To save children from death, 2 doctors in Maryland alter building blocks of life

February 21, 1993|By Liz Bowie | Liz Bowie,Staff Writer

Within weeks, two Maryland doctors will provide a peek at 21st-century medicine. A girl whose short life has been consumed by the struggle against a fatal illness will get an infusion of genetically altered cells -- in a treatment so painless that she'll probably be watching one of her favorite videos, maybe "The Little Mermaid."

If the treatment works, the girl will be cured in a matter of months.

The idea is radically simple: Halt illness at its very core, the genetic code that tells the body how to function. Turning that idea into reality has become the life's work of two doctors at her bedside, R. Michael Blaese and Kenneth W. Culver.

Success in this, one of the world's first gene therapy experiments, would help usher in a new medicine with the potential to cure some of the world's worst scourges -- cancer, AIDS, cystic fibrosis, muscular dystrophy and hemophilia.

As a beginning, the doctors working at the National Institutes of Health are trying to cure a little-known hereditary disorder called adenosine deaminase (ADA) deficiency, which has threatened the girl's life since she was born. Like David, the famous "bubble boy" forced to live in a sterile world in the 1970s, the 6-year-old girl -- and an 11-year-old who will be treated soon after -- have no ADA gene, and therefore, barely functioning immune systems. Until her first gene therapy treatments in 1990, the youngest girl rarely left her house except to go to the doctor. Her parents even kept her sister home from school, for fear that she would carry germs into the house.

Success also would bring personal triumph for Dr. Blaese and Dr. Culver, the culmination of a decade-long quest to cure just one rare disease. They have withstood the sharp tongues of colleagues publicly dissecting their scientific conclusions, and they have tiptoed through the ethical land mines to collaborate with business.

But there's more to the triumph.

Dr. Blaese and Dr. Culver confront daily the anguish of hundreds of terminally ill patients and their families desperate for hope. One woman, for example, offered to fly them to Australia to treat her grandchild for a disease that there is still no medical magic to erase.

So Dr. Blaese, a soft-spoken man who has spent a career treating children with rare diseases, has plenty of reasons to meddle with the building blocks of life: "I have been to more funerals than I care to."

Years of experiments

Dr. Blaese, a gentle, solidly built scientist in midcareer, is chief of NIH's immunology branch. His office is not much bigger than a large, walk-in closet. And his laboratory, with all the colors and fixtures of a 1960s elementary school, is a hodgepodge of computers, microscopes, glassware and notebooks. Refrigerators line the hallways, and there is barely enough space to turn around.

He has been trying to develop a gene therapy treatment since the mid-1980s, when he worked with W. French Anderson, a pioneer in the field who has since left NIH. They wanted to make real what had been imagined since the first advances in the biotechnology revolution.

Essentially, they wanted to insert genes into a human to treat an illness on the most basic molecular level.

Initial attempts would focus on a patient with a hereditary, genetic defect. The broader goal: to manipulate a person's genes to treat all kinds of diseases.

They chose to work with ADA-deficient children, although only 10 babies are born each year in North America with the genetic disorder. The illness seemed a reasonable first choice because it would require inserting only one gene into the body.

Without the ADA gene, white blood cells self-destruct, leaving the body without its usual protection against foreign intruders. The concept was to draw blood from a child, pick out certain cells and grow them in the laboratory. As the cells divided, the researchers would insert the ADA gene -- a gene that is easily cloned in the laboratory.

Then the researchers would hook the child up to an intravenous tube and inject millions of those cells into the child's blood. If all worked well, the new cells with the ADA gene would begin producing an enzyme crucial to the immune system.

Originally, Drs. Anderson and Blaese wanted to put the genes into the bone marrow's stem cells, which, like an assembly line, can stamp out replicas of different kinds of blood cells. Correcting those stem cells would, they thought, eliminate the problem for the rest of someone's life.

After years of lab experiments -- in test tubes and mice -- the researchers were able to get the gene into a stem cell. But when they tried it on larger animals, they failed.

"We beat ourselves against the wall for two years," recalls Dr. Blaese. "You have this cure sitting there and you can't get it to work."

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