Arrival of the Fittest: Solving Evolution's Greatest Puzzle

by Andreas Wagner

  A special creation of each species would leave all these threads of knowledge in a messy tangle. Darwin, one of the greatest synthesizers of all time, wove them into the beautiful fabric of his theory. He threw the gauntlet at creationists by claiming that all life shares a common ancestor, and thereby dismissed biblical Genesis from the debate table.

  That was Darwin’s first great insight. The second one was the central role of natural selection, an insight inspired by the spectacular success of animal and plant breeders.14 The Origin’s entire first chapter marvels at the diversity of domestic dogs, pigeons, crop plants, and ornamental flowers that human breeders had produced. It is indeed stunning to think that humans could create Great Danes, German shepherds, greyhounds, bulldogs, and Chihuahuas, all from a common lupine ancestor, and all within mere centuries. Darwin realized that natural selection is not so different from such human selection, except that it operates on a much grander scale, and over eons of time. Nature incessantly creates new variants of organisms, most inferior, a few of them superior, and all of these variants must pass through the sieve of natural selection. Only individuals best adapted to their environment survive, procreate, and give rise to further variants. Given enough time, this process helps explain all of life’s diversity, so much so that the geneticist Theodosius Dobzhansky could say in 1973 that “nothing in biology makes sense except in the light of evolution.”

  From the very beginning, that light shone more brightly on some of life’s mysteries than on others. One of them was left in especially deep shadows: the mechanism of heritability. Without some mechanism that guarantees faithful inheritance from parents to offspring, adaptations—a bird’s wing, a giraffe’s neck, a snake’s fangs—cannot persist over time. And without inheritance, selection would be powerless. Darwin himself had no idea why children resemble their parents, and his frankness in admitting ignorance is disarming. “The laws governing inheritance are for the most part unknown,” he said in the Origin.15

  Darwin’s theory was a bit like that first movie of a galloping horse, revolutionary when compared to still photography, but only a modest step on the path to full-length feature films. The next step on biology’s path—explaining inheritance—was already made by the time Darwin died, but he did not know it. Nor did any other prominent scientist, although decisive experiments had already started in 1856, three years before Darwin published the Origin.16 Even the scientist who performed these experiments would not live to see the avalanche of progress he triggered, which would eventually engulf all of biology.

  That scientist was the Austrian monk Gregor Mendel, who studied in Vienna and entered St. Thomas Abbey in Brno, where he would experiment on more than twenty thousand pea plants before he became abbot. For his experiments, he deliberately chose pea plants that differed in several discrete features: One plant might produce smoothly round yellow peas, whereas the other would produce wrinkly green peas, but none with in-between color or shape. Other pea plants differed sharply in flower color, pod shape, or stem length. Mendel cross-fertilized these plants and analyzed their offspring, thousands and thousands of plants.

  What he saw was that these features often do not blend in the offspring.17 The offspring’s first or second generation produces either round or wrinkly peas, but none with an intermediate shape. And different features can be inherited independently, such that the offspring might sport combinations—round and green, wrinkly and yellow—that neither parent harbored. The causes of inheritance behaved like discrete and indivisible particles. Each parent carried two particles responsible for traits like roundness or color, but would pass only one of them on to its offspring. Different features were inherited through different kinds of particles, and could thus combine and recombine independently.

  Mendel worked in an academic backwater far from the intellectual currents of his time. And he committed the error that snuffed many an academic career, then and now: He published little and in the wrong place—in his case a local naturalist journal.18 And as bad luck would have it, the abbot who succeeded him would burn Mendel’s papers after his death. But thirty-four years after its publication in 1865, Mendel’s sleeping beauty of a discovery would be roused by the Dutch botanist Hugo de Vries, who independently performed experiments similar to those of Mendel. Historians still argue whether he truly rediscovered Mendel’s laws, or whether he learned about Mendel’s work during his own experiments and tried to hide his knowledge.19 The searing disappointment of having not just been scooped, but scooped by three decades, could certainly explain the impulse to rewrite history. Be that as it may, rediscovered Mendel’s laws were, and from then on they spread like wildfire. They became the basis of a whole new branch of biology, the science of genetics. Traits that behave as Mendel described exist in many plants and animals, including humans. Some of our Mendelian traits are as odd as the consistency of ear wax (wet or dry), but others are as important as the major blood groups (A or B), or diseases like sickle-cell anemia.

  As it turns out, de Vries was to receive a consolation prize. He is the grandfather of the word gene, whose importance endures in both science and popular culture. De Vries had called the particles of inheritance that Mendel had described “pangenes,” and a few years later the Danish geneticist Wilhelm Ludvig Johannsen would simply drop the “pan.”20

  Johannsen contributed two further important words to the language of modern biology. He coined the word genotype and distinguished it from the phenotype. In today’s language, a genotype comprises all genes of an organism, all its DNA, whereas the phenotype comprises everything else you could observe about the organism: its size, its color, whether it has a tail, or feathers, or a carapace. To see this distinction is crucial, because it allows us to tell cause from effect when organisms change. Take the word mutation, which was already used two hundred years earlier for any dramatic change in an organism’s appearance. In the early twentieth century, it was sometimes applied to Mendel’s units of inheritance, and sometimes to the organism (phenotype), leading to endless confusion about causes and effects of change.21 A century later we know that mutations change a genotype, like the mutations that altered the blueprint of light-sensing opsin proteins in some of our distant animal ancestors. Such genotypic change can cause changes in a phenotype, and some changed phenotypes become innovations—novel and useful features—like our ability to see the world in color.

  Only once we have distinguished between genotype and phenotype can we ask a question crucial to understand life’s innovability: How do mutations cause changes in phenotypes and bring forth innovations? Because that was the other great mystery left unanswered at the time of Darwin’s death: Where do innovations come from? Where do the new variants come from that selection needs? And especially those variants that improve an organism, help it survive a little longer, appear sexier to a mate, or have more babies? One could answer this question with a vacuous platitude: New variants arise randomly, by chance. This platitude is still used today, but Darwin was already familiar with it. And he knew that it explains exactly nothing. He opened the chapter on laws of variation in the Origin like this:

  I have hitherto sometimes spoken as if the variations . . . had been due to chance. This, of course, is a wholly incorrect expression, but it serves to acknowledge plainly our ignorance of the cause of each particular variation.

  This is not a small problem, because natural selection is not a creative force. It does not innovate, but merely selects what is already there. Darwin realized that natural selection allows innovations to spread, but he did not know where they came from in the first place.

  To appreciate the magnitude of this problem, consider that every one of the differences between humans and the first life forms on earth was once an innovation: an adaptive solution to some unique challenge faced by a living being. It might have been the challenge of converting the light energy from the sun into living matter. Or the challenge of converting another living thing into food. Or simply of moving from one place to
another. Every square meter of the earth’s surface, every cubic meter of the oceans, every meadow, forest, and desert, every city and suburb is packed to the limits with organisms, and each organism exhibits countless such innovations. Fundamental ones like photosynthesis and respiration. Protective ones like reptilian scales and insulating feathers. Supportive ones like connective tissue and skeletons. Some are complex, with hundreds of moving parts, others are not. But no matter how large or small, from the ten feet of a blue whale’s tail fluke to the ten microns of a bacterium’s flagellum, every single one exists because, at some point since life’s origin, the right variation occurred.

  Selection did not—cannot—create all this variation. A few decades after Darwin, Hugo de Vries expressed it best when he said that “natural selection may explain the survival of the fittest, but it cannot explain the arrival of the fittest” (emphasis added).22 And if we do not know what explains its arrival, then we do not understand the very origins of life’s diversity.

  Life can innovate, it has innovability. What is more, it can innovate while preserving what works through faithful inheritance. It can explore the new while preserving the old. It can be progressive and conservative at the same time. And through the early twentieth century, biologists had no idea how that is possible. As we shall see, there is no way they could have known. Another century of discoveries was needed before the experimental and computational toolbox of biology became powerful enough to tackle this question.

  In fact, looking back, it is remarkable that early-twentieth-century scientists could even distinguish genotypes from phenotypes. They were as ignorant about the material basis of Mendelian inheritance as Muybridge was of color photography. It was not even clear whether genes were intangible concepts, like gravity, or physical objects that could be isolated from a body and studied.23 Only later would it become clear that genes were very physical, lying on chromosomes and consisting of DNA.

  Even before the discovery of genes’ physical reality, Mendel’s discovery fanned the flames under an old controversy that had simmered since Darwin. Discrete, granular, particulate inheritance flies in the face of an obvious fact that all of us are familiar with. If a six-foot-tall man and a five-foot-tall woman have children, then discrete inheritance demands that their children should be as tall as either parent—five or six feet—but never in between.24 But we all know that the children’s heights lie on a continuum, as do the shapes of their faces, the color of their skin, the contours of their bones, and so on. Naturalists since Darwin found such continuous, blending inheritance everywhere around them, in the yield of crops, the weight of eggs, the sizes of leaves—in brief, in most features of organisms.25 This kind of variation is clearly important in nature.

  The controversy raged around the question of which kind of variation, continuous or discrete, was more important for evolution. The naturalist or gradualist school of thought—Darwin was an early adherent—emphasized the small, continuous variation that we see all around us. The other school—“Mendelists,” “mutationists,” or “saltationists”—believed in the large, discrete variants that Mendel had studied. In a cartoon version of this dispute, a gradualist would imagine that the many petals of a garden rose emerged from its five-petaled ancestors through gradual additions of petals over many generations. A mutationist, on the other hand, would argue that the multifoliate rose could have appeared in a single saltational “macromutation” from this ancestor.26

  Looking back, this debate seems just as important as the question that kept medieval scholastics busy: How many angels can dance on the head of a pin? But it just about pierced the heart of Darwinism. For the Mendelists believed less in natural selection than in the power of mutations to bring forth new traits. In their view, the real drivers behind life’s evolution were large mutations that created individuals far outside the norm of their species. “Hopeful monsters” is what the German-born zoologist Richard Goldschmidt would call them, citing as one of his examples the benthic flatfish that live on the ocean floor, which have both eyes on the same side of the head.27

  Although the Mendelists would turn out to be wrong—most evolutionary change does indeed occur gradually and involves natural selection—they did have a point. The real mystery of evolution is not selection, but the creation of new phenotypes. But they were born too early. They could speculate wildly, but had no way to solve the mystery, and the controversy between the two camps continued well into the twentieth century until powerful new insights would dissolve it. That process began when a long-known fact became newly appreciated: Genetic change happens not just in individuals, but in populations.

  The white-bodied peppered moth is a perfectly inconspicuous insect whose white wings are sprinkled with flecks of black. Against a background of tree bark and lichen, this mottled pattern camouflages the moth against ravenous birds. In some moths, a gene affecting wing color can mutate to produce a dark-colored wing. This mutation is usually bad news for a moth, because mutant moths are no longer camouflaged, and birds can rapidly pick them off. But in nineteenth-century England the Industrial Revolution gave the dark mutant moths a much-needed break. During this time, air pollution became so severe that it wiped out most lichen and turned tree bark black. Now the dark moths were well hidden, and the white moths had turned into bird food.

  If natural selection mattered, we would expect that the black moths would become more frequent over time. They would sweep through a moth population, whereas white moths would become rare. This is indeed what happened in nineteenth-century England, as the proportion of black moths in the population rose from 2 percent in 1848 to 95 percent by 1895.28 But this information isn’t nearly as important as the questions it triggers: Can we predict how rapidly they sweep through the population? Or conversely, if we have observed how fast they sweep, can we infer how strongly the dark color affects fitness, a moth’s chances of remaining hidden from birds? These were quantitative, mathematical questions, new to evolutionary thinking. And they created a new quantitative discipline within biology: population genetics.

  One of the central insights of population genetics is to view a population not just as a collection of distinct organisms but as a collective pool of genes. The genes that determine a moth’s wing color, for example, have different forms—the technical term is alleles—responsible for light or dark wings, that occur in different proportions or frequencies in the population. Imagine that at any one time, equal numbers of both types of alleles were present in a population of organisms, and that some new factor—a new predator, or a change in pollution—allowed moths with darker wings to live longer, and so produce more offspring. Their advantage need not be huge, but even a merely 1 percent increase in the dark-winged allele, from 50 percent to 51 percent in the first generation, could accumulate over time and allow the dark-winged variants to occupy a larger and larger percentage of the population. That’s how natural selection works: It changes allele frequencies, and thus the appearance of individuals over time.

  This was revolutionary. The study of life, which had largely depended on the same tools since Aristotle—close observation and dissection in the field and laboratory, recorded in sketchbooks and notes—began to embrace the mathematics of differential equations and the analysis of variance. Through the minds of intellectual giants such as Sewall Wright, J. B. S. Haldane, and the statistician R. A. Fisher, population genetics developed into a theory that could answer precise, quantitative questions about natural selection. At the same time, naturalists studied the frequencies of alleles in wild populations such as that of the peppered moth, and experimentalists created evolution in action in the laboratory, by studying laboratory populations of small, rapidly breeding animals such as fruit flies. The mathematical theory was the mortar that helped join these observations into an intellectual edifice.

  The new evidence from population genetics showed that variation covered a broad spectrum, with “pure” Mendelian variation at one extreme, and continuous variation at the o
ther. Mendelian phenotypes—wing color, pea shape—are influenced by one gene with large effects. Continuously varying phenotypes like height are influenced by multiple genes, each with a tiny effect. Population genetics showed that natural selection affects both kinds of genes. But truly surprising was how powerfully selection could affect them. If a dark-wing allele decreased a moth’s chance to be eaten by a few percent, it could wipe out the light-wing allele within a few dozen moth generations. And both naturalists and experimentalists found far more genes in their populations with small effects than with large ones. Mendel clearly had chosen his peas very carefully, because Mendelian traits that are influenced by a single gene comprise a tiny fraction of all traits.29 Most evolution is gradual and does not make large jumps.30

  By the 1930s, the concept of natural selection, the nature of inheritance, and population thinking had been synthesized into a body of knowledge known as the modern synthesis, named after an eponymous book by the biologist Julian Huxley.31 Despite its name, the synthesis will soon be a century old. But unlike most centenarians, it shows no signs of senescence. Augmented by mathematical refinements and modern data, it is unbroken, and by some measures stronger than ever, playing an increasingly important role in understanding human biology—helping to reconstruct human origins, trace human migrations, and understand genetic diseases. If this edifice of knowledge were a physical building, it would rival everything architects have conceived, from the palaces of Angkor Wat and the mausoleum of the Taj Mahal to the great Gothic cathedrals of the thirteenth century. It is a grand achievement of the human mind.