Despite the fact that, last fall, a teenager from Tucson, Arizona died from a gene therapy experiment at the University of Pennsylvania, gene therapy has been making steady, quiet progress.

Eighteen-year-old Jessie Gelsinger suffered from a metabolic disorder and had volunteered for an experiment to test gene therapy for babies with a fatal form of the disease. His death sparked controversy in both the scientific and political arena. Politicians and the press alike claimed that gene experiments were being conducted too shoddily. Ethical questions also arose. Some said that Gelsinger’s death was a clear indication that people should not interfere in gene organization.

Some researchers are saying that, little by little, they are refining and perfecting methods by which to deliver genes to their target cells. Laboratory experiments of gene-based treatments for hemophilia are showing positive results, and certain cancer patients are responding to gene therapy. In addition, French scientists this past spring reported that they had successfully utilized gene therapy to treat babies born with defective immune systems.

In the first week of this June, over 2500 leading gene therapy scientists from all over the world came together for the third annual conference of the American Society of Gene Therapy. Scientists came with a bit of excitement, sadness, and defiance. The memory of Gelsinger’s death was inescapable as the conference continued.

The theory behind gene therapy is quite simplistic: the idea is to cure or prevent a disease by giving healthy genes to patients with defective ones. Yet in the last decade since researchers at the National Institute of Health in Bethesda, Maryland, conducted the first human experiment the findings or lack thereof, for the most part, have been disappointing. A possible reason for this is that scientists have had trouble devising delivery vehicles, called vectors, that can direct genes into the proper cells and get them to function once they are there. Inserting genes into deactivated viruses that target certain cells, literally infecting them with healthy DNA, usually creates vectors.

Gelsinger’s death raised serious safety questions on one of the most commonly used viruses, the adenovirus, that causes the common cold. In most patients, the adenovirus produces mild, flu-like symptoms. Yet in Mr. Gelsinger’s case, it provoked a fatal immune response.

Even prior to Mr. Gelsinger’s death, molecular biologists began turning to a different virus, the adeno-associated virus, or AAV, which is thought to be a safer alternative to the adenovirus. Now, a team of researchers at Children’s Hospital of Philadelphia, Stanford University, and Avigen Inc., a biotech company, is reporting promising results in patients with hemophilia who received a genetically engineered form of AAV that contains the gene for production of Factor IX, a protein that is needed to make blood clot.

REFERENCES:

1) Stolberg, Sheryl Gay. “Despite Ferment, Gene Therapy Progresses.” New York Times.
June 6, 2000, Science/Health Section.