BOSTON - Again and again, Dr. Evan Snyder checks a big nitrogen-cooled freezer in his lab at Children's Hospital, as anxious about its smooth operation as he might be about an ailing child.
I've even driven halfway home, turned around and come back,'' he admits, just to make certain the unit is humming along as it should, chilling its contents to exactly 220 degrees below zero Fahrenheit.
Call him obsessive. Snyder, laughing at himself, agrees.
But keep in mind that the freezer contains the stuff of a medical revolution in treating everything from Alzheimer's and Parkinson's disease to strokes and spinal-cord injuries.
Snyder lifted the freezer's lid recently to reveal hundreds of small vials containing clumps of brain cells, frozen in suspended animation. These are neural stem cells - immature, generic brain cells that can develop into any of the highly specialized cells that make the brain work.
Snyder was the first to isolate and grow these stem cells in the lab about a decade ago, and, since then, he has rocketed to prominence on the hope of using them to heal a wide range of presently incurable brain disorders.
Now, for the first time ever, the traditional view of the brain as an organ where, after maturity, damaged or dead cells cannot be replaced may be tottering. And the neural stem cells are acting as the battering ram.
Stem-cell biology is enormously exciting right now and holds promise for really novel therapies - not just symptomatic therapies, but maybe cures,'' says Dr. Gerald Fischbach, director of the National Institute of Neurological Disorders and Stroke.
Snyder is even bolder, predicting the first human trials of stem-cell therapy may be only a year or two away, based on the rapid progress in lab animals.
Before the decade is out,'' he said, ``there will be some therapeutic benefits'' from treating disease with neural stem cells. Parkinson's disease, caused by the death of brain cells in a certain region, might be one of the first targets for stem-cell treatment, he said; another is Lou Gehrig's disease, or amyotrophic lateral sclerosis, because it kills so quickly and there's no treatment.
For the victims of incurable brain diseases and their loved ones, Snyder is a beacon of hope, an optimist in the face of some of the cruelest afflictions known to humanity. His optimism and openness to new ways of conducting research has made him a magnet for support and advocacy groups for diseases from ataxia-telangietasia, or A-T, to the rare Canavan syndrome.
Scientists like Evan Snyder are like first-round draft picks: Every disease group wants to get their hands on someone like this,'' said Brad Margus, founder of the Florida-based A-T Children's Project.
Margus has two sons increasingly disabled by A-T, whose victims lose control over their body beginning at a young age and are highly susceptible to cancer. That Snyder is both a pediatrician and a lab researcher ``means a lot to me,'' Margus said, because he has both compassion for his patients and the skills to do cutting-edge research.
We often have a dilemma with a medical doctor who has noble reasons for being in medicine but doesn't understand the research process, or a PhD who gets turned on by working at the lab bench, but can't seem to remember that these are people they're dealing with,'' Margus said.
The excitement about Snyder's work is fueled in part by neural stem cells' astonishing ability to migrate through the brain, homing in on nerves that have been damaged and transforming themselves into specialized nerve cells of the appropriate type.
Somehow, the damage is sending out cries for help - `We need neurons now!' - and the stem cell can become a neuron'' and send out new ``wiring'' that makes the right connections to repair damage, Snyder said.
I have a lot of admiration for Evan,'' said Dr. Paul Sanberg, chairman of neuroscience at the University of South Florida who also does neural transplantation. ``He has started to focus on ALS and Parkinson's diseases, but his real love is these rare disorders in kids and preemies.''
In the most dramatic animal experiment, Snyder implanted neural stem cells into the brain of the mutant ``shiverer mouse,'' a lab creation afflicted with continuous, severe tremors. Snyder found that the implanted cells repaired the damage and eased the mouse's shivering. More recently, he's moved some of the stem-cell work into monkeys, since they more closely resemble humans.
The notion that you can place (neural stem) cells in the nervous system and have them take on the characteristics dictated by the local environment is really revolutionary,'' said Fischbach of the National Institute of Neurological Disorders and Stroke.
The next big push, already underway, is to identify the signals that call the cells to damaged areas, and try to duplicate them with drugs.
Snyder and other scientists also are exploring a strategy for treating inoperable brain tumors by inserting toxic genes into neural stem cells that would deliver the genes to the tumor and its spreading tentacles, like a suicide bomber. What's hoped for is that the gene-carrying stem cells can follow the same pathways the tumor cells take as they weave their way inextricably into the brain.
That goal is a very personal one for Snyder. A close friend of his died from a brain tumor in his 40s, and Snyder vowed to find a way of attacking tumors with his stem cells. He's reminded of this pledge whenever he attends formal functions - his tuxedo used to be that of his friend.
As the excitement about this new attack on brain diseases ripples through the medical field and into public awareness, Snyder, a pediatrician and neurologist at Children's Hospital and Harvard Medical School, is increasingly in the limelight.
As a result, he's in nearly perpetual motion. Flying here and there, he caroms from one scientific meeting to another, writes papers, supervises his laboratory and keeps in touch with myriad scientists with whom he's collaborating.
Besides being a coveted speaker at scientific meetings - he's given more than 35 such talks so far this year - Snyder is much in demand by the media. Engaging and possessing a boyish, telegenic presence, he's recently been on the ``Today'' show, National Public Radio, local television and innumerable print stories on the new frontier in brain science.
Snyder's method for isolating and growing neural stem cells is licensed to Layton Bioscience Inc. of Atherton, Calif., which plans to develop stem-cell treatments. But, despite the potential for profit, Snyder is not a wealth-seeking entrepreneur, said Gary Snable, the chief executive officer at Layton.
He's tremendously dedicated to solving some of the childhood disorders, but he has no interest whatsoever'' in the business part of it, Snable said.
The A-T Children's project and several other disease groups have been funding Snyder directly - bypassing the federal system of research grants - to expand his team to focus on the rare diseases. As a result, he said, ``We're progressing at a pace that is every scientist's dream, but it's very important not to sacrifice our scientific integrity'' in the rush toward a cure.
Nor can the research move into humans before the safety of stem cells is known. ``Can these things be controlled once they're implanted?'' Fischbach asked.
In addition, the Food and Drug Administration will want assurance that the versatile cells won't produce cancers, and that the cells can be produced with consistent quality control.
Fortunately for Snyder, his neural stem cell research doesn't carry the ethical baggage of embryonic stem cell research because the nerve cells don't have to be harvested from human embryos. Snyder's cells were taken originally from a fetus that was aborted for other reasons several years ago. Now that the cells can be maintained and their numbers increased in the lab, he said he doesn't need to use any more fetal material.
Lately, Snyder has been feeling a need to rest a bit from the frantic pace of his work. In the past, he said, he hasn't really taken vacations. Instead, he'd bring his wife along to scenic or luxurious places he'd been invited to speak.
But Snyder said she's wearied of waiting while he spends most of the time talking shop with other researchers, and he's turning over a new leaf.
We're going to take a real vacation this summer,'' he said.
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