what we learn from animal research

n December, scientists from around the world published the genome of the laboratory mouse — a key step in what the journal Nature has called "human biology by proxy." Eighty percent of human genes have a counterpart in the mouse, and many human diseases can be simulated using mice.

At Carolina, some 200 faculty researchers work with animals, and many of these investigators are doing basic studies of mouse genetics for insights into human biology and disease. Oliver Smithies, professor of pathology and laboratory medicine, won the 2001 Albert Lasker Award for Basic Medical Research. Smithies and his colleagues pioneered a technique for gene targeting, making it possible to engineer mice that model various human diseases. As a result, scientists have used the technique to create some 4,000 varieties of custom mice, the mainstays of labs all over the world.

While many of the medical benefits of these basic studies are still years away, research with animals at UNC-Chapel Hill has already contributed to a number of beneficial medical breakthroughs. Here are just a few examples:

  Many children with Lesch-Nyhan disease and other mental-deficiency disorders engage in self-injurious behavior (SIB), such as finger biting, hair pulling, or head banging. George Breese, professor of psychiatry and pharmacology, discovered that rats whose dopamine was eliminated during development can engage in SIB when given drugs that stimulate dopamine receptors. In this rat model, he identified several drugs that reduced SIB. Clinical investigations have found that these drugs ameliorate SIB in some mentally deficient patients with this symptom.

   In 1992, a team of researchers led by Richard Boucher, now director of Carolina's Cystic Fibrosis Center, developed the first mouse model of cystic fibrosis (CF). Research using that model led Boucher and colleagues to discover that the airway cells of CF patients contain too little salt. INSPIRE Pharmaceuticals, a company cofounded by Boucher, has developed a treatment to correct the salt imbalance. The treatment, INS37217, is in clinical trials.

   Ronald Thurman, late professor of pharmacology, and John Lemasters, professor of cell and developmental biology, used a rat model to understand how alcohol and other stresses damage the liver. They found that glycine, an amino acid produced by the body, held promise for preventing such damage. German researchers have had success using supplemental glycine to reduce liver injury in humans.

   Lemasters and Thurman also developed the Carolina rinse solution, which contains glycine, to minimize injury to organs stored for transplantation. Validated in rat models, the solution minimizes injury when cold-stored organs are rewarmed and reoxygenated. Studies at the Mayo Clinic and in Germany show decreased injury to human livers, and the solution is under FDA review.

   By studying tumors and normal tissues in rodents and dogs, James Raleigh, professor of radiation oncology, developed a marker that detects cells that are hypoxic — lacking oxygen. Researchers have used the marker in studies of cancer, alcohol-associated liver damage, kidney damage from immunosuppressive drugs, and changes in bone caused by changes in stress such as occur during space travel.

  In the mid 1980s, Linda Dykstra, professor of psychology, and graduate students from psychology and neurobiology explored the effects of the drug buprenorphine in rats and monkeys. This and later work led to the drug's approval, in November 2002, for use in the treatment of heroin and morphine dependence.

   Kathy Sulik, professor of cell and developmental biology, conducted research in the early 1980s that proved that use of alcohol during pregnancy causes fetal alcohol syndrome. In mice, the equivalent of heavy binge drinking during the third week of human pregnancy resulted in birth defects. These findings influenced the Alcoholic Beverage Labeling Act of 1988, which requires manufacturers to place health-warning labels on all alcoholic beverage containers.

Neil Caudle is the editor of Endeavors magazine.
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