In the Spotlight: Animal-Human Chimeras
Sílvia Llonch reflects on whether animal-human chimeras are an ethical provocation or a useful tool for the medicine of the future.
What do we understand by the term chimera?
When someone says the word ‘chimera’, the first image that comes to many people’s minds is a fire-breathing female monster with body parts from three different animals (lion, goat and dragon). However, a bit of research about the word ‘chimera’ reveals a less mythical and more scientific definition: an animal containing cells with distinct genotypes – in other words, an animal generated by the combination of cells originally from different embryos.
In recent decades, the word chimera has also appeared in scientific publications – for example, as a mandatory experiment to validate newly generated mouse pluripotent stem cell lines. To do so, scientists use the mouse as an animal model. They introduce mouse stem cells into mouse embryos at the very beginning of development and verify whether the introduced cells can indeed be found later on in all the tissues of the newborn mouse. Therefore, a chimeric mouse is created, since mouse cells originally from two different organisms have been combined to generate a new mouse.
Imagine now that this same procedure is done by introducing human stem cells into mouse embryos. The result is indeed an animal-human chimera. Whilst the idea of chimeras has been around for centuries, this new concept of animal-human chimeras represents a revolutionary hot topic in the stem cell and regenerative medicine field.
The potential of animal-human chimeras is now being explored as a possible source of organs for transplantation. However, many from both the scientific and non-scientific communities are unnerved by this line of research.
Isn’t organ donation enough? Is there a real need to create organs for transplantation?
Even though the number of organ transplants per year is quite high in Europe, the number of new patients registered on waiting lists is even higher. 18 patients die every day waiting for a transplant, according to the Council of Europe. One of the critical factors is the requirement for good quality organs, which restricts the number of organs that can be used for transplantation. People who die due to either a traffic accident or a cerebrovascular accident are examples of potential donors. New traffic regulations have made the roads safer, thus decreasing the first type of potential donors. Unfortunately, a shortage in organ donation can also lead to illegal organ trafficking. So, no, organ donation is not enough, and, yes, there is a need to find alternative sources of organs for transplantation.
How can animal-human chimeras contribute to regenerative medicine?
The idea among the scientific community is to introduce human pluripotent stem cells into large animal embryos (pig, for example) and transfer those into a surrogate female of the same animal species (in this example, a female pig), allowing the embryo to continue its development. With appropriate genetic engineering tools (and understanding of development), researchers could potentially guide these human pluripotent stem cells to generate one specific organ of the animal. This “human” organ could eventually be transplanted into patients, saving lives.
Ethical considerations of animal-human chimeras
Nonetheless, the ethical implications of these types of procedures need to be acknowledged. For example, is it acceptable to breed animals knowing that they are eventually going to be sacrificed for human use? Whilst humans already do this for meat production, this is a different ‘use’ of an animal. Another critical point would be the following: what if the human cells that we introduce into the embryos contribute to the central nervous system or the germ cells (the ones that will become eggs or sperm) of the resulting organisms? This raises important questions: Will these animals have higher brain function – for example, will they experience consciousness or have memories the same way we humans do? Do we need to ensure that these organisms are sterile? Or, in other words, what would be the consequences if human stem cells colonise the reproductive system of the generated chimera, including the germ cell lineage? Could this chimera reproduce with other animal-human chimeras? If so, would that mean that we are creating a new species with human traits? In fact, although these ideas may seem like science fiction, some researchers in Japan are already developing systems to prevent the contribution of introduced human stem cells to the brain or the germ cell line of the generated chimera (Hashimoto et al., 2019).
What is clear is that using animal-human chimera to produce organs is a fresh and provocative concept and, naturally, triggers an intensive ethical debate between different communities in our society. Meeting the challenges of providing suitable organs for donation is a problem that we all need to grapple with. As individuals considering whether we might become an organ donor or the preferences of our loved ones. Or as nations, whether we want public funding to be given to research projects exploring whether animal-human hybrids are a potential source of suitable human organs.
But let’s remember these technologies develop at a slow pace. In fact, recent research on animal-human chimeras shows that human stem cells can contribute to pig embryos, but with very low efficiency (Wu et al., 2017). Moreover, human stem cells introduced to pig embryos somehow interfere with normal development, leading to smaller-sized embryos. Therefore, it is clear that we still have a long path in front of us before growing human organs in an animal becomes feasible on a large scale, and most importantly, before these organs are proven safe for transplantation into humans. And this provides us, scientists and non-scientists alike, the time to debate and discuss what this means for us as a global society.
Find out more
Chimeras in the Headlines
Embryo experiments take ‘baby steps’ toward growing human organs in livestock
Scientist working to grow human organs in pigs
Better Living Through Crispr: Growing Human Organs in Pigs
First human-monkey chimera raises concern among scientists
More on eurostemcell.org
The Ethics of Brain Organoids: Interview with bio-ethicist Dr Sarah Chan
(for a deeper discussion about brain function in animal-human chimeras)
Short video: ‘What are Embryonic Stem Cells?’
Fact sheet about Embryonic Stem Cells
More about Organ Shortage
Council of Europe – Organ Donation
European Consensus Document: Meeting the Organ Shortage
Bulletin of the World Health Organisation about organ trade
(Subscription may be required to access)
Hashimoto, H., Eto, T., Yamamoto, M., Yagoto, M., Goto, M., Kagawa, T., Kojima, K., Kawai, K., Akimoto, T., & Takahashi, R. I. (2019). Development of blastocyst complementation technology without contributions to gametes and the brain. Experimental animals, 68(3), 361–370.
Wu, Jun & Platero Luengo, Aida & Sakurai, Masahiro & Sugawara, Atsushi & Gil, Maria & Yamauchi, Takayoshi & Suzuki, Keiichiro & Bogliotti, Yanina & Cuello, Cristina & Morales, Mariana & Okumura, Daiji & Luo, Jingping & Vilariño, Marcela & Parrilla, Inmaculada & Soto, Delia & Martinez, Cristina & Hishida, Tomoaki & Sánchez-Bautista, Sonia & Martinez Martinez, Ml & Izpisua Belmonte, Juan Carlos. (2017). Interspecies Chimerism with Mammalian Pluripotent Stem Cells. Cell. 168. 473-486.
Written by Sílvia Llonch. Reviewed by Niels Menezes and Jan Barfoot. Edited by Amanda Waite.
This is the first in a series in which researchers reflect on stem-cell-related stories in the media. This series was initiated by a group of science writers who attended the Hydra European Summer School on Stem Cell Biology and Regenerative Medicine