First ever human-pig embryo created, destroyed
Researchers at the Salk Institute for Biological Studies have created human-pig hybrid embryos by inserting human stem cells into existing pig embryos. The human cells not only survived the implantation, but grew and began to develop into tissues in vivo — an important step toward growing human organs inside animals to provide much-needed transplants.
The researchers, led by Dr. Jun Wu, intended to discover whether human cells could survive in a gestating animal embryo. The human cells used for this experiment were induced pleuripotent stem cells — adult human cells that have been genetically altered to have the characteristics of embryonic stem cells. The stem cells were inserted into pig and cow embryos, all of which survived the insertion process. Next, the altered pig embryos were implanted into pigs and allowed to incubate. The human cells successfully incorporated themselves into the developing embryos with modestly low rejection rates, and had begun to develop into specialized tissues when the test was terminated at four weeks into gestation.
This is the latest in a series of experiments producing interspecies chimeras — organisms with DNA from more than one species. One well-known procedure in this field involves breeding mice that lack pancreases. Rat stem cells are then used to grow rat pancreases inside the mice. The Salk researchers recreated this experiment at the embryonic stage as a precursor to their pig experiment, using rat stem cells to grow pancreases, hearts, and eyes inside mouse embryos. The rat stem cells also contributed to the development of the mouse gallbladders — an interesting finding, as rats do not have gallbladders. The rat components did not appear to significantly impact the health or lifespan of the mice in the experiment, which is positive news for scientists hoping to explore the medical implications of this study.
Research on interspecies chimeras has great medical significance because it could lead to a reliable supply of transplantable human organs.
Over 100,000 Americans are currently waiting to receive donated organs, a number that has increased dramatically over the past few decades as transplants have become safer and more reliable. Unfortunately, the number of organ donors has remained relatively unchanged. Growing human organs inside animals could alleviate the need for human donors — and if the incubated organs were grown from the stem cells of the intended recipient, it could significantly lower the risk of transplant rejection as well.
Studies on chimeras are fraught with ethical concerns. Though human-animal chimeras have been used for medical research for decades without issue, these earlier chimeras were created by inserting human cells late in the animal’s development, when most or all tissue functions have already been determined. When human cells are incorporated into an embryo, as in many recent studies, the researchers have considerably less control over what happens to those cells, or what they develop into.
Ethicists are concerned that human genes may end up in the animal’s brain cells or gametes, leading to heightened sentience and intelligence, or the possibility of producing offspring. Considerations like these raise questions of animal rights and “violation of the order of nature,” according to medical ethicist Göran Hermerén.
Because of these ethical complications, the National Institute of Health (NIH) temporarily halted funding for human-animal chimera research in 2015. (The Salk Institute chimera research was privately funded.) Carrie Wolinetz, the NIH’s associate director for science policy, asserts that chimera research will be encouraged to continue when there is “an appropriate oversight system so we can make sure it is proceeding responsibly.” However, it is unclear what “ethical responsibility” means for this kind of research.
The Salk research did not violate any current ethical guidelines, but it will be necessary to reevaluate such guidelines in light of the enormous benefit this research could bring to patients in need.