Chapter 30 26 THE STUFF OF LIFE

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 the Mayflower Pilgrims, and you have nofewer 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. —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'sside of the family procreated with some distant cousin from your father's side of the ledger. Infact, 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 abus or in a park or cafe or any crowded place, most of the people you see are very probably relatives. Someone boasts to you that he is descended from William the Conqueror or the Mayflower 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 orogenomes—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 gene package.) Chromosomes constitute the complete set of instructions necessary to make and maintain you and are made of longstrands of the little wonder chemical called deoxyribonucleic acid or DNA—“the most textraordinary 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 103,480,000,000 possible combinations, “guaranteed to be unique against all conceivable odds,” in the word of Du Christian 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 semenin 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 Tubingen in Germany. 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 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 havingan alphabet of just four letters. How could you possibly write the story of life with such arudimentary 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'tdo 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. Ontop of this, it kept turning up, like the suspect in a murder mystery, in experiments. In twostudies in particular, one involving the Pneumonococcus bacterium and another involving bacteria (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 so it life, Clear that proteins were being made outside 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 samelanguage. For almost four billion years they have been the living world's great double act, andyet 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 resumed 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 before gene 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 no ones, knew how, or even really whether, they did this. Morgan chose as his subject of study a tiny, delicate fly formally called Drosophila melanogaster, but more commonly known as the fruit fly (or vinegar fly, banana fly, orgarbage 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 or in ten days , 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, although that is pro an exaggeration), each of which had to be captured with tweezers and examined under a jeweler's glass for any tiny variations 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 crazy in centrifuges—but nothing worked. Morgan wason 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. Aslate as 1933, when Morgan was awarded a Nobel Prize for his work, many researchers stillweren' 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 to foundation cellular activity, but as Wallace, King, and Sanders point out in Biology: 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 wasas absurd to m any of Morgan's peers as the idea that scientists today might capture a strawthought and examine it under a microscope. What was certainly true was that something 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 Oslywald exploded with an ex eri Avery tried in which an innocuous strain of bacteria wasmade 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. Wasworth two Nobel Prizes. Unfortunately, Avery was opposed by one of his own colleagues at the institute, a strong-willed and disagreeable protein enthusiast named Alfred Mirsky, who did everything in his power to discredit Avery's work—including, it has been said, lobbying at the authoritute in Stockholm not to give Avery a Nobel Prize. Avery by this time wassixty-six years old and tired. Unable to deal with the stress and controversy, he resigned hisposition and never went near a lab again. But other experiments elsewhere overwhelmingly supported his conclusions, And soon the race was on to find the structure of DNA. Had you been a betting person in the early 1950s, your money would almost certainly have been on Linus Pauling of Caltech, America's leading chemist, to crack the structure of DNA. Pauling was unrivaled in determining the architecture of molecules and had been a pioneer in the field of X-ray crystallography, a technique that would prove crucial to peering into the heart of DNA. In an exceedingly distinguished career, he would win two Nobel Prizes (forchemistry in 1954 and peace in 1962), but with DNA he became convinced that the structure was a triple helix, not a double one, and never quite got on the right track. Instead, victory fell to an unlikely quartet of scientists in England who didn't work As a team, often weren't on speaking terms, and were for the most part novices in the field. Of the four, the nearest to a conventional boffin was Maurice Wilkins, who had spent much of the Second World War helping to design the atomic bomb. Two of the others, Rosalind Franklin and Francis Crick, had passed their war years working on mines for the Britishgovernment —Crick of the type that blow up, Franklin of the type that produce coal. The most unconventional of the foursome was James Watson, an American prodigy who had distinguished himself as a boy as a member of a highly popular radio program called TheQuiz Kids (and thus could claim to be at least part of the inspiration for some of the members of the Glass family in Franny and Zooey and other works by JD Salinger) and who hadentered the University of Chicago aged just fifteen. He had earned his Ph.D. by the age of twenty-two and was now attached to the famous Cavendish Laboratory in Cambridge. In1951, he was a gawky twenty-three-year-old with a strikingly lively head of hair that appears in photographs to be straining to attach itself to some powerful magnet just out of frame. Crick, twelve years older and still without a doctorate, was less memorably hirsute and slightly more tweedy. In Watson's account he is presented as blustery, nosy, cheerfully argumentative, impatient with anyone slow to share a notion, and constantly in danger of going elsewhere asked . Neither was formally trained in biochemistry. Their assumption was that if you could determine the shape of a DNA molecule you would be able to see—correctly, as it turned out—how it did what it did. They hoped to achieve this, it would appear, by doing as little work as possible beyond thinking, and no more of that than was absolutely necessary. As Watson cheerfully (if a touch disingenuously) remarked in his autobiographical book The Double Helix, “It was my hope that the gene might be solved without my learning any chemistry.” They weren' t actually assigned to work on DNA, and atone point were ordered to stop it. Watson was ostensibly mastering the art of crystallography; Crick was supposed to be completing a thesis on the X-ray diffraction of large molecules. Although Crick and Watson enjoy nearly all the credit in popular accounts for solving the mystery of DNA, their breakthrough was crucially dependent on experimental work done by their competitors, the results of which were obtained “fortuitously,” in the tactful words of the hisistorian Lisa Jard Ahead of them, at least at the beginning, were two academics at King's College in London, Wilkins and Franklin. The New Zealand–born Wilkins was a retiring figure, almost to the point of invisibility. A1998 PBS documentary on the discovery of the structure of DNA—a feat for which he shared the 1962 Nobel Prize with Crick and Watson—managed to overlook him entirely. The most enigmatic character of all was Franklin. In a severely unflattering portrait, Watson in The Double Helix depicted Franklin as a woman who was unreasonable, secretive, chronically uncooperative, and—this seemed especially to irritate him—almost willfully unsexy. “was not unattractive and might have been quite stunning had shetaken even a mild interest in clothes,” but in this she disappointed all expectations. She didn’t even use lipstick, he noted in wonder, while her dress sense “showed all the imagination of English blue-stocking adolescents.” 1However, she did have the best images in existence of the possible structure of DNA, achieved by means of X-ray crystallography, the technique perfected by Linus Pauling. Crystallography had been used successfully to map atoms in crystals (hence “crystallography”), but DNA molecules were a much more finicky proposition. Only Franklin was managing to get good results from the process, but to Wilkins's perennial examinations she refused to finish If Franklin was not warmly forthcoming with her findings, she cannot be altogetherblamed. Female academics at King's in the 1950s were treated with a formalized disdain thatdazzles modern sensibilities (actually any sensibilities). However senior or accomplished,they were not allowed into the college's senior common room but instead had to take their meals in a more utilitarian chamber that even Watson conceded was “dingily pokey.” On top of this she was being constantly pressed—at times actively harassed—to share her results with a trio of men whose desperation to get a peek at them was seldom matched by more engaging qualities, like respect. “I'm afraid we always used to adopt—let's say a patronizing attitude toward her,” Crick later recalled. Two of these men were from a competing institution and the third was more or less openly siding with them. It should hardly come as a surprise that shekept her results locked away. That Wilkins and Franklin did not get along was a fact that Watson and Crick seemed to have exploited to their benefit. Although Crick and Watson were trespassing rather unashamedly on Wilkins's territory, it was with them that he increasingly sided—not altogether belin surprisingly since ginse Fw act in a decidedly queer way. Although her results showed that DNA definitely was helical in shape, she insisted to all that it was not. To Wilkins's presumed dismay and embarrassment, in the summer of 1952 she posted a mock notice around the King's physics department that said: “It is with great regret that we have to announce the death, on Friday 18th July 1952 of DNA helix. . . . It is hoped that Dr. MHF Wilkins will speak in memory of the late helix." The outcome of all this was that in January 1953, Wilkins showed Watson Franklin's images, “apparently without her knowledge or consent.” It would be an understatement to callit a significant help. Years later Watson conceded that it “was the key event . . . it mobilizedus.” Armed with the knowledge of the DNA molecule's basic shape and some important elements of its dimensions, Watson and Crick redoubled their efforts. Everything now seemed to go their way. At one point Pauling was en route to a conference in England at which he would in all likelihood have met with Wilkins and learned enough to correct the misconceptions that had put him on the wrong line of inquiry, but this was the McCarthy era and Pauling found himself detained at Idlewild Airport in New York, his passport confiscated, on the grounds that he was too liberal of temperature to be allowed to travel abroad. Crick and Watson also had the no less convenient good fortune that Pauling's son was working at the Cavendish and innocent tly kept them abreast of any news of developments and setbacks athome. Still facing the possibility of being trumped at any moment, Watson and Crick applied themselves feverishly to the problem. It was known that DNA had four chemical1 In 1968, Harvard University Press canceled publication of The Double Helix after Crick and Wilkins complained about its character, historian Lisa Jardine has described as "gratuitously hurtful." The descriptions quoted above are after Watson softened his comments. components—called adenine, guanine, cytosine, and thiamine—and that these paired up inparticular ways. By playing with pieces of cardboard cut into the shapes of molecules, Watson and Crick were able to work out how the pieces fit together. From this they made a Meccano-like model—perhaps the most famous in modern science—consisting of metal plates bolted together in a spiral, and invited Wilkins, Franklin, and the rest of the world to have a look. Any informed person could see at once that they had solved the problem. It was without question a brilliant piece of detective work, with or without the boost of Franklin's picture. The April 25, 1953, edition of Nature carried a 900-word article by Watson and Crick titled “A Structure for Deoxyribose Nucleic Acid.” Accompanying it were separate articles by Wilkins and Franklin. It was an eventful time in the world—Edmund Hillary was just about toclamber to the top of Everest while Elizabeth II was imminently to be crowned queen of England—so the discovery of the secret of life was mostly overlooked. It received a small mention in the News Chronicle and was ignored elsewhere. Rosalind Franklin did not share in the Nobel Prize. She died of ovarian cancer at the age of just thirty-seven in 1958, four years before the award was granted. Nobel Prizes are notawarded posthumously. The cancer almost certainly arose as a result of chronic overexposure X-rays through her work and needn't have happened. In her much-praised 2002 biography of Franklin, Brenda Maddox noted that Franklin rarely wore a lead apron and often stepped carelessly in front of a beam. Oswald Avery never won a Nobel Prize either and was also largely overlooked by posterity, though he did at least have the satisfaction of living just long enough to see his findings vindicated. He died in 1955. Watson and Crick's discovery wasn't actually confirmed until the 1980s. As Crick said inone of his books: “It took over twenty-five years for our model of DNA to go from being only rather plausible, to being very plausible . . . and from there to being virtually certainly correct.” Even so, with the structure of DNA understood progress in genetics was swift, and by 1968 the journal Science could run an article titled “That Was the Molecular Biology That Was,” suggesting—it hardly seems possible, but it is so—that the work of genetics was nearly at an end. In fact, of course, it was only just beginning. Even now there is a great deal about DNA that we scarcely understand, not least why so much of it doesn't actually seem to do anything. Ninety-seven percent of your DNA consists of nothing but long stretches of meaninglessgarble—“junk,” or “non-coding DNA,” as biochemists prefer to put it. Only here and there along each strand do you find sections that control and organize vital functions. These are the curious and long-elusive genes. Genes are nothing more (nor less) than instructions to make proteins. This they do with a certain dull fidelity. In this sense, they are rather like the keys of a piano, each playing asingle note and nothing else, which is obviously a trifle monotonous . But combine the genes, as you would combine piano keys, and you can create chords and melodies of infinite variety. Put all these genes together, and you have (to continue the metaphor) the great symphony of existence known as the human genome. An alternative and more common way to regard the genome is as a kind of instruction manual for the body. Viewed this way, the chromosomes can be imagined as the book'schapters and the genes as individual instructions for making proteins. The words in which the instructions are written are called codons, and the letters are known as bases. The bases—the letters of the genetic alphabet—consist of the four nucleotides mentioned a page or two back: adenine, thiamine, guanine, and cytosine. Despite the importance of what they do, these substances are not made of anything exotic. Guanine, for instance, is the same stuff that abounds in, and gives its name to, guano. The shape of a DNA molecule, as everyone knows, is rather like a spiral staircase ortwisted rope ladder: the famous double helix. The uprights of this structure are made of a type of sugar called deoxyribose, and the whole of the helix is ​​a nucleic acid —hence the name “deoxyribonucleic acid.” The rungs (or steps) are formed by two bases joining across the space between, and they can combine in only two ways: guanine is always paired with cytosine and thiamine always with adenine. The order in which these letters appear as you move up or down the ladder constitutes the DNA code; logging it has been the job of the Human Genome Project. Now the particular brilliance of DNA lies in its manner of replication. When it is time to produce a new DNA molecule, the two strands part down the middle, like the zipper on ajacket, and each half goes off to form a new partnership. Nucleotide along astrand pairs up with a specific other nucleotide, each strand serves as a template for the creation of a new matching strand. If you possessed just one strand of your own DNA, you could easily enough reconstruct the matching side by working out the necessary partnerships: if the topmost rung on one strand was made of guanine, then you would know that the topmost rung on the matching strand must be cytosine. Work your way down the ladder through all the nucleotide pairings, and eventually you would have the code for a new molecule. That is just what happens in nature, except that nature does it really quickly—inonly a matter of seconds, which is quite a feat. Most of the time our DNA replicates with dutiful accuracy, but just occasionally—about one time in a million—a letter gets into the wrong place. This is known as a single nucleotide polymorphism, or SNP, familiarly known to biochemists as a “Snip.” Generally these Snips are buried in stretches of noncoding DNA and have no detectable consequence for the body. But occasionally they make a difference. They might leave you predisposed to some disease, but equally they might confer some slight advantage—more protective pigmentation, for instance, or increased production of red blood cells for someone living at altitude. Over time, these modification slight accumulate in both individuals and in populations, contributing to the distinctiveness of both. The balance between accuracy and errors in replication is a fine one. Too many errors and the organism can't function, but too few and it sacrifices adaptability. A similar balance mustexist between stability in an organism and innovation. An increase in red blood cells can helpa person or group living at high elevations to move and breathe more easily because more red cells can carry more oxygen. But additional red cells also thicken the blood. Add too many, and “it's like pumping oil,” in the words of Temple University anthropologist Charles Weitz. That's hard on the heart. Thus those designed to live at high altitude get increased breathing efficiency, but pay for it with higher-risk hearts. By such means does Darwinian natural selection look after us. It also helps to explain why we are all so similar. Evolution simply won't let you become too different—not without becoming a new species anyway. The 0.1 percent difference between your genes and mine is accounted for by our Snips. Now if you compared your DNA with a third person's, there would also be 99.9 percent correspondence, but the Snips would, for the most part, be in different places. Add more people to the comparison and you will get yet more Snips in yet more places. For every one of your 3.2 billion bases, somewhere on the planet there will be a person, or group of persons, with different coding in that position. So not only is it wrong to refer to “the” human genome, but in a sense we don't even have “a” human genome. We have six billion of them. We are all99.9 percent the same, but equally, in the words of the biochemist David Cox, “you could sayall humans share nothing, and that would be correct, too." But we have still to explain why so little of that DNA has any discernible purpose. It starts to get a little unnerving, but it does really seem that the purpose of life is to perpetuate DNA. The 97 percent of our DNA commonly called junk is largely made up of clumps of letters that, in Ridley's words, “exist for the pure and simple reason that they are good at getting themselves duplicated.” 2Most of your DNA, in other words, is not devoted to you but to itself: you are a machine for reproducing it, not it for you. Life, you will recall, just wants to be, and DNA is what makes it so. Even when DNA includes instructions for making genes—when it codes for them, asscientists put it—it is not necessarily with the smooth functioning of the organism in mind. One of the commonest genes we have is for a protein called reverse transcriptase, which hasno known beneficial function in human beings at all. The one thing itdoes do is make itpossible for retroviruses, such as the AIDS virus, to slip unnoticed into the human system. In other words, our bodies devote considerable energies to producing a protein that doesnothing that is beneficial and sometimes clobbers us. Our bodies have no choice but to do sobecause the genes order it. We are vessels for their whims. Altogether, almost half of humangenes—the largest proportion yet found in any organism—don't do anything at all, as far aswe can tell, except reproduce themselves. All organisms are in some sense slaves to their genes. That's why salmon and spiders andother types of creatures more or less beyond counting are prepared to die in the process ofmating. The desire to breed, to disperse one's genes, is the most powerful impulse in nature. As Sherwin B. Nuland has put it: “Empires fall, ids explode, great symphonies are written,and behind all of it is a single instinct that demands satisfaction.” From an evolutionary pointof view, sex is really just a reward mechanism to encourage us to pass on our genetic material. Scientists had only barely absorbed the surprising news that most of our DNA doesn't doanything when even more unexpected findings began to turn up. First in Germany and then inSwitzerland researchers performed some rather bizarre experiments that produced curiouslyunbizarre outcomes. In one they took the gene that controlled the development of a mouse'seye and inserted it into the larva of a fruit fly. The thought was that it might producesomething interestingly grotesque. In fact, the mouse-eye gene not only made a viable eye inthe fruit fly, it made a fly's eye. Here were two creatures that hadn't shared a commonancestor for 500 million years, yet could swap genetic material as if they were sisters. The story was the same wherever researchers looked. They found that they could inserthuman DNA into certain cells of flies, and the flies would accept it as if it were their own. 2Junk DNA does have a use. It is the portion employed in DNA fingerprinting. Its practicality for this purposewas discovered accidentally by Alec Jeffreys, a scientist at the University of Leicester in England. In 1986Jeffreys was studying DNA sequences for genetic markers associated with heritable diseases when he wasapproached by the police and asked if he could help connect a suspect to two murders. He realized his techniqueought to work perfectly for solving criminal cases-and so it proved. A young baker with the improbable name ofColin Pitchfork was sentenced to two life terms in prison for the murders. Over 60 percent of human genes, it turns out, are fundamentally the same as those found infruit flies. At least 90 percent correlate at some level to those found in mice. (We even havethe same genes for making a tail, if only they would switch on.) In field after field,researchers found that whatever organism they were working on—whether nematode wormsor human beings—they were often studying essentially the same genes. Life, it appeared, wasdrawn up from a single set of blueprints. Further probings revealed the existence of a clutch of master control genes, each directingthe development of a section of the body, which were dubbed homeotic (from a Greek wordmeaning “similar”) or hox genes. Hox genes answered the long-bewildering question of howbillions of embryonic cells, all arising from a single fertilized egg and carrying identicalDNA, know where to go and what to do—that this one should become a liver cell, this one astretchy neuron, this one a bubble of blood, this one part of the shimmer on a beating wing. Itis the hox genes that instruct them, and they do it for all organisms in much the same way. Interestingly, the amount of genetic material and how it is organized doesn't necessarily, oreven generally, reflect the level of sophistication of the creature that contains it. We haveforty-six chromosomes, but some ferns have more than six hundred. The lungfish, one of theleast evolved of all complex animals, has forty times as much DNA as we have. Even thecommon newt is more genetically splendorous than we are, by a factor of five. Clearly it is not the number of genes you have, but what you do with them. This is a verygood thing because the number of genes in humans has taken a big hit lately. Until recently itwas thought that humans had at least 100,000 genes, possibly a good many more, but thatnumber was drastically reduced by the first results of the Human Genome Project, whichsuggested a figure more like 35,000 or 40,000 genes—about the same number as are found ingrass. That came as both a surprise and a disappointment. It won't have escaped your attention that genes have been commonly implicated in anynumber of human frailties. Exultant scientists have at various times declared themselves tohave found the genes responsible for obesity, schizophrenia, homosexuality, criminality,violence, alcoholism, even shoplifting and homelessness. Perhaps the apogee (or nadir) of thisfaith in biodeterminism was a study published in the journal Science in 1980 contending thatwomen are genetically inferior at mathematics. In fact, we now know, almost nothing aboutyou is so accommodatingly simple. This is clearly a pity in one important sense, for if you had individual genes that determinedheight or propensity to diabetes or to baldness or any other distinguishing trait, then it wouldbe easy—comparatively easy anyway—to isolate and tinker with them. Unfortunately, thirty-five thousand genes functioning independently is not nearly enough to produce the kind ofphysical complexity that makes a satisfactory human being. Genes clearly therefore mustcooperate. A few disorders—hemophilia, Parkinson's disease, Huntington's disease, andcystic fibrosis, for example—are caused by lone dysfunctional genes, but as a rule disruptivegenes are weeded out by natural selection long before they can become permanentlytroublesome to a species or population. For the most part our fate and comfort—and even oureye color—are determined not by individual genes but by complexes of genes working inalliance. That's why it is so hard to work out how it all fits together and why we won't beproducing designer babies anytime soon. In fact, the more we have learned in recent years the more complicated matters have tendedto become. Even thinking, it turns out, affects the ways genes work. How fast a man's beardgrows, for instance, is partly a function of how much he thinks about sex (because thinkingabout sex produces a testosterone surge). In the early 1990s, scientists made an even moreprofound discovery when they found they could knock out supposedly vital genes fromembryonic mice, and the mice were not only often born healthy, but sometimes were actuallyfitter than their brothers and sisters who had not been tampered with. When certain importantgenes were destroyed, it turned out, others were stepping in to fill the breach. This wasexcellent news for us as organisms, but not so good for our understanding of how cells worksince it introduced an extra layer of complexity to something that we had barely begun tounderstand anyway. It is largely because of these complicating factors that cracking the human genome becameseen almost at once as only a beginning. The genome, as Eric Lander of MIT has put it, is likea parts list for the human body: it tells us what we are made of, but says nothing about howwe work. What's needed now is the operating manual—instructions for how to make it go. We are not close to that point yet. So now the quest is to crack the human proteome—a concept so novel that the termproteome didn't even exist a decade ago. The proteome is the library of information thatcreates proteins. “Unfortunately,” observed Scientific American in the spring of 2002, “theproteome is much more complicated than the genome.” That's putting it mildly. Proteins, you will remember, are the workhorses of all livingsystems; as many as a hundred million of them may be busy in any cell at any moment. That'sa lot of activity to try to figure out. Worse, proteins' behavior and functions are based notsimply on their chemistry, as with genes, but also on their shapes. To function, a protein mustnot only have the necessary chemical components, properly assembled, but then must also befolded into an extremely specific shape. “Folding” is the term that's used, but it's amisleading one as it suggests a geometrical tidiness that doesn't in fact apply. Proteins loopand coil and crinkle into shapes that are at once extravagant and complex. They are more likefuriously mangled coat hangers than folded towels. Moreover, proteins are (if I may be permitted to use a handy archaism) the swingers of thebiological world. Depending on mood and metabolic circumstance, they will allowthemselves to be phosphorylated, glycosylated, acetylated, ubiquitinated, farneysylated,sulfated, and linked to glycophosphatidylinositol anchors, among rather a lot else. Often ittakes relatively little to get them going, it appears. Drink a glass of wine, as ScientificAmerican notes, and you materially alter the number and types of proteins at large in yoursystem. This is a pleasant feature for drinkers, but not nearly so helpful for geneticists who aretrying to understand what is going on. It can all begin to seem impossibly complicated, and in some ways itis impossiblycomplicated. But there is an underlying simplicity in all this, too, owing to an equallyelemental underlying unity in the way life works. All the tiny, deft chemical processes thatanimate cells—the cooperative efforts of nucleotides, the transcription of DNA into RNA—evolved just once and have stayed pretty well fixed ever since across the whole of nature. Asthe late French geneticist Jacques Monod put it, only half in jest: “Anything that is true of E. coli must be true of elephants, except more so.” Every living thing is an elaboration on a single original plan. As humans we are mereincrements—each of us a musty archive of adjustments, adaptations, modifications, andprovidential tinkerings stretching back 3.8 billion years. Remarkably, we are even quiteclosely related to fruit and vegetables. About half the chemical functions that take place in abanana are fundamentally the same as the chemical functions that take place in you. It cannot be said too often: all life is one. That is, and I suspect will forever prove to be, themost profound true statement there is. PART VITHE ROAD TO USDescended from the apes! My dear,let us hope that it is not true, but if it is,let us pray that it will not becomegenerally known. -Remark attributed to the wife ofthe Bishop of Worcester afterDarwin's theory of evolution was Explained to her