Science / Medicine : U.S. Ban on Using Fetal Tissue Doesn’t Stop Research : Health: Novel experiments in animals stir excitement among scientists.
The timing was ironic. As 12,000 researchers gathered recently at the Society for Neuroscience’s annual meeting, Health and Human Services Secretary Louis W. Sullivan extended indefinitely a ban on federally funded fetal tissue transplants.
The moratorium, which predominantly affects neuroscientists, forbids federal support for experimental transplants into humans of tissue from intentionally aborted fetuses. Continuing a ban initiated in March, 1988, by the Reagan Administration, it does not apply to transplants of animal fetal cells.
Sullivan, rejecting the conclusions of a National Institutes of Health advisory committee convened last year, decided that “permitting the human fetal research at issue will increase the incidence of abortion across the country.”
Though the extended ban has angered many neuroscientists, researchers at the conference shared a wealth of data from novel experiments in animals--many involving transplants of nonfetal nerve cells that may some day find application in humans. While most neuroscientists doubt nonfetal cells will ever match the therapeutic potential of fetal cells, this work stirs excitement among many researchers.
But whatever the potential of nonfetal substitutes, fetal cells remain neuroscientists’ tissue of choice. Some experiments indicate fetal tissue may prove valuable in treating Parkinson’s disease, Alzheimer’s and other neurodegenerative conditions. For example, the first U.S. patient to receive such a transplant--a 52-year-old man with a 20-year history of Parkinson’s disease--has responded to his surgery with significant improvements in mobility, reports Curt R. Freed of the University of Colorado School of Medicine in Denver, who performed the surgery with private funds in November, 1988.
The federal ban undoubtedly will minimize the number of such surgeries in the near future, further delaying any conclusions about the procedure’s effectiveness in humans, Freed said. Moreover, the few privately funded U.S. researchers continuing to experiment with human fetal cell transplants complain bitterly about being relegated to the status of scientific renegades.
But economic and political problems are not the only factors prompting neuroscientists to seek alternatives to human fetal cells. “The (funding) problems have in part stimulated people to look for alternatives, but this would have evolved even if there hadn’t been a ban on fetal tissues,” said Fred H. Gage of UC San Diego. “We’re expanding our horizons; we’re looking for options.”
Gage and his colleagues recently demonstrated that nonfetal cells do show some promise. Recently, they reported that they had successfully transplanted genetically engineered rat-skin cells called fibroblasts into the brains of rats with a syndrome resembling Parkinson’s disease. Engineered to secrete the brain chemical dopamine, which has been found in short supply in Parkinson’s patients, the cells alleviated the rats’ symptoms by an average of 35% and may hold potential as a treatment for Parkinson’s, said Gage and others. These experiments were described in the November proceedings of the National Academy of Sciences.
Researchers elsewhere are experimenting with other nonfetal cells--some gene-altered and some not--with equally intriguing preliminary results. For example, many presentations at this year’s neuroscience meeting focused on transplants of fibroblasts genetically engineered to produce substances such as nerve growth factor, a protein that stimulates nerve regeneration. These cells, when implanted into the brains of rats suffering from nerve damage, stimulate neuronal repair.
Other researchers have transplanted young astrocytes--star-shaped, central nervous system cells--from donor rats onto injured spinal cord tissue in recipient rats. Astrocytes belong to a class called glial cells, which provide physical and biochemical support for neurons. Reports at the neuroscience meeting indicate that transplanted astrocytes and other types of glial cells appear to improve coordination in the injured rats by stimulating the production of nerve-nurturing substances around the injury and by preventing scarring there. Tiny scars can block regenerating neurons from renewing connections with surviving nerve endings.
“It’s become a very hot area to look for cells that secrete factors that may facilitate repair,” Timothy J. Collier of the University of Rochester (N.Y.) School of Medicine and Dentistry said. “Everyone’s very interested in glial cells, which seem to make damaged cells happier.”
Researchers have begun genetically engineering glial cells in attempts to enhance their therapeutic potential. However, Freed said, “it will be some time before we become as comfortable with custom-made cells as we are with fetal cells, which we understand much better.”
Moreover, scientists have yet to demonstrate that engineered cells can perform all the functions of their fetal counterparts. “I absolutely support (engineered) cell-line research to come up with improved transplant material,” said D. Eugene Redmond, director of the neurobehavior laboratory at Yale University. “But the probability of taking something like a fibroblast and engineering into it all the factors necessary for neuronal function and communication so it knows who to talk to, when to release its transmitter. This may involve a thousand things.”
Added Gage: “It certainly is clear that fetal neuronal transplants are more effective than any of the other cell types at present.”
Indeed, fetal cells today seem awash in scientific praise. “Their ability to survive and multiply necessitates the grafting of only small numbers of cells . . . and they are adaptable to the host environment,” wrote University of Rochester neurobiologists John T. Hansen and John R. Sladek in a review article in the journal Science. “The benefits of studying fetal cells are many, and the clinical potential for their use as therapeutic tools is just now being realized.”
In contrast, Redmond noted, gene-altered fibroblasts and other engineered cells “are going to be extremely suspect” because of their potential to divide uncontrollably, like cancerous tumors. “Some of these alternatives are going to have extreme liabilities.”
At this point, Gage said, no one really knows whether fetal cells can live up to their exalted promise. Ban or no ban, he thinks researchers need to conduct more fetal cell transplants into animals--a procedure allowed under the moratorium--before embarking on widespread human trials.
But until the fetal cell transplants into humans can proceed unimpeded, their value will remain an open question, Gage and others say. And the decision on whether to go ahead with such trials should be based upon scientific rationale, they insist.
“None of the reasons for the ban had anything to do with bad science or good science or whether or not it’s reasonable to pursue this work on scientific grounds,” Gage said. “I can’t believe that patients with degenerative diseases are not up in arms. It doesn’t seem real. But, then, I’m a scientist.”
