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Using a genetically modified pig kidney, doctors at NYU Langone Health completed the first successful investigational animal-to-human organ transplant. The success of the operation moves us one step closer to solving a critical shortage in suitable organs for the thousands of people waiting for life-saving operations.
Approximately 17 people die every single day waiting for an organ donation in the United States alone. There are more than 100,000 people currently on the organ waitlist in the U.S. and another person is added to the list every nine minutes. In 2020, 39,000 transplants were completed, staggeringly low compared to the number of people waiting to receive one. The vast majority of those on the list are waiting for a kidney but only about a quarter of the number needed are donated each year. The need for organs grossly outweighs the supply and there’s no indication that will change anytime soon. In fact, over the last few decades, the number of people waiting for organs has skyrocketed, while the number of donor organs has largely plateaued.
It presents a challenge for doctors who are looking to save lives but are lacking the necessary tools to do so. The easiest way each of us can help is to check yes in the donor box and save a life (or up to eight lives) in the event of our own tragic demise, but scientists are looking for alternative organ sources, and we’re not talking about cloning Ewan McGregor (though, we should do that anyway because the man is a treasure). Instead, researchers are looking to animals with near-compatible organs for human transplantation.
The process, known as xenotransplantation, has been under investigation since the 1960s, when the first xenograft was completed, using a heart from a chimpanzee. Those first xenografts were short-lived, quickly falling to rejection which could not be prevented even with immunosuppressant drugs.
Interestingly, chimpanzees are not the organism of choice for animal-to-human organ transplantation. It turns out pigs are much more compatible, but their tissues contain molecules and proteins which our immune systems rightly detect as foreign. Previous attempts at transplanting pig organs into humans (or other animals) have been met with immediate rejection. The trick is to build a pig with slight modifications, eliminating the troublesome elements while maintaining the basic organ structures. Such a pig could be a perfect match for human transplantation. And, as luck (luck being the result of decades of research) would have it, such a pig exists.
Researchers learned that rejection of porcine organs occurs because of an aggressive immune-response to alpha-gal, a sugar molecule present in pig blood vessels. For this transplant, doctors used a pig engineered to lack the gene that encodes for alpha-gal. They also implanted the pig’s thymus gland along with the kidney, as that has been shown to minimize or prevent novel immune responses.
For this first investigatory surgery, a deceased human donor was utilized. The family of the deceased had intended to donate their organs but, due to extenuating circumstances, that wasn’t possible. Instead, they donated their loved-one’s body for the xenograft.
The surgery was performed by Dr. Robert Montgomery, MD, DPhil, chair of the Department of Surgery at NYU Langone. The operation took only two hours to complete and was observed for a further 54 hours. The short timeline was helped along by the nature of the surgery. Instead of implanting the kidney into the body, it was attached to the blood supply of the leg but remained outside the body, in order to be more easily observed.
Over the following 54 hours, there were no signs of rejection, and kidney function, including urine production and creatine levels, were normal.
“The potential here is incredible,” Montgomery said in a press release. “If the science and experimentation continue to move ahead positively, we could be close to kidney xenotransplantation into a living human being. And the future of this work is not limited to kidneys. Transplanting hearts from a genetically engineered pig may be the next big milestone. This is an extraordinary moment that should be celebrated — not as the end of the road, but the beginning. There is more work to do to make xenotransplantation an everyday reality.”
Tests in non-human animals suggested this should work and the surgery at NYU Langone proves at least that immediate rejection of porcine organs can be prevented via genetic modification. Experiments with non-human primates using the same type of modified pig kidney have lasted more than a year, and it’s that sort of timeframe which will be necessary in order for this to work in humans.
It’s possible, perhaps even likely, that pig organs would still face potential rejection on longer timescales, requiring the introduction of immunosuppressant drugs, similar to those used in human organ transplants. One possible strategy for dealing with the challenges involves a preparatory transplant of pig bone marrow cells in advance of the organ transplant.
The introduction of those cells can trick the immune system into recognizing the porcine tissues as native, rather than foreign. This process is known as the tolerance approach and tests in primates have shown success in maintaining transplanted organs for months without the use of immunosuppressant drugs.
There are still questions to answer and work to be done; whether or not harvesting organs from animals for human use will likely be a matter of debate and we’ll have to collectively decide if that’s something we’re comfortable with. Luckily, it’s not something we’ll have to decide right away, the surgery at NYU Langone was an incredible proof of concept, one which has been decades in the making, but it will be some time before people waiting for an organ will be able to get one from a pig.
There is, as yet, no comment from George Orwell.