A 20-year-old college student, on his way home from a weekend revelry, loses control of his car. It careens off the road and overturns. The driver is rushed to a hospital emergency room where the physician on duty diagnoses a severe spinal cord injury. The patient is injected with a substance that suppresses a gene, called MT-3, at the site of the injury. After a few months of rest and rehabilitation, the injury is completely healed. What would have been a lifelong disability is averted.

    Tests on a 40-year-old woman indicate a much higher than normal probability for suffering a stroke. Her doctor treats her at periodic intervals with the peptide carnosine. The stroke never occurs.

    Sound futuristic? Sure, but the day may not be far off when adults can overcome spinal cord and head injuries without permanent damage, and such debilitating illnesses as stroke, Alzheimer's Disease, and Huntington's Disease can be prevented.

    Work by Dr. Paul Trombley (Ph.D., Oregon) of FSU's Department of Biological Science and Dr. Cathy Levenson (Ph.D. Chicago) within the university's College of Human Sciences is aligned with a vein of biomedical research clearly aimed in that direction. The two scientists are confident that the research of the 21st century holds extraordinary promise for patients suffering from a variety of neurological injuries and diseases, much of it without surgery.

    Levenson and Trombley, colleagues in FSU's Program in Neuroscience, share a curiosity about brain function and the genes and environmental factors that control it. Trombley studies the physiological characteristics that control communication between neurons, or nerve cells, and Levenson homes in on the genes that drive neuron function.

    Copper and zinc, two metals commonly found in the nervous system, play a prominent role in both of their studies. Both scientists are interested in the fascinating roles these metals play in the body. Both elements are absolutely essential for life, yet copper, for example, is highly toxic. Zinc is generally considered safe in moderate amounts, but the two metals have an intriguing relationship that scientists are only now beginning to appreciate.

    "These two metals travel together, often work together and bond together (in living tissue)," said Levenson, now in her third year of a five-year, National Institutes of Health-funded study of zinc and copper's effects on living tissue.

    Last spring, Levenson's findings on the copper-zinc relationship in experiments with rats made headlines. She found that when rats are fed high doses of zinc, their systems became incapable of absorbing enough copper to maintain health. Denied sufficient copper, the animals' pancreases eventually ceased to function and their brains suffered impairment. Even after Levenson's research team fed the animals copper supplements, their health continued to decline, and with a bizarre side effect--the animals' pancreases started growing liver cells instead of pancreas cells.

    The study, which came on the heels of a report published in the Journal of American Medical Association that zinc dietary supplements are essentially worthless as a cold-fighting nostrum, suggests that such highly advertised supplements may be doing more harm than good.

    "If you started popping zinc pills that were giving you really high levels of zinc, you could find yourself at risk for copper deficiency," says Levenson. "This could lead to some loss of immune system function."

    The real focus of Levenson's research is the genetic triggers that govern how, where and when zinc and copper get used in the body's vast nervous network. Her latest work exploits findings about how a particular protein called metallothionein basically sets the limits on what a number of trace metals, such as copper and zinc, can do in the body.

    In the early 1990s, geneticists discovered the set of genes--dubbed MT-3--responsible for producing the type of metallothionein that specifically regulates copper and zinc.

    Levenson has found evidence that the MT-3 gene also may inhibit nerve-fiber growth. The gene is not present in the arms, legs, hands, feet where nerve regeneration normally occurs following an injury. Nor are there many, if any, MT-3 genes in infants who usually are able to recover from brain and spinal cord injuries. But in the brains and spinal cords of adults--organs that once damaged, don't regrow--MT-3 genes are abundant.

    Levenson says that the relationship between MT-3's nerve-growth inhibiting abilities and its role in manipulating copper and zinc suggests that if scientists could figure out how to regulate the gene--turn it on and off--then nerves might be enabled to regrow in regions of the body once off-limits to nerve regeneration such as the brain and spinal cord.

    Levenson's research poses another question: If MT-3 is a gene that inhibits neuronal growth, can it possibly inhibit growth of cells that are undesirable such as certain cancer cells? By hooking up MT-3 to another gene that can be found in cells outside the brain, Levenson believes she will eventually be able to supply the answer.

    Levenson's continued research, then, focuses on how the gene can be regulated and beneficially exploited and how copper and zinc fit into the equation. Answers will go far in determining whether or not nerve damage to the adult brain and spinal cord can be fixed. And, if engineered MT-3 can inhibit the growth of cancer cells, Levenson's research will have implications for other organs as well.

    Trombley's related work, also supported by the NIH, involves the actions of zinc and copper on the nervous system and a peptide called carnosine that can influence their effects. Trombley found that carnosine can completely suppress the toxic effects of copper and reduce those of zinc.

    Laboratory studies have shown that carnosine is not a neurotransmitter--a natural chemical the brain uses to zap messages between neurons--as researchers once thought, says Trombley. However, the compound may modulate or even protect neurons, he said.

    Research has shown that zinc and copper, naturally released into the brain by nerve cells, can affect communication between neurons but that excessive release may occur in several neurological disorders, resulting in nerve cell damage. Trombley's research shows that carnosine protects against copper- and zinc-induced neurotoxicity by binding the metals and possibly acting as an antioxidant.

    No studies to date have shed any light on whether levels of carnosine vary from person to person, whether deficiencies exist, and, if so, how such deficiencies are defined, says Trombley. One possibility, he said, is that people with low levels of carnosine or related chemicals may be more susceptible to nerve damage associated with some neurological disorders. Such injury could result from the inability to prevent toxicity caused by copper and zinc.

    Trombley says that carnosine, or similar compounds, eventually may prove to be beneficial in the treatment of diseases of the nervous system that may be caused by an imbalance of metals and/or the compounds that regulate them. Because it already occurs naturally in the brain, carnosine potentially could be introduced into the body as a healthy way to correct a carnosine deficiency, says Trombley, but at present that poses serious technical problems that would have to overcome.

    "What's more likely, the knowledge we gain from understanding how carnosine and similar compounds work may be used to develop treatments which mimic carnosine's effects," he said.

    Trombley thinks that besides carnosine and metallothionien, the protein Levenson studies, researchers may discover other compounds the brain uses to regulate zinc and copper. Such research could lead to clinical treatments whereby the body's own chemicals could be used to fight or correct a variety of neurological disorders associated with the regulation of trace metals in the brain.

    Copper and zinc--two of the most common elements on earth--have been at work in the mammalian brain and nervous system throughout evolution, as have a variety of other trace metals. Only in recent years have scientists had the tools and know-how to effectively study, at the cellular and molecular level, how and what these elements do in a living organism.