Oliver Sacks, "Remembering Francis Crick" (2005)

Remembering Francis Crick

By Oliver Sacks

Francis Crick
 

1.

I read the famous "double helix" letter by James Watson and Francis Crick in Nature when it was published in 1953 —I was an undergraduate at Oxford then, reading physiology and biochemistry. I would like to say that I immediately saw its tremendous significance, but this was not the case for me or, indeed, for most people at the time.

It was only in 1962, when Francis Crick came to talk at Mount Zion Hospital in San Francisco, where I was interning, that I started to realize the vast implications of the double helix. Crick's talk at Mount Zion was not on the configuration of DNA but on the work he had been doing with the molecular biologist Sidney Brenner to determine how the sequence of DNA bases could specify the amino acid sequence in proteins. They had just shown, after four years of intense work, that the translation involved a three-nucleotide code. This was itself a discovery no less momentous than the discovery of the double helix.

But Crick's mind was always moving forward, and clearly he had already moved on to other things. There were, he intimated in his talk, two "other things," great enterprises whose exploration lay in the future: understanding the origin and nature of life, and understanding the relation of brain and mind—in particular, the biological basis of consciousness. Did he have any inkling, any conscious thought, when he spoke to us in 1962, that these would be the very subjects he himself would address in the years to come, once he had "dealt with" molecular biology, or at least taken it to the stage where it could be delegated to others?

It was not until May of 1986 that I met Francis Crick, at a conference in San Diego. There was a big crowd, full of neuroscientists, but when it was time to sit down for dinner, Crick singled me out, seized me by the shoulders, sat me down next to him, and said, "Tell me stories!" I have no memory of what we ate, or anything else about the dinner, only that I told him stories about many of my patients, and that each one set off bursts of hypotheses, theories, suggestions for investigation in his mind. Writing to Crick a few days later, I said that the experience was "a little like sitting next to an intellectual nuclear reactor.... I never had a feeling of such incandescence."

He was especially eager to hear stories of visual perception, and was fascinated when I told him of a patient who had consulted me a few weeks before, an artist who had experienced a sudden and total loss of color perception following a car accident (his loss of color vision was accompanied by an inability to visualize or to dream in color). Crick was also fascinated when I told him how a number of my migraine patients had experienced, in the few minutes of a migraine aura, a flickering of static, "frozen" images in place of their normal, continuous visual perception. He asked me whether such "cinematic vision" (as I called it) was ever a permanent condition, or one that could be elicited in a predictable way so that it could be investigated. I said I did not know.

During 1986, encouraged by the questions Crick had fired at me, I spent a good deal of time with my colorblind patient, Mr. I., and in January of 1987, I wrote to Crick. "I have now written up a longish report on my patient.... Only in the actual writing did I come to see how color might indeed be a (cerebro-mental) construct." I had now started to wonder, I added, whether all perceptual qualities, including the perception of motion, were similarly constructed by the brain. I had spent most of my professional life wedded to notions of "naive realism," regarding visual perceptions, for example, as mere transcriptions of retinal images—this was very much the epistemological atmosphere at the time. But now, as I worked with Mr. I., this was giving way to a very different vision of the brain-mind, a vision of it as essentially constructive or creative. (I also included a copy of my book A Leg to Stand On, because it contained accounts of personal experiences of both motion and depth blindness.)

I got a letter back a few days later— Crick was the promptest of correspondents—in which he sought more detail about the difference between my migraine patients and a remarkable motion-blind patient described by the German neuropsychologist Josef Zihl. My migraine patients experienced "stills" in rapid succession, whereas in Zihl's patient (who had acquired motion blindness following a stroke), the stills apparently lasted much longer, perhaps several seconds each. In particular, Crick wanted to know whether, in my patients, successive stills occurred within the interval between successive eye movements, or only between such intervals. "I would very much like to discuss these topics with you," he wrote, "including your remarks about color as a cerebro-mental construct."

In my reply to Crick's letter, I enlarged on the deep differences between my migraine patients and Zihl's motion-blind woman. I mentioned too that I was working on Mr. I.'s case with several colleagues. My ophthalmologist friend Bob Wasserman had examined Mr. I. several times and discussed his case with me at length, and we had also been joined by a young neuroscientist, Ralph M. Siegel, who had just come to New York from the Salk Institute, where, as it happened, he had been close to Crick. Siegel collaborated with us, designing and conducting a variety of psychophysical experiments with our patient. I mentioned, too, that the neurophysiologist Semir Zeki had visited us from London, and had tested our patient with his color "Mondrians," using light of different wavelengths, and with these, had confirmed that Mr. I. showed excellent wavelength discrimination. His retinal cones were still reacting to light of different wavelengths, and his primary visual cortex (an area which has been named V1) was registering this information, but it was clear that this wavelength discrimination was not in itself sufficient for the experience of color. The actual perception of color had to be constructed, and constructed by an additional process in another part of the visual cortex. Zeki felt, on the basis of animal experiments, that color was constructed in the tiny areas of the visual cortex called V4, and wondered whether Mr. I. had damage to these areas resulting from his stroke.

At the end of October 1987, I was able to send Crick the paper that Bob Wasserman and I had written, "The Case of the Colorblind Painter," ^[1] and having sent this article off to him, I was assailed by intense anxieties— what would he say?—but also by great eagerness to hear his reactions. Both of these feelings waxed in the weeks that followed, for Crick was out of town, his secretary told us, until mid-December.

Early in January, then, I got a response from Crick—an absolutely stunning letter, five pages of single-spaced typing, minutely argued, and bursting with ideas and suggestions. Some of them, he said, were "wild speculation," but it was the sort of wildness that had intuited the double-helix structure of DNA thirty-five years before. "Do please excuse the length of this letter," he added. "We might talk about it over the phone, after you've had time to digest it all." Bob and I, Ralph too, were mesmerized by the letter. It seemed to get deeper and more suggestive every time we read it, and we got the sense that it would need a decade or more of work, by a dedicated team of psychophysicists, neuroscientists, brain imagers, and others, to follow up on the torrent of suggestions Crick had made.

I wrote back to Crick, saying that we would need weeks or months to digest all he had said, but would be getting to work in the meantime, doing tests of motion vision, stereo vision, and contrast vision in Mr. I., as well as more sophisticated color vision testing, and that we hoped to get high-quality MRI and PET scans to look at the activity in his visual cortex.

In his five-page letter, Crick had written, "Thank you so much for sending me your fascinating article on the color-blind artist.... Even though, as you stress in your letter, it is not strictly a scientific article, it has aroused much interest among my colleagues and my scientific and philosophical friends here. We have had a couple of group sessions on it and in addition I have had several further conversations with individuals." He added too that he had sent a copy of the article and his letter to David Hubel, who, with Torsten Wiesel, had done pioneering work on the cortical mechanisms of visual perception.

Writing to me again in January of 1988, he said, "So glad to hear from you and to learn that you plan more work on Mr. I. All the things you mention are important, especially the scans.... There is no consensus yet among my friends about what the damage might be in such cases of cerebral achromatopsia. I have (very tentatively) suggested the V1 blobs plus some subsequent degeneration at higher levels, but this really depends on seeing little in the scans (if most of V4 is knocked out you should see something). David Hubel tells me that he favors damage to V4, though this opinion is preliminary. David van Essen tells me that he suspects some area further upstream."

He mentioned two of Antonio Damasio's cases: in one of these, the patient had lost color imagery, but still dreamed in color. (She later regained her color vision.) "I think the moral of all this," he concluded, "is that only careful and extensive psychophysics on [such] a patient plus accurate localization of the damage will help us. (So far, we cannot see how to study visual imagery and dreams in a monkey.)"

I was very excited to think that Crick was opening our paper, our "case," for discussion in this way. It gave me a deeper sense of science as a communal enterprise, of scientists as a fraternal, international community, sharing and thinking on each other's work—and of Crick himself as a sort of hub, or center, in touch with everyone in this neuroscientific world.

Eighteen months passed without further contact between us, for I was largely occupied now with other, non-visual, conditions. But in August of 1989, I wrote to Crick again, saying that I was still working with our colorblind patient. I also enclosed a copy of my just-published book, Seeing Voices, on sign language and the culture and history of congenitally deaf people. I was especially fascinated by the way in which novel perceptual and linguistic powers could develop in congenitally deaf people, and the brain changes which both resulted from and allowed a very different perceptual experience in them, and in my book I had cited some of Crick's thoughts in this context—he had just published a paper called "The Recent Excitement About Neural Networks." (I also cited Gerald M. Edelman in the same context, and wondered what the relationship of these two extraordinary figures might be, since Edelman had recently relocated his Neurosciences Institute to La Jolla, practically next door to the Salk Institute, where Crick was working.)

Crick wrote back a few days later, and said that he had read my original articles about the deaf and American Sign Language in The New York Review. He had become intrigued by the subject, and looked forward to reading the book ("including the many fascinating footnotes"). "Over the years," he added, "Ursula [Bellugi, his colleague at the Salk] has been patiently educating me about ASL." He urged me, too, to continue my investigation of Mr. I., and enclosed the manuscript of a new article of his: "At the moment I am trying to come to grips with visual awareness, but so far it remains as baffling as ever."

The "short article" he enclosed, "Towards a Neurobiological Theory of Consciousness," was one of the first synoptic articles to come out of his collaboration with Christof Koch at Caltech. I felt very privileged to see this manuscript, in particular their carefully laid out argument that an ideal way of entering this seemingly inaccessible subject would be through exploring the mechanisms and disorders of visual perception.

Crick and Koch's paper covered a vast range in a few pages, was aimed at neuroscientists, and was sometimes dense and highly technical. But I knew that Crick could also write in a very accessible and witty and personable way —this was especially evident in his two earlier books, Life Itself (1981) and Of Molecules and Men (1966). So I now entertained hopes that he might give a more popular and accessible form to his neurobiological theory of consciousness, enriched with clinical and everyday examples. He intimated, in one of his letters, that he would attempt such a book, and in September 1993, his publishers sent me a proof of The Astonishing Hypothesis.

I read this at once with great admiration and delight, and wrote to Crick right away:

I think you bring together an incredible range of observations from different disciplines into a single, brilliant clear focus.... I am particularly and personally grateful that you make such a full and generous reference to the Colorblind Painter whom Bob Wasserman and I studied. I still cherish that marvellous letter you sent me about him. When Semir [Zeki] developed his new technique for PET scanning V4 etc in humans, we did our utmost to get Mr. I. to him, but sadly, Mr. I. became acutely ill at this time with bronchogenic carcinoma and brain metastases, and died within a few weeks (we were not able to get a post-mortem). So it never became clear exactly what happened.

I enclosed a copy of my new article, "To See and Not See," saying that here, too, Bob Wasserman and Ralph Siegel had been invaluable research collaborators, and that we especially hoped to get serial PET scans as this patient, Virgil (who was born virtually blind and given vision through eye surgery as an adult), struggled to establish basic visual perceptions in the vis-ual tumult suddenly loosed on him. (Though here, too, the patient, as with Mr. I., became unable, owing to an unrelated illness, to have such scans.) "I know your own central interests lie in vision, and the ways in which this can illuminate the fundamentals of mind and brain," I wrote, "and in my own rambling, clinical way, I find it is my own favorite subject, too."

The following year, in June 1994, I met with Ralph Siegel and Francis Crick for dinner in New York. As with that first dinner in 1986, I cannot remember what we ate, only that the talk ranged in all directions. Ralph talked about his current work with visual perception in monkeys, and his thoughts on the fundamental role of chaos at the neuronal level (we had worked together writing about chaos and self-organization in the phenomena of vis-ual migraines, as well as chaos in parkinsonism). Francis spoke about his expanding work with Koch and their latest theories about the neural correlates of consciousness, and I spoke about my upcoming visit to Pingelap, an island in the South Pacific with a genetically isolated population of people born completely colorblind —I planned to travel there with Bob Wasserman and a Norwegian perceptual psychologist, Knut Nordby, who, like the Pingelapese, had been born without color receptors in his retinas.

In February 1995 I sent Francis my new book, An Anthropologist on Mars, which contained an expanded version of "The Case of the Colorblind Painter," much amplified, in part, through my discussions with him on the case. (He had immediately assented to my quoting from some of his letters in the revised version, adding that he liked it even more than the original, "if only because you have conveyed more of Mr. I.'s personality.") I also told him something of my experiences in Pingelap, and how Knut and I tried to imagine what changes might have occurred in his brain in response to his achromatopsia. Would the color-constructing centers in his brain have atrophied, in the absence of any color receptors in his retinas? Would his V4 areas have been reallocated for other visual functions? Or were they, perhaps, still awaiting an input, an input which might be provided by direct electrical or magnetic stimulation? And if this could be done, would he, for the first time in his life, see color? Would he know it was color, or would this visual experience be too novel, too confounding, to categorize? Questions like these, I knew, would fascinate Francis too.

Francis and I continued to correspond on various subjects, and I would always try to see him when I visited La Jolla. From 1997 to 2001, I was preoccupied with my memoir Uncle Tungsten, and less intensely with matters of visual consciousness. I continued to see a stream of patients, however, and I often carried on a sort of mental dialogue with Francis whenever puzzling problems came up with regard to vis-ual perception or awareness. What, I would wonder, would Francis think of this—how would he attempt to explain it?

2.

Francis's nonstop creativity—the incandescence that struck me when I first met him in 1986, allied to the way in which he always looked forward, saw years or decades of work ahead for himself and others—made one think of him as immortal. Indeed, well into his eighties, he continued to pour out a stream of brilliant and provocative papers, showing none of the fatigue, or fallings-off, or repetitions, of old age. It was in some ways a shock, therefore, early in 2003, to learn that he had run into serious medical problems. Perhaps this was in the back of my mind when I wrote to him in May of 2003— but it was not the main reason why I wanted to make contact with him again.

I had found myself thinking of time the previous month—time and perception, time and consciousness, time and memory, time and music, time and animal movement. I had returned, in particular, to the question of whether the apparently continuous passage of time and movement given to us by our eyes was an illusion—whether in fact our visual experience consisted of a series of "moments" which were then welded together by some higher mechanism in the brain. I found myself referring again to the "cinematographic" sequences of stills described to me by migraine patients, and which I myself had on occasion experienced. When I mentioned to Ralph Siegel that I had started writing on all this, he said, "You have to read Crick and Koch's latest paper—it came out just a couple of weeks ago in Nature Neuroscience. They propose in it that visual awareness really consists of a sequence of 'snapshots'—you are all thinking along the same lines."

I had already written a rough manuscript of an essay on time when I heard this, but now I read Crick and Koch's paper, "A Framework for Consciousness," with minute attention. ^[2] It was this which stimulated me to write to both Francis and Christof (whom I had seen a few weeks earlier at Caltech), enclosing a draft of my article (entitled, at that point, "Perceptual Moments"). I threw in, for good measure, a copy of Uncle Tungsten, and some other recent articles dealing with our favorite topic of vision. On June 5, 2003, Francis sent me a long letter, full of intellectual fire and cheerfulness, and with no hint of his illness.

I have enjoyed reading the account of your early years. I also was helped by an uncle to do some elementary chemistry and glass blowing, though I never had your fascination with metals. Like you I was very impressed by the Periodic Table and by ideas about the structures of the atom. In fact, in my last year at Mill Hill [his school] I gave a talk on how the "Bohr atom," plus quantum mechanics, explained the Periodic Table, though I'm not sure how much of all that I really understood.

I was intrigued by Francis's reactions to Uncle Tungsten, and wrote back to ask him how much "continuity" he saw between that teenager at Mill Hill who talked about the Bohr atom, the physicist he had become, his later "double helix" self, and his present self. I quoted a letter that Freud had written to Karl Abraham in 1924 —Freud was sixty-eight then—in which he had said,

It is making severe demands on the unity of the personality to try and make me identify myself with the author of the paper on the spinal ganglia of the Petromyzon. Nevertheless I must be he....

In Crick's case, the seeming discontinuity was even greater, for Freud was a biologist from the beginning, even though his first interests were in the anatomy of primitive nervous systems. Francis, in contrast, had taken his undergraduate degree in physics, worked on magnetic mines during the war, and went on to do his doctoral work in physical chemistry. Only then, in his thirties—at an age when most researchers are already stuck in what they are doing—did he have a transformation, a "rebirth," as he was later to call it, and turn to biology. In his autobiography, What Mad Pursuit, he speaks of the difference between physics and biology:

Natural selection almost always builds on what went before.... It is the resulting complexity that makes biological organisms so hard to unscramble. The basic laws of physics can usually be expressed in simple mathematical form, and they are probably the same throughout the universe. The laws of biology, by contrast, are often only broad generalizations, since they describe rather elaborate (chemical) mechanisms that natural selection has evolved over millions of years.... I myself knew very little biology, except in a rather general way, till I was over thirty...my first degree was in physics. It took me a little time to adjust to the rather different way of thinking necessary in biology. It was almost as if one had to be born again.

By the middle of 2003, Francis's illness was beginning to take its toll, and I began to receive letters from Christof Koch, who by that time was spending several days a week with him. Indeed, they had become so close, it seemed, that many of their thoughts were dialogic, emerging in the interaction between them, and what Christof wrote to me would condense the thoughts of them both. Many of his sentences would start, "Francis and I do have a few more questions about your own experience.... Francis thinks this.... Myself, I am not sure," and so on.

Crick, in response to my "Perceptual Moments" paper (a version of which was later published in these pages as "In the River of Consciousness" ^[3] ), quizzed me minutely on the rate of visual flicker experienced in migraine auras. It is only now, looking through our correspondence, that I realize these were matters which we discussed when we first met, in 1986. But this, apparently, we both forgot—certainly neither of us made any reference to our earlier letters. It is as if no resolution could be reached at that time, and both of us, in our different ways, shelved the matter, "forgot" it, and put it into our unconscious, where it would cook, incubate, for another fifteen years before reemerging. Francis and I both had a feeling of complementarity, I think, converging on a problem which had defeated us before, and was now at least getting closer to an answer. My feeling of this was so intense in August of 2003 that I felt I had to make a visit, perhaps a final one, to see Francis in La Jolla.

I was in La Jolla for a week, and made frequent visits to the Salk. There was a very sweet, noncompetitive air there (or so it seemed to me, as an outsider, in my brief visit), an atmosphere which had delighted Francis when he first came there in the mid-1970s, and which had deepened, with his continued presence, ever since. And indeed, he was still, despite his age, a central figure there. Ralph pointed out his car to me, its license plate bearing just four letters: AT GC—the four nucleotides of DNA, and I was happy to see his tall figure one day going into the lab—still very erect, though walking slowly, perhaps painfully, with the aid of a cane.

I made an afternoon presentation one day, and just as I started, I saw Francis enter and take a seat quietly at the back. I noticed that his eyes were closed much of the time, and thought he had fallen asleep—but when I finished, he asked a number of questions so piercing that I realized he had not missed a single word. His closed-eye appearances had deceived many visitors, I was told—but they might then find, to their cost, that these closed eyes veiled the sharpest attention, the clearest and deepest mind, they were ever likely to encounter.

On my last day in La Jolla, when Christof was visiting from Pasadena, we were all invited to come up to the Crick house for lunch with Francis and his wife, Odile. "Coming up" was no idle term—Ralph and I, driving, seemed to ascend continually, around one hairpin bend after another, until we reached the Crick house. It was a brilliantly sunny California day, and we all settled down at a table in front of the swimming pool (a pool where the water was violently blue—not, Francis said, because of the way the pool was painted, or the sky above it, but because the local water contained minute particles which—like dust— diffracted the light). Odile brought us various delicacies—salmon and shrimp, asparagus—and some special dishes which Francis, now on chemotherapy, was limited to eating. Though she did not join the conversation, I knew how closely Odile, an artist, followed all of Francis's work, if only from the fact that it was she who had drawn the double helix in the famous 1953 paper, and, fifty years later, a frozen runner, to illustrate the snapshot hypothesis in the 2003 paper that had so excited me.

Sitting next to Francis, I could see that his shaggy eyebrows had turned whiter and bushier than ever, and this deepened his sage-like and venerable appearance. But this was constantly belied by his twinkling eyes and mischievous sense of humor. Ralph was eager to present his latest work—a new form of optical imaging, which could show structures almost down to the cellular level in the living brain. It had never been possible to visualize brain structure and activity on this scale before, and it was on this "meso" scale that Crick and Edelman, whatever their previous disagreements, now located the functional structures of the brain.

Francis was very excited about Ralph's new technique and his pictures, but at the same time, he fired volleys of piercing questions at him, grilling him, interrogating, in a minute but also in a kindly and constructive way.

Francis's closest relationship, besides Odile, was clearly with Christof, his "son in science," and it was immensely moving to see how the two men, forty or more years apart in age, and so different in temperament and background, had come to respect and love one another so deeply. (Christof is romantically, almost flamboyantly, physical, given to dangerous rock climbing and brilliantly colored shirts. Francis seemed almost ascetically cerebral, his thinking so unswayed by emotional biases and considerations that Christof occasionally compared him to Sherlock Holmes.) Francis spoke with great pride, a father's pride, of Christof's then-forthcoming book The Quest for Consciousness, ^[4] and then of "all the work we will do after it is published." He outlined the dozens of investigations, years of work, which lay ahead—work especially stemming from the convergence of molecular biology with systems neuroscience. I wondered what Christof was thinking, Ralph too, for it was all too clear to us (and must have been clear to Francis too) that his health was declining fast, and that he would never himself be able to see more than the beginning of that vast research scheme. Francis, I felt, had no fear of death, but his acceptance of it was tinged perhaps with sadness that he would not be alive to see the wonderful, almost unimaginable, scientific achievements of the twenty-first century. The central problem of consciousness and its neurobiological basis, he was convinced, would be fully understood, "solved," by 2030. "You will see it," he often said to Ralph, "and you may, Oliver, if you live to my age."

A few months later, in December 2003, I wrote to Francis again, enclosing a copy of the final proof of "In the River of Consciousness," emphasizing how much of it I owed to his paper in Nature Neuroscience. (I added that I had just been rereading Life Itself, and found it even more wonderful on a second reading, especially since I had become deeply interested in the issues it raised. I enclosed a tiny article I had written for Natural History on the possibility of life elsewhere in the universe.)

In January 2004 I received the last letter I would get from Francis. He had read "In the River of Consciousness." "It reads very well," he wrote, "though I think a better title would have been 'Is Consciousness a River?' since the main thrust of the piece is that it may well not be." (I agreed with him.)

"Do come and have lunch again," his letter concluded.

Notes

^[1] The New York Review, November 19, 1987.

^[2] Nature Neuroscience, February 2003.

^[3] The New York Review, January 15, 2004.

^[4] Reviewed by John R. Searle, The New York Review, January 13, 2005.