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Thursday, Oct. 4, 2001
Putting fear and hope on the genome map
By ROWAN HOOPER
Future historians might well classify this week as typical of the early 21st century, in that there is a flurry of reports linking specific genes to human diseases, and at the same time there is a voice warning against seeing genetics as a "magic bullet," the solution to all our problems.
October's issue of Nature Genetics outlines the next stage in the Human Genome Project -- mapping all the genes predisposing us to common diseases -- and describes candidate genes for Crohn's disease (an inflammatory bowel disease affecting more than a million Americans). Another study in the same journal identifies the genetic causes for some forms of cleft lip and cleft palate. But it is a paper published in Nature today that will stimulate the most talk.
With the publication of "The Descent of Man" in 1871, Darwin really upset the Victorian apple cart. "Man," he said, "has an instinctive tendency to speak, as we see in the babble of our young children, while no child has an instinctive tendency to bake, brew or write."
Nearly 100 years later, the linguist Noam Chomsky took Darwin's ideas further, developing his theory on what he called "universal grammar" -- the idea that humans have built-in, genetic rules of language. There is, Chomsky asserted, a "system of principles, conditions and rules that are elements or properties of all human languages."
Today, Darwin's and Chomsky's ideas on language are supported by the publication of a paper that, for the first time, definitively links a specific gene to language. The discovery will boost the growing feeling among scientists that there is a genetic basis to our ability to talk.
Led by Anthony Monaco at Oxford University's Wellcome Trust Centre for Human Genetics, the researchers focused their studies on the "KE" family, in which speech and language disorders had been seen in several generations. Some family members had problems not only forming words, but also in using and understanding grammar. Researchers traced the disorder to a small segment of chromosome 7. Then, the discovery of an unrelated person called "CS" with a similar speech defect, allowed them to narrow the search down to a specific gene.
The researchers found that the gene makes a special protein called a "transcription factor," which has a managerial role in switching other genes on and off. Affected members of the KE family and CS have a slightly different form of the gene than people without speech difficulties. This means the gene makes a slightly differently shaped protein, which then has a slightly different "style of management." Though the initial difference is small, because the gene's effects trickle down through the brain during development, the results are debilitating.
Steven Pinker, at the Massachusetts Institute of Technology (where Chomsky is, too), said in a commentary article in Nature, "The discovery motivates the search for genetic causes of cognitive and learning disorders more generally, relieving the presumption of guilt from mothers (who are often still blamed for everything that goes wrong with their children)."
Over in Nature Genetics, researchers from the Whitehead Institute Center for Genome Research in Cambridge, Mass., build the case for making a "haplotype" map of the human genome, making it faster, easier and probably cheaper to find disease-causing genes. Haplotypes are segments of chromosomes that are inherited in blocks. Scientists use them to decipher the genetic differences that make some people more susceptible to disease than others.
"Understanding human variation at this level will have a big impact on medical genetics in the future," said Whitehead researcher Mark Daly, first author on the haplotype paper. "We now need to characterize the whole genome and create haplotype maps so this type of work can be done easily for any disease, anywhere in the genome."
With an ever-increasing knowledge of the genetics of human disease, it's all too easy to see gene therapy as a technological fix for the problems that really lie in the structure of our society, says Garland Allen of Washington University in St. Louis. Writing in this week's issue of Science, Allen warns that there are dangerous parallels between today's society and that of the early 20th century, when eugenics took hold in the United States and in Nazi Germany. Back then, he writes, urbanization, industrialization and economic depression gave eugenics its popular appeal.
"I would argue that we are poised at the threshold of a similar period in our own history and are in the process of adopting the same sort of mind frame as our predecessors," he writes. Today's equivalent? "Globalization, shrinking real income and loss of jobs, and decrease in availability of health care to many segments of society."
Allen concedes that today we are unlikely to see blatant calls for sterilization, or claims of ethnic or racial superiority, as were seen in the last century. "The discourse," he says, "has shifted to individuals, with real or imagined genetic defects, who are regarded as below par." Since the health-care system in the U.S. is based on insurance, it is quite probable that health insurance companies will refuse to pay out for birth fees and child care if in utero screening reveals that a baby has a condition deemed as "defective."
The reluctance of insurance companies comes despite the fact that it is difficult to predict the outcome of many genetic conditions. There is a wide possible variety of outcomes, for example, for fetuses diagnosed with Down syndrome and cystic fibrosis. "Do we really want our decisions, such as those about bringing a child into the world," concludes Allen, "to be guided by how much it will cost? If eugenics means making reproductive decisions primarily on the basis of social cost, then we are well on that road."
E-mail Rowan Hooper at email@example.com