Pig Kidney Transplants: A Milestone for Xenotransplantation

For decades, the idea of using animal organs to save human lives seemed like science fiction. However, recent breakthroughs in 2024 have moved this concept from theory to reality. Surgeons have successfully transplanted gene-edited pig kidneys into living patients for the first time. This advancement offers hope to the hundreds of thousands of people currently waiting for a life-saving donation.

The Case of Richard Slayman

The most significant milestone in this field occurred in March 2024. Richard “Rick” Slayman, a 62-year-old man battling end-stage kidney disease, became the first living human to receive a genetically edited pig kidney. The surgery took place at Massachusetts General Hospital in Boston.

The procedure was not just a surgical feat. It was a triumph of genetic engineering. The kidney came from a pig donor provided by eGenesis, a biotechnology company. Scientists used CRISPR-Cas9 technology to make 69 specific genomic edits to the animal’s DNA.

These edits served three distinct purposes:

• Removing harmful pig genes: Three genes were knocked out to eliminate sugars that trigger immediate rejection in the human body.
• Adding human genes: Seven human genes were inserted to help regulate inflammation and blood clotting.
• Inactivating viruses: 59 edits were made to neutralize porcine endogenous retroviruses (PERVs), which are viral elements in the pig genome that could potentially infect humans.

Mr. Slayman recovered well enough to be discharged from the hospital two weeks after the surgery. While he sadly passed away in May 2024, approximately two months post-transplant, his medical team at Mass General stated there was no indication that the transplant itself caused his death. His contribution provided invaluable data that proved a pig kidney could filter blood and produce urine in a living human.

The Second Recipient: Lisa Pisano

Shortly after the success with Mr. Slayman, surgeons at NYU Langone Health performed a similar procedure on Lisa Pisano in April 2024. Ms. Pisano faced a more complex medical situation than Mr. Slayman. She suffered from both heart failure and kidney failure.

Doctors implanted a mechanical heart pump along with a gene-edited pig kidney. This kidney also featured the specific edits to the thymus gland aimed at “educating” the recipient’s immune system to accept the new organ.

The outcome for Ms. Pisano highlighted the difficulties of xenotransplantation in critically ill patients. While the kidney functioned initially, surgeons had to remove it after 47 days due to issues with blood flow related to her heart pump and blood pressure medications. Importantly, the organ showed no signs of cellular rejection. Ms. Pisano passed away in July 2024, but her case demonstrated that these organs can function even in highly complex physiological environments.

Why Pigs are the Ideal Candidates

You might wonder why scientists chose pigs rather than primates, which are genetically closer to humans. Primates grow slowly and raise significant ethical concerns regarding their use in research. Pigs, conversely, are already raised for food, grow rapidly, and have organs that are roughly the same size as human organs.

The primary hurdle has always been a sugar molecule called alpha-gal. This sugar sits on the surface of pig cells. The human immune system recognizes alpha-gal as a threat immediately. Without genetic editing to remove the gene responsible for alpha-gal, a human body would destroy a pig organ within minutes. This is why the work by companies like eGenesis and Revivicor is so vital. They are essentially creating “human-compatible” biological spare parts.

Pre-Clinical Trials on Decedents

Before attempting surgery on living patients like Slayman and Pisano, researchers validated the science using brain-dead donors (decedents). These trials were critical for FDA approval to move forward.

• The Parsons Model: At the University of Alabama at Birmingham (UAB), Dr. Jayme Locke led a study where gene-edited kidneys were transplanted into a brain-dead recipient named Jim Parsons. The study proved the kidneys could clear creatinine (a waste product) from the blood.
• NYU Langone Studies: Dr. Robert Montgomery led similar experiments with brain-dead donors, maintaining the organs for days and eventually weeks to monitor for delayed rejection.

These experiments allowed surgeons to practice the specific vascular connections needed and study the immune response without risking the life of a patient who had other options.

Solving the Numbers Crisis

The driving force behind this research is a simple, tragic math problem. According to the Organ Procurement and Transplantation Network (OPTN), more than 100,000 Americans are currently on the transplant waiting list. The vast majority of them need a kidney.

The current system relies on altruistic living donors or deceased donors. Supply cannot meet demand. Roughly 17 people die every day in the United States while waiting for an organ transplant.

Dialysis serves as a stopgap measure, but it is grueling. It requires patients to be hooked up to a machine for hours, multiple times a week, to filter their blood. It is expensive and takes a heavy toll on the body. Xenotransplantation offers a potential future where kidneys are available on demand, eliminating the waiting list entirely.

What Happens Next?

The surgeries of 2024 were authorized under the FDA’s “compassionate use” pathway. This allows access to experimental treatments for patients with life-threatening conditions who have no other options.

For pig kidney transplants to become a standard treatment, they must undergo rigorous Phase 1 clinical trials. These trials will involve a larger group of patients and standardized protocols to measure safety and efficacy over longer periods.

Researchers are also refining the immunosuppression drug regimens. Even with genetic edits, recipients still need medication to prevent their immune system from attacking the foreign organ. Finding the right balance between the genetic edits and the drug dosage is the next major challenge for the medical community.

Frequently Asked Questions

Who was the first person to receive a pig kidney transplant? Richard Slayman was the first living person to receive a genetically edited pig kidney in March 2024 at Massachusetts General Hospital.

How long do pig kidneys last in humans? The longest survival in a living patient so far has been approximately two months. However, in studies involving brain-dead decedents, kidneys functioned successfully for over 60 days. The goal of ongoing research is to extend this into years.

Are pig kidneys safe from viruses? Scientists use CRISPR gene editing to inactivate Porcine Endogenous Retroviruses (PERVs) in the donor pig’s DNA. This greatly reduces the risk of transmitting animal viruses to human recipients.

When will pig kidney transplants be available to the public? It will likely take several years before this becomes a routine procedure. The FDA requires successful completion of Phase 1, 2, and 3 clinical trials to prove safety and long-term effectiveness before approving it for general use.