Stem-Cell Research: The Quest Resumes

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Even during the dark days of the Bush Administration's stem-cell restrictions, Melton helped keep the field going, culturing cells and getting them into labs.

Gregory Heisler for TIME

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Scientific inspiration can come from anywhere — a person, an event, even an experiment gone awry. But perhaps nothing can drive innovation more powerfully than the passion born of tragedy. Or, in Douglas Melton's case, near tragedy. The co-director of the Harvard Stem Cell Institute (HSCI) is one of the leading figures in the search for cures for presently incurable diseases, and his breakthrough work is challenging many long-held beliefs about the ways biology and human development work.

But it was a very personal experience that brought Melton to stem cells, one that 17 years later he still finds difficult to discuss. When his son Sam was 6 months old, he became ill with what his parents thought was a cold. He woke up with projectile vomiting and before long began taking short, shallow breaths. After several hours, he started to turn gray, and Melton and his wife Gail brought the baby to the emergency room. For the rest of that afternoon, doctors performed test after test, trying to figure out what was wrong. "It was a horrific day," says Melton. (See the top 10 medical breakthroughs of 2008.)

It was not until that evening that a nurse thought to dip a testing strip into Sam's urine and they finally got a diagnosis. The boy's body was flooded with sugar; he had Type 1 diabetes. Then, as now, the disease had no cure, and patients like Sam need to perform for themselves the duties their pancreas cannot — keeping track of how much glucose they consume and relying on an insulin pump to break down the sugars when their levels climb too high. The diagnosis changed not only Sam's life but the lives of his parents and older sister Emma as well. Throughout Sam's childhood, Gail would wake every few hours during the night to check his blood sugar and feed him sugar if his concentration fell too low or give him insulin if it was too high. "I thought, This is no way to live," says Melton. "I decided I was not just going to sit around. I decided I was going to do something."

Trained as a molecular biologist in amphibian development, Melton began the work he pursues today: trying to find a way to make insulin-producing cells by using stem cells. "It was a courageous thing to do because he was at the pinnacle of his career," says Gail. "He brought home textbooks on the pancreas to figure it all out." Nearly two decades later, Melton is convinced that stem cells will be a critical part of new therapies that will treat and maybe cure not only diabetes but also other diseases for which there are no answers today.

Melton's confidence is testament to the extraordinary advances in stem-cell science, some of which have brought the promise of breakthrough therapies for conditions like diabetes, Parkinson's and heart disease closer than ever before. The cells filling petri dishes in freezers and incubators in Melton's lab and others around the world are so vastly different — in provenance, programming and potential — from the stem cells of just two years ago that even the scientists leading this biological revolution marvel at the pace at which they are learning, and in some cases relearning, rules of development. Until recently, the field has revolved around either embryonic stem cells — a remarkably plastic class of cells extracted from an embryo that could turn into any of the body's 200 tissue types — or their more restricted adult cousins, cells taken from mature organs or skin that were limited to becoming only specific types of tissue. On Jan. 23, after nearly a decade of preparation, the Food and Drug Administration approved the first trial of an embryonic- stem-cell therapy for a handful of patients paralyzed by spinal-cord injuries.

But today the field encompasses far more than just embryonic and adult stem cells; it has expanded into the broader field of regenerative medicine, and Melton's lab at Harvard is at the vanguard, bringing the newest type of stem cells, which do not rely on embryos at all, closer to the clinic, where patients will actually benefit. Last summer, Melton stunned the scientific community with yet another twist, finding a way to generate new populations of cells by reprogramming one type of fully mature cell so it simply became another, bypassing stem cells altogether. "If I were in high school, I can't imagine anything more interesting than stem cells," says Melton. "This is so cool. It's so amazing that cells in the body have this potential that we can now unlock by asking question after question."

A Battle Joined
That hidden power in each of us did not become obvious until 1963, when Canadian researchers Ernest McCulloch and James Till first proved the existence of stem cells, in the blood. These cells possess the ability to divide and create progeny — some of which will eventually expire, others that are self-renewing. The pair irradiated mice, destroying their immune cells. They then injected versatile bone-marrow cells into the animals' spleens and were surprised to see a ball of cells grow from each injection site. Each mass turned out to have emerged from a single stem cell, which in turn generated new blood cells.

That discovery led, 35 years later, to James Thomson's isolation of the first human embryonic stem cells, at the University of Wisconsin in 1998. And that milestone in turn inspired researchers to think about directing these cellular blank slates to eventually replace cells that had been damaged or were depleted by disease. The key lay in finding just the right recipe of growth factors and nutrients to induce a stem cell to become a heart cell, a neuron, an insulin-making cell or something else. It would take decades, the researchers all knew, but new therapies were sure to come.

Then, in 2001, everything changed. The use of discarded embryos made embryonic-stem-cell research deeply controversial in the U.S. Citing moral concerns, then President Bush restricted federal funding for the study of human embryonic stem cells. Under the new policy, U.S. government funds could be used only to study the dozens of embryonic cell lines already in existence — many of which proved not to be viable.

Read Stem Cells: The Hope and The Hype.

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