Chimeras: Animal-human Hybrids
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TOM BEARDEN: On the Caribbean Island of St. Kitts, these surgeons are implanting several million human neural stem cells into the brain of an African green monkey. When the human cells mature — the black dots in the picture — they function as living partners with the billions of monkey brain cells that are already there.
Dr. Eugene Redmond hopes the implanted cells in monkeys like this one, which come from federally approved lines of stem cells cultured in U.S. laboratories, will eventually help supply a chemical called dopamine. That chemical is missing from the brains of people who have Parkinson’s disease, which afflicts up to a million Americans.
EUGENE REDMOND: We find that we can get stem cells to survive for long periods of time in the brain. They make into different types of cells. And we have some preliminary results in functionally impaired animals that the stem cells improve their Parkinsonism and make them better.
TOM BEARDEN: Will this eventually lead to a cure for Parkinson’s disease?
EUGENE REDMOND: Well, we would like to think so. This and maybe some other techniques that are coming along will have to be combined in order to make a real cure.
TOM BEARDEN: Dr. Redmond’s implanted animals don’t look or act differently, but they’re now something called chimeras. It’s a reference to ancient Greek mythology. A chimera was a combination of goat, lion and snake. To modern science, it’s an animal that combines components of two different species in one body. Chimeras themselves aren’t really new. In the 1980s, Scottish scientists used cloning techniques to create a half sheep, half goat, a geep. But bringing embryonic human stem cells into the mix is new, and has raised a host of ethical questions that the scientific community is now trying to grapple with.
Biologist Stuart Newman was so concerned he applied for a patent on a human-animal chimera in hopes of drawing public attention to what he saw as the dangers of such research. The patent was denied, which is just what he wanted.
STUART NEWMAN: The goal was to alert the public as to what the technology was capable of, to point out that because of the biological continuity between all different living species, there’s really no obstacle to making something that is midway or part way between different species.
TOM BEARDEN: For example?
STUART NEWMAN: Well, a half human, half chimpanzee.
TOM BEARDEN: Newman and others are concerned that if enough human cells are integrated into the brains of animals, humanlike consciousness might develop. But Redmond and his associates are keeping a close watch on their monkeys, like this one, dubbed XO-47. Redmond hasn’t seen anything remotely like human behavior in this or any of his test subjects.
EUGENE REDMOND: We’re putting maybe eight to ten million cells in a brain that maybe has twenty to forty billion cells. So this is an extremely small impact. It’s not going to make a monkey into a humanized monkey.
TOM BEARDEN: This mouse also has human neural stem cells its brain. Like Redmond, Dr. Irving Weissman and his colleagues at Stanford University are also looking for ways to cure several neurological diseases, including brain cancer.
IRVING WEISSMAN: We put a few thousand cells in this ventricle of the mouse. It seeded here. The cancer cells came out here.
TOM BEARDEN: Weissman’s eventual goal is to create a mouse with a brain made entirely of human cells. He suspects it would still be a mouse brain in every other way — structure, form and function — but theoretically would react to new treatments the same way it would in a human body. It would provide a platform to test new drugs without subjecting a human subject to potential harm.
IRVING WEISSMAN: If you have a human set of neurons — pain, hippocampus, learning, whatever — in the context of the mouse brain you could try a drug and say, What does this do to a simple learning task? What does this do to perception of a smell — and so on.
TOM BEARDEN: But Weissman knew such work would be extremely controversial. He sought ethical advice from Hank Greely, a Stanford law professor who heads theuniversity’s Center for Bioethics. Greely and other members of the center concluded he should go ahead, but in steps, with stopping points if the research produced unexpected results.
HANK GREELY: If everything in the brain looked like a mouse brain, we said the experiment can go forward. If, on the other hand, there were things in the brain that looked wrong, that looked like human structures, or that looked like very odd misshapen mouse structures, our advice was: Stop the experiment and talk about it. Our view was it’s much better to try to decide these issues with some facts in hand, rather than to say in advance, “always go forward; never go forward.”
IRVING WEISSMAN: I mean, the most likely, let’s be honest, is it won’t work at all. The most likely is that it won’t repair the brain at all. But if it starts to repair, whether it’s mouselike or humanlike, and we go back to the ethicists and say, “okay, now what’s next?” If it’s fully human, are you convinced that it’s not a human persona growing up in that brain? And if you are, tell us how.
TOM BEARDEN: Concern about negative public reaction to modern chimeras recently led a National Academy of Sciences Committee to recommend the creation of oversight committees, like the one which advised Dr. Weissman, to review research proposals at each laboratory that wants to work with chimeric animals. The Academy also said no chimera should be allowed to reproduce. The rules aren’t mandatory, but Weissman says they are useful.
TOM BEARDEN: Are scientists like yourself working in this field treading through a legal and ethical minefield when you do this kind of research?
IRVING WEISSMAN: Absolutely. It’s a good thing we’re treading on ethical grounds. It means we’re getting close to important issues.
TOM BEARDEN: But Stuart Newman fears the NAS guidelines might be ignored.
STUART NEWMAN: I think they’re just recommendations, and they may have some force in influencing granting agencies to say you can’t get a grant unless you follow these rules. But that doesn’t force anybody who’s outside of this granting system, possibly working with private money from following those rules.
I think the only way it can really be controlled is if scientific journals decide that certain areas are just kind of outside the pale as far as publishability.
TOM BEARDEN: The chimera debate takes place against the ongoing controversy over any use of human embryonic stem cells. Even though he’s outside the United States on St. Kitts, Dr. Redmond says he’s following all existing research protocols, including the NAS guidelines.
Redmond has operated a primate research facility here for some 20 years, primarily because the island has a feral population of monkeys imported from Africa during colonial times. Studying them here is considerably less expensive than on the mainland. But like Weissman, Redmond remains sensitive to potential public backlash.
TOM BEARDEN: Have you self-censored yourself?
EUGENE REDMOND: Well, as a researcher, I’m eager to try to move research along, and I’d like to help out in the political process by helping people to understand what we’re doing. But at the same time, you don’t want to just wait for the political process. So I’ve been very careful to tailor my research to do things that could get grant support from the government. And so we’re using neural stem cells that were derived within the guidelines, and we’re using embryonic stem cells that also are one of the approved lines.
TOM BEARDEN: As for Newman, he isn’t opposed to all stem cell research, but he thinks some avenues of inquiry should never be undertaken.
STUART NEWMAN: Science can find many routes to curing diseases. There’s no unique route to curing any one disease. I think that this idea, though, that everything should be tried because something good may come out of it, I think that it sacrifices other values. I mean, I think that we have a certain value in kind of the uniqueness of the human species. If we’re willing to kind of undermine that because some people might be helped from it, I think that we’re losing something.
TOM BEARDEN: Many scientists we talked to think the NAS guidelines are adequate for now. But several also hope the federal government will display more leadership in shaping the course of future chimeric research.