Creation (4 page)

Darwin drew up his masterpiece as the study of cells was beginning to emerge from the stagnant pond of spontaneous generation. But his description of evolution is not about the beginning of new life; it is, as is implicit in the title, about the origin of new species. These arise when an organism has acquired so many mutated traits that they are no longer capable of reproducing with what were once their kin. When we are taught natural selection, typically we refer to prominent visible traits—antlers, hair color, and, once in a while, anteaters' tongues. But we now know how biology works at a cellular level, and can transpose evolution by natural selection to the microscopic world of which Darwin was largely unaware. The fictional anteater's tongue is longer because, by the chance of variation within its population, that individual has more (or possibly larger) cells in that tongue, and the genes that generate this disparity of tissue will be passed on through sperm or egg to the next generation. Similarly, when you get a paper cut the reason your platelets form a plug and a wedge to help stop blood loss is effectively because creatures carrying cells in their blood that didn't perform that clotting function as effectively have been deselected by nature thousands of generations (and species) ago (probably by allowing the creature concerned to heal less efficiently, or possibly leak to death). Crucially, we now know that what is being selected is not the individual, nor the cell, but the carrier of the information that bears advantage. As with all biology, the information that confers clotting is held in DNA inside cells, the molecule that will play the central role throughout the whole of this story.

Cell theory and natural selection are reflections of the same truth: life is derived. It's incrementally and ultimately spectacularly modified, but, in essence, life is the adapted continuation of what came before.
¹¹

Public acceptance of evolution by natural selection has waxed and waned over time, and was disputed by scientists at least in its first fifty years or so. But now, at least among scientists and those who generally understand it, natural selection is the only valid explanation for the variety of life on Earth. While science by definition expects to be corrected over time, it now seems extremely unlikely that Darwin's idea will be replaced wholesale. When you tie it together with cell theory, both ideas are compellingly fortified.

Although the concept of evolution—simply that organisms change over time—predated Darwin, in 1859 this idea, as well as that of natural selection, was new and truly revolutionary. They both rebutted the prevailing view across the majority of human history, that creatures were each created distinctly. Without the hard-fought work of Darwin and the closely observed work of the eighteenth- and nineteenth-century microscopists, the idea of multiple routes for life, separate origins not just for plants, animals, fungi, but for every single type of organism, might have seemed plausible. Even taking into account the innumerable variety of distinct cell types, each with highly specialized functions, separate or plural origins might seem reasonable.

Instead, thanks to Darwin and cell theory, we can link every organism on the grandest pedigree. As Darwin writes in the final paragraph of his masterpiece, “There is a grandeur in this view of life, with its several powers, having been originally breathed into a few forms or into one.” These are some of the finest words set to paper, oft quoted, but some things are just worth repeating. Yet he did pose a question in those last five words: “into a few forms or into one.” Which is it? What lies at the base of the tree of life? A single form, a cell, or several? The answer to this deep-rooted historical question lies not in the past, but in the molecular guts of every single living cell. By examining the mechanism by which cells pass on their characteristics and by which those characteristics mutate, we will arrive at an answer to the question of whether life has a single origin—and we will begin to see what it might have looked like when it first emerged.

Into One

L
ook out the nearest window and try to count how many species you can see. As I sit here at my desk looking at the view into the garden, I can count forty species of plant (at least six of which I can name), a spider, a squirrel, and a suspiciously well-fed wood pigeon. I know that there are millions of other beings nestling in the soil, feeding on the leaves, hiding in the mortar between bricks. I know that there are tiny parasitic insects hitching rides on the hairs of the squirrel and in the feathers of the bird, and that those bugs themselves are serving as a rich habitat for thousands of bacteria. I know that on Earth bacteria outnumber and outweigh all other living things by count and by mass, and there are billions in every spadeful of loam. As undergraduates my classmates and I grew cultures of bacteria taken from swabbing our teenage skin and streaking them out in their multitudes on agar plates. You can look down at the end of your nose and be confident that there is more life in that view than in the rest of the known off-world universe. We have classified around two million living species, and we know that number is a massive underestimate, as new ones are discovered and named every day. Life is bewilderingly diverse. What is more confounding, though, is its conformity.

It doesn't take a great leap of faith to see that we are closely related to chimpanzees or gorillas. Only a designer setting out to deceive or fundamentally lacking in imagination or effort would create things so similar and pretend that they were not cousins. It is obvious that dogs in all their human-crafted forms are related closely to wolves, and science confirms it. It takes a little bit more analysis to show that dolphins are much more closely related to hippos than to tuna, but dig deeper and it becomes obvious that all three species have common ancestry visible in their spines, eyes, and the bone structure (among many other things) of their flippers, feet, and fins, respectively. Yet it's admittedly harder to see the commonality between the leaf of a sycamore and the fin of a cichlid. Or a western long-beaked echidna and the recently discovered Malaysian mushroom
Spongiforma squarepantsii
. Or
Turdus philomelos
and
Candida albicans
: one is a pretty songbird, the other a creamy fungus, but both are called “thrush.”

This zoo is made of cells of many different sizes and shapes. And yet all cells are basically the same, just as all gasoline-powered cars are basically the same. Cars have a chassis, an engine, some wheels (usually four), a steering wheel, and so on. The details of the engine, the design, the tires, et cetera comprise the difference between a Porsche 911 and a Pinto. Fundamentally, however, they are both cars, derived via successive iterations from a common ancestor, one that bore an early version of the internal combustion engine built from metal and powered by fossil fuel. And so it is with cells. Under the hood there are mechanisms and parts that vary the performance of a cell depending on its job, as part of an organism or standing alone. Cells, in terms of their overall structure, are basically the same, but are highly specialized to build the complexities and adaptations of all life.

The starting point for those basics of biology was the result of cell scientists making forward strides in the mid-1800s. This was clearly a feverish time, as Darwin was also deducing evolution, and a few thousand miles east, an Austrian holy man was planting a garden that would invigorate biology forevermore. Gregor Mendel is invariably described as a monk, which, while absolutely true, shrouds the fact that his legacy is unequivocally as a scientific genius and world-changing experimentalist.
¹
Around the time Darwin was writing his masterpiece, Mendel had been studying pea plants and was breeding them in the tens of thousands. As any scientist will tell you, large numbers make for good statistics. What Mendel found in impressively large numbers was that, when crossing variants of pea plants with one another, the outcomes in the offspring were entirely predictable. He showed, moreover, that the traits were inherited in a discrete way—that is, independently of the rest of the plant's characteristics. Rather than a blending of flower color, the progeny of a purple-flower pea plant and a white-flower pea plant were not pinkish, but resulted in a predictable number of white ones and purple ones. By repeating these crossbreeds until the patterns were clear, Mendel's pea experiments also resulted in his determining that characteristics were inherited equally, one from each parent, but that some of those characteristics were more equal than others. He bred tall plants with short ones, and their offspring were always tall, rather than an average of the two heights. When he crossed those offspring together, three-quarters of their offspring were tall and one was short. In those proportions he had uncovered not only that characteristics were passed down individually, but also that some characteristics were dominant over others.

The story of Mendel and his peas is high-school biology. What he had discovered (though the name came much later) was the existence of genes—discrete units of inheritance.
²

Having been largely ignored, at the beginning of the twentieth century Mendel's papers were rediscovered. What followed was observation beyond that which is visible to the naked eye. New technologies of the twentieth century meant that the scale of biology was reducing from the organism to the cell, to the molecular and atomic level, and with this zooming in came the birth of modern genetics.

“It has not escaped our notice . . .”

Between Mendel's death in 1884 and the 1950s, there were major successive advances in the study of genes. Mendel had established that inheritance occurred in discrete units. Italian marine biologists looked at the cells of sea urchins and observed chromosomes—neat structures inside the nucleus of all cells, which became visible, resembling tiny sausages, when the cells divided. They came in specific numbers depending on the host, and these marine biologists discovered that altering the number of chromosomes resulted in abominations in their offspring, or prevented reproduction altogether. In the 1920s, Thomas Hunt Morgan inbred fruit flies to show that Mendel's units of inheritance were positioned very precisely on these chromosomes. German researchers, meanwhile, had shown that chromosomes were made of a molecule called DNA, whose chemical composition was clearly different from the proteins that made up much of the cells ingredients, as it contained phosphate.

In the 1940s, Oswald Avery, Colin MacLeod, and Maclyn McCarty demonstrated it was DNA that conferred characteristics and passed them on by performing a neat resurrection trick in New York, perversely a fatal one. They were following the work of Fred Griffiths, a British medical officer who more than a decade earlier had noticed that, during the course of pneumonia, virulent and benign bacteria were both present, but that the latter could acquire the malign characteristics of the former, even if these malign bacteria were themselves dead. He demonstrated this by boiling the lethal bacteria, thereby killing them, and then adding the resultant broth to the benign bugs, which then acquired the ability to kill. Avery and his team repeated Griffiths' experiment, but to figure out how it worked, they systematically eliminated each of the components of the bacteria that were candidates for passing on this characteristic. It was only when they destroyed the deadly bacteria's DNA that the transformation failed to occur. It seemed that DNA, not proteins or anything else in the cell's milieu, was the essential genetic material, the stuff that bestowed characteristics and passed them on.

DNA was clearly a—possibly
the
—key component of inheritance. But it was unclear how this could work. The answer lay in its construction. At King's College London in 1952, a group of researchers including Maurice Wilkins, Rosalind Franklin, and Raymond Gosling were investigating DNA using their expertise in producing photographic representations of three-dimensional molecular structures. X-ray diffraction, a standard technique for establishing three-dimensional models of complex molecules, was brought to London by Wilkins from the Manhattan Project, which created the first atomic bombs. The principle is similar to the kind of silhouette portraits that were fashionable in the eighteenth and nineteenth centuries: shine a beam at your subject and capture the light and dark that is projected past it. The human subject in portraiture is a solid to the visible light that this technique uses, but in the molecular version the X-rays penetrate the molecule under scrutiny and create signature shadows behind it, regular but cryptic swirls cast onto the photographic plate. Mathematical deduction is required to figure out the arrangement of atoms that could produce such a pattern, but the effect is the same: a unique portrait of a molecule otherwise too small to see. Franklin was particularly skilled at this technique, and of the many photographs that Franklin, along with Gosling, developed while performing this arduous method, Photo 51 became the key to one of the great achievements in human history.

The Cambridge scientists Francis Crick and James Watson acquired the photograph. Science always builds on the work of others, but it was with their insight and genius that they deduced from Franklin and Gosling's photo that DNA took the form of a twisted ladder: the iconic double helix. On April 25, 1953, in a brief paper published in the scientific journal
Nature,
Crick and Watson showed that the rungs of this twisted ladder contained paired chemical letters—
A
for adenine,
T
for thymine,
C
for cytosine, and
G
for guanine. Each letter is bound to one vertical section of the ladder and pairs up with a corresponding letter on the other upright to form a rung. It is this pairing that makes the helix doubled, and the pairing is very precise:
A
always pairs with
T;
C
always pairs with
G
. Crick and Watson concluded the paper with one of science's great understatements: “It has not escaped our notice that the specific pairing we have postulated immediately suggests a copying mechanism for the genetic material.”

This is the first marvelous thing about DNA. If you split the double helix into its two component strands, you immediately have the information to replace the missing strand: where there is an
A,
the other strand should have a
T,
and where there is a
C,
the other strand needs a
G.
Therefore, DNA possesses an ability, inherent in its structure, to provide the instructions for its own replication. Thanks to Crick and Watson, building on the work of Wilkins, Gosling, and particularly Rosalind Franklin, we were given a molecule that could be copied and passed from generation to generation.
³

The letter molecules, known as nucleobases or simply bases, bind to one another, holding the two vertical parts of the ladder together. There are millions of such pairings on each strand of DNA, something like six and a half feet of it in every cell that has a nucleus, though it is tightly wound up and then winds up on itself again around small lumps of proteins, like beads on a string. And this winds up on itself yet again, which forms a chromosome, like a thick tug-of-war rope.

The number and length of chromosomes varies hugely between all species, and that variation doesn't appear to relate to either the size or complexity of the host. We have twenty-three pairs, and bacteria tend to have just one, in a neat loop. But some species of carp have over a hundred, and this doesn't come anywhere near the number in some plant chromosomes, which can be in the thousands. The full collection of an organism's DNA, packaged into chromosomes, is called a genome. In humans, those twenty-three chromosomes, our genome, contain around three billion of those little letters,
A, T, C,
and
G,
which is sufficient to fill a two-hundred-thousand-page phone book, if that type of comparison is appealing. But every time a cell splits into two, from the first time your fertilized egg divides to the newborn skin cells in a paper cut, all the DNA in those cells copies itself. The new cell contains all the same DNA of its parent.
⁴

Being able to replicate from generation to generation is a neat trick indeed. But alone, that would just fill the world with a pretty molecule. DNA's secret power is that this string of chemical letters, the bases, is a code that harbors information. That information is an instruction manual for all of the processes of life, including the very instructions required for the replication process itself. Understanding how DNA's code works will unlock not just how mutation and variation take place, drawing us closer to an answer to the question posed in Darwin's “into few forms or into one,” but will give us essential clues as to how life was initially formed.

How DNA Works

All life is made by, or of, proteins. They form the structures and catalysts of biology, and the manufactories of bone, hair, and all the bits of a body that aren't actually made of protein. Naturally, this isn't limited to us, or even to mammals. Every leaf, strip of bark, reptilian scale, horn, fungus, feather, and flower is made of or by proteins. These workhorses of life are themselves made up of strings of smaller units called amino acids—a generic name for a potentially infinite number of molecular parts that qualify for this chemical moniker.

We now know that each gene—those discrete units of inheritance—in a genome is a piece of code made up of the specific pairings of DNA bases that encrypt the construction of a protein. However, only a few parts in many species' genomes are genes. The rest, in fact the overwhelming majority of DNA in humans, comprises notes, instructions, scaffolding, and even insertions from interloping viruses. Some are the remnants of genes from our ancestors whose function has been lost in us, but whose ghosts remain in our genome, free from the pressure of natural selection to slowly rust. Having established in 1953 that DNA was a corkscrewed ladder, and that it had the twin powers of replication and coded meaning, the biggest challenge in biology after Crick and Watson's great leap forward was to decode DNA. This meant first identifying which bits of DNA were genes and which were not.