Local News : Monday, August 20, 2001
By Warren King
Seattle Times staff reporter
She reads voraciously. She adores animals, especially her cat Oreo. She plays, swims and laughs with her sister, Sydney, and a happy gaggle of friends. Yet five years ago, Savannah Jantsch's parents feared she would not last more than a few months.
Struggling with leukemia and a rare blood disorder, Savannah became one of the early recipients of stem cells from the umbilical-cord blood of a newborn. Infused in her body, the cells soon built an entirely new blood-cell system for the Bellingham girl, now a bright-eyed 9-year-old.
"It's a resource that has given our daughter a whole new life," her father, Jeff Jantsch, said last week. "It's like she's been two different people with different lifestyles and a different existence."
Savannah Jantsch is living proof of the healing power of stem cells, one of the basic building blocks of human tissue and the focus of so many headlines in recent weeks.
Eleven days ago, President Bush announced support for limited funding of research on embryonic stem cells, bridging a controversy over the ethics of tampering with the earliest stage of human development, the embryo. In an attempt to balance scientific progress with sometimes competing moral values, he approved federal funding only for research on cells already taken from embryos; no new embryos could be destroyed.
Savannah's treatment for leukemia at the Fred Hutchinson Cancer Research Center did not involve embryonic stem cells. She received "adult" stem cells.
Adult cells descend directly from the multipotential, "blank-slate" cells. They are the specialized forebears of cells ranging from bone, to muscle, to all sorts of other tissue.
For Savannah, they produced the blood cells to fight her cancer and other blood disorder.
By any measure, Savannah's was a monumental fight from birth, when worried doctors gave the newborn an immediate transfusion. Physicians predicted her life would be short.
"It was horrible," said Julie Jantsch, Savannah's mother. "When a child is born, you have all these dreams for the future. You love her, but you know you're going to lose her. ... "
The Jantsches tried to make whatever time their daughter had as normal as possible. Savannah went to school and on family trips to see her grandmother in Wisconsin. She had friends and did what most kids do.
But she also spent days or weeks in the hospital six or seven times a year.
Savannah was born unable to make platelets, crucial blood cells that help clot blood and heal injuries. She needed frequent transfusions, but doctors said she eventually would reject the donated platelets and die.
She also did not make enough of a certain immune cell. And at age 5, she developed leukemia, a blood cancer.
Doctors decided her best chance was a transplant of stem cells contained in a newborn's umbilical cord.
Mothers donate the cord blood anonymously to banks around the country, including one at the Puget Sound Blood Center in Seattle. Rich in stem cells, the blood is stored for use in a variety of cancers.
Savannah first received massive chemotherapy to destroy her diseased cells. Then she received the life-giving stem cells in cord blood from a New York City blood bank at 2 p.m. Nov. 26, 1997. Julie Jantsch remembers with a smile how the blood ran through an intravenous line in Savannah's chest.
"It was about three tablespoons of this beautiful, raspberry nectar," said Jantsch. "It only took about 20 minutes."
A moral dilemma
The recent news has centered on embryonic stem cells, prompting abortion-like debates about the starting point of life.
Many scientists think embryonic cells, which theoretically can be coaxed into producing any cell type, hold the most promise to treat illness. That promise conflicts with moral arguments that harvesting embryos is destroying life.
Some scientists believe the debate may be unnecessary. They think adult stem cells, which are further along in specialization than the embryonic cells, can be converted from one specialty to another, and thus may have as much potential.
For example, laboratory experiments in recent years — almost all with mouse or rat cells — have shown that skin stem cells can be converted to produce muscle or fat stem cells, blood stem cells can be changed to produce liver or heart cells, fat stem cells can be morphed to muscle, bone and cartilage cells.
But skeptics say those early successes may be deceptive.
"You certainly can't take all the lessons we've learned from the mouse and jump to man," said Dr. Beverly Torok-Storb, a Hutchinson Center scientist.
Rodent stem cells, for example, must produce only a tiny fraction of the tissue cells that human stem cells produce. Further, some scientists speculate that mice and humans have the same baseline number of stem cells; that means human cells must work harder to produce enough tissue cells. At the same time, Torok-Storb said, the near-promise of embryonic stem cells has been overstated.
Scientists have shown they can be mixed with growth factors to produce brain cells, heart cells, insulin-producing cells, muscle cells and several other types of tissue cells. But no one knows how to control which cells they make and in what quantity.
"People get false hopes, and the whole research field suffers," Torok-Storb said. "I'm not saying (promising therapies) won't happen. But they won't happen tomorrow."
All the more reason, she said, that research proceed on both embryonic and adult stem cells so that scientists can better understand the potentials of each. Adult stem cells already have a significant track record in one cancer type. As the workhorses of bone-marrow transplants — they are embedded in the bone marrow — they have been used for more than 30 years to treat several different types of leukemia and aplastic anemia.
In recent years, bone-marrow transplants have been increasingly replaced by so-called stem-cell transplants: The patient's stem cells are extracted, next the diseased blood cells are destroyed with chemotherapy or radiation. Then the patient's own stem cells or the matched stem cells of a donor are infused in the patient. The technique also has been used for breast cancer and, more recently, for multiple sclerosis, scleroderma and lupus, all diseases in which the body inexplicably is attacked by its own immune system.
Susan Stross knows all too well the results of an immune system gone awry. At 36, she has lived 17 years with multiple sclerosis, in which immune cells attack the myelin, or insulation, that surrounds nerve cells. Three years ago, she underwent one of the early, experimental stem-cell transplants for the disease at the Hutchinson Center.
No one expected the transplant would improve Stross' condition. The greatest hope was that it would stop the relentless progression of disability.
Before the transplant, Stross needed a wheelchair, suffered severe fatigue and had limited use of her right hand. A former language teacher and record-setting swimmer, she despaired of an even bleaker future.
The transplant has mostly kept her condition stable, and even helped a little.
"About this time of the afternoon before the transplant, I would have bowling-ball head... I just couldn't hold it up. But look, the ball is not here," a smiling, talkative Stross said in her comfortable Capitol Hill condo.
She can sometimes stand, with support, for as long as an hour. She has the energy to assist as caregivers move her out of her wheelchair. A weekend trip to the Oregon beach went smoothly with help only from her mother.
Stross still needs an attendant several hours a day. Her right hand doesn't work very well. But she's grateful: "Generally, I say damn, not bad."
Dr. Richard Nash, Stross' transplant physician, has found similar results in most of 25 other patients that have had the procedure at The Hutch.
Three have declined in health and one died; the rest have held steady or had slight improvements.
Overall, about the same results have been reported in several hundred patients worldwide, including about 40 others in the United States, Nash said.
Multiple sclerosis is one of the more visible targets of recent research on adult stem cells. The Hutch also is considering stem-cell transplants for prostate and kidney cancers.
Nearly 40 projects at UW
University of Washington scientists have 38 projects under way involving adult or embryonic stem cells, virtually all of them in laboratory animals, said Dr. Albert Berger, associate dean of research at the School of Medicine.
Berger said no UW scientists are currently using human embryonic stem cells in research. But he expects scientists nationwide soon to propose projects involving the 60 lines of embryonic stem cells Bush approved for research.
"If we're going to use embryonic stem cells for human disease, it's important to work with human stem cells," Berger said.
Adult stem-cell research under way at the UW includes virtually every area of the body and a variety of diseases. A sampling:
• The heart. Once damaged, heart muscles can't repair themselves. UW scientists are trying to coax human muscle stem cells, which can regenerate themselves, into becoming heart cells, which would be grown into tissue "patches" for disabled hearts.
They're also building tissue scaffolds to allow the tissue to grow in three dimensions and include blood vessels. Dr. Buddy Ratner, director of the UW Engineered Biomaterials Center, said researchers have induced mouse adult muscle stem cells and embryonic cells to become heart cells. The scientists now are considering trying the technique with approved human embryonic cells.
• Fetal blood diseases. Such diseases often kill the fetus. Alpha thalassemia, for example, prevents the fetus from receiving oxygen from red cells. Using ultrasound and tiny needles, scientists have successfully injected stem cells into monkey fetuses that reproduce and appear in bone marrow after the monkey is born. Researchers believe the new cells could replace diseased blood cells.
Dr. Laurence Shields, director of the project, hopes the technique can be tested in human trials within five years.
• The eye. Cells of the human retina cannot regenerate. Damage caused by macular degeneration, diabetes and glaucoma often causes blindness. Scientists have learned a lot from birds, fish and frogs, all of which can regrow retinal cells from stem cells. They have located key stem cells along the margins of those animals' retinas and grown them in culture. They've coaxed stem cells near the iris into becoming retinal cells. And now they're exploring treating the retina directly with growth factors, without removing the cells.
"We're pushing regeneration of part of the nervous system, basically," said Dr. Tom Reh, director of the studies.
• Gene therapy. Researchers are trying to induce blood stem cells to become other specialized cells, such as liver stem cells, then control their growth. To do this, they insert a "growth-switch" gene into the blood cells that cause them and the subsequent liver cells to grow in response to a drug. Take away the drug and the growth stops.
A preliminary version of the technique has worked in mice and research is continuing in dogs. Scientists hope it could be used to replace tissue, such as liver damaged by hepatitis or cirrhosis, said Dr. Tony Blau, project director and an expert in stem-cell biology.
Warren King can be reached at 206-464-2247, or at email@example.com.
Copyright © 2001 The Seattle Times Company