By Rob Stein
Monday, August 30, 2010; A1
Even as supporters of human embryonic stem cell research are reeling from last week's sudden cutoff of federal funding, another portentous landmark is quietly approaching: the world's first attempt to carefully test the cells in people.
Scientists are poised to inject cells created from embryonic stem cells into some patients with a progressive form of blindness and others with devastating spinal cord injuries. That's a welcome step for researchers eager to move from the laboratory to the clinic and for patients hoping for cures. But beyond being loathsome to those with moral objections to any research using cells from human embryos, the tests are worrying many proponents: Some argue that the experiments are premature, others question whether they are ethical, and many fear that the trials risk disaster for the field if anything goes awry.
"We desperately need to know how these cells are going to perform in the human setting," said John Gearhart, a stem cell pioneer at the University of Pennsylvania. "But are we transplanting cells that are going to cause tumors? Will they will stay where you put them and do what you want them to do?"
Supporters of these privately funded, government-sanctioned tests, including patients' advocates, bioethicists and officials at the companies sponsoring them, are confident the research has been exhaustively vetted. The Food and Drug Administration has demanded extensive experiments in the laboratory and on animals to provide evidence that the cells are safe enough to test in people and hold great promise.
"We're very optimistic," said Thomas B. Okarma, president and chief executive of Geron Corp. of Menlo Park, Calif., which after years of delay received a green light in July from the FDA to study patients partially paralyzed by spinal cord injuries. "If we're right, we'll revolutionize the treatment of many chronic diseases."
But some researchers fear that the stakes jumped even higher with the federal judge's decision blocking federal funding. If patients are hurt by the cells - or even if there's no hint the cells help - that could be a devastating blow just as scientists are scrambling for funding from private foundations and benefactors. They cite the case of Jesse Gelsinger, whose 1999 death from a gene therapy experiment set that once highly touted field back years.
"There's a lot of angst around these trials," said Evan Y. Snyder, director of the stem cell program at the Sanford-Burnham Medical Research Institute in San Diego. "There's going to be this perception that if the cells do not perform well, the entire field will be illegitimate."
Most of the apprehension focuses on the Geron trial. Safety worries - most prominently fears that the cells could cause tumors - prompted the FDA to repeatedly demand additional data from Geron, including most recently assurance cysts that developed in mice injected with the cells posed no threat.
"We jumped through a lot of hoops to convince a lot of audiences," Okarma said. "No one wants another Jesse Gelsinger."
While Geron eventually hopes to test the cells on many patients the first trial will involve 10 partially paralyzed by a spinal cord injury in the previous one to two weeks. Surgeons will inject the first patient with about 2 million "oligodendrocyte progenitor cells," created from embryonic stem cells, in the hopes the cells will form a restorative coating around the damaged spinal cord. In tests in hundreds of rats, partially paralyzed animals walked.
The trial is designed primarily to ensure the cells are safe. But researchers will look for signs that the therapy restores sensation or enables patients to regain movement.
"If we were able to do that, it would be a phenomenally positive result," Okarma said.
Spinal cord injuries, however, are highly unpredictable and in many ways mysterious. Patients can often improve on their own, for example, which will make it difficult to evaluate whether the cells had any effect. Some wonder whether trauma victims who have so recently suffered a life-altering injury will agree to the experiments out of desperation without fully grasping the risks.
"Think of it this way: You are a healthy young person, you have had a terrible accident, you wake up in the hospital and are told that you will never walk again, that you will paralyzed for the rest of your life," Stanford University bioethicist David Magnus wrote in an e-mail. "Then you are told that there is a Phase I stem cell clinical trial that you are eligible for, but a decision needs to be made quickly. It would be hard to imagine that would be the optimal scenario from the point of view of informed consent."
In the meantime, officials at Advanced Cell Technology of Menlo Park, Calif., are hoping for the FDA's go-ahead to start possibly even sooner injecting 50,000 to 200,000 cells into the eyes of 12 patients suffering from Stargardt's macular dystrophy. Retinal pigmented epithelial cells, also made from human embryonic stem cells, should replace those ravaged by the progressive loss of eyesight, usually beginning in childhood. Studies in rats found the cells helped prevent further vision loss and even restored some sight. The company hopes the approach will work for many conditions, including the leading cause of blindness among the elderly.
"These diseases are devastating," said Robert Lanza, Advanced Cell Technology's chief scientific officer. "If we could make a difference, it would be profoundly important."
Christopher Goodrich, 55, of Portland, Ore., whose eyes started failing at age 7 and who now sees the world as if looking through a dense fog, hopes he will be one of the first patients.
"The thought of being able to regain some of my vision - to be able to go back to work, to ride a bike, to even be able to see the moon - would just be so awesome," Goodrich said.
But safety worries linger for both studies. Patients risk making their conditions worse - perhaps becoming fully paralyzed or losing whatever vision they have left.
"It's one thing if you are doing a treatment for a disease where the patient is going to die without treatment," Magnus said. "It's another if they could have a relatively good functioning life."
Okarma and Lanza said they are confident the therapies are safe. Only patients 18 or older will be initially considered for the eye study, and the treatment will only be administered to one eye to ensure the patients retain at least some vision in a worst-case scenario, Lanza said. Even if there are problems with the victims of spinal cord damage, Geron's research shows the cells do not leave the site of the injury, indicating patients would not suffer any ill effects, Okarma said. Extra precautions, including assigning each subject an independent advocate, will guarantee that volunteers fully understand their decisions, he said.
"If human embryonic stem cells are going to be useful in treating humans, someone has to be the first one to try it," said Hank Greely, a Stanford lawyer and bioethicist. "They need to have their fingers crossed and hold their lucky rabbit's foot and be really careful in their preparations, because before you try something in humans you never know what's going to happen."