What Just Happened: A Chronicle From the Information Frontier

by James Gleick

  Even before the exact answer was reached, Crick crystallized its fundamental principles in a statement that he called (and is called to this day) the Central Dogma. It is a hypothesis about the direction of evolution and the origin of life; it is provable in terms of Shannon entropy in the possible chemical alphabets:

  Once “information” has passed into protein it cannot get out again. In more detail, the transfer of information from nucleic acid to nucleic acid, or from nucleic acid to protein may be possible, but transfer from protein to protein, or from protein to nucleic acid is impossible. Information means here the precise determination of sequence.♦

  The genetic message is independent and impenetrable: no information from events outside can change it.

  Information had never been writ so small. Here is scripture at angstrom scale, published where no one can see, the Book of Life in the eye of a needle.

  Omne vivum ex ovo. “The complete description of the organism is already written in the egg,”♦ said Sydney Brenner to Horace Freeland Judson, molecular biology’s great chronicler, at Cambridge in the winter of 1971. “Inside every animal there is an internal description of that animal.… What is going to be difficult is the immense amount of detail that will have to be subsumed. The most economical language of description is the molecular, genetic description that is already there. We do not yet know, in that language, what the names are. What does the organism name to itself? We cannot say that an organism has, for example, a name for a finger. There’s no guarantee that in making a hand, the explanation can be couched in the terms we use for making a glove.”

  Brenner was in a thoughtful mood, drinking sherry before dinner at King’s College. When he began working with Crick, less than two decades before, molecular biology did not even have a name. Two decades later, in the 1990s, scientists worldwide would undertake the mapping of the entire human genome: perhaps 20,000 genes, 3 billion base pairs. What was the most fundamental change? It was a shift of the frame, from energy and matter to information.

  “All of biochemistry up to the fifties was concerned with where you get the energy and the materials for cell function,” Brenner said. “Biochemists only thought about the flux of energy and the flow of matter. Molecular biologists started to talk about the flux of information. Looking back, one can see that the double helix brought the realization that information in biological systems could be studied in much the same way as energy and matter.…

  “Look,” he told Judson, “let me give you an example. If you went to a biologist twenty years ago and asked him, How do you make a protein, he would have said, Well, that’s a horrible problem, I don’t know … but the important question is where do you get the energy to make the peptide bond. Whereas the molecular biologist would have said, That’s not the problem, the important problem is where do you get the instructions to assemble the sequence of amino acids, and to hell with the energy; the energy will look after itself.”

  By this time, the technical jargon of biologists included the words alphabet, library, editing, proofreading, transcription, translation, nonsense, synonym, and redundancy. Genetics and DNA had drawn the attention not just of cryptographers but of classical linguists. Certain proteins, capable of flipping from one relatively stable state to another, were found to act as relays, accepting ciphered commands and passing them to their neighbors—switching stations in three-dimensional communications networks. Brenner, looking forward, thought the focus would turn to computer science as well. He envisioned a science—though it did not yet have a name—of chaos and complexity. “I think in the next twenty-five years we are going to have to teach biologists another language still,” he said. “I don’t know what it’s called yet; nobody knows. But what one is aiming at, I think, is the fundamental problem of the theory of elaborate systems.” He recalled John von Neumann, at the dawn of information theory and cybernetics, proposing to understand biological processes and mental processes in terms of how a computing machine might operate. “In other words,” said Brenner, “where a science like physics works in terms of laws, or a science like molecular biology, to now, is stated in terms of mechanisms, maybe now what one has to begin to think of is algorithms. Recipes. Procedures.”

  If you want to know what a mouse is, ask instead how you could build a mouse. How does the mouse build itself? The mouse’s genes switch one another on and off and perform computation, in steps. “I feel that this new molecular biology has to go in this direction—to explore the high-level logical computers, the programs, the algorithms of development.…

  “One would like to be able to fuse the two—to be able to move between the molecular hardware and the logical software of how it’s all organized, without feeling they are different sciences.”

  Even now—or especially now—the gene was not what it seemed. Having begun as a botanist’s hunch and an algebraic convenience, it had been tracked down to the chromosome and revealed as molecular coiled strands. It was decoded, enumerated, and catalogued. And then, in the heyday of molecular biology, the idea of the gene broke free of its moorings once again.

  The more was known, the harder it was to define. Is a gene nothing more or less than DNA? Is it made of DNA, or is it something carried in DNA? Is it properly pinned down as a material thing at all?

  Not everyone agreed there was a problem. Gunther Stent declared in 1977 that one of the field’s great triumphs was the “unambiguous identification” of the Mendelian gene as a particular length of DNA. “It is in this sense that all working geneticists now employ the term ‘gene,’ ”♦ he wrote. To put it technically but succinctly: “The gene is, in fact, a linear array of DNA nucleotides which determines a linear array of protein amino acids.” It was Seymour Benzer, said Stent, who established that definitively.

  Yet Benzer himself had not been quite so sanguine. He argued as early as 1957 that the classical gene was dead. It was a concept trying to serve three purposes at once—as a unit of recombination, of mutation, and of function—and already he had strong reason to suspect that these were incompatible. A strand of DNA carries many base pairs, like beads on a string or letters in a sentence; as a physical object it could not be called an elementary unit. Benzer offered a batch of new particle names: “recon,” for the smallest unit that can be interchanged by recombination; “muton,” for the smallest unit of mutational change (a single base pair); and “cistron” for the unit of function—which in turn, he admitted, was difficult to define. “It depends upon what level of function is meant,” he wrote—perhaps just the specification of an amino acid, or perhaps a whole ensemble of steps “leading to one particular physiological end-effect.”♦ Gene was not going away, but that was a lot of weight for one little word to bear.

  Part of what was happening was a collision between molecular biology and evolutionary biology, as studied in fields from botany to paleontology. It was as fruitful a collision as any in the history of science—before long, neither side could move forward without the other—but on the way some sparks flared. Quite of few of them were set off by a young zoologist at Oxford, Richard Dawkins. It seemed to Dawkins that many of his colleagues were looking at life the wrong way round.

  As molecular biology perfected its knowledge of the details of DNA and grew more skillful in manipulating these molecular prodigies, it was natural to see them as the answer to the great question of life: how do organisms reproduce themselves? We use DNA, just as we use lungs to breathe and eyes to see. We use it. “This attitude is an error of great profundity,”♦ Dawkins wrote. “It is the truth turned crashingly on its head.” DNA came first—by billions of years—and DNA comes first, he argued, when life is viewed from the proper perspective. From that perspective, genes are the focus, the sine qua non, the star of the show. In his first book—published in 1976, meant for a broad audience, provocatively titled The Selfish Gene—he set off decades of debate by declaring: “We are survival machines—robot vehicles blindly programmed to preserve the selfish molecules known as ge
nes.”♦ He said this was a truth he had known for years.

  Genes, not organisms, are the true units of natural selection. They began as “replicators”—molecules formed accidentally in the primordial soup, with the unusual property of making copies of themselves.

  They are past masters of the survival arts. But do not look for them floating loose in the sea; they gave up that cavalier freedom long ago. Now they swarm in huge colonies, safe inside gigantic lumbering robots, sealed off from the outside world, communicating with it by tortuous indirect routes, manipulating it by remote control. They are in you and in me; they created us, body and mind; and their preservation is the ultimate rationale for our existence. They have come a long way, those replicators. Now they go by the name of genes, and we are their survival machines.♦

  This was guaranteed to raise the hackles of organisms who thought of themselves as more than robots. “English biologist Richard Dawkins has recently raised my hackles,” wrote Stephen Jay Gould in 1977, “with his claim that genes themselves are units of selection, and individuals merely their temporary receptacles.”♦ Gould had plenty of company. Speaking for many molecular biologists, Gunther Stent dismissed Dawkins as “a thirty-six-year-old student of animal behavior” and filed him under “the old prescientific tradition of animism, under which natural objects are endowed with souls.”♦

  Yet Dawkins’s book was brilliant and transformative. It established a new, multilayered understanding of the gene. At first, the idea of the selfish gene seemed like a trick of perspective, or a joke. Samuel Butler had said a century earlier—and did not claim to be the first—that a hen is only an egg’s way of making another egg. Butler was quite serious, in his way:

  Every creature must be allowed to “run” its own development in its own way; the egg’s way may seem a very roundabout manner of doing things; but it is its way, and it is one of which man, upon the whole, has no great reason to complain. Why the fowl should be considered more alive than the egg, and why it should be said that the hen lays the egg, and not that the egg lays the hen, these are questions which lie beyond the power of philosophic explanation, but are perhaps most answerable by considering the conceit of man, and his habit, persisted in during many ages, of ignoring all that does not remind him of himself.♦

  He added, “But, perhaps, after all, the real reason is, that the egg does not cackle when it has laid the hen.” Some time later, Butler’s template, X is just a Y’s way of making another Y, began reappearing in many forms. “A scholar,” said Daniel Dennett in 1995, “is just a library’s way of making another library.”♦ Dennett, too, was not entirely joking.

  It was prescient of Butler in 1878 to mock a man-centered view of life, but he had read Darwin and could see that all creation had not been designed in behalf of Homo sapiens. “Anthropocentrism is a disabling vice of the intellect,”♦ Edward O. Wilson said a century later, but Dawkins was purveying an even more radical shift of perspective. He was not just nudging aside the human (and the hen) but the organism, in all its multifarious glory. How could biology not be the study of organisms? If anything, he understated the difficulty when he wrote, “It requires a deliberate mental effort to turn biology the right way up again, and remind ourselves that the replicators come first, in importance as well as in history.”♦

  A part of Dawkins’s purpose was to explain altruism: behavior in individuals that goes against their own best interests. Nature is full of examples of animals risking their own lives in behalf of their progeny, their cousins, or just fellow members of their genetic club. Furthermore, they share food; they cooperate in building hives and dams; they doggedly protect their eggs. To explain such behavior—to explain any adaptation, for that matter—one asks the forensic detective’s question, cui bono? Who benefits when a bird spots a predator and cries out, warning the flock but also calling attention to itself? It is tempting to think in terms of the good of the group—the family, tribe, or species—but most theorists agree that evolution does not work that way. Natural selection can seldom operate at the level of groups. It turns out, however, that many explanations fall neatly into place if one thinks of the individual as trying to propagate its particular assortment of genes down through the future. Its species shares most of those genes, of course, and its kin share even more. Of course, the individual does not know about its genes. It is not consciously trying to do any such thing. Nor, of course, would anyone impute intention to the gene itself—tiny brainless entity. But it works quite well, as Dawkins showed, to flip perspectives and say that the gene works to maximize its own replication. For example, a gene “might ensure its survival by tending to endow the successive bodies with long legs, which help those bodies escape from predators.”♦ A gene might maximize its own numbers by giving an organism the instinctive impulse to sacrifice its life to save its offspring: the gene itself, the particular clump of DNA, dies with its creature, but copies of the gene live on. The process is blind. It has no foresight, no intention, no knowledge. The genes, too, are blind: “They do not plan ahead,”♦ says Dawkins. “Genes just are, some genes more so than others, and that is all there is to it.”

  The history of life begins with the accidental appearance of molecules complex enough to serve as building blocks—replicators. The replicator is an information carrier. It survives and spreads by copying itself. The copies must be coherent and reliable but need not be perfect; on the contrary, for evolution to proceed, errors must appear. Replicators could exist long before DNA, even before proteins. In one scenario, proposed by the Scots biologist Alexander Cairns-Smith, replicators appeared in sticky layers of clay crystals: complex molecules of silicate minerals. In other models the evolutionary playground is the more traditional “primordial soup.” Either way, some of these information-bearing macromolecules disintegrate more quickly than others; some make more or better copies; some have the chemical effect of breaking up competing molecules. Absorbing photon energy like the miniature Maxwell’s demons they are, molecules of ribonucleic acid, RNA, catalyze the formation of bigger and more information-rich molecules. DNA, ever so slightly more stable, possesses the dual capability of copying itself while also manufacturing another sort of molecule, and this provides a special advantage. It can protect itself by building a shell of proteins around it. This is Dawkins’s “survival machine”—first cells, then larger and larger bodies, with growing inventories of membranes and tissues and limbs and organs and skills. They are the genes’ fancy vehicles, racing against other vehicles, converting energy, and even processing information. In the game of survival some vehicles outplay, outmaneuver, and outpropagate others.

  It took some time, but the gene-centered, information-based perspective led to a new kind of detective work in tracing the history of life. Where paleontologists look back through the fossil record for skeletal precursors of wings and tails, molecular biologists and biophysicists look for telltale relics of DNA in hemoglobin, oncogenes, and all the rest of the library of proteins and enzymes. “There is a molecular archeology in the making,”♦ says Werner Loewenstein. The history of life is written in terms of negative entropy. “What actually evolves is information in all its forms or transforms. If there were something like a guidebook for living creatures, I think, the first line would read like a biblical commandment, Make thy information larger.”

  No one gene makes an organism. Insects and plants and animals are collectives, communal vehicles, cooperative assemblies of a multitude of genes, each playing its part in the organism’s development. It is a complex ensemble in which each gene interacts with thousands of others in a hierarchy of effects extending through both space and time. The body is a colony of genes. Of course, it acts and moves and procreates as a unit, and furthermore, in the case of at least one species, it feels itself, with impressive certainty, to be a unit. The gene-centered perspective has helped biologists appreciate that the genes composing the human genome are only a fraction of the genes carried around in any one person, because human
s (like other species) host an entire ecosystem of microbes—bacteria, especially, from our skin to our digestive systems. Our “microbiomes” help us digest food and fight disease, all the while evolving fast and flexibly in service of their own interests. All these genes engage in a grand process of mutual co-evolution—competing with one another, and with their alternative alleles, in nature’s vast gene pool, but no longer competing on their own. Their success or failure comes through interaction. “Selection favors those genes which succeed in the presence of other genes,” says Dawkins, “which in turn succeed in the presence of them.”♦

  The effect of any one gene depends on these interactions with the ensemble and depends, too, on effects of the environment and on raw chance. Indeed, just to speak of a gene’s effect became a complex business. It was not enough simply to say that the effect of a gene is the protein it synthesizes. One might want to say that a sheep or a crow has a gene for blackness. This might be a gene that manufactures a protein for black pigment in wool or feathers. But sheep and crows and all the other creatures capable of blackness exhibit it in varying circumstances and degrees; even so simple-seeming a quality seldom has a biological on-off switch. Dawkins suggests the case of a gene that synthesizes a protein that acts as an enzyme with many indirect and distant effects, one of which is to facilitate the synthesis of black pigment.♦ Even more remotely, suppose a gene encourages an organism to seek sunlight, which is in turn necessary for the black pigment. Such a gene serves as a mere co-conspirator but its role may be indispensable. To call it a gene for blackness, however, becomes difficult. And it is harder still to specify genes for more complex qualities—genes for obesity or aggression or nest building or braininess or homosexuality.