By Antonio Regalado
Braving a funding ban put in place by America’s top health agency, some U.S. research centers are moving ahead with attempts to grow human tissue inside pigs and sheep with the goal of creating hearts, livers, or other organs needed for transplants.
The effort to incubate organs in farm animals is ethically charged because it involves adding human cells to animal embryos in ways that could blur the line between species.
Last September, in a reversal of earlier policy, the National Institutes of Health announced it would not support studies involving such “human-animal chimeras” until it had reviewed the scientific and social implications more closely.
Hiromitsu Nakauchi
The agency, in a statement, said it was worried about the chance that animals’ “cognitive state” could be altered if they ended up with human brain cells.
The NIH action was triggered after it learned that scientists had begun such experiments with support from other funding sources, including from California’s state stem-cell agency. The human-animal mixtures are being created by injecting human stem cells into days-old animal embryos, then gestating these in female livestock.
Based on interviews with three teams, two in California and one in Minnesota, MIT Technology Review estimates that about 20 pregnancies of pig-human or sheep-human chimeras have been established during the last 12 months in the U.S., though so far no scientific paper describing the work has been published, and none of the animals were brought to term.
The extent of the research was disclosed in part during presentations made at the NIH’s Maryland campus in November at the agency’s request. One researcher, Juan Carlos Izpisua Belmonte of the Salk Institute, showed unpublished data on more than a dozen pig embryo containing human cells. Another, from the University of Minnesota, provided photographs of a 62-day-old pig fetus in which the addition of human cells appeared to have reversed a congenital eye defect.
The experiments rely on a cutting-edge fusion of technologies, including recent breakthroughs in stem-cell biology and gene-editing techniques. By modifying genes, scientists can now easily change the DNA in pig or sheep embryos so that they are genetically incapable of forming a specific tissue. Then, by adding stem cells from a person, they hope the human cells will take over the job of forming the missing organ, which could then be harvested from the animal for use in a transplant operation.
“We can make an animal without a heart. We have engineered pigs that lack skeletal muscles and blood vessels,” says Daniel Garry, a cardiologist who leads a chimera project at the University of Minnesota. While such pigs aren’t viable, they can develop properly if a few cells are added from a normal pig embryo. Garry says he’s already melded two pigs in this way and recently won a $1.4 million grant from the U.S. Army, which funds some biomedical research, to try to grow human hearts in swine.
Braving a funding ban put in place by America’s top health agency, some U.S. research centers are moving ahead with attempts to grow human tissue inside pigs and sheep with the goal of creating hearts, livers, or other organs needed for transplants.
The effort to incubate organs in farm animals is ethically charged because it involves adding human cells to animal embryos in ways that could blur the line between species.
Last September, in a reversal of earlier policy, the National Institutes of Health announced it would not support studies involving such “human-animal chimeras” until it had reviewed the scientific and social implications more closely.
Hiromitsu Nakauchi
The agency, in a statement, said it was worried about the chance that animals’ “cognitive state” could be altered if they ended up with human brain cells.
The NIH action was triggered after it learned that scientists had begun such experiments with support from other funding sources, including from California’s state stem-cell agency. The human-animal mixtures are being created by injecting human stem cells into days-old animal embryos, then gestating these in female livestock.
Based on interviews with three teams, two in California and one in Minnesota, MIT Technology Review estimates that about 20 pregnancies of pig-human or sheep-human chimeras have been established during the last 12 months in the U.S., though so far no scientific paper describing the work has been published, and none of the animals were brought to term.
The extent of the research was disclosed in part during presentations made at the NIH’s Maryland campus in November at the agency’s request. One researcher, Juan Carlos Izpisua Belmonte of the Salk Institute, showed unpublished data on more than a dozen pig embryo containing human cells. Another, from the University of Minnesota, provided photographs of a 62-day-old pig fetus in which the addition of human cells appeared to have reversed a congenital eye defect.
The experiments rely on a cutting-edge fusion of technologies, including recent breakthroughs in stem-cell biology and gene-editing techniques. By modifying genes, scientists can now easily change the DNA in pig or sheep embryos so that they are genetically incapable of forming a specific tissue. Then, by adding stem cells from a person, they hope the human cells will take over the job of forming the missing organ, which could then be harvested from the animal for use in a transplant operation.
“We can make an animal without a heart. We have engineered pigs that lack skeletal muscles and blood vessels,” says Daniel Garry, a cardiologist who leads a chimera project at the University of Minnesota. While such pigs aren’t viable, they can develop properly if a few cells are added from a normal pig embryo. Garry says he’s already melded two pigs in this way and recently won a $1.4 million grant from the U.S. Army, which funds some biomedical research, to try to grow human hearts in swine.
Although Nakauchi was a star scientist, Japanese regulators were slow to approve his idea for chimeras—a “pig man” as critics put it—and by 2013 Nakauchi decided to move to the U.S., where no federal law restricts the creation of chimeras. Stanford was able to recruit him with the help of a $6 million grant from the California Institute of Regenerative Medicine, a state agency set up a decade ago to bypass political interference from Washington.
While the NIH funding ban doesn’t affect Nakauchi, it has put researchers under pressure to explain the purpose of their work. “I want to show you some chimeras,” Nakauchi said when I visited his laboratory at Stanford last month. He opened the door to a small room containing incubators where the chimeric embryos are stored. Because an early embryo is almost invisible to the human eye, the room houses special microscopes equipped with micro-needles used to inject the human cells into them.
The type of human cells being added are called iPS cells, made from skin or blood chemically reprogrammed into more versatile stem cells using a Nobel Prize-winning formula developed by one of Nakauchi’s Japanese colleagues. Nakauchi says that as a matter of convenience, most of the iPS cells his team has been placing into animal embryos are made from his own blood, since recruiting volunteers involves too much paperwork.
“We need a special consent if we’re injecting into animals,” he says sheepishly. “So I try to use my own.”
A pig at the swine unit of the University of California, Davis. Scientists hope to grow human organs in such animals.
The word chimera comes from the creature of Greek myth, part lion, part goat, and part snake. Nakauchi says most people at first imagine his chimeras are monsters, too. But he says attitudes change if he can explain his proposal. One reason is that if his iPS cells develop inside an animal, the resulting tissue will actually be his, a kind of perfectly matched replacement part. Desperately ill people on organ waiting lists might someday order a chimera and wait less than a year for their own custom organ to be ready. “I really don’t see much risk to society,” he says.
Credit to technologyreview.com
http://www.technologyreview.com/news/545106/human-animal-chimeras-are-gestating-on-us-research-farms/
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