The tantalizing potential of pig-to-human transplantation, or xenotransplantation, has reached another frontier. For the first time ever, scientists have transplanted a genetically edited pig lung into a living human body.
Researchers in China reported the medical feat in a study published Monday in Nature Medicine. The gene-edited left lung survived for nine days inside a person declared to be brain dead. More work has to be done to ensure the long-term viability of these organs, the researchers admitted.
The dire need for more organs
Despite recent strides, there simply aren’t enough living or deceased human donors to meet the urgent need for organs. More than 100,000 Americans are on the waiting list for a donated organ, and over 5,000 die annually without having received one. That’s why scientists have been hopeful about the promise of xenotransplantation for decades.
It’s only recently, however, that this approach has seemed within reach, thanks to gene-editing advances that are allowing scientists to create pigs more compatible with human biology. One of these vital modifications removes a pig’s ability to produce the sugar alpha gal in their muscles—a sugar that humans don’t make.
In recent years, scientists have transplanted kidneys, livers, and hearts from gene-edited pigs into a human body. But this new research appears to show the first recorded instance of a gene-edited lung transplant.
A novel but flawed accomplishment
As with most xenotransplantation studies in humans so far, the research involved a person who was declared brain dead (according to the researchers, this status was verified by four separate assessments). They transplanted a pig’s left lung into the 39-year-old recipient, who was also given immunosuppressant therapy. Then they tracked how the new lung functioned as well as the host’s immune response to it.
The lung wasn’t immediately rejected by the body, the researchers found, and it was both viable and functioning for at least nine days. But within a day, they spotted lung damage that was possibly caused by the sudden return of blood flow. On days three and six, they observed signs of rejection from the recipient’s antibodies that actively damaged the lung. And though there was some recovery afterward, the researchers decided to end the experiment at day nine.
Important as this research is, the findings also show just how far these transplants are from becoming a clinical reality.
“Although this study demonstrates the feasibility of pig-to-human lung xenotransplantation, substantial challenges relating to organ rejection and infection remain,” the researchers wrote.
Xenotransplantation in general is still in its infancy, and a bona fide breakthrough hasn’t quite yet happened. Doctors have started to transplant gene-edited kidneys and hearts into living recipients on an experimental basis (these recipients are usually terminally ill and have few other options available). But to date, none of these patients have lasted more than a few months with the new organ. In April, for instance, 53-year-old Towana Looney relinquished her pig kidney four months post-transplant after it began to fail (she has since returned to regular dialysis).
That said, scientists still are learning lots from these early studies and failures. These lessons will hopefully narrow down the exact mix and amount of gene edits needed to make a pig organ human enough, as well as the precise regimen of drugs that will keep these organs safe from rejection. And the technology is certainly moving forward.
Earlier this February, for example, the Food and Drug Administration granted two companies— eGenesis and United Therapeutics—permission to move forward with phase I clinical trials of xenotransplantation for people with kidney failure. In April, eGenesis received further FDA clearance for a separate phase I trial of liver xenotransplantation.
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