Pigs are wonderful creatures that provide us with sausages, bacon and so many more delicious porcine treats. Currently there are several labs around the world interested in getting pork inside people, but not via the dinner table.
Pigs are being investigated as a source for replacement organs in patients who need a transplant. Replacing an organ with one from another species is called xenotransplantation and it’s an idea that’s been around for a while.
If you haven’t been to the Hunterian museum near Holborn tube station in London, I strongly suggest you go along. The museum showcases an impressive collection of preserved animals and medically-relevant specimens. One in particular that stands out is a rooster that has a human tooth grafted onto the comb of its head. At first sight it seemed like a perverse operation. However, it represents one of the earliest chapters in the story of xenotransplantation.
John Hunter performed this surgery, and in his manuscript he adds "I may here just remark, that this experiment is not generally attended with success. I succeeded but once out of a great number of trials." Despite the 230 odd years since this operation, scientists still haven’t ironed out all of the kinks in xenotransplantation. But they are getting closer.
One of the most challenging hurdles in transplantation from one species to another is the issue of host-recipient compatibility – otherwise known as organ rejection. At the root of this problem is the host’s immune system, which has evolved to detect infections. If a normal pig organ were transplanted in to a human, there would be a massive immune response because as far as the human immune system is aware, the pig cells are infecting the human. This immune response would cause a lethal blood clot within minutes of the transplantation procedure.
In the early 1990s, researchers discovered a molecule on the surface of pig cells that provoked the primate immune system. Scientists genetically engineered the pigs so that they no longer had that molecule on the cell surface. Thanks to this change, organs from these pigs could go un-detected by the immune system of a host baboon for weeks, not minutes. Despite the eventual and lethal immune response, it was already a 10,000-fold improvement.
In the early 2010s, another group set out to improve the lifetime of the transplant further. They introduced two genes into the transgenic-pig’s genome, which both produce proteins involved in reducing blood clotting. Hearts from these transgenic pigs were transplanted in to the abdomens of baboons. To dampen the immune response and the likelihood of a blood clot even further, the baboons were treated with blood-thinning drugs and an antibody called anti-CD40 that works by muddling the immune response.
Remarkably, some baboons on this trial survived for over two years. The baboons only died when the researchers reduced the level of anti-CD40 in order to test if the baboon’s immune system had developed a tolerance for the pig heart – it hadn’t. Now, researchers know that more effort needs to be focused on the role of anti-CD40 in order to produce more immune-compatible organs.
Xenotransplantation has come a very long way since John Hunter was sticking human teeth onto rooster’s heads. We aren’t quite at the stage where pig organs are a medically viable option to replace human ones, but technology is rapidly progressing to a world where organ donation waiting lists could be a thing of the past. Thanks largely to pigs.
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Mohiuddin M.M. et al. Nature (2016) 7, 1-10
Oriol, R., Ye, Y., Koren, E. & Cooper, D. K. Transplantation (1993) 56, 1433–1442