The recent and thrilling news about the successful transplant of a pig kidney into a human seems revolutionary. But it comes out of decades-long efforts by doctors and other scientists to perfect the practice of xenotransplantation, that is, transplanting other species’ organs into humans.
The child who would become known to the world as “Baby Fae” was born on October 14, 1984, with a fatal congenital heart defect known as hypoplastic left-heart syndrome. Faced with the certainty that her baby would die, Baby Fae’s mother decided to allow something extraordinary.
A cardiothoracic surgeon named Leonard Bailey had been working on xenotransplants (transplants between different species) for years. Though he had never before tried one on a human patient, he would replace Baby Fae’s heart with one from a baboon—a primate known to be genetically, developmentally, and physiologically similar to humans.
Six baboons were available as donors, and Bailey’s surgical team chose the most tissue-compatible one. On October 26, the surgery was successfully performed. Within days, Baby Fae, who was being treated with the relatively new immunosuppressant cyclosporine, was off the ventilator and eating.
As she recovered, her story became a worldwide media sensation. Responses ran the gamut from pro-animal-rights protesters to those who wrote cards and letters of support to Baby Fae’s young parents.
But around two weeks post-surgery, her condition took a downward turn. The medical team stepped up their immunosuppressive efforts, believing it to be a typical organ transplant “rejection episode,” but nothing worked. Baby Fae passed away on November 15.
Bad Blood
Although the cause of death was initially a mystery, Bailey eventually determined that it was due to mismatched blood types—Baby Fae had type O blood, while the baboon had type AB blood. This created an autoimmune response in Baby Fae, and her body’s immune system began to attack her own organs.
Though Baby Fae’s story had a tragic ending, it raised public awareness about the need for donor organs of all ages. Today, an urgent shortage still exists, and some researchers continue to work on perfecting xenotransplants for potential use in humans, though their focus has switched to pigs as donors, due in part to their large litter sizes.
Experiments using the genome editor CRISPR are underway, too, not only to prevent pig organs from being rejected by the human immune system but also to edit out genetic sequences that lead to porcine viruses, which could potentially be transmitted to humans. One spectacular result of xenotransplant research can be seen below recent headlines about the successful transplant of a pig’s kidney into a human body by surgeons at N.Y.U. Langone Health. Though their results are preliminary, it is clear that xenotransplants have come a long way from the 17th-century practice of transfusing the blood of sheep into human recipients.
As I discovered while working on my new book Pump: A Natural History of the Heart, researchers are also taking different approaches to addressing the desperate need for donor organs. A few physicians, such as Harald Ott at the Harvard Stem Cell Institute, are attempting to grow their own—though not quite from scratch, as they start out with hearts from cadavers.
In addition to difficulties obtaining and transporting donor organs, doctors face problems related to tissue incompatibility. Ott’s team is dissolving away those cells and tissues on the cadaver hearts that could cause rejection, leaving behind a “regenerative scaffold” of connective tissue that maintains the three-dimensional shape of the original.
To make a complex story short, their ultimate goal is to take skin cells called fibroblasts from the organ’s recipient, convert them into stem cells, stimulate them to become cardiac-muscle cells, and seed them onto the regenerative scaffold, where they will then grow. The end result, which they hope will occur during the next decade, will be a grown-to-order heart, or liver, or kidney—organs with little chance of rejection, since the bulk of the tissues in the regenerated organ will match those of the recipient.
These research efforts aren’t the only grow-your-own cardiac studies out there. There are medical researchers who are attempting to use the veins in store-bought leafy greens to construct human blood vessels. Others are attempting to mimic the amazing growth of cardiac muscle that occurs in recently fed Burmese pythons. Some even study zebra fish, popular aquarium denizens with the ability to regenerate roughly 20 percent of their heart mass after having it bitten off by a predator (or snipped off by a scissor-wielding researcher).
In the nearly 40 years since Dr. Bailey’s heroic efforts to save Baby Fae, much has changed within the field of cardiac medicine. Today, the prognosis for newborns suffering from the heart syndrome that afflicted Baby Fae has improved tremendously, thanks to a surgical procedure known as “staged reconstruction,” which literally frees the weakened left side of the heart of its important duties.
But as the epidemic of heart disease, and the need for donor organs, continues, 21st-century researchers are exploring new and innovative ways to save their patients. In doing so, they continue to ask the same question posed by Dr. Bailey and the medical pioneers who came before them: Why can’t we do that?
Bill Schutt is a vertebrate zoologist and the author of several books. His latest, Pump: A Natural History of the Heart, is out now from Algonquin
