Inter-species hybrids and chimera are entities created from the mixing of two or more different species.  Hybrids are organisms whose genetic make up has been created by mixing the genes of two or more species; typically the gametes of two species are fused to create a single zygote.  Chimera are organisms consisting of two or more different populations of genetically distinct cells; for example two fertilised eggs or early embryos may be fused together and develop as a single organism.

Somatic Cell Nuclear Transfer (SCNT) may be used to create ‘mixed species’ or hybrid embryos.  The nucleus from an egg cell of one species may be removed, and replaced with the nucleus from a somatic cell from another species. (A somatic cell is a ‘diploid’ non gamete cell, possessing the full set of chromosomes required for development.)  Development of the cell, as though it was an ordinary fertilised egg, is stimulated by an electric shock and/or specific biochemicals.

Prior to ‘modern science’: 

Hybrids and chimera have been the subject of fascination in myth for thousands of years, long before the advent of modern science.  In Greek mythology the Chimera was a fire breathing creature, described as having the body of a goat, the tail of a snake or dragon, and the head of a lion.  The Chimera’s brother, Cerberus, was a monstrous multiple-headed dog, with a snake for a tail.  Other mythical hybrids and chimera include the Sirens, the Griffin, and the Sphinx. Some hybrids occur naturally, or may be bred without the assistance of modern science. The plant wheat can form hybrids naturally; but artificial hybridisation in botany is also widespread.The mule, the offspring of a male donkey and a female horse, is the best know animal hybrid, though others, such as the ‘dzo’ or ‘yakow’, a cross between a male yak and a cow, also exist.  Animal hybrids are usually infertile. 

Modern scientific milestones: 

Chimera:

Þ      In 1984 a “geep” was produced by combining embryos from a goat and a sheep, at Institute of Animal Physiology in Cambridge, England¹. 

Þ      In 2001, researchers at the University of Nevada, USA, injected human stem cells coming from bone marrow or umbilical cords into sheep foetuses. The sheep then grew up with a small proportion of human cells throughout their bodies².

Þ      Also in 2001, researchers injected human neuronal stem cells into the skulls of three unborn monkeys. These cells were incorporated into the developing brains of the animals³. 

Hybrids:

 Ãž      For many years, scientists have been creating transgenic bacteria and animals in which some foreign (human or non-human) genes are deliberately inserted into the genome of living beings.  Human insulin was the first medication produced using modern genetic engineering techniques. In this procedure, actual human DNA is inserted into a host cell (E. coli in this case). The host cells are then allowed to grow and reproduce normally, and due to the inserted human DNA, they produce actual human insulin.

Þ      In addition, mice with human immune system cells and organ-donor pigs with human genes have been created which can also pass on the human genes to subsequent generations.  

Þ      In 1989, American researchers reported the introduction of human chromosome fragments into fertilized mouse eggs, which they could then follow as the embryos grew into mice. The scientists indicated that human chromosomes were detected in the tail of at least one mouse⁴.

Þ      The company Advanced Cell Technologies was reported, in November 1999, to have created the first animal-human hybrid embryo by SCNT. The nucleus of an adult human cell was inserted into a cow’s egg stripped of its chromosomes in order to create a cloned embryo. This embryo was left to develop and divide for 12 days before being destroyed ⁵,⁶.

Þ      In 2003, a team of scientists at Cambridge University fused the nuclei of adult human cells with frog eggs, with the aim of producing rejuvenated master cells that could be grown into replacement tissues for treating disease. In this experiment some kind of very early biological development was initiated, the extent of which is difficult to ascertain from an ethical perspective⁷.  

Policy History 

1. UK policy development and consultations

Scientific abilities often develop faster than parliament is able to anticipate.  As a result chimera-hybrid research in the UK has often existed in a legal limbo and public discussion of the issues has lagged behind scientific activity.  For example the fusion of adult human nuclei with frog eggs in Cambridge in 2003 exploited the regulatory vacuum.⁸ 

The Human Fertilisation and Embryology Authority (HFEA) is the statutory regulator for human fertilisation and embryology, under the 1990 Human Fertilisation and Embryology Act (1990).   However, as the 2005 House of Commons Science and Technology Committee report Human Reproductive Technologies and the Law ⁹ found, the 1990 act did not anticipate the matter of animal-human chimeras and hybrids, and consequently failed to clearly indicate whether such entities fall under the jurisdiction of the HFEA.  The Science and Technology Committee joined a growing body of opinion recommending that the law be clarified. 

In August 2005 the British government launched a public consultation in advance of proposed changes to the 1990 Human Fertilisation and Embryology Act.  Responses were published in March 2006.  This was a wide ranging consultation and many of the 535 respondents did not comment on the question pertaining to hybrids and chimera.  Nonetheless, the consultation did indicate broad public resistance to the development of hybrids and chimera in research.  

On January 11^th 2007, the Human Fertilisation and Embryology Authority (the HFEA is the statutory regulatory body established under the 1990 HFE Act) announced a public consultation specifically about hybrid and chimera research.  Some have alleged that because hybrid and chimeric research is not specifically prohibited under UK legislation, the HFEA is jeopardising the interests of scientists.  However, for others the consultation is controversial because if is far from clear that, under the 1990 Act, the HFEA has jurisdiction over hybrid and chimeric embryos, and secondly because the public had already been consulted about hybrid-chimera research under the broader 2005 consultation (though not in such detail).  Moreover, on January 10^th, the House of Commons Science and Technology Committee announced another similar consultation (though this consultation is running to a much tighter timeframe). 

During spring 2007, the government is expected to publish the “Draft Tissues and Embryo Authority (RATE) Bill”.  The principle effect of the bill will be the establishment of a new body, the Regulatory authority for Tissues and Embryos (RATE), is expected to replace the HFEA and the Human Tissue Authority (HTA).  However, the bill will have implications for chimera-hybrid regulation and government intentions in this area will likely be indicated. 

The New Inter-Species Future? An Ethical Discussion of Embryonic, Fetal and Post-Natal Human-Nonhuman Combinations

This report is addressed to the UK House of Lords and House of Commons Joint Committee on the draft Human Tissue and Embryo Bill which was published by the UK Government on the 17th of May 2007.

Click here to read and download a PDF copy of of the report.

2. Overseas legislation and policy:

 Ãž      Australia: The Prohibition of Human Cloning for Reproduction and the Regulation of Human Embryo Research Amendment Act 2006

This act, which modified and partially repealed the Prohibition of Human Cloning Act 2002, states that is it prohibited to:

§         Place a human embryo clone in the body of a human or the body of an animal.
§         Create a chimeric embryo.
§         Develop a hybrid embryo without a licence, or for more than 14 days.
§         Place a human embryo in an animal.
§         Place an animal embryo in the body of a human for any period of gestation.

Þ    Canada: Assisted Human Reproduction Act 2004
§         Clause 5 indicates that it is prohibited to create a chimera or hybrid, or to transplant a chimera or hybrid into either a human being or non-human life form ¹⁰ 

3. International legislation pertaining to hybrid/chimeric embryos:

For

Þ      Advancing medical knowledge
Advancing medical knowledge in order to develop new medical treatments is the strongest and most often cited justification of the creation of hybrids and chimera for research.   However some experts, such as Australia's Chief Scientist Jim Peacock oppose animal-human hybrids on the grounds that the mixing of DNA in the resultant embryo would make it a poor model for research into human disease.  Such technical objections would not apply to research on fully human embryos and stem cell lines.  Additional considerations motivate the desire to research human-animal hybrid embryos rather than fully human embryos. 

Þ      Avoid exploiting women to procure human eggs
Firstly, research cloning using human eggs risks exploiting women.  The hormonal treatment required to procure a harvest of eggs from a woman can be painful and carries medical risks such as the rare but potentially fatal ovarian hyper stimulation syndrome.  Many consider it unethical to expose women to such risks, especially if they are socio-economically vulnerable women drawn by financial incentive.  Secondly, human-animal hybrid research applications are motivated by a scarcity of supply of human eggs for research cloning.

Against

Þ Human dignity and the ambiguous status of mixed species entities

The moral and legal status that should be afforded to mixed species entities is unclear.  The blurring of this seminal boundary would threaten the principle of human equality and equal rights which are foundational in our culture and law.  The President’s Council on Human Bioethics accepted in 2004 that society should not be put into a position to judge the humanity or moral worth of ambiguous hybrid entities.  Moreover critics are concerned that even if hybrid entities are destroyed early in their development, the mixing of human and animal embryos will further diminish the respect afforded to the human embryo. Xeno-transplants, by contrast, do not raise this dilemma.  Provided that no brain or reproductive tissue is used, it is generally  accepted that a human with a transplanted animal organ does not jeopardise their essential human identity.

Þ Risk of new disease creation

Chimeric and hybrid entities risk the transmission of unknown diseases between species.  This could occur regardless of the type of chimeria or hybrid.  This is one of the reasons for the low uptake of xenotransplantation: pathogens could be introduced into the human body bypassing mechanisms that would otherwise prevent animal diseases from jumping the species barrier.  On the transgenic level, experiments have demonstrated that unexpected side effects may occur, such as the joint pain experienced by the Beltsville pigs with a human growth gene12.  Finally, human-animal hybrid embryos created by SCNT could transfer animal mitochondrial diseases to humans if the stem cell lines derived were used therapeutically.

Þ Animal rights

Human rights are not the only rights at stake when animal-human entities are considered.  Transgenic animals created for medical experimentation, transplant or to produce pharmaceuticals may experience exploitation and risk.