When the call came in late March, Louise Markert was ready. Across campus, through the hospital and into the operating room she marched. Nestled inside the sterile plastic container she held close to her body were precious slivers of a living human organ.
Those tiny slices held the promise of life for an innocent baby sleeping just beyond the operating doors. And Markert was the only doctor in the world who could deliver the experimental therapy they represent.
It was a similar phone call 16 years ago that brought Markert to these OR doors. She had been a pediatric immunologist on call when “I got a call about a baby in Knoxville, Tenn.,” she recalls in a staccato voice rounded by remnants of her northern New York origins. “The baby had DiGeorge syndrome and they wanted to know if we could help.”
DiGeorge syndrome is a quirk of nature that occurs when something goes terribly wrong during the first trimester of an embryo’s development. It sets the stage for a complicated disease and a host of maladies, including heart defects and calcium problems. In less than 1 percent of infants affected, a severe disruption of the immune system means almost certain death.
The Knoxville doctors had turned to Duke for help because of its leaders in clinical and basic immunology, including the late Bernard Amos, Rebecca Buckley and Barton Haynes. Among Duke’s notable achievements in this area was the tissue typing that led to the success of modern-day organ transplants.
Markert, who fell in love with immunology in high school, trained at Duke under Amos. “He recommended I do pediatrics. I didn’t like kids much at that time.” But that would soon change.
Markert eventually focused her efforts on the thymus. This vital but overlooked organ is located behind the breastbone and guides the immature white blood cells from the bone marrow so they can develop into T-cells that fight off infection.
“The thymus is like a schoolhouse,” Markert says simply, offering the analogy she uses with her patients. “When you open the doors, the students — in the form of immature white blood cells — are the children who run in. Eventually they graduate to be T-cells.”
Each year, fewer than 10 infants are born with complete DiGeorge, in which they lack a thymus entirely. Without the gland, babies have little to no chance of living past their second year.
Although thymus transplants had been attempted as early as the late 1960s for other immunodeficiency diseases, there had been little success, in part because no one knew which infants could benefit.
There also were concerns about the tissue’s viability. The thymus had to be harvested from a living donor and kept alive by being sliced into tiny pieces, which allows oxygen to reach all of the tissue’s cells while it’s being tested for safety prior to implant.
Pediatric heart surgeons routinely cut through the thymus to get to the heart, and it is normally discarded during open heart surgery on very young patients. That meant there was a fairly plentiful supply of the glands, but Markert keenly remembers her mounting frustration with keeping them viable for a transplant.
“I’d slice the tissue and after a week of culture, I’d bring it to Dr. Haynes’ lab where his technicians would section it. Then I’d go over to meet with Bart Haynes (an authority on T-cells and head of Duke’s human vaccine institute) who would tell me it was dead.”
Over and over again she tried. She learned how to sustain the thymus in a lab dish of special fluid and to slice it very gently. “That’s key,” she says. “If you use too much pressure, you kill the whole thing.”
Markert distinctly remembers the day when she arrived at Haynes’ door and learned that her persistence had paid off. “It was wonderful when he finally smiled and said, ‘It’s alive.’”
“The first transplant was so stressful, you can’t imagine. The child developed a horrible rash. I thought I had given her cancer. She was a real mess.”
The 3-month wait to biopsy that thymus seemed to take forever. Finally, she and Haynes peered into the microscope. “It looked like a normal thymus. It was unbelievable.”
Although that baby lived, complete success was not yet at hand. The next three babies died. By the time the fifth child survived, Markert was recognizing some of her missteps.
“We learned a lot about how to manage the children and do better.”
She also figured out why the first child developed the rash. “I run into it all the time. The child had developed rogue T-cells. Now I use cyclosporine (an anti-rejection drug) and have no problems.”
Today, that first baby is a healthy 14-year-old. And, after 52 transplants, Markert’s procedure now boosts a 73 percent success rate. Although still considered experimental, thymus transplants are covered by some insurance companies.
Markert receives funding from the National Institutes of Health and the Food and Drug Administration to continue the research. The amount of paperwork needed to track her program and continue its funding can feel insurmountable. Stacks of papers, files and folders consume her office, yet Markert remains committed. Her staff makes her work possible, and helps her field daily referrals from around the world.
She’s had highs when patients live, and lows when she thought her entire program would be put to a penniless death. But none of it has dampened Markert’s enthusiasm for what’s become her life’s passion.
“When I started, I was told I’d never get grants and that I should work with mice. I don’t really like mice,” she says matter-of-factly.
“Now I’m helping babies live who would die otherwise. That’s what’s important to me.”
Debbe Geiger is a senior media relations specialist in the Duke Medical Center