Bad consequences for human populations: Health risks

Objections to chimera experimentation are not only based on consideration for chimeras or other interspecifics, i.e. the novel beings created. There are also direct concerns for the security and health of already existing beings – especially human beings. The most concrete concern of this type is the thought that experiments that involve cross-species grafts could lead to or heighten the risk of diseases.

In this respect, xenotransplantation/xenografting is associated with two types of health risk: risks that only concern the host individual, and risks that also concern others.

Several types of risk are considered that are limited to the recipient of nonhuman material: Immunoresponse, i.e. the risk that the recipient has an immediate adverse reaction to animal material; Tumorigenicity, the risk that the recipient has long-term adverse reactions to the animal material, and Zoonosis, the risk of contracting a disease via transferred animal material. A connected third-party risk that would also affect non-recipients is seen in the scenario of an epidemic or even pandemic spread of zoogenic pathogens.

My introduction to xenotransplantation (chapter 1, section B.5 above) already explained that immunoresponse was, and still is, a serious problem for transplantation from animal to human recipient, especially when whole organ transplants are considered. Immunoresponse in xenotransplantation is much stronger than in allotransplantation. Additionally, with the porcine material that is commonly used, this risk is even more pronounced than it would

322 _{The question of "enhancement" is, today, predominantly discussed in regard to humans; though, e.g.}

Hughes explicitly mentions as a future challenge to politics "The intellectual enhancement of animals, forcing a clarification of the citizenship status of intelligent non-humans."Hughes (2006),"Human Enhancement and the Emergent Technopolitics of the 21st Century", in: Roco and Bainsbridge (eds.) Managing Nano-Bio-Info- Cogno Innovations: Converging Technologies in Society.

be with material from more closely related species (i.e. nonhuman primates). Immunoresponse is usually the most massive problem preventing or complicating xenotransplantation.

Tumorigenicity, on the other hand – i.e. the disposition of certain material to lead to the formation of tumours in the recipient – is a problem for embryonic stem-cell-based therapies. Stem cells have the advantage of being able to "morph" into several types of cells, but also the disadvantage of sometimes morphing into a teratoma, a certain type of tumour. This risk is also present in interspecific grafts,323 _{and thus must be considered in}

cases where animal embryonic stem cells are xenografted into human hosts. Immunoresponse and tumorigenicity are risks that are not specific to xenograft/- transplantation but also known from allotransplantation.

Things are even more complicated concerning the risk of pathogen transfer. A disease that is subject to trans-species transmission from animal to human is commonly called zoonosis. The danger of zoonoses has been discussed and recognized as a severe problem in the context of xenotransplantation. Here, apart from the danger of an infection of the individual recipient, there is a much bigger danger: that of a xenogenic epidemic or even pandemic which could potentially kill thousands or even millions of people.

For understanding this risk, it is important to realize that the precursors of many or even most of the most dangerous and ravaging diseases throughout human history – bubonic plague, typhus, measles, smallpox, influenza, HIV, and many others – were originally transmitted from animals to humans. The "jump" of a pathogen from one species to another, i.e. a shift of the disease host, brings the risk of a pandemic – this is what happened when the SARS virus "jumped" from civet cats to humans, and this is what scientists fear is about to happen in the case of porcine influenza (swine flu) and/or avian influenza (bird flu). The transmission of such viruses to humans and the associated pandemic risk is a constant matter of concern for epidemiologists.

In the case of xenotransplantation, there is a quite specific zoonosis concern: it is feared that a cross-species jump of porcine endogenous retroviruses (PERVs) could produce a virus that recombines with human DNA and results in a highly pathogenic, fatal virus aimed at human hosts (such as the HI virus, which probably originates from a retrovirus in chimpanzees, SIV). If there is a danger of "species jump" and pandemic, transplanting

323 _{E.g. in a case were a cell line derived from pig embryonic stem cells was transferred to diabetic mice – see}

Fujikawa, Oh, et al. (2005), "Teratoma Formation Leads to Failure of Treatment for Type I Diabetes Using Embryonic Stem Cell-Derived Insulin-Producing Cells", American Journal of Pathology, 166(6).

living body parts of one species into another seems to be a surefire way of increasing this risk, since live xenografts make it hard to eliminate eventual pathogens. Additionally, xenografting eliminates virtually every barrier viruses usually face when crossing from one species to another – keeping in mind that strict immunosuppression is necessary in the host. Previous zoonoses have emerged because of close contact with animals or their excrements, or because of consumption of animal products – in comparison, the introduction of live material into the (immunosuppressed) host organism itself seems to be an even closer kind of contact between species, and to open the door to species jumps. Normal pathogens, in this context, do not constitute such a big danger of xenozoonosis, since they can be eliminated before introduction of animal material into the human organism, by keeping the animals under "specific pathogen free" (i.e. partly sterile) conditions, vaccination, and by breeding selection for uncontaminated animals. Endogenous retroviruses are characteristically wired into the DNA of animals, though – they are integrated into the genome of their host organism, not acquired by infection, and cannot be removed from the tissue nor can one selectively breed uncontaminated animals. All vertebrates have such endogenous retroviruses that do not figure as pathogens in the original species, but which have pathogen potential when transferred to other species, leading to immunosuppression or tumours in the host, and possibly to a disease that can also be transmitted to other humans (or other species). The question of whether being subject to porcine (or other) xenotransplantation leads to a high risk of PERV (or other, especially primate, ERV) zoonosis is a highly complex one which cannot be discussed in depth here – it seems that studies have come to the conclusion that, though PERVs can transfer to human material in test-tube settings,324 _{transmission in subjects of pig-human}

xenograft of living material is not easily established.325 _{An EU study done in 2003 comes to}

the conclusion that nonhuman primate material should not be used for xenotransplantation because of xenozoonosis risk of easily transmittable primate endogenous retroviruses, while pig material can be used as long as certain safety measures are in place.326 _The

moratorium on clinical xenotransplantation that was demanded in the 1990s327 _{and which}

324 _{Patience, Takeuchi, et al. (1998), "Infection of human cells by an endogenous retrovirus of pigs", Nature}

Medicine, 3.

325 _{E.g. a search for transmission of PERVs to 160 human subjects 12 years after they had been treated with}

living pig tissue was unsuccessful, see Paradis, Lanford, et al. (1999), "Search for Cross-Species Transmission of Porcine Endogenous Retrovirus in Patients Treated with Living Pig Tissue", Science, 185(5431).

326 _{Working Party on Xenotransplantation (CDBI/CDSP-XENO) (2003), "Report on the State Of The Art in}

the Field of Xenotransplantation ."

327 _{E.g. Bach and Fineberg (1998), "Call for moratorium on xenotransplants", Nature, 391(6665); Butler}

was, de facto, in place in many countries at the end of the century has today in most nations been replaced by more stringent control and regulation.328

What about the risk of zoonosis in other types of interspecifics? The Scottish Council on Human Bioethics regards zoonoses as a risk to be considered when thinking about "human-animal mixtures" (of chimeric and transgenic origin – i.e. not only products of "classic" whole organ xenotransplantation). The council concludes that

"This infectious danger is therefore sufficiently serious to induce physicians and biologists to publicly raise the question of whether it is ethical to allow humankind to run the risk of devastating and uncontrollable pandemics since animal-human mixtures will never concern more than a limited group of procedures."329

In the case of transgenesis and (micro)-chimerism, the risk of epidemics is crucially lower than in the case of xenotransplantation. This is simply because the (animal) host does not or at least need not necessarily come into contact with humans which would allow contamination with potentially dangerous new pathogens. Unlike in organ xenotransplantation, the danger of zoonosis can be limited to the animal host which can easily be subject to stringent control (as compared to free-roaming human transplant recipients).

The scenario of a zoonotic infection and resulting epidemic is even more unlikely in the case of cybrids – the UK Academy of Medical Sciences report of 2007 judged this risk to be "not greater than" in normal (non-interspecific) cell cultures.330