Bill Bryson - A short history of nearly everything

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 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 increments-each 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.

I had a dream, which was not all a dream.

The bright sun was extinguish’d, and the stars

Did wander . . .

– Byron, “Darkness”

IN 1815 on the island of Sumbawa in Indonesia, a handsome and long-quiescent mountain named Tambora exploded spectacularly, killing a hundred thousand people with its blast and associated tsunamis. It was the biggest volcanic explosion in ten thousand years-150 times the size of Mount St. Helens, equivalent to sixty thousand Hiroshima-sized atom bombs.

News didn’t travel terribly fast in those days. In London, The Times ran a small story-actually a letter from a merchant-seven months after the event. But by this time Tambora’s effects were already being felt. Thirty-six cubic miles of smoky ash, dust, and grit had diffused through the atmosphere, obscuring the Sun’s rays and causing the Earth to cool. Sunsets were unusually but blearily colorful, an effect memorably captured by the artist J. M. W. Turner, who could not have been happier, but mostly the world existed under an oppressive, dusky pall. It was this deathly dimness that inspired the Byron lines above.