We've become sufficiently accustomed to announcements of medical or technological breakthroughs that today we tend to skim past them, headlines with "Scientists Discover Amazing _________" having lost their punch. Nevertheless, two reports of clinical trials last week should inspire in us both wonder and pause, for they herald the beginning of the end of Homo sapiens, as our species is presently constituted. Researchers in Paris and Houston reported success in using genetic therapy to treat severely ill patients. In the last 20 years, there have been scientists who have made many, many attempts--all unsuccessful--to infuse new genes into the bodies of those suffering genetic illnesses. Finally, such an attempt has worked, and the likely outcomes are two: First, that an important new round of disease reduction is in store, and second, that humanity is on the verge of acquiring the ability to alter its genetic destiny.
Genetic therapy has been possible in principle for years but has consistently frustrated physicians. The idea is simple. Many diseases--among them cystic fibrosis, sickle-cell anemia, and, in some instances, cancer--are caused by defective DNA. What if you could infuse diseased cells with healthy DNA? The obvious way to do this seemed to be to splice healthy DNA into the kinds of viruses that were designed by nature to attack human genetic material, thereby "infecting" patients with something that would make them better: new DNA dedicated to faltering cells. Try after try ended in failure. Gene-therapy pioneers such as the renowned physician W. French Anderson, of the University of Southern California, knew only grief. Anderson saw many parents bring him babies or children suffering grave genetic conditions such as thalassemia, a hemoglobin disorder. He infused them with genes to make healthy hemoglobin, but the therapies simply didn't work. The new DNA ended up in the wrong part of the body, or failed to "express" (activate). Anderson grew sufficiently discouraged that he proposed attempting genetic therapy on fetuses still in utero, on the theory that "once the child is older,"--older in this usage meaning anyone who's been born--"the cells may just be too developed to accept new genes."
But now researchers appear to have broken that barrier. One team in Paris appears to have cured two toddlers of SCID, or severe combined immunodeficiency X1, a genetic disorder that causes immune-system collapse and is best known to the public as "boy in the bubble disease." After genetic therapy, the immune systems of the two toddlers began to function again, though the cure won't be considered certain until the toddlers stay healthy for several years. In the United States, teams in Houston and elsewhere appear to be curing some types of cancer caused by a defective gene called p53, which, when healthy, contains the DNA codes that help control cell growth. Infusing healthy p53 genes into cancer patients is the first type of DNA therapy to go into Phase III clinical trials, the stage that precedes general availability of a drug. Within a few years, this type of genetic therapy may be generally available, and researchers hope it will be effective against some types of cancers, including brain, breast, lung, and prostate cancer.
From the standpoint of the research world, these happy results could not have come at a better time. Last fall, an 18-year-old volunteer who had a rare but probably not life-threatening genetic disease died during a gene-therapy experiment at the University of Pennsylvania; this week it was revealed that a Tufts University researcher had failed to report another death in a gene-therapy test. Federal regulators at the Food and Drug Administration and the National Institutes of Health were beginning to wonder if gene-therapy researchers were overselling their idea, or even cultivating a cowboy mentality, brushing aside risks in their zeal for the Nobel Prize that will surely go to those who perfect gene therapy. Now, proponents of this idea can argue that they really are acquiring the knowledge of genetics and biochemistry necessary to make the concept work. Among other things, researchers have learned how to refine the viral "envelopes" in which healthy genes are placed so they will act like little guided missiles aimed straight at the diseased DNA.
For others who have been or might be sick--that is, everyone--this initial stage of genetic-therapy success also seems auspicious. There is now good reason to hope that cystic fibrosis, sickle-cell anemia, Tay-Sachs disease, and many other DNA-based illnesses will become curable soon, perhaps even soon enough to save those now imperiled by these diseases. Cures or treatments for diseases with a genetic component, such as cancer, may become practical. More generally, the precision-guided features of genetic therapy may help physicians refine their approaches to all kinds of problems, reducing the use of synthetic chemicals and substituting self-healing substances from the body's own genetic arsenal. A new era in which illness dramatically declines, and technological and alternative medicine converge, may be the result.