Francis Crick, thinking about the brain in 1985

Last week’s post recalled a DNA anniversary meeting 30 years that Francis Crick didn’t attend. That prompted me to dig out this lengthy interview with the man himself a couple of years later. My favourite profile piece? Probably. I wrote to him (one did in those days) while planning a trip to California. He rarely gave interviews but maybe he’d be nice to an Englishman coming out West. He replied promptly, saying he was in Cambridge in the Summer, why not come visit? We talked. Odile gave us lunch. We talked some more. This was pretty much my journalist’s dream day. Now, there are two good biographies, one the full deal with access to all his papers. Back then, there was some stuff here which people who only knew he had gone off to the US to do neurobiology hadn’t heard about. The thing I failed to convey here, I think, is how extraordinarily wide-ranging his curiosity was. I lack even a fraction of Crick’s mental powers, but I reckon I’m interested in quite a few things. He knew something, usually quite a lot, about all of them…   Amazing man!

If you won’t want to wade through 2,500 words from me, you can watch him on video on much the same subject a few years later.

Few scientists would seek to start serious work in a new field at 60, and few would be given the opportunity. But Francis Crick’s solution to the problem of growing old in science has been just that. Nine years ago, he ended a 30-year sojourn in Cambridge to join the Salk Institute in Southern California, and decided to think about the brain. The motive was simple: “Because it’s a lot of fun”.

Now nearly 70, Crick still gives the impression that being active in science is the most fun you can have. And by his account he has found the ideal conditions to carry on. The sun shines, he is well paid, has no specific duties and can work as he pleases. “It’s difficult to convey how nice it is working there.” A far cry from working for the Medical Research Council, whose reward for the classic solution of the structure of DNA which Crick achieved with James Watson in 1953 was the offer of a seven-year appointment.

But perhaps there are other motives besides financial security and fun. It would surely have been difficult to sustain the level of his contribution to the subject he helped found just after the war – molecular biology: not because his stature has diminished but because of the enormous scope of the subject as success has prompted expansion. For many years, as richly documented in Horace Judson’s history of the subject in The Eighth Day of Creation, Crick was the universal catalyst in studies of how genes and proteins work at the molecular level. Judson quotes another great theoretician, Jacques Monod: “No one man discovered or created molecular biology. But one man dominates intellectually the whole field because he knows the most and understands the most. Francis Crick.”

For a deeper motivation, go back to Crick’s re-entry into research after war service designing mines for the Admiralty. Although trained as a physicist, his strong materialist conviction drew him to two new areas – how genes worked, and the problem of consciousness. Both seemed to offer a chance of removing the mystery from biology. He plumped for genes then, but the other interest remained. And the Crick now working on the brain is the same optimistic atheist, still convinced science must make its own way forward without reference to other belief systems: the Crick who resigned his founding fellowship of Churchill College, Cambridge, when they built the college chapel.

Returning to neurobiology now carries echoes of the state of molecular biology immediately before and after the war. As Crick sees it, “It’s in a very primitive and simple state. It’s rather like people in the 1920s and 1930s trying to imagine what the structure of a gene should be.” But it was not possible to wait any longer – when he decided to go to California he was mindful of his age: “I thought that if I was going to make the change I’d better get on with it.”

Not that Crick’s powers show any serious decline. The sandy hair is now white, but he is still the tall, lean, garrulous figure who directed the traffic of ideas in molecular biology for so long.

The Crick you may meet on one of his annual summer visits to Cambridge is not the cartoon Crick of Watson’s stylised memoir The Double Helix, with its famous opening: “I have never seen Francis Crick in a modest mood.” Nor is it the reminiscent Crick, the historical figure who fills page after page of Judson’s book with well-turned quotes about the way it was – in the days of the DNA discovery, or unravelling the genetic code, or piecing together the mechanism of protein synthesis. It is a Crick still deep in the business of science, and eager to talk about the field which now fills his thoughts.

And a remarkably complex field it is. The few pounds weight of grey matter in our heads contains around one hundred thousand million neurons *- the building blocks of the nervous system. And each neuron is linked to as many as ten thousand others, and influences them through a combination of chemical and electrical signals. Although the system’s speed of operation at the level of cellular messages is slow compared with human-built computers, its richness and interconnection still makes a myriad of tasks which leave computers looking stupid so simple for us re rarely realise how remarkable they are – seeing, hearing, speaking of listening all remain essentially mysterious.

Of course, Crick’s approach to neurobiology is shaped by his deep knowledge of molecular biology, as well as being influenced by the same metaphysical conviction. HIs own focus is on the visual system, partly because of a long tradition of work in the field, partly because he has a sense it may be possible to make progress there. Crick is not particularly interested in “black box” descriptions of vision, or in whether it can be successfully modelled on a computer – he wants to know how it actually works in the brain. “You have to think in a very different way – once you’ve got away from the idea that there’s someone inside your head looking at what’s going on. You have to explain how it is that you perceiving things is all done by neurons firing. It’s a very, very strange thing”.

You can hear the molecular biologist talking when he describes others working on the same problems, feeling that many of them, especially if they have come from physics or mathematics, have no idea what a biological system is like. “They know in principle it evolves through natural selection, but they don’t know what sorts of things you tend to get in biological systems.”

Crick thinks he does. And he is dubious about the search for very general algorithms to account for feats like vision, which many researchers seek under the influence of ideas from computer science. “It doesn’t look like that to me. It looks like a lot of devices, and bits of gadgetry which are put together and all interact in fancy ways.” If this sounds like the picture of the cell built up in the 1960s, it could just as well describe the intricate designs for mines, detectors, and devices to fool the detectors which Crick dreamed up in the war years.

He also notices the contrast with the spectacular progress of studies of genes and proteins. In neurobiology, he finds, especially studies of cognitive processes, “there’s no-one with any real experience of success. They hardly know what it is to discover something. It’s very peculiar!”

If he is modest about the field as a whole, he also deprecates his own contribution, pointing out that it would be foolish to go into a new field at 60 and expect to overturn it. He has high standards on what counts as a genuine contribution. “A striking success has to be something which the people in the field initially won’t believe…   because if it’s so commonplace that it’s obvious, why do you have to have a theorist to tell you?”

On this criterion, the jury is still out on his most recent sustained piece of work, on how the brain fixes on small regions of the visual field in turn to keep track of the big picture – the problem of visual attention.

A sequence of eye movements in series accounts for part of the scanning process, but there is also evidence for a further serial scanning within the brain itself. This trick, christened the searchlight by the psychologist Anne Triesman, is described by Crick in a paper published last year: The searchlight is not supposed to light up part of a completely dark landscape but, like a searchlight at dusk, it intensifies part of a scene that is already visible to some extent.”

Characteristically, Crick argues that the natural question to ask is where this could be going on in the brain. And he has suggested that what is known of the properties of groups of neurons in the thalamus fits them to control the searchlight – amplifying the inputs received in small regions of visual cortex, one at a time.

It has proved a hard theory to devise tests for, and Crick himself is not equipped to do experiments at the Salk by his own choice. He hopes his hypothesis will prove correct, but it does not seem to have mobilised many experimenters eager to take up the challenge. “It would be nice to report it has really got things moving”, he admits, but it has not yet. And experiments are ultimately the key. As he wrote in Life Itself, a popular book about the origin of life: “Thirty years of experience in molecular biology has taught me that plausibility is not enough. It will not do just to put the nail on end and give it a little tap. It is essential to drive it home. To give a theory the degree of certainty we need, we have to hit it hard, again and again.”

Hitting the nail perhaps grows harder as the years pass. And it is probably also harder as Crick has yet to find a close co-worker to sign up for the Salk. Apart from being a great scientist, he has been a great collaborator – first with Watson on DNA, later with Sidney Brenner and others**. He does work with others now, notably with the Englishman Graeme Mitchison, whose interests overlap and who stays at the Salk from time to time developing simulations of neural networks. But aside from this, there is no long-term partnership in view.

One product of his continuing intermittent discussion with Mitchison was an assault on another mystery of the brain – human dreaming. A widely publicised joint paper in Nature two years ago proposed that the function of sleep is “to remove certain undesirable modes of interaction of networks of cells in the cerebral cortex”, through a kind of reverse learning.

This paper, which Crick now seems to regard as a bit of a sideline, nevertheless bears the hallmarls of his scientific style: there is a carefully constructed theoretical argument – there needs to be a way of activating spurious connections between neurons, and modifying the connections so they are less likely to recur; the argument is tightly linked to evidence about sleep and about properties of neural networks; it is elegantly expressed – “we dream in order to forget”, the authors write at one point. All it lacks is any way of testing the proposal rigorously by experiment.

It also shows why his style is often unpalatable to non-scientists. The drams paper is fascinating to read, but puts forward ideas which rob the nocturnal images we remember of any meaning. By this argument, the dreams which stay in the mind are aberrations, failures to erase nonsense messages in an information processing system. This treatment of problems with wide popular resonance – the origin of life, the nature of inheritance, consciousness, dreaming – in what Crick regards as a properly scientific spirit makes one believe the feeling he describes in Life Itself, that a modern scientist lives in a different culture.

In some ways, he now finds it easier to find common ground in chance encounters. He recalls how 20 years ago “you could go to a party in Cambridge and talk to a perfectly intelligent person who didn’t know that the sun was a star.” That happens less often now, but it is still hard to put across the thinking behind work in progress, especially work on the brain, where we have many problems and few solutions.

On a more philosophical level, he now takes a long view. “If you want to establish that dualism is wrong, for example, it’s not going to be done in a short time – there will be many tens of years of work.”  Even in molecular biology, the reductionist approach is not completely secure, though there is every reason to be confident. “We can see how powerful it is to have genes producing proteins and proteins interacting…   but we couldn’t answer someone who was extremely sceptical because we just don’t have detailed answers. We couldn’t say how you build a hand.”

Again, the difference in looking at the brain is that we do not yet see how such a question could be answered. As Crick puts it, we have not yet found the right idiom for solving problems of brain function. Artificial intelligence research has been helpful, but chiefly in showing how complex faculties like vision are. And even if there are hints about how to solve problems of vision for machines, they do not look to Crick as if they are going to be the same as the solutions which have evolved inside the head, any more than the flight of aeroplanes is exactly like the flight of birds.”

If the hope of progress in brain research stretches far into the future, Crick’s own scientific life clearly cannot. But he intends to remain active in the field for a while yet. He gives the impression of preparing to grow old, but he is certainly not ready now. And while he will debate the merits of returning to London when he finally retires, perhaps to write a book on the brain, he also avers that he and his artist wife Odile now feel like California natives***.

His career has spanned an extraordinary era in biology. The science obsessed Mill Hill schoolboy who began work as a physicist before the war can now look back on a string of successes in unravelling the intimate workings of the cell. Along the way, he acquired a Nobel prize, for the solution of the double helix with which his name will always be linked, and a kind of celebrity. (He relates with a grin how he did not have the heart to tell the Cambridge publican who showed him the helical plant frame in his garden that he had built a wrong-handed helix).

Yet for all the changes of the last 40 years, his own pattern of work has remained unusually stab;e. He has taught little, and never directed any large-scale research. He declares himself allergic to committees, and turned down a couple of Cambridge masterships because they involved all the things he did not like. In a way, it has been an indulgent life, reading, writing and talking – and Crick can talk on a sparkling variety of subjects. But the indulgence has always been underpinned by a fecundity of ideas and an intellectual zest rarely matched in any field. No doubt the luminosity of Crick’s intelligence has dimmed somewhat since he first started t exercise his talent for solving problems of biological gadgetry. But that seems no reason to stop work. Asked to describe his role in neurobiology today, he laughs and recommends asking others how they see him. “My point of view is that I’m having a good time.” (1985)

*1985 figure – latest counts somewhat reduced

** Leslie Orgel deserved a mention here as another hugely important partner – as Crick politely pointed out after this piece appeared. He did later find his neurobiology partner, Christof Koch.

*** He stayed at the Salk, and went on working and publishing up to his death in 2004…

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