Right now, there are over 120,000 patients in the US who are waiting for an organ transplant. Despite the fact that the number of organ donors has nearly doubled between 1994 and 2014, the gap between viable organs and the patients who need them continues to widen.
While cell culture, organ scaffolds and even 3-D printing have been used to human grow organs in the lab, this technology needs to be further refined and significantly scaled-up before it can be used to generate organs at the rate of which they are currently in demand.
Scientists are now looking to pigs for a consistent source of transplantable, biocompatible human organs. By exposing pig embryos to human stem cells, it’s hoped that the resulting chimeric animals could grow specific human organs which could be harvested for human transplantation.
Xenografts and Synthetic Replacement Parts
This isn’t the first time that pigs have been used as a source of xenograft tissue. As early as the 1960s, surgeons began using porcine heart valves to repair faulty valves in patients with heart disease.
As the pig heart is most similar to the human heart in both size and structure, the valves are a suitable replacement for humans. Early researchers also found that the risk of organ rejection could be mitigated by treating the xenograft with a chemical – usually formalin – to denature any foreign pig antigens.
Despite their effectiveness, porcine heart valves are usually replaced about 10 to 20 years after they are implanted. Newer, mechanical valves are longer-lasting, however patients must take anticoagulant medications for the rest of their lives to prevent blood clots from forming on the implanted device.
Though synthetic replacements for human tissue may be useful on the small scale – as is the case with the mechanical heart valve – it’s very difficult to create a synthetic structure as complex as an organ. This is where the idea of growing human organs inside pigs comes in. If scientists could create viable human-pig chimeras, the organs could be farmed on a large scale, making them more readily available than human donors and less expensive than tissue engineering.
Human Organs In Pigs
Research on the creation of chimeric pigs carrying human organs has been led by University of California, Davis scientist, Dr. Pablo Ross. Using the much talked-about new gene editing technique, CRISPR, Ross and his colleagues have knocked-out the genes necessary for pancreas development in pig embryos.
By introducing induced pluripotent human stem cells, the researchers hope a human pancreas will develop. As these stem cells can be produced using a sample of skin cells from a patient, the pig-grown human organ has the potential to reduce the risk of organ transplant rejection. These human-pig embryos are implanted into the uterus of adult female pigs, where they will be allowed to grow and develop.
So far, the implanted chimeric embryos have not been allowed to go to term, which would require a 114 day period in pigs. The fetuses have been removed before 28 days of gestation to study the behavior and migration of the human cells within the developing piglet.
Ethical Implications Of Human-Pig Chimeras
While the technique has the potential to solve the organ shortage crisis around the world, it certainly poses many questions including the ethical implications of this work. As yet, it’s unclear whether chimeric piglets carrying human pancreas would be viable as previous attempts to create chimeric mice have ended in a high proportion of fatalities.
Scientists have however, had some success creating chimeric animals in the past. In 2010, researchers at the University of Tokyo in Japan created a mouse capable of growing a rat pancreas. That same year, a team from the Salk Institute in California created a liver in a mouse that was composed of 95% human cells. As mice are too small to grow human organs to size, researchers have started to focus their efforts on creating chimeric pigs.
Animal rights activists are also concerned about what effects this type of experimentation could have on the welfare of the pigs. If such organ farms were to be established, how much suffering would the pigs experience for the sake of a human needing a new pancreas?
“I’m nervous about opening up a new source of animal suffering,” said Peter Stevenson, from Compassion in World Farming, the world’s leading farm animal welfare organization. “Let’s first get many more people to donate organs. If there is still a shortage after that, we can consider using pigs, but on the basis that we eat less meat so that there is no overall increase in the number of pigs being used for human purposes.”
The research also raises the question of redundancy and waste: as multiple chimeric embryos are implanted into a single sow to increase the chances of a successful pregnancy, the odds are that multiple embryos could attach to the uterine wall at the same time.
Much like the field of human reproductive biology where procedures like in vitro fertilization increase the chances of multiple births, the pregnant pigs could deliver multiple chimeric offspring growing the same organ. If the organ is designed to be biocompatible for a single patient, would the additional organs simply be discarded?
This research is so controversial in fact, that the National Institutes of Health (NIH) – the top heath agency in the US – has issued a ban on government funding of these human-animal chimera research projects. While researchers wishing to do these types of experiments are free to source their funding from private agencies – including the California Institute for Regenerative Medicine and the University of California, Davis – the NIH wishes to review both the scientific and the social implications of the research before reconsidering their position.
Ethicists are also concerned about the potential results of mixing human cells with those of a pig at such an early stage. As induced pluripotent stem cells have the ability to become any cell type in the body, some are worried that these cells could eventually differentiate into human reproductive cells or even the neurons found in the brain.
Even Ross is concerned about the prospect of creating a human-like pig and whether sacrificing such an animal for the benefit of a patient waiting on the transplant list, would be entirely ethical. “My view is that the contribution of human cells is going to be minimal, maybe 3 percent, maybe 5 percent,” said Ross. “But what if they contributed to 100 percent of the brain? What if the embryo that develops is mostly human? It’s something that we don’t expect, but no one has done this experiment, so we can’t rule it out.”