A Holiday Season Poll: What do you think about pig-to-human organ transplants?

Have researchers really smoothed out the genomic kinks—or are they rushing to normalize potentially risky xenographic transplants?

There’s a tragic transplant organ shortage in the U.S. (and elsewhere in the world), with kidneys topping the list of organs needed but mostly unavailable. This week, numerous news outlets reported that a 53-year-old woman who received a pig kidney transplant is “dialysis free” and appears to be thriving after years of suffering. (1)

Kristen Monaco reported in MEDPAGE Today that the seven-hour transplant surgery took place at NYU Langone Health November 25; the recipient is one of only three individuals to receive a genetically tweaked pig kidney. The other two did not survive.

The kidney came from an animal genetically modified by scientists at Revivicor, the company that created the first cloned sheep (remember 1996’s Dolly?) and is now devoted to creating pigs that will produce organs suitable for transplantation to humans. (2)

“The pig kidney had gene edits removing three immunogenic antigens (Gal, Sda, and Neu5Gc) and a porcine growth hormone receptor, plus six human transgenes added to reduce the likelihood of rejection,” Monaco detailed December 17.

The recipient, Towana Looney, had a complex medical history. Having donated a kidney to her mother, Looney developed preeclampsia during pregnancy that resulted in chronic kidney disease, which progressed to kidney failure. She had been on dialysis since 2016. (1)

Director of the NYU Langone Transplant Institute Robert Montgomery, MD, DPhil, worked with Revivicor to develop the gene-edited pig. He told MEDPAGE Today that a clinical trial of similar xenographic transplants will begin “by this time next year or even sooner.” (1)

Why a pig?, you may be asking.

Researchers at Aarhus University in Denmark think they have the answer to that question. “Pigs and humans are pretty similar. Our organs, our skin and the way many diseases develop are largely the same,” researcher Jeppe Kyhne Knudsen wrote in an online update on the university’s website. (3)

“And now pigs may become even more valuable as laboratory animals, because researchers from the Center for Quantitative Genetics and Genomics at Aarhus University have mapped the most important genetic similarities between pigs and humans,” Knudson continued.

“Pigs and humans are very similar. Human and pig organs are almost the same size, and many tissue types are almost identical. This is why pigs are useful when developing and testing new drugs. Thanks to the new findings, we know have even better knowledge about the similarities between pigs and humans.” Photo: Jesper Rais, AU Communication.

Lingzhao Fang, also a researcher at Aarhus University, noted that their team has not only identified the genes that are the same in humans and pigs, but that “they have also identified the so-called 'transcriptome' across a number of tissue types. … Where the genome includes all the genes found in the DNA of our cells, whether active or inactive, the transcriptome includes the genes that are active in the different types of cells in our body.” The Danish team hopes that these findings will facilitate organ transplantation between species. (3)

But if humans and pigs are so similar genetically, why haven’t we been performing pig-to-human transplants for decades?

Pigs, it turns out, are major mixing vessels for novel viruses that can infect people.

“Pigs can act as intermediate and amplifying hosts for viruses with pandemic potential including NiV [Nipah virus], IAV [influenza A virus] and JEV [Japanese encephalitis virus], and they have become established as hosts for novel coronaviruses,” Rebecca K. McLean and Simon P. Graham reported in a Science Direct review article. It appears that “significant changes to traditional pig husbandry practices [are] leading to an environment conducive to increased emergence and spread of infectious diseases.” (4)

It may be necessary to gene-edit pigs before transplanting their organs into humans because, left to themselves, pigs can create brand-new viruses through a process called gene recombination. Pigs are susceptible to avian (bird), swine, and human flu viruses; novel influenza viruses are created every year by genetic recombination in pigs. In 2009, a novel swine flu virus resulted from “triple-reassortant whereby there were six gene segments from at least three parent viruses and two separate segments from the H1N1 swine virus lineage,” according to McLean and Graham, and this novel virus caused a deadly influenza pandemic. (4)

They also expressed concern about “novel porcine coronaviruses” currently being found in “high pig-density countries which have pandemic potential. ... In this review, we discuss the role that pigs play as intermediate/amplifying hosts for zoonotic viruses with pandemic potential...” (4)

As with all infectious diseases, those passed from pigs to humans can most severely affect people with damaged immune systems. There is an illness of pigs, African Swine Fever, that an expert in the field called “an acquired immune deficiency syndrome of pigs,” because it produces symptoms that are so similar to those of AIDS. African Swine Fever is caused by a virus, African Swine Fever Virus (ASFV). (5)

Like AIDS, there is no cure or effective treatment for African Swine Fever. When African Swine Fever is suspected, entire herds are slaughtered to prevent the spread of the extremely contagious virus. (5)

The U.S. agricultural bureaucracy refuses even to investigate the possibility that ASFV has recombined enough—like numerous other viruses infecting pigs—to make it capable of infecting humans. This position has hardened since 1986 when two young scientists—Harvard’s Dr. Jane Teas and Boston University’s Dr. John Beldekas—published a paper in The Lancet showing that they’d found evidence of ASFV infection in AIDS patients. Federal agricultural regulators refused even to consider the possibility that ASFV could be found in the country’s pigs, never mind in its people. (6)

In fact, a group of scientists were gathered in 1986 by the U.S. Department of Agriculture at Cold Spring Harbor Laboratory (on Long Island, New York) to issue a memorandum mandating that no further research should be performed to test people for possible ASFV infection. (5)

Well, that’s not suspicious, no matter how many decades ago it happened.

And now, researchers are enthusiastically modifying pig genomes to grow kidneys, hearts, and livers suitable for human transplantation, despite knowing that pigs are nature’s mixing vessels for novel viruses that can infect those same transplant recipients.

What do you think? Should we continue to breed and genetically modify pigs so they can serve as sources of organs for humans? Tell us: Would you accept an organ transplant from a pig?

BIBLIOGRAPHY
1. Kristen Monaco. “Woman Dialysis-Free After Receiving Gene-Edited Pig Kidney— Clinical trials of xenotransplantation expected to kick off next year.” MEDPAGE Today. December 17, 2024. https://www.medpagetoday.com/transplantation/kidneytransplantation/113437?xid=nl_mpt_morningbreak2024-12-18&mh=b16d206507dcd05ca898a8f2ec2648f0&utm_source=Sailthru&utm_medium=email&utm_campaign=MorningBreak_121824&utm_term=NL_Gen_Int_Daily_News_Update_active
2. Revivicor Health. https://www.revivicor.com
3. Jeppe Kyhne Knudsen. “Large-scale mapping of pig genes could pave the way for new human medicines.” Aarhus University (Denmark) Faculty of Technical Sciences News. 4 January 2024. https://tech.au.dk/en/about-the-faculty/news/show/artikel/large-scale-mapping-of-pig-genes-could-pave-the-way-for-new-human-medicines
4. Rebecca K. McLean, Simon P. Graham. “The pig as an amplifying host for new and emerging zoonotic viruses.” Science Direct “One Health” issue, Vol. 14, June 2022. https://doi.org/10.1016/j.onehlt.2022.100384
5. Neenyah Ostrom. “A Pig ‘Acquired Immune Deficiency Syndrome’ Virus May Cause CFS and AIDS.” Chapter Fifty in AMERICA'S BIGGEST COVER-UP: UPDATED 2ND EDITION 50 More Things Everyone Should Know About the Chronic Fatigue Syndrome Epidemic and Its Link to AIDS. March 9, 2022. Available on Amazon.com
6. John Beldekas, Jane Teas, and James R. Hebert; “African Swine Fever Virus and AIDS”; The Lancet, March 8, 1986.