Groundbreaking milestone: US surgeons transplant world's 1st genetically edited pig kidney into patient

Doctors at Massachusetts General Hospital have successfully performed a groundbreaking kidney transplant surgery on a 62-year-old man from Weymouth. In a historic medical achievement, the patient received a kidney from a genetically engineered pig, marking the first instance of an animal kidney being transplanted into a human recipient.

The four-hour operation, conducted on Saturday, has initially yielded positive results, with the patient reportedly in good condition several days post-surgery. However, the true measure of success will be determined in the coming weeks and months as doctors closely monitor the patient's kidney function, watch for signs of rejection, and remain vigilant for any potential infections.

Prior experiments have entailed the transplantation of pig kidneys into brain-dead individuals and nonhuman primates. Over the past two years, two men have undergone surgeries to receive genetically modified pig hearts, with both surviving for as long as seven weeks.

The recent operation conducted on Saturday utilized a pig whose genetic makeup had been modified to reduce the likelihood of organ rejection. This development sparks optimism regarding an alternative solution to address the scarcity of organs, particularly kidneys. In the United States alone, over 100,000 individuals are currently awaiting organ transplants, with an unfortunate average of 17 deaths occurring daily among those on the waiting lists, as reported by the US Health Resources & Services Administration.

“It is super exciting because I can see that he is doing so well. It’s almost breathtaking to see that this is working,” said Dr. Winfred Williams, associate chief of the renal division at Mass. General and a transplant nephrologist who has known the patient for a decade. “If this technological advance gives us access to a continual robust supply of organs for transplantation, that will change the whole nature of the waiting lists for transplant.”

The recent operation at Mass. General marks another significant stride in the field of xenotransplantation, where organs or tissues are transplanted between different species. This area of research has seen notable acceleration in recent years.

At institutions such as NYU Langone Health and the University of Alabama at Birmingham Heersink School of Medicine, teams have conducted experiments involving the transplantation of pig kidneys into brain-dead individuals who volunteered for the procedure. In one case, the transplanted kidney lasted for a remarkable two months. Similarly, in 2022 and 2023, doctors at the University of Maryland attempted pig heart transplants on two men, although unfortunately, both patients passed away within two months of the surgeries. Additionally, recent research revealed promising results wherein gene-edited kidneys functioned effectively in monkeys, with one animal maintaining kidney function for over two years.

The pigs providing organs for these experiments, including the one involved in Saturday's operation, are sourced from the same company, eGenesis, based in Cambridge. Utilizing CRISPR gene-editing technology, eGenesis has made significant modifications to the pig genome, eliminating features that trigger rejection in humans and deactivating pig viruses that could pose a threat to human recipients.

Under the FDA's "compassionate use" policy, which permits experimental treatments for individuals with life-threatening conditions and limited treatment options, the transplant procedure received approval.

The patient, Richard “Rick” Slayman, a manager at the Massachusetts Department of Transportation, suffered from kidney failure due to complications from diabetes and hypertension—common causes of this condition, according to Williams, the patient's doctor. After enduring seven years of dialysis, which involves diverting blood to a machine for purification, Slayman received a human kidney transplant in 2018. However, the transplanted kidney failed after five years, necessitating Slayman's return to dialysis—a particularly arduous experience for him due to recurrent difficulties in accessing his blood vessels.

“His vessels were constantly clotting and failing,” Williams said. Efforts to fix the problem with surgery were unsuccessful.

When presented with the opportunity for a highly experimental solution—a pig's kidney—Slayman expressed to Williams his willingness to take the chance, citing the misery of his current condition.

Slayman emerged as a suitable candidate for the experiment due to his overall health, aside from kidney failure and diabetes, which Williams described as "reasonably good." Moreover, his familiarity with the transplant process further bolstered his candidacy.

On Saturday, Dr. Tatsuo Kawai, director of the Legorreta Center for Clinical Transplant Tolerance, and Dr. Nahel Elias, interim chief of transplant surgery, traveled to a designated facility to perform surgery on the pig, which had been transported from another state.

Both kidneys were extracted, with one kept as a backup, and the pig was euthanized while under anesthesia, with its remaining organs preserved for research purposes.

The surgeons then transported the kidneys on ice back to the hospital, where Slayman was already under anesthesia on the operating table.

Three surgeons—Elias, Kawai, and Shoko Kimura—alongside two postdoctoral fellows, commenced the procedure. They made an incision in Slayman's lower abdomen on the left side and began attaching the blood vessels, ensuring to clamp them closed to prevent bleeding.

The pig kidney, drained of its own blood prior to the operation, lay in a pale, beige state. As the surgeons removed the clamps, Slayman's blood began flowing into the transplanted organ, causing it to turn a vivid pink, indicating signs of life. The scene prompted cheers and applause from everyone present, with Elias expressing that "Everybody was just elated."

In approximately one-third of human transplants, the kidney may not immediately function; however, the pig kidney transplanted into Slayman began producing urine right away. It has successfully undertaken crucial kidney functions, including regulating creatinine and potassium levels and secreting hormones.

Upon Williams' visit to Slayman on Wednesday, he found him sitting up on the side of his bed, resembling his former self. Williams remarked on Slayman's daily improvements, indicating positive progress.

Assuming his current trajectory continues, Slayman is expected to be discharged within the next few days. He will return for regular tests twice a week during the initial month, with a potential return to work in approximately six weeks, as outlined by Williams.

To prevent rejection of the organ, Slayman will adhere to a regimen of immune-suppressing medications, along with medications tailored for xenotransplantation.

Doctors will closely monitor the kidney's functionality, evaluate for signs of rejection, and remain vigilant for any indications of infections.

However, as Elias noted, there are still unknown factors to consider. Unforeseen challenges may arise, as not all potential issues may have been uncovered in animal studies.

In the event of kidney failure, Slayman will need to resume dialysis. Fortunately, his place on the transplant list will remain secure. Nonetheless, finding a suitable kidney match, particularly for African-Americans like Slayman, can be notably challenging, given his over two-year wait on the list.

Despite the uncertainties, Slayman's medical team remains hopeful, reflecting on the remarkable progress achieved through xenotransplantation. Elias expressed astonishment at the realization of this medical breakthrough within their lifetime, emphasizing the unexpected strides made in this field.