A recording from my enthralling conversation with Prof Matthew Cobb about the life and science contributions of Francis Crick, regarded as one of the most influential biologists of all times, along with Darwin and Mendel. As you’ll see, there’s so much more to Crick’s story than cracking DNA’s double helix structure in a matter of weeks with James Watson. Matthew Cobb, Emeritus Professor of the University of Manchester, has written several award-winning books on life science, but I think this is his most important one to date, deeply researched and a thrilling account of Crick’s life, clearing up, as best as one can, many questions, and presenting some surprises.The transcript is available (A.I. generated) by clicking at the top right.A few things we discussed—Crick’s reaction to James Watson’s bookCrick contrasted his own approach to science writing with Watson’s memoir: “The difference between my lecture and your book is that my lecture had a lot more intellectual content and nothing like so much gossip. (...) Your book on the other hand, is mainly gossip and I think it a pity in this way that there is so much of it that it obscures some of the important conclusions which can be drawn of what we did at the time”.—The Peyote Poem, by Michael McClure (part 1) that had a big influence on Crick—Crick’s 1994 neuroscience book “The Astonishing Hypothesis”“You, your joys and your sorrows, your memories and your ambitions, your sense of personal identity and free Weill, are in fact no more than the behavior of a vast assembly of nerve cells and their associated molecules.”—CrickThe book has been reviewed at Science, Nature, The Economist and many other journals. Here is a gift link to The Economist It has deservedly been named a best book of 2025 by The Guardian, The Economist, and many other media.Thank you Bruce Lanphear, Harshi Peiris, Ph.D., Elisabetta Pilotti, Allan Konopka, Stephen B. Thomas, PhD, and over 500 others for tuning into my live video with Matthew Cobb! *********************Upcoming, this Wednesday 9AM PT, live podcastI will be interviewing Dan Buettner founder of the Blue Zones Join us!**********************Thanks to US News for recently being named one of the 25 best leaders in the United Stateshttps://www.usnews.com/news/leaders/articles/best-leaders-2025-eric-topol^^^^^^^^^^^^^^^^^^^^^^Thanks to 190,000 Ground Truths subscribers from every US state and 210 countries. Your subscription to these free essays and podcasts makes my work in putting them together worthwhile.If you found this interesting PLEASE share it!Paid subscriptions are voluntary and all proceeds from them go to support Scripps Research. They do allow for posting comments and questions, which I do my best to respond to. Please don’t hesitate to post comments and give me feedback. Let me know topics that you would like to see covered.Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past two years. It enabled us to accept and support 47 summer interns in 2025! We aim to accept even more of the several thousand who will apply for summer 2026. Get full access to Ground Truths at erictopol.substack.com/subscribe
Chapter 1: What insights does Matthew Cobb provide about Francis Crick's character?
And just so as we're getting warmed up here, this is Matthew Cobb's seventh book, okay? And He has another one that he's working on, on Heredity. So he's not going to stop writing, and he is amazing. Now, I thought we'd start with all the insights I learned about Francis Crick from such a deep interrogation of what he was like. He, in many ways, was a challenging dogma, a boat rocker,
But interestingly, besides being agnostic, he would throw racy parties, he's bohemian, he's a philanderer, he had an open marriage with his wife Odile, is how do you say it? For 55 years, even though he had affairs and whatnot. He was an intellectual snob, he never voted, he had no radio or TV until 1980. So arrogant, ruthless. He wrote about stuff that would be eugenics, quick-witted.
But on the other hand, he would give talks to children. There are a lot of paradoxes about this man. And maybe you can kind of tell me, did I have it right that this guy was just a very unique character?
Well, I certainly don't think he'd last very long in modern-day academia. Not only because he was a rubbish at doing experiments and asking for money, he only ever applied for one large grant in his life, but clearly aspects of his behavior would now be deemed unsuitable.
I mean, having been said, he had no... I mean, you know, I knew about his affairs, which is one of the things that a lot of people want to talk about, and I realized very soon on that that was not going to give me much insight into his science, which is what I was really interested in. And so... out of respect for the various people involved.
I haven't actually named any names and they're mentioned every now and again as kind of little bits of information.
they're not really important in understanding him unlike say picasso right i mean if you don't understand picasso's affairs you can't understand the various phases of his of his art because they're all linked with relationships with women whereas this is just something that goes on but that being said i just want to make clear in case it was unclear he none of his affairs with students or anybody with whom he had a position of authority so
You know, he wouldn't be drummed out for that. I just think people would raise their eyebrows. And certainly his views on eugenics, which continued into the 1970s, would be seen as unacceptable today. Although I noticed that a lot of the tech bros have very similar ideas. Because Crick's main interest, as he put it, was he had a prejudice against the poor. Which seems very strange.
And I think this is one of the actually really interesting things that I found in working on the book. Because most of the science is either, there's bits of it, especially in his youth and early career, which are very detailed and a bit boring. But most of his later work is really big ideas. And what I wanted to do was to work out how on earth he was able to have all these ideas in his head.
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Chapter 2: How did Crick's personal life influence his scientific work?
There are parts of the world, in particular the social world, that he just doesn't understand and doesn't make the effort to try and work out what's going on. So there were times, most of the time, I was just kind of astonished by quite how clever he was. But there are these other parts where I can see, no, you don't get it. You don't understand. So why don't you understand it?
And the book that I ended up putting him on was that these ideas come from his Edwardian past. He was born in 1916, right? So that's a long time ago. Yeah. And he imbibed all these ideas in the 1920s, which were as kind of nationalistic and stupid and, you know, racist as you might expect, and never really interrogated them.
And for most of his life, it had no consequence because he wasn't thinking about such things. But when he did, he kind of flipped back to this very old way of thinking.
Yeah, no, and I thought there was some common ground there with James Watson, who also was known for his eugenics, race. I don't know. He also was a misogynist. But, I mean, they shared these bad traits, wouldn't you say?
Yeah, well, Jim's actually a bit more interesting because one of the things I noticed was in 1972, there was a petition to the academies, the National Academies of Science in the USA, to say that there should be support for research into the genetic basis of intelligence. Now, we know what they mean, right?
Yeah.
We know nothing about black people or anything like that was mentioned, but we know what they meant. And it was all to do in particular with the work of Arthur Jensen. And Crick signed this petition and he got people like Jacques Monod to sign it. Jim Watson did not sign it. And it was all coached in terms of academic freedom.
And Jim was much more left-wing and very supportive, for example, of women in science in the 1960s. Something happened to him in the 80s and 90s where he changed his mind about a lot of these issues.
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Chapter 3: What were the pivotal moments in Crick's transition from physics to molecular biology?
And that will be the topic of, not my book, but my good friend Nathaniel Comfort's forthcoming biography of Watson. And that's the riddle he's got to try and work out the answer to. And that will be out in a year or so.
That'll be really interesting. Okay. Yeah. Now we're going to go into, you know, how did Francis Crick get to this two careers, if you will, or to starting two fields in science. in many respects. But before we get to that, some background. I guess he was influenced by two scientists and their work, Linus Pauling and Edwin Schrodinger, and also by his child's children's encyclopedia.
Tell us a little bit about that.
Well, he called it the most important book he ever read. And that's partly what gave me the clue to understanding him as having Edwardian aspects. So I thought, okay, he said this when he was about 80, that this was the most important book he ever read. He kept it to the end of his life. His son Michael now has it, and it's incredibly well-thumbed. The Cricks had the eight-volume bound edition.
So this is an incredibly successful encyclopedia. And lots of people I've met since have said, oh, I had that. My parents bought it. It went out of fashion about 1960, but it went through many editions. And I was able to read it online. And it is extraordinary in its breadth of topics that it covers. The edition that Francis had was from 1908. So the gene had barely been mentioned.
barely been named, and there was nothing about heredity or anything like that in the book. But it was all these, it covered absolutely everything, you know, from flowers to fairy stories to explanations of science. And in particular, it was aimed at kind of preteens, and it is so clearly written. And that's what he took from it.
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Chapter 4: What controversies surrounded the discovery of DNA's double helix structure?
Not only the ideas, including the, you know, because it was a British book about the empire and all the rest of it, but the clarity, how to write clearly and simply words. about science. And that's what he always tried to do. And yeah, that was definitely the most important book he read. And then the two inspirations that led him to make this shift in 1947.
So you've got to remember, he's born in 1916. He started a PhD on what he described as the most boring topic in the world, which is the viscosity of water under pressure, because he was a physics student. Starts that in 1939. War breaks out. His lab gets shut. A German landmine falls on the equipment he built, so it was all out of... Couldn't be done anyway.
He then does various things during the war. He works on mines, making mines that blow up ships. After the war, he does something rather mysterious that I still don't know about, really, in naval intelligence.
And then in 1947, he's read one Linus Pauling talk about X-ray crystallography, and he's also read Schrödinger's What is Life?, which again says you can use physical methods to get at the gene, to understand biology. And he decides there are two things he's really interested in, what he wants to study.
He wants to understand the nature of consciousness, and he wants to understand the nature of life. So in 1947, he's charted out the next 67 years or 57 years of his existence. And that's what he did. He decided that he'd deal with life first because it seemed a bit easier. Plus there was the x-ray crystallography that might help. And that's what happened.
So that's really everything that follows from that decision in 1947.
Yeah, no, it's amazing, because that was his first major pivot from the viscosity of hot water to go into biology and chemistry rather than physics to start to build up molecular biology. So a lot of people, and this has been a very controversial thing about the discovery in February 1953 of the DNA structure and the other players, Rosalind Franklin,
Maurice Wilkins, and you set the record straight. You really went into this. I tried to. Yeah, yeah. Well, I mean, I've always wondered what the hell happened there. You know, what really happened? What was the contribution of these different people? And everybody thinks that Watson and Crick, they worked together for decades when it was like weeks. Yeah, absolutely.
You can fill in the holes there.
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Chapter 5: How did Crick's views on consciousness evolve throughout his career?
Neither of them were supposed to be studying it. Crick, as his boss Sir Lawrence Bragg said, was a chap who liked doing other people's crosswords. So if you had a problem, Crick would find the answer to it, even if you didn't want to. You know, he was always interested in other people's things and experiments that had just come out. How could you interpret them and so on?
Probably quite infuriating. Certainly Bragg found it himself. Watson was much younger. He was, what, eight years younger. And he arrived in 1951 at Cambridge. And he, too, was not working on DNA. They were both working on protein structure, which is what they studied at Cambridge.
But Crick's very good friend, Morris Wilkins, had been working on DNA first using microscopes and then using X-ray crystallography for about six years. Indeed, Crick nearly went and worked with him at King's College, Cambridge, London, but it didn't work out.
Now, so Crick knew what was happening all along in London because Wilkins would come along and they'd have dinner and have a drink and Wilkins would chat and he would also... complain about Rosalind Franklin. And because Franklin and Wilkins just didn't get on. Wilkins was very introverted, very quiet, didn't like argument. Franklin was very vivacious.
She came from an intellectual Jewish family that liked to have a good argument about anything, because that's the way you develop your ideas, you know? So these two people just could not work together. And that's part of the tragedy. And Watson always said this, that if they'd been able to work together...
We talk about the Wilkins Franklin or Franklin Wilkins structure, not about Watson and Crick. They would have been nowhere. So there's been lots of problems, incredibly slow work in, in, in, in King's College, London. And then. At the end of 1952, they hear, the people in Cambridge hear, that Linus Pauling has produced a version of the structure of DNA.
And they knew this because Linus's son, Peter, happened to be doing his PhD in Cambridge in the same office as Watson and Crick. So he says, oh, we're going to get this letter. And Crick has been warning the people in London, saying the big bad wolf is going to find the solution if you people don't.
So now we've got a situation in which they've got this manuscript from Pauling, Linus Pauling, which is not right. It's similar to an idea that Watson and Crick had about 15 months earlier. And it's inside out. It's got three helices.
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Chapter 6: What role did poetry play in Crick's life and work?
It's not right. And Bragg, who really didn't like Watt Crick and didn't really know much about Watson at all, is persuaded because he's got a beef. He's had a beef with Pauling for reasons we don't need to go into. And so the idea... stealing a march on Pauling is too much for him to resist. And he says, OK, Watson and Crick, you've got a few weeks to try and do this.
And above all, he does not contact his colleagues in London saying, oh, by the way, we're moving in on your territory. Meanwhile, back in London, things have gone from bad to worse. And Franklin, I mean, she decided virtually as soon as she met Wilkin, she wanted to leave, right? But she's now on the way out. She's going to another laboratory in London in Birkbeck to work with J.D.
Bernal, but not on DNA because the head of the King's College group has said, you can't take DNA with you. It's our project, which to be fair was true. They'd come up with the idea. She had just been brought in to work on it. And then it gets tricky. This is where it gets murky.
Because if most people know, or they believe they know, that Jim Watson sees one of Rosalind Franklin's photographs, something called Photograph 51, which has got this kind of X shape, and that gives them the double helix. Now, the question in all things is, how do you know that? It's expression in science. It's epistemology. How do you know what you know? Even more so in history.
And the actual source of this is very, very hard to pin down. Jim Watson in The Double Helix, he says, it's very vague what he says. He says that he saw, Wilkins showed him some images of the two forms of DNA that there were, the A form and the B form. And we know that from a letter that he actually wrote in March 1953. So we've got contemporary evidence.
He did see something that excited him and made him sure that they could crack the problem. But if it was so obvious... that Jim Watson, this neophyte, who didn't know much about X-ray crystallography at all, he was a zoologist like me, he knew about birds, you know?
If he could see it instantly, then how come Rosalind Franklin, this very, very clever, trained physical chemist, how come she didn't get it? So there's a problem in the story, right? It doesn't quite make sense.
And to cut a very long story short, what we know from Crick's notes that he wrote in 1960 and from a series of interviews that he did in the middle of the 1960s with Robert Olby, who was the first historian to kind of track his work, we know that, in fact, what Watson and Crick did, they knew that the problem could be solved, but that was more because it seemed to be a simple molecule
unlike the proteins they were studying, which are horrendously complicated. So that's what this, whatever Watson saw, it gave him the idea that it was solvable. It was soluble. They could do it. And just using basic chemistry, what was already known, the chemical structure of DNA, and these very simple two-dimensional models of the components, the bases that they're called, they fiddled around.
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Chapter 7: How did Crick's contributions shape modern neuroscience?
The chemistry didn't work. So they went back and they tried over and over and over and over again. And eventually they get a... watson is that they're trying to get the bases to fit on the inside and it doesn't fit and watson literally he turns one of these bits of cardboard over so the base looks like that imagine and then the other base he's trying to get to fit to it he turns it like that
And now he can see that the four kinds of bases make two pairs. A and T make the shape, and C and G, as they're called, make the same shape. So now you can imagine we've got strands on the outside, and the rungs of the ladder are always the same size.
Right.
Now, when they saw that, What Crick said was that it fitted with some evidence from Franklin that they had been shown by their boss, Max Perutz. And this evidence was in a semi-public report that Perutz had been given in December. And which, in fact, one of the things I discovered in writing this book, Franklin had kind of invited Crick to find out about.
Because in January, she was giving a farewell talk. January 53, and she, through a friend, she sent a message to Crick saying, you're welcome to come to this lecture, but it's not going to be very, not going to be much X-ray crystallographic detail. And Max, Max Perutz, Crick's boss, knows all about it, so you may not think it's worth coming.
So this isn't a smoking gun, but it strongly suggests that Franklin was saying, okay, if you want to work on this, this is okay. If you want to know more, ask Max. So the simple answer is nothing gave Watson and Crick the double helix. It was a lot of luck. A lot of luck and trying anything and seeing if it would work and fiddling about for five, six weeks and...
then they were just incredibly lucky. I think that's the real answer. Is that okay? It was a bit long.
Yeah, I mean, a lot of people are going to still believe that.
Oh, yeah, yeah, yeah. You know, there's that XKCD cartoon of the guy at his computer and his wife says, come to bed. And he says, I can't. Someone is wrong on the internet. Well, that's me, right?
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Chapter 8: What is the legacy of the Francis Crick Institute?
And then in 2016, at the centenary meeting at Cold Spring Harbor, Watson said, yeah, I made it up for dramatic effect. And he told Crick's granddaughter the same thing. So read the book, but don't believe it.
All right. So it didn't stop there, of course, regarding the birth of molecular biology. I'm going to get to the 62 Nobel Prize in a minute, but That was 53. In 57, Francis Crick took it a big step further with the central dogma. And then in 61 with the codon three-letter. So he wasn't happy with just structure. He wanted to keep up about what was the functionality of this double helix.
And that seemed to be something that was distinctly that he owned. Is that true?
I think so. I mean, there are lots of people working on these topics, but he's the only person who put it all together, and that's what makes it even more striking. So, for example, messenger RNA, so the intermediate between DNA and protein. We all know about messenger RNA now because of the fantastic things it's done for vaccines.
And Crick is there at the moment that it is conceptualized, it is born. He and Sidney Brenner have this public or semi-public, there's about 10 people in the room, and they start jabbering about all the various results that people have been working on and nobody could fit them together. And they suddenly realize that
that there's this intermediary, and what happens is that it's like, as they said at the time, it's like a piece of tape. It's like a tape. This information comes from the chromosome, from the DNA, and then it's turned into a bit of RNA, which is like a tape, which then goes through the ribosome, which is this structure that was a bit mysterious, to help the cell make a protein.
And that's Crick's thinking, and it's thinking about... Information. That's what's in a gene. It's information. Now, he's not involved in doing any of the experiments. And other people, like Jim Watson, did do experiments that also showed that this mRNA existed. And Jacob and Mono had named it, in fact. But it's Crick and Brenner, his friend Sidney Brenner, who actually have this idea.
So, yeah, he very much... you know, pushed the field forward. I mean, there were hundreds and hundreds of people working in the area by now. But he's the one who actually really, he becomes, especially after they've discovered the triplet code, that it's a trip, almost certainly, the bases are read in three letters, groups of three letters.
And then everybody starts trying to work out what those three letters mean, these 64 possible combinations there are. He becomes like the godfather of code, I said. You know, he travels around
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