Public Health Issues Posed by the Use of Porcine Xenografts

Xenotransplant researchers and biotechnology companies have implied that it would somehow be safer to use pigs rather than baboons as sources for organs, cells, and tissue in xenotransplants ¹ because, they say, humans have co-existed with, and eaten, pigs for centuries with allegedly no ill effects.² But these statements ignore several important facts.

Scientists acknowledge that "little or nothing is known about the pathogenic potential of endogenous retroviruses introduced directly into other species."³ The U.S. Department of Health and Human Services has publicly acknowledged that xenotransplantation poses inherent disease risks to patients and non-patients alike. (Non-patients include animal handlers, surgical team members who harvest and implant animal organs, lab workers handling clinical specimens from xenotransplant recipients, nurses⁴ and others who would provide medical care to the patient(s),⁵ relatives and friends of the patient, and the public at large.) The swine flu epidemic of 1918, which killed 20-40 million people worldwide, is a grim reminder of what happens when diseases jump the species barrier. Placing animal organs directly into humans circumvents all the natural barriers designed to prevent infection.⁶ CRT believes that using pigs as source animals for xenotransplants would not only be dangerous, but irresponsible.

Several documents have described the nature of porcine infectious diseases;⁷ and it is known that pigs can carry bacterial, fungal, protozoal, helminth and viral pathogens.⁸

All vertebrate species, including humans, harbor endogenous retroviruses, acquired during the course of evolution, some of which are capable of infecting other species. Pigs, like nonhuman primates, harbor endogenous retroviruses. It is estimated that hundreds of different endogenous retroviruses may be present in one animal.⁹

Viruses infecting pigs that cannot be guaranteed to be absent from a xenograft include porcine retrovirus, porcine polyomavirus, porcine parvovirus, porcine circovirus, porcine cytomegalovirus, porcine reproductive and respiratory syndrome virus, influenza virus,¹⁰ porcine hepatitis E virus,¹¹ and porcine herpesvirus.¹²

In pigs, the expression of retroviruses has been associated with the development of leukemia and lymphoma.¹³ In humans, retroviruses can induce chronic, life-long infections, "long latency malignancies, neurological disorders, wasting diseases and immunodeficiencies, for which treatment is limited or unavailable."¹⁴ Some retroviruses, such as simian foamy virus (SFV) and simian immunodeficiency virus (SIV), have spread to animal handlers with occupational exposures to baboons and rhesus monkeys, proving that transmission of retroviruses can occur under conditions that are less intimate than xenotransplantation.¹⁵

The potential for transmission of porcine retroviruses to xenograft recipients is a significant concern for xenotransplantation.

Pigs harbor type C endogenous retroviruses. Most cell lines derived from porcine tissues actively produce type C retroviruses.¹⁶ At least two infectious variants of porcine endogenous proviruses, dubbed PERV-A and PERV-B, are widely distributed in different organs, cells and tissues (spleen, heart, kidney, liver, lung, thymus) of different breeds of pigs. These retroviruses are passed from mother to offspring and therefore cannot be eliminated by the conventional techniques used to generate specific pathogen-free animals.¹⁷ Furthermore, specific-pathogen-free pigs may be silent carriers of enteric organisms such as micrococci, streptococci D, and colibacillus; and contamination by as-yet unrecognized pathogens will always be possible.¹⁸ Veterinarian M.M. Swindle asserts that "it will be impossible to provide complete individual animal screening in a timely fashion prior to performing a xenograft transplant."¹⁹

Recent studies have shown that:

• porcine endogenous retroviruses (PERVs) can infect human cells in test tubes,²⁰

• PERVs' replication capacity was found to increase when passaged in human kidney cells,²¹ and

• journal articles have suggested possible transmission of porcine viruses, such as pseudorabies, to human recipients of porcine islet cells.²²

There is also evidence of human contamination and/or infection by:

• porcine rhabdoviruses (i.e. vesicular stomatitis virus),

• picornaviruses (i.e. foot-and-mouth disease, swine vesicular disease virus),

• swine influenza,²³

• paramyxovirus,²⁴

• and the novel "Nipah" viral encephalitis virus that recently infected over 250 people, induced relapses in several patients,²⁵ killed 117, and led to the mass slaughter of some one million pigs and thousands of dogs, goats and sheep in Malaysia.²⁶

Borie, et al., write that, in the context of xenotransplantation:

• Bacteria could theoretically be transmitted to humans in the event of bacteremia, occurring during organ harvesting. Current procedures of organ preservation before grafting would not necessarily circumvent the risk because bacterial growth at temperatures close to 0O C has been documented for bacteria like Yersinia. Detection of bacteria with current assays may prove difficult.

• In humans, liver abcesses caused by Entamoeba histolytica, and gastrointestnal infection by Entamoeba polecki, commonly found in pigs, have been documented. Pig organs may be infested with parasites. Such parasites may not currently be recognized as zoonoses and might become established in immunosuppressed patients.

• Numerous fungal infections, in humans and pigs, are latent in healthy individuals, but may become activated after host defenses are weakened by immunosuppression.

• Pigs carry a broad spectrum of potentially zoonotic viruses. These cause a wide range of symptoms in humans, including fever and general malaise, sores on the face or feet, neurological disorders, meningitis, and death. Pigs may also act as "mixing vessels" for viruses from other mammals and birds.²⁷

Pigs also carry prion proteins (associated with "mad cow disease") that could be transmitted to humans, and are likely to carry numerous viruses and infectious organisms that have yet to be identified.

Therefore, all recipients of porcine cells, tissue, or organs would be exposed to PERVs and possibly other infectious organisms.

Finally, the genetic modification, or "humanization,"of pigs could provide an opportunity for animal viruses to fool the human immune system and "hide" inside the human body. German virologist Joachim Denner and others point out that retroviral infections from pigs may recombine with human endogenous retroviruses, leading to recombinant "superviruses" with unknown, and possibly more virulent properties. These could become preadapted for human infection and subsequent human-to-human transmission.²⁸ Some recombinant retroviruses have been shown to induce cancer.²⁹ Accurate screening for such viruses may be difficult.

In this vein, some scientists are concerned that xenotransplants could alter the human gene pool, by favoring the evolution of porcine-human chimeras (beings containing the genes of both pigs and humans)³⁰ — a profoundly disturbing issue that has received little attention.³¹

It is inconceivable that the FDA would continue to approve clinical experiments with porcine organs, cells and tissue³² in light of the above facts. CRT believes that, if the FDA's mission is truly to "protect the public health," it would ban xenotransplantation outright.

Adapted from CRT's Comments to the U.S. Food and Drug Administration on "Public Health Issues Posed by the Use of Nonhuman Primate Xenografts," submitted July 2, 1999.