A short history of nearly everything (55 page)

Darwin was often honored in his lifetime, but never forOn the Origin of Species orDescent of Man. When the Royal Society bestowed on him the prestigious Copley Medal it was for his geology, zoology, and botany, not evolutionary theories, and the Linnaean Society was similarly pleased to honor Darwin without embracing his radical notions. He was never knighted, though he was buried in Westminster Abbey—next to Newton. He died at Down in April 1882. Mendel died two years later.

Darwin’s theory didn’t really gain widespread acceptance until the 1930s and 1940s, with the advance of a refined theory called, with a certain hauteur, the Modern Synthesis, combining Darwin’s ideas with those of Mendel and others. For Mendel, appreciation was also posthumous, though it came somewhat sooner. In 1900, three scientists working separately in Europe rediscovered Mendel’s work more or less simultaneously. It was only because one of them, a Dutchman named Hugo de Vries, seemed set to claim Mendel’s insights as his own that a rival made it noisily clear that the credit really lay with the forgotten monk.

The world was almost ready, but not quite, to begin to understand how we got here—how we made each other. It is fairly amazing to reflect that at the beginning of the twentieth century, and for some years beyond, the best scientific minds in the world couldn’t actually tell you where babies came from.

And these, you may recall, were men who thought science was nearly at an end.

IF YOUR TWO parents hadn’t bonded just when they did—possibly to the second, possibly to the nanosecond—you wouldn’t be here. And if their parents hadn’t bonded in a precisely timely manner, you wouldn’t be here either. And if their parents hadn’t done likewise, and their parents before them, and so on, obviously and indefinitely, you wouldn’t be here.

Push backwards through time and these ancestral debts begin to add up. Go back just eight generations to about the time that Charles Darwin and Abraham Lincoln were born, and already there are over 250 people on whose timely couplings your existence depends. Continue further, to the time of Shakespeare and theMayflower Pilgrims, and you have no fewer than 16,384 ancestors earnestly exchanging genetic material in a way that would, eventually and miraculously, result in you.

At twenty generations ago, the number of people procreating on your behalf has risen to 1,048,576. Five generations before that, and there are no fewer than 33,554,432 men and women on whose devoted couplings your existence depends. By thirty generations ago, your total number of forebears—remember, these aren’t cousins and aunts and other incidental relatives, but only parents and parents of parents in a line leading ineluctably to you—is over one billion (1,073,741,824, to be precise). If you go back sixty-four generations, to the time of the Romans, the number of people on whose cooperative efforts your eventual existence depends has risen to approximately 1,000,000,000,000,000,000, which is several thousand times the total number of people who have ever lived.

Clearly something has gone wrong with our math here. The answer, it may interest you to learn, is that your line is not pure. You couldn’t be here without a little incest—actually quite a lot of incest—albeit at a genetically discreet remove. With so many millions of ancestors in your background, there will have been many occasions when a relative from your mother’s side of the family procreated with some distant cousin from your father’s side of the ledger. In fact, if you are in a partnership now with someone from your own race and country, the chances are excellent that you are at some level related. Indeed, if you look around you on a bus or in a park or café or any crowded place,most of the people you see are very probably relatives. When someone boasts to you that he is descended from William the Conqueror or theMayflower Pilgrims, you should answer at once: “Me, too!” In the most literal and fundamental sense we are all family.

We are also uncannily alike. Compare your genes with any other human being’s and on average they will be about 99.9 percent the same. That is what makes us a species. The tiny differences in that remaining 0.1 percent—“roughly one nucleotide base in every thousand,” to quote the British geneticist and recent Nobel laureate John Sulston—are what endow us with our individuality. Much has been made in recent years of the unraveling of the human genome. In fact, there is no such thing as “the” human genome. Every human genome is different. Otherwise we would all be identical. It is the endless recombinations of our genomes—each nearly identical, but not quite—that make us what we are, both as individuals and as a species.

But what exactly is this thing we call the genome? And what, come to that, are genes? Well, start with a cell again. Inside the cell is a nucleus, and inside each nucleus are the chromosomes—forty-six little bundles of complexity, of which twenty-three come from your mother and twenty-three from your father. With a very few exceptions, every cell in your body—99.999 percent of them, say—carries the same complement of chromosomes. (The exceptions are red blood cells, some immune system cells, and egg and sperm cells, which for various organizational reasons don’t carry the full genetic package.) Chromosomes constitute the complete set of instructions necessary to make and maintain you and are made of long strands of the little wonder chemical called deoxyribonucleic acid or DNA—“the most extraordinary molecule on Earth,” as it has been called.

DNA exists for just one reason—to create more DNA—and you have a lot of it inside you: about six feet of it squeezed into almost every cell. Each length of DNA comprises some 3.2 billion letters of coding, enough to provide 103,480,000,000possible combinations, “guaranteed to be unique against all conceivable odds,” in the words of Christian de Duve. That’s a lot of possibility—a one followed by more than three billion zeroes. “It would take more than five thousand average-size books just to print that figure,” notes de Duve. Look at yourself in the mirror and reflect upon the fact that you are beholding ten thousand trillion cells, and that almost every one of them holds two yards of densely compacted DNA, and you begin to appreciate just how much of this stuff you carry around with you. If all your DNA were woven into a single fine strand, there would be enough of it to stretch from the Earth to the Moon and back not once or twice but again and again. Altogether, according to one calculation, you may have as much as twenty million kilometers of DNA bundled up inside you.

Your body, in short, loves to make DNA and without it you couldn’t live. Yet DNA is not itself alive. No molecule is, but DNA is, as it were, especially unalive. It is “among the most nonreactive, chemically inert molecules in the living world,” in the words of the geneticist Richard Lewontin. That is why it can be recovered from patches of long-dried blood or semen in murder investigations and coaxed from the bones of ancient Neandertals. It also explains why it took scientists so long to work out how a substance so mystifyingly low key—so, in a word, lifeless—could be at the very heart of life itself.

As a known entity, DNA has been around longer than you might think. It was discovered as far back as 1869 by Johann Friedrich Miescher, a Swiss scientist working at the University of Tübingen in Germany. While delving microscopically through the pus in surgical bandages, Miescher found a substance he didn’t recognize and called it nuclein (because it resided in the nuclei of cells). At the time, Miescher did little more than note its existence, but nuclein clearly remained on his mind, for twenty-three years later in a letter to his uncle he raised the possibility that such molecules could be the agents behind heredity. This was an extraordinary insight, but one so far in advance of the day’s scientific requirements that it attracted no attention at all.

For most of the next half century the common assumption was that the material—now called deoxyribonucleic acid, or DNA—had at most a subsidiary role in matters of heredity. It was too simple. It had just four basic components, called nucleotides, which was like having an alphabet of just four letters. How could you possibly write the story of life with such a rudimentary alphabet? (The answer is that you do it in much the way that you create complex messages with the simple dots and dashes of Morse code—by combining them.) DNA didn’t do anything at all, as far as anyone could tell. It just sat there in the nucleus, possibly binding the chromosome in some way or adding a splash of acidity on command or fulfilling some other trivial task that no one had yet thought of. The necessary complexity, it was thought, had to exist in proteins in the nucleus.

There were, however, two problems with dismissing DNA. First, there was so much of it: two yards in nearly every nucleus, so clearly the cells esteemed it in some important way. On top of this, it kept turning up, like the suspect in a murder mystery, in experiments. In two studies in particular, one involving thePneumonococcus bacterium and another involving bacteriophages (viruses that infect bacteria), DNA betrayed an importance that could only be explained if its role were more central than prevailing thought allowed. The evidence suggested that DNA was somehow involved in the making of proteins, a process vital to life, yet it was also clear that proteins were being madeoutside the nucleus, well away from the DNA that was supposedly directing their assembly.

No one could understand how DNA could possibly be getting messages to the proteins. The answer, we now know, was RNA, or ribonucleic acid, which acts as an interpreter between the two. It is a notable oddity of biology that DNA and proteins don’t speak the same language. For almost four billion years they have been the living world’s great double act, and yet they answer to mutually incompatible codes, as if one spoke Spanish and the other Hindi. To communicate they need a mediator in the form of RNA. Working with a kind of chemical clerk called a ribosome, RNA translates information from a cell’s DNA into terms proteins can understand and act upon.

However, by the early 1900s, where we resume our story, we were still a very long way from understanding that, or indeed almost anything else to do with the confused business of heredity.

Clearly there was a need for some inspired and clever experimentation, and happily the age produced a young person with the diligence and aptitude to undertake it. His name was Thomas Hunt Morgan, and in 1904, just four years after the timely rediscovery of Mendel’s experiments with pea plants and still almost a decade beforegene would even become a word, he began to do remarkably dedicated things with chromosomes.

Chromosomes had been discovered by chance in 1888 and were so called because they readily absorbed dye and thus were easy to see under the microscope. By the turn of the twentieth century it was strongly suspected that they were involved in the passing on of traits, but no one knew how, or even really whether, they did this.

Morgan chose as his subject of study a tiny, delicate fly formally calledDrosophila melanogaster , but more commonly known as the fruit fly (or vinegar fly, banana fly, or garbage fly).Drosophila is familiar to most of us as that frail, colorless insect that seems to have a compulsive urge to drown in our drinks. As laboratory specimens fruit flies had certain very attractive advantages: they cost almost nothing to house and feed, could be bred by the millions in milk bottles, went from egg to productive parenthood in ten days or less, and had just four chromosomes, which kept things conveniently simple.

Working out of a small lab (which became known inevitably as the Fly Room) in Schermerhorn Hall at Columbia University in New York, Morgan and his team embarked on a program of meticulous breeding and crossbreeding involving millions of flies (one biographer says billions, though that is probably an exaggeration), each of which had to be captured with tweezers and examined under a jeweler’s glass for any tiny variations in inheritance. For six years they tried to produce mutations by any means they could think of—zapping the flies with radiation and X-rays, rearing them in bright light and darkness, baking them gently in ovens, spinning them crazily in centrifuges—but nothing worked. Morgan was on the brink of giving up when there occurred a sudden and repeatable mutation—a fly that had white eyes rather than the usual red ones. With this breakthrough, Morgan and his assistants were able to generate useful deformities, allowing them to track a trait through successive generations. By such means they could work out the correlations between particular characteristics and individual chromosomes, eventually proving to more or less everyone’s satisfaction that chromosomes were at the heart of inheritance.

The problem, however, remained the next level of biological intricacy: the enigmatic genes and the DNA that composed them. These were much trickier to isolate and understand. As late as 1933, when Morgan was awarded a Nobel Prize for his work, many researchers still weren’t convinced that genes even existed. As Morgan noted at the time, there was no consensus “as to what the genes are—whether they are real or purely fictitious.” It may seem surprising that scientists could struggle to accept the physical reality of something so fundamental to cellular activity, but as Wallace, King, and Sanders point out inBiology: The Science of Life (that rarest thing: a readable college text), we are in much the same position today with mental processes such as thought and memory. We know that we have them, of course, but we don’t know what, if any, physical form they take. So it was for the longest time with genes. The idea that you could pluck one from your body and take it away for study was as absurd to many of Morgan’s peers as the idea that scientists today might capture a stray thought and examine it under a microscope.

What was certainly true was thatsomething associated with chromosomes was directing cell replication. Finally, in 1944, after fifteen years of effort, a team at the Rockefeller Institute in Manhattan, led by a brilliant but diffident Canadian named Oswald Avery, succeeded with an exceedingly tricky experiment in which an innocuous strain of bacteria was made permanently infectious by crossing it with alien DNA, proving that DNA was far more than a passive molecule and almost certainly was the active agent in heredity. The Austrian-born biochemist Erwin Chargaff later suggested quite seriously that Avery’s discovery was worth two Nobel Prizes.