• Surgeons at New York University’s Langone Transplant Institute have successfully performed a pig kidney transplant using a genetically modified pig as the donor.
  • This is a momentous step towards saving the lives of tens of thousands of people awaiting a transplant.
  • But there are still many unanswered questions surrounding the ethics and efficacy of cross-species transplants: more robust, longer-term trials will have to take place.

Earlier this week, surgeons at New York University’s Langone Transplant Institute successfully performed a pig kidney transplant. This in itself would be unremarkable. What does mark the achievement as unprecedented is the identity of the donor – a genetically modified pig.

Some days post-surgery, the recipient, a brain-dead patient whose family consented to the experimental procedure, has not rejected the kidney and tests show that it is functioning normally. This incredible feat is significant both as a demonstration of scientific control over biological systems and as a beacon of hope to others in line for a transplant.

Cross-species organ transplants: Pigs, CRISPR and immunity

The idea of using other species for organ transplants is not new; we have used pig heart-valves for over 50 years. Yet whole organs have presented several challenges, most notably the risk of rejection. This occurs because the body believes the transplant is an invader that must be destroyed, leading to an immune response that attacks the organ. While the triggers for rejection are not completely understood, one of the biggest barriers to cross-species transplantation is a molecule known as alpha-gal, a carbohydrate that immediately elicits a massive immune response.

To counteract this, scientists used a powerful tool of genetic engineering, CRISPR, to modify the pig’s genome so that it does not produce alpha-gal. CRISPR has existed for less than a decade, yet its ability to accurately ‘cut and paste’ specific pieces of genomes is already leading to breakthroughs in many areas of biology – including in the development of COVID-19 vaccines.

Organ donors: Demand outstrips supply

At present, over 100,000 people in the United States are awaiting an organ donation, among whom 83%, ~91,000, are in need of a kidney. Though 54% of US citizens are registered organ donors, less than 1% of deaths result in useable organs, so supply will always outstrip demand.

Consequently, wait times for a kidney can range from four months to six years depending on blood type, geographic location, disease severity, immune system activity, and other factors. Most of those on the waiting list must have their blood cleaned via hemodialysis, a process that entails commuting to a dialysis centre and spending four hours a day, three times a week, attached to a machine simply to stay alive. The longer they are on dialysis, the smaller their chance of a successful kidney transplant becomes as the procedure can only partially compensate for the damaged organ.

Lack of donors is a global health concern

Every year, 5,000 people die waiting for a transplant and another 5,000 are removed from the list because they are no longer healthy enough to receive it, meaning that only 65% of those placed on transplant lists will receive a kidney in time. This latest development could prove to be a gamechanger.

kidney-transplant-patient-wait-list

The ethics and efficacy of pig kidney transplants

But there will be difficult questions about the ethics of modifying other species to fit our needs, and the event may spark further dialogue on the conditions pigs and other animals are currently raised in. There are also still many unanswered questions surrounding the efficacy of cross-species transplantation. Can pig kidney transplants to humans save lives? Well, before we get to an answer, more robust, longer-term trials will have to take place.

Yet the significance of this pig kidney transplant demonstration should not be underestimated – this is a momentous step towards saving the lives of tens of thousands of people awaiting a transplant, not to mention the half a million with kidney failure who do not even qualify because of scarcity. It also speaks to the potential of biotechnology more broadly to transform the health outcomes of millions of people.