The Great Chains of Being


The stock prices for Celera, Incyte and Human Genome Sciences soared in 1999, even beyond the market's soaring average—and little wonder. Investors are excited because these companies, at the cutting edge of biotech research, are well on their way to reading the complete digital recipe for making human beings.

This may sound ominous, but it's not. The recipe amounts to a map of our chromosomes, from which (investors hope) biotech miracles will emerge. And indeed, genomics, as the field is called, does promise amazing new drugs and new treatments to fight disease, including cancer. A first "map" may be available sometime later this year.

Now Matt Ridley, a British zoologist and a former American editor for the Economist magazine, brings this research alive for the general reader. "Genome" (HarperCollins, 344 pages, $26) is not a book about the much-ballyhooed Human Genome Project—the massive scientific undertaking itself. Instead, Mr. Ridley looks at what the scientists are finding as they read the text of the book of life.

The human genome is all the genes found on the 23 pairs of chromosomes in most human cells. Biologists estimate that it consists of 70,000 to 120,000 genes (we'll know soon just how many). Genes themselves are spelled out in DNA sequences that consist of a four-letter alphabet of chemical bases: adenine, cytosine, guanine and thymine (ACGT). In turn, any three DNA letters specify one of 20 amino acids that, when strung together, form the proteins that make up our bodies.

Mr. Ridley adopts a structure of 23 chapters—one for each of the 23 chromosome pairs. He then selects one or two genes that researchers have found on each chromosome and discusses how they affect the body and mind.

For example, Mr. Ridley takes a close look at the TP53 gene on Chromosome 17—the so-called Guardian of the Genome. This gene makes a protein called p53, whose job it is to tell a diseased cell to stop dividing until its damaged DNA is repaired. If the DNA can't be repaired, p53 tells the cell to commit suicide. Such a command prevents the cell from becoming cancerous—that is, from dividing rapidly and morbidly.

The discovery of TP53, as one can imagine, is auspicious. Until recently, doctors thought that chemotherapy and radiation therapy were effective largely because they destroyed rapidly dividing cells. Instead these therapies are effective because they damage DNA a little, which alerts p53 to order the cells to commit suicide. If the TP53 gene isn't working properly, then chemo and radiation therapies are much less effective. Finding ways to repair and turn on TP53 genes could be a huge breakthrough in the war on cancer.

Of course, cancer isn't the only enemy that a genome map will help us fight. Mr. Ridley cites one expert who estimates that "age-influencing genes" constitute about "ten percent of the total." In brief, the cell-code puts a limit on the number of times human cells can divide, and once they reach that limit they stop and die. Central to this process are telomeres, which consist of the DNA "word" TTAGGG repeated about 2,000 times at the ends of chromosomes. Telomeres are like aglets, the plastic bits on the ends of shoelaces that keep them from fraying. Each time a chromosome divides and is copied, the teleomeres get shorter. As Mr. Ridley writes: "That is why cells grow old and cease to thrive beyond a certain age."

There are, however, cells that don't age—cancer cells. They reactivate a gene on Chromosome 14 that restores, by means of an enzyme, the fraying telomeres to their youthful lengths. The biotech company Geron is using this fact to develop cancer therapies and eventually—it believes–immortal tissues for transplant.

The genome can tell us about disease probabilities, too. On chromosome 19, for instance, lies the APOE gene. There are three versions of this gene, and people who carry copies of APOE4 are particularly susceptible to Alzheimer's. The risk that a person with two copies of APOE4 will get Alzheimer's is 91%, and the mean age of onset is 68. In those with one copy, the risk drops to 47%, the age of onset to 75. Those without APOE4 genes have only a 20% chance of getting Alzheimer's, and the age of onset rises to 84. Researchers can now offer a genetic test to determine these probabilities, for anyone who is interested. But should they? Yes, Mr. Ridley concludes, and quite rightly.

Nowadays it is common to hear that biotech research is fraught with moral peril. In this context, Mr. Ridley examines the sorry history of the eugenics movement, which sought to "improve" the human genetic stock by sterilizing people who were deemed "inferior." But "there is a world of difference," he states, "between genetic screening [like that for APOE4] and what the eugenists wanted in their heyday—and it lies in this: genetic screening is about giving private individuals private choices on private criteria. Eugenics was about nationalising that decision to make people breed not for themselves but for the state."

Far from showing science to be "out of control," eugenics (Mr. Ridley reminds us) is "an example of the danger of letting government out of control." The moral of the story? We should constantly be on guard against government attempts to limit genetic research—and, no less, against efforts to impose interventions based on genetic discoveries.

In the end, then, Mr. Ridley provides not only a fascinating tour of the human genome but a persuasive argument against the skeptics of biotech research. If you want to catch a glimpse of the biotech century that is now dawning, and how it will make life better for us all, "Genome" is an excellent place to start.