Gene Therapy May Make It Possible For Adults To Grow New Teeth

May 22, 2001 SAN ANTONIO (San Antonio Express-News) - Squirreled away down a labyrinth of hallways at the University of Texas Health Science Center, Mary MacDougall presides over a crowded and busy laboratory, making big plans for the Tooth Fairy. Twenty years from now, if this dental researcher has her way, the mythical sprite will be more than just a figure of childlike imaginations making stealth visits to 7-year-olds who have parted with baby cuspids and incisors. She will walk around in broad daylight, wearing a lab coat and employing gene therapy to grow new teeth for 50-year-olds who have lost their original choppers to periodontal disease, decay or trauma. That sounds far-fetched, but MacDougall and other prominent dental researchers say it is a very possible future for dentistry, as the Human Genome Project bears fruit in the coming decades. Someday, MacDougall said, dentures and fillings will be forever banished to the museums. Dentists will know how to turn on long-dormant genes and prompt patients to fix their own cavities or grow their own replacement teeth. "It sounds like science fiction," said MacDougall, associate dean of the dental school at the health science center. "But it's something that can be done eventually." MacDougall has taken steps toward accomplishing that task in animals. Researchers in her lab have taken root buds from laboratory mice and successfully grown mice molars in a culture dish. The roots, crown and finishing enamel are assembled into perfectly formed teeth not much bigger than a pinhead. Humans are far more complicated, though. First, researchers must find the genes responsible for building the 25 major proteins that make up a tooth. Then, there may be dozens of other genes involved in telling the body when and how and where to build a particular tooth. Other prominent dental researchers are watching the ongoing work with interest. "There's a lot of hurdles there, but I wouldn't say anything isn't doable," said Frederick Eichmiller, director of the American Dental Association's Paffenbarger Research Center in Gaithersburg, Md. "It's an enormously complex process," Eichmiller said. "You'll have to have all the genes that generate that one tooth, so you get a tooth that will match all the characteristics of the one that was lost. If you lose a front tooth, you want a front tooth back." Progress will come in increments, beginning with development of fillings and crowns that more closely resemble real human teeth. Scientists in MacDougall's laboratory already have undertaken this first piece of the puzzle, and believe that they will have new products on the market within five years. Beyond that, researchers hope to be able to grow laboratory teeth that can be implanted in a human mouth. These would not be living teeth with nerves and blood vessels, but they would be made of the same materials as human teeth. The final step will come perhaps 20 years from now, MacDougall said, when a dentist's arsenal will include treatments that cause teeth to repair themselves. "I tell my students, one of the wonderful things about science is, when you answer one question, you get five new questions. You never run out of things to investigate," MacDougall said. Unlike skin, bone and muscle cells, the cells in human teeth do not replenish themselves. Teeth form twice during our lives. Twenty primary or "baby" teeth erupt in stages between the ages of 8 months and 3 years. Those are displaced by 32 permanent adult teeth between ages 6 and 17. Then the teeth-forming genes go silent for the duration of human lives. Still, they remain in the nucleus of every cell, part of the 6-foot-long ringlet of DNA that make up the 23 chromosomes. The recently completed genome project has sequenced the chemical code along each of the chromosomes. Scientists now are investigating precisely where the estimated 30,000 genes are, and what each gene is programmed to do. Researchers have found some of the major genes involved in tooth formation, but have quite a way to go, MacDougall said. "There may be as many as 10 percent of the total genes that are somehow involved in the formation of teeth," she said. The biggest search is for key regulator genes; the ones that tell the body when to form a tooth, where in the mouth it should erupt and whether it should be a molar or an incisor. Once these are found, MacDougall said, scientists will be on their way to knowing how to generate new teeth. The San Antonio Express-News.

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