CHAPTER 26: THE STUFF OF LIFE
IF YOUR TWO parents hadnt bonded just when they didpossibly to the second, possibly to the nanosecondyou wouldnt be here. And if their parents hadnt bonded in a precisely timely manner, you wouldnt be here either. And if their parents hadnt done likewise, and their parents before them, and so on, obviously and indefinitely, you wouldnt 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 forebearsremember, these arent cousins and aunts and other incidental relatives, but only parents and parents of parents in a line leading ineluctably to youis 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 couldnt be here without a little incestactually quite a lot of incestalbeit 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 mothers side of the family procreated with some distant cousin from your fathers 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 beings 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 percentroughly one nucleotide base in every thousand, to quote the British geneticist and recent Nobel laureate John Sulstonare 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 genomeseach nearly identical, but not quitethat 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 chromosomesforty-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 body99.999 percent of them, saycarries 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 dont 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 DNAthe most extraordinary molecule on Earth, as it has been called.
DNA exists for just one reasonto create more DNAand 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. Thats a lot of possibilitya 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 couldnt 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 keyso, in a word, lifelesscould 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 didnt 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 days scientific requirements that it attracted no attention at all.
For most of the next half century the common assumption was that the materialnow called deoxyribonucleic acid, or DNAhad 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 codeby combining them.) DNA didnt 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 dont speak the same language. For almost four billion years they have been the living worlds 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 cells 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 Mendels 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 jewelers glass for any tiny variations in inheritance. For six years they tried to produce mutations by any means they could think ofzapping the flies with radiation and X-rays, rearing them in bright light and darkness, baking them gently in ovens, spinning them crazily in centrifugesbut nothing worked. Morgan was on the brink of giving up when there occurred a sudden and repeatable mutationa 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 everyones 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 werent convinced that genes even existed. As Morgan noted at the time, there was no consensus as to what the genes arewhether 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 dont 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 Morgans 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 Averys discovery was worth 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 Averys workincluding, it has been said, lobbying the authorities at the Karolinska Institute in Stockholm not to give Avery a Nobel Prize. Avery by this time was sixty-six years old and tired. Unable to deal with the stress and controversy, he resigned his position 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, Americas 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 (for chemistry 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 didnt work as a team, often werent 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 British governmentCrick 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 calledThe Quiz Kids (and thus could claim to be at least part of the inspiration for some of the members of the Glass family inFranny and Zooey and other works by J. D. Salinger) and who had entered 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. In 1951, 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 Watsons account he is presented as blustery, nosy, cheerfully argumentative, impatient with anyone slow to share a notion, and constantly in danger of being asked to go elsewhere. 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 seecorrectly, as it turned outhow 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 bookThe Double Helix , It was my hope that the gene might be solved without my learning any chemistry. They werent actually assigned to work on DNA, and at one 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 historian Lisa Jardine. Far ahead of them, at least at the beginning, were two academics at Kings College in London, Wilkins and Franklin.
The New Zealandborn Wilkins was a retiring figure, almost to the point of invisibility. A 1998 PBS documentary on the discovery of the structure of DNAa feat for which he shared the 1962 Nobel Prize with Crick and Watsonmanaged to overlook him entirely.
The most enigmatic character of all was Franklin. In a severely unflattering portrait, Watson inThe Double Helix depicted Franklin as a woman who was unreasonable, secretive, chronically uncooperative, andthis seemed especially to irritate himalmost willfully unsexy. He allowed that she was not unattractive and might have been quite stunning had she taken even a mild interest in clothes, but in this she disappointed all expectations. She didnt even use lipstick, he noted in wonder, while her dress sense showed all the imagination of English blue-stocking adolescents.[44]
However, 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 Wilkinss perennial exasperation she refused to share her findings.
If Franklin was not warmly forthcoming with her findings, she cannot be altogether blamed. Female academics at Kings in the 1950s were treated with a formalized disdain that dazzles modern sensibilities (actually any sensibilities). However senior or accomplished, they were not allowed into the colleges 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 pressedat times actively harassedto 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. Im afraid we always used to adoptlets 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 she kept her results locked away.
That Wilkins and Franklin did not get along was a fact that Watson and Crick seem to have exploited to their benefit. Although Crick and Watson were trespassing rather unashamedly on Wilkinss territory, it was with them that he increasingly sidednot altogether surprisingly since Franklin herself was beginning to 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 Wilkinss presumed dismay and embarrassment, in the summer of 1952 she posted a mock notice around the Kings physics department that said: It is with great regret that we have to announce the death, on Friday 18th July 1952 of D.N.A. helix. . . . It is hoped that Dr. M.H.F. Wilkins will speak in memory of the late helix.
The outcome of all this was that in January 1953, Wilkins showed Watson Franklins images, apparently without her knowledge or consent. It would be an understatement to call it a significant help. Years later Watson conceded that it was the key event . . . it mobilized us. Armed with the knowledge of the DNA molecules 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 temperament to be allowed to travel abroad. Crick and Watson also had the no less convenient good fortune that Paulings son was working at the Cavendish and innocently kept them abreast of any news of developments and setbacks at home.
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 chemical componentscalled adenine, guanine, cytosine, and thiamineand that these paired up in particular 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 modelperhaps the most famous in modern scienceconsisting 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 Franklins picture.
The April 25, 1953, edition ofNature 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 worldEdmund Hillary was just about to clamber to the top of Everest while Elizabeth II was imminently to be crowned queen of Englandso the discovery of the secret of life was mostly overlooked. It received a small mention in theNews 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 not awarded posthumously. The cancer almost certainly arose as a result of chronic overexposure to X-rays through her work and neednt 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 Cricks discovery wasnt actually confirmed until the 1980s. As Crick said in one 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 journalScience could run an article titled That Was the Molecular Biology That Was, suggestingit hardly seems possible, but it is sothat 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 doesnt actually seem todo anything. Ninety-seven percent of your DNA consists of nothing but long stretches of meaningless garblejunk, 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 a single 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 books chapters 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 basesthe letters of the genetic alphabetconsist 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 or twisted 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 acidhence 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 a jacket, and each half goes off to form a new partnership. Because each nucleotide along a strand 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 quicklyin only a matter of seconds, which is quite a feat.
Most of the time our DNA replicates with dutiful accuracy, but just occasionallyabout one time in a milliona 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 advantagemore protective pigmentation, for instance, or increased production of red blood cells for someone living at altitude. Over time, these slight modifications 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 cant function, but too few and it sacrifices adaptability. A similar balance must exist between stability in an organism and innovation. An increase in red blood cells can help a 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 its like pumping oil, in the words of Temple University anthropologist Charles Weitz. Thats 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 wont let you become too differentnot 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 persons, 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 dont even have a human genome. We have six billion of them. We are all 99.9 percent the same, but equally, in the words of the biochemist David Cox, you could say all 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 Ridleys words, exist for the pure and simple reason that they are good at getting themselves duplicated.[45]Most 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 geneswhen it codes for them, as scientists put itit 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 has no known beneficial function in human beings at all. The one thing itdoesdo is make it possible 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 does nothing that is beneficial and sometimes clobbers us. Our bodies have no choice but to do so because the genes order it. We are vessels for their whims. Altogether, almost half of human genesthe largest proportion yet found in any organismdont do anything at all, as far as we can tell, except reproduce themselves.
All organisms are in some sense slaves to their genes. Thats why salmon and spiders and other types of creatures more or less beyond counting are prepared to die in the process of mating. The desire to breed, to disperse ones 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 point of 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 doesnt do anything when even more unexpected findings began to turn up. First in Germany and then in Switzerland researchers performed some rather bizarre experiments that produced curiously unbizarre outcomes. In one they took the gene that controlled the development of a mouses eye and inserted it into the larva of a fruit fly. The thought was that it might produce something interestingly grotesque. In fact, the mouse-eye gene not only made a viable eye in the fruit fly, it made aflys eye. Here were two creatures that hadnt shared a common ancestor 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 insert human DNA into certain cells of flies, and the flies would accept it as if it were their own. Over 60 percent of human genes, it turns out, are fundamentally the same as those found in fruit flies. At least 90 percent correlate at some level to those found in mice. (We even have the same genes for making a tail, if only they would switch on.) In field after field, researchers found that whatever organism they were working onwhether nematode worms or human beingsthey were often studying essentially the same genes. Life, it appeared, was drawn up from a single set of blueprints.
Further probings revealed the existence of a clutch of master control genes, each directing the development of a section of the body, which were dubbed homeotic (from a Greek word meaning similar) or hox genes. Hox genes answered the long-bewildering question of how billions of embryonic cells, all arising from a single fertilized egg and carrying identical DNA, know where to go and what to dothat this one should become a liver cell, this one a stretchy neuron, this one a bubble of blood, this one part of the shimmer on a beating wing. It is 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 doesnt necessarily, or even generally, reflect the level of sophistication of the creature that contains it. We have forty-six chromosomes, but some ferns have more than six hundred. The lungfish, one of the least evolved of all complex animals, has forty times as much DNA as we have. Even the common 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 very good thing because the number of genes in humans has taken a big hit lately. Until recently it was thought that humans had at least 100,000 genes, possibly a good many more, but that number was drastically reduced by the first results of the Human Genome Project, which suggested a figure more like 35,000 or 40,000 genesabout the same number as are found in grass. That came as both a surprise and a disappointment.
It wont have escaped your attention that genes have been commonly implicated in any number of human frailties. Exultant scientists have at various times declared themselves to have found the genes responsible for obesity, schizophrenia, homosexuality, criminality, violence, alcoholism, even shoplifting and homelessness. Perhaps the apogee (or nadir) of this faith in biodeterminism was a study published in the journalScience in 1980 contending that women are genetically inferior at mathematics. In fact, we now know, almost nothing about you is so accommodatingly simple.
This is clearly a pity in one important sense, for if you had individual genes that determined height or propensity to diabetes or to baldness or any other distinguishing trait, then it would be easycomparatively easy anywayto isolate and tinker with them. Unfortunately, thirty-five thousand genes functioning independently is not nearly enough to produce the kind of physical complexity that makes a satisfactory human being. Genes clearly therefore must cooperate. A few disordershemophilia, Parkinsons disease, Huntingtons disease, and cystic fibrosis, for exampleare caused by lone dysfunctional genes, but as a rule disruptive genes are weeded out by natural selection long before they can become permanently troublesome to a species or population. For the most part our fate and comfortand even our eye colorare determined not by individual genes but by complexes of genes working in alliance. Thats why it is so hard to work out how it all fits together and why we wont be producing designer babies anytime soon.
In fact, the more we have learned in recent years the more complicated matters have tended to become. Even thinking, it turns out, affects the ways genes work. How fast a mans beard grows, for instance, is partly a function of how much he thinks about sex (because thinking about sex produces a testosterone surge). In the early 1990s, scientists made an even more profound discovery when they found they could knock out supposedly vital genes from embryonic mice, and the mice were not only often born healthy, but sometimes were actually fitter than their brothers and sisters who had not been tampered with. When certain important genes were destroyed, it turned out, others were stepping in to fill the breach. This was excellent news for us as organisms, but not so good for our understanding of how cells work since it introduced an extra layer of complexity to something that we had barely begun to understand anyway.
It is largely because of these complicating factors that cracking the human genome became seen almost at once as only a beginning. The genome, as Eric Lander of MIT has put it, is like a parts list for the human body: it tells us what we are made of, but says nothing about how we work. Whats needed now is the operating manualinstructions for how to make it go.We are not close to that point yet.
So now the quest is to crack the human proteomea concept so novel that the termproteome didnt even exist a decade ago. The proteome is the library of information that creates proteins. Unfortunately, observedScientific American in the spring of 2002, the proteome is much more complicated than the genome.
Thats putting it mildly. Proteins, you will remember, are the workhorses of all living systems; as many as a hundred million of them may be busy in any cell at any moment. Thats a lot of activity to try to figure out. Worse, proteins behavior and functions are based not simply on their chemistry, as with genes, but also on their shapes. To function, a protein must not only have the necessary chemical components, properly assembled, but then must also be folded into an extremely specific shape. Folding is the term thats used, but its a misleading one as it suggests a geometrical tidiness that doesnt in fact apply. Proteins loop and coil and crinkle into shapes that are at once extravagant and complex. They are more like furiously mangled coat hangers than folded towels.
Moreover, proteins are (if I may be permitted to use a handy archaism) the swingers of the biological world. Depending on mood and metabolic circumstance, they will allow themselves to be phosphorylated, glycosylated, acetylated, ubiquitinated, farneysylated, sulfated, and linked to glycophosphatidylinositol anchors, among rather a lot else. Often it takes relatively little to get them going, it appears. Drink a glass of wine, asScientific American notes, and you materially alter the number and types of proteins at large in your system. This is a pleasant feature for drinkers, but not nearly so helpful for geneticists who are trying to understand what is going on.
It can all begin to seem impossibly complicated, and in some ways itisimpossibly complicated. But there is an underlying simplicity in all this, too, owing to an equally elemental underlying unity in the way life works. All the tiny, deft chemical processes that animate cellsthe cooperative efforts of nucleotides, the transcription of DNA into RNAevolved just once and have stayed pretty well fixed ever since across the whole of nature. As the 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 mere incrementseach of us a musty archive of adjustments, adaptations, modifications, and providential tinkerings stretching back 3.8 billion years. Remarkably, we are even quite closely related to fruit and vegetables. About half the chemical functions that take place in a banana 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, the most profound true statement there is.