For 12 years, the world followed the life of David, the boy who lived in a germ-free bubble at Baylor College of Medicine in Houston.
Because he was born with a defective gene, David's immune system failed to develop, leaving him vulnerable to common, normally harmless bacteria and viruses. Earlier this year, David's physicians tried to create the immune system he was born without. The attempt failed, and in February David died.
The current treatment for David's disorder, called severe combined immunodeficiency disease or SCID, "is a bone marrow transplant," says Dr. W. French Anderson, chief of the laboratory of molecular hematology at the National Heart, Lung and Blood Institute. "But there are not enough compatible bone marrow donors."
Soon, however, there will be another alternative for SCID victims: gene therapy. The Congressional Office of Technology Assessment (OTA) released a report on Monday examining the technology and the ethics of repairing defective human genes.
The first human trials of gene therapy "will probably be started in about a year," says Anderson. Science fiction becomes science fact.
Genetic defects can cause between 2,000 and 3,000 disorders, concluded the OTA study. The first experiments will try to fix the single-gene defects that cause dozens of diseases -- including SCID, Lesch-Nyhan, sickle cell anemia, Tay-Sachs and perhaps eventually cystic fibrosis.
Genes are portions of deoxyribonucleic acid, or DNA, a chemical shaped like a twisted ladder. Each gene carries the information needed to make a particular protein. A human cell carries thousands of genes on the six feet of DNA packed into its 46 chromosomes.
If damaged, a gene loses its ability to direct the production of its protein, or it produces a defective protein. If the protein carries out a key enzyme function, then that function is lost and a genetic disease results.
In SCID, the gene that makes adenosine deaminase, or ADA, is defective. Without ADA, the body fails to make normally functioning infection-fighting white blood cells.
"We know that if you have no ADA enzyme, you are sick, but if you have a few percent of a normal level, you may be quite well," says Dr. Stuart Orkin, associate professor of pediatrics at Harvard University and member of the Boston Children's Hospital team working on a gene therapy for this defect.
Although current experiments are limited to animals, Orkin says the Children's team may -- within a year -- use the following procedure in humans:
Defective bone marrow will be removed from a SCID child and infected with a special virus that can be modified to carry the normal human ADA gene into bone marrow cells. There, the normal gene becomes part of the permanent genetic makeup. Once in place within the cell, the replacement gene should begin directing the production of the ADA enzyme, allowing the infection-fighting white blood cells to develop normally.
The gene-treated bone marrow would then be injected back into the patient. If it works, the patient would be cured of this lethal disease.
A number of technical details remain to be worked out, Orkin says, including how much bone marrow must be removed for gene therapy and whether the remaining defective marrow must be destroyed with radiation or drugs.
Human gene therapy technology currently remains limited to simple disorders in which a single gene is missing. "At present, the only human tissues that can be used for gene transfer are bone marrow and skin cells," says NIH's Anderson. The technology cannot repair multigene defects, which cause diseases like cancer, or chromosomal abnormalities, which cause diseases such as Down's syndrome.
As researchers learn how to package genes in modified viruses that infect only specific organs, gene therapy could someday become as simple as an injection, says Anderson.
Gene therapy also carries some risks. "The problem is what the viruses might do," says Anderson. Some viruses might cause infections in areas of the body other than those receiving the gene therapy. Teams of researchers on both coasts have developed viruses that self-destruct after infecting one cell.
Cancer is another possible problem, Anderson says. Viruses deposit the transplanted gene randomly in the cell's chromosomes. If it lands in a control region for one of the 20 so-called oncogenes -- genes that can turn a normal cell into a cancer cell -- a tumor could result.
Although human gene therapy raises many ethical questions -- specifically, that altering genes could change the human race -- the OTA study concluded that gene treatments that cannot be passed on to succeeding generations are essentially the same as any other medical treatment.
Jeremy Rifkin, head of the Foundation for Economic Trends in Washington and a leading critic of gene research, says that while he does not object to genetic repairs in an individual, he and a coalition of religious leaders object to gene changes in sperm and egg cells, which would be passed on to succeeding generations.
But even with the current research "there is an open question about whether changes in the genetic code in [body] cells might have some impact into the sex cells," Rifkin says, especially since viruses are used to introduce the new genes.
Anderson says that by developing viruses that infect only specific tissues, "the danger of inadvertently infecting [sperm and egg] cells could be eliminated."