October 20, 2021

expert reaction to media reports about US surgeons testing attaching a pig kidney to a brain-dead human patient with signs of kidney dysfunction

There have been news reports revealing that surgeons in New York have successfully attached a kidney grown in a genetically altered pig to a brain-dead human patient.

Mr Hynek Mergental, Honorary Senior Lecturer at the University of Birmingham’s Institute of Immunology and Immunotherapy, and Consultant Surgeon at University Hospitals Birmingham NHS Foundation Trust’s Liver Unit, said:

Is there enough info and detail to be able to assess to robustness of these claims?

“This news article does not include technical nor scientific robust details to draw firm conclusions, however, this news is a significant scientific achievement in the xenotransplantation field, and when is the announcement is supported by rigorous peer-reviewed data it would be a major step forward in the organ transplant field that might solve the critical shortage of donor organs.

Is this a peer-reviewed scientific paper?

“No, this announcement was not peer reviewed.

What more info and data would we need to be able to assess what was done and how successful it was or wasn’t?

“The provided data demonstrated immediate kidney function, without hyper-acute rejection that was the universal reason for failure in xenotransplantation experiments in the past.  The missing data is about any immunosuppressive treatment and/or any other interventions needed to keep the kidney functioning, detailed histology assessment of the kidney acceptance by the recipient body, and if the kidney can maintain its function beyond few days.

Any other comments about these news reports?

“To best of my knowledge, this is the first proof of concept in humans, there were done similar experiments in the past on non-human primates.  There were done several xenotransplantations of hearts and livers back in 80 and 90, but all patients died within the first month.

“This is a significant scientific achievement, and if this was published in a medical journal and supported by robust data, then it would be a scientific breakthrough, however, its move into pilot clinical trial will need to answer ethical questions and address areas about the risk of xenogenic infections (recipient infections by animal viruses).”

Prof Alan Archibald, Chair of Mammalian Molecular Genetics, The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, said:

“The news from the US is limited to news reports.  There does not appear to be a peer-reviewed paper that could be read in order to get a clearer understanding of how robust the information is.

“Nevertheless this is potentially an interesting step along the road to the use of genetically modified pigs as a source of organs for transplantation.

“There is insufficient information in the news reports in order to check the details.  However, it appears that the original GalSafe pigs from which the kidney donor is descended was created by scientists from Scotland’s PPL Therapeutics about 20 years ago.  Scientists at Roslin Institute, including myself, worked with PPL Therapeutics in the late 1980s into the 1990s to develop transgenic sheep as sources of human proteins for therapeutics.  Dolly the Sheep (born 25 years ago) was developed by Ian Wilmut and colleagues at Roslin Institute together with PPL Therapeutics.  Assuming the GalSafe pigs used for this kidney transplant experiment are derived from the PPL Therapeutics GalSafe pigs created 20 years ago, then the work involved the use of nuclear transfer (cloning) technology as used to create Dolly.

“These news reports illustrate the time lag between scientific idea, through basic research to applied research and application.  This development was also underpinned and enabled by research in the UK at Roslin Institute.

“I have attached a couple of relevant papers – the PPL Therapeutics paper describing the GalSafe pigs in 2002¹ and a commentary earlier this year on the regulatory approvals².”

1 https://www.nature.com/articles/nbt0302-251

2 https://www.nature.com/articles/s41587-021-00885-9

A spokesperson for NHS Blood and Transplant, said:

“We are always interested in new research that may allow more patients to benefit from transplant in the future.  While transplant operations carried out today are very successful; there are still not enough donor organs to help all those in need.

“We have been watching this particular field of research for many years – the possibility of transplant between animals and humans.  However there is still some way to go, before transplants of this kind become an everyday reality.

“While researchers and clinicians continue to do our best to improve the chances for transplant patients, we still need everyone to make their organ donation decision and let their family know what they want to happen if organ donation becomes a possibility.”

https://www.nytimes.com/2021/10/19/health/kidney-transplant-pig-human.html

Declared interests

Mr Hynek Mergental: “I do not have any conflict of interest to disclose.”

None others received.