A handful of scientists around the United States are trying to do something that some people find disturbing: make embryos that are part human, part animal.
The researchers hope these embryos, known as chimeras, could eventually help save the lives of people with a wide range of diseases.
One way would be to use chimera embryos to create better animal models to study how human diseases happen and how they progress.
Perhaps the boldest hope is to create farm animals that have human organs that could be transplanted into terminally ill patients.
But some scientists and bioethicists worry the creation of these interspecies embryos crosses the line. "You're getting into unsettling ground that I think is damaging to our sense of humanity," says Stuart Newman, a professor of cell biology and anatomy at the New York Medical College.
The experiments are so sensitive that the National Institutes of Health has imposed a moratorium on funding them while officials explore the ethical issues they raise.
Nevertheless, a small number of researchers are pursuing the work with alternative funding. They hope the results will persuade the NIH to lift the moratorium.
"We're not trying to make a chimera just because we want to see some kind of monstrous creature," says Pablo Ross, a reproductive biologist at the University of California, Davis. "We're doing this for a biomedical purpose."
The NIH is expected to announce soon how it plans to handle requests for funding.
Recently, Ross agreed to let me visit his lab for an unusual look at his research. During the visit, Ross demonstrated how he is trying to create a pancreas that theoretically could be transplanted into a patient with diabetes.
The first step involves using new gene-editing techniques to remove the gene that pig embryos need to make a pancreas.
Working under an elaborate microscope, Ross makes a small hole in the embryo's outer membrane with a laser. Next, he injects a molecule synthesized in the laboratory to home in on and delete the pancreas gene inside. (In separate experiments, he has done this to sheep embryos, too.)
Like human embryonic stem cells, iPS cells can turn into any kind of cell or tissue in the body. The researchers' hope is that the human stem cells will take advantage of the void in the embryo to start forming a human pancreas.
Because iPS cells can be made from any adult's skin cells, any organs they form would match the patient who needs the transplant, vastly reducing the risk that the body would reject the new organ.
But for the embryo to develop and produce an organ, Ross has to put the chimera embryos into the wombs of adult pigs. That involves a surgical procedure, which is performed in a large operating room across the street from Ross's lab.
The day Ross opened his lab to me, a surgical team was anesthetizing an adult female pig so surgeons could make an incision to get access to its uterus.
Ross then rushed over with a special syringe filled with chimera embryos. He injected 25 embryos into each side of the animal's uterus. The procedure took about an hour. He repeated the process on a second pig.
Every time Ross does this, he then waits a few weeks to allow the embryos to develop to their 28th day — a time when primitive structures such as organs start to form.
Ross then retrieves the chimeric embryos to dissect them so he can see what the human stem cells are doing inside. He examines whether the human stem cells have started to form a pancreas, and whether they have begun making any other types of tissues.
The uncertainty is part of what makes the work so controversial. Ross and other scientists conducting these experiments can't know exactly where the human stem cells will go. Ross hopes they'll only grow a human pancreas. But they could go elsewhere, such as to the brain.
"If you have pigs with partly human brains you would have animals that might actually have consciousness like a human," Newman says. "It might have human-type needs. We don't really know."
That possibility raises new questions about the morality of using the animals for experimentation. Another concern is that the stem cells could form human sperm and human eggs in the chimeras.
"If a male chimeric pig mated with a female chimeric pig, the result could be a human fetus developing in the uterus of that female chimera," Newman says. Another possibility is the animals could give birth to some kind of part-human, part-pig creature.
"One of the concerns that a lot of people have is that there's something sacrosanct about what it means to be human expressed in our DNA," says Jason Robert, a bioethicist at Arizona State University. "And that by inserting that into other animals and giving those other animals potentially some of the capacities of humans that this could be a kind of violation — a kind of, maybe, even a playing God."
Ross defends what his work. "I don't consider that we're playing God or even close to that," Ross says. "We're just trying to use the technologies that we have developed to improve peoples' life."
Still, Ross acknowledges the concerns. So he's moving very carefully, he says. For example, he's only letting the chimera embryos develop for 28 days. At that point, he removes the embryos and dissects them.
If he discovers the stem cells are going to the wrong places in the embryos, he says he can take steps to stop that from happening. In addition, he'd make sure adult chimeras are never allowed to mate, he says.
"We're very aware and sensitive to the ethical concerns," he says. "One of the reasons we're doing this research the way we're doing it is because we want to provide scientific information to inform those concerns."
Ross is working with Juan Carlos Izpisua Belmonte from the Salk Institute for Biological Studies in La Jolla, Calif., and Hiromitsu Nakauchi at Stanford University. Daniel Garry of the University of Minnesota and colleagues are conducting similar work. The research is funded in part by the Defense Department and the California Institute for Regenerative Medicine (CIRM).
AUDIE CORNISH, HOST:
Scientists are trying to do something that some people find disturbing - create embryos that are part human, part animal. These experiments are so sensitive that the National Institute of Health is refusing to pay for them. A Few researchers are trying anyway with private funding, and they hope these embryos known as chimeras could eventually help save thousands of people dying from terrible diseases.
NPR health correspondent Rob Stein got unusual access to one of these labs. He brings us this inside look at whether scientists can and should be taking this unprecedented step.
ROB STEIN, BYLINE: The word chimera comes from a Greek myth about a three-headed, firebreathing monster - part lion, part serpent, part goat. The scientists creating real chimeras today say they're nothing like that. They use everyday farm animals like pigs, like this one at a research farm at the University of California in Davis. I went there to meet Pablo Ross.
What are you going to use these pigs to do?
PABLO ROSS: So we're creating a chimera, which is an animal that has cells from two different species.
STEIN: For example, a pig and a human.
ROSS: We're not trying to make a chimera just because we want to see this kind of, you know, monstrous creature. We're doing this for a biomedical purpose.
STEIN: You see, Ross wants to grow human organs inside pigs, sheep and cows, organs like pancreases, livers, kidneys, even hearts.
ROSS: This could be one of the possible solution for shortages of organs - so potentially could save many, many people.
STEIN: But to do that, Ross has to first try to make embryos that are part human, part animal, and that's something critics like Stuart Newman at New York Medical College say should be off-limits.
STUART NEWMAN: You're getting into unsettling ground that I think is damaging to our sense of humanity.
STEIN: Because, Newman says, it blurs the line between humans and other species and raises all kinds of possibilities that start to sound like something straight out of science fiction. We'll get into all that in a moment.
But first, Professor Ross takes me to his lab to show me exactly what he's doing. He pulls open a thick, black curtain. On the other side is an eerie scene. There's a big microscope. Something under the microscope's glowing orange and yellow. It's a dish that's lit up from below.
ROSS: So there is 15 embryos there in the dish.
STEIN: Fifteen pig embryos, embryos that have been genetically engineered so they can't grow their own pancreases. The idea is to put human cells into the pig embryos so a human pancreas will grow instead.
Everything on the microscope is projected onto a big computer screen. The embryos look like big circles. Ross uses the tip of a thin glass tube to hold one of the embryos by its shell.
ROSS: We are going to use a laser to make a hole in that shell.
STEIN: After he makes the hole, Ross moves to a cluster of little black dots on the screen.
What are those?
ROSS: So those are human stem cells.
STEIN: Human stem cells, which can be made from anyone's own skin cells and then can become anything in the body. Ross hopes they'll become a human pancreas. He pulls five of the stem cells into a tiny needle under the microscope.
ROSS: And then through that small hole, I can advance my needle containing the cells, and now we're putting two, three, four, five cells into the cavity of the embryo.
STEIN: And with that, he's created a part pig, part human embryo - a pig-human chimera. He does this over and over again. In less than an hour, he's got 50 chimera embryos.
ROSS: By putting these cells inside the embryo, we hope that they will contribute to the tissues of the developing embryo.
STEIN: And hopefully do something that's never been done before - start to grow a human organ inside a pig embryo. After the animal's born and matures, it would be sacrificed to remove the human organ so surgeons could transplant a perfectly matched pancreas into a patient with diabetes.
But for any of that to happen, Ross has to take the next step - put the chimera embryos into the wombs of female pigs. He does that across the street in a big operating room.
JOAN ROWE: I just need to set up the scrubbing area, the gowns and the surgical...
STEIN: Dr. Joan Rowe and her surgical team are getting ready for the operation. After the pig's asleep, Rowe and her team get to work.
ROWE: We're just now entering the abdominal cavity and then taking a minute to locate the uterus - retract that.
STEIN: As soon as she has the uterus, Ross rushes over with a special syringe filled with chimera embryos...
ROSS: You got it.
ROWE: Come on underneath. That's yours.
STEIN: ...So they can insert the end of the syringe into the uterus.
ROWE: Wait; wait; wait; wait; wait; wait. It's got to go down at that angle, though. I'm going to thread it don't just a little more.
ROSS: Yeah, thread it down.
ROWE: The tip is turned a little bit, so I want to be real gentle advancing. Go ahead.
STEIN: Ross squeezes the plunger, injecting the embryos into the pig's womb.
ROWE: OK, beautiful.
STEIN: After that, the surgeons start closing up the pig.
ROWE: That looks good.
STEIN: And Ross finally relaxes. The genetically engineered chimera embryos are safely in the pig's womb. And now he just waits. In a few weeks, he'll retrieve the embryos to see what the human stem cells are doing inside the pig embryo. He's doing this with sheep and cow embryos too.
ROSS: We're going to harvest the embryos and look to see if they contributed to the pancreas and where else did the cells go.
STEIN: And that's what makes this so controversial. Ross can't know exactly where the human stem cells will go. He hopes they'll only grow a human pancreas, but they could go someplace else like the brain, and that makes critics like Stuart Newman very nervous.
NEWMAN: If you have pigs with partly human brains, you would have animals that might actually have consciousness like a human. It might have human-type needs. We don't really know.
STEIN: Or the stem cells could accidentally form human sperm or human eggs in the chimeras.
NEWMAN: And if a male chimeric pig mated with a female chimeric pig, the result could be a human fetus developing in the uterus of that female chimera.
STEIN: Or maybe some kind of part human, part pig creature. Jason Robert is a bioethicist at Arizona State University.
JASON ROBERT: One of the concerns that a lot of people has is that there's something sacrosanct about what it means to be human expressed in our DNA and that by inserting that into other animals and giving those animals potentially some of the capacities of humans, that this could be a kind of violation, a kind of maybe even playing God.
STEIN: Newman and Robert are not alone. Government scientists are worried about this too, so the National Institutes of Health has imposed a moratorium on funding any research like this. For his part, Pablo Ross defends what he's doing.
ROSS: I don't consider that we're playing God or even close to that. We're just trying to use the technologies that we have developed to improve people's life.
STEIN: His dream would be big farms breeding sheep, cows and pigs with human pancreases, livers, kidneys and hearts to save thousands of people who would otherwise die on the waiting list for new organs.
But Ross is moving very carefully. He's only letting his chimera embryos develop for 28 days so he can stop and dissect them to see where the human stem cells are going. If the stem cells are going to the wrong places, he'll tinker with them to stop that. And he says he'd make sure any adult chimeras are never allowed to mate.
ROSS: We're very aware and very sensitive to the ethical concerns. One of the reasons we're doing this research the way we're doing it is because we want to provide scientific information to inform those concerns.
STEIN: Ross hopes his research will convince the NIH to lift the moratorium on funding these kinds of experiments so he and other scientist can figure out the best way to create chimeras that help save lives without crossing any troubling ethical lines. Rob Stein, NPR News, Davis, Calif. Transcript provided by NPR, Copyright NPR.