A 4-year-old girl born without a working immune system yesterday became the first human being to undergo gene therapy, the long-awaited attempt to treat and perhaps cure diseases by splicing new genes into the patient's cells.

The experiment at the National Institutes of Health in Bethesda transforms a long academic debate about the possibilities of curing human ills at the genetic level into a medical reality that researchers expect will revolutionize the treatment of many human illnesses, from heart disease to cancer.

The girl, whom the hospital and her family refused to identify, was born with a rare gene defect that leaves her cells unable to produce an enzyme essential to the functioning of the body's defenses against infection. Only about 10 children each year are born with this disorder -- called severe combined immune deficiency -- and, until recently, most of them have died in childhood from chronic infections.

"She was very ill," her father said in a telephone interview from the hospital during which he would not reveal his identity. "She started getting very ill from the age of just under one."

Shortly before 1 p.m. yesterday, doctors inserted an intravenous needle into a vein on the shy, dark-haired child's hand as she sat on a bed, and began injecting some of the girl's own white blood cells back into her body. The cells had been removed two weeks earlier and genetically altered so that each now carried a normal copy of the defective gene.

About one billion genetically altered cells were injected. Doctors will now wait for six months to a year to see whether they manufacture the missing enzyme and, if so, whether that causes the girl's body to develop an immune system.

Until yesterday's experimental treatment, the girl had been receiving weekly injections of an experimental drug called PEG-ADA, which supplies the missing enzyme. The treatment helps boost the patient's immunity, but does not restore it to normal.

"We really don't know in the long term how it {PEG-ADA} is going to work," her father said. Gene therapy "gives us the hope that there will be a more permanent-type solution to her illness. I really am convinced that this is going to work and she will not have to undergo the regular shots in the long run."

To prepare for the gene therapy, a team of scientists, led by W. French Anderson of the National Heart, Lung and Blood Institute and R. Michael Blaese of the National Cancer Institute, removed some of the girl's blood and began culturing the cells in a laboratory vessel to mass produce certain white blood cells, called T cells, that are a central part of the immune system. After 10 days, the researchers added a virus that had been genetically altered so that each carried a copy of the human gene for the missing enzyme, the ADA gene.

The engineered virus infected the girl's T cells, automatically splicing its genes, including the ADA gene, into those of the blood cells. These genetically altered cells, now able to make the normal enzyme, grew and multiplied in the laboratory until they numbered in the billions.

At 12:52 p.m. yesterday, a small test dose was injected into an intravenous tube in the girl's left hand as she sat, wearing turquois pants and a white top that her mother had made, on a bed in the pediatric intensive care unit of the NIH's clinical center.

"We watched her for about seven or eight minutes," Anderson said. "At 1 p.m., we continued the infusion of cells. It took about 20 minutes. Altogether, we gave back approximately 1 billion cells. That represents about one-one thousandth of her circulating white blood cells."

The child, who was not sedated, played with cartoon stickers throughout the treatment. "She put a sticker on each of our lab coats," Anderson said. "I have a rabbit on mine.

"She was waiting for something to happen," Anderson said. "She is 4 years old and heard about this big thing that was going to happen, but nothing happened." At least nothing that she could feel.

The scientists, however, hope that the genetically repaired cells will begin multiplying in her body over the next six months to a year -- making their own copies of the ADA gene and passing them on to newly formed cells -- and "will repopulate her immune system with gene-corrected cells," Anderson said. "If that happens, we will have helped her substantially."

After spending the night in the NIH's clinical center, the child is expected to be released today and go home with her family. She will return to the NIH every two weeks for tests and to have more white blood cells removed and retreated with the repair gene. At the end of six months, the NIH team may begin increasing the number of cells she is receiving.

Several members of the team talked about the nervousness before the procedure. Blaese joked about how everything was going extremely well, as long as nobody dropped the gene-altered cells on the way to her room.

Later, Anderson admitted to exhaustion and not having eaten for the previous 24 hours. After it was all over, he said, "I am very pleased because it was very important that the first gene therapy experiment begin well."

The promise of gene therapy has been discussed for most of a decade and this experiment itself has been hotly debated for more than 3 1/2 years. Earlier gene transfer experiments into human patients were conducted on cancer patients expected to live only a few months. They involved foreign genes that acted only as markers to show the cells were surviving in the body.

Theoretically, there are some risks, though safety experiments have shown that the genetically crippled virus used to infect the cells cannot reproduce or threaten the patients. Anderson said that there is a small chance that inserting genes into a cell could cause it to become cancerous. Critics have cited that risk to oppose the experiments.

The controversies and debate lengthened the time it took for the team to win governmental approval for yesterday's experiment. Although versions of this experiment have been discussed for years, the final approval became a mad dash to the finish line. By midweek, the Food and Drug Administration, the last agency that had to give approval, called Anderson to say the team had cleared all the hurdles and could bring the patient to NIH.

But the final papers were not signed until yesterday morning. The treatment began four hours later.

Through it all, the child sat serenely on the bed.

"She was wonderful, just a great kid," Blaese said. "She was a lot calmer than I was."