When two infants received gene therapy in California last weekend, doctors were making a dramatic attempt to create working immune systems that nature was obligated to provide but didn't.
The newborns inherited a rare fatal immune disorder. They carried two copies of a defective gene for the enzyme adenosine deaminase (ADA) that is crucial for the immune system to fight infections. To correct their condition, doctors extracted from the umbilical cord blood stem cells that give rise to all blood cells, then placed them in a nurturing culture with genetically-altered viruses containing normal ADA genes.
Cells don't recognize genes, so genes can't get inside the cells on their own. They need to slip inside in a Trojan horse. The Trojan horse was the virus, genetically crippled so that it wouldn't harm the human host yet would maintain its ability to sneak inside cells. Tucked inside these viral vessels, the normal ADA genes were expected to enter the stem cells. Afterward, the stem cells (that now, doctors hoped, contained the healthy gene) were injected into the babies.
This is what is known as gene therapy. And gene therapy has come a long way, babies.
The two California infants brought to 114 the number of people who have had genes inserted inside their bodies either as therapy or as "markers" for progression of disease and treatments, according to records kept by the National Institutes of Health. Four years ago last week, the first gene marker was placed in a patient. And only three years ago, the first human received gene therapy.
She was a four-year-old girl who, like the two California infants, was born with defective ADA genes, and, therefore, no immune system. Doctors at NIH made medical history in 1990 by treating her and in 1991 by treating a nine-year-old girl with the same disorder by putting healthy ADA cells into the girls' T-lymphocyte blood cells, which are the white blood cells responsible for immune system protection. But T-lymphocytes do not live forever as do blood stem cells. And so, the treatment has had to be repeated.
The girls' immune systems improved significantly, according to Dr. R. Michael Blaese, chief of the National Cancer Institute's Cellular Immunology Section, who was involved with the girls' early treatment and with the stem cell gene therapy of the infants and the two girls. Although the girls have been going to school and doing well, last year Dr. Blaese told the Recombinant DNA Advisory Committee of NIH and the Food and Drug Administration, which authorizes all gene therapy experiments, that they may have "holes" in their immune system.
