Organ transplants to replace failing human organs and tissues save and improve the quality of many lives every year.
Up until now suitable organs for transplantation have been available only from human donors, and donor organs are in very short supply. The number of people waiting for transplants always significantly exceeds the supply of available organs.
About 120,000 require organ transplants annually in the US, but only 30,000 people receive them. In Ireland some 150 organ transplants are carried out annually and about 650 people are currently waiting for transplants.
Xenotransplantation, the transplantation into humans of organs or tissues from a nonhuman animal source, would solve this supply problem, but xenotransplantation has not been feasible to date. However, recent developments indicate it will soon be possible to harvest large-scale supplies of organs from genetically engineered pigs that are suitable for transplantation into humans.
Although baboons are a possibility, pigs are probably the optimal choice as a source of organs for transplantation into humans. We understand pig biology well, and the physiology of pigs is quite similar to human physiology. Other advantages are that pigs are about the same size as humans, have big litters, are easily raised and mature quickly.
Baboons are genetically closer to humans than the pig, but they reproduce more slowly and are more difficult to raise. Also, the closeness of the baboon to the human elicits much greater feelings of squeamishness at the thought of farming animals as a source of spare parts for humans than are elicited by thoughts of the pig fulfilling this role.
Transplanting pig organs into humans has not been feasible to date because viruses (porcine endogenous retroviruses) that cannot be treated or neutralised are embedded in the pig genome. It is feared that these viruses could infect humans and cause disease if pig organs were transplanted into humans. The human immune system would also strongly reject pig organs.
Grounds for optimism
It now looks very likely that these difficulties have been overcome, and there is great optimism that we might not have to wait long before xenotransplantation from pigs to human becomes a reality.
Harvard Medical School geneticist George Church has just announced that his team has successfully inactivated 62 virus locations in the DNA of pig embryos using a powerful new gene- editing technique called Crispr/Cas9. In another set of pig embryos, Church's team has also modified more than 20 other genes that would cause immune rejection or blood clotting when pig organs are transplanted into humans. These virus deletions and gene modifications will be incorporated into the pigs eventually used for xenotransplantation. Church will soon be ready to implant the genetically modified pig embryos into surrogate sows, and he and has cofounded a biotech company called EGenesis to produce the genetically engineered pigs cheaply and on a large scale.
This work marks a major advance in the field and will be widely welcomed by both medicine and the public. However, objections will undoubtedly be raised by some people on ethical or religious grounds.
The animal rights movement objects to using animals as a source of tissues and organs for humans because it believes that this reinforces the ethos that animals exist merely to satisfy human needs. The genetically modified pigs may also have to be reared in isolation to keep them sterile and healthy. Pigs are social animals and so isolation and frequent monitoring could be hard on them.
Various other groups would object on the grounds that it is wrong to use animals for “unnatural” purposes.
And on the religious side, many Muslims and Jews would object and would not avail of the new procedure.
In summary, there is much on the ethical and religious fronts for the researchers who are pioneering this new form of xenotransplantation to sort out.
William Reville is an emeritus professor of biochemistry at UCC. http://understandingscience.ucc.ie