There is still no consensus on the best way to humanize pig organs, but recent progress has convinced the Food and Drug Administration (FDA) to greenlight the first clinical trial.

The trial will begin enrolling six participants, and could expand to 44 if early results are promising. A six-month survival after the xenotransplant will be considered a success indicator, although it’s unclear how many patients will need to reach this milestone to win the agency’s approval.

While we await the start of the trial, authorized last February by the FDA, all eyes are on Timothy Andrews, who, more than four months ago, received a gene-edited pig kidney under a one-time compassionate use authorization. He has surpassed the previous record held by Towana Looney (four months and nine days with a xenokidney) and, at the time of writing, remains in good health.

A comprehensive overview of recent developments and the field’s current mood is offered in a feature article by Jon Cohen in Science, which traces the tumultuous history of this biomedical frontier—from the first, premature attempt with a chimpanzee kidney in 1963 to the famous case of Baby Fae, who received a baboon heart in 1984; from the wave of enthusiasm for cloning in the late 1990s to the renaissance marked by the invention of genome editing about a decade ago.

Today, China is very active in the field, but little is known about the transplants carried out there. Europe has lagged behind, although Germany is trying to keep pace. The epicenter of research is clearly in the United States, home to both the leading companies in the field and several emerging players.

Last year, United Therapeutics—the company that received the first FDA approval—opened a $75 million breeding and research facility in Virginia and is investing another $200 million to build additional centers in Texas and Minnesota. The goal: to supply 2,000 organs per year. eGenesis, another key player, is preparing its own FDA submission and plans to produce 1,000 donor pigs annually at its two facilities.

The main bottleneck remains cloning—a slow and expensive process still used because it preserves the precise genetic modifications introduced through gene editing, avoiding the complications of sexual reproduction. Lesser-known companies like XTransplant and Choironex, as well as China’s ClonOrgan, use cloning only in the early stages, then switch to conventional breeding between closely related animals—an approach that could simplify production.

Technical differences don’t end there. Each company has its own strategy for making pig organs more compatible with human recipients using CRISPR. One essential step is removing certain surface sugars that trigger hyperacute rejection, starting with the most important one: alpha-gal. Beyond that, each has its own recipe. eGenesis, for instance, removes all traces of PERVs (porcine endogenous retroviruses) from the pig genome, despite the theoretical and minimal risk they could reactivate. Revivicor, part of United Therapeutics, instead selects pig breeds with naturally low PERV content.

Revivicor also inactivates the growth hormone receptor to prevent the organs from growing too large, while others use mini-pigs to sidestep this issue. Additionally, Revivicor inserts human genes into the pig genome to better modulate immune responses. Choironex is testing an alternative approach: co-transplanting a portion of the thymus along with the kidney to retrain the recipient’s immune system, especially T cells.

This new era of xenotransplantation began in 2021 with trials on brain-dead patients who had donated their bodies to science. This was followed by surgeries on living patients in critical condition, offering the transplanted organs little chance of long-term function but teaching useful lessons to the field. So far, no patient has survived more than two months post-transplant, either due to causes unrelated to the xenotransplant or for unclear reasons. Yet studies in pigs transplanted into primates suggest that with the right protocols and healthier patients, survival could extend from months to years.

The first person to surpass the two-, three-, and four-month marks was 53-year-old Towana Looney. After donating a kidney to her mother, she lost function in the remaining one due to pregnancy-related complications. On November 25, 2024, she received a kidney with ten genetic modifications from United Therapeutics, transplanted at NYU Langone Health. After 130 days, on April 4, 2025, the organ was removed, and she returned to dialysis, likely due to an unrelated infection that required reducing her immunosuppressive drugs.

The current record holder is a 66-year-old man operated on at Massachusetts General Hospital on January 25, 2025. He received a kidney from eGenesis.

Before his operation, Timothy Andrews contacted Looney on Facebook to hear her story, and the two became friends. In a curious twist, the day he entered the OR was the same day Towana became famous as the first patient to survive beyond two months.

So far, Timothy has recovered from an unrelated infection—possibly thanks to a different immunosuppressive strategy. His regimen includes a monoclonal antibody targeting CD154, a molecule on the surface of human cells that may contribute to rejection. Some experts believe anti-CD154 could be a key factor in achieving long-term success.

[Translated from an article by Anna Meldolesi in Osservatorio Terapie Avanzate]