In historic first, surgeons transplant a genetically modified pig heart into a dying patient
Two and a half months after an NYU team dubiously claimed to have performed the first ever pig-to-human organ transplant, a team at the University of Maryland Medical Center appears to have actually done it.
The center announced Monday evening that surgeons there successfully transplanted a genetically modified pig heart into a 57-year-old patient with terminal heart disease. The patient, David Bennett, was too sick to qualify for a human donor and had run out of other options.
“I consider this a tremendous breakthrough for the field,” Jim Markmann, head of transplant surgery at MGH and a xenotransplant expert not involved in the UMD case, said in an email.
In the decades-long effort to make xenotransplantation a reality, the new report differed from October’s in key respects. Most glaringly, the patient at NYU was already brain-dead. Doctors sutured a porcine kidney to the outside of her body and could only track whether the patient immediately rejected the foreign organ. As predicted by years of monkey experiments, she didn’t.
The new procedure may offer the first test of whether porcine organs, when bred with the right battery of genetic edits, can actually serve as a replacement or supplement to human organ donation and allow patients to live functional lives.
So far, so good, according to UMD, although doctors cautioned that it’s still early. Bennett is doing well three days after the procedure, the center said. The New York Times reported he was still on a heart-lung bypass machine, but that is common for any new heart transplant recipient.
“It was either die or do this transplant. I want to live. I know it’s a shot in the dark, but it’s my last choice,” Bennett said, in a statement provided by UMD. “I look forward to getting out of bed after I recover.”
The news comes as xenotransplantation, after years on the medical margin, appeared to be inching closer to reality, potentially offering an alternative to the hundreds of thousands of patients in the US and around the world waiting for organs. After a high-profile attempt to transplant a baboon heart into a baby with a congenital heart defect failed in 1983, researchers and several companies tried to use recombinant DNA techniques to make pigs with organs that humans can accept.
Those efforts disintegrated virtually overnight after the discovery of a retrovirus common to pigs, terrifying health officials then dealing with the height of the US’s HIV crisis. But in the last decade, as further research lowered concerns that porcine endogenous retrovirus, or PERV as the retrovirus is known, can transmit to humans and as new genome-engineering tools became available, the field has revived itself.
Bennett’s new heart came from Revivicor, a subsidiary of the $9 billion rare disease biotech United Therapeutics. It’s the same company that provided the NYU kidney, but Bennett’s heart came from pigs with far more genetic edits: 10 in total — four pig genes knocked out to prevent rejection, six human genes knocked in to promote tolerance, and one additional pig gene knocked out to prevent excessive tissue growth.
Scientists are divided on the exact number of edits needed to prevent rejection. Revivicor has been competing with a couple academic labs and eGenesis, the venture capital favorite, to make xenotransplantation a reality. eGenesis, founded by genetic engineer Luhan Yang and backed with over $260 million from private investors, makes an even higher number of edits — they’ve never said quite how many — as they try to eliminate PERV entirely.
To be clear, though, Bennett’s surgery is still a remarkably early step by the standard process of drug development. The FDA OK’d the procedure under compassionate use, an emergency measure to make experimental therapies available to patients with no other options.
For xenotransplantation to actually become a medically approved product, one company or academic team will have to show the modified porcine organs are safe and effective in a clinical trial.
Revivicor, eGenesis and others are trying to complete the monkey studies necessary to receive clearance for such a trial. They will likely need to show the non-human primates have consistent survival after transplant. Experts suggest one could begin in 2023.