By Rick Weiss
Washington Post Staff Writer
Thursday, March 1, 2001; Page A04

Scientists in Philadelphia have combined pieces from two of the world's deadliest microbes, the ebola virus and the virus that causes AIDS, to make a hybrid virus they hope will someday cure cystic fibrosis when sprayed into patients' lungs.

The idea of intentionally infecting someone with a blend of the two killer viruses may seem bizarre, scientists said, but the new creation lacks key components needed to cause disease. The goal is to make a virus with ebola's unusual talent for attaching to lung cells and the AIDS virus's exceptional ability to persist in the body, then use that new virus to deliver curative genes to patients with the lung disease.

The hybrid virus, not yet ready for human testing, is the most extreme and controversial example of a new strategy emerging in the field of gene therapy, which aims to cure diseases by giving people new genes. After a decade of failures using other methods to get helpful genes into patients' cells, researchers are turning to some of the world's most notorious microbes as tiny vehicles for delivering therapeutic payloads.

Hybrids made from the human immunodeficiency virus (HIV) and the ebola virus, which causes the fatal bleeding disease featured in the nonfiction thriller "The Hot Zone," are not to be feared, according to the University of Pennsylvania researchers who created them. The team removed the parts of both viruses most responsible for their deadliness. Now, they plan to add copies of the gene that cystic fibrosis patients lack.

Some researchers agreed that the approach is safe. "It's not even HIV anymore; it's just pieces," said W. French Anderson, a gene therapy pioneer at the University of Southern California. "And ebola sounds horrible, but this has nothing to do with the ebola virus that knocks out all your defense mechanisms and kills you. Those genes are all gone."

But others said they are not so sure.

"I wouldn't want this thing put into me," said Robert Gallo, director of the Institute of Human Virology in Baltimore and co-discoverer of HIV.

It's possible that the new virus could prompt an immunological response severe enough to harm the patient, Gallo said. Equally frightening, he said, the hybrid virus might combine with wild HIV to create an entirely new kind of contagious virus.

The Food and Drug Administration has already raised those and other yellow flags. At a conference in 1998, FDA official Anne M. Pilaro warned that such viruses would present "unique issues regarding determination of safety."

The new work comes from Penn's Institute for Human Gene Therapy and its director, James Wilson. The institute has focused on inventing new gene delivery methods since the FDA ordered it last year to halt all human clinical studies after a young gene therapy patient died there.

Wilson, who in November settled a lawsuit filed by the patient's father and is now fighting additional sanctions from the FDA, declined to be interviewed. But another scientist on the project, Gary Kobinger, said the research offers early proof that the approach is worth pursuing.

"The words are scary or sound scary, but for now we are on the level of science, not on the level of recruiting someone to try it," Kobinger said.

The team combined the genes that allow ebola to attach to lung cells, those that help HIV infect and persist inside cells, and "marker" genes that helped the researchers track the fate of their new creation. The hybrid virus infected, in test tubes, lung cells from mice and people, the team reports in the March issue of Nature Biotechnology. And when squirted into the windpipes of mice, the viruses infected the animals' lungs and delivered the marker genes.

Work on the viruses was conducted on the Penn campus in a "biosafety level 3" containment module, a double-doored, specially ventilated lab space that federal regulations require for all experiments involving exotic microbes that "may cause serious or potentially lethal disease as a result of exposure by the inhalation route."

Many questions remain unanswered, Kobinger and others said. Will the virus attach to lung cells in cystic fibrosis patients, who typically have lots of mucus in their lungs? Will a patient's immune system attack and neutralize the virus? Could the new virus, like related viruses, disrupt genes inside lung cells, causing lung cancer or other problems?

"It's quite a ways from being useful," said Melissa Ashlock of the Cystic Fibrosis Foundation in Bethesda. "But it's definitely a step forward in a field that has not had many forward steps."

© 2001 The Washington Post Company