Roanoke Times
Copyright (c) 1995, Landmark Communications, Inc.
DATE: SUNDAY, January 23, 1994 TAG: 9401260026
SECTION: HORIZON PAGE: D-1 EDITION: METRO
SOURCE: BY JAMES SCHULTZ LANDMARK NEWS SERVICE
DATELINE: LENGTH: Long
Gene therapy, the attempt to edit out errors in a living person's genetic blueprint, promises to radically change the practice of medicine and, in the process, cure the incurable.
The technique wasn't involved in the pioneering work announced Jan. 14 by Dr. Gary D. Hodgen, president of the Jones Institute for Reproductive Medicine in Norfolk. Hodgen led a team who performed pre-embryonic genetic screening, enabling a Louisiana couple to conceive a child free of the fatal genetic disorder known as Tay-Sachs disease.
Gene therapy is, however, the next logical step even for babies in the womb.
In 1991, then 4-year-old Ashanthi DeSilva became the first person to receive cells that had been treated with genetic material to cure an inherited immune system disease.
Ashanti's own cells carrying the defective gene were withdrawn and injected with normal genes, then returned to her body to multiply.
Since then, several other children have received similar treatments. All appear to be thriving.
Several dozen clinical trials in Norfolk and abroad are evaluating other gene therapy treatments for genetic disease, everything from cystic fibrosis to breast cancer.
If genetic therapy lives up to its billing, doctors could conquer a host of inherited maladies by the year 2000, including Tay-Sachs, cystic fibrosis, sickle cell anemia, Alzheimer's disease, hemophilia, muscular dystrophy and many others.
Correcting the genetic code also implies improvement, being able to select genetic characteristics on the basis of superficial appeal: blue eyes, red hair and long legs. Those leery of gene therapy worry that the temptation to tinker with the body's blueprint beyond the disease-curing point will be too strong to resist.
Hodgen disagrees with those who fret that the future will run rampant with genetic abuse. What strikes him is the great medical good that gene therapy is likely to do.
To cure those who suffer is medicine's calling, he says. Gene therapy is the latest, potentially the best, way to do so.
``We don't want to make anyone superhuman,'' Hodgen said. ``We want to bring the genetically disadvantaged to a normal level. We replace what nature didn't provide.''
Twenty years of rapid scientific advance are enabling researchers to make right nature's wrongs, which is the essence of gene therapy. To accomplish this, scientists must first decipher chapters and verse of the complex manuscript of the book of life.
The entire blueprint for an individual is present in the billions upon billions of cells that compose the human body. Within each of those cells are 46 chromosomes and, within the chromosomes, thousands of genes.
The trick is figuring out which gene does what, when, and exactly where on each chromosome.
The genetic code is made up of more than 6 billion chemical ``letters,'' called nucleotides. These letters are arranged in pairs; the nucleotide adenine pairs up with thymine and cytosine with guanine to make up a double-helix strand of deoxyribonucleic acid, or DNA.
Scientists want to spell out the genetic code letter by letter so that defects and mutations within the estimated 100,000 genes can be pinpointed, analyzed and, ultimately, repaired.
Trying to break the code is enough to fry the circuits of the fastest supercomputer but it's the central aim of the Humane Genome Project, a 15-year effort to draw a complete genetic map.
Producing a final blueprint may be impossible. Sometimes, genes ``jump,'' moving from one location to another for reasons scientists have yet to fathom.
Pinning down exact genetic location may not be feasible.
Gene mutations can be caused by a lone missing nucleotide molecule, or by several-molecule gaps in the genetic code. So finding these relative molecular drops in a vast genetic ocean will require sleuthing of a most sophisticated kind.
But gene therapists aren't waiting for a perfect chart of the genome, the term used to describe the total of all genetic material in a human being.
Scientists are already working to identify the best ways to repair defective genes. The most common approach is to remove a cell from the patient and send a sort of molecular ambulance - a specialized virus that has been made harmless by genetic engineers - into the cell to chase down the defective gene.
Once inside, the genetic contents of the virus, which contain the ``good'' gene, make the necessary changes to the cellular DNA. The repaired cell is injected into the patient, where it divides and redivides normally. Copies of the healthy gene correct the original condition that caused the illness.
At least, that's how the process works under ideal conditions.
In practice, gene therapy may be short-lived. For instance, the repaired gene may not make enough of a key chemical necessary to cure a genetic disease, requiring repeat treatments. Or the engineered virus may not release its contents in the proper sequence, or do so incompletely.
And there are dozens of other, more subtle reasons that gene therapy may go awry, all having to do with the complex interactions between the various molecules that make life possible.
Yet, for all its potential drawbacks, the promise of gene therapy appears vast. What gene therapy offers to those who suffer from inherited defects is the opportunity to escape a blueprint gone bad.
Apart from the Human Genome Project, the next step for gene scientists is to, in the words of Gary Hodgen, ``immortalize the repair'' by extending gene therapy to cells in developing embryos. That way, succeeding generations will bear corrected genes within their own cells.
Gene therapy appears to offer all of us and our children the chance to live longer and better if we are able to rewrite, however modestly, the basic human code.
by CNB