by Bill Bryson
If Franklin was not warmly forthcoming with her findings, she cannot be altogether blamed. Female academics at King’s 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 college’s senior common room but instead had to take their meals in a more utilitarian chamber that even Watson conceded was “dingily poky.” 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 towards 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 the two of them were trespassing rather unashamedly on Wilkins’s territory, it was with them that he increasingly sided—not 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 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 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 Franklin’s images, “apparently without her knowledge or consent.” It would be an understatement to call it a significant help to him. Years later, Watson conceded that it “was the key event…it mobilized us.” 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 Wilkins and learned enough to correct the misconceptions that had put him on the wrong line of enquiry; 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 Pauling’s son was working at the Cavendish and innocently kept them abreast of any news of developments and setbacks at home.
James Watson (left) and Francis Crick with their famous model of a molecule of DNA at the Cavendish Laboratory in Cambridge. (Credit 26.10)
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 components—called adenine, guanine, cytosine and thiamine—and 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 Meccanolike 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 25 April 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 to clamber to the top of Everest, while Elizabeth II was shortly to be crowned Queen—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 not awarded posthumously. The cancer almost certainly arose as a result of chronic over-exposure to X-rays through her work and could have been avoided. In her much praised recent biography, 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.
Nobel Prize winners for science and literature in 1962 (from left): Maurice Wilkins, Max Perutz, Francis Crick, John Steinbeck, James Watson and John Kendrew. Rosalind Franklin did not share the prize; she had died four years earlier. (Credit 26.11)
Watson and Crick’s discovery wasn’t 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 journal Science could run an article entitled “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 per cent of your DNA consists of nothing but long stretches of meaningless garble—“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 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 book’s 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 bases—the letters of the genetic alphabet—consist of the four nucleotides mentioned a page or two back: adenine, thymine, 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 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 thymine 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 zip 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 g
uanine, 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—in only 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 non-coding 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 slight modifications accumulate both in 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 must exist between stability and innovation in an organism. 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 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.
This cartoon imagines Uncle Sam and John Bull companionably knitting DNA to create the human genome. (Credit 26.12)
The 0.1 per cent 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 per cent 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 6 billion of them. We are all 99.9 per cent 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 per cent of our DNA commonly called junk is largely made up of clumps of letters that, in Matt Ridley’s words, “exist for the pure and simple reason that they are good at getting themselves duplicated.”2 Most of your DNA, in other words, is devoted not to you but to itself: you are a machine for the benefit of 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, as scientists 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 has no known beneficial function in human beings at all. The one thing it does do is make it possible for retroviruses, such as HIV, 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 make it because the genes order it. We are vessels for their whims. Altogether, almost half of human genes—the largest proportion known in any organism—don’t do anything at all, as far as we can tell, except reproduce themselves.
All organisms are in some sense slaves to their genes. That’s why salmon and spiders and other types of creature more or less beyond counting are prepared to die in the process of mating. 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 point of view, sex is really just a reward mechanism to encourage us to pass on our genetic material.
A female black widow spider prepares to devour her much smaller male partner after mating—a striking demonstration of genetic enslavement. (Credit 26.13)
Scientists had only barely absorbed the surprising news that most of our DNA doesn’t 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 mouse’s 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 a fly’s eye. Here were two creatures that hadn’t 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 per cent of human genes, it turns out, are fundamentally the same as those found in fruit flies. At least 90 per cent correlate at some level with 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 on—whether nematode worms or human beings—they 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 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 do—that 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 doesn’t 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 that matters, so much as 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 one hundred thousand 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 thirty-five thousand or forty thousand genes—about the same number as are found in grass. That came as both a surprise and a disappointment.
It won’t 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 journal Science in 1980 contending that women are genetically inferior at mathematics. I
n 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 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 of physical complexity that makes a satisfactory human being. Genes clearly, therefore, must co-operate. A few disorders—haemophilia, Parkinson’s disease, Huntington’s disease and cystic fibrosis, for example—are 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 comfort—and even our eye colour—are determined not by individual genes but by complexes of genes working in alliance. That’s why it is so hard to work out how it all fits together and why we won’t be producing designer babies any time 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 man’s 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 still see the mice often not only born healthy, but sometimes 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.
