On the afternoon of March 8, local time, David Bennett, a patient who had received a pig heart transplant, passed away.
About two months ago, David Bennett, 57, underwent this special transplant at the University of Maryland Medical Center, transplanting a genetically modified pig heart into the body, the first in the world.
After Bennett underwent surgery, nothing went wrong during the most critical 48 hours. At the time, researchers said they hoped similar surgery could bring hope to more than 500,000 U.S. patients waiting for kidney or other organ transplants in the future. But Bennett was ultimately unable to escape the clutches of the disease.
In January 2022, in Maryland, USA, Bennett, an American man, underwent surgery, becoming the first patient in the world to receive a pig heart transplant. Figure/IC photo
Still, The New York Times commented that the heart transplant was a major advance in medicine.
Bennett's Son: Expecting a father's surgery is the beginning, not the end, of hope
Bartley Griffith, the surgeon who performed the procedure, said hospital staff were saddened by Bennett's departure. "He (Bennett) was a brave, respectable patient who fought until the end."
Researchers still don't know whether pig organs trigger an immune rejection in the patients. A spokesperson for the University of Maryland Medical Center said, "When Bennett died, (we) failed to confirm a clear cause of death. Doctors have not yet conducted a thorough examination of Bennett, and they plan to publish the findings in peer-reviewed medical journals.
The New York Times commented that Bennett's swine heart transplant is still seen as a major medical advance because the pig heart is not immediately rejected and has been operating for at least a month.
In the early postoperative period, the pig's heart function is normal, and the University of Maryland Medical Center also regularly releases Bennett's personal condition, and he seems to be slowly recovering. Last month, the medical center also released a video of it watching the Super Bowl from a hospital bed with staff. But just a few days ago, the hospital said its condition was getting worse.
Bennett's son issued a declaration after his father's death, thanking the University of Maryland Medical Center and its staff for expecting his father's transplant to be the starting point, not the end, of hope. "We hope that the experience gained from his surgery will benefit future patients."
Muhammad Mohiuddin, scientific director of the Xenotransplant Organ Program at the University of Maryland Medical Center, said he learned valuable lessons from Bennett that genetically engineered pig hearts can indeed function properly in the human body and that the immune system is sufficiently suppressed.
According to Xinhua News Agency, many patients around the world need to wait for organ transplants due to different disease conditions, but donated human organs cannot meet such needs. Under the "transplant organ shortage", xenotransplantation offers hope for thousands of patients.
Practice of xenotransplantation: baboon heart, pig kidney and pig heart
"Either die or have a transplant." Bennett said the day before the surgery.
In early January this year, after consulting Bennett, experts decided that his condition was not suitable for traditional heart transplantation, but it was extremely urgent, and heart transplantation was the last hope to save his life, and finally the expert team obtained urgent authorization from US regulators and patient consent.
In January 2022, Bennett was undergoing surgery in Maryland, USA. Figure/IC photo
The pigs used in the procedure were genetically modified in 10 ways. The researchers "knocked out" 3 genes that cause human rejection and 1 specific gene to prevent overgrowth of pig heart tissue implanted in humans. At the same time, the researchers embedded 6 human genes in the pig's genome to make their organs more acceptable to the human immune system.
Bennett is not the first patient to receive a xenotransplantation. Last September, a U.S. hospital transplanted a pig kidney to a brain-dead patient without immediate rejection.
The patient has brain death, there are signs of renal insufficiency, after obtaining the consent of the patient's family, the doctor connected a pig kidney to a pair of large blood vessels of the patient, and the pig kidney remained outside the patient to observe the effect of the operation.
Chief surgeon Robert Montgomery said that because the transplanted pig kidneys were genetically modified, there was no immediate rejection response after the operation. After being connected to the patient's blood vessels, the pig kidneys normally play the role of filtering waste products and producing urine, and the level of urination is comparable to that of transplanted human kidneys. The patient's creatinine level was abnormal before surgery and returned to normal after transplantation. Creatinine level is one of the indicators of healthy kidney function.
Montgomery said that a sugar molecule called alpha-gal in pig cells causes a rejection reaction in the human body, and the "kidney source" of this operation is a pig that has been genetically modified to remove this sugar molecule, so the patient did not have a rejection reaction.
3 days after the transplant, the patient's life support device is removed on the scheduled date. In January, the University of Alabama at Birmingham released a peer-reviewed study outlining how the procedure was successfully performed with a pig kidney transplant. They expect to launch small clinical trials in human patients by the end of this year.
In addition, according to the Associated Press, in the 1980s, a critically ill baby in the United States underwent a baboon heart transplant and died 21 days after the operation.
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Why Pigs? What are the difficulties of pig organ transplantation?
According to Xinhua News Agency, pigs are regarded as one of the best animals for heterogeneous organ transplant donors because their organ tissue structure, physiological functions and size are similar to human organs.
According to npr, pigs have long been widely used in human medicine, including the implantation of pig skin and heart valves, but the transplantation of entire organs is much more complicated than the use of tissues from highly processed pigs' bodies.
Xinhua News Agency pointed out that at present, xenotransplantation is still facing technical difficulties such as xenovirus transmission and immune compatibility. The pig genome carries endogenous retroviruses, which may be "toxic" after transplantation into humans, and pig organs may trigger immune rejection in patients.
Faced with the dilemma of "transplant organ shortage", many countries are trying to carry out xenotransplantation research with pigs, and some breakthroughs have been made in recent years.
Researchers in China, the United States and other countries reported in 2017 that they used gene editing technology to "knock out" all endogenous retroviruses in the pig genome, and that the organs of these pigs would not be at risk of infection if transplanted to humans.
Research on immune compatibility is also making progress. Mayana Zatz, a professor at the Institute of Biological Sciences at the University of São Paulo in Brazil, reported in 2019 that scientists have identified three genes in pigs that can cause the human rejection response, and turning off these genes with gene editing techniques such as CRISPER/Cas9 has the potential to eliminate rejection of pig organs by the human immune system.
Bennett's transplanted pigs were genetically modified to "knock out" 3 genes that cause rejection. It is because of the above results that Bennett's body did not immediately re-respond to the animal's heart in the early stages after completing the transplant.
Beijing News reporter Hou Wuting
Edited by Zhang Lei, Proofreader Wu Xingfa