Beta thalassemia is one of the most common genetic diseases in the world, affecting an estimated three hundred thousand people, with another sixty thousand born every year. (Evolutionary biologists speculate that the gene has survived for so long because, like the sickle-cell mutation, it may confer resistance to malaria.) Beta thalassemia is prevalent in Africa, Asia, the Middle East, and, especially, the Mediterranean. Its name comes from the Greek words thalassa, meaning “sea,” and haema, meaning “blood.” In many countries, including England, Greece, Iran, Saudi Arabia, and Taiwan, couples are screened for the disorder before they conceive, so that they know the chances of their child inheriting it. Once a patient shows symptoms of beta thalassemia, treatment is essentially palliative, consisting of regular transfusions of red blood cells from healthy donors. But with these life-saving transfusions come large amounts of iron, which builds up in the liver, heart, and other organs, amplifying the damage of the disease itself. At Hadassah, few of the patients with the severe form of beta thalassemia lived into adulthood. The years before death were typically marked by broken bones, recurrent infections, and overwhelming fatigue.
Now, a little more than four decades after I cared for these young patients, science is on the cusp of curing the disease. This week, the New England Journal of Medicine published a landmark paper on beta thalassemia by researchers in the United States, France, Australia, and Thailand. Twenty-two patients with the condition, treated at six centers around the world, underwent so-called gene therapy, a process in which the normal variant of a gene is inserted into the patient’s DNA, compensating for the abnormal one. In this case, the researchers retrieved immature stem cells from each patient’s bone marrow—the body’s blood factory—and isolated them in the laboratory. Next, they used an otherwise harmless virus to infect the cells with a copy of the normal globin gene. They cleared the patient’s marrow of diseased cells using chemotherapy, then reintroduced the genetically altered cells into the bloodstream—what is known as an autologous transplant. The cells found their own way back into the marrow.
The researchers’ hope was that the modified stem cells would mature into red blood cells and produce robust amounts of healthy hemoglobin. That hope was realized. Nine of the twenty-two patients suffered from severe beta thalassemia, and, after treatment, the number of blood transfusions they required fell by seventy-four per cent. Three of the nine no longer need any transfusions at all. The same is true of twelve of the thirteen patients with the less severe version of the disease. So far, the subjects of the trial have been observed for a maximum of forty-two months, but they will be monitored long into the future, to insure that the benefits of the therapy persist and cause no serious side effects. One early concern—that the procedure could disrupt the DNA of the stem cells, potentially triggering leukemia—has not, fortunately, come to fruition.