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Stem cell study gets personal
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Stem cell study gets personal
After a ski accident paralyzed his daughter, an NU neurologist devoted his career to curing her. But he fears U.S. limits on stem cell research will hinder his progress.
Dr. Jack Kessler says his daughter Allison's resolve in recovering from her spinal cord injury adds to his own determination to help her walk again. (Tribune photo by Jill Toyoshiba and Alex Garcia)
Stem cell research
By Jeremy Manier
Tribune staff reporter
Published August 18, 2002
In his career as a neurologist Dr. Jack Kessler had treated many paralyzed patients with no hope of recovery, but he never felt so powerless as he did on an emergency midnight flight last year to be at the side of his injured daughter.
Kessler, chair of neurology at Northwestern University, knew his 15-year-old daughter Allison had just lost virtually all movement from the waist down in a skiing accident. As a father, he hoped beyond reason that she might just shake off the injury to her spine; but as a doctor he knew she had little chance of ever walking unaided again.
Still on the plane, Kessler decided to drop his previous research on nerve disorders linked to diabetes and seek out stem cell treatments for paralysis.
Kessler placed his hope in embryonic stem cells, which can multiply into huge quantities and become virtually any kind of tissue. Many scientists believe such cells have the remarkable potential to replace diseased organs or repair damaged spinal cords.
So it felt like a personal blow to Kessler last August when President Bush issued his policy allowing only limited federal funding for research on embryonic stem cells. Kessler feared the move would stymie his new work on spinal cord regeneration--and possibly threaten the future of his family.
One year after Bush's decision, many experts say its effects have been mixed, with exciting lab results tempered by frustrating limits on access to cells.
Only a few federally approved sources of stem cells have actually begun shipping to other labs, and federal overseers say there have been too few researchers seeking funding--about 20 fully reviewed applications so far.
"It's been slow," said Wendy Baldwin, deputy director for extramural research at the National Institutes of Health. "To date, am I disturbed? No. But it needs to pick up for the future."
No one appreciates the urgent stakes of stem cell research more than Allison and Jack Kessler.
From a standing start last year, Kessler's lab has retooled and begun several new spinal cord studies, including one effort to treat paralyzed mice with neural stem cells genetically engineered to blaze a path through damaged tissue. In the last month, Kessler's group ordered its first batch of human embryonic stem cells from the University of Wisconsin--one of only four stem cell labs to receive major federal research grants so far.
Despite the slow pace of federal funding, Kessler said stem cells are the best long-term hope for healing spinal cord patients like his daughter.
"I absolutely, firmly believe, with every ounce of my intellect, that stem cell biology is going to revolutionize medicine," Kessler said. "I don't know what the timetable will be. But whatever it is, I do know that every impediment that gets thrown up delays it. And that's very personal for me now."
Allison Kessler, an ebullient teenager with a near-constant smile, had learned to ski almost as soon as she could walk, reaching up to her three older brothers' arms for balance. She gravitated to sports in high school, competing in soccer, diving, lacrosse and hockey. "I've always been able to pick up any sport," Allison said.
When Allison and her boyfriend first visited a skiing hill near her Connecticut prep school in January 2001, she said she almost backed away--because the slope was too small.
"I laughed at the hill," Allison said.
But the next afternoon they decided to try some of the hill's small ski jumps. Allison cleared a few with no problem, then moved to another ramp that she assumed was like the others.
She sensed a problem as soon as she got airborne. Instead of a gentle, sloping ramp on the other side, she saw nothing but level snow.
"It turned out to be a snowboarding jump, which means it didn't have a landing on the other side," Allison said. "I wasn't expecting it to drop like that."
Allison's momentum sent her flipping over backward. She remembers trying to use her gymnastics training to hit the ground safely, but instead she landed flat on her back.
"My back hurt a lot," Allison said. "I was conscious all the time. I've done enough different sports to know when I'm screwed."
Jack Kessler quickly grasped the seriousness of his daughter's injury. From Chicago he spoke with Allison's neurosurgeon, who said that one of her lower vertebrae had been pushed forward and crushed her spinal cord. The doctors classified her injury as complete, meaning they could detect no movement in Allison's legs and believed no nerve signals could pass the injury.
"I knew exactly what questions to ask, and the answers told me a prognosis that I didn't want to know," Kessler said.
When Allison woke up from surgery to stabilize her vertebrae, she told her parents she still wanted to graduate with her high school class. She also asked whether she could still have children.
"It's not the first thing a guy would be thinking about," said Kessler, who told her the answer was yes.
The next day Kessler gave his daughter a neurological exam, hoping to find some trace of mobility in her legs that the hospital team had missed. He tested each muscle with his hands and fingers until he found one faint flicker of movement in her left leg.
"We worked very hard to find one tiny little muscle that she could just make move a little bit," Kessler said.
That small movement was the beginning of a long, partial recovery in Allison's left leg. It would take 18 months before she learned to walk with a half-leg brace.
Yet Kessler knew that nothing short of fundamentally new therapies could ever truly reverse an injury like Allison's. He immediately set about the arduous task of shifting his research focus from peripheral nerve disorders to treating spinal cord damage.
Soon Allison began joking that her dad's new job was to cure her.
"I'm not going to cure spinal cord injury, not personally. But I will do everything I can to contribute to it," Kessler said in his family's North Side home, which has been extensively renovated with an elevator and hydraulic lifts to accommodate Allison's wheelchair.
"I always wanted to regenerate the nervous system," he said. "That's what I've spent my whole life wanting to contribute to. And now ...
"Now you've got more reason to," Allison said. "You'll get to it faster."
Change in path
Kessler's wife, Marilyn, a professor of gynecology at Northwestern, said she knew right away that Allison's accident would make her husband switch his work to spinal cord research.
"We didn't have to talk about it--it was clear," Marilyn Kessler said.
Kessler barely had time to plot his career change when, eight months after Allison's accident, the father and daughter found themselves in the thick of last summer's debate over funding of embryonic stem cell research.
Opponents of such work argued that President Bush should withhold federal funds on moral grounds because the research involved the destruction of human embryos. Biologists said the potential benefits of embryonic stem cells as replacement tissue for numerous diseases outweighed such concerns.
Bush's compromise, announced in a speech at his Texas ranch Aug. 9, 2001, permitted funds for research on stem cells that already had been taken from embryos left over from in vitro fertilization treatment. But Bush prohibited federal funding for work on cells developed after the date of his speech.
Although Jack Kessler was pleased to see any funding approved, he and other stem cell advocates feared those limits would dampen interest and impede progress in the field.
The subject also brought out raw feelings for Allison Kessler toward opponents of embryonic stem cell research.
"I wouldn't want to wish my accident on anybody," she said last summer, "but in a way I wish it would happen to somebody in their family, and see what they think about it. To them it's just an abstract idea.
"See what happens if their child gets hurt, and then they're told, `Well, we're not going to be able to cure them, you know, while they're young. Maybe when they're older, but you'll never see them well again.'"
As Allison focused on returning to school last fall, her father steadily brought his graduate students at Northwestern into new spinal cord research projects.
Encouraging new work
New studies encouraged Kessler that embryonic stem cells could help to heal the spinal cord. Some of the most intriguing work on spinal cord recovery has come from the lab of Thomas Jessell, a stem cell scientist at Columbia University in New York.
Earlier this year, Jessell's team published a paper in the journal Cell about a study in which they coaxed stem cells from mice into becoming motor neurons--specialized cells that transmit signals for movement from the spinal cord to muscles. Jessell also showed that the cells could integrate into a living spinal cord and develop connections with their targets in muscle.
"If I had to pick one paper from this year that demonstrated something substantive, that would be it," said Douglas Melton, a stem cell researcher at Harvard University.
Another dramatic but more preliminary result has come from John Gearhart, a researcher at Johns Hopkins University and co-discoverer of human stem cells.
In lectures to scientists in recent months, Gearhart has presented the results of a still-unpublished study using fetal-derived human stem cells to repair the brain cells of mice paralyzed with a special virus.
After losing use of their hind legs to the virus, mice treated with the stem cells recover some movement by two months. The videos Gearhart uses in his presentations show that after three months the mice can walk, albeit slowly and with much shaking.
The study has not cleared review by other researchers, and experts say the results could prove to be a fluke of Gearhart's methods. Still, videos of the Hopkins mice have produced a quiet stir in research circles, said Melton.
"If that preliminary result is right and turns out to be reproducible, it takes your breath away," Melton said.
But even if researchers can create new nerve cells, regenerating the complex biological circuitry of the spinal cord poses an immense challenge.
The most difficult task may not be adding new nerve cells but getting them to grow through the damaged part of the spinal cord. Kessler chose to focus on using stem cells to spur the growth of existing neurons, forming a new bridge for signals to travel from the brain to muscles in the arms or legs.
"We're not trying to physically regrow the cells. We're blazing a path for them," Kessler said.
For reasons experts still do not fully understand, severe trauma in the spinal cord leads to the release of destructive compounds that kill nerve cells and prevent others from growing in their place. Such secondary damage, which unfolds in the hours after an injury, can be as harmful as the original accident.
Kessler's group used mouse stem cells to form special cells called astrocytes, which normally help provide a supportive scaffold for other nerve cells. The Northwestern team made new astrocytes that were genetically modified to produce laminin, a protein thought to foster the growth of nerve cells.
By injecting the modified astrocytes and other growth factors at the site of an injury, the researchers hope to overcome the damaged spinal cord's resistance to nerve growth. Neurons that were there all along could then grow through the injured part of the spinal cord and establish new connections with muscles.
Even if successful, any applications of the technique for human patients are many years away, Kessler said. The first step this year will be to inject the modified mouse stem cells into mice with laboratory-induced spine injuries.
The Northwestern lab has embarked on several other new spinal cord projects. One team will attempt to promote the growth of nerve cells through spinal tissue using a special gel as a kind of tunnel for the cells to follow.
The human embryonic stem cells that Kessler has ordered from Wisconsin are part of an effort to make new stem cells with genes taken from adults. If successful, such an approach could allow researchers to genetically tailor stem cell treatments for individual patients. The technique could also provide an alternative to therapeutic cloning, a controversial method that would take stem cells from a patient's own cloned embryo.
Amount of research lacking
Despite progress in the last year, many researchers are concerned about work that is not being done. Some link the slow pace of applications for federal stem cell grants to Bush's decision limiting the number of cell colonies that are eligible for funding.
"If you make it so difficult to do the research, maybe it's not surprising if the best and brightest young researchers think twice before entering that field," said Harvard's Melton.
Yet Melton and other experts also point to the fact that few labs have gained the experience necessary to work with human embryonic stem cells. Such cells were discovered only in 1998 by researchers at Wisconsin and Johns Hopkins, who are slowly teaching other scientists how to grow the cells and use them in experiments.
"You can only get approved (for federal grants) if they think you have the wherewithal to grow the cells," said Catherine Verfaille, director of the stem cell institute at the University of Minnesota. Verfaille's lab recently received a supplemental federal grant of about $50,000 to compare adult and embryonic stem cells.
Questions also have persisted about the number of stem cell lines--groups of genetically identical cells--that are eligible for federal funding. Bush's secretary of Health and Human Services, Tommy Thompson, stated in a newspaper opinion piece earlier this month that, "Seventy-eight embryonic stem cell lines exist that meet the president's criteria for research, more than we originally thought would be eligible."
Some scientists believe that figure is an exaggeration.
"I like Thompson, but I don't understand why he goes around saying there are 78 stem cell lines," said Melton. "I don't think it's true. My sense is there are close to 10 lines that one can get."
Rising to challenge
The hope for new treatments has lost some of its urgency for Allison Kessler, now 17, who will begin her senior year at Choate Rosemary Hall prep school in Connecticut this fall.
She still deals with occasional anger about her injury and the unexpected challenges of life in a wheelchair--"I've noticed curbs I never knew were there," she said.
But far from driving Allison out of sports, the accident merely changed her choice of activities. She tried her hand at golf with an adaptive chair, played tennis, went snorkeling, and even did some water skiing. Last year she became coxswain of Choate's varsity crew team, steering and shouting out directions for the oarsmen rowing the boat.
"I'm loud, and I can tell people what to do," Allison said with a shrug. "I didn't want to sit around and do nothing."
Allison said she got her best grades ever at Choate last year, even as she worked on physical therapy enabling her to use leg braces for walking.
"Before, I paid more attention to going out and hanging out with my friends," Allison said.
Allison and her father said they know it could be decades before stem cell research yields any useful treatment for spinal cord injury. But they both harbor the same hope--that somehow, the advance of science will allow Allison to walk with her children, and that her father will see that happen.
"I'd like that time to be as soon as possible, but I'm realistic," Jack Kessler said. "You don't go in believing you'll take a scourge of humanity and get it fixed right away. It's not going to be one single step."
Allison said she feels at times that her father intentionally doesn't tell her about progress in his field, to avoid getting her hopes up.
"He should know I know better," she said.
As he searches for a treatment, Kessler said watching his daughter's resolve in recovering from her injury has added to his own determination.
"I always loved her more than anything," Kessler said. "But I guess I never really knew how strong she was. I'm sorry I had to find out this way."
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