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N.I.H. May Fund Experiments With Human Stem Cells in Animal Embryos N.I.H. May Fund Human-Animal Stem Cell Research
(about 4 hours later)
The National Institutes of Health announced on Thursday it is planning to lift its ban on funding some research that injects human stem cells into animal embryos. The National Institutes of Health announced on Thursday that it was planning to lift its ban on funding some research that injects human stem cells into animal embryos.
The N.I.H. announced its proposal in a blog post by Carrie Wolinetz, the associate director for science policy, and in the Federal Register.The N.I.H. announced its proposal in a blog post by Carrie Wolinetz, the associate director for science policy, and in the Federal Register.
The purpose of trying to grow human tissues or organs in animals is to better understand human diseases and further progress in developing therapies to treat them. While no one is proposing making, for example, a mouse with a human brain, the work is an extension of something researchers have long been doing like putting pieces of human tumors in a mouse to test drugs that might destroy the tumor. The purpose is to try to grow human tissues or organs in animals to better understand human diseases and develop therapies to treat them.
But the very idea can be chilling: human cells getting into animal brains or human organs grown in pigs that would then be used for transplant, killing the animals, for example. Scientists have already grown a rat pancreas in a mouse. Researchers have long been putting human cells into animals like pieces of human tumors in mice to test drugs that might destroy the tumors but stem cell research is fundamentally different. The stem cells are put into developing embryos where they can become any cells, like those in organs, blood and bone.
The end goals of the science are to improve human health, to develop new therapies and to understand diseases like schizophrenia. The means to those goals, however, by making human-animal chimeras, will never meet with universal acceptance. If the funding ban is lifted, it could help patients by, for example, encouraging research in which a pig grows a human kidney for a transplant.
The path ahead can be fraught, noted Paul Knoepfler, a stem cell researcher at the University of California, Davis. When human cells injected into an animal embryo develop into part of that animal’s brain, he said, difficult questions arise. “There’s no clear dividing line because we lack an understanding of at what point humanization of an animal brain could lead to more humanlike thought or consciousness,” he cautioned. But the very idea of a human-animal mix can be chilling, and will not meet with universal acceptance.
The N.I.H.’s plan will likely go into effect this fall perhaps with some modifications after a 30-day comment period that is now open for members of the public and researchers to express their opinions. In particular, when human cells injected into an animal embryo develop in part of that animal’s brain, difficult questions arise, said Paul Knoepfler, a stem cell researcher at the University of California, Davis.
The N.I.H had put a moratorium on funding some stem cell work last September to consider some concerns that were being raised. For scientists, who had exciting plans to move forward with this type of research, the moratorium was “a little jarring,” said Dr. George Q. Daley, a Harvard professor and director of the stem cell transplantation program at Boston Children’s Hospital. “There’s no clear dividing line because we lack an understanding of at what point humanization of an animal brain could lead to more humanlike thought or consciousness,” he said.
Two months later, the N.I.H. convened a workshop to hear from researchers and experts in animal welfare. The N.I.H.’s plan will most likely go into effect in the fall perhaps with some modifications after a 30-day comment period that is now open to the public and researchers.
Two types of experiments that are now being considered for funding would still have to undergo a review by an N.I.H advisory committee. The first is adding human stem cells to the embryos of animals except nonhuman primates like monkeys or chimpanzees, before the embryos reach a stage when organs are starting to develop. With nonhuman primates, , according to the proposal, researchers would have to wait until an embryo was further developed before adding human stem cells. The N.I.H., which would be a major source of federal funds for this type of work, imposed the moratorium in September to consider concerns about the research. The studies were just beginning, and the N.I.H. did not have any projects underway involving human-animal chimeras, a term derived from mythological creatures that were part goat, lion and snake. But Renate Myles, a spokeswoman, said, “We watch the state of the science and knew that this was where the science was heading.”
The second type of study that would get extra scrutiny involves introducing stem cells into embryos of animals other than rodents where the cells could get into and modify the animals’ brains. For scientists, the moratorium was “a little jarring,” said Dr. George Q. Daley, a Harvard professor and the director of the stem cell transplantation program at Boston Children’s Hospital. Two months later, the N.I.H. convened a workshop to hear from researchers and experts in animal welfare.
Two types of experiments that are being considered for funding would still have to undergo a review by an N.I.H. advisory committee. The first involves the addition of human stem cells to the embryos of animals before the embryos reach a stage when organs are starting to develop. Because nonhuman primates like monkeys and chimpanzees are so genetically close to people, researchers working with such primates would have to wait until an embryo was further developed before adding human stem cells, according to the proposal.
The second type of study introduces stem cells into embryos of animals other than rodents where the cells could get into and modify the animals’ brains. Of particular concern is creating chimeras with human cells in the brain.
The N.I.H. would continue its ban on funding any research that could result in an animal with human sperm or eggs that would then be bred.The N.I.H. would continue its ban on funding any research that could result in an animal with human sperm or eggs that would then be bred.
Dr. Daley described some of the work researchers have been doing in this area. All of the N.I.H.’s proposals, though, apply only to the work that is financed with taxpayer money. Research supported by private donors or companies would not be affected.
First, they wanted to know if they had isolated new types of stem cells even more primitive than classical embryonic stem cells ones that could turn into any type of tissue of organ. Accomplishing that involves putting the new cells into an embryo and seeing if they turn into the placenta, as well as every cell type in the adult animal.. Dr. Daley described some of the work researchers had been doing in this area.
In other experiments, they wanted to look at human stem cells that developed into very specific tissues. For example, one research team found that if they put rat stem cells into the embryo of a mouse that was missing genes needed to make a pancreas, they ended up with a mouse that had a rat pancreas. First, they wanted to know if they had isolated new types of stem cells ones that could turn into any type of tissue of organ. Accomplishing that involves putting the new cells into an embryo and seeing if they turn into the placenta, as well as every cell type in the adult animal.
In other experiments, they wanted to look at human stem cells that developed into very specific tissues. For example, one team of researchers found that if they put rat stem cells into the embryo of a mouse that was missing genes needed to make a pancreas, they ended up with a mouse that had a rat pancreas.
Now, Dr. Daley said, the hope is to do the same sort of experiments with pigs missing genes for organs like a kidney or a liver and see if human stem cells can be used to grow human organs in the animals for transplants.Now, Dr. Daley said, the hope is to do the same sort of experiments with pigs missing genes for organs like a kidney or a liver and see if human stem cells can be used to grow human organs in the animals for transplants.
“It’s science fiction today but there has been enough progress in rat to mouse and even in pigs that it is at least theoretically possible,” Dr. Daley said. “It’s science fiction today, but there has been enough progress in rat to mouse and even in pigs that it is at least theoretically possible,” Dr. Daley said.
Another team studied mice with mutations that do not allow glial cells of the brain to develop. Glial cells support and protect neurons in the brain. The scientists added human stem cells to the mouse embryos and ended up with mice whose brains harbored human glial cells. One goal is to do the same experiment with stem cells from people with psychiatric disorders to create new animal models to understand disease. Another team studied the use of human stem cells in mice embryos in the hope of eventually understanding human psychiatric disorders.
Dr. Wolinetz of the N.I.H. said during a teleconference that said she expected “some on the job learning.” As other types of brain research advance and as the stem cell research leads to new insights, the effects of putting human cells in animal brains will become clearer, she said. Dr. Wolinetz of the N.I.H. said during a teleconference that said she expected “some on-the-job learning” about what would happen with chimeras that had human cells in their brains.
“There is a lot we don’t understand about the brain,” she said, which is one reason the possibility of these animal models is really exciting.” “There is a lot we don’t understand about the brain,” she said, “which is one reason the possibility of these animal models is really exciting.”
The work is disturbing to many. But does the unease reflect the novelty of the ideas, like concerns that surfaced with the advent of heart transplants, which were first met with revulsion and then embraced by the public? Or is this work of a different ilk?
Jeffrey P. Kahn, the director of the Johns Hopkins Berman Institute of Bioethics, points to two looming ethical issues.
One is to decide if there is a fundamental difference between adding DNA from one species into another — the technology used to produce genetically modified foods — and putting human cells into an animal. Many people can accept genetically modified organisms, but would a human-animal chimera eventually become acceptable? After all, Dr. Kahn said, in both cases, you could say “it’s just DNA.”
Where to draw the human boundary is another issue. If it is O.K. to put human cells into an animal, why does it seem clearly wrong to put animal cells into a human? As more and more human cells are added to an animal, at what point is the result different from adding more and more animal cells to a human embryo?
“What are we doing when we are mixing the traits of two species?” Dr. Kahn asked. “What makes us human? Is it having 51 percent human cells?”
Those questions, he added, “are part of what make people react to this issue.”