Human-animal chimeras: should other countries follow Japan's lead?

Under the new Japanese guidelines, a Japanese scientist, Dr Hiromitsu Nakauchi, is the first to receive government approval to produce animal embryos that have human cells and transplant them into surrogate animals (see BioNews 1009). The revised rules from Japan's Ministry of Education, Culture, Sports, Science and Technology in March lift a previous ban on the making of chimeras beyond 14 days. The new rules also enable the transplantation of chimeric embryos into animals (previously forbidden) while banning the transplantation of such embryos into humans.

Research involving chimeras could lead to increased knowledge of human biology and development, with important implications that could significantly impact human health. This type of study could lead to progress in the regenerative medicine field, such as generating human tissues and organs for transplantation. For instance, induced pluripotent stem (iPS) cells could be derived from the patient by reprogramming their skin cells to create organs.

In the recently-approved experiment, Dr Nakauchi and his team plan to create an animal embryo that lacks a particular gene essential for the formation of an organ, eg a kidney and then to add human iPS cells into the animal embryo. As the animal grows, the human iPS cells create the kidney. Dr Nakauchi intends to start with developing hybrid mice, followed by hybrid rats, and then hybrid pigs. Their ultimate aim is to produce animals with organs made of human cells that may eventually be transplanted into a human.

However, creating chimeras is ethically contentious. There are various objections put forward, such as the human dignity argument and the concern for animal welfare/animal rights. Growing human organs within a chimera raise challenging issues on the moral status of these beings that are not fully human or animal. For instance, one concern is that the human cells may even drift to the animal's brain and could affect their cognitive abilities.

There is fear expressed of the blurring of species lines, invoking the image of the chimera of Greek mythology: a monstrous mix of lion, goat and serpent. For some people, reproduction with animals is taboo. Opponents of the process claim that mixing even a small amount of human genetic material with that of an animal amounts to the same, and is unnatural, objectionable and wrong. Such research has triggered protests from social conservatives. Even among scientists, there is scepticism.

Despite the controversies surrounding the creation of chimeras, the International Society for Stem Cell Research (ISSCR) applauds the revised Japanese rules permitting research on chimeric embryos. Under the existing ISSCR guidelines, Recommendation 2.1.5 supports research creating chimeras as long as it is under appropriate ethics review and strict oversight.

It provides that: 'Research that entails incorporating human totipotent or pluripotent cells into animal hosts to achieve chimerism of either the central nervous system or germ line requires specialised research oversight. Such oversight should utilise available baseline animal data grounded in rigorous scientific knowledge or reasonable inferences and involve a diligent application of animal welfare principles.' The Japanese new rules build on this recommendation.

In the USA, while chimeras have been made but they were not brought to term. The US National Institutes of Health (NIH) recommended lifting a moratorium on this research in 2016. However, there has been no policy change.

In Australia, the creation of chimeras falls within the loopholes of the current law. While the Prohibition of Human Cloning Act for Reproduction (PHCR) Act 2002 bans the deliberate creation of 'chimeric embryos' (section 17) and the development of a 'hybrid embryo' for more than 14 days (section 18), a chimera would not meet the legislative definitions of these types of embryos. In the statute, a chimeric embryo is defined as 'a human embryo into which a cell, or any component part of a cell, of an animal has been introduced'.

A hybrid embryo is defined as an embryo created by the fertilisation of a human egg by animal sperm (or vice versa) or where a human egg into which the nucleus of an animal cell has been introduced (or vice versa). Indeed the making of a chimera does not breach the legislation in Australia. Given the ethical issues associated with chimera research, law reform is essential to stringently regulate this type of research. Currently, ethics review committees may not have sufficient knowledge and thus, experts are needed to sit in such committees in an advisory capacity.

These complex issues should be fully explored in forums involving ethicists, scientists and the civil society. And scientists could lead the discussions. As researcher, Dr Tetsuya Ishii of Hokkaido University in Sapporo, Japan, said: 'It is good to proceed stepwise with caution, which will make it possible to have a dialogue with the public, which is feeling anxious and has concerns'. We certainly need to have a conversation on whether we should follow Japan's lead.