Study on Human Gene Therapy
Study on Human Gene Therapy
In 1990, a three-year-old Cleveland, Ohio, girl named Ashanthi DeSilva made history when doctors infused her with genes to produce an infection-fighting enzyme called ADA that she lacked.
A decade later, the ashes of Jesse Gelsinger were scattered on an Arizona mountaintop after the 18-year-old died of respiratory distress -- essentially, his lungs shut down -- after getting a massive dose of a modified cold virus intended to carry a gene to his cells.
Somewhere in between, the promise of gene therapy has fallen short.
"This severe death in a relatively healthy individual makes us say that we have a lot more to learn," says Philip Marsden, an associate medical professor at the University of Toronto who conducts research on the genetics of blood vessels. "Clearly, with the development of gene therapy vectors, we will have to slow down."
Last week, it was reported that a clinical trial in Philadelphia, intended only to prove the treatment was safe, allowed haemophiliacs to greatly cut their ordinary treatment with synthetic blood clotting drugs. Meanwhile, it was recently disclosed that James Dent, a Toronto brain cancer patient, died unexpectedly in April, 1997, two days after beginning the second stage of a gene therapy.
Gene therapy has always sounded simple and elegant.
Put a "healthy" gene inside a "harmless" virus, infuse a patient, and the virus will carry the gene into cells by infecting them.
How can it fail?
The answer is proving complicated. Much of the problem is caused by the viral vectors used to transport genes.
In order to make a virus harmless, two things must be done.
First, its toxic components must be stripped away. Second, it must be made "replication incompetent," so that it will not make billions of copies of itself, bursting cells apart and spreading throughout the body. Otherwise, the immune system will destroy the virus, along with the helpful gene it is transporting. "So you give the virus all you need but you leave out a couple of chapters of the book of how to live as a virus," explains Marsden. If too much of the virus is removed, it will lose its native ability to enter cells to inject its DNA. No viral vector is perfect. Some are too small to transport the large genes that rectify some inherited disorders. The larger...