In 1990, geneticist William French Anderson injected cells with altered genes into a four-year-old girl with severe immunodeficiency disorder. This was the first sanctioned test of gene therapy, in which genetic material is used to treat or prevent disease.
“If we’re lucky,” Anderson told The Chicago Tribune, “with this little girl we’ve opened the door for genetic engineering to attack major killers and cripplers, particularly AIDS, cancer and heart disease.”
Gene therapy has never fulfilled these grand hopes. In the decades since Anderson’s experiment, thousands of clinical trials of gene therapies have been carried out. But the first gene therapy was only approved for sale in the U.S. this week. The Food and Drug Administration announced its approval of Kymriah, a gene therapy produced by Novartis for a form of childhood leukemia. A few gene therapies have previously become available in China and Europe.
An FDA press release emphasizes the “historic” nature of the approval. “We’re entering a new frontier in medical innovation with the ability to reprogram a patient’s own cells to attack a deadly cancer,” FDA Commissioner Scott Gottlieb says.
As I have noted in previous posts (see Further Reading), the hype provoked by genetic research has always outrun the reality. Gene-therapy proponents have long predicted that it will eliminate diseases such as cystic fibrosis and early-onset breast cancer, which are traceable to a defective gene, as well as disorders with more complex genetic causes. Enthusiasts also envisioned genetically engineered "designer babies" who would grow up to be smarter than Nobel laureates and more athletic than Olympians.
Gene therapy turned out to be extremely difficult, because it can trigger unpredictable, fatal responses from the body's immune system. The National Institutes of Health warns that gene therapy “can have very serious health risks, such as toxicity, inflammation, and cancer.”
Kymriah is a case in point. The FDA press release warns that Kymriah can cause “life-threatening” immune reactions and “neurological events,” as well as “serious infections, low blood pressure (hypotension), acute kidney injury, fever, and decreased oxygen (hypoxia).” According to The New York Times, the FDA “is requiring that hospitals and doctors be specially trained and certified to administer [Kymriah], and that they stock a certain drug needed to quell severe reactions.”
Kymriah illustrates another problem with gene therapy: high cost. Novartis is charging $475,000 for Kymriah. As a recent Reuters article notes, over the past five years two gene therapies have been approved for sale in Europe, one for a rare blood disease and the other for the “bubble-boy” immunodeficiency disorder. The therapies cost $1 million and $700,000, respectively. So far, the companies that make the therapies have achieved a total of three sales.
As journalist Horace Freeland Judson points out in this excellent 2006 overview, “The Glimmering Promise of Gene Therapy,” biology and economics have conspired against gene therapy. Judson notes that “most individual diseases caused by single-gene defects–the kind that seem most likely to be cured by gene therapy–are rare. (Sickle-cell anemia and some other hemoglobin disorders are among the few exceptions.)”
Judson adds that because different diseases “have different genetic mechanisms and affect different types of tissue, each presents a new set of research problems to be solved almost from scratch. As the millions burned away, it became clear that even with success, the cost per patient cured would continue to be enormous. And success had shown itself to be always glimmering and shifting just beyond reach.”
The advent of CRISPR, a powerful gene-editing technique, has inspired hopes that gene therapy might finally fulfill expectations. Researchers recently employed CRISPR in human embryos to counteract a mutation that causes heart disease. “Potentially,” The New York Times reported last month, the method “could apply to any of more than 10,000 conditions caused by specific inherited mutations.”
CRISPR has also renewed concerns about the ethics of engineering people with enhanced physical and mental traits. These concerns are grossly premature. As Science noted recently, CRISPR poses some of the same risks as other gene therapies. The method “still has a long way to go before it can be used safely and effectively to repair—not just disrupt—genes in people.” And in fact questions have now been raised about the CRISPR research on embryos mentioned above.
Some day, applied genetics might live up to its hype, but that day is far from arriving.