The lords of the flies

June 4, 1999

Flies, like us, have genes for time, love and memory. Scientists are already manipulating them. And it won't be long before they are able to do this for people too, says Jonathan Weiner

My father is a physicist who doodles atoms and formulas on his dinner napkins and once appalled me by saying coolly, looking at our cat Bobo: "What a remarkable machine." I spent the first years of my adult life trying to be as different from him as I could, starting in college, when I made a U-turn away from science, read John Keats, and wrote - or tried to write - lyric poetry. And now here I am, in spite of everything, thinking constantly about atoms, molecules and behaviour. I am fascinated by a field that Keats might have hated more than any other, a field that often feels, to the romantic in me, like a threat to reduce us all to the status of remarkable machines.

The scientists I follow are exploring the first links between genes and behaviour, between what is often referred to in the headlines as DNA and destiny. They are not psychologists. They do not administer personality tests, they do not interview identical twins. They are laboratory biologists who look at life from the genes up, from the molecules up. Until recently, their work stayed out of the headlines, because they do their experiments with flies, worms and mice, not with people. But lately, their experiments are coming closer to home. The time I've spent hanging around in fly rooms has given me a preview of the sort of difficult truths that this science may soon be telling us about ourselves.

If we pinpoint genes linked to schizophrenia, or aggression, or the pursuit of happiness - and there are, of course, biologists who doubt such genes exist - are we allowing science to paint us into a corner? What might it mean if one group of people on this planet tends to carry the most aggressive versions of that aggression gene, and another group tends to carry the mildest versions? Finding a genetic basis for schizophrenia may lead to better treatments but if you are not planning to take a mood pill, what advantage would there be to knowing that you are programmed to be just plain happy or miserable?

These problems are in many ways the logical and inevitable conclusion of twentieth century biology. The modern theory of the gene was born in a fly bottle in 1910, when the biologist Thomas Hunt Morgan noticed a single mutant male fly with white eyes. Morgan and his students allowed that fly to mate with female flies that had normal, bright red eyes. Then Morgan traced the patterns of white eyes in the mutant's family tree as the gene travelled down the generations. Soon he and his students were tracing the inheritance of all kinds of variant genes: genes that gave the flies pale yellow bodies instead of brown, or wrinkled hairs instead of straight, or short wings instead of long. In Morgan's fly room, biology began to travel out of the realm of the 19th-century naturalists and into the realm of the chemists and the physicists.

In the early 1960s, a physicist-turned-biologist named Seymour Benzer used flies to take what seemed to him the next inevitable step. Benzer had been watching his two young daughters play at the beach and wondering how much of their behaviour was inherited. He hit on a novel and simple approach to this oldest of questions: he would go back to the point of origin of modern genetics, the fly bottle. And he would do just what Morgan had done; but rather than tracing the inheritance of mutant eyes, wings and hairs, he would trace mutant behaviour.

The first big breakthrough came in 1971 when Benzer and one of his first students in the fly room announced their discovery of a fly with a warped sense of time. Most flies live according to circadian rhythms: even when taken out of sight of the sun and placed in a pitch-dark room they will still wake and sleep with a roughly regular rhythm, just as most humans do. But Benzer's crew found flies with fast clocks, slow clocks, broken clocks, and they traced the problem to specific mutations in a fly gene they called period. Since then clock genes have become a cottage industry. Half a dozen more clock genes have been discovered. These are genes that evolved many hundreds of millions of years ago, but they are still ticking virtually everywhere in the living world. Flies, worms, mice, butterflies and mustard weeds have these genes, and so do we.

Benzer and his students also explored the genes that shape flies' sexual instincts, and their memories - because, as Benzer's fly room was the first to demonstrate, even tiny fruit flies can remember and forget. Some of those genes have since turned up in human beings too. In fact, an amazing number of the genes they found in the fly rooms are closely related to genes that we watch in action in our living rooms and bedrooms. In the mid-1990s, one of Benzer's student's students found a particularly interesting memory gene called creb. Ordinary flies need ten lessons to learn to avoid a shock. The creb mutant needs just one lesson. The fly has the fly equivalent of a photographic memory.

I visited Tim Tully at Cold Spring Harbor Laboratories, on Long Island, just after he made his key discoveries with creb. While I was there, a few fly people (as they call themselves) showed me how to inject a piece of DNA into a fly embryo. It is like playing a video game. You watch the embryo on a big TV monitor. With a joystick, you micro-manipulate the tip of a needle toward the embryo's rear end. Step on a foot pedal, there is a tiny burst of turbulence at the tip of the needle, and the deed is done. If that ribbon of DNA takes - and if it takes in just the right place - then a new gene will run in that fly's family, generation after generation, and give thousands of the fly's children and grandchildren a photographic memory. Yes, the creb gene shapes human memory too. With the same foot-pedal, joy-stick and needle, it could be injected into a human embryo.

Studies of twins, and our most everyday observations around the dinner table, argue that we do inherit a significant fraction of our behaviour. I know I sound more like my father every day. Lately I have reached the point of no return, the point at which our growing resemblance does not even bother me. How much of this is nurture, and how much is in the genes?

So far, most studies of human genes and behaviour are nowhere near as solid as Benzer's studies of flies, although you wouldn't know that from the stories in the newspapers, which tend to wear a sort of cocky know-it-all half-smirk. Front-page headlines about the discovery of "The happiness gene," "The gay gene," or "The novelty-seeking gene" make it sound as if all this human behaviour is now understood and nailed down. Actually, these studies are extremely difficult, the papers are quite tentative, and they are often retracted.

But within a year or two, every letter in the human genome will have been transcribed. Soon biologists will explore the links between DNA and human behaviour more easily than Benzer explored those links in fruit flies.

This is the kind of research in which knowledge leads to power, sometimes terribly fast. The same tools I played with at Cold Spring Harbor can inject a human gene into a fly or a mouse, and create what ancient Greeks and young molecular biologists call a chimera, like the lion-goat-and-serpent hybrids of legend. And some day sooner than we think, these same tools may allow biologists to inject genes that shape memory, or musical ability, or even (who knows?) a poetic or a mathematical temperament into the early embryo of a human being in a laboratory dish.

Last week I had lunch with Benzer in Pasadena. I asked him if he ever feels queasy for helping start the human species on this adventure. Lunch with Benzer is a queasy proposition in itself, because he eats crocodile tail, fillet of snake and live shrimp, anything strange, squirming and exotic, and he encourages his dining partners to enjoy every bite with him: "You didn't eat the eyeballs!" Benzer brushed my question aside. He belongs to the old school of investigators who believe it is their job to explore, and it is society's job to decide what to do with the territory they open. He has always done his best work at the very start of scientific revolutions, and he pointed out that he could not have predicted at the outset where any of them would go. His tinkering with geranium alloys in 1943 helped lead to the invention of the transistor and the electronics revolution, which is now exploding in directions that no one could then foresee. On the one hand, he said to me, electronics have given us guided missiles that can kill millions in minutes. On the other hand they have also given us the world wide web, in which Benzer delights. So he refuses to join in the general agitation over the directions genetics are leading us.

Benzer's studies of genes and behaviour are now helping to unravel the genetic causes of neurodegenerative disasters such as Lou Gehrig's disease and Alzheimer's (a disease that Benzer's own wife, Carol Miller, a neuropathologist, is studying today, with the help of discoveries her husband made in his fly room). Benzer himself, at 77, has become interested in the problems of ageing. One of his latest discoveries is a mutant fly that lives more than 100 days; he calls it methuselah. Now he is searching for the human equivalent of methuselah genes.

I would not want Benzer and his school to stop working on methuselah or on any of the other genes he studies, and I think Keats would approve. This is the point at which we connect, for the first time, the outer, objective world of the physicist with the inner, subjective world of the poet. This is where we take what we have learned about stones, and rocks, and trees, the universe of matter, and connect it with everything inside us and everything we do, which is, for the poet in us, the universe that really matters. But I do still feel queasy. Science in the 20th century has put us all into the fly bottle and we may spend the 21st century trying to get out. We all want to feel that we are free agents - not only chips off the old block but sculptors of our particular chip. Will we lose that possibility - which is the possibility of possibilities? Is science painting us into a corner? Or, as my father put it when I started hanging around with fly people and mutant flies, "Have they found the free-will gene yet?" Jonathan Weiner is the author of Time, Love, Memory: A Great Biologist and his Quest for the Origins of Behaviour, Faber, Pounds 18.99. His previous book, The Book of the Finch, won the Pulitzer prize in 1995.

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