Instead of waiting in a years-long queue, could a person in need of a kidney transplant get it from a farm pig instead? Backed by gene-editing tools like CRISPR-Cas9, scientists have renewed their effort to make this a reality over the last couple of years. That happened a week ago with the 62-year-old Richard Slayman receiving a genetically modified kidney in the United States.
While there are a lot of unknowns, there is a sense of cautious optimism about xenotransplantation — transplanting organs from animals to humans — as it could be the solution to the current organ shortage. This idea is not new — what has enabled scientists and doctors now are the gene editing tools that have allowed them to make the animal organs more compatible with humans. Scientists genetically modified the kidney that was given to Slayman in three key ways.
What Is Gene Modification?
Explaining the need for gene modification, Dr Arvinder Soin, chairman, Medanta Institute of Liver Transplantation, says, “First, certain genes in a pig carry the code to produce sugars that have antibodies, which our immune system can immediately recognise. These have to be edited out to prevent acute rejection. Second, there is a specific pathway, called complement-mediated rejection, which is activated when an organ is transplanted across species. When activated, it can lead to clotting, which stops the blood supply to the organ and it dies. The scientists have added complement inhibitor and anti-clotting genes from humans to prevent that. Third, pigs have certain viruses coded in their genes called porcine endogenous retroviruses (PERVs) and when humans receive pig organs they can contract these infections. These are not common otherwise in human beings. So this trait too has to be edited out.”
There were 69 genome edits that the scientists did in the pig kidney in total. These edits were done by a xenotransplantation therapy company called eGenesis founded by a Harvard Medical School geneticist George Church. His team, in fact, solved one of the key challenges to using pig organs in humans — that of PERVs causing infections in humans. His lab published the results of the genetic engineering feat of eliminating all 62 PERVs in the pig genome in one swoop in 2015. This was described as “the most widespread CRISPR editing feat to date,” with the previous record being of just six edits at one go.
Challenges of pigs as the chosen animal donor
Pigs are chosen for xenotransplants because the size and function of their organs match that of humans very well. “There are, of course, significant challenges that come with using pig organs. First of all, the human immune system is extremely complex. The only organ that it recognises as its own is the one that comes from an identical twin. The next best match comes from siblings and then parents. We have brought down rejection over the years by better managing the anti-rejection medicines. Now, imagine introducing genes that are not even of human origin. That is a big challenge,” says Dr Harsha Jauhari, a renowned kidney transplant specialist from Sir Ganga Ram Hospital. “The use of pig organs also introduces infections that don’t happen in humans now. And it is not just about one person; these infections can then start transmitting in humans. While it is a good start, it is still years from becoming the standard of care,” he adds.
Slayman lived with Type-2 diabetes and hypertension, putting him at risk of chronic kidney disease. He received a kidney transplant for the first time in 2018. However, the kidney started showing signs of failure after five years and he was back on dialysis — a procedure where the machine takes over the kidney’s function of removing waste from the body. The use of pig kidney was allowed on compassionate grounds when he needed a kidney transplant again.
With the prevalence of lifestyle diseases such as diabetes and hypertension on the rise, there is an increasing demand for organ transplants. An estimated 2 lakh people in India reach end-stage kidney failure every year and only around 12,000 manage to get a transplant.
What are chances of survival?
The big question, however, is how long can Slayman survive on the pig kidney. “We still don’t know how many years this kidney can survive but based on our preclinical research, we are aiming at years — more than two years,” said Dr Tatsuo Kawai, surgeon at Massachusetts General, who led the surgery.
There have only been two heart transplants using pig organs. Both the patients died within a couple of months after transplantation. There have also been experiments with pig liver and kidney in brain dead patients. In fact, doctors from China transplanted the first genetically modified pig liver around the same time in a 50-year-old deceased person.
While Dr Jauhari imagines xenotransplantation can be a solution for the future, he remains optimistic about other alternatives coming in first. Scientists have been working on growing organs in laboratories with the help of stem cells, which are capable of becoming other types of cells. “And, we might also be able to control many of the diseases that necessitate transplants by then,” says Dr Jauhari.
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First uploaded on: 23-03-2024 at 10:31 IST
Rohit Malhotra is a medical expert and health journalist who offers evidence-based advice on fitness, nutrition, and mental well-being. His articles aim to help readers lead healthier lives.
