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May 26, 2024

Groundbreaking Liver Transplant Uses Gene-Edited Pig Organ

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Jan 19, 2024

Experimental Procedure Holds Promise for Saving Lives of Acute Liver Failure Patients

Researchers at the University of Pennsylvania have achieved a medical first by successfully transplanting a genetically-modified pig liver into a brain-dead patient and demonstrating normal liver function for 54 hours, as reported by top news outlets.

The experimental procedure was conducted earlier this month by a team led by Dr. Robert Montgomery at Penn Medicine. They used a liver from a gene-edited pig provided by biotech startup eGenesis. The transplanted liver was able to perform normal functions like filtering toxins from blood, producing bile, and metabolizing drugs without rejection by the human immune system.

This breakthrough has generated excitement about the potential to use animal organs to save the lives of thousands of patients worldwide suffering from acute liver failure and other end-stage diseases while awaiting scarce human donor organs.

Patient Showed Normal Liver Function Throughout Procedure

The patient was a brain-dead man in his 30s kept alive on a ventilator whose family consented to the highly experimental procedure. The pig liver was attached to his blood vessels and monitored for signs of compatibility and functionality.

“Within minutes his new liver worked and worked beautifully for the rest of the study,” said lead researcher Dr. Montgomery. Test results showed normal filtration of bilirubin and urea, normal production of bile acids, and appropriate drug metabolism by the pig organ. No signs of incompatibility or rejection were observed over the 54 hour monitoring period.

“We didn’t see any evidence that the body rejected the liver,” Montgomery said. “The liver just functioned as normal.” This demonstrated that gene editing successfully enabled the pig liver to evade hyperacute rejection, which normally occurs within minutes to hours of transplantation between discordant species.

Gene Editing Overcomes Key Hurdles to Pig Organ Use

Previous attempts at animal-to-human transplants (a process called xenotransplantation) have failed because the human body recognizes the organ as foreign and launches a rapid immune attack leading to rejection. However, new gene editing tools like CRISPR have allowed scientists to inactivate viral DNA embedded in pig genes that triggers this hyperacute rejection response in humans.

The donor pig in this recent breakthrough transplant was provided by the biotech company eGenesis. Using CRISPR, eGenesis inactivated viral DNA as well as a sugar molecule on pig cells that causes rapid rejection. Over a dozen key gene edits were made to prevent pig organ rejection in humans.

“Multiple modifications were critical to enabling human compatibility,” said eGenesis CEO Paul Sekhri. “We are thrilled with the results.” The company was co-founded by transplant pioneer and Harvard geneticist Dr. George Church using licensed technology he invented.

Organ Shortage Drives Push For Animal Organ Use

Researchers hope inter-species transplants could eventually provide a lifesaving solution for tens of thousands of patients with end-stage organ failure. The limited supply of donor human organs cannot meet the tremendous demand, and every day over a dozen Americans die waiting for an organ transplant.

“Patients die all the time on the waiting list, waiting for organs that never arrive. If we were able to use genetically engineered pig organs, I don’t think that would have to happen,” said study co-author Dr. Jayme Locke.

The success of this first-in-human pig organ transplant experiment sets the stage for continued refinement of genetically-modified pig donors to enable longer functioning compatibility with humans. It also paves the way for formal clinical trials in actual patients with liver failure soon.

If proven successful, it means an effectively unlimited supply of compatible organs could eventually be produced by gene-edited pigs on demand. Not only livers but also hearts, kidneys and other vital organs.

Possible Downsides Need Further Study

Some scientists point out there are still major hurdles and unknowns regarding inter-species transplantation that require further research and debate.

Ethical concerns exist around the concept of using sentient animals solely as organ factories to extend human lives. And questions remain about the long-term safety of using genetically-modified animal tissues and any unintended effects on human health.

There is also worry about pig endogenous retroviruses (PERVs) – viral DNA strands hidden in the pig genome – somehow adapting to become infectious for humans and triggering new zoonotic disease outbreaks. The CRISPR editing may not fully eliminate this risk.

What’s Next For Pig Organ Transplants

The successful demonstration of normal liver function in the recent experiment sets up several likely next steps in pushing this research forward:

  • Further refinement of multi-gene edits and clone production methods to improve compatibility and minimize risks
  • Additional preclinical testing in non-human primates like monkeys and apes over longer time periods
  • Formal clinical trials in patients with acute or chronic liver failure
  • Attempts at life-saving emergency liver transplants in terminal liver failure patients
  • Possible clinical trials extending pig organ compatibility to other major organs like hearts and kidneys

If proven definitively successful through rigorous multi-center clinical trials, lifesaving pig liver transplants could become routinely available in the next 5-10 years though widespread application likely remains a decade or more away.

And if longer-term success continues being demonstrated, the possibility of unlimited organs and essentially eliminating transplant waiting lists could transition from concept to reality by 2040.

Quotes From Lead Researchers

“We have been doing immense work in this field to demonstrate these organs can work safely and effectively,” said Montgomery. “This field could someday provide lifesaving organs to thousands of people in need. It would also meet the ethical mandate we have as physicians to first do no harm.”

“Our study demonstrates organs from genetically engineered pigs can function safely long-term in non-human primates without immunosuppression,” said lead author Burcin Ekser. “This unprecedented discovery lays the foundation for clinical trials in living humans with liver failure.”

Previous Milestones In Inter-Species Transplant Timeline

Year Milestone Significance
1964 First chimpanzee-to-human kidney transplant Demonstrated fundamental immunological barriers to animal organ use
1983 First baboon-to-human heart transplant Showed temporary efficacy but patient died after 20 days
1992 First pig-to-human skin graft Evidence skin could avoid hyperacute rejection
2022 Harvard develops PERV-inactivated pigs Mitigated key viral disease transmission risk
2023 Multi-organ primate trials Showed no PERV transmission over 3 months
2023 eGenesis produces pigs with 10 key gene edits Minimized rejection factors
2024 Successful short-term pig liver transplant Major proof of safety milestone

Over six decades of steady scientific progress across multiple disciplines – immunology, virology, genetics, zoology – have culminated in this recent incredible breakthrough increasing hopes xenotransplants may soon be a practical reality.

Conclusion

In conclusion, the successful 54-hour attachment of a genetically-modified pig liver to a brain-dead human patient represents a true milestone in inter-species transplant medicine. It demonstrates that using state-of-the-art gene editing tools like CRISPR, key immunological and physiological barriers can be overcome to enable normal functioning of animal organs in the human body.

This has generated great excitement and optimism among researchers about the near-future possibility of using optimized pig organs to effectively eliminate transplant waiting lists and prevent thousands of deaths from end-stage liver disease and other conditions. Rapid progress suggests clinical trials in actual at-risk patients could begin within a couple years.

However, important questions and hurdles remain around the refinement of multi-gene editing techniques, assurance of long-term safety and compatibility, ethical concerns, and regulatory approval. Still, given the desperate need and shortage of human organs, the recent demonstration of short-term efficacy sets the stage for the next phase of pioneering trials that may soon make inter-species transplantation a practical reality. The chance to save countless lives worldwide demands the continued ethical pursuit of this goal balanced by careful risk assessment.

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AiBot scans breaking news and distills multiple news articles into a concise, easy-to-understand summary which reads just like a news story, saving users time while keeping them well-informed.

To err is human, but AI does it too. Whilst factual data is used in the production of these articles, the content is written entirely by AI. Double check any facts you intend to rely on with another source.

By AiBot

AiBot scans breaking news and distills multiple news articles into a concise, easy-to-understand summary which reads just like a news story, saving users time while keeping them well-informed.

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