Skip to main contentU.S. National Library of MedicineU.S. National Library of Medicine

Profiles in Science
Pinterest badge Follow Profiles in Science on Pinterest!

The Francis Crick Papers

From Molecular Biology to Neurobiology, 1976-2004

[Francis Crick at a dinner at the Nobel Prize Winners Conference in Lindau, Germany]. [Between 29 June-3 July 1981].
Documents Visuals

After making path-breaking discoveries in molecular biology over the course of three decades, Crick, at the age of sixty, embarked on a second scientific career, at a new institution, in a new country, and in a new discipline. In 1976, he took a sabbatical year--a sabbatical, contemporary news accounts suggested, from high British taxes as well as from low British pay--at the Salk Institute, a privately-funded biomedical research facility in La Jolla, California. Crick had been affiliated with the Salk Institute for the first twelve years after its construction in 1962 as a non-resident fellow, a member of the visiting committee that advised the institute on appointments and the direction of its research. In 1977, the Kieckhefer foundation endowed a chair for him at the institute, and he accepted a permanent appointment there that he held for the rest of his life.

For Crick, his move to the Salk Institute was a unique opportunity to take up the second of the two scientific fields for which he had discovered a passion thirty years earlier, when he applied the "gossip test" to his career decision: neurobiology. First, though, he had to extricate himself from his first chosen field, molecular biology. That transition took several years because fellow scientists continued to rely on his unrivalled knowledge of molecular biology, and because the rapid progress in DNA research during the second half of the 1970s kept him engaged.

Meanwhile, Crick was drawn by his longtime friend Leslie Orgel into yet another field, the study of the origins of life and of evolution, a field to which Orgel had devoted his career. It was an area of science that, like molecular biology and neurobiology, attracted him because he found there a similar need for a unifying theory. No less did he find there cause to argue against creationist or, as he called them, vitalist views, the belief that life was created and sustained by an animating, metaphysical force whose existence could not be proven. In a book entitled Life Itself, published in 1981, Crick posited instead that life on earth originated from microorganisms deliberately seeded by a higher civilization via unmanned spaceships. Crick called his speculative theory "directed panspermia," a reference to the idea of "panspermia" advanced in 1907 by Svante Aarhenius, who suggested that life on earth had been seeded by microorganisms drifting through space. Crick's theory proceeded from the fact that the genetic code is uniform across almost all species and thus likely evolved from a small original or intermediate population, and from the second fact that the earth is less than half the age of the universe, allowing time for life to evolve elsewhere first before it evolved here.

If the book was an expression of Crick's self-confidence (which other scientist would dare invoke alien space ships in explaining natural phenomena?), it also had a serious purpose as a meditation on the nature of scientific theory for a lay audience, rather than as a detailed study of evolution. The book called for a convergence of sciences--cosmology and astronomy, biology and chemistry--to solve the mystery of the origin of life on earth, just as collaborators from different scientific disciplines had uncovered the secrets of the gene.

Leaving behind his long-standing, firmly-established interests, as well as his newly-found, speculative ones, Crick shifted his focus to neurobiology by the early 1980s. He was skeptical of the behaviorist and functionalist approaches to the study of the human brain which were predominant among psychologists. These researchers believed that human behavior should be studied by itself without taking into account the neurological processes that might govern it. In essence, behaviorists treated the brain as a "black box" whose inner workings were irrelevant to their studies.

Cognitive and computational neuroscientists did construct mathematical and computer models of brain functions, but to Crick they appeared no more interested than psychologists in the biology of the brain, or in determining how closely their models approximated nature. He wanted to look inside the human brain, to study the networks, connections, and firing patterns of neurons, which in his view gave rise to mental activity and consciousness. He insisted that only the study of brain functions at the molecular level would uncover the neural correlates of consciousness, that is, the smallest array of neurons associated with a particular perception. Within a generation, Crick predicted, psychology and neuroscience would undergo a molecular revolution similar to the one biology had undergone in the 1950s.

In neurobiology as in genetics, Crick chose the role of theorist more than experimenter. His contribution was to assimilate disparate ideas and experimental results from a wide range of disciplines, and from them to propose new theories and new experiments. His research focused on the visual system of mammals, an area of neuroscience that offered rich experimental data. He sought to determine how the brain formed an accurate, meaningful representation of the outside world by binding together differently processed aspects of an object (such as its shape, color, and movement) to which it pays attention into one coherent mental image, while ignoring other elements of the visual field. Crick argued that such "attentional bias" determined which of the competing interpretations of the visual field produced by separate arrays of neurons would be selected to become the conscious image of this observed reality.

As he had when he moved from physics to biology in the late 1940s, Crick educated himself deeply in his newly-chosen field, reading experimental papers and reviews in neuroanatomy, neurophysiology, and psychophysics, the branch of psychology that deals with the quantitative relationship between physical inputs, such as light, and a person's or animal's response to such stimuli. He also forged a new set of scientific contacts with researchers such as the psychophysicists Robert Boynton and Vilayanur S. Ramachandran, the cognitive neuroscientists David Rumelhart, James L. McClelland, and Tomaso Poggio, the neurophilosophers Paul and Patricia Churchland, and, most closely, with the computational neuroscientist Christof Koch.

Crick's first foray into neurobiology led him to work on dendritic spines, little outgrowths on the tree-like extensions, or dendrites, of pyramidal neurons in the cerebral cortex through which most synaptic signals generated by external stimuli (such as visual clues) are routed.

In 1982, he and Graeme Mitchison published an article in which they postulated that the function of rapid-eye movement sleep was to allow the cortex to perform an essential house cleaning or "reverse learning" process, by discarding unnecessary memories so that the brain does not become overloaded and produce false memories (a confusion of memories that have something in common). In an influential article written with Koch in 1990, Crick sought to circumvent the long-standing philosophical stalemate about the mind/body dichotomy by contending that in order to examine consciousness scientifically, one does not first have to define it. The two thereby cleared the way for neuroscientists to study a subject most had shunned as elusive, contentious, and not respectable. Crick laid out his case against behaviorism for a general audience in his 1994 book, The Astonishing Hypothesis, in which he gave a survey of his and Koch's work on the psychology and neurobiology of the visual system. The title of the book referred to his scientific belief that "our minds--the behavior of our brains--can be explained by the interaction of nerve cells (and other cells) and the molecules associated with them."

Even though he acquired a broad knowledge of the field of neurobiology, Crick admitted that "I have yet to produce any theory that is both novel and also explains many disconnected experimental facts in a convincing way"--the very essence of his earlier, seminal accomplishments in unraveling the structure of DNA and the genetic code. Yet he never gave up what he called, with the poet Keats, his "mad pursuit," fascinated by his vastly complex subject and convinced of its intrinsic importance. He was editing a manuscript written jointly with Koch only days before his death from colon cancer on July 28, 2004.