files no:34 www.cmf.org.uk chimeras, hybrids

By Calum MacKellar and ‘cybrids’ In biotechnology it is now scientists created the world’s first - This reluctance to involve possible to combine elements by fusing a sheep embryo cells and embryos is also found in between organisms of and a goat embryo. The resulting ‘geep’ European documents such as Article consisted of goat cells and sheep cells. 13 of the Council of Europe’s European different species. It is also Externally this combination was obvious, Convention on Human Rights and possible to create cloned as the skin that grew from the sheep Biomedicine, which prohibits any action using parts of embryo was woolly, while the areas of skin that aims to modify the human genome eggs from one species and that originated from goat cells bore hair. 3 in a way that will be passed on to future generations. In effect this would ban any nuclear genetic material from The potential power of inter-species genetic technologies applied at a very another. It is even possible combinations became clearer with a series early embryonic stage of life. European to create novel organisms via of experiments conducted in the late policy makers are clearly anxious interspecies combinations 1990s. In these, small sections of brains about the technology, though the UK from quail embryos were transplanted of gametes. Should such government has not so far signed up to into the developing brains of . procedures ever be permissible this convention. between species? If When they hatched, the resulting chickens exhibited quail-like vocal trills and head In his January 2006 State of the Union so, should we ever combine bobs, showing that the transplanted parts address, American President George human beings with animals? of the brain were not only incorporated W Bush expressed his position when into the brain, but that such mixing of he slipped in a small but significant Early in 2007 a UK parliamentary tissues could allow complex behaviours to comment that announced his intention committee met to discuss the be transferred between species. 4 to ban human-animal hybrids: ‘A technological and ethical issues hopeful society has institutions of surrounding any possible mixing together The next step for many scientists is to start science and medicine that do not cut of human and animal species. They sat combining human and nonhuman cells. ethical corners, and that recognize the as a response to proposed legislation The immediate objective is not to generate matchless value of every life. Tonight I which, if enacted, would have banned beings that are fully grown half-, ask you to pass legislation to prohibit such work. After effective lobbying but to create a source of stem cells that the most egregious abuses of medical from scientists and other associated could potentially be used in research and research: human cloning in all its interest groups, the committee decided therapy. Initial requests for permission forms, creating or implanting embryos in favour of the creation and limited use to perform this work envisage that any for experiments, creating human- of human-nonhuman hybrids, chimeras embryo created by mixing human and 1 animal hybrids, and buying, selling, or and ‘cybrids’. nonhuman cells would not be allowed to patenting human embryos. Human life develop beyond the 14-day stage. The interest in mixing species is neither is a gift from our Creator - and that gift new, nor is it confined to the realms of myth Political landscape should never be discarded, devalued or or fiction. True, many ancient cultures told This push to develop the combining of put up for sale.’ 6 stories and built statues of entities such as human and nonhuman cells has come This File will examine what is currently human- sphinxes and winged , from technological developments since possible, and what is envisioned for the but the natural mixing of animals has the 1990 legislation. Anxiety about this near future. By drawing on Christian occurred for centuries. A , for example, new possibility can however be seen principles it will ask whether any starts life when a male mates with in a 2001 UK report from the Home form of species mixing is ethically a female (a cross between a female Office’s Animal Procedures Committee, justified, particularly where one of the donkey and male horse is less common, and which recommended that ‘No licences components is human. called a hinney). The gametes (sperm and should be issued for the production of egg) fuse and the resulting embryo develops embryo aggregation chimeras, especially What’s been done so far into a healthy animal. Though normally not cross-species chimeras between One complication is that there are infertile, there are even occasional reports of humans and other animals, nor of hybrids various ways of deliberately mixing two giving birth. 2 which involve a significant degree of species of animal (see box). Each process But in recent years, research has raised hybridisation between animals of very produces a different outcome and raises a host of new possibilities. In 1984 dissimilar kinds’. 5 different issues. CMF file number 34 hybrids hybrids CMF file number 34 Genes from humans in bacteria Defining terms 100 trillion micro-organisms that live that we should prevent future ethical At the simplest end, there are the many primarily on our skin and in our guts. dilemmas by forbidding anyone from chimera examples of genes harvested from the One paper estimates that humans trying to create an animal that may to An organism made up of cells that come An organism created by combining eggs 15 human genome and placed inside from two genetically distinct individuals. and sperm cells of different species, so that carry more than 500 different species some extent exhibit human capacities. all of its cells contain a mixture of both of micro-organism, and that together bacteria. These transgenic bacteria have This can occur when embryos from two Biblical views of humanity different species are brought together in components. Human-animal hybrids can this means we carry 100 times as many huge medical and commercial potential. potentially be created when:9,10 One way to address the ethical issues early development, and the two sets of cells 12 For example, most insulin is now genes as are found in our ‘own’ cells. merge. In a chimera, each set of cells - a human egg is fertilised by nonhuman sperm incurred by creating human-animal produced from E. coli with the insulin contains components from only one species. - a nonhuman egg is fertilised by human sperm A further argument used against mixtures is to see in what way the gene from a human inserted amongst An example of this is the so-called ‘geep’ mixing individuals is that it will violate resulting creatures would show other genes. These bacteria consequently that was created by combining two A hybrid has two parents of embryos, one from a goat, one from a sheep. different species their genetic uniqueness. That, again, is diminution of features commonly held by produce an individual human protein, It is interesting to note that the geep not as clear as it might seem, because Christians to be important characteristics but are far from bearing any distinctively genetic inheritance would come from the consequently had four parents. ‘cybrid’ same-species chimeras are probably of human beings. human characteristics. Artificial chimeras, nucleus donor. However, considerable (a cytoplasmic hybrid) quite frequent in nature. Some will such as the geep, have four parents information stored in proteins and other Image of God Genes from humans in mice An organism that, like hybrids, has cells components of the egg’s cytoplasm would occur when two embryos fuse as they that all contain components from two also be present, at least in the early embryo, A critical feature all Christians agree on Moving up in scale, there are also many grow in the womb (see box), but other different species. This time, however, the and would most probably influence is that God created human beings to be thousands of strains of mice that have naturally occurring chimera situation is more complex. development. ‘microchimeras’ are created when cells Not all chimeras have four parents. Egg from another in his image and likeness.16 There is less A ‘cybrid’ would be created when nuclear species - without had sizable pieces of genetic code that Human-human chimeras often occur quite from the fetus and placenta break off genetic material from one species was nucleus, but some agreement on the exact meaning of those originated from the human genome naturally. This can happen when two genes and information during pregnancy and birth and enter placed inside an egg from another species. Complete nucleus carrying proteins in separately fertilised embryos growing from one species cytoplasm terms, but most Christians agree it at least spliced into their genes. Many of these In the case of a human-nonhuman ‘cybrid’ the mother’s blood stream. Colonies of side-by-side in the womb merge into one. A implies that humans are in some sense this could be human material placed in a are used in cancer and pharmaceutical variant of this is when a single cell these cells may persist for decades, and nonhuman egg with its nucleus removed, or special and distinct from other parts of experiences a significant genetic change, research as experimental animals that vice versa. on occasions these cells have found such as the loss of a chromosome, but creation. mimic human disease. In terms of each their way across the placentas in future carries on growing. The resulting individual The result of this is that the new individual specific disease they have distinctly can then be made of a mixture of cells, some would have the full set of nuclear genes pregnancies and become part of the Of all created beings, humans are the only humanised traits, but they are still with the full genetic complement, and from the species that donated the nucleus, makeup of the bodies of subsequent ones God talks to directly and with whom others with a reduced genome. In each of but would start with the cytoplasmic clearly mice. these situations the resulting individual composition of the other species. siblings. Some estimates claim that he has a special relationship. God also A ‘cybrid’ has two unequal ‘parents’, will have just two parents. Although there is the possibility that genes up to 50% of women who have been expects humans to respond to him and to Andi – with jellyfish gene of two different species. residing in mitochondria (organelles within pregnant will be chimeric. 13 relate to each other. It comes as no surprise In the first two examples a small element At least one parent (the egg donor) Naturally occurring chimeras have two parents. the cytoplasm containing some genetic to Christians that almost all cultures of human DNA has been incorporated The chimera occurs as twins fuse. material) have the potential of being passed will be female; the other (the cell donor) Arguments from ‘nature’ could be either male or female. encourage some recognition and worship of with a mass of another organism’s genes. into the new individual, the majority of the From all these points, it is difficult to the divine, differentiate people from other In the case of Andi, the process was the argue against hybrids or chimeras on animals, and expect individual members of other way around. Andi was the first Researchers hope the technique will human, half-chimpanzee. One of the if at all, from the versions found in a purely genetic basis. The issue then their societies to respect each other. primate to have a package of foreign remove a very important barrier in Soviet Union’s top scientists, Professor humans. This is why people quote figures becomes less the actual composition of genes inserted into its genome. The current research into embryonic stem cell Ilya Ivanov, tried to impregnate female such as ‘humans are 50% banana’. It is individual people’s genomes, but how Taken together, all this causes Christians genes came from jellyfish and although transplantation therapies, namely the chimpanzees with human sperm in Africa therefore difficult to describe these so- that composition came into being. to see human beings as more than clever present in his cells, they did not function need for fresh human eggs of which there in order to create a human-chimpanzee called ‘housekeeper’ genes as belonging Does the simple fact that something apes. This is not because they may have particularly well. Andi, however, shows is a very limited supply for the creation hybrid (a ). These experiments to any particular species. occurs in nature give us permission physically identifiable superior features, the possibility of introducing new genes of cloned embryos. Scientists are eager to were unsuccessful, but at the time many Secondly, the human genome carries to do the same in the laboratory, and but because God has created them in his into primate cells, and thus that it would obtain these embryos in order to harvest colleagues believed it was probably feasible.8 many genes that have no known extend it further? image and given human beings added potentially be possible to add new genes their stem cells for biomedical research. dignity by becoming fully man in the Genetic barriers – function in humans, but are known to We need to be careful of falling into to human beings. If the gene were merely 17 Rabbit-human hybrid embryos a helpful concept? have specific roles in other animals. The person of Jesus Christ. repairing the function of an organ such the trap of assuming that if something In August 2003, Hui Zhen Sheng of It may be said that any form of mixing human genome, for example, carries the Kinds as the liver, then most people would occurs in ‘nature’ then it must be good. Shanghai Second Medical University, violates natural boundaries – it breaks the entire gene sequence for the mouse tail; 18 probably accept this as a legitimate Nature presents plenty of examples of In the opening chapter of Genesis, China, announced that rabbit-human species barrier. To pursue this, however, the cells simply miss the switch to turn it 19 medical intervention. But what would actions that seem undesirable, ranging and subsequently, there are repeated ‘cybrid’ embryos had been created. we need to understand the strengths and on. 11 Some people therefore argue that happen if the gene were expressed in the from disease to earthquakes. Similarly, references to living things being made in adding more mouse genes to a human brain and altered the individual’s ability Researchers fused adult human material weaknesses of the concept of species medicine is a discipline that aims to fight different ‘kinds’. Within Christianity there to think, or their innate behaviour? with rabbit eggs stripped of their boundaries. Although it is rare for species cell would not be doing anything new, off the worst effects of natural actions is debate about the meaning of this term, chromosomes and created rabbit-human to interbreed, the ‘barrier’ is in reality though of course there would be the – if nature really shows us the way, then but one possibility is the idea that God Cow egg-human clone hybrid embryos which developed to difficult to define. intention of introducing a new structure medicine should be confined to helping intended a world in which animals could In 1999 the US company Advanced approximately the 100-cell stage, about or function. In addition, retroviruses people who have physical injuries. exist and adapt within each kind, but Cell Technology Inc announced that it First, if each species has a clearly defined four days of development. Moreover, the constantly carry new genetic material intended no interbreeding between kinds. had developed a method for producing genome, then mixing species means Undermining human dignity scientists claimed to derive from these across species into chromosomes. A primitive human embryonic stem cells mixing up two distinct genomes. But Some people worry that to produce It would thus be acceptable to try mixing embryos stem cells similar to conventional careful analysis of any organism shows by uniting human adult material with a with the human genome, things are not creatures that blur the boundaries animals within a kind, such as generating human embryonic stem cells. that these viruses have been frequent cow egg. 7 This egg had previously had that clear. To start with, around half the between humans and animals could different breeds of , but not to try visitors throughout generations. its nucleus removed. The company hopes Historic attempts at human-ape genes in human cells create proteins threaten to undermine the concept mixing between different kinds. The this method will enable them to produce There are well-documented reports that keep cells alive and growing. These Another, more intriguing, view of of human dignity since it is a dignity problem here would be drawing up a list ‘unlimited’ supplies of stem cells for that a few scientists in the mid-1920s genes are found in many different living human beings sees us as communities specifically reserved to humankind.14 of biological features that would allow research into transplant medicine. made serious attempts to create a half- organisms where they vary only slightly, of organisms. Each of us carries around Moreover, other commentators suggest division of species into distinct ‘kinds’.20

CMF file number 34 hybrids Therefore, in the biblical perspective, species into bacteria to create human insulin, References integrity is ultimately defined by God, are clearly aimed at treating lost function 1 House of Commons Science and Technology Committee Report. rather than by physical features. The fusion and ‘restoring the masterpiece’, other Government proposals for the regulation of hybrid and chimera embryos. 2007. HC 272-1 of human and nonhuman genomes may manipulations such as creating ‘cybrids’ 2 news.bbc.co.uk/1/hi/sci/tech/2290491.stm therefore be perceived as running counter to involve crossing an ethical boundary to 3 Roth TL et al. Survival of sheep x goat hybrid inner cell masses after injection into ovine embryos. Biol Reprod 1989; 41(4):675- the sacredness of human life and humanity create something new. 682 created in the image of God.21 4 Balaban E. Changes in multiple brain regions underlie species Abuse of human embryos differences in a complex, congenital behavior. Proc Natl Acad Historicity Quite apart from the specific question of Sci USA 1997; 94(5):2001-2006 5 Animal procedures committee report on biotechnology. 2001. Throughout the Bible, there is a constant mixing species, many Christians will also para 57 emphasis on the importance of historical be troubled by the fact that much of the 6 www.whitehouse.gov/stateoftheunion/2006 research will involve using or creating semi- 7 www.advancedcell.com/press-release/advanced-cell-technology- roots and genealogies. The Old Testament, announces-use-of-nuclear-transfer-technology-for-successful- in particular, is in many ways the story of human embryos for research. generation-of-human-embryonic-stem-cells 8 Rossiianov K, Beyond Species: Il’ya Ivanov and His Experiments the history of a community, with that story In 2007 many people are celebrating the on Cross-Breeding Humans with Anthropoid Apes, Science in often recorded at a very personal level. bicentenary of the British abolition of Context 2002;15 (2): 277-316 9 Canadian Assisted Human Reproduction Act 2004, www.canlii. The New Testament then endorses that slavery. It is therefore interesting to note org/ca/sta/a-13.4/sec3.html significance by repeatedly drawing on the that the basic argument for maintaining 10 Australian Prohibition of Human Cloning Act 2002. 22 11 Waterston RH et al. Initial sequencing and comparative analysis genealogies of Christ. slavery was that it was good for our of the mouse genome Nature 2002; 420: 520-562 economy. Similarly many of the arguments 12 Nicholson JK et al. The challenges of modeling mammalian Many forms of biotechnological biocomplexity. Nat Biotechnol 2004; 22(10):1268-1274 intervention around the start of life destroy used to defend the development of human- 13 Bianchi DW et al. Proc. Nat. Acad. Sci USA 1996; 93: 705-8 animal embryonic combinations are based 14 Committee on Guidelines for Human Embryonic Stem Cell those senses of ancestry, parentage and Research, Guidelines for Human Embryonic Stem Cell Research identity for the resulting individual, and this around the benefit to the economy. There is (Washington, DC: National Academies Press, 2005), 55. even the acknowledgement that by being 15 Karpowicz P et al. Developing Human-Nonhuman Chimeras in is a key problem. If ever a person came into one of the few countries in the world to Human Stem Cell Research: Ethical Issues and Boundaries, existence after a cell had been taken from a Kennedy Institute of Ethics Journal 15.2 (June 2005): 107-134 give free permission for research in this area male donor and fused with a cow egg, the 16 Genesis 1:26-27 we can gain global dominance. For many 17 John 1:14 resulting child would (most probably) look 18 Genesis 1:11, 12, 21, 24, 25 Christians, using large numbers of human and behave like any other human, but that 19 eg Genesis 7:2-3; Leviticus 19:19 embryos for commercial benefit is just as 20 Animal procedures committee report on biotechnology. 2001. para person’s parentage would be controversial 55 abhorrent as slavery. Even if the claimed in the extreme. There is a world of difference 21 Jones NL, Could Animal-Human Chimeras be on the Way? www. end of treating illness is good, the end does cbhd.org/resources/genetics/jones_2003-01-09_print.htm between genetically altering an existing 22 Matthew 1:1-17; Luke 3:23-38; Acts 13:22-23 not justify the means.25 human being who has come about through 23 Genesis 2:24 24 Wyatt J. Matters of Life and Death. IVP/CMF, 1998 the fusion of human sperm and egg and Conclusion 25 Romans 3:8 bringing a ‘human’ being into existence by The word ‘science’ derives from the Latin Past titles in the CMF Files series: other means. scientia, knowledge, and science is rightly concerned with ‘the systematic study of the No. 11 The Human Genome Relationship No. 12 Therapeutic Cloning and Stem Cells nature and behaviour of the material and In a similar way the notion of relationship, No. 13 Do Not Resuscitate Dilemmas physical universe, based on observation, No. 14 Genes and Behaviour and in particular relationship within experiment and measurement’. However, No. 15 Human Experiments families, is a key aspect of biblical thought. No. 16 Reproductive Cloning questions like whether to create human- No. 17 Resource Allocation Any technique that encourages the creation nonhuman embryonic combinations No. 18 The Mind-Body Problem of human life outside a family unit is No. 19 Advance Directives require more than knowledge, they require No. 20 Homosexuality therefore not giving the new person the best wisdom. Wisdom is knowledge tempered No. 21 Sex Selection start in life. It is also creating communities No. 22 Euthanasia by judgment. Science cannot just pursue No. 23 Abortion where children live in less than ideal the acquisition of knowledge without any No. 24 Globalisation and Health families, which in turn is likely to create consideration of the means involved; it No. 25 Gender Identity Disorder No. 26 Speciesism less stable societies. God’s design is that must operate within ethical boundaries. No. 27 Neonatal Ethics children should be the fruit of marriage No. 28 Saviour Siblings – a public, lifelong, committed, sexual Christians are pro-science, but look for No. 29 Autonomy - who chooses? ways of conducting science within an No. 30 Quality of Life relationship between a man and a woman.23 No. 31 Transhumanism ethically justifiable framework. If the No. 32 Human Suffering ‘Restoring the masterpiece’ world’s scientific community decided not to No. 33 World Population - challenge or crisis? 24 John Wyatt has used the analogy that pursue this particular direction of research, human beings made in the image of then new avenues would almost certainly This series arose out of discussions within the Medical Study Group of the Christian Medical Fellowship. God are ‘flawed masterpieces’. We have open up and lead to alternative modes of a Christian duty to correct flaws in the finding cures and treatments. The series editor is Pete Moore PhD. The views expressed in these papers are not necessarily those of the publisher. masterpiece to restore it as much as possible to God’s intention, but we have CMF is a Registered Charity, No. 1039823. no mandate to cross boundaries to create Dr Calum MacKellar Visit www.cmf.org.uk to download all the Files in pdf format and something new. While some cross-species Director of Research for more information about medical ethics. manipulations, like inserting human genes Scottish Council on Human Bioethics.