Can Animal Organ Transplants Save Thousands of Dying People?
BMC’s kidney transplant director discusses Mass General’s landmark pig kidney operation
Rick Slayman died after receiving a pig kidney for his end-stage kidney failure, but his Massachusetts General Hospital caregivers said the transplant was not the cause of his death. Photo by Massachusetts General Hospital
Can Animal Organ Transplants Save Thousands of Dying People?
BMC’s kidney transplant director discusses Mass General’s landmark pig kidney operation
An average of 17 people waiting for organ transplants die each day in the United States. Might patients and doctors have a life-saving workaround in animal organs?
The tantalizing prospect follows the transplant at Massachusetts General Hospital in March of a pig kidney into a 62-year-old with end-stage kidney failure. The patient, Rick Slayman, died almost two months later, although the hospital says it has no indication that his death was related to the transplant. The kidney had been genetically edited to purge harmful pig genes and add human ones.
BU Today asked Jean Francis, an associate professor of medicine at Boston University’s Chobanian & Avedisian School of Medicine, about the state of the field. Francis is medical director of the kidney transplantation program at Boston Medical Center (the medical school’s teaching hospital and New England’s largest safety net hospital) and medical director of the pancreas transplant program at Boston’s Brigham and Women’s Hospital.
This interview was edited for clarity and brevity.
Q&A
with Jean Francis
BU Today: Which organs—and from which animals—show the most promise for successful transplantation into humans? Are any of these animal organ transplants in clinical trials?
Francis: As of now, very limited trials have occurred, using organs from pigs only. The organs trialed are the heart and kidneys. Two patients underwent heart transplants at the University of Maryland under an extremely strict immunosuppressant regimen. One heart transplant lasted a bit above 40 days and the other close to two months. Both hearts ended up being rejected (although this is still debatable), but both patients died after the transplant failed. This was one of the first trials showing the feasibility of such transplants and giving clinicians some ideas about what to expect regarding complications.
A program in New York City transplanted two potentially [terminal] patients on life support with pig kidneys, connected to the radial arteries in the forearm, for two days before withdrawing support on those patients. Both kidneys showed no signs of rejection, produced urine, and as a proof of concept, they were able to show that no super-acute rejection would happen if such transplants are performed in the future.
Those trials encouraged the MGH group to move forward recently with the first swine-to-human kidney transplant on a patient who has been on dialysis for a couple of years, after losing his first kidney transplant from a deceased human donor.
As of now, the only animal that has the potential to be an organ transplant donor for humans is the pig. Those animals are genetically engineered to make them human-compatible. Further refinements of those modifications are always being revised. More than 100,000 patients are currently on the kidney transplant list [in the United States], and close to 5,000 patients die yearly while waiting for kidney donors. If the modified pig kidney proves its efficacy, it will eliminate the organ shortage and the waiting time. Before widespread use of those organs, a well-organized, large, multicenter trial is needed to support the benefit of such a procedure.
BU Today: At the moment, what are the medical obstacles to successful animal-to-human transplants?
Francis: The main obstacles are genetic compatibility. Without genetic manipulation of the pig kidneys, we will reject them automatically upon transplant. We have to make those kidneys human-compatible by removing or eliminating some antigens expressed on the inner layers of the blood vessels of those pig organs. Humans have preformed antibodies against those antigens, and they will trigger acute rejections. Those antigens are eliminated by genetic manipulation.
Other modifications are needed to render those organs less able to induce clotting, and also make those organs more resistant to the potent immune system humans have, which we call the complement system. Complement activity needs to be controlled to prevent injury to swine grafts. Those swine organs are protected from the complement injury with special medications given at time of transplant. Also, the genetic modifications on those swine organs render them more resistant to the complement attack and injury.
Last, those swine organs come to us with endogenous viruses that are part of the pig genetic material. Genetic engineering has been able to remove some of the swine retroviruses, but we don’t know if others are still there. So, close monitoring for transmitted infections from swine to human recipients is also of concern, although the data support safety so far on those very limited cases.
I am very optimistic that swine transplant will become available for a lot of patients with no other options. I feel this is the future, the moonshot of transplant.
BU Today: Does Mr. Slayman’s death affect your optimism about swine organ transplants?
The unfortunate passing of Mr. Slayman should not affect our determination to move forward with xenotransplantation, especially given that as of now there is no indication that his passing is attributed in any way to his pig kidney. This is based on what has been released from the treating team. Mr. Slayman was determined to be the first candidate to receive such a kidney in the hope of helping advance the field. I am very confident that Mr. Slayman [would] not want his passing to stop us from achieving his desired wish of making xenotransplantation possible.
Definitely, every caution should be taken to prevent any future complications. This is going to be a long process until we fully grasp all the issues related to xenotransplantation, but we should be determined for the sake of our patients to keep advancing this field until it becomes available for many patients.
I am very optimistic that swine transplant will become available for a lot of patients with no other options. I feel this is the future, the moonshot of transplant. This will come only after rigorous studies supporting safety, patients’ and organ survival, and after optimization of those engineered organs. Stay tuned.
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