The upshot was that embryonic stem cell research appeared stuck in neutral. During the eight years of the George W. Bush administration, it was limited to a few cell lines, some of them sickly, and was barred from federal funding—the only source of money plentiful enough to push such cutting-edge biology into high gear. Year after year, progress was glacial.
And then, even with the restrictions in place, the breakthroughs began. One of the greatest came in November 2007, when scientists in Japan and the United States reported that they could make adult skin cells from mice revert to the embryonic state. This feat was later achieved in humans as well. The reverted cells, called induced pluripotent cells, appear to be capable of transforming into a wide range of cells. No embryos are involved, and because the cells come from a person’s own body, the pitfall of rejection is eliminated.
In 2008 a group of medical researchers led by Robert Lanza at Advanced Cell Technology in Worcester, Massachusetts, reported another leap: They discovered a way to avoid destroying the embryo by deriving an entire stem cell line from a single embryonic cell. The cell, taken from the embryo between the zygote and blastocyst stages, can be collected without damaging the embryo, and yet it is still versatile enough to give rise to whole classes of tissue types. Some of these harvested cells produce blood, for instance, and others neuronal tissue or muscles or retinal cells.
Now stem cells are being combined with gene and immune therapies, compounding the pace of progress. For instance, researchers at the Salk Institute in California have taken skin cells from a patient with the genetic disease Fanconi’s anemia, often associated with leukemia. The cells were reverted to the embryonic state and then retrofitted with healthy genes lacking the Fanconi mutation. In lab tests the refurbished cells cured the disease in mice and in human blood. The researchers have not yet injected the cells back into the patient but say this is “proof of principle that this technology could be used to cure a disease.”
While stem cell science is in fast-forward, the political climate is changing as well. Under the auspices of President Obama, the National Institutes of Health has loosened its guidelines so that new, hardier, and more experimentally useful embryonic stem cell lines can be studied and deployed. Fresh research funding appears poised to give an extra jolt to the revitalized field.
Stem cell treatments are already a reality for diseases of the blood, such as leukemia and sickle-cell anemia (like Paizley’s), and for tissue repair of the skin and the cornea. Projects that loom ahead include treatments for Parkinson’s, Alzheimer’s, and even paralysis.
Funded by the U.S. Army, tissue engineers have begun developing designs for replacement organs—kidneys, hearts, and lungs. The Army hopes the effort will make it possible to regenerate arms and legs lost by soldiers in war. Even autoimmune diseases, in which the body attacks itself, promise to recede in the face of coming stem cell treatments as defective immune cells are replaced with healthy ones. As if all this were not enough, Japanese scientists have announced an emerging capability to regenerate organs in place, inside the body itself. Their proof of concept, published this past August, enlists stem cells to regenerate teeth in mice.
Many researchers have found it hard to check their euphoria. There was a thrilling moment in 2007 when stem cells cured an HIV patient who received a bone marrow transplant to treat his leukemia. Aiming to treat the HIV as well, the hematologist chose a donor with a rare genetic mutation that makes cells immune to HIV. As hoped, the donor’s stem cells took over, treating the leukemia and apparently banishing the HIV.
But in medicine, dramatic cures are rarely as simple as they may seem. Bone marrow transplants can cause deadly immune reactions, turning the decision to proceed into a perilous judgment call; HIV patients are better served with today’s drug cocktails unless they need the transplant for another disease, experts say. In short, stem cell therapies remain uncertain and risky, hampered by unforeseen complexities. Stem cell clinics in India and Mexico may proclaim that they can heal everything from autism to cancer, but clients who spend millions of dollars there may be buying snake oil. The reality, say leading stem cell researchers, is that every disease and disorder needs its own special formula, including just the right promoter chemicals given at just the right dose, and just the right kind of stem cells introduced at just the right stage.
Where the promise is great, the risk is great as well. “Embryonic stem cells represent the good, the bad, and the ugly,” says Doris Taylor, director of the Center for Cardiovascular Repair at the University of Minnesota. “When they are good, they can be grown to large number in the lab and used to give rise to tissues, organs, or body parts. When they are bad, they don’t know when to stop growing and give rise to tumors. The ugly—well, we don’t understand all the cues, so we can’t control the outcome, and we aren’t ready to use them without more research in the lab.” The potential can become reality only through costly research and the words that every patient dreads: more waiting.
Let the trials begin
With most stem cell therapies so new or experimental, the best place to access them is in a clinical trial—but you might want to hold back unless you are close to death. That was the grim dilemma facing Deanna Graham, whose joints began to swell and hurt in the fall of 2007, about the same time the 49-year-old accountant noticed the wrinkles on her fingers disappearing as if she were aging in reverse. Within a few months, her fingers began to turn cold and changed color from a dusky red to a deathly white. Then she began to have kidney problems, high blood pressure, and difficulty breathing. Her joints became so painful that, she says, “I was walking like Quasimodo.” Just months after Graham’s symptoms appeared, her doctors made a diagnosis of a systemic form of scleroderma, an autoimmune disease in which the body overproduces collagen, the fibrous supporting structure of the body. The disorder causes the skin to become thick and hard. If it affects internal organs, too, the patient is said to have systemic sclerosis, an often-fatal condition with no known cure.
Graham looked to the Internet for treatment options and came across Duke University oncologist Keith Sullivan, who was comparing standard chemotherapy and stem cell therapy as part of a large-scale clinical trial for scleroderma. The first group of volunteers received intensive chemotherapy, which wipes out the marrow that produces the immune cells responsible for the disease. The fix eliminated these immune cells but failed to replace them with healthy cells able to fight off infection. The second group received chemotherapy along with adult stem cells taken from their own bone marrow. Sullivan’s hope was that after the chemo destroyed the original, defective immune cells, the reintroduced stem cells would settle in the bone marrow and turn out healthy immune cells—permanently.
Sullivan, who strives to be completely honest with his patients, gives clinical-trial volunteers a brochure explaining that the treatment “may be ineffective and could be more harmful than receiving no treatment at all.” Graham decided to enroll anyway. A small and articulate woman, she explained her decision from a hospital bed at Duke University Medical Center. Facing a “50 percent chance of death” from scleroderma, she could not imagine not taking a chance.
That was a year ago, and Graham says she is now “doing great,” though problems persist. Her hands still curl into claws and her knees and hips are still weak, she says, but “the list of healed areas is much longer. I feel hopeful, happy, and am much more active today.” Other ongoing stem cell trials are targeting blood disorders like aplastic anemia, leukemia, lymphoma, and, of course, sickle-cell disease.