The First Pig Kidney Transplant into Humans
Issue 7, Volume 112
By Andy Chen
From genetically modified organisms and the cloning of Dolly the sheep to CRISPR, a technology that can edit genes, there have been many breakthroughs in genetic engineering. In September, surgeons in New York took another step forward: they transplanted genetically modified pig kidneys into a human patient.
Surgeons at New York University Langone Health operated on a brain-dead patient, through xenotransplantation, the transplantation of nonhuman tissues or organs into a human. In this operation, the donor pig contained a genetic modification that made the surgery a success by knocking out the gene encoding glycan, also known as alpha-gal, responsible for evoking an immune response that leads to foreign tissue rejection in humans. Furthermore, the pig’s thymus gland, which helps the immune system to recognize the kidney as an addition to the body, was surgically attached with the kidney to the patient, lowering the chance of rejection by the body.
Generally, the body rejects large, foreign objects like organs. However, with the genetic modification and the thymus gland, the immune system cannot detect any alpha-gal in the pig kidney, lowering the chance of an adverse reaction. After the kidney was attached to a blood vessel in the patient’s upper leg, scientists monitored urine production and creatinine levels indicative of kidney function for the next 54 hours. Their results matched their prediction: the measured levels matched up with those seen in human kidney transplants, and no signs of rejections were noted. Remarkably, the kidney began urine and creatinine production almost immediately after the procedure concluded, resembling a transplant from a living human donor.
While the kidney was attached outside the body rather than inside, the fact that urine and creatinine were produced provides strong evidence that the kidney would work inside the body as well. Many researchers view this surgery as proof-of-concept that an alternative supply of organs for patients with severe conditions could be developed. With this experiment, pigs could eventually supply essential organs, such as hearts, lungs, and livers, to humans.
The results of this experiment are important, as the demand for organ transplants has been dramatically increasing while the availability of donated organs has only increased marginally. In the United States, 100,000 Americans require life-saving organ transplants, 90 percent of whom need a kidney. Twelve people on this list die every day. These numbers also do not include the roughly half a million Americans suffering kidney failure who need kidney transplants to live a fully normal life. The critical shortage of organs makes the recent advancement in xenotransplantation ever so more important.
Though xenotransplantation seems promising, there are still many obstacles to overcome. The largest hurdle is making sure that the kidney can function properly long-term. For pig organs to be used widely, scientists need to prove that the organ defends against infections and can survive in the body for a lifetime. Over time, the organ may become susceptible to T-cells, a white blood cell that could recognize the organ as foreign and attack. The body could recognize the donated organ as a bacteria or virus and damage it, causing organ failure and potentially death. Though immune-suppressing drugs could be used to reduce immune responses and thus, the rejection chance, their side effects, such as an increased risk of infections, are significant. Immunosuppressants weaken the body’s overall defense system, impairing responses to the constant attacks from bacteria, viruses, and even cancer. Another problem is that pig organs can be dangerous, as retroviruses incorporated into the pig’s genome can be activated at any time. Currently, scientists are experimenting with CRISPR to edit out the retroviruses to make the organs much safer. Overall, xenotransplantation faces many problems that prevent its implementation into medical practice just yet.
As one might expect, there is also great controversy and ethical concerns around the prospect of raising pigs to gather organs. Pigs were chosen in the experiment because of how anatomically similar their organs are to human organs. They are also easy to raise, mature quickly, and grow to adult size in only six months. Additionally, transplanting parts from pigs is nothing new. Patients have been receiving heart valves from pigs for over 30 years, and some diabetics obtain pancreatic cells from pigs as well. Despite the familiarity of pigs, there is still an ongoing argument about whether harvesting organs from them is ethical or not, especially since this could be seen as further animal exploitation. In the United States alone, nearly 100 million pigs are slaughtered for food. If organ transplants are approved, then millions more will be killed. The expansion of the pig industry for organ transplants would also increase the greenhouse gas emissions associated with pigs, further endangering the environment. Making pig organ transplants possible will take an enormous sum of money ensuring that pigs are treated humanely and that damage to the environment is as limited as possible.
Ultimately, researchers need to seek approval from the U.S. Food and Drug Administration to ensure that pig organ transplants are safe and reliable. The discussion about using pigs for organs other than kidneys also needs to take into account challenges presented by each of the 78 different organs present in our body. However, at the rate that xenotransplantation is moving, it is bound to provide many benefits to people, fulfilling the sci-fi fantasy that an unlimited supply of cells, tissues, and organs could be available to humanity.