Doctors map out
genetic treatments

Fighting disease with gene
therapy is like 'molecular white-out'

By Helen Altonn
Star-Bulletin

A doctor who was involved in the world's first gene-therapy treatment of children says the movement to fight diseases with altered or new genes is just beginning.

"More and more, we will be able to treat either by giving genes for therapy or going into a cell and correcting the misspelling," says R. Michael Blaese.

"It's like a molecular 'white-out.' "

Blaese, chief of the Clinical Gene Therapy Branch of the National Institutes of Health's National Center for Human Genome Research, will be among the key speakers at a conference here next week on genetics and molecular biology.

"From Discovery to Practice" is the theme of the meetings sponsored by the Queen's Medical Center and Ohio State University James Cancer Hospital Monday through Wednesday at the Hilton Hawaiian Village.

Blaese will discuss "Gene Therapy, The Science Beyond the Story" in a public lecture at 6:30 p.m. Monday in the East-West Center's Keoni Auditorium.

He was co-leader of a team at the NIH that in September 1990 performed successful gene therapy on Ashanthi "Ashi" DeSilva, now a normal 12-year-old. Four months later, the group performed the same therapy on Cindy Cutshall, then 9.

The girls have a rare disease called ADA deficiency that killed the "bubble boy" in 1984. Because of a flawed gene, the T-cells of their immune system weren't able to produce ADA, an enzyme necessary for survival.

To treat the children, the NIH team took viruses from mice, engineered them to remove the genes, then replaced them with normal ADA genes, Blaese said.

"We're still very early in development of this treatment," he said in a telephone interview from Bethesda, Md.

"But worldwide, several thousand patients have received gene therapy directed at one or another disorder."

A whole series of gene therapies for cancer are going through clinical trials and other trials are under way, he said.

"Genes are the sets of instructions that direct the function and structure of all living things," Blaese explained.

"So when you have a disease that is caused by a garbled set of instructions, which is really what genetic diseases are, the most elegant way to treat them would be to put in a new set of instructions."

That is basically gene therapy, he said.

Although a lot of trials are going on testing different gene treatments, Blaese said, "My guess is very few will ever make it to something your personal physician will use. That is true of so many medicines. Most don't work. We're lucky if a few do."

He said the first stage of molecular medicine is directed toward treatments to "make patients' lives healthier, more productive and less painful."

It may be possible ultimately to identify and eliminate serious genetic disorders, but that is a different kind of technology a long way in the future, he added.

Blaese said he will touch on the controversy and promise of gene therapy in his lecture and discuss what medicine might be like in the next century.

"It's not going to impact on physicians in Hawaii for the next few years, but it's going to be coming, certainly," he said.

The Human Genome Project was launched about 10 years ago to map the biochemical code for the 100,000 or more genes that determine human physical characteristics.

Blaese said it is "one of the few federal projects ahead of schedule and under budget." The first sequence will be completed in about four years, he said.

"Then we have to figure out what all that stuff means," he said. "The genome project will evolve over the next decade or two as we move from obtaining the raw sequence of information and uncode what it actually does."