So eyes are on Geron, a biotechnology company that this year won the Food and Drug Administration's approval to conduct the first-ever study of embryonic stem cells in humans. The small trial will probe the safety of the treatment in patients with spinal cord injuries; subsequent trials will be required to determine if it's effective. There are reasons for caution. For one, embryonic stem cells can form tumors. And because the cells are biologically foreign—like a transplanted organ—recipients will need to take powerful immunity-suppressing drugs, which have a host of side effects, to prevent rejection.
It's that latter problem that makes scientists particularly excited about iPS cells, which would have the clinical potential of embryonic cells but can be created from a patient's own cells. Reprogramming an adult cell into an embryolike, more malleable state sidesteps the issue of immune rejection, not to mention the moral debate. It's also simple in concept—adding just four genes to an adult cell can do the trick. But the virus needed to transport the genes into adult cells poses a cancer risk. In late April, scientists reported a breakthrough in mice: They induced pluripotency by inserting proteins, which don't require a virus to carry them, instead of genes, which do. In June, researchers said they'd accomplished the same thing with human cells.
Less than perfect. Some scientists, including Geron founder Michael West, who's now CEO of the stem cell technology company BioTime, are betting iPS cells will eventually supplant embryonic stem cells. "But right now," he says, "iPS cells are less than perfect, and they're enough less than perfect that I don't know any scientist who feels they would be safe in humans as of today." For that reason, this is no time to scrap research on embryonic cells, he says.
It will be years, if not decades, before iPS cells can be refined enough to use in patients. But even if treatments are years off, Chernoff says iPS cells have another, more immediate use: to study the progression of a disease. Researchers could take normal and malignant cells from a pancreatic cancer patient, for example, turn back the clock on both, and then reprogram the cells to form pancreatic tissue. They could then monitor the cancer-derived cells to see what, exactly, goes wrong.
Despite the obstacles, scientists are cautiously optimistic that iPS, embryonic cells, or both can lead to new therapies. Type 1 diabetes and certain disorders of red blood cells are good targets, says Gasson. Replacing retinal cells damaged by macular degeneration, regenerating the immune system, and creating new cartilage in arthritis patients are, in theory, also relatively straightforward applications, adds West. If stem cells can be made to work in those simpler cases, they may be able to tackle more complex conditions, like Alzheimer's or even limb regeneration, he says. And more technical leaps may be coming; research in mice suggests it might be possible to avoid turning an adult cell's clock back entirely and instead reprogram it directly into another type of adult cell.
As for Clegg, it's too soon to tell if his will be an early success story in a stem cell treatment revolution. So far, 13 other patients have enrolled in the same trial, and the company running it, Aastrom Biosciences, aims to recruit a total of 40. (Recruitment temporarily halted after one participant died and resumed only after the FDA and other experts determined the patient had died of causes unrelated to the stem cell treatment.) Meantime, doctors are monitoring Clegg. Within months after his surgery, his ejection fraction, a measurement of the percentage of blood pumped from the heart with each beat, had improved to almost 30 percent. While shy of what's normal, that's nearly three times what it was before his procedure.
"His heart function has improved, and he's going to the gym. Can I say it's all [a direct result of] the stem cells? No," says Brian Bruckner, Clegg's primary surgeon and principal investigator of the trial at Methodist. "It's potentially an isolated instance, or it may be the tip of the iceberg."