Are pigs among our closest kin? Heart transplant revives debate

Ethics,  genetics,  & relationship of pigs to humans

            BALTIMORE, Maryland––The world’s first pig-to-human heart transplant,  performed on January 7,  2022 at the University of Maryland Medical Center,  may or may not extend the life of transplant recipient David Bennett,  57.

Certainly it shortened the life of the pig,  trucked five hours from a company called Revivicor,  in Blacksburg,  Virginia,  before being killed to facilitate the transplant.

But the pig-to-human heart transplant is “also renewing a debate about pigs and other animals as the source of human organs,”  observed StatNews science writer Megan Molteni almost as soon as the University of Maryland medical center released word of the transplant on January 10,  2022.

Saving lives vs. pork chops

“Animals are not tool sheds to be raided but complex,  intelligent beings,”  People for the Ethical Treatment of Animals argued in a prepared statement.

“Animals have a right to live their lives, without being genetically manipulated,  with all the pain and trauma this entails,  only to be killed and their organs harvested,”  opined the British animal rights charity Animal Aid.

“Using pigs to produce meat is much more problematic than using them to save lives,”  offered Oxford University bioethicist Katrien Devolder to Jack Hunter of BBC News,

Both Judaism and Islam forbid human consumption of pork.

But United Kingdom Health Department moral and ethical advisory group rabbi Moshe Freedman told Hunter,  “Since the primary concern in Jewish law is the preservation of human life, a Jewish patient would be obligated to accept a transplant from an animal if this offered the greatest chance of survival and the best quality of life in the future.”

Continued Hunter,  “Egypt’s Dar al-Ifta,  the country’s central authority for issuing religious rulings,  has said in a fatwa that pig heart valves are allowed if ‘There is fear for the patient’s life, the loss of one of his organs,  exacerbation or continuation of the disease , or an overwhelming deterioration of the body.”

Echoes of Baby Fae

The pig-to-human transplant “was not performed as part of a formal clinical trial,  as generally required for experimental treatments,”  pointed out Molteni.  “And the immunosuppressive drugs the patient was administered are also novel and have not yet been tested for this use in non-human primates.”

But in view that David Bennett was suffering from heart disease that was expected to be imminently terminal,  and in view that he consented to the transplant as a last resort,  few people quibbled about his right to waive normal experimental protocols.

Otherwise,  ethical debate surrounding the pig-to-human transplant mostly recycles older arguments,  many of them dating back to 1984,  when a surgical team at the Loma Linda University Medical Center in California,  led by Leonard Lee Bailey,  M.D.,  transplanted a baboon heart into a premature baby born with a fatal cardiac defect.

Baby Fae,  as she became known,  survived for 21 days.

Dolly the sheep

The pig supplier,  Revivicor,   Molteni explained,  is “a biotechnology company spun off in 2003 from PPL Therapeutics,  the U.K. firm that produced Dolly the sheep (1996-2003),   the first mammal cloned from a cell from another animal,  in itself a hugely controversial experiment.

“In 2011,”  Molteni wrote,  “Revivicor was acquired by United Therapeutics,  the pharma company founded and helmed by xenotransplantation enthusiast and futurist Martine Rothblatt.

“In December 2021,”  Molteni continued,  “Revivicor won approval from the U.S. Food & Drug Administration for its GalSafe pigs,  which have been genetically engineered not to produce a sugar that triggers organ rejection,  as well as an increasingly common meat allergy caused by [an Asian longhorn] tick bite.”

Genetic modification

Elaborated New York Times writer Roni Caryn Rabin,  “The pig [used for the transplant] had 10 genetic modifications.  Four genes were knocked out,  or inactivated,  including one that encodes a molecule that causes an aggressive human rejection response.

“A growth gene was also inactivated to prevent the pig’s heart from continuing to grow after it was implanted,”   Rabin learned from University of Maryland School of Medicine professor of surgery Muhammad Mohiuddin,  M.D.

Mohiuddin,  Rabin said,  “established the cardiac xenotransplantation program with Bartley Griffith,  M.D.”  who actually led the transplant team.

Recipient Bennett,  Rabin mentioned,  is “being monitored for infections,  including porcine retrovirus,  a pig virus that may be transmitted to humans,  although the risk is considered low.”

PERVs

The Roslin Institute of Scotland,  where Dolly the sheep was cloned four years earlier,  and Geron Bio-Med of California,  both long-time leaders in genetic research,  in August 2000 temporarily suspended efforts to produce transplantable organs for humans in pigs to prevent the risk of accidentally transmitting pig endogenous retroviruses into humans.

Called PERVs for short,  pig endogenous retroviruses do not harm pigs,  and may not harm people,  but British virologist Robin A. Weiss demonstrated in 1997 that cross-species infection can occur.

Because PERV invades cells much as does HIV,  integrating itself into the genetic program of the host,  the Roslin Institute and Geron Bio-Med sought to avoid the potential liability if a PERV strain ever attacks humans.

This is,  for the most part,  no longer considered likely,  but the University of Maryland School of Medicine is not altogether dismissing the risk.

Pigs in our woodpile?

The pig-to-human heart transplant may also revive a debate kindled in 2013 by evolutionary geneticist Eugene McCarthy, who holds––against the weight of most scientific opinion––that humans and pigs are distant cousins,  more closely related than humans are to most other primates.

McCarthy outlined his theory in a book-length paper entitled Human Origins:  Are we hybrids?,  offered as a free download from:  http://www.macroevolution.net/human-origins.html#.Ud5d8GSgn6k.

McCarthy in his argument noted “the frequent use of pigs in the surgical treatment of human beings.”

For example,  McCarthy wrote,  “Pig heart valves are used to replace those of human coronary patients.  Pig skin is used in the treatment of human burn victims.  Serious efforts are now underway to transplant kidneys and other organs from pigs into human beings.  Why are pigs suited for such purposes?  Why not goats,  dogs,  or bears––animals who in terms of taxonomic classification are no more distantly related to human beings than pigs?”

McCarthy asserts that pig tissues can be transplanted into humans relatively easily because humans,  somehow,  are hybrids mingling chimpanzee and pig genetics.

Hybridization as engine of evolution

McCarthy,  a former faculty member at the University of Georgia in Athens,  established his expertise about hybridization as author of the Oxford University Press Handbook of Avian Hybrids of the World,  published in 2006.

Framing both McCarthy’s work on birds and Human Origins:  Are we hybrids is his contention that hybridization is not nearly as rare as is conventionally believed,  and though seldom recognized,  is the major engine of species evolution.

Gradual adaptation leading to natural selection for useful traits,  as postulated by Charles Darwin,  may also have a role,  McCarthy concedes.

However,  since it is hard to see how evolution might have favored long sequences of initially not very useful small changes in body structure,  McCarthy believes hybridization provides a better explanation of how mutations emerge and convey a survival advantage to the species who have them.

“An impressive body of evidence”

John Hewitt,  director of the Institute for Behavioral Genetics at the University of Colorado and executive editor of the journal Behavior Genetics,  in the online science journal Phys.Org conceded that McCarthy “has amassed an impressive body of evidence suggesting that human origins can be best explained by hybridization between pigs and chimpanzees.

“Extraordinary theories require extraordinary evidence,”  Hewitt wrote,  “and McCarthy does not disappoint.  Rather than relying on genetic sequence comparisons,  he instead offers extensive anatomical comparisons,  each of which may be individually assailable,  but are startling when taken together.”

Anatomical specializations

“It is not yet clear if or when genetic data might support,  or refute,  our hybrid  origins,”   Hewitt added.  “The list of anatomical specializations we may have gained from porcine philandering is too long to detail here.  Suffice it to say, similarities in the face,  skin,  and organ microstructure alone are hard to explain away.

“A short list of differential features, for example,  would include multipyramidal kidney structure,  presence of dermal melanocytes,  melanoma, absence of a primate baculum (penis bone),  surface lipid and carbohydrate composition of cell membranes,  vocal cord structure,  laryngeal sacs,  diverticuli of the fetal stomach,  intestinal ‘valves of Kerkring,’  heart chamber symmetry,  skin and cranial vasculature and method of cooling,  and tooth structure.”

“An intelligent animal”

Wrote McCarthy,  “Features found in human beings,  but not in other primates,  cannot be accounted for by hybridization of a primate with some other primate.  If hybridization is to explain such features,  the cross will have to be between a chimpanzee and a nonprimate––an unusual,  distant cross to create an unusual creature.

“The other parent in this hypothetical cross that produced the first human,”  McCarthy continued,  “would be an intelligent animal with a protrusive, cartilaginous nose,  a thick layer of subcutaneous fat,  short digits, and a naked skin.  It would be terrestrial,  not arboreal,  and adaptable to a wide range of foods and environments.

“These traits may bring a particular creature to mind.  In fact,  a particular non-primate does have,  not only each of the few traits just mentioned,  but all of the simple,  non-synergistic traits distinguishing humans from their primate kin.

“The color of relationship”

“Any attempt to account for these details in terms of natural selection seems inadequate,”  suggested McCarthy.  “It is difficult to see what selective pressures could have caused human beings and pigs to converge in so many different respects.  Perhaps it is all just a coincidence,  but after a certain point coincidence begins to assume the color of relationship.”

Cautioned McCarthy,  “No claim whatever is made that it is actually a fact that humans somehow arose through hybridization of pigs with chimpanzees.  I merely propose an evaluation of two distinct hypotheses by the usual scientific criterion:  the hypothesis less consistent with available data should be rejected.”

Of course McCarthy’s theory has been rejected out of hand by most scientists who have considered it.

Genes & chromosomes

Wrote science journalist Steph Yin for The Outline in May 2017,  “The most damning refutation of McCarthy’s hypothesis is ‘the absence of any pig or pig-related genes in the human genome,’  according to Roger Butlin, a professor of evolutionary biology at the University of Sheffield in Britain.”

Because pigs have 38 chromosomes,  while chimpanzees have 48,  the odds are overwhelmingly against an actual pig/chimpanzee mating producing an offspring,  let alone reproductively viable offspring,  are overwhelming.

Even if that happened,  pointed out University of Minnesota biology professor PZ Myers to Yin,  pig and chimp embryos “develop at such different rates and such different times that any embryo carrying both sets of genes would be getting very confusingly mixed signals.”

Geography

Further,  Arizona State University assistant professor of genomics and evolution Melissa Wilson Sayres told Yin,  she summarized,  that “In addition to there being no evidence of ancient humans resembling pigs anywhere in the fossil record,  hairless pigs arose in Asia and Europe, while chimpanzees lived in Africa.”

That argument,  though,  is somewhat diminished by observing that Africa and India,  last linked about 70 times longer ago than protohumans have existed,  were still close enough together when the common ancestors of whales and hippopotamuses lived,  about 25 times longer ago than the first known protohumans,  that the fossil evidence of their relationship turned up 3,000 miles apart,  in Kenya and Pakistan.

In addition,  science is increasingly often discovering that genes have migrated among species by means other than mating,  in particular through retroviruses––like PERVs.

(See The Tangled Tree: A Radical New History of Life .)

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