Perhaps nothing known to modern science is as unlikely and outrageous as the daily work of our genes. From food, water, and air, they make a human being. Genes make proteins. Proteins are us.
And from this audacious process come humans, who are themselves audacious. Not content simply to sit back and marvel at this infinitesimal artistry, people seek to control and improve it. Medical manipulators aim to insert a normal gene in place of a defective one, or perhaps more boldly, to insert an “improved” gene in place of a normal one.
So far, the Food and Drug Administration has not approved any human gene-therapy product for sale, but the day is coming. In 2001 Philippe Leboulch of MIT and Harvard University used gene therapy on mice afflicted with sickle-cell anemia and wrought what may prove to be the technique’s first outright cure. Human trials are about one year away.
In the future, some hope, diseases will have nowhere to run; they will be flanked and overwhelmed by the traditional top-down approach of drugs and surgery and the bottom-up techniques of genetic therapy. Little wonder, then, that optimism reigns in medical schools. “Students used to say, ‘I want to understand basic biology,’” says Tom Curran, a former president of the American Association of Cancer Research. “Now they are saying, ‘I want to cure something.’”
Despite the progress, they won’t lack for challenges. The looming riddles of medical research are still overwhelming and will require extraordinary amounts of money, as well as brainpower, to solve. Here are eight unanswered questions that leading medical researchers say will command most of the attention and funding in the next decade.
Why Is Asthma Raging Out of Control?
Over the last 20 years, the incidence of asthma in the developed world, and of related disorders such as eczema, hay fever, and food allergies, has tripled. Yet asthma and the rest don’t appear to be communicable, and two decades aren’t enough for a genetic change to have become so widespread.
“The question must be: ‘What has changed in the last 20 years?’” says Paul Hannaway, who is himself an asthmatic and head of the asthma-immunology division at North Shore Medical Center in Salem, Massachusetts. A clue has come from studies in Austria, Canada, Germany, and Finland, where researchers found that children raised on farms are less likely to have asthma than those reared in more populated areas. Other studies show that children in day care have less asthma and fewer allergies than those raised at home, and younger siblings have a lower incidence of these syndromes. In each case, an answer may lie in the amount of exposure to pathogens at an early age.
The biochemical on-off switch for asthma lurks within what are called T-helper cells, specialized white blood cells that marshal other kinds of T cells to combat invaders. There are two basic types of T-helper cells: Th1, or the nonallergic variety, and Th2, the proallergic sort. All healthy infants are born with a proallergic Th2 system, which protects the fetus from being rejected as a foreign object by its mother’s body. But, according to the hygiene hypothesis, early childhood exposure to the natural world’s microbial menagerie can reconfigure an infant’s immune system into the nonallergic Th1 variety, while antiseptically reared infants are stuck with Th2 systems and develop asthma.
Holes remain in the theory. “It doesn’t explain adult-onset asthma,” says Hannaway. “You’re 50 years old, and all of a sudden you get asthma out of a clear blue sky. How does that happen?” It also doesn’t explain why asthma is on the rise in some parts of rural Africa. Hannaway reckons the hygiene hypothesis will be part of the ultimate theory but adds, “in all likelihood there are many reasons for the emerging epidemic.”
Until the theory is complete, Hannaway thinks the case for the hygiene hypothesis is strong enough to warrant mixing some messiness into the spotless world of the modern infant. “There may indeed be some sense in letting your kid go outside and eat a little dirt,” he says. “And maybe we should not be such fastidious housekeepers.”
