Bacon, yogurt, and a viable heart for transplant. What do all these things have in common? In the near future, we’ll be able to get each of these important grocery list items from Old MacDonald.
When the public got word that biotech companies were genetically engineering pigs so that their organs were compatible with the human body, the news spread like wildfire. Now, scientists are pushing the boundaries even further. They are growing 100% human organs in pigs, sheep, and other animals to be harvested for transplant. This new research has the potential to dramatically shrink the donor waiting list. However, getting stem cells of one species to thrive in the embryo of another will be a huge feat for scientists and is riddled with ethical landmines.
All over the world, scientists are playing Frankenstein. In May of this year, a research team in the United States reported that they had successfully grown chimpanzee stem cells in monkey embryos. Across the ocean in Japan, regulations have been revisited, and researchers are now pursuing experiments in which human stem cells are to be developed in embryos of rodents and pigs. The vision is to reprogram a person’s cells during an early developmental state in which they can form most any tissue. Then, these cells will be injected into another species’ emnbryo. Once the embryo has reached full maturity, it can then serve as an organ donor. There are two approaches to this transplant option. Either the developmental cells would come from the transplant candidate, or an IKEA of sorts for organs could be created. The latter case would potentially be faster and less costly as organs would be grown in advance and would match key immune signaling proteins to prevent rejection once transplanted.
Thus far, the only evidence to support the viability of this new transplant model has been seen in rodents. Stem cell biologist Hiromitsu Nakauchi and his team at the University of Tokyo in 2010 grew pancreases in mice that were unable to form the organ themselves. In 2017, he and his team returned to a similar problem and treated diabetes in mice by giving them transplants of insulin-producing pancreas tissue that had been grown in a rat.
Unfortuantely, the success seen in rodents hasn’t translated when experimenting with large and more evolutionarily-distant animals. Trials in San Diego, California involving human cells implanted in pig embryos proved inviable. Approximately half of the subject pigs were unable to develop properly, while the other half grew to normal size but ethusiastically evicted most of the human cell tenants after only one month of gestation.
The same scientist involved with the experiments in San Diego, Jun Wu has moved on to the University of Texas Southwestern Medical Center in Dallas but remains attached to the same aspirations. He and his current team have discovered an interesting phenomenon when human stem cells interact with that of distantly related animals: the human cells tend to die off. So much for being at the top of the food chain, right? Along with cell competition, the issue of complexity with primate cells versus non-primate cells has also been attributed to the cell death seen in earlier experiments.
Research teams are very limited in their use of human developmental cells due to the noted public disapproval. Misao Fujita, a bioethicist at Kyoto University in Japan, conducted a survey to gain a better understanding of people’s attitudes toward animal-human chimeras, organisms containing a mixture of genetically different tissues. Respondents were particularly concerned with the blur between human and animals, such as animals with enhanced intelligence or animals carrying human sperm and egg cells. Anyone seen Splice? Not on my top 10 recommendation of movies, but if this article gives you the heebie jeebies, the movie will scare your pants off.
While in America, specifically, there are no outright legal restrictions on using human stem cells in non-human vertebrates, the U.S. National Institutes of Health (NIH) froze all reviews of grant applications for research involving such experimentation. However, significant protest erupted from researchers, and the agency lifted the broad ban and instead are cutting off funding to a more narrow spectrum of chimera experiments, such as breeding chimera animals with human reproductive cells. Again, see Splice.
In light of these ethical considerations, xenotransplantation, or the use of non-human tissue, like modified pig organs, for transplants will likely beat the transplant model that involves chimera experimentation due to regulations slowing down its progress. Whichever reaches markets first, however, will make its mark on history for either its medical impact or for the ethical tsunami that will surely ensue as a result.
Servick, K. 26 Jue, 2019. Embryo experiments take ‘baby steps’ toward growing human organs in livestock. Retrieved from https://www.sciencemag.org/news/2019/06/embryo-experiments-take-baby-steps-toward-growing-human-organs-livestock.