BY DAVID VILLANO

n a tiny room behind a glass door in a drab, inauspicious building near downtown Miami, the secrets of the human brain are locked away. The room houses two stainless steel freezers, each secured with a padlock. One is an upright model like that you'd find in a kitchen; the other is a low chest with a hinged lid. On the front of each, a bright red LCD readout flashes the interior's temperature: a glacial minus 85 degrees centigrade, or 121 degrees below zero Fahrenheit. Wearing thick rubber gloves, neuroscientist Deborah Mash removes the lock from the upright freezer and pulls open the door. A cloud of cold vapor rolls toward the floor, revealing a rack of sliding drawers stuffed with coded, sandwich-size plastic bags. Each contains a small section of light gray tissue. "Not much to look at," says Mash with a sweep of her hand. "But their value to science cannot be measured." Welcome to the University of Miami Brain Endowment Bank. Within these two freezers and several others at the medical campus, brain tissue from more than 400 donors awaits the research that may one day lead to a cure for Alzheimer's, Parkinson's, schizophrenia, and many other diseases and disorders. It is one of only three major brain banks in the nation. (The others are at Harvard University and the University of California at Los Angeles). The banks collect postmortem tissue from people who have willed their brains to science. The tissue is distributed free of charge to researchers across the country. "There is only so much we can learn by studying animals," says Mash, professor of neurology and molecular and cellular pharmacology at the School of Medicine and director of research for the Brain Endowment Bank. "In fact there are no exact animal models for Alzheimer's and schizophrenia. And so without a supply of human tissue, the ability of researchers to understand the brain is severely limited." According to Mash, increased public awareness of Alzheimer's disease in recent years has created a ground-swell of interest in brain research. That interest has spawned demand for postmortem brain tissue with its chemical structures cryogenically preserved. Such preservation allows researchers to view mechanisms of the brain as they existed prior to death. Until recently, brain research had been one of the last unexplored frontiers of medical science. Why was Alzheimer's the catalyst for this new wave in brain research? As Mash explains, Alzheimer's cannot be positively diagnosed, much less cured, in a living patient; doctors can suspect the disease, but they won't know for sure until a brain autopsy is performed after death. nderstanding the disease has proved equally enigmatic: Brain tissue not removed and preserved within hours of death yields few clues to science. These frustrations left researchers with few alternatives. To learn about the disease, they argued, cryogenically preserved brain tissue must be made available to medical researchers around the country. Hence, brain banks like the University's opened their doors, placing donated tissue in deep freeze before it has time to deteriorate. The availability of brain tissue has encouraged research in other diseases and fields of study, among them Parkinson's, epilepsy, schizophrenia, head and spinal cord injury, addiction, depression, stroke, and chronic pain. As a consequence, says Mash, we've learned more about the human brain during the last ten years than throughout all of history. Yet neuroscience (the study of brain tissue) is still in its infancy. "We know so little about the brain that anything we do will open up entirely new avenues of investigation," she says. To encourage and promote research, Congress has declared the 1990s "The Decade of the Brain." The Brain Endowment Bank was, for lack of a better term, the brainchild of Mash. After earning her Ph.D. in 1984 from the University of Miami, Mash did two years of postdoctoral research at Harvard University. When she returned to the University of Miami, she proposed the idea of a brain bank. But Mash, whose research interests include Alzheimer's, Parkinson's, and drug addiction, found funding for the project elusive. Brain bank operating costs are steep-close to $2,000 per donated brain, and awareness of Alzheimer's and other brain-based diseases remained minor. Eventually, seed money for the University's bank was pledged by the National Parkinson's Foundation. In 1986, after Mash crisscrossed the state to raise awareness, the bank opened its doors with 21 donors. Today the bank has more than 400 brains in storage and nearly 800 more pledged for donation. The bank receives about 50 new brains each year. In 1997, further recognition and support came from the National Parkinson Foundation, when Mash was awarded the $1 million Jeanne Levey Endowed Chair for Parkinson's Disease Research. espite the bank's growth, donor recruitment is an ongoing challenge. Few people outside of scientific circles know of the brain bank's existence; even fewer understand its irreplaceable role as an aid to research. Compounding the problem is the negative perception some people have of brain tissue donation. While traditional organ donation offers the prospect of saving a life by way of a heart or liver transplant, or of bringing sight to the blind with a cornea transplant, donated brains are used for research only. The rewards are less immediate and less dramatic. Indeed, tissue may be in deep freeze for years before reaching a research lab. The bank's staff attacks the problem by making their plea directly to sufferers of brain-based diseases or disorders. "We tell prospective donors that, virtually overnight, we went from knowing nothing about Alzheimer's to exponential growth in our understanding of the disease, and this happened precisely because families were mobilized to make that gift," Mash explains. Of the bank's initial 21 donors, 16 were afflicted with Alzheimer's, two with Parkinson's, and one with schizophrenia. Only two were healthy. Today the bank houses tissue from sufferers of a variety of other diseases and disorders including Huntington's disease, Pick's disease, amyotrophic lateral sclerosis (known more commonly as ALS or Lou Gehrig's disease), dystonia, Down's syndrome, and depression. Those tissues are vital to understanding the mechanisms of brain-based afflictions, but so are healthy brains, which provide a control sample for research. Only by comparing healthy brains with diseased ones can researchers unlock their secrets. "Healthy people can be the toughest sell," says Lilian Dominkovics, program coordinator of the Brain Endowment Bank. "But without healthy brains, researchers have nothing to compare to brains afflicted with the disease or disorder they are studying." In greatest demand, says Dominkovics, is brain tissue from healthy young donors. Indeed, most of the bank's donors are the elderly. Some heard of the bank from friends who already have pledged; others heard Mash speak at retirement centers, nursing homes, and senior citizens' groups around the state. Getting the word out to young people requires a different strategy. "This might be the last thing people want to think about," she says, "but if you're concerned enough to carry a donor card for other organs, there is no reason you shouldn't make the same arrangements for donation to a brain bank." That's been the message of George and Helen Wayne of Venice, Florida. George, 89, and Helen, 86, pledged their brains to the Brain Endowment Bank after learning that it could be a meaningful complement to traditional organ donations. "The mind is a terrible thing to waste," jokes George Wayne, who receives a free neurological assessment each year from the brain bank. The Waynes have carried traditional donor cards for years and donate blood every eight weeks. (Since 1969, George Wayne says proudly, he's donated 17 gallons. Helen, slowed by surgery a few years ago, is one gallon behind him). Whenever he gets the chance, George says, he tells others about the work being done at the Brain Endowment Bank. "People need to know how important it is to make arrangements in advance," George says, explaining the pitch he often makes to family and friends on behalf of the bank. "They need to understand that they can make a difference in someone else's life by taking the time to make this commitment." Many prospective donors don't realize that provisions for brain tissue usage are not normally part of traditional organ donation plans. Typically, organs such as the heart, lungs, kidneys, liver, or eyes are "harvested" while the patient is brain dead, but still breathing with the aid of a respirator. But after brain death, the chemical structures of the brain are no longer intact. They are of little use to researchers. To avoid that problem, explains Dominkovics, brain bank personnel are on alert 24 hours a day to coordinate the brain harvest of a deceased donor. Brain bank donors carry a special donor card alerting emergency and medical workers of the need for special arrangements following death. The brain must be removed and frozen within 12 hours after death to be of use to researchers. When a donor dies within the South Florida area, they are transported to Jackson Memorial Hospital, where a surgical team completes the 30-minute procedure. If a donor dies outside of the area, the brain bank can call upon pathologists in its national network of cooperating physicians to perform the procedure. With modern surgical techniques, along with the ease of transportation, donors to the University's brain bank can reside anywhere within the United States. o remove the brain, an incision is made along the back of the head (to allow for an open-casket service). Once removed, the brain is flash-frozen in a special chemical solution and is stored in one of the bank's heavy-duty freezers. Before being frozen, donated brains are sectioned in half and cut into nine, one-centimeter slices. Each slice is placed in a numbered storage bag and returned to the freezer. Each freezer is backed up with an emergency power and cooling system. (During Hurricane Andrew in August 1992, Mash slept at the bank to monitor the freezers, but they never shut down.) Much is known about each brain long before it reaches deep freeze. After a donor registers, a complete medical and family history is compiled and filed in the bank's database. The goal is to assemble a comprehensive catalog of the physical, psychological, and environmental factors that may have affected the brain. Each donor's record is updated annually following a neurologic and neuropsychometric checkup. The more detailed the data, the more useful the brain tissue is to researchers. "We want to know everything-from what they eat, to where they've lived, to how many silver fillings they have in their teeth," Mash says. "Any bit of information, as inconsequential as it may seem, could provide a clue toward an important discovery." One researcher benefiting from the Brain Endowment Bank is Assistant Professor of Neurology Carlos Moraes. For the past two years Moraes has been investigating the mitochondria in Parkinson's patients. The mitochondria is the source of energy in cells. Moraes has found that mitochondria functioning in brain tissue is somehow affected during the onset of Parkinson's disease. His discovery is a small but nonetheless important piece of the Parkinson's puzzle. "This kind of work cannot be done without access to brain tissue," says Moraes, whose research specialty is neuromuscular disease. "The brain bank has changed the way we are able to approach our investigations." Unfortunately, not all researchers are as lucky as Moraes. Brain bank tissue is available free of charge to any qualified researcher, but demand is still much greater than supply. A scientific review committee evaluates and ranks each proposal for tissue use before approving or denying the request. "We'd love to be able to provide brain tissue to everyone, but that's just not possible," says Mash. "It's a shame that so much work is waiting to be done, and the only thing holding us back is that we don't have enough brains in the bank to go around."

Brain Bank Holds Hope for Cures rain diseases and disorders affect an estimated 50 million Americans. Until recently, many of these afflictions remained a mystery to modern science. The University of Miami Brain Endowment Bank is advancing knowledge of the brain by providing both healthy and diseased brain tissue to researchers engaged in a variety of basic and clinical research projects. Here are some of the areas of research supported by the brain bank: Alzheimer's disease. The gradual and debilitating loss of memory that characterizes this disease affects an estimated 10 percent of our population over the age of 65. It typically strikes in the seventh or eighth decade of life, but can also occur in middle age. By the middle of the next century some 14 million Americans could be afflicted. Researchers believe they have found a genetic link to the disease. Drug compounds, now undergoing testing, are aimed at delaying the onset of the disease's symptoms. Parkinson's disease. An estimated 400,000 Americans suffer from this neurodegenerative disease, which most often afflicts people in late middle age. Symptoms include uncontrollable tremors, rigidity of the limbs, and slowed movement. Researchers believe that the use of amphetamines and cocaine may be a risk factor. Environmental toxins also may be a cause, but much remains unknown. A variety of drug treatments are being investigated by brain researchers. Schizophrenia. This neuropsychiatric disorder, often associated with paranoia and delusionary thinking, affects an estimated 1 percent of all people between the ages of 18 and 25. As many as 200,000 new cases are diagnosed in the United States each year, typically within the adolescent and young adult populations. There is little doubt that a genetic predisposition exists, but researchers are still looking for the precise mode of inheritance. More recent studies suggest that fetal injuries may be a contributing factor to this perplexing disorder. Depression. Affecting 20 percent of the people in this country, depression is the most common of all mental disorders. Manic-depressive illness, characterized by dramatic mood swings, affects at least 1 percent of all Americans. Traditional drug therapy has proved successful, but has grown increasingly controversial. Current research is focusing on alternative treatments that reduce the risk and side effects of existing drugs. Stroke. The nation's third-leading killer, stroke is typically caused when blood clots or other deposits travel to the brain, blocking blood flow and thereby depriving the brain of oxygen. New "emergency treatment" drugs are being designed to restore blood supply to the brain and limit long-term injury. Epilepsy. Often characterized by violent, uncontrollable convulsions, epilepsy can also cause brief, barely noticeable seizures. More than 40 forms-one-third of them inherited-have been identified. Other forms can be the result of a traumatic event, such as head injury. Researchers recently learned that seizures caused by one form of epilepsy originate in a specific cluster of nerve cells. Drugs that act only at the affected area are being tested. Aging. Among those who do not suffer from Alzheimer's or other forms of dementia, some people maintain razor-sharp mental capacity, while others do not. Researchers suspect that certain chemicals influence memory and cognitive functioning of the brain, but they are not sure what these chemicals are or how they are produced. Drug addiction. A vaccine for cocaine abusers may be on the horizon. Researchers are reporting progress in the development of a drug compound that triggers the production of "anti-cocaine" antibodies in the body. After being inoculated, it is hoped, people who use cocaine will not experience the euphoric sensations of the drug. Pain. Researchers have learned that chronic pain can change the molecular structures in the brain and spinal cord. These changes often lower the threshold at which a person experiences pain. Researchers are investigating how these pain messages are transmitted and amplified. Many new non-opiate pain relievers are now being tested.

David Villano (A.B. '83) is a Miami-based freelance writer. Photography by John Zillioux.

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