Elusive Genes Discovered

It was the year of the brian.

It was also the year of the gene.

At Harvard's extensive network of research laboratories, from Cambridge to Charlestown, scientists engaged in desperate searches, some successful and some not, for the genetic causes and cures of dozens of ailments, fostering progress in earlier detection and treatment of disease.

Kicking off with a November Massachusetts General Hospital (MGH) symposium on neuroimaging, where scientists, doctors and philosophers delved into the brain without use of any scalpels or other invasive tools, neurobiology took center stage.

Throughout the year, Medical School Professor of Genetics James F. Gusella and his colleagues at the MGH Molecular Neurogenetics Unit reported several "candidate" genes for the defect which causes Huntington's Disease, the usually fatal neurodegenerative disorder which killed folk singer Woody Guthrie.

Finally, in the March 26 issue of Cell, Gusella, who in 1983 discovered the general location of the defective sequence, announced that he and researchers from 10 other institutions around the globe had identified the defect.

The discovery of the defect, a "genetic stutter" of three nucleotides, the basepairs which make up DNA, should make possible a quicker and more inexpensive test for the disease, and eventually a better understanding of the mechanism which kills brain cells in the approximately 25,000 U.S. Huntington's patients.

And another hopeful finding was announced on March 4, when an international team of more than 30 scientists, led by Medical School Associate Professor of Neurology Robert H. Brown Jr., reported in Nature that they had found an altered gene most probably responsible for one form of Lou Gehrig's Disease, a degenerative disease of the central nervous system.

The finding of the altered gene, which codes for an enzyme necessary for mopping up dangerous free radicals roaming in the central nervous system, suggests that scientists may find a cure for the disease if they can mimic the effects of the enzyme in sufferers of familial amyotrophic lateral sclerosis (ALS). Familial ALS affects 5 to 10 percent of Gehrig's Disease sufferers.

Doctors are hopeful that treatment of familial ALS will shed light on the mechanism which causes other forms of Gehrig's Disease. Researchers suspect that the loss of motor neurons and subsequent loss of muscular control which characterizes all forms of the disease is caused by the action of such dangerous free radicals.

In other genetic discoveries, Medical School Assistant Professor of Pediatrics Dr. Stephen H. Friend reported a new technique designed to make testing for breast and other cancers easier, quicker and cheaper.

While still in the testing stages, Friend hopes the technique, which measures the levels of the product of a genetic tumor suppressor known as p53, will decrease the amount of time necessary to screen patients from weeks to just hours.

The biggest headline grabber, however, which eventually led to so much publicity that the MGH News Office placed a general blackout on further interviews with laboratory personnel, involved a triple therapy designed by fourth-year M.D.-Ph.D. student Yung-Kang Chow that had successfully knocked out HIV-1, the most common virus which causes AIDS.

Chow found that when he combined AZT and ddl, two common anti-AIDS drugs approved by the FDA, with Pyrodine, which inhibits DNA duplication by HIV-1, the virus could no longer replicate to infect other cells.

After a general media blitz, followed by hundreds of calls to MGH by AIDS sufferers requesting trials of the new drug therapy, however, Chow and others scrambled to strongly caution AIDS sufferers that the discovery was only a first step toward a cure for the deadly disease.