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Friday, July 25, 2008

Where Is Human Evolution Heading?

By Nancy Shute
If you judge the progress of humanity by Homer Simpson, Paris Hilton, and Girls Gone Wild videos, you might conclude that our evolution has stalled—or even shifted into reverse. Not so, scientists say. Humans are evolving faster than ever before, picking up new genetic traits and talents that may help us survive a turbulent future.

Much remodeling has gone on since the dawn of agriculture about 10 millenniums ago. "People who lived 10,000 years ago were much more like Neanderthals than we are like those people," says John Hawks, a professor of anthropology at the University of Wisconsin. "We've changed."

Hawks is among a growing number of scientists who are using whole-genome sequencing and other modern technologies to zero in on just how we've changed. Their research is helping illuminate not only how humans became what we are but also where we might be headed. For instance, some scientists speculate that changes in human mating patterns may be contributing to the increase in autism. Others track how humans have morphed in response to changing circumstances, including enhanced abilities to metabolize sugar and fight disease. Some people are genetically more resistant to the HIV virus, for instance, and that trait should become more common in the future, as those people are more likely to survive and have children who are resistant. Yet for some people, the makeover isn't big enough or fast enough. Some parents have started using DNA testing to choose the genetic makeup of their children, rejecting embryos with inherited flaws or embracing those with desired traits—such as being the right sex.

New mutations. Until recently, anthropologists thought that human evolution had slowed down. But last December, Hawks reported that it has actually accelerated 100-fold in the past 5,000 to 10,000 years. He figured that out by comparing chunks of DNA among 269 people from around the world. Over time, DNA accumulates random mutations, just as the front of a white T-shirt tends to accumulate spots. The bigger the chunks of DNA without random spots, the more recently it had been minted. Using this system, Hawks concluded that recent genetic changes account for about 7 percent of the human genome. Much of the increase, he says, has been fueled by the growth of the world's population, which has expanded by a factor of 1,000 over the past 10,000 years. Having more people increases the odds of mutations.

At the same time, the human genome has been scrambling to adapt to a rapidly changing world—11,000 years ago, nobody farmed, nobody milked domesticated animals, and nobody lived in a city. People with a mutation that aided survival were more likely to thrive, reproduce, and pass that mutation along to offspring. For example, the capacity to digest lactose, the sugar in milk, has become common only over the past 3,000 years. Now, about 95 percent of the people in northern Germany have the mutation, which also popped up independently among the Masai in Africa and the Lapps in Finland. Hawks says: "This is really rapid evolution."

Humans will continue to change to cope with new diseases, if history is any guide. Genes that defend against infectious disease have been among the most rapidly evolving parts of the human genome. People whose ancestors lived in European cities are more likely to have some resistance to smallpox, while people in sub-Saharan Africa are more likely to be genetically resistant to malaria. Just weeks ago, researchers reported that one genetic variant that protects against malaria also makes people more susceptible to AIDS, a discovery that could lead to tailored treatment for AIDS in Africa.

Right now, our genes are playing catch-up against modern scourges—like diabetes. Native Americans and Polynesians, whose cultures only recently adopted a European-style diet of refined grains, have the world's highest rates of diabetes. The theory is that the "thrifty genes" that helped those groups survive famines haven't had time to adapt to the glucose spikes caused by eating starchy food. "How we move sugars around and how we burn them has really changed a lot," says Gregory Wray, an evolutionary biologist at Duke University.

It's even possible that very recent changes in society and the workplace could underpin the recent rise in cases of autism. Simon Baron-Cohen, director of the Autism Research Centre at the University of Cambridge, was struck by how many of the parents of children with autism who he tested were really good "systematizers"—people who understand the world according to rules or laws. They also were more likely to have a father who worked in engineering. He wonders if the increase in autism diagnoses could be partly due to "assortative mating"—that is, people picking mates like themselves. People with autism spectrum disorder are often detail oriented and analytical, and today they might have an easier time finding a spouse with similar abilities than they would have in past eras. Baron-Cohen notes that in the late 1950s, only 2 percent of the undergraduates at Massachusetts Institute of Technology were women; now, 50 percent are. So, he's setting up a study to test whether assortative mating among people with a genetic predisposition for autism could be fueling the birth of more children with autism.

The human brain, which has evolved into a cognitive machine unique in the world, is likely to change even more in the future. Our niche in nature, says Stephen Pinker, an experimental psychologist at Harvard University who studies the evolution of language and the mind, is the "cognitive niche." In research published last year, Wray identified genes that control glucose metabolism in the brain as among those most recently evolved. Those changes may have been essential to fueling the human brain's growth to a size twice that of our nearest cousin, the chimpanzee. "If you make a big brain, it's an energy hog," Wray says. "It's like putting a V-8 engine in a tiny little car." It could also help explain why chimpanzees don't get diabetes, while humans do.

Tinkering. Take that souped-up brain and put it in the texting, Twittering, 24-7 world we've recently created for ourselves, and it's easy to imagine that we will become superspeedy multitaskers—or more complacent cubicle dwellers. However, this progress comes too slowly for some. "The world is changing so rapidly that biological evolution is not where the action is," says Nick Bostrom, a professor at the University of Oxford and cofounder of the World Transhumanist Association, which seeks to use science to improve humankind. He, for one, doesn't care to wait through a few hundred generations for improvements. Genetic engineering will help short term, he says, and then nanotechnology will step in, altering the biochemistry of the human body at the flip of a switch. "If we're thinking several hundred years out, then much more radical intervention may be feasible."

Unfortunately for those like Bostrom, who see humans as one big fixer-upper project, the human genome has so far proved to be remarkably resistant to tinkering. Since 1990, when gene therapy was first tested in humans, doctors have been trying to repair defective genes by injecting healthy ones. The method has shown only limited success and has failed to deliver as a treatment for common conditions such as heart disease. And gene therapy fixes only somatic genes, which aren't inherited. Germline therapy, which would create heritable mutations, is a far more complex—and contentious—challenge.

Notwithstanding the obstacles, Bostrom's wish list for improved human traits includes a longer "health span," with fewer years of human life spent struggling against cancer, heart disease, and dementia. Enhanced cognitive abilities would be nice, too. "Perhaps physical attractiveness would be a popular trait," he says.

There's as yet no way to select for attractiveness, but parents can choose a few of an offspring's genes if they're willing to try preimplantation genetic diagnosis. In PGD, doctors carefully vacuum a single cell from a 3-day-old embryo and test certain genes before deciding whether to place the embryo into a woman's uterus. The technique, which must be used in combination with in vitro fertilization, was invented almost 20 years ago as a way to reduce the odds of a child inheriting a deadly genetic disorder, such as Tay-Sachs.

It didn't take long for prospective parents to realize that the same method could be use to sort embryos for other reasons. Since 2000, parents have been able to use PGD to choose an embryo's tissue type, so that the ensuing child could serve as a stem cell or bone marrow donor to a sick sibling. More recently, a few have used PGD to reject embryos that have genes that merely increase the risk of disease in adulthood, such as the BRCA breast cancer genes. A few parents with disabilities such as deafness have used PGD to choose a deaf child. And PGD is increasingly used to reject embryos that have no problems at all—unless you consider being the wrong sex a problem. A number of fertility clinics in the United States advertise PGD to parents who want to be guaranteed the child will have the sex they choose. One California clinic boasts of "over 3,800 cases: 100 percent sex selection success." With PGD largely unregulated in the United States, it doesn't take a Nobel Prize in genetics to imagine that babies could soon be ordered up in custom sizes and colors, like a Mini Cooper.

The next step: children with genes from three parents. In the late 1990s, IVF clinics started injecting cytoplasm from younger women's eggs into those of older women, in an effort to increase the odds of pregnancy. About 30 babies have been born worldwide as a result, and those children carry genes from both women. But that rejiggering of the human germline was almost inadvertent. Scientists are now intentionally making that mix. Earlier this year, researchers at Newcastle University in England deliberately created human embryos that had DNA from one father and two mothers, in order to avoid the risk of a mitochondrial disease from the original mother.

But it's too early to lie awake worrying that genetically manipulated superkids are going to ace your grandkids out of varsity soccer, says Thomas Murray, a bioethicist and president of the Hastings Center. "Our capacity to do these kinds of intentional designs is vastly overrated." But, he says, it's not too early to start thinking about what's really important about being a parent. The traits that people most value, Murray says—being smart, being kind, being a successful competitor—are the ones least likely to be determined by a few tweakable genes. For that kind of control over the next generation, it still takes good old-fashioned nurturing, teaching, and love.

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