Time, Love , Memory

by Jonathan Weiner

  But when he talks this way at the Red Door, his postdocs are likely to give him the same raised eyebrows and molecular smiles they have learned from Benzer. “If flies had free will,” they tell Benzer, “your lab would be empty.”

  Benzer gets no further when he talks about this question with Carol, describing the zigzags of his flies in the countercurrent machine. “So what is that?” he asks. “Is that free will? If the fly makes up its own mind?”

  “Well, the problem is, you don’t know what its mind is to make up,” Carol says.

  “I’d say free will means, if you are subjected to identical stimuli, you don’t necessarily do the same thing …”

  And so they go around and around, even people who live with their hands in rubber gloves deep in genes and brains. Perhaps it is still too soon to talk about the question. A sense of paradox still hovers over the whole picture of life, from the smallest scale to the largest.

  How is it possible that these two things should be true at once? Schrödinger asks in What Is Life?: first, that his body is a mechanism, a clockwork, and runs according to the laws of nature; second, that he knows “by incontrovertible direct experience” that he is running the show, that he is directing the motions of his body, that he can foresee what he is doing, and that he can take responsibility for his actions. As he struggles to answer these questions in the last pages of What Is Life?, Schrödinger begins to sound a little like Berger on the wall of Seymour’s Sandwich Shop. He quotes Schopenhauer and Kant; the cultural milieu (Kulturkreis); the Upanishads’ recognition that ATHMAN = BRAHMAN (the eternal self); and the Christian mystics’ phrase DEUS FACTUS SUM (I have become God). Schrödinger concludes that there is only one consciousness “and that what seems to be a plurality is merely a series of different aspects of this one thing, produced by a deception (the Indian MAJA); the same illusion is produced in a gallery of mirrors, and in the same way Gaurisankar and Mt. Everest turned out to be the same peak seen from different valleys.”

  Each of us feels like an “I.” “What is this ‘I’?” Schrödinger asks. How is it that each of us feels like one single person even though we began life so long ago that we have lived through a succession of more identities than the instars of insects, and the world of our first memories feels to us like a distant country? In spite of all the living and all the forgetting that we have done, and in spite of all the mechanisms that science has discovered over our heads and inside our heads, we are all still here living life. “In no case,” Schrödinger wrote, “is there loss of personal existence to deplore.”

  And, he concluded, “Nor will there ever be.”

  NERVES, as they grow in an embryo, seem to wander like flies in a countercurrent machine. Each of them is guided by genes, yet on each scale there seems to be some play in the system.

  Likewise, there seems to be play in the system for each of us as we make the choices we do. “A human behavior pattern is not a monument to a life that is gone, but a drama full of life,” writes the philosopher Abraham Heschel. “It is a system as well as a groping, a wavering, a striking forth; solidity as well as outburst, deviation, inconsistency; not a final order but a process, conditioned, manipulated, questioned, challenged, and guided.”

  “Diversity is as wide as all the tones of voice, ways of walking, coughing, blowing one’s nose, sneezing,” writes Pascal. “We first distinguish grapes from among fruits, then muscat grapes, then those from Condrieu, then from Desargues, then the particular graft. Is that all? Has a vine ever produced two bunches alike, and has any bunch produced two grapes alike?

  “I have never judged anything in exactly the same way,” he continues. “I cannot judge a work while doing it. I must do as painters do and stand back, but not too far. How far then? Guess.…”

  Even in the behavior of our thoughts, there is play in the system. We all feel them zigzag, heading for the light, but on again, off again, like the fly in the countercurrent machine. “Thoughts come at random, and go at random,” Pascal wrote. “No device for holding on to them or for having them.

  “A thought has escaped: I was trying to write it down: instead I write that it has escaped me.”

  Emerson wrote, “Thoughts come into our minds by avenues which we never left open, and thoughts go out of our minds through avenues which we never voluntarily opened.”

  “I am lying in bed, for example, and think it is time to get up,” wrote William James,

  but alongside of this thought there is present to my mind a realization of the extreme coldness of the morning and the pleasantness of the warm bed. In such a situation the motor consequences of the first idea are blocked; and I may remain for half an hour or more with the two ideas oscillating before me in a kind of deadlock, which is what we call the state of hesitation or deliberation.

  Somehow or other, after lolling around in the bed like this for half an hour, the philosopher confessed, “I shall suddenly find that I have got up.” It is as if his mind had a mind of its own. Is his springing out of bed free will? (“Free will,” Seymour says to Carol, “is if you get back in.”)

  Even with the wanderings of science, there is play in the system. Science blunders along, like every sort of behavior. Max Delbrück knew that science is always improvisatory: “The grand edifice of Science, built through the centuries by the efforts of many people in many nations, gives you the illusion of an immense cathedral, erected in an orderly fashion according to some master plan. However, there never was a master plan. The edifice is a result of channeling our intellectual obsessive forces into the joint program. In spite of this channeling, the progress of science at all times has been and still is immensely disorderly for the very reason that there can be no master plan.” In science, as in the rest of life, the paths are paths only in retrospect.

  And in the tree of life itself there seems to be play in the system: what look like swerves and random branches. The shape of a growing nerve tree in the brain, the shape of the decision trees of an individual lifetime, and the shape of the whole tree of life share the same branching form on successively larger and larger scales. What is the Tree of Life but a decision tree, a drawing of a series of choice points in which one line of life went one way and another another way? And were those choices forced or free? Some of them were based on new behavior at choice points, as when a fish first began hanging around longer and longer at the margins of the sea and taking gulps of air.

  “The things we thought would happen do not happen;/The unexpected God makes possible,” Euripides wrote in the last lines of one of his last plays. Since we see paradox at all scales, is it possible that the answer to this paradox on one scale will someday unlock them all? In his laboratory, Jeff Hall is trying to move from the particular to the general, exploring more and more interconnections among the time, love, and memory genes, continually e-mailing Tim Tully and Ralph Greenspan, who was Hall’s first graduate student, now at the Neurosciences Institute in San Diego. One of their clock genes seems to mesh with one of their memory genes like the teeth of two gears. Clock genes also seem to mesh with the genes that build the body of the fly from the egg. And the human period gene is expressed not only in the human brain but in the pancreas, kidney, skeletal muscle, liver, lung, and placenta—almost everywhere its discoverers have looked for it. Although no one is sure what that means, they are sure that the fly clock is interwoven with the rest of the fly’s genes and that the human clock is interwoven with much of what is human.

  In Tokyo, Yoshiki Hotta, who helped Konopka find the clock mutants, is also thinking about the way the genes fit together. So is another old student, Alberto Ferrús, in Madrid. Ferrús thinks we stand in relation to the atomic theory of behavior now the way biologists stood in relation to the atomic theory of inheritance at the turn of the twentieth century. Then, biologists had accumulated an enormous amount of information about what happens when you cross different species of plants or different species of animals. But they did not understand the basis of heredity. Then, in
1900, they rediscovered Mendel’s laws. When these laws were rediscovered, vast amounts of information were wiped out because there was no need for them anymore. Biologists now had an organizing principle by which they could understand heredity in any organism. “And maybe we need for neurobiology a similar type of breakthrough,” says Ferrús. “We would like to find some sort of neural code to understand how perception is encoded in our brains, for instance.” Or how we memorize a piece of information we have perceived. “Code. How does a brain of a fly or a man operate? The basic principle. The details are going to be different in every organism, of course. But maybe, maybe there is such a basic principle, such a code that it is of universal value. And if such a thing is once discovered, then we would have made a gigantic step ahead, as gigantic as Mendel’s laws were for genetics.”

  The next generations of genetic dissectors are beginning to think about systems of genes. They are beginning to think about genes the way Konrad Lorenz thought about instincts: “Unless one understands the elements of a complete system as a whole, one cannot understand them at all.” Like the rest of molecular biology, genetic dissection has always pushed toward the particular. The genetic scalpel uncovered one gene in one behavior at a time. But each gene is involved in many kinds of behavior. Hall, Tully, and Greenspan are writing a book on the subject of genes as networks, genes as systems, genes as constellations. They mail their manuscripts back and forth, struggling toward a difficult vision that they cannot put into words. One day Greenspan scribbled in his draft in huge letters: “I’M GROPING, NOT TRACKING HERE. There’s an idea struggling to get out. HELP!!!” Sometimes Greenspan seems to get a dim glimpse of a web of interweavings, a web that feels something like a new view of life and something like inner experience. Being alive does not feel like an assortment of conflicting separate instincts, pieces, and inclinations; we feel, when we introspect, that there are many parts but that they are at least loosely woven together, loosely connected in what Lorenz called “the great parliament of instincts.” In life, emotional wisdom resides in seeing around particles of mood, moments of mood, to the whole in time, putting it all together. In life we are not particles but evolution. The word “religion” comes from the Latin religare, “to bind loose things together.” Hall, Greenspan, and Tully struggle with thoughts of networks; the book will not come together. And Hall escapes more and more to Gettysburg and drives home with the bumper sticker SAVE THE BATTLEFIELDS.

  Could it be that the answer to the paradox has something to do with the way we break the world into categories, and will we see the answers to all these paradoxes when we have learned to think in new categories? Maybe the free-will problem has to do with categories of thought we cannot see because they are innate in us, because they are part of the instincts with which we are born.

  “What is your aim in philosophy?” Ludwig Wittgenstein asked in his Philosophical Investigations in 1953, the year that Watson and Crick put together their model of the double helix, and Benzer figured out how to map the interior of a gene. The philosopher answered himself, “To show the fly the way out of the fly bottle.” Well, the fly is out of the bottle now. Whether we like it or not, the fly zigzags through all our meditations “like crack through cup,” as the poet Rilke writes in one of his Duino Elegies. In ways we may love or hate, the science that came out of the fly bottle is changing our sense of what it means to live. And maybe the science will help us understand this overarching paradox. This is the question that the fly bottle has posed from the beginning, and maybe the answer, too, will come out of a fly bottle. “Who’s turned us around like this?” Rilke asks in his elegy. “Who’s turned us around like this, so that we always, do what we may, retain the attitude/of someone who’s departing?” Maybe the fly will lead, in someone’s night thoughts, to a new union of Pascal’s two infinites. Maybe the fly will lead us out of the bottle into territory that is as blurred and vague now as the gene was before the first flies flew in the window.

  Butler’s line about eggs making eggs is a variation on the theme of the old riddle: Which came first, the chicken or the egg? Maybe the answer to that riddle will prove to be the answer to them all: some kind of engagement, collaboration, development involving both gene and world. And maybe it is the same with consciousness. Maybe all these branches have the same shape because they are all products of some interaction, some drama or dance of life and world that we have yet to find a way to wrap our minds around. Maybe this is the way out of the fly bottle of the twentieth century. Our genes and brains work only by engagement with the world around them, so we are not imprisoned by our genes and brains. “Denmark’s a prison,” says Prince Hamlet. “Then is the whole world one,” his college friend replies. If our genome is a prison, then is the whole world one.

  This is the kind of problem that more and more neurobiologists and neurophilosophers are trying to solve, but Benzer only raises his eyebrows and smiles his molecular smile: “Oh, they can have it. I’ll leave it to them.”

  Notes

  Between 1994 and 1998, I spoke with almost 150 biologists who have made, or watched the making of, what I call in this book the atomic theory of behavior. With some of them I spoke once, with some many times. Unless otherwise noted, all quotations in the book come from those interviews.

  1 “The Fly”: William Blake, The Portable Blake (New York: The Viking Press, 1946), 107.

  PART ONE: OCCAM’S CASTLE

  1 “Would it be too bold”: Erasmus Darwin, Zoonomia; Or the Laws of Organic Life, 4th American ed. (Philadelphia, 1818), I, 397. Quoted in John C. Greene, The Death of Adam (Ames, Iowa: The Iowa State University Press, 1959), 167.

  “My handwriting”: Charles Darwin, Metaphysics, Materialism, and the Evolution of Mind: Early Writings of Charles Darwin, transcribed and annotated by Paul H. Barrett, with a commentary by Howard E. Gruber (Chicago: University of Chicago Press, 1980), 21.

  CHAPTER ONE: FROM SO SIMPLE A BEGINNING

  1 “The ancient precept”: Ralph Waldo Emerson, “The American Scholar,” in Essays and Poems (New York: The Library of America, 1996), 56.

  “The nearest gnat”: Walt Whitman, “Song of Myself,” in Complete Poetry and Collected Prose (New York: The Library of America, 1982), 84.

  2 “legs with joints”: Blaise Pascal, Pensées, A.J. Krailsheimer, trans. (London: Penguin Books, 1995), 60. “The eternal silence”: Ibid., 66

  3 “The way in which”: Ibid., 65. The passage is from Saint Augustine, City of God, XXI.10

  like panpipes: For his own description of this experiment, see Benzer, “Behavioral Mutants of Drosophila Isolated by Countercurrent Distribution,” Proceedings of the National Academy of Sciences USA 58 (1967): 1112–19. The paper was reprinted in 1994 with interviews and commentaries in the “Landmarks” series of The Journal of NIH Research 6: 66–73. Very little has been written about this work outside the technical literature. Benzer has published one popular article about his research: “Genetic Dissection of Behavior,” Scientific American (December 1973): 24–37. For a witty and accessible historical review of the development of the field, see Ralph J. Greenspan, “The Emergence of Neurogenetics,” Seminars in the Neurosciences 2 (1990): 145–57. See also R. J. Greenspan, “Understanding the Genetic Construction of Behavior,” Scientific American 272, no. 4 (1995): 72–8.

  4 Benzer got the idea: My account is based on several extended visits and interviews with Benzer in Pasadena between 1995 and 1998. I have also drawn on transcripts of an excellent series of unpublished interviews that Heidi Aspaturian of Caltech conducted with Benzer as part of an in-house oral history project in 1990 and 1991.

  5 Aristotle mistook them: For two vignettes of early fly history, see B. Peyer, “An Early Description of Drosophila,” Journal of Heredity 38 (1947): 194–9; and G. H. Müller, “Drosophila: A Contribution to Its Morphology and Development by W. F. von Gleichen in 1764,” Journal of Natural History 10 (1976): 581–97. Aristotle describes the flies in Historia Animalium, Book 5, Chapter 19 (cited in
Peyer).

  first published laboratory study: F. W. Carpenter, “The Reactions of the Pomace Fly (Drosophila ampelophila Loew) to Light, Gravity, and Mechanical Stimulation,” Contributions from the Zoölogical Laboratory of the Museum of Comparative Zoölogy at Harvard College 162 (1905): 157–71. For a discussion of the experiment’s place in the early history of fly work, see Garland E. Allen, “The Introduction of Drosophila into the Study of Heredity and Evolution: 1900–1910,” Isis 66 (1975): 322–33.

  6 happy medium: S. Benzer, “From the Gene to Behavior,” Journal of the American Medical Association 218 (1971): 1015–22. Presented as an Albert Lasker Basic Medical Research Award Lecture, New York, November 11, 1971. The award was for his work on splitting the gene, but Benzer took the occasion to talk about his new passion, the study of behavior, about one hundred thousand neurons: Ibid. No one has ever actually counted. This number is an order-of-magnitude estimate; the actual number may be three times higher.

  7 “There is enough light”: Pascal, Pensées, 50.

  8 “from Crudity to Perfect Concoction”: Francis Bacon, Sylva Sylvorum; Or a Naturall Historie (1626), 838; quoted in The Compact Edition of the Oxford English Dictionary (Oxford: Oxford University Press, 1971), 3459.

  “that sweetness is not bitterness”: John Locke, An Essay Concerning Human Understanding (Amherst, N.Y.: Prometheus Books, 1995 [1690]), 19.

  9 “Have you not noticed”: Freud, “The Question of Lay-Analysis,” first published in 1926, translated in Volume 20 of The Standard Edition of the Complete Psychological Works of Sigmund Freud, J. Strachey, ed. (London: Hogarth Press, 1953–1974); excerpted in The Study of Human Nature, Leslie Stevenson, ed. (Oxford: Oxford University Press, 1981), 164–192.

  One of Tinbergen’s books: Niko Tinbergen, The Study of Instinct (Oxford: Oxford University Press, 1969 [1951]), 78. See also N. Tinbergen, “Social Releasers and the Experimental Method Required for Their Study.” Wilson Bulletin 60 (1948): 6–52.