View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by PubMed Central Open access, freely available online Obituary Francis Crick’s Legacy for Neuroscience: Between the α and the Ω Ralph M. Siegel*, Edward M. Callaway ‘You’, your joys and your sorrows, your memories Hubel and Wiesel wrote of functional new ideas of a theoretical neurology and your ambitions, your sense of personal architectures, embedded in beautiful, to the brain (Marr 1969, 1970). And identity and free will, are in fact no more than almost crystalline structure. The he saw the tragedy of Marr being cut the behavior of a vast assembly of nerve cells…” comprehension of mind invoked by a off from solving the big problems for —Crick (1994, p. 3) biological mechanism appeared ripe which he was so clearly destined. for the sort of thoughtful, theoretical During those early years, Francis rancis Crick was an evangelical science he had applied to DNA. Francis must have thought that consciousness atheist. He believed that scientifi c was now sixty years old and moved from was tractable—if only the right way of Funderstanding removed the need Cambridge to the Salk Institute in La thinking was brought to bear on it. for religious explanations of natural Jolla, California. Francis began with the Francis’s brain was capable of collecting phenomena. From James Watson’s brightest young minds he could fi nd. and fi ling away many disparate and his early work, the structure of David Marr was a young data, which he could then combine DNA explained the α, the origins of mathematician and physiologist uniquely and imaginatively, leading life. This was a starting point; from the whose doctoral thesis on a theory to that “dramatic moment of sudden elucidation of the structure of DNA, of mammalian brain function at enlightenment that fl oods the minds there was an explosion, a massive Cambridge had brought him into some when the right idea clicks into place” diversity of science that in part removed contact with Brenner and Francis. (Crick 1990, p. 141). Whatever his the need to postulate a creator or a A professor at the Massachusetts initial thoughts about the nature of the creation myth. Francis still felt that life Institute of Technology, he began problem, Francis soon came to realize was no less astonishing just because it working with Tomasio Poggio of the that the problem of consciousness was was biological and natural in origin. Max Plank Institute in Tübingen on a even tougher than he imagined, that He had a consistent and completely computational theory of neuroscience. the “click” was not happening with rational world view without a need to Following an invitation from Francis, consciousness. In 1988, he wrote, “I invoke vitalism, or any non-material Poggio and Marr spent the month of have yet to produce any theory that force (M. Crick 2004). And in the last April, 1979 extending their intense is both novel and also explains many decades of his life, he applied this examination of the core problems of disconnected facts in a convincing way” philosophy to the Ω, consciousness. visual perception. They spent hours (Crick 1990, p. 162). Once the structure of DNA was sitting at the most western end of Over the quarter century he was at known, the physicist George Gamow the Salk Institute, at the cafeteria or the Salk Institute, Francis did propose formed the RNA Tie Club, with Francis in Francis’s offi ce, gazing into the solutions to some smaller problems and eighteen others including his Pacifi c Ocean with all its daily changes, in neuroscience (Sejnowski 2004) close friends Leslie Orgel and Sydney discussing not only architecture of and brought consciousness into the Brenner (2001); it was an ingathering visual cortex and visual perception, scientifi c fold (Rich and Stevens that sowed seeds for future molecular but the ramifi cations of a good theory 2004). But something else was going biologists (Judson 1996). DNA had of brain function. We know of these on quietly and behind the scenes. become the “α,” the beginning conversations, as the probing of Marr (Bronowski 1978), not just of Francis’s by Francis is captured in the fi nal Citation: Siegel RM, Callaway EM (2004) Francis Crick’s career, but of a whole new culture of chapter of Marr’s now classic book legacy for neuroscience: Between the α and the Ω. PLoS Biol 2(12): e419. scientifi c life and understanding (Crick “Vision” (Marr 1982). (Although Marr 1966). speaks of a three-way conversation, Copyright: © 2004 Siegel and Callaway. This is an Ten years later, the secrets of judging from our own experiences open-access article distributed under the terms of the Creative Commons Attribution License, which DNA transcription and translation as Francis’s younger colleagues, permits unrestricted use, distribution, and reproduc- unmasked, Francis turned to the interlocutor simply seems to be tion in any medium, provided the original work is consciousness. He admitted he knew Francis.) properly cited. little at fi rst, only that the structure of Marr had been diagnosed with acute Ralph M. Siegel is an associate professor in the Center consciousness was as tough a problem leukemia in the winter of 1978 (Marr for Molecular and Behavioral Neuroscience, Rutgers University, Newark, New Jersey, United States of as DNA’s structure. DNA was certainly and Vaina 1991). The one-month visit America. Edward M. Callaway is an associate professor not played out, but the Ferrier Lectures to the Salk Institute was an intellectual in the Systems Neurobiology Laboratories, The Salk in the Proceedings of the Royal Institute for Biological Studies, La Jolla, California, gift, for eighteen months later, Marr United States of America. Society of London by David Hubel died. Francis had simultaneously lost and Torsten Wiesel were just available, a young friend and colleague who had *To whom correspondence should be addressed. E-mail: [email protected] tempting Francis with an almost brought an “incisive mind and creative physicist’s view of neurons in action. energy” (Crick 1994, p. 77) and his best DOI: 10.1371/journal.pbio.0020419 PLoS Biology | www.plosbiology.org 2029 December 2004 | Volume 2 | Issue 12 | e419 DOI: 10.1371/journal.pbio.0020419.g001 Francis Crick in his offi ce. Behind him is a model of the human brain that he inherited from Jacob Bronowski. (Photo: Marc Lieberman) Francis was building an army to help and post-doctoral trainees, with described three needed methods: him take on consciousness. This was conversation ranging across science— fi rst, a method by which all the not empire building with Francis as the Francis listening to their stories of their connections to a single neuron could head of a group of directed scientists explorations and encouraging them to be stained; second, a method by which in the Cambridge or German model. reach beyond their horizons. Francis “all neurons of just one type could be Francis continually encouraged and had a “love of the truth and helped inactivated, leaving the others more or assisted young scientists to approach others to move to the truth” (Watson less unaltered”; and third, a means to the hardest problems of the brain. 2004). differentially stain each cortical area, Marr and Poggio were just the fi rst When Francis worked on the “…so that we could see exactly how recruits he helped embolden. He structure of DNA, he had some simple many there are, how big each one is started his long-time collaboration with facts, such as Chargaff’s Laws, and and exactly how it is connected to other Christof Koch, once a post-doctoral means to make point mutations from areas.” By the mid-1980s, Francis had trainee with Poggio, on “The Problem which it could be determined how realized that these massive holes in our of Consciousness” (Crick and Koch function followed structure. But not a understanding of the most simple brain 1990, 1992). His door was always open single neuroanatomist knew how many facts were not being fi lled. Something to graduate students, postdoctoral neurons actually converged in their needed to be done. trainees, faculty who wanted to discuss input to a particular single cell. No one Over the twenty years since the those problems as many others and knew how to eliminate a specifi c cell RNA Tie Club, molecular biology we can attest. Francis could be found type from a circuit— to make a point had matured. Francis actively began daily at tea time, an ingathering of mutation, so to speak, in the structure encouraging the inclusion of the the Salk Institute computational and of consciousness. His 1979 article in critical tools of molecular biology in the vision laboratories of Simon LeVay, Scientifi c American, “Thinking about study of neural circuits and perception; Terry Sejnowski and Thomas Albright, the Brain,” did not have much impact in his thinking, molecular biology was surrounded by graduate students at the time, even when it explicitly critical to understand how the brain PLoS Biology | www.plosbiology.org 2030 December 2004 | Volume 2 | Issue 12 | e419 worked because it provided tools. He same hopes to open the doors of of consciousness might outlast him. would encourage junior scientists, post- consciousness (to paraphrase Huxley Francis was walking with a cane, doctoral trainees, and faculty—all those 1963). Watson and Crick used their still not waiting for anyone, nor who had visited him over the years—to intuition to fi ll in the gaps. But Francis allowing anyone to wait for him. He think about using these tools. He would found that there were just too many continued to fi nd time for new faces give short homilies about the plethora possibilities, and the gaps in knowledge in the fi eld and continued to work on of sub-types of neurons in the retina; were still just too big for consciousness.