Imagine a world where people in desperate need of a life-saving organ transplant could use their own stem cells to grow replacement organs inside a pig or a sheep.
The procedure would also come with the ancillary benefit of freedom from immunosuppressive medications for the rest of their lives.
That's the long-term goal of a handful of vanguard researchers at Stanford University, the University of Minnesota, and The Salk Institute for Biological Studies in La Jolla, California.
By adding human pluripotent cells to animal embryos — creating so-called human-animal chimeras — these leading-edge labs are taking the first step toward growing human tissue inside vertebrate animals with an eye toward eventually harvesting viable replacement hearts, livers, and kidneys.
Pioneers in this field, including Dr. Hiromitsu Nakauchi, a genetics professor at Stanford who started his chimera research project eight years ago at the University of Tokyo, are propelling the field of regenerative medicine not only beyond what was conceivable just a decade ago but also well past some folks' comfort level.
Maybe it's the name. A chimera, to anyone who studied Greek mythology in junior high school, conjures up the image of a monster, a hybrid creature most commonly described as part lion, part goat, and part snake. The shorthand is as apt as it is discomforting, at least for now.
"A chimera is a mixture of human cells and pig cells and no genetic manipulation or alterations are involved," Nakauchi told Healthline. "We are not creating a new species that can mate and expand. We will never see something like a pig with human face."
Chimera Research in Its Infancy
These chimeras are confined to petri dishes with pig or sheep embryos that are only allowed to develop for two to four weeks after human stem cells are introduced, a process called embryo complementation.
But this brief period of time gives researchers the opportunity to determine whether or not these animal fetuses can provide an environment for growing human tissue and organs.
More than 120,000 people in the United States are currently in need of an organ transplant and about 22 people die each day because a suitable donor organ never materializes. According to the Organ Procurement and Transplantation Network (OPTN), more than 30,000 organ transplants were performed in the U.S. last year, an all-time record, and 81 percent of those organs were harvested from deceased donors.
Among those transplant recipients who are lucky enough to find an organ match, there's always a chance of outright rejection. In addition, studies have concluded that the barrage of immunosuppressive medications these patients require can make them more vulnerable to a variety of infections and diseases, including cancer, later in life.
"There is a greater chance of forming functional organs this way, [something that is more] difficult in a test tube," Nakauchi said. "If we can generate organs from a patient’s own stem cells, then it will be an autologous transplantation and there will be a true cure."
Ethics and Politics
Research of this sophistication requires lots of money.
The National Institutes of Health (NIH), a U.S. Department of Health and Human Services agency, and the largest biomedical research institution in the world, allocates close to $30 billion a year in extramural grants for research of all types.
In September, the NIH issued a guide notice to the research community announcing it would not fund research "in which human pluripotent cells are introduced into non-human vertebrate animal pre-gastrulation stage embryos while the agency considers a possible policy revision in this area."
The agency added that it would like to initiate a "deliberative process to evaluate the state of the science in this area, the ethical issues that should be considered, and the relevant animal welfare concerns" associated with human-animal chimera research.
Bottom line: At least from the federal coffers, there will be no funding for chimera research until the NIH completes a thorough review of the research and determines whether additional policies and guidance are needed.
Not unlike the space program in the 1950s and 1960s, there's a great deal of uncertainty about this emerging science. At the heart of the debate is the fear of the unknown, elements of both intellectual and faith-based reluctance to mess around with the fundamental biology of animals, humans or both.
"Research in which human pluripotent cells are introduced into non-human vertebrate animal pre-gastrulation state embryos is an area of some concern given the possibility of human cell contribution to multiple organs and tissues," the NIH office of science policy said in a statement to Healthline.
"A significant contribution of human cells in an animal, if that were to occur, may raise concerns for the welfare of the animal, particularly if there are significant alterations of the animal's cognitive state," the statement added.
Nakauchi and other researchers reiterate that their research thus far is concluded long before these animals are born and introduce only a fraction of a percentage of human cells to the pig or sheep embryo, eliminating any chance that an animal could develop anything resembling human cognition and awareness.
"Of course I understand the ethical concerns," Nakauchi said. "We try to maintain transparency for what we are doing. I [hope] that we will reduce people's concern by showing successful organ generation and its usefulness."
Other Funding Sources
While the NIH is taking a wait-and-see approach to chimera research, other private and state agencies are moving forward.
The California Institute for Regenerative Medicine (CIRM), a state-funded agency birthed after voters in 2004 approved Proposition 71 (also known as the California Stem Cell Research and Cures Act) continues to invest millions for a variety of stem cell-related research projects, including chimeras.
In a statement issued just two weeks after the NIH released its guide notice, the CIRM affirmed it was authorized to support research including studies involving the transplantation of human cells into vertebrate animals.
"These studies are conducted in accordance with CIRM regulations, which include a system of review and oversight to ensure the responsible conduct of research," the agency said in its statement.
Finding a balance between meaningful exploratory research while maintaining a sense of propriety and establishing protocols is nothing new for the medical field.
Dr. Charles Burton, a neurological spine specialist and a board member at the Association for Medical Ethics (AME), recalls similar controversy when artificial cardiac pacemakers arrived on the scene nearly 50 years ago.
"I remember there were people I worked with in this field who would leave the room and not participate in procedures that introduced electronic devices into human bodies," Burton told Healthline. "But eventually perceptions and beliefs changed. People realized it was important for us to live."
Burton said as long as research teams and their benefactors monitor chimera research with reasonable precautions and an eye toward the fundamental principles of medicine, the experimentation will likely lead to meaningful and serendipitous discoveries long before any viable organs are produced.
"As an ethicist, there are agreed upon rules that will help ensure this research becomes something of value and not something that will spin out of control," he said. "Right now [chimera research] is limited and primitive. But sometimes it's important to explore the unknown."