The U.S. Food and Drug Administration has given the go-ahead for a California biotechnology company to inject humans with embryonic stem cells for the first time - a turning point in the decade-long debate over whether the potential of the cells to heal injuries and cure diseases outweighs the ethical questions raised by their use.
Geron Corp. plans to inject up to 10 recently injured paraplegics with the living cells this summer and monitor the patients throughout the year that follows. While the purpose of the study is to determine whether the treatment is safe, investigators also will be looking to see if it works.
"Any return of bowel or bladder function, a return of sensation or a return of lower extremity locomotion would be a very exciting finding," Dr. Thomas B. Okarma, Geron's president and chief executive, told reporters yesterday during a conference call to announce the approval. The Menlo Park, Calif., firm, which funded the University of Wisconsin researchers who first isolated embryonic stem cells in 1998, received permission to begin the Phase I safety study from the FDA this week.
Newly inaugurated President Barack Obama has pledged to broaden federal support for embryonic stem cell research, but an FDA spokeswoman called the timing of the approval "purely coincidental." Geron submitted its request last year to begin testing the treatment, and is not using federal funds for the trial. Obama has yet to appoint new FDA leadership.
Dr. Peter Gorman, a professor of neurology at the University of Maryland, said Maryland Shock Trauma Center and Kernan Hospital are likely to be among the sites at which the trial will be conducted. Gorman said he has been in conversations with Geron for several months, and the company has sent representatives to visit the facilities, both in Baltimore. A spokesman for Geron said the test sites have not been finalized.
Dr. Douglas Kerr, a neurologist at Johns Hopkins, called the approval both "very big" and "really important."
"I hope it gets us some answers we can then build on," he said.
Scientists see embryonic stem cells, which are able to develop into any type of cell found in the human body, as a potential source of replacement tissues that could be used to treat a broad range of maladies, including Alzheimer's and Parkinson's diseases, leukemia and spinal cord injury.
"Embryonic stem cells are really nature's own way of making more of ourselves," Okarma said. "We are simply harnessing the biology of normal human development in our attempts to achieve permanent cure to chronic disease and injury."
But harvesting the cells destroys the embryos, and so has drawn opposition from the Roman Catholic Church and others. President George W. Bush twice vetoed legislation that would have broadened federal funding for embryonic stem cell research.
Obama, who supported broader funding as a member of the Senate, has said he would sign such legislation as president.
The Maryland medical community, while enthusiastic about yesterday's announcement, expressed concerns about the planned trial. Kerr questioned the decision to study new injuries, as opposed to chronic spinal cord problems. If patients improve, he said, it will be difficult to know whether it was because of the treatment or if they would have improved on their own.
"Part of me worries that this may not be the best first trial," he said. For the first subjects, Kerr would have preferred a group of patients who would not have recovered under conventional treatment - such as children with spinal muscular atrophy, who usually die before the age of 2.
"What Geron has tried to do is set expectations very low - this is purely a safety study," he said. "A likely outcome is [the embryonic stem cells] will probably be safe ... but we won't have more of an understanding of the biology of what these stem cells can do and their ability to repair in human spinal cord injury."
Dr. Curt I. Civin, a stem cell pioneer at Hopkins, says low expectations are appropriate.
"What they're really testing in this study is ... can you give these stem cells to people and do they cause any harm?" said Civin, who is to leave Hopkins next month to become director of the new University of Maryland Center for Stem Cell Biology and Regenerative Medicine. "We should condition ourselves to grit our teeth and hope this is not toxic."
Ruth Faden, director of the Berman Institute for Bioethics at Hopkins, expects discussion of the moral and ethical controversies surrounding the use of the cells. But she wants attention paid to the welfare of those who agree to participate in the trial.
"We have to be thinking about what's going to be happening to these people," she said.
One concern is the safety of the cells being used, which Kerr called "very powerful." The cells in the trial are supposed to behave as nervous system cells, but he said it is possible that "one or two or 10 or 100" could retain the properties of embryonic stem cells - meaning they could continue to divide and differentiate in ways scientists didn't expect.
"They can become anything," Kerr said, "and what if they become the wrong thing?"
Okarma said tests involving more than 2,000 animals showed that such differentiation did occur in some, but added that it had "no clinical consequence. ... There's no effect on the animal's life, mortality, and we've shown in separate studies that these cells avoid recognition by the human immune system."
The treatment showed benefits in rats, Okarma said. The stem cells reinsulated damaged nerves, leading to "improvement in locomotor activity."
"This approach is one that reaches beyond pills and scalpels to achieve a new level of healing," he said. "We hope to achieve the restoration, perhaps permanently, of organ and tissue function by the injection of healthy replacement cells."
In the human trial, to be conducted at up to seven medical centers in the United States, patients will be injected in the spine at the site of the injury. They will be given anti-rejection drugs for the first 60 days and will be followed for at least a year.
A successful trial could help shift the debate over embryonic stem cells. Opponents have long argued that the potential benefits have never been proved.
"Several politicians have said over the years, 'Tell me when this is going to benefit a patient,' and then they'll loosen the restrictions," Civin said. He expressed hope that the trial would help provide an answer.
"Whether it's going to be a home run or the single," he said, "I don't know."
Read more news about stem cell research at baltimoresun.com/stemcell