A short history of nearly everything

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 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 genes-the largest proportion yet found 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 creatures 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.

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 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 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 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 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, 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 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. 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 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 cooperate. A few disorders-hemophilia, 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 color-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 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 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 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. 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 term proteome didn’t even exist a decade ago. The proteome is the library of information that creates proteins. “Unfortunately,” observed Scientific American in the spring of 2002, “the proteome is much more complicated than the genome.”

That’s 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. That’s 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 that’s used, but it’s a misleading one as it suggests a geometrical tidiness that doesn’t 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, as Scientific 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 it is impossibly 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 cells-the cooperative efforts of nucleotides, the transcription of DNA into RNA-evolved just once and have stayed pretty well fixed ever