Advances in Genetics Leave Strong Impact on Diagnosis, Therapy, Ethics

Gene therapy may be dominating the headlines, but other advances in human genetics already are having a dramatic impact on medical diagnosis and therapy--and raising ethical concerns as well.

Spectacular progress has been made in identifying genes responsible for dozens of hereditary diseases, including such blood disorders as sickle cell anemia, thalassemia and hemophilia.

Just last month, an international team reported that it has identified an abnormal gene that predisposes some people to heart disease in middle age. Presumably, people who carry such a gene might someday be advised to alter their behavior to lessen their chances of heart disease, such as by eating low-fat foods and getting more exercise.

The pursuit also is well under way for genes that may predispose a person to cancer, alcoholism, arthritis, schizophrenia--or even criminal behavior. Eventually, such research may lead to better treatments or cures.

The identification of specific genes responsible for certain diseases also has opened the way for genetic screening, in which new-borns and even fetuses can be tested for predisposition to certain hereditary diseases.

But such screening is not without controversy. A case in point is cystic fibrosis, an inherited lung and digestive disease that afflicts about 30,000 Americans.

Last October, researchers in Toronto reported finding the approximate location of the gene that causes the disease. A prenatal diagnostic test is being developed and will soon be tested at several universities, including Baylor College of Medicine in Houston.

But if a fetus is found to be positive, would-be parents face an agonizing decision--to abort or not to abort. Until recently, most cystic fibrosis patients died as children or young adults. Now, with improvements in treatment, some are surviving into their 20s and beyond, and are marrying, holding jobs and even having children.

Most genetic screening is done for families with a history of birth defects or inherited diseases, or when the pregnant women is over age 35 and thus at higher risk for producing children with chromosomal abnormalities such as Down’s syndrome.

In such screening, fetal material is obtained in two ways. At about 10 weeks of pregnancy, a technique called “chorionic villous biopsy” can be used to obtain a sample of the blood-rich placental tissue, through which the fetus takes nourishment and gets rid of wastes.

More commonly, amniocentesis is performed between 16 and 20 weeks of pregnancy. In this technique, fluid from around the fetus is extracted through the abdomen with a needle and syringe and analyzed in the laboratory.

California this year began an unprecedented statewide screening program, which requires all pregnant women to be offered a blood test for serious neural tube and other birth defects.

A small number of expectant mothers who take the “alpha fetoprotein” blood test will be found after confirmatory tests, such as amniocentesis, to be carrying severely malformed fetuses. These women then will be offered the options of abortion or special medical care if they wish to continue their pregnancy.

Researchers by the end of 1985 had mapped 831 human genes (out of the more than 50,000), including the approximate location of those for Duchenne’s muscular dystrophy and Huntington’s chorea, an incurable disease that causes loss of muscular control and dementia.

In the laboratory, scientists have made copies of about 250 different genes, thus allowing them to make and study large quantities of the proteins produced by the genes.

For some diseases, such as sickle cell anemia, the exact mutation responsible for the illness is known. But for others, such as muscular dystrophy, or cystic fibrosis, scientists have yet to isolate the aberrant gene. Instead, they use techniques that identify pieces of the neighboring genes.

The largest protein made to date from a gene is a key blood-clotting substance called Factor VIII. The absence or deficiency of this factor leads to hemophilia, a hereditary blood disorder that usually affects men.

Gene therapy for hemophilia is not currently a possibility. But the cloned Factor VIII gene is already serving as the basis for a more reliable diagnostic test.

Cloning of the gene should allow for a safe, cheaper and more abundant supply of Factor VIII to treat bleeding episodes, researchers say. They predict that clinical trials of the biologically engineered protein will begin within a year or two.