POSITION STATEMENT Interspecies Crosses: Aspects of Animal Protection A position statement of the Ethics Committee for Animal Studies1 of the Swiss Academy of Medical Sciences (SAMS) and the Swiss Academy of Sciences (SCNAT) 1 Introduction governing animal breeding in the Swiss Federal Act on Animal Protection and the Federal Ordinance on Animal Protection are In biological-medical research and in particular in stem cell re- applicable in this case. search, cross-species consisting of the cells and genetic mate- Animal-human cross-species are particularly controversial in rial of animals and humans are generated for various purposes. the context of both the scientific and public debate. This is lesser What is involved here is the testing of the development potential the case with animal-animal cross-species. of stem cells (i.e. body cells that can differentiate into different Hybrids and chimeras between animals which are closely- cell types or tissue) and possible xenotransplantation applica- related within the zoological system are already known. The tions (i.e. removal of animal organs, tissue or cells and their former include big cat hybrids between lions, tigers, jaguars transfer to human patients). The resulting cross-species are dif- and leopards and the mule and somewhat rarer hinny, which ferentiated into chimera and hybrids. The definitions are sum- are hybrids of the horse and donkey. The best known example marized in Annex 1. The different possible combinations of of a chimera cross-species is the sheep-goat chimera, which is cells or genetic material from animals and humans are presented sometimes referred to as a “geep”. with corresponding examples in Annex 2. A distinction should The focus in the debates surrounding animal-human crosses be made between intra-species and inter-species combinations. is on ethical issues in relation to the protection and dignity of The ethical assessment of their generation will differ, depending humans and, to a lesser extent, the protection and dignity of on the species and the scale on which they are involved in the the animal. The Nationale Ethikkommission im Bereich Hu- generation of cross-species and, moreover, whether the chimera manmedizin (NEK) (Swiss National Advisory Commission on or hybrids generated are intended for use in research, therapy, Biomedical Ethics) has considered the human-ethical aspects of or, where applicable, the farm animal or companion animal sec- research on human and animal embryos and foetuses and de- tors, and the stage to which the resulting organism should de- veloped concrete recommendations which also cover chimeras velop. The generation of such cross-species for the purposes of and hybrids (NEK, 2006). The majority of the members of NEK research and human medical therapy comes under the definition oppose the creation of chimeras consisting of cells from humans of animal experimentation and is regulated by the corresponding and animals (inter-species chimeras) because an experiment provisions of the Swiss animal protection legislation. However, could involve the formation of partial human structures within certain applications in the farm animal and companion animal the animal organism. A minority of NEK members believe that breeding sectors do not come under the definition of animal ex- limited authorization could be possible if it is ensured that the perimentation and are excluded from licensing. The regulations control of the development of the organism is not partly as- 1 Members of the Ethics Committee for Animal Studies: Prof. M. Geiser Kamber, Berne (President since 2008), Prof. A. Steiger, Berne (President until 2008), PD Dr. C. Aus der Au, Basel, Prof. B. Baertschi, Geneva, Prof. A. Bondolfi, Lausanne (until 2008), PD Dr. A. Brenner, Basel, Prof. K. Bürki, Zurich, Prof. H. Durrer, Oberwil (until 2008), Dr. A. Gutzwiller, Posieux, Dr. B. Heiniger, Langenthal, Prof. E. Hummler, Lausanne, Prof. S. Jakob, Berne, Dr. K. Kuehnle, Basel, Prof. B. Lanzrein, Berne, PD Dr. B. Ledermann, Basel, Dr. M. Leuthold, Basel (until 2007), Dr. B. Matter, Olsberg (until 2008), PD Dr. B. Riederer, Lausanne, PD Dr. K.-P. Rippe, Zurich (until 2008), Prof. B. Stadler, Bern (until 2008), lic. iur. M. Tinner, Zurich, Dr. Th. Wannier, Fribourg. ALTEX 26, 3/09 227 227-231-AltexStatement.indd 227 4.10.2009 18:12:11 Uhr POSITION STATEMENT sumed by the implanted cells of humans. The majority of NEK thermore, the St. Galler Kommentar zur Bundesverfassung (St members support the prohibition of the creation of hybrids (fu- Gallen Commentary on the Federal Constitution) notes in rela- sion of human and animal gametes). tion to this, that “The combining of human and animal can harm not only the dignity of humanity but also the human dignity and personality of the unique individual human being. In addition 2 Biological aspects of experimentally-generated to the introduction of non-human genetic material into human cross-species reproductive material, the provision also prohibits the formation of so-called inter-species hybrids (mongrels) through the fusion Experimentally-generated cross-species are divided into two of the gametes of different species, and of inter-species chime- categories: chimeras (cell crosses) and hybrids (genetic crosses). ras” (Ehrenzeller et al., 2008). Two further categories are differentiated among chimeras. Pri- The Swiss Federal Act on Reproductive Medicine (Fort- mary chimeras arise through the aggregation of embryonic cells pflanzungsmedizin-Gesetz, FMedG) of 18 December 1997 reg- prior to organogenesis. These chimera are generally complete ulates this issue as follows (Article 36, Generation of Clones, mixtures. Secondary chimeras are formed through cell exchange Chimeras and Hybrids): “The generation of a clone, chimera or or transplantation after organogenesis. Their mixture of cells is hybrid is punishable by imprisonment. Anyone who transfers a usually limited to one or a few tissues. As annex 1 shows, exam- chimera or hybrid to a woman or animal will also be punished.” ples of naturally occurring chimeras exist. These are exclusively The St Gallen Commentary on the Federal Constitution makes intra-species crosses. A series of examples of experimentally- the following comments on this provision: “Article 36 of the generated interspecific crosses also exists. Some examples are Reproductive Medicine Act prohibits, in addition, inter-species established experimental models, for example transplantations chimeras formed from two human embryos”. The following are of human tumour tissue to the nude mouse. not covered by letter b (of Article 119 paragraph 2 of the Fed- The creation of cross-species has certain biological limits. Ex- eral Constitution) and thus only come under the reservation of perience has shown that primary inter-species chimera are not the prohibition of abusive practices: i.e. the introduction of non- usually capable of development. The combination of sheep-goat human genetic material into the somatic cells of humans; the in- embryos is an exception here. Secondary inter-species chimera troduction of human genetic sequences into non-human genetic can usually only be generated in host animals with naturally material or reproductive material as occurs, for example, in the or induced immunoincompetence (i.e. they lack the capacity generation of transgenic animals. for immune defence). Inter-species hybrids can only be gener- The Swiss legislation is, therefore, highly restrictive and far ated between very closely related species and are often sterile more stringent than, for example, that of Great Britain where the (e.g. the mule and the hinny). No genetic technology processes generation of chimeras for research is allowed. Thus, it may be are used in the formation of all of the aforementioned cross- expected that the ethical and political debate on the justifiability species. of the generation of cross-species will continue. The extent to The generation of inter-species clones in the context of thera- which standards are necessary in relation to the status of the peutic cloning is also of interest in the context of the creation human embryo and the protection of its dignity will have to be of cross-species. This process is not based on genetic technol- clarified. ogy. The nucleus of a cell of human origin is transferred to a However, the subject of this position statement is the effect denucleated animal oocyte and a cytoplasmic hybrid embryo is of chimera/hybrid generation on the animal. These are legally created. The intention here is to avoid the use of human oocytes. restricted solely by the animal protection legislation. Initial results indicate that it is difficult to obtain cells capable of reproduction from such embryos; there may be an incompatibil- ity between the nucleus and mitochondria. This approach may 4 Animal protection legislation soon become obsolete, moreover, because the dedifferentiation of adult body cells to induced pluripotent stem cells (iPSCs) has According to Article 4 of the Swiss Federal Act on Animal Pro- been successfully carried out for mice and humans. These cells tection (Tierschutzgesetz, TSchG) of 16 December 2005, “no share the characteristics of embryonic stem cells. Again, chime- person shall inflict unjustified pain, suffering or injury on an ras, inter alia, will play an important role in the research of the animal or cause it to experience fear or violate its dignity in therapeutic potential of these cells. any other way. The abuse, neglect or unnecessary overexer- tion of animals