The girl with the round face and dark hair sat quietly on the bed in the National Institutes of Health clinical center while pediatrician Kenneth Culver slid the needle of a catheter into a vein running along the top of her left hand.

This 4-year-old doesn't cry from needles anymore. "She just pulls back a little bit," said the 35-year-old, bearded and bespectacled pediatrician. "She is a tough, stoic kid."

She knows all about needles and doctors and drugs because she has been sick nearly since birth. The girl inherited a defective gene that cripples her immune system so it no longer protects her from the chronic ear and lung infections that ultimately could kill her.

A week and a half ago, she became the first patient to enter the promising new world of human gene therapy. She suffers from severe combined immune deficiency, which is caused by inheriting a damaged gene that blocks the production of a vital single enzyme. If the experiment works, her fatal disease -- up to now temporarily held at bay by weekly injections of the missing enzyme -- could be cured at its genetic roots.

Until the doctors know whether the treatment is working or not, the family has refused to disclose the girl's name. The NIH team expects to begin treating a small number of other children with the same disease in the next few months.

This experiment has opened the door to a wide range of new gene therapies that many scientists believe will eventually revolutionize the treatment of a large number of illnesses. Initially, gene therapy will be aimed at some of the nearly 4,000 inherited illnesses caused by defects in single genes -- among them muscular dystrophy, Huntington's disease and sickle cell anemia.

At the same time, researchers are making significant progress in using the same approach to attack diseases not usually thought of by the public as genetic disorders -- cancer, heart disease, Parkinson's disease and others. Gene therapy may even one day be used to lower cholesterol levels.

The pressure to find permanent genetic solutions to such diseases is rapidly increasing.

Last week, researchers announced an important advance toward a gene treatment for one of the most commonly inherited genetic diseases of childhood -- cystic fibrosis. Howard Hughes Medical Institute scientists at the University of Michigan Medical School and the University of Iowa College of Medicine reversed the defect in CF patients' lung and pancreas cells growing in the laboratory. While this raises the promise of future gene therapy for CF patients, experiments in humans are years away.

"For CF clearly, what has been done here is a step in the right direction," said the University of Michigan's Francis Collins, who helped discover the genes that cause cystic fibrosis and neurofibromatosis, once called Elephant Man's disease. "It shows it is possible to make the correction in cell culture. But the problem is going to be delivery, getting the gene to an awful lot of cells in the patient."

Even as advances in the field speed up, some scientists are warning of over-promises of dramatic genetic cures at a time when formidable technical problems remain.

"I don't want to argue that gene therapy will never be achieved," said Stanford University's Paul Berg, who won a Nobel prize for being the first to put new genes into living cells. "I just want to dampen this near hysteria that we have solved the problems of genetic disease. We have not."

Moreover, a few gene therapy researchers, some of whom are competitors, have publicly criticized the NIH gene team that treated the 4-year-old girl.

In published remarks, Richard Mulligan, a genetics researcher from the Whitehead Institute of Molecular Biology in Cambridge, Mass., and a long-time critic of the NIH team, said, "The possible benefits of the experiment don't outweigh the risks. It should be scuttled."

The risks include the small, but real, chance of causing cancer when the new gene is randomly inserted into a white blood cell.

Other critics include Arthur Bank of Columbia University, who called the NIH effort "not good science," and Stuart Orkin of the Harvard Medical School, who said it was a long shot that the first patient would be helped.

W. French Anderson of the National Heart, Lung and Blood Institute, the gene therapy pioneer who pushed for permission to treat this first patient, defended the experiment by pointing to more than 3 1/2 years of public and scientific debate and extensive review by federal committees, including the Food and Drug Administration.

Some of these debates were heated, but when the votes came, the NIH researchers won near-unanimous approval. Only Mulligan, a member of a key review panel, voted against the project.

Once the approvals started coming, the NIH team got into a high-pressure race against time to have everything ready to treat the first patient when the FDA gave its final approval on Sept. 14. Four hours later, the first patient began receiving the gene-altered cells.

That moment, however, was rather anticlimactic. The thousands of pages of documents, years of review and a couple of sleepless nights all came down to a simple half-hour transfusion of gene-altered white blood cells.

The NIH team of Anderson, Culver and R. Michael Blaese removed white blood cells from a vein in the patient's arm. After growing the cells in the laboratory for a few days, they infected them with a genetically engineered virus designed to carry the gene for the missing enzyme.

The virus, a retrovirus distantly related to the virus that causes AIDS, is called a "vector," or carrier, for its ability to transport human genes and insert them into the a target cell's chromosomes without causing a harmful infection.

After the girl's white blood cells had been exposed to the gene-carrying vector, they were squirted back into her body, where, it is hoped, they will begin making the missing enzyme and restore her immune system.

During the injection, the pioneering patient "was waiting for something to happen," Anderson said. "And nothing happened. She didn't feel anything."

When the treatment was finally over, all she wanted to do was play. "She said, 'Hey Dad, can I go back to the Children's Inn playroom?' " Culver recalled. "That's how good she felt afterward."

The doctors sent her to the playroom for a while, watched her overnight and sent her home on Saturday.

"This is the blast-off," Anderson said. "Even if this first experiment doesn't make it, it was still a moon shot."

The thunder of that launch has galvanized scientists and physicians around the country.

"There is a much greater sense of optimism that gene therapy will find a niche in a number of diseases," Collins said. "Now it may have early success in non-genetic diseases, particularly cancer, maybe AIDS. No one talked about that until a year or so ago."

With NIH funding, the University of Michigan has begun a project to conduct several kinds of gene therapy experiments. "We have a weekly seminar on gene therapy," Collins said. "There is a lot of enthusiasm for it around here."

The excitement has spread to other places, too. Anderson already has received nearly a dozen requests from scientists around the world -- mostly in the United States but also in Canada, Italy, Belgium and Holland -- to collaborate on new experiments. "We are pulling new people into the field," Collins said.

"It is not just a little retrovirus club now," Blaese said. "There are lots of people in academic clinical medicine who are now thinking about how they can apply gene therapy" to the diseases they study.

"I think gene therapy is here to stay, no matter how it may stumble in the early phases," said Nelson A. Wivel, head of the NIH Office of Recombinant DNA Activities, which conducted a key scientific review of the first experiment. "It's clearly is a rational way to go for a lot of diseases."

What's less clear is how fast different gene therapies can be developed to treat the sick.

The biggest problem is getting the right gene into the right cell in such a way that it functions. In the early 1980s, scientists believed that they had to insert the new gene into a type of bone marrow cell called the stem cell because it gives rise to all other blood cells. Human stem cells, however, are hard to identify and target, so few of these key cells take up the new gene. For several years, this problem seemed unsolvable, slowing advances.

Now, however, scientists have come up with new approaches.

"I think the logjam that had gotten a number of people a bit discouraged is breaking not because we solved the stem cell problem," Collins said, "but because we thought of other targets."

In the case of the first human trial, for example, the NIH team put the repair gene into the girl's T cells, a type of white blood cell that controls the immune system and can persist in the body.

T cells may or may not be the solution. No one knows how long they will last, though animal experiments in Italy suggest they alone could restore a defective immune system. The NIH team expects to inject the patient with gene-altered T cells once a month for the next six months and look for improvement in the functioning of her immune system.

T cells also have been targeted for a type of gene therapy aimed at killing cancer cells. The NIH gene team, working with Steven A. Rosenberg at the National Cancer Institute, plans to put the gene for tumor necrosis factor, a protein that causes cancer cells to die, into a type of T cell that attacks melanoma, a form of skin cancer. Rosenberg hopes that supercharging the T cells with this toxic gene will provide better cure rates. These experiments, still awaiting FDA approval, could begin later this year.

Other research groups are developing alternative ways to get genes into human cells to fight diseases.

Research groups from NIH, Johns Hopkins and Harvard have shown that genes can block the growth in the test tube of several types of cancer cells, including cancers of the breast, lung, colon, bone and brain.

While all of these experiments offer the hope that similar genes could be put into sick people to treat their disease, some scientists are skeptical. "We cured Lesch-Nyhan disease in the test tube five years ago," Berg said, speaking of an unusual form of mental retardation. "That is no big deal doing it in culture, but doing it in a person is a very different ball game."

Another University of Michigan group recently reported inserting genes into cells that line blood vessels, opening the possibility of producing clot-dissolving proteins near a narrowed artery to prevent a heart attack or of manufacturing anti-cancer drugs near a tumor.

A research team at the University of Wisconsin and another at the University of Michigan have been trying to put genes for a cholesterol receptor into liver cells. Increasing the number of these receptors should pull more cholesterol into the liver, lowering the level of cholesterol in the blood. Lowering cholesterol has been shown to decrease the risk of heart attack and stroke. This kind of gene therapy might help prevent heart attacks.

Last year, Theodore Friedmann and Fred Gage at the University of California at San Diego showed that cells could carry the gene to make nerve growth factor, and that putting these cells into an animal's brain could protect the nerves from damage similar to the damage of Alzheimer's disease. Their current work shows that inserting genes into rats can cause the animals to produce a chemical that reverses the symptoms of Parkinson's disease.

For all these promising efforts, Anderson believes there are limits to the current approach.

"I am going back into the lab to develop an {approach} so a doctor can take a vial off the shelf and just shoot {the gene} into the body," Anderson said. "Until we can {inject genes directly} into the body, gene therapy is not going to be a major therapeutic option. You can do a few hundred patients a year, but not millions" with the current approach. He predicted, in fact, that gene therapy would not be used widely until early in the next decade.

Several scientists nonetheless said gene therapy could be expected to move rapidly in the next year or two, including therapy for some forms of cancer, hemophilia and, perhaps, AIDS.

"I always wondered if we were going to do it," Blaese said of the first gene therapy experiment. "Now, the era has begun."