My brief interview of Matthew Cobb about his new biography of Francis Crick

Matthew Cobb’s new biography of Francis Crick has been out for only a short time, but I’ve never seen a review less than enthusiastic (check out this NYT review). I finished it last week, and was also enthusiastic, finding it one of the best biographies of a scientist I’ve ever read. It concentrates on Crick’s science, but his accomplishments were inseparable from his personality, which focused not only on science but also on poetry (the book begins and ends with a poet), drugs, women, and philosophy (he was, by the way, a hardcore atheist and determinist).

But I digress. I really recommend that if you have any interest in the man and his work, which of course includes helping reveal the structure of DNA, you get this book and read it. It is a stupendous achievement, based on tons of research, sleuthing, and interviews, and only a geneticist could have written it. But it’s not dull at all: Matthew has always written lively and engaging prose. Crick is also a good complement to Matthew’s previous book, Life’s Greatest Secret, about how the genetic code was cracked.

As a complement, a biography of Jim Watson by Nathaniel Comfort is in the works, but hasn’t yet been published.

After I finished the book,  I had a few questions about Crick and his work, and asked Matthew if I could pose them to him and post his answers. on this site  He kindly said “yes,” and so here they are. My questions are in bold; Matthew’s answers in plain text. Enjoy:

What one question would you ask Crick if he could return from the dead? (Perhaps something that you couldn’t find out about him from your research.)

I think I would probably ask him about his view of the state of consciousness research. His key insight, with Christof Koch, was that rather than trying to explain everything about consciousness, researchers should look for the neural correlates of consciousness – neurons that fired in a correlated manner with a visual perception – and ask what (if anything) was special about how they fired, their connections, and the genes expressed within them. Since his death, we have obtained recordings from such neurons, but far from resolving the issue, consciousness studies have lost their way, with over 200 different theories currently being advanced. What did he think went wrong? Or rather, is it time to use a more reductionist approach, studying simpler neural networks, even in animals that might not be thought to be conscious?

 

Why did it take ten years—until the Nobel prize was awarded—for people to appreciate the significance of DNA?

Most people imagine that when the double helix was discovered it immediately made Watson and Crick globally famous and the finding was feted. That was not the case, mainly because the actual evidence that DNA was the genetic material was restricted to Avery’s 1944 work on one species of bacterium (this was contested) and a rather crappy experiment on bacteriophage viruses (this was the famous paper by Hershey and Chase from 1952; the experiment was so messy that Hershey did not believe that genes were made solely of DNA). So although the structure of DNA was immediately obvious in terms of its function – both replication and gene specificity, as it was called, could be explained by reciprocal base pairs and the sequence of bases – there was no experimental proof of this function. Indeed, the first proof that DNA is the genetic material in eukaryotes (organisms with a nucleus, including all multicellular organisms) did not appear until the mid-1970s! Instead, people viewed the idea that DNA was the genetic material as a working hypothesis, which became stronger through the 1950s as various experiments were carried out (eg., Meselson and Stahl’s experiment on replication) and theoretical developments were made (eg Crick’s ideas about the central dogma). Its notable that the Nobel Prize committee awarded the prize in 1962, just after the first words in the genetic code were cracked and the relation between DNA, RNA and protein had been experimentally demonstrated.

A lot of the latter part of the book is on Crick’s work on neuroscience (and, later, consciousness). You claim that he made enormous contributions to the field that really pushed it forward. Could you tell us a bit about what those contributions were?

Although he did not make a great breakthrough, he helped transform the way that neuroscience was done, the ideas and approaches it used. From the outset – a 1979 article in a special issue of Scientific American devoted to the brain – he focused attention on one particular aspect of brain function (he chose visual perception), the importance of theoretical approaches rooted in neuroanatomy, the need for detailed maps of brain areas and the promise of computational approaches to neural networks. All these things shaped subsequent developments – in particular the work on neural networks, which he played a fundamental part in, and which gave rise to today’s Large Language Models (he worked with both Geoffrey Hinton and John Hopfield, who shared the 2024 Nobel Prize in Physics for their work on this in the 1980s). And, of course, he made the scientific study of consciousness scientifically respectable, taking it out of the hands of the philosophers who had been tinkering with the problem for three thousand years and hadn’t got anywhere. Later, in a perspective article he published on the last day of the old millennium, he reviewed recent developments in molecular biology and predicted that three techniques would become useful: classifying neurons not by their morphology but by the genes that are expressed in them, using genetic markers from the human genome to study the brains of primates (the main experimental system he advocated using), and controlling the activity of neurons with light by using genetic constructs. All these three techniques – now called RNAseq, transcriptional mapping and neurogenetics – are used every day in neuroscience labs around the world. Indeed, within a few months of the article appearing, Crick received a letter from a young Austrian researcher, Gero Miesenböck, telling him that his lab was working on optogenetics and the results looked promising. During his lifetime, Crick’s decisive leadership role was well known to neuroscientists; now it has largely been forgotten, unfortunately.

 

Is there anything a young scientist could learn from Crick’s own methods that would be helpful, or was he a one-off whose way of working cannot be imitated?

I think the key issue is not so much Crick as the times in which he worked. As he repeatedly acknowledged, he was amazingly lucky. From 1954-1977 he worked for the Medical Research Council in the UK. He did no teaching, no grading, was not involved in doctoral supervision (I’m not even clear how many PhD students he technically supervised – 4? 3? 5? – which highlights that even if he had his name on a bit of paper, he had little to do with any of them). Apart from a couple of periods, he had no administrative duties, and only one major leadership post, at the Salk, which nearly killed him. He wrote one major grant application at the Salk (the only one he ever wrote), but basically he was funded sufficiently well to simply get on with things. And what did he do? ‘I read and think,’ he said. Try getting that past a recruitment or promotions panel today! In a way, the onus for the creation of more Cricks does not lie with young researchers, but with established scientists – they need to allow young people the time to ‘read and think’, and value failure. Most ideas will turn out to be wrong; that’s OK. Or at least, it was to Crick. Many senior researchers (and funders) don’t see things that way. However, even without such changes, young scientists can adopt some of Crick’s habits. Here’s my attempt to sum up what I think were the lessons of his life and work:

• Read widely and avidly, even engaging with ideas that might seem eccentric or pointless, as ‘there might be something in it’ (one of his favourite phrases).
• Talk through your ideas with your peers – try to find the weak spots in each other’s arguments.
• At least in the initial stages of research, don’t get bogged down in the details that might counter your interpretation/theory – Crick and Brenner called this the ‘don’t worry’ approach. They figured that unconnected contrary data points might not undermine their ideas, and would eventually turn out to have specific, varied explanations.
• Write down your ideas in the form of memos or short documents (keep them short). Writing helps you clarify your ideas and shaped your mind – do not use AI to do this! You can then share your writing with peers, which can be used as a target for discussion and debate.
• Master the art of clear writing. Avoid jargon, keep your ideas straightforward. Again, the only way to develop this skill is to write – badly at first. So rewrite, edit, recast your writing – it will improve your thinking.
• Above all, make sure that the science you do is *fun*. That was a word that Crick repeatedly used, and he genuinely got great pleasure from doing science and thinking about it. Seek out an area in which you can have fun and aren’t bogged down by drudgery.

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