Chimeras: Groundbreaking Phenomenon or Merely a Chance to Play God?

By Anushka Gupta

Some may think this peculiarity is simply a myth, stemming from Greek mythology wherein a ‘chimera’ was a fire breathing creature – an unusual mélange of a lion, goat and dragon. It is easily unimaginable to some people that these hybrids exist in real life. A chimera is in fact “an organism whose cells are derived from two or more zygotes” (Madan, 2020). Simply put they are organisms (whether it be human or animal origins) that contain two sets of DNA so they are composed of cells with more than one distinct genotype. The multitude types emanate from a variety of natural or artificial means. Human chimeras occur from natural means, the first being reported in 1953. 

According to an article in the British Medical Journal, Mrs McK was found to have two different blood types in her blood, AO,  resulting from her twin brother’s cells living in her body. “Genetically, under normal circumstances AO is impossible, as a person with alleles for types A and O will automatically have type A blood, because the type A is dominant.”(MacDonald, 2015) She had also not received any transfusion. Mrs McK’s twin had died as an infant. Therefore, In that time, they sequestered this case as “the consequence of vascular communication with her twin” (Dunsford et al., 1953). In other words, twins developing in the womb should have completely separated placental villous tissues however in this case they had an abnormal marked vascular communication between the two placentas causing an uneven blood distribution so the lighter twin receives less blood than the heavier one.(Hagihara et al., 2003). In the early development stage, proto cells called erythroblasts transferred from the twin’s embryo into hers, permanently changing her blood type but not her genome. At this stage some cells are undifferentiated stem cells, whilst others are determined and building to become specific tissues. Normally a twin’s influence alters the genome through the stem cells, but in this case Mrs McK’s genome remained unchanged. 

Another similar form of a human chimera emerges from ‘twin embolization syndrome’. It is   “a rare complication of a monozygotic twin pregnancy following an in utero demise of the co-twin” (Weerakkody, n.d.). In layman’s terms, a fetus ‘absorbs’ its twin in the womb. This occurs with fraternal twins, if one embryo dies very early in pregnancy, due to absorption the living fetus will have two sets of cells, its original one and the one from its twin. A striking example featured in the news recently. A woman named Karen Keegan needed a kidney transplant and underwent genetic testing along with her three sons, to see if one of them was compatible and could donate to her. However the tests led to a profound discovery that Keegan could not be the mother of her sons. “Initial tests indicated that the three men are brothers, but that two of them are not her sons.” said Lynne Uhl, a transfusion medicine specialist, who was part of the team that discovered Keegan’s chimerism. “ We hypothesized that two eggs were fertilized and very early on fused together. It wasn’t that there actually was a twin that went fairly far along in development then was resorbed, but more likely that very early on the two fertilized eggs fused together” (Wolinsky, 2007).

The third possible type of human chimera arises if they undergo bone marrow transplant. . During these transplants, to treat leukemia for example, the patient will have their own bone marrow destroyed and replaced with bone marrow from the donor. Bone marrow contains stem cells that will develop into red blood cells. The patient who gets the transplant will have the blood cells, for the rest of their life, that are genetically identical to those of their donor. All of the blood cells in a person who received a bone marrow transplant can match the DNA of their donor in some cases. In other cases however, the recipient may have a mix of their own and the donor’s blood cells (Rettner, 2016). According to the Tech Museum of Innovation in San Jose, California, A blood transfusion temporarily gives a person cells from someone else, but in a bone marrow transplant, the new blood cells are permanent (Understanding genetics, 2007).

The more visually obvious chimeras are animal and animal human hybrids and are created in the lab for research purposes, so they can be deemed as ‘artificial’ chimeras. According to Richard R Behringer, an expert in genetics,  “When cell’s of different parent organisms come together to form a chimera, they can incorporate into multiple parts of the chimera’s body. These cells can be somatic cells or they may be incorporated into germline tissues, where specialized reproductive cells, or gametes, such as sperm and egg cells, are produced,” (Vidyasagar, 2016). Chimeric mice, also known as ‘transgenic’ to an extent, are bred for use in genetic research. They contain two types of mouse cells that express different genes: one type is  where mouse cells are intact, the other type is one copy of a particular gene is deleted or “knocked out”. They are a vital tool to investigate critical processes including cell specification, differentiation and the function of specific genes as well as  disease mechanisms or tissue repair and regeneration. (Eckardt et al., 2011) 

Human animal chimeras are formed by human cells and tissues being grafted into embryos, fetuses or adult vertebrate animals, or by introducing human stem cells into animals during various developmental stages. They serve as a useful living environment to help scientists better understand human biology and human disease mechanisms. Behringer justifies that “using laboratory animals as models of human biology or diseases doesn’t fully replicate human physiology. Thus, the primary goal of human-animal chimera research is to produce human cellular characters in animals,” (Vidyasagar, 2016).

There are a number of ethical debates surrounding artificial chimeras. There is a perception that creating human-animal chimeras are a taboo as well as general concerns on animal testing and handling in the lab. “As such, these beings threaten our social identity, our unambiguous status as human beings,” the authors, Jason Scott Robert and Francoise Baylis, wrote. The view that scientists are playing ‘god’ to create new species is a long withstanding controversy but the questions remain if creating these are actually causing scientific  breakthroughs and also to ensure it is a safe and  feasible option.  

References:

Dunsford, I., Bowley, C. C., Hutchison, A. M., Thompson, J. S., Sanger, R. and Race, R. R. (1953) ‘Human blood-group chimera’, Br Med J, 2(4827), pp. 81–81. doi: 10.1136/bmj.2.4827.81.

Eckardt, S., McLaughlin, K. J. and Willenbring, H. (2011) ‘Mouse chimeras as a system to investigate development, cell and tissue function, disease mechanisms and organ regeneration’, Cell Cycle, 10(13), pp. 2091–2099. doi: 10.4161/cc.10.13.16360.

Hagihara, S., Matsubara, S., Kuwata, T., Baba, Y., Shimada, K., Yamanaka, H., Watanabe, T. and Suzuki, M. (2003) ‘Discordant twin: marked vascular communication between separated dichorionic diamniotic placentas’, Twin Research: The Official Journal of the International Society for Twin Studies, 6(4), pp. 267–269. doi: 10.1375/136905203322296593.

MacDonald, J. (2015) Human chimeras, JSTOR Daily. Available at: https://daily.jstor.org/human-chimeras/ (Accessed: 3 November 2020).

‘Natural human chimeras: A review’ (2020) European Journal of Medical Genetics, 63(9), p. 103971. doi: 10.1016/j.ejmg.2020.103971.

Rettner,LiveScience, R. (no date) 3 human chimeras that already exist, Scientific American. Available at: https://www.scientificamerican.com/article/3-human-chimeras-that-already-exist/ (Accessed: 3 November 2020).

Understanding genetics (no date). Available at: https://genetics.thetech.org/ask/ask208 (Accessed: 3 November 2020).

Vidyasagar, A. (2016) Human-animal chimeras: biological research & ethical issues, livescience.com. Available at: https://www.livescience.com/56309-human-animal-chimeras.html (Accessed: 3 November 2020).

Weerakkody, Y. (no date) Twin embolisation syndrome | radiology reference article | radiopaedia. Org, Radiopaedia. Available at: https://radiopaedia.org/articles/twin-embolisation-syndrome (Accessed: 3 November 2020).

Wolinsky, H. (2007) ‘A mythical beast. Increased attention highlights the hidden wonders of chimeras’, EMBO Reports, 8(3), pp. 212–214. doi: 10.1038/sj.embor.7400918.

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