Recently, a team from the University of Alabama in Birmingham performed the first-ever pig-to-human organ transplant . The general process of animal-to-human organ transplantation is called xenotransplantation (“xeno” meaning foreign in Greek), and brings to mind images from science fiction . However, the achievement of the doctors and scientists from Birmingham brought the possibility of xenotransplantation one step closer to reality. While xenotransplantation is still a long way from being done in normal human patients, it holds great promise and may revolutionize the field of transplant surgery. It is worthwhile to consider the science behind this advancement, as well the potential impacts it may have on healthcare broadly.
The process of procuring an organ for transplant is a difficult one. There are several factors that may lead the recipient’s immune system to reject the transplanted organ. Notably, blood type is an important determinant for organ compatibility. Further considerations must also be made for other components of the immune systems of the donor and the recipient, specifically a protein found on the surface of white blood cells known as HLA. If a poorly matched organ is transplanted, blood clots may form in and around the new organ due to the body attacking the organ. These clots may damage the organ or move through the bloodstream to the brain or lungs, which can lead to strokes or pulmonary embolisms . The difficulty of finding compatible organs appears to be an intractable problem for traditional transplantation.
This difficulty is particularly important when it comes to kidneys due to the high level of demand for them. Data from September 2021 shows that 83% of people on the organ transplant list are waiting for kidneys, but only around 25,000 kidney transplants are performed per year . This translates to nearly 800,000 people left living with end stage kidney disease, which means they require dialysis, an invasive and continual medical treatment that uses a machine to do the work of a kidney. It is important to consider the human aspect of this crisis, as dialysis is a significant financial and emotional burden on patients. Dialysis, on average, costs $90,000 per year. While dialysis is usually covered by health insurance, deductibles and related expenses can make this treatment unaffordable for people who rely on it to live . Dialysis also impacts quality of life due to the time-intensive nature of the treatment. Patients on dialysis often have a regimen that includes going to a dialysis clinic two to three times per week for four hours each. Patients on dialysis also experience dialysis-related symptoms and are at a high risk for infection. On top of this, dialysis is related to chronic cardiovascular problems, and an overall reduced life expectancy . Xenotransplantation promises to solve these problems, and ultimately free hundreds of thousands of patients to live freer and fuller lives.
Xenotransplantation seeks to solve this problem by providing surgeons with a plentiful supply of organs from an unlikely source: pigs. Pigs are preferred for a number of reasons. First, they are easy to breed, allowing scientists to maintain a population of pigs with genes that are useful for the transplant procedure. Second, pigs have organs that are almost the same size as human organs . Despite these benefits, there are also a variety of problems that arise when attempting pig-to-human transplants. Eighty million years of evolution separate humans from pigs, which leads to some biological barriers that make kidney transplant difficult. Specifically, the cells of pig kidney have carbohydrate structures that make them look like pathogens to our immune systems, which leads to rejection. The pig genome is also missing some genes found in humans that help regulate blood coagulation, inflammation and immune responses, which are believed to play important roles in the acceptance of a transplanted organ . Thankfully, with the advent of gene editing technology, geneticists are able to regulate which genes are present and absent in a given organism. This is precisely what scientists did with the kidney used in the transplant done at UAB. Four pig genes were “knocked-out” or deactivated, while six human genes were “knocked-in”, reducing the chance that the recipient’s immune system would reject the kidney. Further precautions were also taken to ensure that the kidney would not trigger an immune response in the recipient by raising the pig in a facility free from pathogens and testing the pig regularly for infection .
Even with all these precautions, the result of the transplant was far from certain. This was a unique undertaking, and there was a real possibility that the kidney would trigger an immediate immune reaction. Thankfully, the transplant was a success, and surprisingly, one of the kidneys began producing urine nearly immediately. In a normal kidney transplant, it takes a few hours or days for the kidney to begin producing urine . The recipient showed no signs of rejection for the three days that the kidneys were in place before they were removed for further analysis, which is an extremely promising result for xenotransplantation .
Despite the results of this experimental transplant, there are a few reasons to be cautious. First, the transplant was done in a brain-dead patient. This is a very different environment from what would be seen in a normal transplant recipient. This also made it difficult for researchers to accurately measure kidney function after the transplant. Further, the kidneys were removed after only three days. Although no signs of rejection were present, some organs were rejected later on after transplantation. The limited timeframe of the study makes it difficult to predict if pig kidneys match the longevity needed for transplantation . However, the successful results of this study and the promise of a nearly endless supply of kidneys make further investigation both intriguing and necessary.
Xenotransplantation is an exciting new advancement in medicine that promises to alleviate the demand for organs that cannot currently be met. Recent progress in this field suggests that we are closer to practical xenotransplantation than ever before. These advancements were made possible through a number of significant scientific developments over the last twenty years, particularly in genetic engineering and transplant surgery. Xenotransplantation appears to be a particularly promising solution to the problems associated with kidney disease and failure, conditions that impact hundreds of thousands of Americans. Ultimately, xenotransplantation is a perfect example of the potential of science to help people live healthier and happier lives, and it holds much promise to revolutionize transplant surgery and how we treat kidney disease.
Edited by: Vicky Cadena
Illustrated by: Shanthi Deivanayagam