With thousands of Americans dying every year waiting for an organ transplant, researchers have been searching for a way to provide organs to those in need.
Even if it means exploring the possibility of pig-to-human transplants.
The possibility of animal-to-human organ transplants, or xenotransplantation, has been investigated for decades since it could essentially provide a nearly unlimited supply of organs.
However, issues with immune response, animal-based viruses, and other inherent differences between animals and humans have kept this option in the realm of science fiction rather than in reality.
In the 1960s a few doctors used primate organs for human transplantation, but patients typically died after their immune systems swiftly attacked the organs.
Despite these setbacks, physicians have persisted in looking for a way to transplant organs from animals to people.
Gene-editing breakthroughs can make a difference
Now that new technology has simplified gene editing, it may allow scientists to create animals that are primed to be organ donors for humans.
A recent study highlighted how genetic breakthroughs can “fine tune” animal genomes, potentially making them organ donors for humans in the future.
The scientists published their findings in the journal Science earlier this month.
Scientists from eGenesis biotech company, Harvard Medical School, Zhejiang University, and other institutions, used the gene-editing breakthrough technology called CRISPR-Cas9 to see if they could remove remnants of viruses called porcine endogenous retroviruses from pig genomes.
The viruses are the cause of a major hurdle in xenotransplantation.
By using the CRISPR-Cas9 technology, researchers were able to take out these remnants that are inherent in the pig genome and can be passed down through generations.
The reason these remnants needed to be removed is because they could possibly infect human patients after a transplant. As a result, there’s a risk that these remnants, also known by the acronym PERVs, could affect humans in unpredictable ways.
They could combine with viruses in a human patient and cause a deadly infection.
In a more dangerous scenario, they could cause a totally new kind of virus to develop that would be a combination of pig and human viruses, which could spread to other people, potentially causing a deadly outbreak.
“We observed in our studies that PERVs can be transmitted from pig to human cells and transmitted among human cells in vitro,” the study authors wrote. “These results substantiate the risk of cross-species viral transmission in the context of xenotransplantation.”
By using CRISPR-Cas9 technology researchers were able to genetically engineer pig cells to create pig fetuses and piglets without the viral remnants in the genome. They were able to engineer 37 piglets without these PERVs, 15 of which are still alive. The oldest animal is 4 months.
The study authors acknowledged much more study is needed to ensure that organs could be made safe for humans. But they hope that their findings are the basis for new research.
“Most importantly, the PERV-inactivated pig can serve as a foundation pig strain, which can be further engineered to provide safe and effective organ and tissue resources for xenotransplantation,” the authors wrote.
The obstacles to xenotransplantation
Dr. Seth Karp, professor and chair of the Department of Surgery and director of the Vanderbilt Transplant Center, said the study is one important step toward xenotransplantation, but he cautioned it’s still not likely to happen anytime soon.
“There are different compounds, molecules... that don't exist in humans in the same fashion,” Karp told Healthline.
As a result of these differences, the human immune system swiftly attacks these molecules, injuring the tissue.
“Getting past that barrier is very hard,” Karp noted.
Karp did explain that this study could help doctors overcome one huge obstacle in xenotransplantation.
“People are very concerned about viruses moving along with the organ and then creating a new type of virus in humans,” Karp said.
Getting rid of the PERVs in the genome could help ensure some viruses could not get passed along.
However, Karp said that despite medical breakthroughs, doctors still have difficulty controlling the immune response in patients even 60 years after organ transplants became a reality.
“When an organ goes in, the body sees it as foreign,” Karp explained.
The immune system response has “been much more difficult than we originally thought.”
Karp stresses that for now the organ shortage will likely continue unless more people volunteer to be organ donors.
“These therapies are doing better and better,” he said of treatments to prolong the patients’ lives. But, “there are still tens of thousands of people who are dying,” currently on wait lists.
As for why pigs are considered the most likely supplier of organs, Karp explained it has a lot to do with size and temperament.
“It’s a nice size match... there are pigs whose internal organs are a good size [to match].” he said. “From an experimental standpoint, they are easy to keep and easy to breed.”
He also said that the animals “have to be docile enough” for experiments so that they’re not a danger to scientists.
“You wouldn't do this in tigers,” he said.