The Stem Cell Hope
How Stem Cell Medicine Can Change Our Lives
A landmark book by the senior science writer at Time magazine introduces us to a medical breakthrough that can save our lives. Few people know much about stem cell research beyond the ethical questions raised by using embryos. But in the last decade, stem cell research has made huge advances toward eliminating some of our most intractable diseases. Now this sweeping and accessible book introduces us to this cutting-edge science that will revolutionize medicine and change the way we think about and treat disease. Alice Park takes us from stem cell's controversial beginnings to the recent electrifying promise of being able to create the versatile cells without using embryos at all. She shows us how stem cells give researchers an unprecedented ability to study disease while giving patients the promise of replacing diseased cells with healthy new ones. And she profiles the scientists and leaders-many with their own compelling stories-who have fueled the quest and will continue to shape the field in years to come.
Sam Melton was not a happy baby. For several days, the six-month-old's tiny body had been trying to tell himand his parentsthat something wasn't quite right. A generally healthy and easygoing infant, he had taken to lying listless in his crib, barely acknowledging his mother, father, or older sister when they tried to play with him or pick him up. Even more disturbing, he had stopped making eye contact with them, and a worrying red rash had bloomed across his bottom. He wasn't eating as much, but it was winter, in Boston. It was probably just a cold, his parents thought.
On this morning, something was different. After waging a frustrating battle with his own body for days, Sam had finally had enough.
He started to vomit. Or, more accurately, projectile vomit, shooting what little remained in his stomach straight across the room. Alarmed, his mother, Gail O'Keefe, immediately called the pediatrician. Hearing the symptoms, he wanted to make sure Sam wasn't getting dehydrated, so he suggested Pedialyte. Still flustered, O'Keefe realized after hanging up the phone that she had forgotten to mention another of Sam's symptoms: His breathing was getting faster and faster, as if he were gasping for air. But she gave him a spoonful of the medicine and started rocking him in her arms.
By midday, though, the syrup hadn't had much effect. Sam's complexion, normally a glowing, rosy pink, had darkened to a sickly gray. Nestled in his mother's arms, he hadn't kicked or stretched or fidgeted as he normally would. And try as she might, she couldn't get him to nurse. "I got really nervous," she says, "so I called the doctor again, and said I forgot to tell him about his respiratory rate." Unwilling to wait any longer, she also phoned her husband, Douglas Melton, and told him she was taking Sam to the doctor. She asked a friend to watch over her daughter, Emma, and rushed to the pediatrician's office. When they arrived, the doctor took one look at the baby and instructed O'Keefe to take her son to the emergency roomimmediately. His nurse, who had overseen Sam's pediatric visits since he was born, started to cry; she wasn't sure the baby would make it.
Melton met his wife and son at Children's Hospital Boston, one of the leading pediatric medical institutes in the country. Not knowing what was wrong with Sam, doctors launched a series of tests that would stretch the Meltons' growing anxiety well into the early evening. Blood tests, some poking and prodding, and more poking and prodding provided no answers. Was it a gut issue? Something Sam had eaten? A reaction to something he had touched? Complications from the flu? At one point, they gave the baby a barium enema to clear his digestive tract, suspecting that he had a blockage in his intestine. It was their best guess as to what was ailing the six-month-old, given that he had been vomiting a few hours before.
But the enema was clear, and the emergency team moved on to ever scarier possibilities. The situation was getting more and more desperateSam remained lethargic, and O'Keefe and Melton were frantic that their baby son might not survive the day. "He was about to expire," says Melton, who two decades later still finds the events of that day difficult to discuss. The very life seemed to be seeping out of Sam. There was talk about doing a spinal tap to rule out meningitis, but like all the other tests they had been performing over the course of eight hours, it was only a guess. Time was running out.
And then it happened. Sam's ailing body mustered one final cry for help. He was losing the fight, and there was only one way that his cells could get the help they needed.
Lying on the examination table, Sam relieved himself in a puddle that proved far more informative than any of the high-tech tests he had endured that day. As a liquid deposit for the by-products of the body's metabolism, urine generally carries waste without much diagnostic value. But because it concentrates the body's biochemical castaways, it can also serve as an indicator of what is off balance. And in Sam's case, it was his pancreas. Rather than simply wiping the puddle away, a nurse noticed that the urine smelled sweet and decided to stick a test strip into the mess on the tablejust in case. What she found changed the Meltons' livesand quite possibly the course of stem cell science.
Sam's urine was full of ketones. For hours, and possibly days, his body had come dangerously close to shutting down in a desperate and ultimately futile search for the insulin that it needed to keep all of his metabolic functions going. When his cells couldn't find any, his body began burning up its own fat stores and releasing the acidic ketones as a by-product. It wasn't that he hadn't been fedhe had. But his body was starving. He was consuming glucose but his pancreas wasn't making enough insulin to break it down from the milk he was drinking.
Sam was diabetic.
In retrospect, it's such an obvious diagnosis, and the doctors at a leading children's hospital might have considered the possibility that Sam was suffering from the buildup of ketones in his blood much sooner. But diabetes doesn't normally show up in infants so young. In fact, at the time, Sam was the youngest baby on record diagnosed with the disease in the hospital's 122-year history.
Once the diagnosis was confirmed, the medical team acted fast. Nurses inserted an IV with insulin into his tiny arm, and, says O'Keefe, "Within twenty-four hours, in intensive care, he was on his hands and knees, and he was nursing. He was a baby again. It was just the most amazing thing in the worlda little insulin. It was an incredibly dramatic presentation of this disease that we knew nothing about."
But she and her husband quickly learned. The diagnosis certainly gave Sam a very different life from the one his parents had envisioned. He would always be dependent on outside sources of insulin hormone to compensate for what his body could not make. He would have to keep careful track of what he ate and how much energy he expended, to make sure his body was getting the right amount of glucose at the right time.
The diagnosis changed Melton's and O'Keefe's lives as well. Melton had been trained as a biologist, and while he was a scientist, not a physician, he knew what lay ahead for his baby son: years of constant finger pricks to check the sugar in his blood, and repeated insulin shots to mop up the excess that his body could no longer process.
O'Keefe became, in essence, her son's pancreas, developing almost a sixth sense for when he needed more insulinin the middle of the night, or after an exhausting afternoon of soccer practiceor for when his insulin levels had climbed too high and he needed a candy bar to soak up the overflow.
The week that Sam was diagnosed, Melton put his research duties in the lab on hold and stayed home with his wife, daughter, and son. Those days following Sam's diagnosis, he says, were a "horrific time, not one I like to remember." A professor in developmental biology at Harvard University, Melton was already well known and respected for his work on early amphibian development. Frog embryology, not human development, was his specialty. But after Sam returned home from the hospital, Melton was haunted by the constant blood checks and insulin injections in Sam's future. In his worst moments, he confronted the possibility that even with the most vigilant care, Sam could have severe health problems as he reached adolescence and adulthood. He knew that a bottomed-out blood sugar could lead to blackouts, organ failure, even blindness or amputations. He considered all of this and came to a realization. "I was not just going to sit around," he tells me as he relives that painful day as we talk in his office on the Harvard campus. "I was going to do something."
If a cure didn't exist for type 1 diabetics like Sam, Melton and O'Keefe decided, then Melton would find one. Or at least try.
As radically different as amphibians are from humans, Melton's shift wasn't as preposterous as it initially seemed. Both involved a similar appreciation for the intricate choreography of development, an understanding of what drives a cell to turn on certain genes and turn off others as it maps out its fate. Compared to the changes his son would face, Melton determined, the career turnaround was not such a sacrifice.
In type 1 diabetics, the beta cells, the specialized factories in the pancreas designed to dole out insulin in response to glucose levels in the blood, no longer function. It's still not clear why, but the leading hypothesis is that the body's own immune forces somehow see these cells as foreign, and launch an all-out attack on the unsuspecting tissue. Without a built-in way of distributing insulin when it's needed, type 1 diabetics need to provide the hormone from an outside source and, for all intents and purposes, find a substitute for their pancreas.
Sam would spend the rest of his life looking at food in a special way. Every bite would be a calculation, a mental tally of calories and glucose content that would need to be counteracted with a shot of insulin. An insulin pumpa device inserted just under the skin in the abdomen, hips, or thigh that delivers insulin continuouslycan make the delivery easier, but as smart as the machine is, it still cannot calculate, as a normal pancreas does, when and how much insulin a diabetic needs at any given time. So it's still up to the wearer to decide when, and what dose, to dispense.
It wasn't a future that Melton could simply accept for his son. "I had the facility to do something about it. I was trained so that I could change my career path." So, he says, he gave up working on something he was familiar with and decided instead to take on something he knew nothing about. He then quickly counters any suggestion that his decision was a heroic or even exceptional act. "Remember the larger context. I was a tenured professor at one of the nation's best universities. I was a Howard Hughes Medical Institute investigator," he says. "If I couldn't take the risk, who could? And it's not like I switched from being a reporter to be a nuclear physicist. I was working on how animals develop, using frogs, and I switched to work on how mammals make a pancreas."
While there is ample literature on the anatomy of the pancreasO'Keefe recalls her husband lugging home probably every textbook on the organ from the medical school librarythere is precious little on its development, much less specifics on generating the different types of pancreatic cells. Melton, it appeared, had quite a mountain to climb.
But returning home every day, he was reminded of why he was making the journey. As a frog biologist, Melton was a scientist who happened to be a father. When he returned to the lab after his week's hiatus, he was a father who happened to be a scientist. And as a father, he explained in an emotional meeting with his lab members, he was redirecting his research focus away from amphibians and toward the human pancreas. His lab now had a mission, and that mission was to find a cure for diabetes. To find a cure for Sam.
It was the week after the most stunning and tragic terrorist attack on the United States, and like most American families, the Kleins, though still stunned, were attempting to reestablish the rhythm of their lives. Robert Klein, a successful real estate developer in Northern California, had watched the horrifying events of 9/11 unfold on television from Europe, where he was traveling with his daughter on a long-promised trip to celebrate her high school graduation.
Back home in Portola Valley, his youngest son, Jordan, was starting seventh grade at a new middle school. Anxious, excited, apprehensive, and expectant, the eleven-year-old hadn't been feeling quite right. He was losing weight, and inexplicably experienced intense stomach pains that would suck the breath right out of him. His mother noticed that he was also drinking copious amounts of water and going to the bathroom constantly. She recognized the symptoms, which she'd seen in one of Jordan's friends who had been recently diagnosed with diabetes, and she suspected that her son, too, might have the metabolic disorder. But it was too difficult a reality to face quite yet. Maybe Jordan was just nervous about the new school, and the stress was triggering his headaches and stomachaches and fueling his frequent trips to the bathroom. Maybe.
It didn't take long for her suspicions to be confirmed. Sitting in an English class and trying hard to pay attention, Jordan was seized by a breath-robbing punch of pain that knocked him off his chair. With his entire body on fire, feeling as if all of his blood had turned instantaneously into caustic battery acid, Jordan saw nothing but black.
His mother rushed to the school and took him to the hospital. After a series of tests, the doctors told her what had been ailing Jordan.
Klein had been calling in every day from overseas to check in, and was completely unprepared for what his wife told him after the harrowing trip to the hospital. "We know what's wrong with Jordan," she said to her husband over the phone. "He has juvenile diabetes."
The next thing Klein heard over the receiver was a chilling screama raw, wrenching outburst that left him feeling as if he'd been physically struck in the gut.
It was Jordan.
His mother had planned on discussing the diagnosis first with his father before breaking the news to him, so had spared her son the news initially. She had not realized that he was listening.
"He screamed one of those uncontrolled kind of primitive screams that… represents total fear, as if something was going to destroy you in the middle of the night," Klein tells me, taking long pauses as he struggles to contain the painful memories our conversation brings up. "If you can imagine the worst fear of your life… and you hear… this was a primitive scream of terror. He was terrified that his life was being taken away from him. Because he knew what the disease could do."
Unlike Sam, who was only six months old at his diagnosis, Jordan was fully aware of what juvenile diabetes, or type 1 diabetes, could do. For years, he had watched a Cub Scout friend deal with the disease. He knew all about the insulin injections that kept his friend alive, as well as the myriad potential dangers looming in his buddy's futurethe threat that the ever-undulating levels of glucose posed to his kidneys, his heart, his eyesight, even his arms, legs, fingers, and toes as they began to compromise his body's ability to circulate blood and nutrients to his limbs. Jordan was well aware of all of this because he and his father had talked about it.
But now it was happening to him. That future of potential kidney damage, blindness, even amputation was no longer someone else's to worry about. It was his. And suddenly everything was different.
Five thousand miles away, Klein could not hug his son, could not provide a shoulder to lean on or the physically soothing presence that only a parent can give a child. He had only his voice. "I think I said to him… I'll be there for you," Klein says, tears beginning to well in his eyes. "We'll get through this together."
Getting to his son, however, would prove to be a problem. For days, air traffic into the United States had been completely shut down, and still, a week later, flights were booked to capacity as airlines struggled to accommodate the pent-up demand and scrambled to implement new security measures. For two days, Klein worked the phones from his hotel, desperate to find a way to reach his son before the following week, when he and his daughter had originally been scheduled to leave. When that failed, he turned to research. If he couldn't physically be there for Jordan, he would become his son's ultimate source for all things diabetes. Over the next week, he nearly wore out the fax machine at the hotel, tallying up about a thousand dollars in fees when his office beamed over as many pages from books on the disease as they could. Hungry for any information that might help Jordan, Klein read them all. At the time, those textbook sources still did not contain any mention of stem cells and how they might be used to treat or even cure diabetes; the science was still too new.
Klein had yet to fully appreciate stem cells, either for their scientific potential in alleviating diseases such as diabetes or for the formidable political challenges they raised. But it wouldn't take long. Joining the Juvenile Diabetes Research Foundation (JDRF) as a board member, he could hardly miss the growing excitement over the mother of all cells. These cells, many scientists were telling the foundation's members, could finally break the back of diabetes, and crack open the door to a cure. He couldn't help but get caught up in the hope the cells represented. If embryonic stem cells could be grown up and manipulated to form insulin-producing cells, then these cells might be transplanted into patients like Jordan to save them from the tyranny of needles and glucose monitors and the always looming threat of complications.
The scientific challenges to making that happen were certainly daunting, and the person tempering these researchers' enthusiasm more than anyone or anything else was the president of the United States. Just a month before Jordan's diagnosis, George W. Bush had taken the unprecedented step of restricting federal funding of the very embryonic stem cell studies that many scientists were beginning to believe would be critical to finding new therapies for diabetics. Citing concerns over the only available source of the cells at the timehuman embryosBush limited taxpayer support to a small number of stem cell lines already in existence, and prohibited government dollars from funding any new lines. If these cells were to hold a cure for Jordan, Klein knew, there would have to be more lines.
As a successful real estate developer in California's booming housing market, Klein did not possess the scientific skills to push the biological limits of what stem cells could do, as Melton had begun to do nearly a decade before. But he did have the ability to address the challenges facing the field outside of the labin Congress, on the streets, and in the minds of the American people. With the debate over the embryonic origins of the stem cells threatening to overwhelm and suffocate their scientific potential, Klein took on the task of changing the public image of embryonic stem cells. Without government funding of the field, he knew, progress in finding cures for patients like Jordan would slow to a crawl. But convincing legislators to change the restrictive policies would take too long. Researchers needed more lines to fully explore the potential of these cells, and if the federal government wasn't willing to step in and support the work, Klein thought, then perhaps a state legislature could. And what better state than California, with its embodiment of the pioneer spirit and as home to some of the field's most talented stem cell scientists, to forge the way? No state, however, had ever taken on the role of single-handedly financing a biomedical science. Public works projects, yes. Schools and highways and utilities, yes. But backing stem cell research would be an unprecedented challenge, as Klein would find out.
“A tour de force of storytelling.” — Sharon Begley, author of Train Your Mind, Change Your Brain
“Infuses a difficult scientific subject with intrigue, passion, and fun.” — Michael F. Roisen, M.D., coauthor of the YOU series
“Park’s book proves there is truly stem cell hope for all of us, not just hype.” — J. Craig Venter, sequencer of the human genome and author of A Life Decoded
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