Monday, May. 25, 1981
Helping Babies in the Womb
A test for toxicity; a prenatal use for vitamins
The use of thalidomide to relieve anxiety and morning sickness in pregnant women resulted in the birth of thousands of children with cruel deformities, from flipper-like limbs to malformations of the heart. The drug, it is now known, produces a similar effect in the offspring of monkeys and rabbits. But during the premarket tests of thalidomide in the 1950s, it was mainly studied in laboratory rats because they are easy to handle and relatively cheap. No evidence of damage to offspring of rats given the drug was found.
The question of which animals to use for such safety testing has always been a vexing one, and by the time it was discovered that thalidomide causes birth defects in monkeys and rabbits, many human casualties had already occurred. Last week researchers from Johns Hopkins University announced the development of a simple test that could both signal whether certain drugs might be harmful and indicate the animal species that should be used to check them.
For the test, described by Medical Researchers David Blake and Stephen Spielberg, white blood cells from humans are mixed with liver tissue from humans or other species plus the drug under study. Then the preparation is examined to see if enzymes in the liver have metabolized the drug into a substance that kills white cells. The researchers believe that such toxic metabolites may be responsible for birth defects; some of their studies suggest that thalidomide works that way. The new test, for instance, shows that thalidomide does form a toxic metabolite, areneoxide, in the presence of liver tissue from rabbits, monkeys and humans, though not from rats.
Blake and Spielberg caution that this test will not alert investigators to all drugs with the potential for causing birth defects, only to those that form toxic metabolites. But they think their work could help researchers design more reliable experiments. For example, if a test shows that a .particular drug forms a toxic metabolite in humans and rabbits, but not, say, in dogs, then by a process of elimination rabbits would be designated the appropriate species for future birth defect studies related to that drug.
Last week there was also encouraging news about helping babies with genetic disorders--while they are still in the womb. The success, described by doctors at the University of California in San Francisco, was in a tiny patient with a rare inherited disease called biotin dependency. Biotin, a B vitamin, is necessary for certain metabolic processes. In people with the disease, the body's use of biotin is somehow disrupted. Symptoms include hair loss, lethargy, coma and susceptibility to infection. The only treatment is daily doses of the vitamin.
When Mrs. Debra Whitmore was 16 weeks pregnant, doctors used amniocentesis to collect a sample of the amniotic fluid cushioning the fetus. (They performed the procedure because she had already borne a son who is biotin dependent.) Examining fetal cells in the fluid, they discovered that the unborn child would also have the disease. Deciding that the baby's chances would be enhanced if treatment started before birth, doctors began giving the mother large quantities of the vitamin, starting in the 24th week of pregnancy, after the organs in the fetus had developed. As they hoped, enough biotin passed through the placenta so that the baby, a girl named Nicole, was born healthy. Nicole Whitmore is now 5 1/2 months old. Like her brother, she takes biotin daily. Her doctors say she should grow up to live a normal life.
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