Nare?

  Is very low as compared to 16 or 32 or 64.

• 27:15Krishna Choudhary?

  Yeah. And the, and the order of those bits is what matters.

• 27:18Lester Nare?

  Is what matters.

• 27:18Krishna Choudhary?

  You can't just be 01, 01, 01, 01.

• 27:21Lester Nare?

  Right.

• 27:21Krishna Choudhary?

  It's gotta be a different, and that sequence is what tells you what the information is.

• 27:26Lester Nare?

  Because DNA ultimately runs a variety of biological processes. And so like, what are the, how are the, how are the instructions?

• 27:36Krishna Choudhary?

  Stored.

• 27:37Lester Nare?

  Stored.

• 27:37Krishna Choudhary?

  Mm hmm.

• 27:37Lester Nare?

  And you need a lot, you need basically a system of enough different component parts or variables to store that complexity.

• 27:46Krishna Choudhary?

  Yeah.

• 27:46Lester Nare?

  And so we have the treasure map and then with Watson and Crick, we have the treasure hunters.

• 27:51Krishna Choudhary?

  Yes, that's a very good way of putting it. Yeah. They, they read this book and they're like, this is a treasure that I want to find.

• 27:58Lester Nare?

  Let's go find the gold of whatever. What's the, what's that famous place where they had all the gold, the ancient place that back in the day?

• 28:08Krishna Choudhary?

  Yeah, I know what you're saying. I, I saw, I saw National Treasure 2, one of my favorite movies.

• 28:13Lester Nare?

  It's, it's.

• 28:13Krishna Choudhary?

  The city of gold, right?

• 28:14Lester Nare?

  It's the city of gold. Yeah, yeah, yeah, yeah. The city of gold. They were looking, because frankly, with the things we live, we'll get there.

• 28:22Krishna Choudhary?

  Yeah, it's, it's, so, so they're trying to find this thing. They, they read this book.

• 28:26Lester Nare?

  Yes.

• 28:27Krishna Choudhary?

  It's an incredibly influential book for them.

• 28:29Lester Nare?

  Yes.

• 28:29Krishna Choudhary?

  And they're like, we want to go find what this a periodic crystal is and what does this crystal look like?

• 28:36Lester Nare?

  Right.

• 28:36Krishna Choudhary?

  Okay?

• 28:38Krishna Choudhary?

  This is around 1944. So at this point, people are already trying to justify that DNA is really the thing that carries the genetic information.

• 28:50Lester Nare?

  Right.

• 28:51Krishna Choudhary?

  Erwin Charagaff, at the University of Columbia in Manhattan, I should say Columbia University.

• 29:00Krishna Choudhary?

  He uses this technique of partition chromatography to look at what is the base composition of this DNA across species.

• 29:08Lester Nare?

  Okay.

• 29:08Krishna Choudhary?

  Because, you know, back then, when Levine was trying to look at the base composition, he just said, everything's the same, right? There's an A, a C, a T, and a G, and they all just come together and it's all equal parts. He didn't have the resolution to figure out if there was more A or more T and so on and so forth, right? Charagaff uses this new method called partition chromatography to quantify how much A is there in a species. How much T is there? How much G and how much C?

• 29:41Lester Nare?

  As an analogy, it's like, you can say, oh, it's all soda, but it's like, is it Coke?

• 29:46Krishna Choudhary?

  Yeah.

• 29:47Lester Nare?

  Sprite?

• 29:47Krishna Choudhary?

  Yeah.

• 29:48Lester Nare?

  Is it Fanta?

• 29:48Krishna Choudhary?

  Yeah. Are they all in equal proportions?

• 29:50Lester Nare?

  Right, like, is there, what is the, is it Coke Zero?

• 29:53Krishna Choudhary?

  Yeah.

• 29:53Lester Nare?

  Right? Or Diet Coke? What's the sugar volume? I'm trying to identify, like, create a.

• 29:58Krishna Choudhary?

  Well, there's only four different types of sodas, right?

• 30:00Lester Nare?

  So Coke, Sprite, Fanta, grape soda.

• 30:04Krishna Choudhary?

  Yeah. And those are the four, but Levine has said that they're all equal and they're just creating the scaffold, right?

• 30:11Lester Nare?

  Okay.

• 30:12Krishna Choudhary?

  And Charagaff went out to say, okay, is this actually true? And he actually dismantled that hypothesis by showing that there's species-specific variation, meaning, like, the amount of As and Ts 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. And he came up with a rule that said, there's actually a pairing ratio.

• 30:38Lester Nare?

  Okay.

• 30:38Krishna Choudhary?

  The A and the T are always the same amount. And the G and the C are always the same amount. And if you look at that, um, this is, this is an expert from his paper. The source is actually, this is for humans. It actually comes from human semen.

• 30:58Lester Nare?

  Ah, we love it.

• 30:59Krishna Choudhary?

  Yeah. I mean, these, these guys, when you're doing science at the cutting edge, you gotta get down into the weeds.

• 31:06Lester Nare?

  You gotta go to the source.

• 31:07Krishna Choudhary?

  Yeah. And, and the advantage of human semen is like, most of the stuff is DNA.

• 31:13Lester Nare?

  I get it. It's a, it's a good source.

• 31:15Krishna Choudhary?

  Like, like with cell, with normal cells, there's so many proteins that like, it's gonna cloud whatever.

• 31:20Lester Nare?

  It's a secondhand, thirdhand source.

• 31:22Krishna Choudhary?

  With, with human semen, the sperm cell is like mostly just packaged DNA and a tail.

• 31:29Lester Nare?

  So it's pure, it's, it's pure sigma, pure alpha.

• 31:32Krishna Choudhary?

  Yeah, yeah, exactly, exactly. Like the, the most of the stuff that's in there is like your DNA.

• 31:37Lester Nare?

  It's what you're looking for.

• 31:38Krishna Choudhary?

  It's what you're looking for. So, so he used that and he showed that, you know, with humans, the, the A and Ts were about 35% and the C and Gs were the rest. And then when he looked at, let's say cows, he found a different ratio. And with pigs, he found a different ratio, but the ratios always came in these pairs.

• 31:59Lester Nare?

  So the point is A and C, A and Cs, A and Ts like to hang out and Cs and Gs like to hang out.

• 32:05Krishna Choudhary?

  Yes.

• 32:05Lester Nare?

  And that's true across species.

• 32:07Krishna Choudhary?

  Across species. The, the numbers could be different.

• 32:09Lester Nare?

  The proportion of it is a little different.

• 32:11Krishna Choudhary?

  Yeah.

• 32:11Lester Nare?

  But in everything, the A and Ts are, are, are hanging out and the Cs and Gs are hanging. Okay.

• 32:19Krishna Choudhary?

  Exactly.

• 32:20Lester Nare?

  Which is like another level of, of fidelity that we're going down.

• 32:25Krishna Choudhary?

  Yes. So we're getting clues into what DNA is, right?

• 32:28Lester Nare?

  Right.

• 32:29Krishna Choudhary?

  We're getting slowly, we're, we're honing down into this. These are called Targass rules, which is the A equals the T, the C equals the G, and they all add up to a hundred percent.

• 32:38Lester Nare?

  Everything we have today is building off of the shoulders of the people who came before, who asked maybe simpler questions.

• 32:45Krishna Choudhary?

  Yeah. Figured out the simpler question that allowed us to ask now more complex questions. Yes, yes, exactly. And we're kind of going through an example of that journey. Yeah, and I, that's why I love this story is like, it's really building up this, you know, crown jewel. Right. It's not, it's not just randomly these guys came up with it. They didn't walk into a cave and find it. Yeah. They had to be crafted. There were, there were a bunch of people, there was an entire community trying to figure this out, right? And maybe these guys just got lucky. Right. You know? Right, look, that happens. It happens. And now, after all that, we get to the setting of the story. After all that, 1951, England. Oh, so what's great is we were in Liverpool.

• 33:30Krishna Choudhary?

  Mm-hmm. Speaking Scouse. We were in Liverpool, we were in Columbia. Columbia. We were in Rockefeller Institute. Yes. In Manhattan. And now we're finally getting to where, the room where it happens. The room where it happens. There's two rooms where it happens, it turns out. Okay. In the Cavendish Lab. Okay. Which is the physics department of Cambridge University. Yeah, yeah. And King's College, London. I'm feeling a little Cavendish right now. What? I don't know. Yeah. Yeah, but those are the two rooms where it happens, okay? The Cavendish Lab, which is a storied lab. Yep. It's the, it's where, you know, all sorts of stuff have happened, right? J. H. Thompson discovered the electron.

• 34:13Krishna Choudhary?

  This is the, you know, crucible of experimental physics before America took over post-war. Okay? And this is actually one of the last big things that they did. Tough. But it's, it's good. It's, they had a good run while they were at it. And look, we, and we appreciate. Oh, yeah, incredible, incredible work. And one day, one day when this podcast is big, I want to go there and, and record. We'll, we're gonna do a lot, yeah. And show the room where it happens. Because they, they still have the old Cavendish Lab there. They, they have a new building now in Cambridge that is off-campus, that has all of the big facilities, obviously. And Cavendish Lab in Cambridge, don't get me wrong, okay? Cavendish Lab in Cambridge is still one of the.

• 34:56Krishna Choudhary?

  The foremost institutions for experimental physics research, right? But the old building, which is in the center of town, um, in the, in like the old Gothic architecture, I mean, you can't beat that.

• 35:09Lester Nare?

  You can't beat it.

• 35:09Krishna Choudhary?

  Right? It's kind of like the first campus center.

• 35:12Lester Nare?

  I was gonna say, yeah.

• 35:12Krishna Choudhary?

  At Princeton, right?

• 35:13Lester Nare?

  Yeah.

• 35:13Krishna Choudhary?

  First campus center there, it says Palmer Physics Lab and you've got, uh, you've got these statues of Benjamin Franklin and Joseph Henry.

• 35:23Lester Nare?

  Yep.

• 35:23Krishna Choudhary?

  Which are some of the founders of American physics. You can't beat the building where Einstein had.

• 35:29Lester Nare?

  Yeah.

• 35:29Krishna Choudhary?

  An office, right? You know, now, now we've got Jadwin Hall, which is, 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?

• 35:47Lester Nare?

  Yeah, I, it, it, when you look at it, cause there's a lot of beautiful amazingness to look at on Princeton's campus.

• 35:54Krishna Choudhary?

  Yeah, no. And Jadwin Hall is not one of them.

• 35:56Lester Nare?

  It's pretty depressing.

• 35:57Krishna Choudhary?

  No, it's, it's awful. Yeah. But it does its job. It does its job and it's still pumping out amazing research.

• 36:03Lester Nare?

  Look, and, and Nobel Prize winners.

• 36:05Krishna Choudhary?

  Yeah, yeah, all the time. So, so anyways, let's get back to Cavendish Lab.

• 36:09Lester Nare?

  Yes.

• 36:10Krishna Choudhary?

  And King's College.

• 36:11Lester Nare?

  Yes.

• 36:11Krishna Choudhary?

  These are the two rooms where it happens, okay? We're first actually gonna run into Rosalind Franklin.

• 36:16Lester Nare?

  Okay.

• 36:17Krishna Choudhary?

  Rosalind Franklin is this young, uh, PhD right out of Paris. She joins John Randall's group at the MRC, which is the Medical Research Council, the biophysics unit at King's College.

• 36:32Lester Nare?

  Okay.

• 36:32Krishna Choudhary?

  Okay? And Randall writes to her and assigns her responsibility for the DNA project. But he does not clearly inform the guy who he already has on staff, Maurice Wilkins, that he's doing this.

• 36:47Lester Nare?

  Oh.

• 36:48Krishna Choudhary?

  So Maurice Wilkins.

• 36:51Krishna Choudhary?

  Thinks that Rosalind Franklin is joining as kind of a lab assistant.

• 36:56Lester Nare?

  Here we go.

• 36:57Krishna Choudhary?

  But Randall has explicitly wrote in a letter to Rosalind Franklin that, no, you're gonna have your own lab. She's been doing a lot of X-ray crystallography, which we're gonna get into, in Paris. She's been actually investigating the structure of coal using X-rays and trying to figure out the crystalline properties of coal. 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 Rosalind Franklin. These are two players at King's College in London.

• 37:31Lester Nare?

  Maurice is like, I'm here. Oh, you're bringing someone new? They're my executive assistant. They're gonna help me take out the trash.

• 37:37Krishna Choudhary?

  Yeah.

• 37:38Lester Nare?

  Give me coffee.

• 37:39Krishna Choudhary?

  Yeah, yeah. If I'm gonna be like, I need this particular scan done, they're gonna do it. They're not really gonna have the intellectual autonomy that is required for a true scientist.

• 37:49Lester Nare?

  Right. They're not gonna be smart enough and they're not gonna have agency, was Maurice's viewpoint.

• 37:53Krishna Choudhary?

  Yeah.

• 37:54Lester Nare?

  But Randall was like, no, no, no, no, no. Like, you're gonna, you're, you're at, you're...

• 37:59Krishna Choudhary?

  You're at equal level.

• 38:00Lester Nare?

  Yeah, right.

• 38:00Krishna Choudhary?

  But he didn't tell Maurice. You know, and obviously that's gonna cause issues.

• 38:07Lester Nare?

  A hundred percent.

• 38:08Krishna Choudhary?

  Right? Especially because like Rosalind Franklin is a woman, so like, it's like, and she's coming in, at the time she's coming in, it's like, oh, this is my secretary. Right?

• 38:17Lester Nare?

  This, this, this is actually in the same era, maybe a little bit earlier as Mad Men, the TV show.

• 38:23Krishna Choudhary?

  No, no, exactly.

• 38:24Lester Nare?

  Just in terms of for context.

• 38:26Krishna Choudhary?

  Yeah, it's, it's the same dynamic, right? There's a new person that comes in, she's really good at what she does, but no one's taking her seriously, least of all Maurice Wilkins, because he didn't, he didn't get the memo that this is someone that you need to take seriously as an equal.

• 38:40Lester Nare?

  Right.

• 38:40Krishna Choudhary?

  Right?

• 38:40Lester Nare?

  Right.

• 38:42Krishna Choudhary?

  Right. So at the time, they, they both get into King's College. Maurice Wilkins is already there. He's, he's established there. Rosalind Franklin is a new researcher. And they start researching DNA. They get these samples from Rudolf Signer in Austria. And this guy Rudolf Signer is...

• 39:04Krishna Choudhary?

  An incredible DNA experimentalist. And what he's really good at is getting pure samples of DNA.

• 39:13Lester Nare?

  Okay.

• 39:13Krishna Choudhary?

  Okay, and we've got pure samples of DNA that are coming in from this guy. All the way from Austria.

• 39:20Lester Nare?

  Okay.

• 39:21Krishna Choudhary?

  Right? They're originally obtained by Wilkins. But now because Rosalind Franklin is kind of this equal player, she's getting samples too. And these are very precious. Because it's really hard to extract DNA. Signers found some secret formula.

• 39:36Lester Nare?

  Yeah.

• 39:37Krishna Choudhary?

  To do it.

• 39:38Lester Nare?

  He found the Krabby Patty secret formula.

• 39:39Krishna Choudhary?

  Yeah, yeah, yeah, and he's not telling anyone how he does it. But he's like, I'll give you my samples. Just like, you know, cite me in your paper.

• 39:45Lester Nare?

  Right, right, right, right, right.

• 39:46Krishna Choudhary?

  And.

• 39:47Lester Nare?

  A little quid pro quo.

• 39:48Krishna Choudhary?

  Yeah, yeah, and then, and then we'll do it. So Rosalind Franklin, she's incredible at X-ray crystallography, which is taking pictures with X-rays.

• 39:56Lester Nare?

  Yes.

• 39:57Krishna Choudhary?

  She builds her own camera apparatus and she starts doing humidity controlled photographs of DNA.

• 40:04Lester Nare?

  Okay.

• 40:05Krishna Choudhary?

  And she actually starts creating the best pictures there are ever of DNA.

• 40:10Lester Nare?

  Morris, eat your heart out.

• 40:11Krishna Choudhary?

  Yeah. Rosalind Franklin is just incredible. Her and her PhD student Raymond Gosling.

• 40:17Lester Nare?

  Yeah.

• 40:18Krishna Choudhary?

  Are just incredible at taking pictures of DNA.

• 40:20Lester Nare?

  Ryan Gosling, no relation?

• 40:22Krishna Choudhary?

  No, no relation. Oh, maybe, I don't know. But in this case, Raymond Gosling is, is learning from Rosalind Franklin.

• 40:28Lester Nare?

  So she has an underling.

• 40:30Krishna Choudhary?

  Mm hmm.

• 40:30Lester Nare?

  Right, and they're coming in and they're just crushing.

• 40:32Krishna Choudhary?

  They're just crushing.

• 40:33Lester Nare?

  Crushing the high quality capture.

• 40:35Krishna Choudhary?

  Yeah.

• 40:36Lester Nare?

  Using X-ray crystallography of DNA.

• 40:38Krishna Choudhary?

  Yeah.

• 40:38Lester Nare?

  And it's just like, it's like.

• 40:40Krishna Choudhary?

  Yeah, and the personalities are crashing because Rosalind Franklin is very, you know, she's a woman in science and at the time, you gotta be confrontational.

• 40:48Lester Nare?

  Yeah, you gotta be tough.

• 40:49Krishna Choudhary?

  You gotta be tough.

• 40:50Lester Nare?

  You gotta be tough.

• 40:50Krishna Choudhary?

  Maurice Wilkins is this really shy guy, you know, and so even personalities are crashing.

• 40:56Lester Nare?

  And he always got what he wanted in his life.

• 40:57Krishna Choudhary?

  Yeah, yeah, and now all of a sudden.

• 40:58Lester Nare?

  And all of a sudden, this tough, you know.

• 41:00Krishna Choudhary?

  Yeah.

• 41:00Lester Nare?

  Charismatic, you know, attitude, he doesn't know what to do.

• 41:03Krishna Choudhary?

  Exactly, yeah.

• 41:04Lester Nare?

  Okay.

• 41:04Krishna Choudhary?

  Okay, so that's, that's the situation at King's College in London.

• 41:08Lester Nare?

  Understood.

• 41:08Krishna Choudhary?

  Now let's go to Cambridge in the Cavendish lab.

• 41:11Lester Nare?

  Again, we're in 1951.

• 41:13Krishna Choudhary?

  Mm hmm.

• 41:14Lester Nare?

  These are happening simultaneously.

• 41:16Krishna Choudhary?

  Simultaneously. Simultaneously, James Watson moves there to Cavendish Lab. Okay, he had just come out of a PhD in Chicago. He had done a postdoc at Copenhagen.

• 41:26Lester Nare?

  Yes.

• 41:26Krishna Choudhary?

  And there in Cavendish Lab, he meets Francis Crick. At the time, the Cavendish Lab, the director was Lawrence Bragg. Lawrence Bragg is very famous for being the youngest Nobel Prize winner of all time in the sciences.

• 41:40Lester Nare?

  In the sciences.

• 41:41Krishna Choudhary?

  In the sciences, right? He won in 1915 at the age of 25. That's unreal. Unreal.

• 41:49Lester Nare?

  Physics. That's, yeah.

• 41:51Krishna Choudhary?

  Right?

• 41:52Lester Nare?

  Physics.

• 41:52Krishna Choudhary?

  Yeah, this is a really, really interesting story. Okay, so he won it with his dad, William Bragg. William Bragg and Lawrence Bragg won it together.

• 42:02Lester Nare?

  That's crazy.

• 42:03Krishna Choudhary?

  Okay.

• 42:04Lester Nare?

  They're also the only, they're the only LeBron Bronny James.

• 42:07Krishna Choudhary?

  Yeah, to win it at the same time. Niels Bohr and Niels Bohr's son also won, but at separate.

• 42:12Lester Nare?

  At separate times.

• 42:13Krishna Choudhary?

  At separate times.

• 42:14Lester Nare?

  Doesn't matter.

• 42:14Krishna Choudhary?

  This is the same prize going to father and son duo.

• 42:17Lester Nare?

  NBA players who have sons that play. No one cares about that.

• 42:19Krishna Choudhary?

  Yeah, yeah, yeah.

• 42:20Lester Nare?

  But did you play on the same team?

• 42:22Krishna Choudhary?

  At the same time? Yeah, yeah. So this is, this is William and Lawrence Bragg, right? They, they won for developing X-ray crystallography. 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? You've got electron densities here and here and here where the atoms are. And X-ray comes in. Remember, the X-ray has a wavelength that is about the size of the atomic spacing, about one angstrom. 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 and it's going to cancel out. So at certain angles, it's going to add up and you're going to get a bright spot.

• 43:05Krishna Choudhary?

  At other angles, it's going to cancel out and you're going to get nothing, right? By looking at the angles. Of where stuff adds up and where stuff cancels out. You can, you know, by looking at the angle, what I mean is you can rotate this crystal and keep shooting X-rays.

• 43:22Lester Nare?

  Right, right. So I'm shooting a beam, some, some, a beam.

• 43:25Krishna Choudhary?

  Of X-rays.

• 43:26Lester Nare?

  Of X-rays at a crystal.

• 43:28Krishna Choudhary?

  Mm-hmm.

• 43:28Lester Nare?

  And then it's going to go through that crystal. And on the other side.

• 43:33Krishna Choudhary?

  I have a photographic plate.

• 43:34Lester Nare?

  I have something that I'm going to track and I can move the crystal around. And I'm going to get different, a different map.

• 43:42Krishna Choudhary?

  Mm-hmm.

• 43:43Lester Nare?

  Based on how, and that map allows me actually then reconstruct.

• 43:47Krishna Choudhary?

  What the crystal is.

• 43:48Lester Nare?

  What the crystal is, even though the map is like a 2D.

• 43:51Krishna Choudhary?

  Yeah.

• 43:51Lester Nare?

  Structure, but because I rotate and then I can reverse engineer.

• 43:55Krishna Choudhary?

  Yeah, yeah, yeah. You're, you're, in technical terms, you're getting a kind of Fourier transform.

• 44:00Lester Nare?

  Okay.

• 44:00Krishna Choudhary?

  In frequency space of like, what frequencies at what angles are doing what?

• 44:05Lester Nare?

  Okay.

• 44:05Krishna Choudhary?

  And then from that, I can then back calculate.

• 44:07Lester Nare?

  Right.

• 44:08Krishna Choudhary?

  Right? And, um, the funny thing about this, right? You, you think Lawrence Bragg and William Bragg, father-son duo, sounds like Nepo baby.

• 44:17Lester Nare?

  Yeah, yeah, yeah.

• 44:17Krishna Choudhary?

  Sounds like a Nepo baby, right?

• 44:19Lester Nare?

  Yeah.

• 44:19Krishna Choudhary?

  Lawrence Bragg, who's the son, is actually the guy who came up with this technique.

• 44:24Lester Nare?

  No way.

• 44:26Krishna Choudhary?

  Yeah. His dad, William Bragg, was in charge of the lab at the time. And he set up the experimental apparatus, but Lawrence Bragg is the guy who came up with the mathematics and the equations for it.

• 44:37Lester Nare?

  That's incredible.

• 44:38Krishna Choudhary?

  And when his dad, William Bragg, reported their results at the meetings and in a paper, he gave, he gives credit to his unnamed son, saying that my, this person, my son, came up with the equation, but the son is not a co-author on the paper. And this is something that like Lawrence Bragg had to deal with for the rest of his life. It was kind of like a trauma that he got from his dad.

• 45:04Lester Nare?

  No way, bro. You're telling me.

• 45:07Krishna Choudhary?

  Dude, it wasn't, yeah, dude, this is, he's not a Nepo baby. The dad is a Nepo dad.

• 45:13Lester Nare?

  You know who this, this is, there's a viral story right now about Simon Cowell.

• 45:17Krishna Choudhary?

  Uh-huh.

• 45:17Lester Nare?

  The like judge from American Idol or whatever. He's come out in public in the last like two weeks and said, "My son is going to get none of my whatever, $500 million empire, zero."

• 45:30Krishna Choudhary?

  Yeah.

• 45:30Lester Nare?

  "All my money is going to go to charity."

• 45:32Krishna Choudhary?

  Yeah.

• 45:32Lester Nare?

  "And he's going to have to figure it out."

• 45:33Krishna Choudhary?

  Yeah.

• 45:34Lester Nare?

  And it's not quite the perfect analogy, but it's like the dad basically took the son's work and it was like, oh. I guess I'm the only named person.

• 45:43Krishna Choudhary?

  Yeah. Oh, that's nice.

• 45:44Lester Nare?

  That's convenient.

• 45:45Krishna Choudhary?

  Yeah, this, I mean, I, I wouldn't say that because with the Simon, with the Simon thing, at least Simon's the guy who like did the.

• 45:51Lester Nare?

  The thing.

• 45:52Krishna Choudhary?

  The thing.

• 45:52Lester Nare?

  He did the thing.

• 45:53Krishna Choudhary?

  This is Lawrence Bragg actually came up with X-ray crystallography.

• 45:56Lester Nare?

  Kid's work, he put in the paper and said, ah, my name's on it.

• 46:00Krishna Choudhary?

  Yeah, yeah. He wasn't even a co-author. They both got the Nobel Prize, but to be honest, only the son should have gotten the Nobel.

• 46:09Lester Nare?

  Prize. The dad just had this name on the building.

• 46:12Krishna Choudhary?

  Yeah.

• 46:13Lester Nare?

  He just had the facility.

• 46:13Krishna Choudhary?

  Yeah, so he was a nepo dad.

• 46:15Lester Nare?

  I don't think you have the facilities for that, bro.

• 46:17Krishna Choudhary?

  But at this point, like Lawrence Bragg is clearly extremely talented. And at this point, he is the director of the Cavendish Lab for good reason.

• 46:25Lester Nare?

  Right.

• 46:25Krishna Choudhary?

  Twenty-five, he wins a Nobel Prize. He's astute and he wants, he, he, he's been, he's been using the Cavendish Lab to create X-ray crystallography of a bunch of crystals. They're just getting into biological compounds, creating protein crystals and finding the structure of those. He really wants this. He really wants the DNA.

• 46:48Lester Nare?

  Yeah.

• 46:48Krishna Choudhary?

  Structure.

• 46:49Lester Nare?

  Yeah.

• 46:49Krishna Choudhary?

  To be.

• 46:50Lester Nare?

  Yeah.

• 46:50Krishna Choudhary?

  To be in England. Okay?

• 46:52Lester Nare?

  Okay.

• 46:52Krishna Choudhary?

  In Cavendish.

• 46:53Lester Nare?

  Okay.

• 46:54Krishna Choudhary?

  Okay?

• 46:54Lester Nare?

  Okay. I see what you're doing.

• 46:55Krishna Choudhary?

  Right?

• 46:56Lester Nare?

  I see what you're doing.

• 46:56Krishna Choudhary?

  And now, and now, so he hires Francis Crick. Francis Crick is a physicist. And at the time Francis Crick, he starts studying with a bunch of other colleagues at the time. He starts studying just X-ray crystallography in general. And he's asking, what would X-ray crystallography look like for different types of molecules? Specifically, he's trying to ask, what would a helical molecule look like?

• 47:21Lester Nare?

  Okay.

• 47:22Krishna Choudhary?

  In X-ray photograph?

• 47:23Lester Nare?

  Helical meaning helix?

• 47:24Krishna Choudhary?

  Helix meaning a spiral.

• 47:26Lester Nare?

  Okay.

• 47:26Krishna Choudhary?

  A spiral monic molecule, I subjected to X-rays, what is it going to look like? He comes up with the Cochrane-Crick-Van theory with his two colleagues in nineteen fifty-two, and he publishes this paper. And what it shows is that the, the scattering amplitude, like the, where the, the, the dark spots and the light spots should be, they should come up in X. They should have these spots. And they should have the cross shape as a signature of a helix. The angle of the cross tells you what the pitch of the angle is of that helix. Right. And things like that.

• 48:00Lester Nare?

  So they came up with a formula for if you're looking at a helix object.

• 48:05Krishna Choudhary?

  Yeah. And I, and I have the photograph from the x-ray. What would that tell me about the structure of the helical object?

• 48:11Lester Nare?

  Got it. Got it. It's kind of like a dictionary or like a translation between a results list. And what is the like interpretable meaning of like the raw results?

• 48:21Krishna Choudhary?

  Exactly. Okay. So Watson, at this time moves there after a PhD in, uh, in Chicago.

• 48:27Lester Nare?

  Yes.

• 48:27Krishna Choudhary?

  Postdoc in Copenhagen, and he strikes up an immediate friendship with Francis Crick. They think very alike in terms of these scientific problems. They're very much alike. Okay. So they start working on the DNA structure with whatever information that they have.

• 48:43Lester Nare?

  We're going to need a photo like that on Princeton's campus in black and white.

• 48:46Krishna Choudhary?

  Yeah.

• 48:46Lester Nare?

  In the, in the hole, in the whole garb. We're going to need one of those.

• 48:50Krishna Choudhary?

  Yeah, we're definitely going to need one. Yeah. Um, so this is sort of setting up.

• 48:55Lester Nare?

  Yes.

• 48:56Krishna Choudhary?

  That situation, right? Cavendish.

• 48:59Lester Nare?

  Versus.

• 49:00Krishna Choudhary?

  Cavendish, you've got these theorists and these extra crystallographers that are trying to figure out what an X-ray crystal picture would look like. And then in King's College London, they're the guys that are actually taking the photos. Right?

• 49:12Lester Nare?

  Okay. So you have the people taking the pictures.

• 49:14Krishna Choudhary?

  Mm hmm.

• 49:15Lester Nare?

  And then you have the people creating the framework for the interpretation of the picture.

• 49:19Krishna Choudhary?

  Yes.

• 49:20Lester Nare?

  And they're both kind of cooking.

• 49:21Krishna Choudhary?

  They're both kind of cooking, right?

• 49:23Lester Nare?

  At the same time.

• 49:23Krishna Choudhary?

  Yes. And they're cooking at the same time and they're kind of competing against each other.

• 49:26Lester Nare?

  Cause they want to be, each one of them wants to be first.

• 49:29Krishna Choudhary?

  For the whole thing. They realize, they realize what this is.

• 49:32Lester Nare?

  Right. Yeah.

• 49:32Krishna Choudhary?

  Right?

• 49:32Lester Nare?

  Yeah.

• 49:33Krishna Choudhary?

  Everyone knows what this is.

• 49:34Lester Nare?

  The treasure map was already created.

• 49:36Krishna Choudhary?

  Yes.

• 49:36Lester Nare?

  They know that there's a city of gold.

• 49:38Krishna Choudhary?

  Yes. Yes. And they're trying to find it. Right? Franklin and Gosling. Now we're back in King's College, London.

• 49:46Krishna Choudhary?

  What they figure out is there's actually two different types of DNA in the sample that they got.

• 49:51Lester Nare?

  Okay.

• 49:51Krishna Choudhary?

  Okay. There's A DNA and B DNA, and it has to do with two different types of humidity. Okay. Something that has, something that's super dehydrated is called A DNA, and that's what Rosalind Franklin was really after. And then there's something that has a bunch of humidity, a bunch of water molecules there, and that's the B DNA. The way they're doing this is actually incredible. They take single bits of DNA, like strings, okay? And they, they, they pull these wires like spider webs, and they put it in front of their X-ray machine. And they take photographs with the X-ray machine, and the exposures are something like 60 hours. They're exposing this thing because it's a tiny little thing, right?

• 50:36Krishna Choudhary?

  So you need a really long time exposure to capture all of that information.

• 50:40Lester Nare?

  That makes sense.

• 50:41Krishna Choudhary?

  Right? So there's two different types of DNA that they're looking at. Franklin is looking at both. She gives an internal talk at King's.

• 50:50Lester Nare?

  Okay.

• 50:50Krishna Choudhary?

  Explaining that there's these two different types, the phosphates, the phosphate groups that I was talking about in those building blocks, those phosphates lie on the outside, and there's some kind of helical structure that they've already found because they see these Xs, right? The, the stuff that Francis Crick was talking about.

• 51:09Lester Nare?

  Right.

• 51:09Krishna Choudhary?

  They've already seen these Xs. So they're seeing a helical form.

• 51:12Lester Nare?

  Okay.

• 51:15Krishna Choudhary?

  Rosalind Franklin gives a seminar.

• 51:17Lester Nare?

  Okay.

• 51:18Krishna Choudhary?

  In King's College.

• 51:19Lester Nare?

  Yes.

• 51:20Krishna Choudhary?

  Where she's talking about her work.

• 51:21Lester Nare?

  Yes.

• 51:22Krishna Choudhary?

  James Watson is in attendance.

• 51:25Lester Nare?

  Okay.

• 51:25Krishna Choudhary?

  In that seminar.

• 51:26Lester Nare?

  Okay, so the ops, so the point is, we have, we have, we have someone from this block and someone from that block.

• 51:31Krishna Choudhary?

  Yeah.

• 51:31Lester Nare?

  They're both trying to be the best.

• 51:32Krishna Choudhary?

  Yeah.

• 51:33Lester Nare?

  And then, so Franklin on her block is like, I'm gonna preach the gospel.

• 51:37Krishna Choudhary?

  Yeah, I'm, I'm gonna do the actual experimental work.

• 51:40Lester Nare?

  And then, and then Watson rolls up.

• 51:42Krishna Choudhary?

  Watson rolls up, he, he's in the back of the seminar.

• 51:44Lester Nare?

  He's kind of peeping game. He's like, what's going on over here?

• 51:47Krishna Choudhary?

  Yeah. And, and he's, and he, and he goes to the seminar.

• 51:51Lester Nare?

  Okay.

• 51:51Krishna Choudhary?

  He's extremely excited. He comes back to Cavendish.

• 51:54Lester Nare?

  Yeah.

• 51:54Krishna Choudhary?

  He goes to Crick, and he's like, this is, this is all the stuff that they were talking about in the seminar. He misremembers what happened in the seminar.

• 52:02Lester Nare?

  He didn't have a voice memo.

• 52:03Krishna Choudhary?

  No, he, he didn't have the chemistry background, really.

• 52:07Lester Nare?

  To understand.

• 52:08Krishna Choudhary?

  To really understand what was going on and internalize. So he tells. Francis Crick about all these things, they get to working. Yeah. They create a model. And at that time, Watson and Crick were really 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, 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, but he's like really excited. He's like, oh, this might work.

• 52:53Krishna Choudhary?

  So the Cavendish group called the King's London, the King's College group to, to come on down. Get your car, come on down, check it out. So Rosalind Franklin rolls up. Okay. Demolishes them.

• 53:07Krishna Choudhary?

  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.

• 53:19Krishna Choudhary?

  Right? And in, in Watson's garbled account, they've, they've built this three stranded helix. And the, the data contradicts what the model they've built. Cavendish is embarrassed. Embarrassed. Embarrassed. Okay. Lawrence Bragg is like, you need to stop.

• 53:40Krishna Choudhary?

  This is in 1951. You're making us look bad. Yeah. Yeah. Stop it. Stop it. So Lawrence Bragg is like, this, this is no, this is not what we do in Cavendish. Right. The most, one of the most, like again, one of the most legendary. Yeah. This, he, this guy's a legend. He won the Nobel Prize at 25. He's telling you to stop. He's in charge. Stop. They stop. Okay. They stop. In 1951, they stop. This is incredible. It's, it's, it's, it's actually incredible. Then. Okay. The King's College group still keeps going on. They still keep collecting data.

• 54:15Krishna Choudhary?

  In 1953, early 1953, they get wind of a guy named Linus Pauling.

• 54:21Lester Nare?

  When you say they, who?

• 54:23Krishna Choudhary?

  This is both King's College.

• 54:25Lester Nare?

  And Cavendish.

• 54:26Krishna Choudhary?

  And Cavendish. The Brits.

• 54:28Lester Nare?

  Okay, the Brits?

• 54:29Krishna Choudhary?

  The Brits get wind of the Americans.

• 54:31Lester Nare?

  The Americans.

• 54:32Krishna Choudhary?

  Okay? Because Linus Pauling at Caltech.

• 54:37Lester Nare?

  Yeah.

• 54:38Krishna Choudhary?

  Has just discovered the structure of the Alpha Helix. The Alpha Helix is a fundamental building block of proteins. Okay? There's a helical structure that almost a lot of proteins have this helical structure.

• 54:54Lester Nare?

  Okay.

• 54:54Krishna Choudhary?

  That is sort of, it's called a secondary structure that is used to build the tertiary big 3D structure.

• 55:02Lester Nare?

  Okay.

• 55:02Krishna Choudhary?

  Okay, you build a bunch of these Alpha Helixes together and you make like whatever protein you want. But this is a.

• 55:08Lester Nare?

  It's a single Lego block that makes the thing you want to make of your Lego.

• 55:11Krishna Choudhary?

  Exactly, exactly, right? And, and Linus Pauling comes out with this manuscript of the Alpha Helix. He's incredibly good at chemistry, trained under Niels Bohr.

• 55:24Lester Nare?

  Yeah, dangerous.

• 55:25Krishna Choudhary?

  Dangerous, okay?

• 55:27Lester Nare?

  Everyone's sweating over that.

• 55:29Krishna Choudhary?

  And, and, and he's, he comes out with this, the Cavendish guys are like, wow, he just scooped us.

• 55:34Lester Nare?

  Yeah.

• 55:34Krishna Choudhary?

  Because they were working on the same thing.

• 55:36Lester Nare?

  Okay.

• 55:36Krishna Choudhary?

  Okay?

• 55:37Lester Nare?

  Okay.

• 55:37Krishna Choudhary?

  And at the same time, in 1953, Linus Pauling comes out with his version of the DNA helix.

• 55:46Lester Nare?

  Okay.

• 55:46Krishna Choudhary?

  It is the same triple helix, very similar. This three stranded helical structure that Watson and Crick had done that was wrong.

• 55:55Lester Nare?

  Correct.

• 55:55Krishna Choudhary?

  Right?

• 55:56Lester Nare?

  Right.

• 55:56Krishna Choudhary?

  Because he has limited data. He doesn't actually know the data.

• 55:59Lester Nare?

  Cause, cause he doesn't have the source.

• 56:00Krishna Choudhary?

  Yeah, he hasn't been to King's College.

• 56:02Lester Nare?

  Where they have.

• 56:03Krishna Choudhary?

  If he was at that seminar, he's a chemist.

• 56:05Lester Nare?

  Yeah, yeah, yeah.

• 56:06Krishna Choudhary?

  He would have figured it out.

• 56:07Lester Nare?

  So the point is that, that at King's, they were getting source data because of their expertise in being able to do the X-ray crystallography.

• 56:15Krishna Choudhary?

  Exactly.

• 56:16Lester Nare?

  And so they like had basically the best map. For where the treasure is.

• 56:20Krishna Choudhary?

  Yes.

• 56:21Lester Nare?

  And, and the, uh, Watson and Craig only got, were able to get to it because they were local.

• 56:25Krishna Choudhary?

  They were local.

• 56:26Lester Nare?

  Down the road, whatever, and were able to see it. Now at Caltech, Paul Ling, he, he is intuiting this without having a really good map.

• 56:36Krishna Choudhary?

  No, no, he's, he's intuiting it from published data.

• 56:39Lester Nare?

  Right, right, right, right.

• 56:40Krishna Choudhary?

  From stuff that's already out.

• 56:41Lester Nare?

  Right, right.

• 56:42Krishna Choudhary?

  But this is a huge red flag for everyone in Great Britain.

• 56:47Lester Nare?

  Yeah, they're like freaking out.

• 56:47Krishna Choudhary?

  It's like, oh, no, Linus Pauling is on it.

• 56:49Lester Nare?

  Yeah, the, the Americans are coming.

• 56:51Krishna Choudhary?

  We got, we got like, we got like a few months tops.

• 56:54Lester Nare?

  Right.

• 56:54Krishna Choudhary?

  We're in the final lap of this race.

• 56:56Lester Nare?

  Mm-hmm.

• 56:57Krishna Choudhary?

  Okay, no more pit stops, this is it. Whatever tires we have now.

• 57:02Lester Nare?

  Yeah.

• 57:02Krishna Choudhary?

  We need to get to the finish because otherwise this, Linus Pauling is like Max Verstappen.

• 57:08Lester Nare?

  Yeah, he's coming.

• 57:09Krishna Choudhary?

  He's coming. And he, if, if he figures it out, he's gonna figure it out very soon. This guy's, this guy has the credentials.

• 57:16Lester Nare?

  Right.

• 57:16Krishna Choudhary?

  Trained under Niels Bohr, knows quantum mechanics.

• 57:19Lester Nare?

  Yeah, yeah.

• 57:20Krishna Choudhary?

  Like, discovered the pi bond, which is like the way in which the, the quantum mechanics of how atoms bond to each other. Like, he's done incredible work, okay? This guy is dangerous.

• 57:30Lester Nare?

  Yeah, yeah, yeah. Right? If he has a little bit more information, he's gonna.

• 57:33Krishna Choudhary?

  He's gonna do it.

• 57:34Lester Nare?

  He's gonna do it.

• 57:35Krishna Choudhary?

  Okay, so, so Watson actually gets wind of this manuscript because Linus Pauling's son brought an early version of the manuscript to Cambridge.

• 57:47Lester Nare?

  I love nineteen, or mid 20th century.

• 57:51Krishna Choudhary?

  Yeah, because there's no online, right? It's not, it's not like just, it goes on Nature website 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 and they, they might wanna see it.

• 58:06Lester Nare?

  Right.

• 58:07Krishna Choudhary?

  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, but this guy's Linus Pauling.

• 58:14Lester Nare?

  Yeah.

• 58:14Krishna Choudhary?

  Okay, I am concerned.

• 58:16Lester Nare?

  Yeah, yeah.

• 58:16Krishna Choudhary?

  So he, he, he goes to King's College.

• 58:19Lester Nare?

  Okay.

• 58:20Krishna Choudhary?

  And he tries to show the manuscript to Rosalind Franklin and Maurice Wilkins. He's like, guys. We need to set our differences aside.

• 58:29Lester Nare?

  This is like local ga- this is like in LA, it would be like two gangs in LA in different parts, right? The blood and the curse being like, look, we have a bigger enemy right now.

• 58:37Krishna Choudhary?

  Yeah.

• 58:37Lester Nare?

  Can we just for like have moratorium for a moment?

• 58:40Krishna Choudhary?

  Yeah, like New York is coming up.

• 58:41Lester Nare?

  New York is coming.

• 58:42Krishna Choudhary?

  Yeah.

• 58:43Lester Nare?

  Yeah, uh, we fifty just dropped get rich or die trying.

• 58:47Krishna Choudhary?

  Yeah.

• 58:48Lester Nare?

  It's gonna be a problem.

• 58:49Krishna Choudhary?

  It's gonna be, yeah.

• 58:50Lester Nare?

  He's hooked up with Jimmy Iovine, Eminem.

• 58:54Krishna Choudhary?

  Yeah.

• 58:54Lester Nare?

  And Dr. Dre.

• 58:56Krishna Choudhary?

  Yeah, exactly. So, so this is when Watson goes to King's College.

• 59:00Lester Nare?

  Okay.

• 59:00Krishna Choudhary?

  And he's like, look, we got a problem here.

• 59:03Lester Nare?

  Yeah, yeah, yeah.

• 59:04Krishna Choudhary?

  He goes to Rosalind Franklin. This is where things get sketchy.

• 59:08Lester Nare?

  Okay.

• 59:09Krishna Choudhary?

  He goes to Rosalind Franklin's office, she's not in there.

• 59:12Lester Nare?

  Okay.

• 59:14Krishna Choudhary?

  I guess the door is open. This is where, you know, I don't know if the door is open or not.

• 59:20Lester Nare?

  Okay.

• 59:21Krishna Choudhary?

  Okay, he just goes in, Rosalind Franklin walks up on him in her office, looking through her stuff.

• 59:30Lester Nare?

  Yeah, no, no, no, no.

• 59:31Krishna Choudhary?

  Never a good look.

• 59:33Lester Nare?

  No, no, no, no.

• 59:33Krishna Choudhary?

  Okay, never a good look. At this point, this is nineteen fifty-three, Rosalind Franklin has already had it with Maurice Wilkins.

• 59:41Lester Nare?

  Yeah.

• 59:42Krishna Choudhary?

  Because of the dynamic.

• 59:43Lester Nare?

  Yeah.

• 59:43Krishna Choudhary?

  Where like they're just not getting along.

• 59:45Lester Nare?

  Yeah.

• 59:45Krishna Choudhary?

  So Rosalind Franklin is about to leave in about six months to go to another university.

• 59:50Lester Nare?

  Right.

• 59:50Krishna Choudhary?

  Okay?

• 59:51Lester Nare?

  Right.

• 59:51Krishna Choudhary?

  And um, the head of the group has told Ros- 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? Because you're no longer gonna be part of this group, all of that is gonna go to you. Gosling, who is the PhD student, is also now gonna go under Maurice Wilkins because he needs to finish his PhD.

• 1:00:16Lester Nare?

  Yeah, he's gotta do what he gotta do.

• 1:00:17Krishna Choudhary?

  And um, in this whole time, Watson is in her lab, just like looking through her stuff.

• 1:00:24Lester Nare?

  Rifling through papers.

• 1:00:25Krishna Choudhary?

  Right, I mean, the guy is desperate, I get it, but my guy.

• 1:00:28Lester Nare?

  No, no, that's.

• 1:00:29Krishna Choudhary?

  Like, what are you doing? Okay, Rosalind Franklin catches him, it's like, what are you, what are you doing? They have, they have a little, they have a little, you know, tiny argument. Watson's like, well, I wanted to show you this paper from Linus Pauling, you know, we're on the same team. Rosalind Franklin is not having any of this. You were just in my office.

• 1:00:48Lester Nare?

  We're on the same team.

• 1:00:49Krishna Choudhary?

  And now all of a sudden, like, we're on the same, no. Okay, get the hell out of my office. Okay, he's like, fine, I'll go. Down the hall, he goes to Maurice Wilkins' office. Maurice Wilkins is in his office. He goes to Maurice Wilkins, he's like, maybe I can talk to this guy. He's like, look, this is the manuscript, Linus Pauling, he's coming at it. Wilkins has all of the data from Rosalind Franklin.

• 1:01:15Lester Nare?

  Right.

• 1:01:15Krishna Choudhary?

  Right? Because the transfer is happening.

• 1:01:17Lester Nare?

  Right.

• 1:01:18Krishna Choudhary?

  And Wilkins shows him the famous photo 51.

• 1:01:22Lester Nare?

  Okay.

• 1:01:23Krishna Choudhary?

  Okay?

• 1:01:23Lester Nare?

  Okay.

• 1:01:23Krishna Choudhary?

  This is the famous photo of B-DNA. This is an extremely famous photo of the X, the characteristic X that gets you the helix.

• 1:01:32Lester Nare?

  Yes.

• 1:01:33Krishna Choudhary?

  It's so well done. This is the photo that Ryan Gosling took at...

• 1:01:38Lester Nare?

  Not Ryan.

• 1:01:39Krishna Choudhary?

  No, not Ryan. What was his name? Raymond. Sorry.

• 1:01:41Lester Nare?

  I just screwed up on that.

• 1:01:43Krishna Choudhary?

  Yeah, this is the photo, this is the photo that Raymond Gosling took. Incredible detail.

• 1:01:48Lester Nare?

  Yeah.

• 1:01:48Krishna Choudhary?

  Right? The spots, the, the, you can tell the angle, so you can tell the pitch of the helix.

• 1:01:53Lester Nare?

  Right.

• 1:01:54Krishna Choudhary?

  You can tell that it's a helix because of the X. The distance between the spots tells you how far apart each nucleotide is.

• 1:02:03Lester Nare?

  I want to, for, for people who are listening and not watching, I want to describe what we're seeing here. So there's two, there's two photos next to each other. There's sort of a black and white. If you've ever looked at photos of like 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.

• 1:02:21Krishna Choudhary?

  Of what it would look like, yes.

• 1:02:22Lester Nare?

  So what I want to, the point is there's a 2D, there's a 2D black and white image.

• 1:02:27Krishna Choudhary?

  Yes, and it's rich in information.

• 1:02:30Lester Nare?

  And you can derive the, the three dimensional double helix from a variety of the angle and...

• 1:02:39Krishna Choudhary?

  The angle, the spacing of the dots.

• 1:02:41Lester Nare?

  All of these things in this black and white.

• 1:02:43Krishna Choudhary?

  The fact that there's nothing in the middle means that one strand goes one way and the other strand goes the other way. So it's anti-parallel, right? There's so much information in this. And Wilkins shows Watson this photograph. Watson is immediately enamored. He tries to memorize this photograph.

• 1:03:01Lester Nare?

  There were ops. Kind of because they were kind of competing with each other. And then it came to a situation where the enemy of my enemy is my friend.

• 1:03:09Krishna Choudhary?

  Yes.

• 1:03:10Lester Nare?

  Right? Because Pauling showed up.

• 1:03:12Krishna Choudhary?

  Yeah.

• 1:03:12Lester Nare?

  And we're like, at the end of the day, we're not gonna let New York win. The Americans like.

• 1:03:16Krishna Choudhary?

  We're not gonna let Caltech win.

• 1:03:18Lester Nare?

  Right, right. So in the, in the.

• 1:03:19Krishna Choudhary?

  They already won.

• 1:03:20Lester Nare?

  They already won.

• 1:03:21Krishna Choudhary?

  With Alpha Helix.

• 1:03:22Lester Nare?

  Right. So like, we, and so now Maurice is like, okay, let me.

• 1:03:26Krishna Choudhary?

  Yeah, let me, let me show you what we got.

• 1:03:28Lester Nare?

  Here's what we got. She's leaving anyway.

• 1:03:29Krishna Choudhary?

  Yeah. Yeah, exactly. Exactly. Let me show you what we got.

• 1:03:33Lester Nare?

  Okay.

• 1:03:34Krishna Choudhary?

  Um, Watson immediately heads back to Cambridge to tell Crick about this photo that he saw.

• 1:03:39Lester Nare?

  He saw it.

• 1:03:40Krishna Choudhary?

  Right? At the same time, um, Franklin publishes an internal report, which is something the institutions do where they talk about the research that they've done over the past year. And it's an internal, um, Medical Research Council report and King's College report that

• 1:03:58Krishna Choudhary?

  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? She has that original print. So she can measure the distance between those, those black spots and say that, okay, these things are 3.4 angstroms apart. Each turn of the helix is 10 nucleotides, 34 angstroms. And all of these little details. This is a Medical Research Council report. Crick gets wind of this and gets a copy of it.

• 1:04:30Lester Nare?

  Of course he does.

• 1:04:30Krishna Choudhary?

  Okay? All of this stuff is happening without Franklin knowing. That's the key.

• 1:04:37Lester Nare?

  Yeah.

• 1:04:37Krishna Choudhary?

  It's not with consent.

• 1:04:39Lester Nare?

  You're right.

• 1:04:39Krishna Choudhary?

  Informed consent.

• 1:04:40Lester Nare?

  Right. Right.

• 1:04:41Krishna Choudhary?

  Okay?

• 1:04:41Lester Nare?

  And especially in this world at, when the stakes are as high as they are, it is a very.

• 1:04:47Krishna Choudhary?

  They're working on DNA.

• 1:04:48Lester Nare?

  Yeah.

• 1:04:49Krishna Choudhary?

  They're working on the physical substrate of genetics.

• 1:04:52Lester Nare?

  I mean, obviously they're, they're working on a Nobel Prize level.

• 1:04:56Krishna Choudhary?

  Everyone knows.

• 1:04:57Lester Nare?

  Everyone knows.

• 1:04:58Krishna Choudhary?

  That this is what's happening.

• 1:04:59Lester Nare?

  The treasure map. We know.

• 1:05:01Krishna Choudhary?

  Right? And so Watson and Crick get to work. They have all of this information.

• 1:05:06Lester Nare?

  Right.

• 1:05:07Krishna Choudhary?

  They go up to Bragg and they're like, look, Bragg,

• 1:05:11Krishna Choudhary?

  Linus Pauling is working on it. We have all this information. We need you to let us work on this again.

• 1:05:17Lester Nare?

  Because at 1951, he's like, stop embarrassing us.

• 1:05:20Krishna Choudhary?

  Stop embarrassing us. Bragg does not like Pauling.

• 1:05:25Lester Nare?

  Ah.

• 1:05:31Krishna Choudhary?

  I love it. It's such a human story. Yeah, it's such a human story. Bragg does not like Paulette. So he's on board. Okay, so he's like, do what you gotta do. Right, right, right. Don't screw it up. This time, do not embarrass me again. I want this for Cavendish. Okay? Yeah. This is, this is ours. Yeah, yeah. You need to do it. So, um, Watson and Crick go down to the machine shop. They're like, boys, we're back in business. I need you to make me little models of it so that we can tinker around.

• 1:06:02Krishna Choudhary?

  They get these models of nucleotides, those base pairs that I was showing you earlier. And they start trying to put them together in the way that they know now, right? Things have to be anti-parallel. The phosphates have to be on the outside. The nitrogenous bases have to be on the inside. 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. And he's like, actually, um, you're doing it wrong. The, given the pH of the cell and the temperature of, of living organisms, the, the hydrogen there isn't actually gonna be there. It's gonna be over here.

• 1:06:44Krishna Choudhary?

  And Watson's like, oh, okay. And then he goes back to the machine shop. He's like, make me new ones. And the new ones work out splendidly. Oh, my God. They fit like puzzle blocks. Oh, my God. Like that, like single, singular subtle insight. That subtle insight from his lab mate, Jerry Donahue, to, to turn from keto. They exist in keto and amino forms and not in the enol form. Okay. Meaning that the hydrogen was in the wrong place. Right. But now, when the hydrogen is in the right place, the hydrogen of one is gonna hydrogen bond with the nitrogen of the other or the oxygen of the other. And they're, you're gonna create these weak bonds in the middle. The other thing that was crazy was that when they had the A and the T

• 1:07:28Krishna Choudhary?

  and the G and the C, there was structural consistency because the A and the T is pairing.

• 1:07:37Krishna Choudhary?

  Two carbon rings with one carbon ring and two carbon rings with one carbon ring. Meaning the distance between the backbones was gonna be the same, right? And there's a, you see? You've got, you've got the C and the G.

• 1:07:53Lester Nare?

  Yes.

• 1:07:54Krishna Choudhary?

  Those have three hydrogen bonds between them.

• 1:07:56Lester Nare?

  Yeah, yeah, yeah.

• 1:07:57Krishna Choudhary?

  The A and the T have two. In that case, that's a U, but same thing, right?

• 1:08:02Lester Nare?

  Yep, yep.

• 1:08:03Krishna Choudhary?

  But notice that the distance between the phosphate backbone on the top and the bottom are the same.

• 1:08:09Lester Nare?

  So, 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. And on the right, the, the A and the, I guess it's supposed to be a T?

• 1:08:20Krishna Choudhary?

  Yeah, that's a U for the RNA, but it's, it's the same structure.

• 1:08:23Lester Nare?

  There's a T with two hydrogen bonds. And the point is, when you look at it at like top to bottom, even though there's a difference in pair and number, the, the vertical distance is, is identical.

• 1:08:35Krishna Choudhary?

  Yes.

• 1:08:36Lester Nare?

  Which means it can be a, a, a structure.

• 1:08:38Krishna Choudhary?

  Which means it can be a structure. It can be a Lego block where I can swap out As and Ts and As and Ts. But the overall structure remains the same.

• 1:08:45Lester Nare?

  Yes.

• 1:08:46Krishna Choudhary?

  So I've just created a code.

• 1:08:48Lester Nare?

  Yes.

• 1:08:49Krishna Choudhary?

  Where?

• 1:08:49Lester Nare?

  Yes.

• 1:08:50Krishna Choudhary?

  The, the, the Lego blocks themselves are different, but when you extrapolate to the larger molecule.

• 1:08:59Lester Nare?

  It fits.

• 1:09:00Krishna Choudhary?

  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 As and less Ts. In that location, there's the other way around. The physics is gonna be the same. The rope is gonna look the same.

• 1:09:12Lester Nare?

  Yes.

• 1:09:13Krishna Choudhary?

  Right?

• 1:09:13Lester Nare?

  Yes, no, this.

• 1:09:14Krishna Choudhary?

  The rope might be colored differently.

• 1:09:16Lester Nare?

  Right, right, right, right, right.

• 1:09:17Krishna Choudhary?

  But the physics of the rope is gonna be the same. It's the aperiodic crystal that Schrodinger was talking about.

• 1:09:24Lester Nare?

  Has finally, they finally now found the missing piece for what is required to actually create the physical structure of this aperiodic crystal.

• 1:09:33Krishna Choudhary?

  Yes.

• 1:09:34Lester Nare?

  Which initially there was like, oh, it's a triple helix. Cause again, we have to remember, there's no conception of the structure. There's no concept.

• 1:09:42Krishna Choudhary?

  Yeah.

• 1:09:43Lester Nare?

  Of what the structure is.

• 1:09:44Krishna Choudhary?

  They're just trying to figure out what, what, what is going on. They know that these are the building blocks, but they're like, does it go this way? Does it go this way? Are there three? Are there five?

• 1:09:53Lester Nare?

  And that one flip of the not enal form, but the keto and amino form.

• 1:09:59Krishna Choudhary?

  Yeah.

• 1:09:59Lester Nare?

  That of the hydrogen.

• 1:10:01Krishna Choudhary?

  Yeah.

• 1:10:01Lester Nare?

  Which creates the three and two pairing, which now is like, that's how everything can now click together.

• 1:10:06Krishna Choudhary?

  Yes. And then this also explains char gas rules, right?

• 1:10:08Lester Nare?

  Yeah.

• 1:10:09Krishna Choudhary?

  Because now the A's and the T's are pairing and the C and the G is pairing.

• 1:10:13Lester Nare?

  Because it's the two and the three hydrogen bonds as what creates, that's the reason why they're paired in that way.

• 1:10:19Krishna Choudhary?

  Yes. There's a physical understanding there, right? And it's, it's, it's an incredible like story, right?

• 1:10:26Lester Nare?

  That's good.

• 1:10:27Krishna Choudhary?

  All of this stuff coming together because they hate the Caltech guy.

• 1:10:31Lester Nare?

  Look, I just want everyone to know California is still the best.

• 1:10:34Krishna Choudhary?

  Yeah, yeah, yeah. But like, they were scared. They were scared.

• 1:10:38Lester Nare?

  And they were scared for a good reason because nothing's happened since. So that they were correct in their fear.

• 1:10:44Krishna Choudhary?

  Dude, Linus Pauling was, was, was really scaring them. So it's like, so, so now they finally figured this out. April 1953.

• 1:10:53Lester Nare?

  Yes, okay.

• 1:10:53Krishna Choudhary?

  Is when they decide, okay, we're going to publish this.

• 1:10:55Lester Nare?

  Okay.

• 1:10:57Krishna Choudhary?

  They have a triple publication. Watson and Crick published their very famous molecular structure of nucleic acid. A, structure for deoxyribonucleic acid. It's just a two-page paper in Nature.

• 1:11:10Lester Nare?

  No way.

• 1:11:11Krishna Choudhary?

  It's a two-page paper in Nature. There's no experimental findings because they didn't do any experiments.

• 1:11:16Lester Nare?

  They just put it out.

• 1:11:16Krishna Choudhary?

  They just put it out. They're like, this is the.

• 1:11:18Lester Nare?

  They're going to war first.

• 1:11:19Krishna Choudhary?

  Yeah.

• 1:11:19Lester Nare?

  Because we have to beat them.

• 1:11:21Krishna Choudhary?

  Uh, Wilkins, Stokes and Wilson, they provided supporting evidence of the helical structure. And then Franklin and Gosling posts had the third paper in the same issue, same issue of Nature.

• 1:11:31Lester Nare?

  Oh my god.

• 1:11:31Krishna Choudhary?

  Back to back to back.

• 1:11:32Lester Nare?

  No way.

• 1:11:33Krishna Choudhary?

  Yeah.

• 1:11:33Lester Nare?

  All three?

• 1:11:34Krishna Choudhary?

  All three. All three, back to back to back had these papers, presented the empirical data with the, with the famous photograph 51.

• 1:11:42Lester Nare?

  I'm going to need to get a copy of this April version.

• 1:11:45Krishna Choudhary?

  Oh, I bet it's worth a lot of money and I would love to have that on the wall.

• 1:11:49Lester Nare?

  So we're going to, we're, okay. So if you, audience, if you are currently in possession of the April 25, 1953, Nature triple publication of DNA.

• 1:12:01Lester Nare?

  Please DM us.

• 1:12:03Krishna Choudhary?

  Yeah.

• 1:12:03Lester Nare?

  If you know somebody that's in possession of that copy, please DM us because it will make a great addition as one of our first pieces on the wall. We've now decided we're going to put the annals and history of science and great memorabilia on the walls behind us.

• 1:12:21Krishna Choudhary?

  And this would be just absolutely incredible. It's a single issue of nature that has all three of these publications.

• 1:12:27Lester Nare?

  So crazy.

• 1:12:27Krishna Choudhary?

  Yeah.

• 1:12:28Lester Nare?

  That is so crazy.

• 1:12:29Krishna Choudhary?

  They approached the editor of nature and they're like, this is, we got, we got, we got three things and they're these three. And the editor of nature was like, yeah.

• 1:12:39Lester Nare?

  Obviously, we gotta put it together.

• 1:12:41Krishna Choudhary?

  Yeah, we gotta put it together and, and they put it back to back.

• 1:12:44Lester Nare?

  That's incredible.

• 1:12:45Krishna Choudhary?

  This order though, the fact that Watson and Crick were first, it sort of cemented that priority in the narrative, right? Because they're the guys who, who came up with the structure. Rosalind Franklin comes up with the empirical data that suggested that structure is true.

• 1:13:00Lester Nare?

  Right. But, but she didn't come up with the structure, technically.

• 1:13:02Krishna Choudhary?

  Yeah, technically she did not come up with a structure. She was incredibly close. If you look at the laboratory notes, she has notes in her labs about how this has to be two strands. They're anti-parallel, all from her data because she took the data.

• 1:13:16Lester Nare?

  Maurice didn't leak. If Maurice didn't leak.

• 1:13:19Krishna Choudhary?

  She could have had a little bit more time.

• 1:13:20Lester Nare?

  She would have had time and who knows?

• 1:13:21Krishna Choudhary?

  Who knows?

• 1:13:22Lester Nare?

  Yeah. But it, you know, she was, and she was there. She had the source.

• 1:13:27Krishna Choudhary?

  She had, she was there.

• 1:13:28Lester Nare?

  She was really the source.

• 1:13:30Krishna Choudhary?

  And if you look at her notes, she didn't have the pairing, which was crucial.

• 1:13:33Lester Nare?

  That's the, that's the key, that Don, Don you.

• 1:13:35Krishna Choudhary?

  Yeah, yeah. And she didn't, she didn't have that guy who was like, no, it's not that form. It's this other form, right? And one of the other great things about Watson and Crick's paper is they, they say that it doesn't escape us that the replication mechanism is now obvious. Because you've got a double helix, you unzip. Now there's a C here, you attach a G. Yeah, exactly. If there's a T, you attach an A. Yeah. Right? Because of the hydrogen bonding, which is unique, a two goes with a two. A three goes with a three. And the length constrains, the spacing of the latter constrains that an A will not go with an A. Even though an A and an A have a two, um, two hydrogen bonds, it's gonna be too wide for the latter. That's a good point. Right? Yeah, yeah, that makes sense.

• 1:14:20Krishna Choudhary?

  So it's obvious now. Yeah, yeah. Given the structure. Yeah. How you would replicate this information. Right, right, right. Which was a huge deal. Right. Like, how, how can you have a, a molecule that does both? That stores and also is able to replicate really quickly. Right, right. Right? Um, it, it's an incredible story. So now there's a shift in research. Franklin, as I was saying, she moves to Berkbach College. Yeah. And she focuses on the tobacco mosaic virus. She does incredible work on the tobacco mosaic virus with a colleague named Aaron Klug. Unfortunately, given that she was working with x-rays, it's, um, it's thought that the x-ray research actually contributed to ovarian cancer that she developed later on in life. Not that much later. She died actually in 1958 at the age of 37.

• 1:15:05Krishna Choudhary?

  This is a photo of her when she was visiting California, um, in Yosemite. And she had visited Berkeley to give some talks and UCLA to give some talks. Um, it's really unfortunate that she died so young. Yeah. At the age of 37. Yeah, that's cra- and, and it was incandescently bright. Yes, incredibly bright, incredibly bright. Um, and she figured out the structure of the tobacco mosaic virus. Her colleague, Aaron Klug, who was her subordinate at the time, went on to win the Nobel Prize for the tobacco mosaic virus. So very, very likely that had, had she lived, she would have won the Nobel Prize. Along. For that as well. Um, 1958 is when she dies.

• 1:15:46Krishna Choudhary?

  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, the Literature Prize there. So he's, he's in the, in the group photo as well. Yeah. Um, obviously, you can't give the Nobel Prize for. Possumously. Possumously, right? And, um, Rosalind Franklin was already four years.

• 1:16:15Krishna Choudhary?

  Passed away. The problem is, there is not a single mention of her in their novel lectures.

• 1:16:23Lester Nare?

  That's crazy.

• 1:16:23Krishna Choudhary?

  That's crazy.

• 1:16:24Lester Nare?

  That's crazy.

• 1:16:25Krishna Choudhary?

  Given, given Photograph 51, like, that is just insane.

• 1:16:28Lester Nare?

  Yeah, you guys wouldn't have been, you would have been in the dark but for Maurice leaking, leaky ass.

• 1:16:36Krishna Choudhary?

  Yeah, Leaky Wilkins.

• 1:16:37Lester Nare?

  Leaky Wilkins, uh, giving you, for his own beef that he, his personal tension.

• 1:16:42Krishna Choudhary?

  Yeah.

• 1:16:43Lester Nare?

  Is probably a non-zero driver.

• 1:16:45Krishna Choudhary?

  Yeah.

• 1:16:46Lester Nare?

  Opening the books up.

• 1:16:46Krishna Choudhary?

  One hundred percent.

• 1:16:47Lester Nare?

  To a local competitor.

• 1:16:48Krishna Choudhary?

  Yeah.

• 1:16:49Lester Nare?

  Right? And so, you can't not.

• 1:16:53Krishna Choudhary?

  Yeah, you cannot say anything.

• 1:16:55Lester Nare?

  Nothing?

• 1:16:55Krishna Choudhary?

  That's insane.

• 1:16:56Lester Nare?

  Nothing is crazy.

• 1:16:57Krishna Choudhary?

  And Rosen Franklin would have, would have sort of gone under the radar. 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 Rosen Franklin.

• 1:17:11Lester Nare?

  I mean.

• 1:17:12Krishna Choudhary?

  Because, because of the resurgence of her persona. And all of that happened because she was so wronged. One, she was not given due credit in the novel lecture. And then second, in 1968, James Watson publishes The Double Helix. Which is this book. My dad bought this book, um, it's in terrible condition because he bought this in, uh, the late 90s. When he first came to America, this is one of the first books that he bought. And he brought it all the way back to India and we've brought it back when we moved back. Um, The Double Helix was published in 1968. It's a firsthand, um, memoir, first-person memoir about the scientific discovery.

• 1:17:56Krishna Choudhary?

  It's unusual for its time because a lot of scientists didn't really talk about the human story. But James Watson put, puts this out in print. He wanted to get it published in the Harvard. Press.

• 1:18:08Lester Nare?

  Yeah.

• 1:18:09Krishna Choudhary?

  But Francis Crick and Wilkins were like, no, we don't want that because they read copies of it. And it was a lot of self aggrandizing.

• 1:18:20Krishna Choudhary?

  The other thing is, he calls Rosie by her nickname. He calls Rosalind Franklin by her nickname Rosie, which at the time was actually, uh, no one, no one said that to her face. Because she wasn't really a rosy personality, right? As I was saying, she's a tough woman. She's a woman in science and a man's field. She's a tough woman. So he's calling her Rosie. He's basically saying that like Rosalind Franklin did not have the scientific expertise and the brain to figure it out on her own. And, and yeah, and the men had to do it. This creates a lot of tension among all of her colleagues. And they're like, what are you talking about? And then that's what starts this movement to be like, no, you're not going to get away with this.

• 1:19:06Krishna Choudhary?

  We're going to start talking about Rosalind Franklin and her contributions. Right?

• 1:19:11Lester Nare?

  That's the, that's so crazy, given the context. Because like, y'all were putting Legos together in the lab.

• 1:19:22Krishna Choudhary?

  Yeah.

• 1:19:22Lester Nare?

  She was doing X-ray crystallography.

• 1:19:25Krishna Choudhary?

  Yeah.

• 1:19:26Lester Nare?

  And actually got the key image.

• 1:19:29Krishna Choudhary?

  Yeah.

• 1:19:29Lester Nare?

  That created the entire unlock.

• 1:19:31Krishna Choudhary?

  Yes.

• 1:19:32Lester Nare?

  For everything downstream.

• 1:19:33Krishna Choudhary?

  Exactly.

• 1:19:33Lester Nare?

  And to not even like, just be able to.

• 1:19:36Krishna Choudhary?

  Acknowledge?

• 1:19:37Lester Nare?

  Acknowledge that is weird, bro.

• 1:19:39Krishna Choudhary?

  It's weird.

• 1:19:39Lester Nare?

  That's like weird.

• 1:19:40Krishna Choudhary?

  It's really weird. It's really, really weird.

• 1:19:43Lester Nare?

  It doesn't make your insight any less important.

• 1:19:46Krishna Choudhary?

  No.

• 1:19:47Lester Nare?

  Like, it didn't have to be, anyway.

• 1:19:49Krishna Choudhary?

  No, yeah.

• 1:19:50Lester Nare?

  That's crazy.

• 1:19:51Krishna Choudhary?

  It's weird. It's really weird. James Watson goes on to be appointed the director of the Cold Spring Harbor National Lab. This is a private, nonprofit research institution. It's kind of like the. Institute for Advanced Study, but for biology and chemistry and biochemistry. At the time, it was very small. James Watson really transforms this into a research environment that is unparalleled. And I will have to give him credit for that. 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.

• 1:20:28Krishna Choudhary?

  They have eight Nobel Prizes to their name. For a single institution that is not a university. That's not a university? It's just like an institution. It's pretty good. Bio Archive, which is the biology archive, is hosted by them. Okay. They discovered telomeres, jumping genes, a bunch of other things. Oh, we just talked about telomeres. Yes. Uh, in one of the two episodes ago. Yeah, yeah, so, so they've done a bunch of research and, and James Watson was really one of the pioneer drivers of creating that institution. So I have to give him credit for that. Sure. Um, in 1990, he actually became head of the Human Genome Project. Yep. Before it was taken over by Francis Collins. Yep. He left two years later because the NIH director at the time, Bernadine Healy,

• 1:21:11Krishna Choudhary?

  was proposing acquiring patents on gene sequences. And he opposed any ownership of laws of nature. So I have to give him credit for that too. Because he said that genes are something that belong to humanity. Yes. You can't like patent something that is within me. Yes. That sounds completely absurd. Yes. So that's also really great. Yes. Um, in 1994, he goes back to Cold Spring Harbor and that's where things get unhinged. Okay. Okay, starts getting old. Maybe he starts thinking he's invincible. Yeah. We've seen that story before. Yeah. So in 2000, in Berkeley, Watson gives a lecture where he suggests there's a link between skin color and sex drive.

• 1:21:53Lester Nare?

  No.

• 1:21:55Krishna Choudhary?

  At Berkeley. Bro. Like of all institutions at Berkeley, you're gonna say this shit?

• 1:22:00Lester Nare?

  I mean, I mean, for Berkeley is like in the Oakland area of California, which is very diverse, very black.

• 1:22:09Krishna Choudhary?

  Yeah, Berkeley is extremely liberal.

• 1:22:11Lester Nare?

  Yeah, like it's because they have people around anyway.

• 1:22:16Krishna Choudhary?

  Yeah, yeah. And he hypothesizes that dark skinned people have stronger libido.

• 1:22:20Lester Nare?

  That's the dumbest thing.

• 1:22:21Krishna Choudhary?

  And the lecturer argues that like melanin, which is the, the thing that's giving us the brown and black color.

• 1:22:27Lester Nare?

  Yes.

• 1:22:28Krishna Choudhary?

  That's somehow a derivative of a compound that boosts sex drive. And then quote, he says, that's why you have Latin lovers. You've never heard of an English lover, only an English patient.

• 1:22:42Lester Nare?

  Oh, bro.

• 1:22:44Krishna Choudhary?

  Like, bro, what are you doing?

• 1:22:46Lester Nare?

  I cannot cringe any harder.

• 1:22:47Krishna Choudhary?

  Okay.

• 1:22:48Lester Nare?

  That's actually pretty, that's pretty wild.

• 1:22:49Krishna Choudhary?

  That's pretty wild. And that's not even the start, dude. Okay. So these are some other quotes from him. Whenever you interview fat people, you feel bad because you know you're not going to hire them. And then, and then he goes, he doubles down later and he says that like, like thin people are smarter.

• 1:23:06Lester Nare?

  Why?

• 1:23:06Krishna Choudhary?

  What are you talking about?

• 1:23:08Lester Nare?

  Why is this the consistent anyway?

• 1:23:10Krishna Choudhary?

  Yeah, you know, in earlier in the episode, when I, when I said like, you know, this guy's controversial.

• 1:23:14Lester Nare?

  Yeah, yeah.

• 1:23:15Krishna Choudhary?

  It's more than controversial, right? Yeah, like.

• 1:23:19Lester Nare?

  It could, the behavior was not only problematic during the discovery.

• 1:23:24Krishna Choudhary?

  Yeah, yeah. During the discovery, he's already like.

• 1:23:26Lester Nare?

  Sketch. Then afterwards trying to like rewrite history, act also sketch.

• 1:23:33Krishna Choudhary?

  Also sketch.

• 1:23:34Lester Nare?

  And now you're just like, just pointing fingers at everyone.

• 1:23:37Krishna Choudhary?

  Now, now you're just saying nonsense, right? And I just want to read you some of the other crazy stuff you said. People say it would be terrible if we made all girls pretty. I think it would be great.

• 1:23:49Krishna Choudhary?

  Bro.

• 1:23:49Lester Nare?

  I just.

• 1:23:50Krishna Choudhary?

  Just stop talking.

• 1:23:51Lester Nare?

  I just.

• 1:23:51Krishna Choudhary?

  So at this point, at this point, Cold Spring Harbor suspends any affiliation to him.

• 1:23:57Lester Nare?

  Wait.

• 1:23:58Krishna Choudhary?

  There's an, oh yeah, he doesn't, he, he, he doesn't even leave the Indians alone.

• 1:24:01Lester Nare?

  Yeah.

• 1:24:02Krishna Choudhary?

  So this is what he said about the Indians.

• 1:24:03Lester Nare?

  That's one more quote here.

• 1:24:04Krishna Choudhary?

  Yeah, there's one more. I, I gotta keep going. So, uh, so, uh, he, he doesn't leave the Indians alone.

• 1:24:08Lester Nare?

  Yeah.

• 1:24:08Krishna Choudhary?

  He's like, uh, Indians are servile because of selection under caste and dogamy. Caste and dogamy, meaning castes, um, you know, marry within castes in the, in the Hindu tradition.

• 1:24:19Lester Nare?

  Yeah.

• 1:24:20Krishna Choudhary?

  And because of that, we're servile. Nothing to do with, uh, maybe the 200 years of colonialism that was subject to us by the British.

• 1:24:27Lester Nare?

  Never love, we love to never touch on that.

• 1:24:29Krishna Choudhary?

  Yeah, yeah, yeah.

• 1:24:30Lester Nare?

  It doesn't matter.

• 1:24:31Krishna Choudhary?

  And the other thing is, uh, uh, look, uh, with the caste system, it's like, he's only basically interacted with the top tier of castes, probably. Because the way the caste system works is the lower castes haven't really had the kinds of opportunities that the higher castes have because of the messed up nature of the caste system.

• 1:24:49Lester Nare?

  Correct.

• 1:24:49Krishna Choudhary?

  So, uh, the, the stereotype doesn't, the argument doesn't even make sense.

• 1:24:54Lester Nare?

  Hundred percent.

• 1:24:55Krishna Choudhary?

  Because he's interacting with the higher, you know, it's like, at least be scientific in your bigotry.

• 1:25:01Lester Nare?

  Africans are less intelligent than Westerners. Watson said his intention was to promote science, not racism, but some UK venues canceled his appearances.

• 1:25:11Krishna Choudhary?

  Yeah, he was going on a book tour and the UK canceled his appearances. Um, the, in 2007, the Cold Spring Harbor Laboratory suspended any affiliation.

• 1:25:22Lester Nare?

  Even though that he was, it was, he, he was the father.

• 1:25:24Krishna Choudhary?

  He basically created, but, well, I mean, he's doubling down on this stuff. He's not even apologizing. He's just saying that, no, this is, this is how it is. And, um, there's this YouTube, there's this YouTube page called Web of Stories. It's one of my favorite YouTube channels.

• 1:25:40Lester Nare?

  Big plug for Web of Stories.

• 1:25:41Krishna Choudhary?

  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 Bethe, um. They also have Edward Teller and they're just, it's just stream of consciousness about their life. Okay. The ones from Hans Bethe and Edward Teller, I really enjoyed. They talk about their time in Manhattan Project and all of the physics that they did. They talk about their experience with Niels Bohr and things like that. Um, right. So, so, so they also did James Watson because he is a titan of science. Let's be honest. The 20th century, he discovered DNA, the structure of DNA. He, he got there in weird ways, but at the end of the day, he's the one who got there first.

• 1:26:22Lester Nare?

  He won.

• 1:26:22Krishna Choudhary?

  He won. Yeah, he won that race.

• 1:26:23Lester Nare?

  Max Verstappen, he might be a little bit of a dirty race, but he, but he wins.

• 1:26:26Krishna Choudhary?

  Yeah, he wins. And, um, so there was this one, there was this one clip where he's asked about Rosalind Franklin. The first thing he says was, I can't give, I can't give a lecture anywhere without a few questions about Rosie. It's like, yeah, no, because you stole her data.

• 1:26:44Krishna Choudhary?

  Like, okay, so he's clearly already not in a good mood because the interviewer is asking him about Rosalind Franklin and he thinks that Rosalind Franklin doesn't deserve all of this attention. Um, and then, and then the most unhinged thing was like, you know, Rosalind, she was a woman and, um, she was also Jewish and they say that the, the, the, the woman brain does not think in 3D and neither does the Jewish brain. The Jewish brain does not think in 3D.

• 1:27:12Lester Nare?

  Crazy, bro. What are you talking about?

• 1:27:15Krishna Choudhary?

  Saying this, right? And then the interviewer is like, oh, what about like Einstein?

• 1:27:20Krishna Choudhary?

  Right? Like I, Einstein literally did like 4D mathematics and, and he's just like, yeah, well, you gotta go.

• 1:27:28Lester Nare?

  But he was a man. He had a penis.

• 1:27:29Krishna Choudhary?

  So like, it's so insane, the stuff that this guy is saying. So really, I don't really have a good appreciation for how unhinged and problematic this guy was. But, but I, I saw that video and I was like, oh my God. Like he's just saying this.

• 1:27:46Lester Nare?

  Like it's everyone, it's, it's fair game on everybody. If you're a woman, if you're a person of color, if you're Jewish, like it doesn't matter. Like unless you're Watson.

• 1:27:57Krishna Choudhary?

  Yeah.

• 1:27:57Lester Nare?

  You ain't shit.

• 1:27:58Krishna Choudhary?

  Dude, it was, it was insane. I was watching these, I was, I was watching these videos just going like, this is the guy who discovered the double helix and like that we celebrate. And, you know, it really, it. I don't even know what to think, right? Because clearly, he's a, he's a great scientist, and he's a great thinker, and he's a great manager of science. But man, oh, man.

• 1:28:24Lester Nare?

  Terrible human being.

• 1:28:25Krishna Choudhary?

  Terrible human being, I gotta say. Like, one of the worst.

• 1:28:30Lester Nare?

  I mean, there was such a great opportunity to actually uplift Rosalind in that context.

• 1:28:35Krishna Choudhary?

  Yeah.

• 1:28:35Lester Nare?

  Like, and, and have this, like, the UK is better than you. Like, you could have had a whole, like, narrative and story around.

• 1:28:44Krishna Choudhary?

  There could have been so many other ways to go about.

• 1:28:47Lester Nare?

  Right. And.

• 1:28:49Krishna Choudhary?

  Handling that situation.

• 1:28:50Lester Nare?

  And what's interesting, because when we were growing up and we heard the story about Watson and Crick, none of this stuff was really kind of like.

• 1:28:57Krishna Choudhary?

  No, dude, I read, I read The Double Helix. I read this, this version, right? And it's, it just shows that he's like this brilliant guy. Everyone else around him is dumb.

• 1:29:04Lester Nare?

  Yeah, yeah, yeah. And like, you know, taken at face value.

• 1:29:07Krishna Choudhary?

  Yeah.

• 1:29:08Lester Nare?

  Which is why, if you're gonna do anything, make sure you write your own biography, autobiography, because the world will make the story up of your life. You either die a hero, or you live long enough to see yourself become the villain.

• 1:29:24Krishna Choudhary?

  Yeah.

• 1:29:24Lester Nare?

  Watson lived long enough to see himself become the villain.

• 1:29:27Krishna Choudhary?

  Yeah, but it's out of his own making.

• 1:29:30Lester Nare?

  Right.

• 1:29:30Krishna Choudhary?

  He didn't have to say any of these things. He could have just been a quiet old man.

• 1:29:34Lester Nare?

  The thing is, he didn't have to say any of it.

• 1:29:36Krishna Choudhary?

  No, none of this.

• 1:29:38Lester Nare?

  This, this was so cool, though, because, like, again, this, I know we kind of talk about it. If you've reached this part of the episode, in, in the comments, I want you to put, Watson is not the guy.

• 1:29:55Krishna Choudhary?

  Yeah, yeah, that's a good one.

• 1:29:56Lester Nare?

  Watson is not the guy. If that's how we'll know that people, like, really enjoyed this journey. I really enjoyed this journey.

• 1:30:03Krishna Choudhary?

  Yeah.

• 1:30:03Lester Nare?

  It's, it's, it's, because DNA is one of these things that, again, we learn about in school. We talk about, it's Watson and Crick. And it's like, that's the only part of it. Understanding this, like, Cavendish versus Kings.

• 1:30:15Krishna Choudhary?

  Versus Caltech.

• 1:30:16Lester Nare?

  Versus Caltech, sort of like, energy. The, the starts and stops, the actual fundamental science that led to, like, how do we know?

• 1:30:26Krishna Choudhary?

  Yeah.

• 1:30:28Lester Nare?

  How do we into like, how did we get there? It was a triple helix at first. Yeah. Crazy, obviously dumb. Yeah. Now, now we're thinking about it.

• 1:30:37Lester Nare?

  Triple helix, fucking idiot. Asshole. But like, but like really, and why like from an image, from a 2D image of, of X-ray crystallography of like what the double, being able to then extrapolate to the structure. Yeah. And shout out to Donahue, who no one ever talks about. No. But it's kind of like the last. The last little peg, yeah. Peg in the, in the, in the structure to like get to the point of insight. 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.

• 1:31:18Lester Nare?

  It is always a team effort, whether that's one person gives 98% and another person gives 2% or 50/50, or there's a hundred people, or there's a thousand people. We are not sufficiently all-knowing as individuals. Yeah. And it requires collaboration. Yeah, yeah. It requires teamwork and, and just dogged commitment and unwillingness to give up. Yeah. To get to like these places, like this is such a cool. It's such a cool story. It's such a cool story. And because of the, and again, science is not. And these characters are so, it's like Game of Thrones-y. Yes, yes. You know? It is all science is a human story. Yeah.

• 1:32:02Lester Nare?

  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. No. That is, is digestible without framing and reference and context.

• 1:32:20Lester Nare?

  An unbelievable story. Unfortunately, James Watson, again, as we mentioned at the beginning of the story, has recently passed away at age 97. Mm-hmm. Clearly karma does not exist. Yeah. Because, you know, that's a whole thing.

• 1:32:34Krishna Choudhary?

  Yeah, he lived till 97. Rosalind Franklin only lived till 38.

• 1:32:38Lester Nare?

  38. It's like, how do you, how does that, how does that work? However, um, one of, one of our best deep dives.

• 1:32:45Krishna Choudhary?

  Yeah, I really enjoyed doing the research for this.

• 1:32:48Lester Nare?

  This was, this was a good one. Um, we're in December now. It's the holidays.

• 1:32:53Krishna Choudhary?

  Yes.

• 1:32:54Lester Nare?

  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. Maybe we'll do a little bit of a twist. Had this idea of analyzing and breaking down the science of movies and TV. Famous scenes we all know.

• 1:33:15Krishna Choudhary?

  Yeah.

• 1:33:15Lester Nare?

  When Dr. Ian Malcolm talks about chaos theory.

• 1:33:19Krishna Choudhary?

  Yeah.

• 1:33:19Lester Nare?

  And the amphibian DNA and you can just take some frog and mix it with something. So the amber or we're not going to do Interstellar. Everyone's already done that. 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 it over with the best content. You guys are the best audience. We're so grateful. My name is Lester Nare. As always, joined by our co-host and resident PhD. And the better brown person than Chamath, Christian Choudhary. This is from First Principles. We'll see you guys next week.

• 1:33:55Krishna Choudhary?

  Peace.