The little girl who may hold the secret to aging

From 2014: Mackenzee Wittke, a five-year-old Alberta girl with the body of an infant, might just hold the genetic key to how we age
Mackenzee Wittke in Edmonton, Alberta, June 12, 2014. Photograph by Todd Korol for Maclean’s
Todd Korol for Maclean's
Todd Korol for Maclean’s

Every year, on her birthday, Mackenzee Wittke gets the same cake. It’s a homemade Rice Krispies treat, gooey with marshmallows and butter, moulded into the shape of a number: one for her first birthday, two for her second, and so on. Every year, as she hits another milestone, her parents, Kim and Matt Wittke—who live in the Edmonton suburb of Sherwood Park—snap a photo of her next to the cake. These pictures are a timeline of five-year-old Mackenzee’s life so far, and they reveal something startling: From one year to the next, as the number-shaped cakes tick upward, this girl has barely aged. Today, about to turn six, Mackenzee weighs 16 lb. and measures just under 30 inches. Doctors and specialists say that, physically and cognitively, she’s the age of a six-month-old baby.

No medical expert has ever been able to explain Mackenzee’s condition; all genetic and chromosomal tests come back normal. One scientist, who has dedicated his career to understanding aging, has a theory about what affects her. Solving the mystery of why Mackenzee Wittke seems frozen in time will, Richard Walker believes, answer one of life’s biggest questions: how we grow old.

The Wittkes are among a tiny group of families participating in his new study, which will sequence the genomes of seven girls (six in the U.S., and Mackenzee) who all seem impervious to aging. For the Wittkes, it’s an opportunity to better understand their daughter’s condition. Mackenzee wears baby onesies, and rides in an infant car seat. She can’t walk or speak, but she will giggle and coo; when she’s upset or hurt, she cries. Her condition has brought with it a suite of medical problems, which flare up unpredictably, and have seen her in and out of hospital. Her life expectancy is unknown. As for Walker’s study, “I think this may be our biggest shot at finding some answers,” says Kim Wittke, 37.

Walker’s work could finally shed light on what ails Mackenzee. “What if there’s another Mackenzee born tomorrow?” Kim says. “Those parents could have some answers, where we never did.” For Walker, now 74, this would be a welcome outcome. But he also sees in Mackenzee a chance to find a way to slow aging, or maybe even to stop it altogether.

Aging is a part of life, one we accept as a given. But, while there are lots of theories—maybe it’s preprogrammed into our genes; maybe environmental factors gradually damage our cells and, like a rusted old car, we begin to break down—scientists still can’t say exactly why our muscles slowly weaken, and our organs fail. For Walker, a retired professor of biochemistry and molecular biology at the University of South Florida in Tampa, and editor-in-chief of the journal Clinical Interventions in Aging, this question has been a lifelong fixation. During the Vietnam War, he served with the military medical corps, on the island of Guam, where he saw his share of wartime injuries. But many types of injury, he notes, are still more treatable than age-related diseases, like cancer. “Aging has always been repugnant to me,” he says. “I didn’t like the way my grandparents suffered. My grandma died of pancreatic cancer. Something in me found that to be abysmal.”

Walker, whose career spans almost 50 years, crafted his own hypothesis to explain the decay of age. “We start off life as two cells,” he says. “These have to become a mature man or woman.” He believes each of us may contain a genetic program that pushes us toward sexual maturity, while coordinating the body’s systems to grow and work together, like instruments playing in an orchestra. But once we reach our physical peak, our body’s tendency to remodel itself doesn’t switch off. Something, perhaps a gene (or genes), keeps driving it forward, and problems begin to accumulate. Its systems fall out of sync, and the music, so to speak, grows dissonant. As age grinds away at us, its accompanying diseases—cancers, Alzheimer’s, heart disease—start to show up.

Walker saw no way of testing his theory, until one evening in 2005. “I was sitting at my desk, and my wife was in another room,” he recalls. “She yelled, ‘Rich, you’d better come look at what’s on TV.’ That’s when I discovered Brooke.” Brooke Greenberg, who lived near Baltimore with her family, was a preteen at the time; she resembled an infant. Nobody could say why. (Her pediatrician referred to her condition as “syndrome X,” which is sometimes applied to others in Walker’s group, too.) “I thought, ‘Maybe she has a mutation of this theoretical gene,’ ” Walker says. He reached out to the Greenbergs, who let him examine Brooke. Her genetic markers were normal; her condition couldn’t be pinned on disruptions in her hormones, chromosomes, or anything else known to cause developmental delays. Brooke’s development was not only stalled, but “disorganized,” as Walker puts it, which his theory predicted: Her various physical parts weren’t developing in sync. Her program had gone out of whack, and the instruments in the orchestra weren’t playing together.

At 16, Brooke’s height and weight were those of an 11-month-old; she showed no signs of puberty. Her teeth and bones resembled those of a preteen, yet the length of her telomeres (the tiny caps on our chromosomes whose length corresponds to biological age) were right for her 16 years. A bona fide medical mystery, Brooke’s story attracted national media attention—she was on TLC, Katie Couric, in People—and other families reached out to Walker about their kids. In most cases, he could find a cause for the child’s condition. But, in a few of them, he couldn’t.

About four years ago, Kim Wittke, who used to work in the insurance industry but now stays home with Mackenzee, also watched a TV show about Brooke Greenberg. “At the time, I think she was 15 or 16, but she looked like a toddler,” Kim says. “Something resonated with me. Mackenzee was 18 months, but she looked like a newborn. I remember them saying, ‘Nothing grows but her hair and fingernails.’ And I said, ‘Yeah. That’s the same with Mackenzee.’ ” She reached out to Walker, but it wasn’t until last summer that the Wittkes felt ready to work with him. “We’ve kind of run out of options here,” Kim says. “There are days where it just turns in you, and you’re ready to find out what’s going on.”

It was around that time that Brooke’s father abruptly broke off contact with Walker. (Howard Greenberg declined to comment for this story.) As Walker set out to find other subjects like Brooke, the Greenbergs formed a new alliance, with Eric Schadt, director of the Icahn Institute for Genomics and Multiscale Biology at Mount Sinai Hospital in New York. When Greenberg first told Schadt that his daughter, then 19, resembled a toddler, “I was a little skeptical,” Schadt tells Maclean’s. “It seemed hard to believe.”

Schadt sequenced Brooke’s genome, parsing six billion letters of DNA to search for tiny quirks that might have contributed to her condition. (His team sequenced the genomes of her parents and three developmentally normal sisters, too.) That left him with a handful of genes that “look interesting,” Schadt says. His team has created a line of stem cells from Brooke’s skin, and are using them to grow liver cells, fat cells, neurons, and other building blocks of her body, to study the impact of each mutation, and how it may relate to aging and disease. If any of these genes are connected to aging, Schadt suggests, manipulating them could boost longevity and help erase age-related disease. “We’re on a path where we will absolutely gain control over aging,” he says.

Walker sees it, too. Imagine switching off the right gene in a healthy 20-year-old, he suggests, whose body is developmentally mature, its systems working perfectly in sync, and hasn’t yet begun to crumble with age. “Here’s the science fiction,” Walker says. “We could create a biological immortal.”

Schadt and Walker praise each other’s work, although, in a sense, they’re rivals; each takes a different approach. Walker, for his study, has collected blood samples from seven girls and their family members: 36 people, all told. Each will have his or her genome sequenced. At the University of California at Los Angeles, a collaborator will also perform epigenetic studies to help determine these girls’ “biological age,” Walker says. One of his subjects is 25, he notes, but looks like she’s about seven years old. “So, biologically, is she 25, or seven?” After identifying the most interesting mutations, Walker plans to test any that seem related to growth or aging, in a mouse. “You take a young mouse, shut that gene off,” and see if the mouse is still able reproduce past the point when fertility would normally be lost to old age, Walker explains. If so, it’s possible this scientist will have finally found his long-hypothesized aging switch.

If a true biological clock does exist, in these girls it’s broken. Because their development is “disorganized,” they have been left vulnerable to disease. Each girl (all of Walker’s subjects are girls, but he doesn’t know why; it could be meaningful, or just a coincidence) suffers from multiple health problems. Mackenzee has pulmonary hypertension and serious stomach issues that led to the removal of half her colon. She takes several medications daily, including heart medication, a diuretic and an antibiotic. She consumes baby formula through a feeding tube and needs her oxygen intake topped up through nasal prongs. Her “perpetual youth,” for what it’s worth, has come at a high cost.

It’s a Thursday in June, around 4 p.m., and Matt Wittke is coming home from work. He pulls into the garage, in a neatly kept cul-de-sac surrounded by parks, walking trails, highways and strip malls, and heads inside. His oldest daughter, Emilee, who’s about to finish Grade 3, sits at the table working on an origami project, as Kim bustles around the kitchen. Mackenzee, reclined in a baby bouncer seat, smiles brightly when she sees her dad. Matt, who works for Bradken, a major supplier of pipe to the Alberta oil sands, picks up his daughter and holds her in his lap, as Kim gets dinner ready. “Matt, would you carve the chicken?” Kim asks, and he puts The Little Mermaid on TV for Mackenzee, and goes to help Kim.

The first sign Mackenzee was different came during Kim’s pregnancy, when doctors detected heart and brain abnormalities on her standard 20-week ultrasound scan. This prompted a series of tests, from more ultrasounds to blood work to an MRI, but no real answers. Fearing possible complications, Kim declined amniocentesis, which can diagnose chromosomal problems in a fetus, including Down’s syndrome. (The test, which involves inserting a needle into the uterus, slightly ups the risk of miscarriage.) She’s happy she made that decision. “The amnio would have shown that all her chromosomes are normal,” Kim says. “I think I would have prepared myself a bit differently, hearing that.”

As it was, doctors told her Mackenzee was extremely small for her gestational age. She was in the 10th percentile; then the fifth; then the third; finally, she dropped off the charts. Four weeks shy of the due date, doctors determined they’d need to deliver the baby. Kim’s voice still gets shaky when she recalls Mackenzee’s first days. As she recovered from delivery, “my parents and Kim’s and I sat down with the doctor,” Matt says. “They said, ‘Take lots of pictures. She’ll be gone in a week.’ ”

Doctors tested for “one syndrome after another,” Kim says, from Down’s to trisomy 18 (half of all infants with this genetic disorder don’t survive beyond their first week). Mackenzee spent her first six months in hospital before coming home. Doctors said there was a slim chance she’d see her fifth birthday, yet she has survived. To this day, her only medical diagnosis is pulmonary hypertension, Kim says.

Of the genetic and chromosomal testing she’s since undergone, “what we have is all normal,” says Lyle McGonigle, Mackenzee’s trusted pediatrician since she was two months old. With no better explanation for her condition, the front of her chart says “ECS” in big, handwritten letters: “Extremely cute syndrome,” a joke Kim likes to make. (“It’s inherited from the mother,” Kim says.) McGonigle, who’s been practising for 30 years, focuses on special-needs kids. “I’d say she has the Mackenzee Wittke syndrome,” he says, “because she’s unique.”

The Wittkes long ago adapted to a new way of life—one that, today, feels normal. Because of a sensitivity to light, Mackenzee can’t be outside in the bright sun, and family outings take a fair bit of planning. They find other ways of including their little daughter: In their “family dance parties,” Kim, Matt and Emilee play music and dance around Mackenzee, as she giggles away. “Emilee’s taken her hits sometimes, when we’ve planned something fun and it has to be cancelled because Mackenzee was sick,” Kim says, but they’ll bring in respite care now and then to look after Mackenzee, and take Emilee out somewhere, maybe to a movie. Emilee dotes on her sister. Despite an age gap of just three years, Emilee can cradle Mackenzee—“Kenzee,” she calls her—in her lap. “We’ve been told many times, when she’s sick even with a bad virus: This may be what takes her,” Kim says. “We’ve learned to take it one day at a time. Sometimes that’s too much, and it’s five minutes at a time. I put her to bed every night, give her a kiss, tell her how much I love her, and pray I get another day with her.”

If anyone can relate, it’s Mary Margret Williams, mother of Gabrielle (who goes by Gabby), a nine-year-old in Billings, Mont., and another participant in Walker’s study. Gabby’s symptoms aren’t identical to Mackenzee’s—she can feed from a bottle and is partially blind—but she also wears baby onesies and travels in a stroller. Gabby weighs 12 lb., five ounces. “All her life now, they’ve told me: ‘This little girl’s not going to last very long,’ ” says Williams, who has six children (Gabby is second-oldest). “Whenever she gets sick, it’s like, this is it. But she pulls herself back up, and sticks with us.”

In October 2013, Brooke Greenberg died at age 20. No cause of death was publicly disclosed, but, like Mackenzee and Gabby, she’d suffered various health problems. That’s the irony: These ageless children remain, in reality, quite fragile. When McGonigle speaks about Mackenzee, he’s blunt. “The prognosis is grave,” he says. “She could die anytime, and someday she will, from the complications of one of the problems she has. But that day is not today; and it wasn’t yesterday; and it may not be tomorrow. It may be six months from now. It may be 10 years from now; I don’t know. As long as her life is good, we should support her.” Mackenzee is happy and well cared for, he says, despite all the tests and procedures she’s undergone. “It’s a tribute to her parents. They’ve dedicated themselves to making this child’s life as good as it can be.”

Neither Kim nor Mary Margret shares Walker’s desire to find an off switch for aging—for us all to remain perfect 22-year-olds forever. “Our goal is not to have a fountain of youth,” says Mary Margret, a staunch Catholic. “I think we’re all meant to be babies, and grow old and die, and that’s the way God made our world.” Although she and Kim have never met or spoken, both express a desire for Walker’s research to help slow the age-related diseases that are on the rise, such as Alzheimer’s, cancer and heart disease. “If my daughter can help with that, I think it would be astounding,” Kim says. “But the main thing, for us, is to find out something for Mackenzee.”

When asked whether we’ll truly understand aging within his lifetime, Walker acknowledges that the answer is probably no. Despite his vigorous exercise regimen, and the vitamins he takes, “I don’t expect to live beyond the normal lifespan,” he says, “maybe another 10 years.” Both he and Schadt know immortality is a polarizing topic. “Most people I’ve talked to want to live forever,” Schadt says. “But there are such dramatic social implications, it’s overwhelming.” Walker has heard the objections—that the planet is overpopulated; that we weren’t meant to live forever—but he doesn’t entertain them. “These are not issues I’m willing to enter into. I’m strictly a scientist,” Walker says. “Even if I find out I’m wrong, I will be happy.”

Time is ticking down, and he’s moving as fast as he can. By August, Walker expects to have results from sequencing the genomes of the seven girls; then, he’ll start drilling into the various mutations to see which ones are good candidates for further examination. That same month, Mackenzee will hit another landmark: her sixth birthday. There will be another photo taken, of her next to a six-shaped Rice Krispies cake. Although she won’t be able to eat a slice, her parents will touch it to her lips. She likes the sweet taste.

In September, for the first time, Mackenzee is going to school. Kim has enrolled her in a Grade 1 program in Sherwood Park, for medically fragile kids (there will be only five or six in her class). They’re having a tiny wheelchair built, to “give her a different perspective on the world,” Kim says. Instead of facing backward toward her parents, as she does in the stroller, Mackenzee will look forward. For Kim and Matt both, Mackenzee’s transition into Grade 1 is “nerve-wracking,” Kim says. They worry about exposure to germs; about this little girl being out of their sight, even for a few hours a day. “She’s been my sidekick for almost six years,” Kim says. But the days keep moving forward, and her parents don’t want her to miss out. As Kim says, “Mackenzee’s got to live her life.”