Metaphors and Dreams

The DNA revolution may be just too big to take in: beyond words, even 50 years on. Think of four chemical bases coupled exclusively to each other, adenine with thymine, guanine with cytosine, in a double helix. Then think of this double helix having the power to unwind and duplicate, to make new helixes. So far, so simple. The structure spells out a gene that makes a protein, and makes more DNA. But like the double helix itself, the challenges divide into questions of scale and complexity. In

By | January 13, 2003

The DNA revolution may be just too big to take in: beyond words, even 50 years on. Think of four chemical bases coupled exclusively to each other, adenine with thymine, guanine with cytosine, in a double helix. Then think of this double helix having the power to unwind and duplicate, to make new helixes. So far, so simple. The structure spells out a gene that makes a protein, and makes more DNA.

But like the double helix itself, the challenges divide into questions of scale and complexity. In the nucleus of one cell of one human, tiny braids of DNA twist into two sets of 23 chromosomes. These add up to 3 billion bases, or 200 telephone books of information, or 750,000 pages of typescript, or a procession of nucleotides, which, if read aloud at the rate of one a second, would take almost 100 years to recite. The human body hosts 100 million million cells, and carries the same DNA in almost all of them. Every fragment of this skein of identity was begat by another helix, and every set of chromosomes is descended from two pairs of chromosomes in one single inherited cell.

DNA is not a stable thing. In every cell, the skein is broken and mended, not always correctly, 20,000 times an hour: The joint is jumping, and so is the ligament, and the blood vessel. Much of this DNA is meaningless--human genes are a tiny proportion of the whole--but also unique. Each of the six billion people on the planet carries variants in the genes that make that person different, and lengths of DNA that serve as an identity badge, not just for that person, but also for membership of a family, a clan, a people. So the thread of life links one human to all other people. Forensic scientists use DNA to make family connections: to the bodies of the Romanovs at Ekaterinaburg, to the black slave who bore Thomas Jefferson's children, to the disappeared citizens of Chile and Argentina.

Anthropologists use DNA to trace human lineages: The deeper but still intimate ties between Europeans, Asians, the peoples of the New World and Oceania, all now seem to lead back 100,000 or 200,000 years to a woman in Africa. So DNA makes nonsense of the old idea of race--those notions of purity and separateness so dear to racists--while bewilderingly endorsing the argument that because people inherit propensities to this or that condition, people of different ethnic origins benefit from different medical approaches.

But the thread extends beyond humanity. It ties us to all the other hominids that ever chipped a hand axe, and to all the primates and far beyond, back across hundreds of millions of years to the first creature that crawled gasping from the ancient seas, and far, far beyond that, too, to some last common ancestor in Darwin's warm little pond 3.8 billion years ago. Genes at work in the Cambrian 550 million years ago are still at work in lawyers, lynxes, and lilacs today.

MEMORY AND FEAR So DNA is all our yesterdays. In the unreadable string of four banal letters is the story of who we are and where we come from. This implies a trajectory, which in turn implies that the journey goes on. Dizzyingly, therefore, our DNA may tell us where we might be going. How much rides on that "may"? What ominous signals lurk in that "might"?

One reaction to these unanswered queries has been an increase in a condition termed biophobia. If DNA is universal, then so is the tissue that it makes. Tinker with the pig insulin gene, and it makes human insulin. Adjust another pig gene, and its heart and lungs and liver start to become compatible with human hearts, lungs, and liver. In the double-helix world, life becomes not some unique, precious property, but a toolkit, a child's Lego set of building blocks, with which to make so many things that nature overlooked: a goat with spider's silk in its milk, a banana that grows vaccines, a mouse with a human ear on its back.

But few embrace the unknown; most of us shrink from it. At its mildest, biophobia is a retreat from laboratory-based science towards the "natural" and the so-called organic: A whole generation clutches the ginkgo biloba bottle instead of the dry martini. At its most dramatic, biophobia has become a batty rejection of science in favor of witchcraft, or the healing power of crystals, or comfrey, or faith itself.

Why be surprised? The biology revolution--Darwin plus DNA--implies that creatures are the sum of their genes plus the selective action of the environment, and that human actions and appetites are rooted in genetics and evolutionary history, just like those of budgerigars, bison, or Mexican jumping beans. Such an empirical history troubles those who think of humankind as separately created by God, as well as those who believe some unique evolutionary advance distinguishes people from their mammalian relatives, so they can confront a higher destiny.

DNA IDENTITY But how much can our own DNA distinguish us? The code is just that: data, a message. The mysteries deepen within the cell, in which the 30,000 or so genes strung along the DNA switch on and off, in response to some unimaginable cascade of signals, and set up a shuttling of molecules, and a trafficking of energy--an import and export business of nutrients and wastes, to launch a process that ends in a discrete life. The DNA directs a single cell towards a blastocyst, and then an embryo, and then a fetus, and then a baby, and then directs that dainty, moist little being into a sentient, self-aware identity of 100 trillion cells of perhaps 300 specialized kinds.

How does this happen? The DNA doesn't do it; the cell does it. We think of DNA as the software for the cell's computer. That is another analogy we seize upon gratefully, but unhelpfully. The cell itself looks like the leading player in the great game of life. To make sense of the software, we must make sense of the hardware. To reread James Watson's The Double Helix is to see once again the power of the scientific method: Reduce the problem to little solvable bits and attack them serially. The book shares the exhilaration of the discovery of why DNA must be the secret of life.

METAPHOR AND MYSTERY But "must be" is a prediction, not an explanation. The secrets are still there. How could DNA inside the cell make trillions of cells behave as one? What is it about DNA and the cell that makes a protein, that triggers a process, that ends in a firing of electrical signals and discharge of transmitters that assembles a thought, like this one, in these 40 words? What flickering community of a spin doctor's genes set in motion the thought expressed by President Clinton upon the completion of the first drafts of the human genome, on June 26, 2000? He said (and compared to some other things people said, it seemed quite modest), "This is the most important, the most wondrous map ever produced by mankind. It will revolutionize the diagnosis, prevention, and treatment of most, if not all, human diseases." And could there have been a genetic basis for the response of 100,000 clinicians, biomedical researchers, health managers, and patients: "Yes, but how? And when?"

Encouraging initiatives have emerged from the decade that ended in Clinton's hyperbole. A group of boys in the United Kingdom and France born with X-linked severe combined immune deficiency have begun to lead almost normal lives, although one has now developed leukemia. Gene-based medicine has yet to help a child with cystic fibrosis, or an adult with Huntington disease, or patients with more than a handful of the so-called single-gene disorders. Yet therapies for these conditions were supposed to be the foothills of gene-based medicine. The big challenges, everybody said, lay in the complexity of cardiovascular afflictions and cancers.

Right now, more than half of all gene-based therapy trials are aimed at cancer, and the juries could be out a long time. Treatment to extend life will, by definition, take at least a lifetime to validate. The paradox of the DNA revolution is that it shows us a shining future without telling us how to get there.

It will be a long time before gene-based medicine cures diabetes, stops migraine, or reverses neurodegeneration. It may never do these things. But if you have the complete maker's manual for the pathogen that gives you malaria, tuberculosis, or flu, and if you also have the complete instruction kit for the assembly not just of any human, but the one with the infection, then you ought to be able to think of a treatment.

In the 18th Century, doctors prescribed medicines--arsenic, sulfur, that sort of thing--with no idea of whether they would work. In the 20th century, doctors discovered medicines that would sometimes work, but the physicians didn't know why. Tomorrow's doctors will understand exactly why some infections kill, and how they can be circumvented. Once doctors were valued for their bedside manners. Some future generation of medics may cure illnesses even without seeing the patient.

TOMORROW'S SCIENCE But the great leap forward will not simply be in more--and more expensive--medicines. At some point in the future, people studying the genetic data and the survival of patients will also begin to understand how the immune system really works. If they can understand that, then perhaps they can help people not to fall ill in the first place.

There will be a much greater understanding of the link between diet and health. Akin to the ginkgo biloba approach, this time, the recipe for health will be based on true biochemistry. If antioxidants in red wine, rhubarb, or rice pudding really do protect the heart and demolish tumor cells, then they will be enthusiastically cultivated. The phrase, "a hearty meal," will take on new meaning. And then seamlessly from the chef's fork to the surgeon's knife, surgery will continue to become more precise and more effective, and recovery less painful.

But the same intricate knowledge of how cells act and interact is already pointing to other things: tissue engineering, for instance. Researchers now grow human skin. One day, someone could be injecting you with cultured versions of your own brain cells. Phrases like "fresh thinking" will also take on a new meaning.

We have embarked on the second information revolution; we are about to know ourselves in a way that was once unimaginable. Maybe we really are blinded by science. It could be that we have opened a door into a future so brilliant that all we can do is blink, until our eyes adjust. And maybe--with bioterrorism, ecodestruction, gross economic inequality, or just old-fashioned hubris--we will increase the scale of human suffering in the course of trying to alleviate it.

No ordinary, prescriptive language can encompass the DNA revolution; for the moment, it is beyond words. This is why scientists and fundraisers and journalists alike fall back upon metaphors. But metaphors can mislead. It might be fair, however, to compare the DNA revolution with the Promethean theft of fire from heaven. Fire is a source of light, and part of alchemy's tool-kit. It enables life and threatens it, too. Of course we will burn our fingers. But who now could imagine life without fire?

Tim Radford (Tim.Radford@Guardian.co.uk) is science editor of The Guardian.

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