Dr. Carol Wise uses CSI techniques to find mutated human genes.
Dr. Carol Wise uses CSI techniques to find mutated human genes.
Mark Graham

Genetic Criminals

On a recent Saturday, a group of wide-eyed wannabe mystery writers, aware of the forensic fascination that is sweeping the country and anxious to lend authenticity to their novels-in-progress, followed Dr. Carol Wise as she led them on a tour of her laboratory. Her guests dutifully made notes as she often spoke in what sounded like a foreign language: There, she said, is the denaturing high-performance liquid chromatographer. And this is our polymerase chain reaction machine. Soon she arrived at the DNA sequencer/genotyper.

Ah, the polished, high-tech tools of modern-day science and crime fighting.

Wise, however, does not use her well-equipped, grant-funded lab to aid law enforcement in the apprehension and conviction of serial killers and rapists. Director of molecular genetics and cellular biochemistry at Dallas' Texas Scottish Rite Hospital for Children, she and her three-technician staff work to track down another kind of social enemy. Yet her procedures are much the same as those you see on television's CSI or Forensic Files or read about in Patricia Cornwell best sellers.

The "criminals" Wise is looking for are mutated human genes responsible for inherited diseases.

And, the 40-year-old is quick to point out, the research procedures used in the Scottish Rite lab are similar to those employed by crime lab technicians attempting to match a DNA sample to a suspected law-breaker. "We do the same kind of investigating, run into many of the same pitfalls along the way and--when we get lucky--we find the perpetrator of the crime," she says.

Her adversaries, however, are genes that cause ailments like debilitating juvenile rheumatoid arthritis, idiopathic scoliosis and bone-growth disorders. And while she admits that her pursuits are often "worse than looking for a needle in a haystack," she and fellow researchers are making progress, thanks to the past decade's rapid improvement in DNA testing capabilities. "I'm fortunate to be at the right place at the right time," Wise says. "Breakthroughs are beginning to happen. Ten years ago it would have been difficult--if not impossible--to do some of the things we're now doing."

She traveled an indirect route to what she now refers to as her calling. When she graduated from Forney High and enrolled at Texas A&M, she was convinced she would one day become a chemical engineer. Only after beginning graduate school at Dallas' University of Texas Southwestern Medical Center did she find herself drawn to the study of molecular biology. A doctoral thesis and a couple of one-year fellowships later, she found herself working with famed researcher Dr. Michael Lorett on a study of rare pediatric bone disorders. "At one point, someone suggested we get in touch with doctors at Scottish Rite who were treating patients with the same disease we were looking at," she recalls.

It was only then that she realized the degree of specialized treatment offered at the 80-year-old Scottish Rite children's hospital, a facility supported solely through private donations. Soon it came to her attention that the hospital was planning to expand its research in the field of genetics. In 1996, Wise was hired to direct the program.

"Three years ago I was hidden away in a small corner over at Southwestern," she recalls, "and I had one assistant." Today she and her staff work in a 2,000-square-foot, state-of-the-art laboratory funded by a Crystal Charity Ball grant.

Still, the work being done there--and in an estimated 150 similar gene research labs across the country--remains in its infancy. Today, successful treatment for the ailments she researches is the primary goal. Tomorrow, a cure. Perhaps somewhere in the distant future, even prevention.

And, to date, there has been enough success to provide optimism.

She tells of three siblings, ages 10 to 13, who were being treated by Scottish Rite doctors for arthritis conditions that were both painful and debilitating to the point that the children could not lead normal lives. One of the youngsters had suffered swelling of his joints so severe that it caused cystic skin lesions. Thus began a research project that led to the realization that the ailment had been handed down through generations. "The condition was clearly genetic," Wise says, "so we began contacting members of the family, going back to great-grandparents of the children." Ultimately, blood samples were taken from 15 family members--some requiring out-of-state visits to test--and the mutated gene was finally isolated.

"When we started the project," she says, "we didn't even know what to call the disease. And, while we still don't have a cure, we now have a treatment that is working."

At times, she says, something as insignificant as simply providing a name for a person's infirmity or explaining its cause is comforting to a patient and family. "There is a great deal of guilt associated with hereditary diseases," Wise points out.

A few years ago, for instance, a 60-year-old grandmother who suffered from severe scoliosis (an abnormal lateral curvature of the spine) and was aware of the research being done at Scottish Rite arrived at Wise's office with every living member of her family. The woman had even urged her daughter to fly to Dallas from London for the meeting.

"I have it, my daughter has it and soon my grandchildren will have it," the distraught woman said.

Thus began a new project: the search for the defective gene that causes idiopathic scoliosis. "Despite the fact it has been around forever," the doctor says, "we've never been able to determine what causes it--thus the term 'idiopathic.' All we really know is that it typically seems to affect females in their teen years.

She's convinced the technology now exists for more rapid advancement, not only in the discovery of cell disorders that cause diseases but in finding a way to reverse the degeneration of cells that lead to such common ailments as hearing loss and lower back pain. "During the aging process," she explains, "certain cells simply begin to wear out. That, for instance, is why as we grow older we have a harder time hearing. I find it exciting to think there is a real possibility that process can be reversed. It's targets like that researchers are going to be aiming at in the next 10 to 20 years."

It is something she wants to be around for. And while a hint of impatience occasionally creeps into her conversation, she expresses confidence that the rapidly improving technology will, just as it has done for criminologists, lead her and her fellow researchers to the answers they're seeking. Already, doctors from throughout the country and as far away as Italy are contacting Scottish Rite and Wise about the advancements being made at the Dallas facility.

As she continues her quest for new knowledge, daily searching for and closing in on the microscopic Gordian knots that cause human pain and misery, the mother of two has come to a greater appreciation of her own family's health. She and her orthodontist husband, John, regularly hike down to a spring-fed creek near their rural home outside Lucas, north of Dallas. There, joined by sports-minded son Ben, 12, and musically inclined daughter Madeline, 9, they fish for perch in the creek that winds through their property. "What I wish for every day," their mother says, "is that every child, regardless of the cruel hand dealt them at birth, might one day be able to enjoy the same simple pleasures my children do."


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