Gene Therapy Has Vast Potential Despite Setbacks; Push On With Human Trials
The recent news that two boys in France have been diagnosed with a leukemia-like disease after undergoing gene therapy for “bubble baby” syndrome has sent shock waves through the scientific community. In the United States, the Food and Drug Administration halted certain gene-therapy trials.
For those of us outside the U.S. who are engaged in gene therapy research, the shadow of the 1999 death of Jesse Gelsinger from gene therapy at the University of Pennsylvania, plus this latest news, has brought us to a fork in the road as we take stock of the powerful tools we are learning to manipulate.
A look backward can sometimes show us which path leads forward. The first chemotherapeutic drug was discovered by accident more than 60 years ago when an explosion at a chemical warfare plant in the port of Naples exposed sailors to high doses of nitrogen mustard. The sailors later developed bone marrow tumors as a result of the chemical’s effect of enhancing cell growth. Later, it was discovered that lower doses of such agents had the opposite effect and could be used to stem the rapid growth of tumor cells. By the early 1940s, we saw their first applications in cancer therapy in the U.S. Initially, patients experienced tumor remission, which caused great excitement. This was followed by deep disappointment, however, when tumor growth recurred and all the patients died.
Fortunately, the strength of the human scientific spirit prevailed, and this initial setback did not halt drug development but instead stimulated further research into improved chemotherapeutic agents, which eventually were tested in human cancer patients.
If fear caused by the initial failures of chemotherapeutic agents had halted further research and clinical trials, there would be no therapy today for cancer, one of the most common causes of death worldwide. Similarly, if we had given up after early unsuccessful attempts at transplantation, patients with blood disorders or end-stage liver, kidney or heart disease who benefit from bone marrow or organ transplantation would have no chance for survival today.
Though it may represent a leap of faith and science to try out in humans what is initially observed in a test tube or in lab animals, human clinical trials are the only way to narrow the gap. We now are in the infancy of genetic therapy. These treatments are as mysterious, yet ultimately as promising, as early chemotherapy and organ transplantation.
Researchers believe that many diseases -- cancer and infectious, metabolic, genetic and even psychiatric disorders -- might be treated by the appropriate gene therapy protocol. Thousands of patients already have been treated for a wide array of diseases in hundreds of human gene-therapy trials. Yet there has been only one death directly attributable to genetic therapy.
Unfortunately, the two infants in France were born with a rare genetic immunodeficiency and would have died during their first year of life without gene therapy. They developed a malignant disease attributable to an error in the insertion of the gene given to cure the immunodeficiency.
We must see the big picture: These unfortunate patients were two of 10 children in the trial. While this technical failure is tragic for the patients and their families, eight other immunodeficient children treated in the same way are healthy and have a good chance of a normal life.
Gene therapy has huge potential and needs public support. By banning certain procedures, the FDA is misguidedly attempting to protect the public from a treatment whose absence may be more harmful than its practice.
The history of recent drug development teaches us that, more often than not, there are impediments along the road to medical achievements. Humanity will gain much from taking the new therapeutic avenues opening up through genetic therapy. Some rewards are down the path, just after the fork. Others will come into view much later.
