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 t’s not just a question of identifying genes and their function – though that’s a critical first step, says neurologist Leslie Weiner. “We’re also talking about how we can correct these conditions and even prevent them.”
A medical utopia? Not quite, but certainly a brave new world of healing.
As Weiner puts it, “How long we live is not the issue. The ultimate goal is to make the quality of life better.” People are living to ripe old age. Their hearts are strong, they look great. But in many cases, they’re demented, he says.
“Why live to 105 if your brain is not functioning? That’s not good for individuals, and it’s not good for the society.”
Diseases like Alzheimer’s, Parkinson’s and stroke are diseases of the aged, he points out, but not necessarily part of the aging process. Rather, he says, “we think they are abnormalities.” Using the new tool kit of genetic medicine, neurologists expect to fix these abnormalities, along with the defects causing epilepsy and Lou Gehrig’s disease.
Stephen J. Ryan
DEAN, KECK SCHOOL OF MEDICINE OF USC
“It’s the right time in the history for Keck and USC to come together. The Keck School of Medicine needs a solid base in private practice and a solid research base with emphasis on strengthening clinical and basic research.”
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In his own research, Weiner will soon beginPhase II trials on a project that could literally represent the difference between life and death for some 300,000 Americans: a vaccine for chronic progressive multiple sclerosis.
He based the vaccine on an ingenious strategy for controlling the runaway immune response that causes this incapacitating disease of the brain and spinal cord. Weiner developed the drug using a genetic theraptechnique. It works in mice, and has shown promise in a small human test group.
Other degenerative diseases will be vulner-able to similar attacks, Weiner believes, if not with his technique, then with other ones like it.
Looking at the same issues from yet another perspective is Martin Weiss, who also will be affiliated with the new institute. Chair of the Keck School’s Department of Neurological Surgery and one of the nation’s top neurosurgeons, he occupies a professorship named after him – the Martin H. Weiss Chair in Neurosurgery – endowed by a grateful member of the USC Board of Trustees after Weiss successfully operated on the trustee’s sister for a brain tumor. Despite surgical successes, Weiss looks to the Neurogenetics Institute to help relieve his biggest professional frustration: the limitations of his craft in treating lesions.
“Malignant brain tumors are currently not curable by any means,” he says flatly. “We now know that virtually every tumor of the central nervous system, both benign and malignant, results from an alteration in the genetic structure of usually a single cell.”
If neurologists could reverse that genetic aberration, they could profoundly alleviate or even cure brain cancers. The trick is to marry existing technologies with an understanding of the molecular biology of malignant brain tumors. “We could then alter the aberrant molecular biology and cure these lesions. This will happen in the next generation,” Weiss promises.
And much of it will happen at USC, in part driven by such representatives of the “next generation” as ophthalmologist Jeannie Chen, a young scientist starting a promising career at a run. Knowledgeable people wonder if she will be the person to find a cure for the now-untreatable progressive blindness known as “retinitis pigmentosa.”
The disease is caused by a breakdown in the system that enables the body to manufacture rhodopsin, a photosensitive substance found in the retina. Rhodopsin’s chemical reaction to incoming light starts the process that leads to retinal nerves firing. These firings send impulses down the optic nerve to the brain, where they are interpreted as images of the outside world.
As an indication of the speed at which research in this field is developing, the first mutation in the rhodopsin gene was discovered 10 years ago. Since then, more than 100 other mutations have been identified.
Chen, an assistant professor at the Keck School’s Doheny Eye Institute, has developed an experimental system in which rhodopsin defects can be studied – and various possible interventions evaluated – on a laboratory slide.
Her technique is of some interest to neurobiologist Cheryl Craft, holder of the Mary D. Allen Chair in Vision Research. Craft studies the internal signals modulated by genes – in other words, the biological systems (such as the rhodopsin vision system) that translate the external world to the brain. Another set of problems that interests Craft is the neurogenetics of schizo-phrenia and depression.
Jean Shih
PROFESSOR, USC SCHOOL OF PHARMACY
"I am very sensitive to the issue of incurable disease. I have always hoped my efforts would be able to reduce some human suffering. This is an exciting period for our research because of these new techniques. We are now in a position to answer questions that we could not answer years ago.”
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“Previously, large groups of people were treated with a single drug,” she says. “Some would react positively, others would not. Now we’re getting to the level where individuals can be treated with a designer drug. What we need to do in the 21st century is carry the molecular biology and genetics of neuropsychiatric disorders to the next level – which is working with the individual patients so that they have a better quality of life.”
The multi-faceted Craft is also part of USC’s program in Neural, Informational and Behavioral Science – an interdisciplinary effort that seeks to compare the operation of “wet” computers (brains) and silicon ones to learn more about both. Headquartered on the University Park Campus, the NIBS program is the convergence point for a whole other group of star researchers from USC’s College of Letters, Arts and Sciences and School of Engineering, including program director Richard F. Thompson, a noted neurophysiologist and holder of the William M. Keck Chair of Psychology and Biological Sciences; brain-mapper Larry Swanson; neural theorist Michael Arbib; biomedical engineer Theodore Berger; and computer scientist Christoph von der Malsburg.
The Neurogenetics Institute will likely tap other sources of expertise from University Park – for example, researchers at the renowned Ethel Percy Andrus Gerontology Center. The Andrus Center is home to the laboratory of neurogerontologist Caleb Finch, one of the world’s leading experts on aging and the neurogenetics of Alzheimer’s disease. Many other notable scientists are based at USC’s Leonard Davis School of Gerontology, including Gerontology Research Institute director Thomas H. McNeill.
LAS’s strong programs in molecular and computational biology round out the roster of likely Neurogenetics Institute scientists with such luminaries as molecular biologists Norman Arnheim and Myron Goodman and mathematician Michael Waterman – co-discoverer of the Smith-Waterman algorithm that has been a key tool for gene-finders during the past two decades.
 imon Ramo, overseer extraordinaire, knows science, and knows the time is right to make this vision happen. “We have begun to learn, down to the level of molecules and atoms, the distinction between living matter and inanimate matter,” he says. “This is a revolution in biology comparable to what took place in physics 50 and 100 years ago, when we learned what was going on in the nucleus of the atom.”
Thanks to the events of 1999, USC will be a player in this revolution. Day describes his grandfather, oilman William Myron Keck, who founded Superior Oil Co., as “a risk taker and a wildcatter.” On the morning he signed the papers making the gift that created the Keck School of Medicine, Day wore his grandfather’s cufflinks.
“I believe my grandfather would like this bet,” he said as he pushed them back and inscribed his name in USC history.
SEPTEMBER 2085: The 200th anniversary of the founding of the Keck School of Medicine. Thanks to the work started in 1999, you, reader, may be there in sound mind and body to appreciate it.
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Gene therapy has particular relevance to the brain. The human genetic software library, or “genome,” is believed to consist of approximately 100,000 genes. Of these, as many as 60 percent control the brain and its functions. Many diseases affecting the brain, including stroke, are associated with increased age. Many of these “neuro-degenerative” diseases are caused, experts now believe, by genetic malfunction, and can be cured by neurogenetic intervention. More and more people live into their 80s, 90s and beyond. Older people are a larger and larger proportion of the population. Mental fitness is the key element in enabling an aging population to enjoy their increased life spans independently and creatively. Gene therapy holds out the promise of successful treatments to prevent or cure Alzheimer’s, stroke and the whole complex of brain prob-lems called senility. Neuro-genetics is thus the key to extended, fruitful life. |
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