Experts discuss use of human stem cells in ape and monkey brains

Jul 14 2005

An expert panel of stem cell scientists, primatologists, philosophers and lawyers has concluded that experiments implanting, or grafting, human stem cells into non-human primate brains could unintentionally shift the moral ground between humans and other primates. Writing in the July 15 issue of Science, the panel reports its recommendations for minimizing the chances that experiments with human stem cells could change the cognitive and emotional capabilities -- and hence the "moral status" -- of the animals.

"We quickly realized that a fundamental issue was whether such experiments might unintentionally alter the animals' normal cognitive capacity in ways that could cause considerable suffering," says Ruth Faden, Ph.D., M.P.H., director of the Phoebe R. Berman Bioethics Institute at The Johns Hopkins University. Faden, John Gearhart, Ph.D., of Johns Hopkins' Institute for Cell Engineering, and Guy McKhann, M.D., of Hopkins' Zanvyl Krieger Mind/Brain Institute, were co-organizers of the panel.

The panel's deliberations focused on the potential effects of grafting human stem cells into the brains of non-human primates. Gearhart notes that such experiments are already under way and that some people see them as a necessary step toward using human stem cells as treatments to replace or repair brain cells lost in conditions like Parkinson's disease or Lou Gehrig's disease.

"We agreed to disagree about whether non-human primates should be used for invasive biomedical procedures at all, and to focus instead on whether experiments with stem cells and the brain posed any new, unique ethical dilemmas," says Faden.

Although the assembled experts agreed it was unlikely that grafting human stem cells into the brains of non-human primates would alter the animals' abilities in morally relevant ways, they also felt strongly that the risk of doing so is real and too ethically important to ignore.

"Our group struggled with many fundamental questions," says Faden. "Are there cognitive or emotional capacities that are unique to humans in ways that make us worthy of higher moral status? What sets one primate, including us, apart from another primate, cognitively speaking?

"There are biblical injunctions and secular reflection over the course of centuries, but nothing is certain or universally accepted, either scientifically or morally," she adds. "Debate is complicated by uncertainty and uncharted territory in all of our fields of expertise. It quickly became clear how little is known."

"Many of us expected that, once we'd pooled our expertise, we'd be able to say why human cells would not produce significant changes in non-human brains," says Mark Greene, Ph.D., then a Greenwall Fellow at Hopkins and now a professor at the University of Delaware. "But the cell biologists and neurologists couldn't specify limits on what implanted human cells might do, and the primatologists explained that gaps in our knowledge of normal non-human primate abilities make it difficult to detect changes. And there's no philosophical consensus on the moral significance of changes in abilities if we could detect them."

Although unable to rule out the possibility of morally significant changes resulting from implantation of human stem cells into the non-human primate brain, the panel concluded that cognitive and emotional changes are least likely to occur when such work is conducted on healthy adult members of species distantly related to humans, such as macaques, rather than early in the brain development of our closest biological relatives, the chimpanzees and other great apes.

The panel also recommends that specific ethical oversight be applied to studies that propose grafting human stem cells or cells derived from human stem cells into the brains of other primates.

"And, to fill in the gaps in our knowledge, proposed studies should measure and monitor behavioral, emotional and cognitive changes," says Faden. "We need to know whether the human cells have an effect on cognition, but right now, the experts aren't even quite sure what 'normal' is for some of these primates. These studies should have a component to look into that question."

Faden says the panel's work, started more than two years ago, complements the recent report on stem cell research by the National Academy of Sciences. The NAS report called for in-depth consideration of the ethics of implantation of human stem cells into the brains of non-human primates.

The panel's work was part of the Program for Cell Engineering, Ethics and Public Policy of the Berman Bioethics Institute and the Institute for Cell Engineering at Johns Hopkins. The work was funded by grants from the Greenwall Foundation.

Authors on the paper and members of the panel are Mark Greene of the University of Delaware; Kathryn Schill of Case Western Reserve University; Shoji Takahashi, Hilary Bok, Peter Donovan, Lee Martin, Andrew Siegel, John Gearhart, Guy McKhann and Ruth Faden of Johns Hopkins; Alison Bateman-House of Columbia University; Thomas Beauchamp of Georgetown University; Dorothy Cheney of the University of Pennsylvania; Joseph Coyle of Harvard University; Terrence Deacon of the University of California at Berkeley; Daniel Dennett of Tufts University; Owen Flanagan of Duke University; Steven Goldman of the University of Rochester; Henry Greely of Stanford University; Earl Miller of the Massachusetts Institute of Technology; Dawn Mueller of the University of Maryland; and Davor Solter of the Max Planck Institute of Immunobiology.