It was only three months ago that surgeons successfully attached a kidney from a genetically altered pig to a human recipient. Since then, new successes continue to pile on. In December, the kidney procedure was successfully repeated. Then, earlier this month, we celebrated another huge leap forward in such xenotransplantation: Surgeons successfully transplanted a pig heart into a human patient who lives in the Baltimore area. For this accomplishment, congratulations are in order.
The success of these procedures hinged on the incredible talent of surgeons and medical professionals, and it also required decades of behind-the-scenes research to build the foundations of genetic engineering in pigs. It was a continuum of work that I was part of at a lab in Missouri beginning over two decades ago and is now offering hope to the more than 100,000 people waiting for organ transplants.
But there was also a time when that initial research was derided as, pardon the pun, pork barrel spending.
In 2001, I and a team of collaborators at the University of Missouri, and Robert Hawley at Immerge Biotherapeutics in Boston, first patented the technology to create so-called “knockout pigs.” In simple terms, our research showed how to remove — or knock out — a molecule on the surface of a pig’s cell. These “knockouts” affect the genes that control for a variety of traits. To develop the technology’s potential, we began with projects that to some may have seemed silly. Through our genetic engineering research, we showed it’s possible to develop bioluminescence in pigs, basically making them emit a low level of light.
This development was a vital proof of concept (and those “green” pigs remain essential to scientists by providing cells that can be easily tracked, for example, to study the use of stem cells to repair organ damage). We showed that pigs could be produced from genetically engineered cells, like the process used to clone Dolly the sheep.
Next came a steady drumbeat of progress that benefited both human and animal health. For example, we’ve been able to disrupt the gene that makes pigs vulnerable to porcine reproductive and respiratory syndrome virus. These pigs are now resistant to a deadly virus that every year kills thousands of animals and costs pork producers in North America and Europe an estimated $6 million each day.
Taken collectively, all of these milestones were part of the slow process that helped us find how knockout pigs and gene editing could help people.
By developing these and other enabling technologies, we were able to create pigs that help us study a range of ailments, including cystic fibrosis, retinitis pigmentosa and cancer. Fast-forward to 2022; Revivicor was able to use knockout pig technology licensed from the University of Missouri (one of the 10 genetic modifications included by Revivicor) to develop a heart and kidney that resist hyperacute rejection. This is critical because hyperacute rejection occurs when the body’s defenses attack a foreign organ. It ensues within minutes without this specific knockout.
It’s clear we are now taking the first steps into a new era of human health and well-being. I’ve mentioned that there are more than 100,000 people on transplant lists, a vast majority of them awaiting a kidney. Those patients have the option to go on dialysis while they wait. For those who need a heart, options are more limited. Basically, there are two ways off any transplant list: You either receive an organ or you die. It’s been reported that the patient in Baltimore was facing just this choice, and receiving a pig heart was the final (and best) option.
This is the unique hope xenotransplantation provides, built on decades of foundational discoveries and the enabling technologies that make genetic engineering in pigs possible. There is a direct line from glowing pigs to saving lives — it just takes time for scientists to discover what is possible.
About the writer: Randall Prather is a Curators’ Distinguished Professor of Animal Sciences at the University of Missouri and director of the National Swine Resource and Research Center.
