Arrival of the Fittest: Solving Evolution's Greatest Puzzle (4 page)

There is, however, a dirty secret behind its success. The architects of the modern synthesis focused on the genotype at the expense of the organism and its phenotype. They neglected the marvelous complexity of organisms with their trillions of cells, each inhabited by billions of molecules whose functions are themselves incredibly complex. And they neglected how all this complexity unfolds from a single fertilized cell, and how genes contribute to this unfolding. By neglecting this complexity, the architects of the modern synthesis effectively ignored its product: the organism itself. They did so knowingly, since they wanted to understand how gene frequencies change over time. In focusing on the genotype, they simplified an organism’s phenotype down to simpler quantities, such as
fitness,
the average number of genes a typical individual transmits to the next generation. (Fitter organisms contribute more genes to the next generation’s gene pool.) What is more, they also assumed that individual genes play a simple role in determining fitness, for example that fitness is the sum total of many small gene effects.

Don’t get me wrong. It is hard to see how the modern synthesis could not have ignored the organism. The price of understanding is always abstraction, neglecting most of a staggeringly complex world to understand one tiny fragment of it. Take it from another theorist, Albert Einstein, who knew what he was talking about when he said that “everything should be made as simple as possible, but no simpler.”
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The modern synthesis was just as simple as it needed to be to answer thousands of questions about the evolution of genes and genotypes. Its very success in understanding natural selection in action was built on getting rid of organismal complexity. But whenever a theory is successful, it is also easy to forget its limitations, and this is exactly what happened in the heyday of the modern synthesis, when the grandeur of life’s evolution became redefined and demoted to a “change in allele frequency within a gene pool.”
³³
The principal limitation—a high price to pay—was the inability to answer the second great question the
Origin
had left open: Where do innovative phenotypes come from? The modern synthesis could explain how innovations spread, but not how they originate.

To say that all evolutionists had thrown the organism under the bus, however, would be unfair to a minority of them, those who compared how the complexity of different organisms unfolds in their embryos. But these embryologists, whose forebears had helped Darwin to recognize the common ancestry of all living things, were sidelined by the modern synthesis and its advocates, who had no need for the embryo. In 1932, one year before he would win the Nobel Prize for showing how genes are organized into chromosomes, the fly geneticist Thomas Hunt Morgan would say that it does not matter much “whether you choose an ape or the foetus of an ape as the progenitor of the human race.”
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But even though population geneticists ruled in biology’s halls of power, some embryologists in the back rows kept heckling the opinion leaders, pointing out that they were ignoring the very thing they were trying to explain. Their voices got louder toward the end of the twentieth century. That’s when evolutionary developmental biology, or “evo-devo,” emerged as a new research discipline, one that aims to integrate embryonic development, evolution, and genetics. Evo-devo produced fantastic insights into how genes cooperate, like orchestra musicians, to make embryonic development possible.

So far, though, these insights have not yet added up to a theory rivaling the modern synthesis. And only theory can turn a heap of facts into a tower of knowledge. The culprit is once again the enormous phenotypic complexity of whole organisms. Even today, we struggle to fully understand the phenotype of even the simplest organisms, and hundreds of thousands of biologists laboring over many decades have still not fully understood how genes help shape this phenotype.
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Where the modern synthesis has a theory without phenotypes, the embryologists have phenotypes without a theory.

Evo-devo, however, has taught us an important lesson. To understand innovability we cannot ignore the complexity of phenotypes. We must embrace it. And even though we do not yet understand all of an organism’s complexity, we now understand the parts of the phenotype that ultimately bring forth all innovations. This is where the next chapters will take us.

The same century that led biology from Darwin to Mendel and the modern synthesis also gave birth to biochemistry, a science that had been conceived more than seven thousand years earlier, when humans started to produce beer and wine. The mechanism by which yeasts transform sugar into ethanol remained mysterious, however, until Louis Pasteur showed, three years before Darwin’s
Origin,
that living organisms cause fermentation. And even that truth was toppled a few decades later, when Eduard Buchner proved in 1897 that fermentation does not require living organisms, because yeast extracts containing no living cells can ferment sugar. His discovery helped dispel vitalism, the notion that life required an enigmatic vital force and obeys laws different from those of the inanimate world.

To teach us that life is based on prosaic chemistry is important, but Buchner is even better remembered as a pioneer in the discovery of enzymes, those gigantic protein molecules consisting of dozens to thousands of amino acids.
³⁶
They can speed up chemical reactions that cleave, join, or rearrange atoms up to a billionfold. Biochemistry honors Buchner to this day by using his naming system for enzymes, adding the suffix -
ase
to the chemical reaction they catalyze. An enzyme that can process the sugar sucrose would be
sucrase,
one processing lactose would be
lactase,
and so on.

His discoveries also spun off another branch of biochemistry. It focused not on enzymes but on the reactions they catalyzed, and would unveil a new chemical world, that of metabolism with its bewildering complexity. Broadly speaking, an organism’s metabolism—the word itself comes from the Greek for “change”—comprises two sorts of chemical transformations. The first kind cleaves energy-rich molecules such as the sugar glucose to extract energy from them. The second uses this energy to transform nutrient molecules into a cell’s own molecular building blocks, which comprise dozens of molecules like the amino acids in proteins. Along the way, a metabolism must also manage a body’s waste, disarming toxic molecules into harmless ones. Taken together, these tasks are complex and require more than a thousand chemical reactions—and the enzymes that catalyze them—in order to build and maintain our bodies.
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The discovery that protein enzymes help build our phenotype is a monumental insight of twentieth-century biochemistry. (It also led to a key insight about life’s creativity: Even the largest changes in an organism result from alterations in individual molecules.) But this discovery was dwarfed by an even greater one: the chemical structure of our genes.

Its story also begins at Darwin’s time, in 1869, the same year as the fifth edition of
The Origin of Species
.
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That is when the Swiss chemist Friedrich Miescher first identified a new mysterious substance, different from protein.
³⁹
He called it
Nuklein,
but its chemical structure would not become clear until decades later. Not until 1910 would we know that the substance—by then renamed deoxyribonucleic acid (DNA)—contains the four bases adenine (A), cytosine (C), guanine (G), and thymine (T), molecules that we now call the four letters of the DNA alphabet. And it would be 1944 before biologists realized that DNA is the stuff of inheritance. In that year Oswald Avery showed that DNA from a disease-causing strain of the bacterium
Streptococcus pneumoniae
helps another, harmless strain kill mice.
⁴⁰

Less than a decade later, James Watson and Francis Crick would reveal that DNA is a supremely beautiful molecule. Its two strands form the famed double helix, a twisted ladder in which two paired bases from opposite strands make up each rung. In each rung, two bases are always paired, A always with T, and C always with G. This structure also suggests how DNA could be copied, and thus how inheritance works at the level of molecules.
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Genes had turned out to be so much more than Johannsen had thought.

It had taken seventy years to get from Muybridge’s zoopraxiscope to color television—to get from recording individual black-and-white images on silver plates to encoding color images as electric signals, transmitting them wirelessly, and displaying them on cathode-ray tubes. During the same seventy years, biology had also progressed dramatically and embraced new discoveries just as enthusiastically. It had married the mathematics of population genetics and birthed the modern synthesis. It had revealed the function of enzymes and discovered the structure of DNA (brought to us at about the same time as color television). It had incorporated the knowledge of chemistry that would become essential to understanding the origins of innovation. It wasn’t there yet. But it was getting closer.

Watson and Crick’s discovery rang in the age of
molecular biology
. Within the next twelve years, biologists would learn that DNA is transcribed into the closely related ribonucleic acid (RNA), which is then translated, three nucleotide letters at a time, into a protein string of amino acids (figure 1). This translation follows a genetic code in which most of the sixty-four possible three-letter words encode a single amino acid. Only a few words are set aside to signal the beginning and the end of a protein string.

Knowing the DNA letter sequence of a gene, a child could predict the amino acid sequence of a protein. But this is where simplicity ends. Proteins fold into intricate three-dimensional shapes that wobble and vibrate. To understand how they perform their tasks, such as to accelerate chemical reactions, both the shapes and their vibrations need to be known. And to this day we are unable to predict either one from the underlying amino acid string, so complex and subtle are the rules underlying this folding. To be sure, experiments to identify protein folds were already under way in the 1950s, beginning with the oxygen-storing globin proteins of our blood and muscles.
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But these experiments were laborious and could take years. Whereas finding the amino acid string encoded by a DNA letter sequence is as easy as looking up a word in a dictionary, predicting a protein fold is much harder—a bit like translating a poem by Yeats into Chinese.

This is not good news for anyone hoping to understand where innovative phenotypes come from. Understanding an organism’s phenotypes—any of its aspects, whether the color of a wing, the acuity of an eye, or the strength of a bone—comes down to understanding the molecules that build a body, the smallest building blocks of the phenotype. If we cannot predict their shape, it is impossible to travel the road from the genotype all the way to the phenotype. But that road is where nature innovates. Without understanding its twists and turns, its speed limits and traffic signs, we know little more about innovability than Darwin.

And it gets worse, because proteins don’t operate on their own. They cooperate like worker bees in solving a complex task. Take the protein hormone insulin, a messenger molecule produced by the pancreas that commands your liver cells to absorb and process glucose. Insulin cannot enter the liver directly. Instead, it binds to a protein on a liver cell’s surface, the insulin receptor. In response, this receptor modifies another protein inside the cell, which starts a chain of handshakes between further proteins that, eventually, turn on the genes needed to process glucose. At every moment of our existence, thousands of such molecular signals crisscross our body and are processed inside cells. Since Watson and Crick’s discovery, molecular biologists have increasingly studied processes like these. Pulling on a few loose strands, they have unearthed the molecular webs that allow us to eat, move, see, hear, think, taste, sleep, and do just about everything else we do.