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Chimerism: Where Science Meets Mythology

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Joans Pires Jul 2, 20171 Response

" What a chimera then is man. What a novelty! What a monster... what a contradiction, what a prodigy." -Blaise Pascal

 

 

The Chimera, in Greek mythology, is a famously fierce creature having parts of various creatures – it had the head of a lion, body of a goat, back of a serpent – all whilst possessing the savageness of a beast and human-like intelligence. Though Chimera is a broad term often applied to many different mechanisms of mixing of cells from two different species; Chimeras, in the field of genetics, are living creatures that contain two or more genetically distinct lines of cells that originate from one or more different zygotes. In simple terms, chimeras are complexes of two genetically different organisms.

 

The existence of chimeras has been noted by scientists for long: examples being the extremely rare fertile male tortoiseshell cat that carries both male and female chromosomes due to the fusion between the brother and sister embryos during fetal attachment. The parasitic chimerism that occurs in Ceratioid Anglerfish wherein the ceratioid male attaches itself to the chosen female fish, slowly fusing its body to that of the female thus forming a chimera. In such a case, the male is nourished by the female fish via their interconnected circulatory systems and eventually loses most of its organs and focuses on the development of testes, thereby reaching sexual maturity. Germline chimerism occurs when germ cells i.e. sperm and egg cells of an organism are not genetically identical to that of its own; a common example of it being discovered in marmosets who always give birth to fraternal twins and are seen to carry reproductive cells of their twin siblings. Natural chimeras are rarely detected unless they exhibit various abnormalities such as male/female or hermaphrodite characteristics or uneven skin pigmentation or in cases of animals ambiguous sex organs.

Tortoiseshell cat (source: Pinterest)
Chimerism, in the case of humans, is quite rare and occurs in two specific types: microchimerism and tetragametic chimerism. Microchimerism is when only a specific portion of the body has a distinct cell line from the rest of the body. Microchimerism usually occurs due to stabilisation of foreign cell inside the host. The foreign cells may originate from the maternal-fetal exchange during pregnancy wherein the fetus may pass its stem and progenitor cells to the mother via placenta and these cells may be able to survive and proliferate in the maternal system due as they are undifferentiated. Tetragametic chimerism occurs when two separate ova are fertilised by two sperm and in turn produce two zygotes. The fusion of these zygotes forms an organism having two distinct cell lines wherein the resulting fetus may be male, female or hermaphroditic usually occurring in fraternal (dizygotic) twins often forming in zygotes produced artificially through in vitro insemination. For example, a certain set of DNA may appear in his/her reproductive organs while another in his or her stomach.

 

In humans, post fertilisation an egg embeds itself to the walls of the uterus where it starts to develop. Given the egg is microscopic at this point; the uterus has more than enough space to accommodate fraternal twins (two fertilised eggs). In an absorption process called the Vanishing Twin Syndrome, the two eggs embed themselves quite close to each other where in some cases one growing zygote is absorbed by another creating a being with two DNA coding sequences. Generally, one of these two sequences will dominate most of the body’s tissues while cells from the other zygote will continue to replicate itself and spread throughout the body, creating body tissues in the right places but different DNAs.  In this case of foreign DNA, the immune system recognises the resulting foreign tissue as natural and does not attack the foreign tissue as it would otherwise result in the unpredictable functioning of the said tissue.

 Ultrasound of Vanishing Twin Syndrome  (Image via Flickr/ Anfueher)

It has been taught to us for as long as we can remember that our genetic composition is our unique identity having forged a link between genomes and individuality wherein ones’ genetic system matches with only one genetic body. A juxtaposition to that are human chimeras who possess two different sets of DNA, wherein the DNA may or may not be manifested as physical abnormalities. It may appear as differential hair growth, phenotypical difference in eye colour, “checkerboard” skin patterns or missing or extraneous sexual organs. Human chimeras, in most cases, are not aware of their conditions. Some famous cases of chimerism till date are the linked cases of Lydia Fairchild and Karen Keegan.

 

Lydia Fairchild, who then pregnant with her third child, in the event of her separation from her partner James Townsend, was required to prove her biological relationship with her two older children in order to obtain state welfare. Unfortunately, for Fairchild the DNA tests proved negative making it impossible, on paper, for Fairchild to have conceived and given birth to her children as they bore no genetic similarity to her whatsoever. The prosecution believes the DNA tests to be irrefutable proceeded to prosecute Fairchild for illegal surrogacy and welfare fraud – even threatening to take her children away from her. The conflicting evidence in favor of Fairchild eventually (among which was the testimony of Dr. Leonard Dreisbach, the obstetrician who had helped Fairchild give birth), resulted in the Washington State court ordering immediate DNA tests of her third child at birth, which to Fairchild’s own surprise showed no genetic similarity to her – the mother.

 

A similar experience was recorded in the case of Karen Keegan. Keegan in need of a kidney transplant began testing for a DNA match but failed to match with her two eldest sons who showed no genetic similarities to her. Fortunately for her, the doctors working with her, were familiar with the concept of chimerism and suggested further testing.  Further testing of her brothers and husband to her sons resulted in a DNA match. Though subsequent testing of her hair and skin proved to be futile; eventually a DNA match was found in her thyroid gland.

 

Lydia Fairchild was found to be a genetic chimera with a second set of DNA found in her cervical smear as per the report by New England Journal of Medicine. The conclusion given was that both Keegan and Fairchild were tetragametic chimeras.

 

The existence of chimerism is seen as an acknowledged problem for DNA testing with severe implications for family and criminal law. The cases of Fairchild and Keegan challenged the blind faith placed in the irrefutability of DNA testing by the scientific community. Forensic science can no longer rely on DNA testing as the sole source of evidence as done before due to the reaffirmation of the concept of chimerism. From the cases mentioned above; it can be said that maternal and paternal DNA testing can be contested against and will have to be reevaluated. The unknown effects of chimerism on individuals’ and the accomplishments of the same will continue to puzzle the scientific medical field more than before with the current research indicating two opposing views of chimerism in humans. The first hypothesis argues that the presence of foreign cells in the body during development cause growth of various autoimmune diseases such as scleroderma, Type 1 diabetes and lupus while the other argues that these foreign cells facilitate the body’s ability to self-repair. Research studies are looking into using chimerism as a basis for improving the existing organ transplant process that would hopefully result in lower risks of organ rejections as chimeras host two DNA lines and are capable of receiving organs from individuals with either set of DNA. Chimeras are known to have immunological tolerance to at least two different cell lines leading to theories that suggest the potential for drastic improvement in the field of medicine with the most promising future for chimeras lying in the field of genetic engineering.

 

While true genomic chimeras of humans and animals are yet to be produced, surprising studies of the successful production of hybrid embryos or cybrids have been mentioned and animal chimeras have been artificially produced by physically mixing two zygotes together. Notable example being: “geep” chimera, produced in 1984 by British scientists, comprises of goat and sheep cells. A 2003 study at the Shanghai Second Medical University was successful in producing stem cells by merging rabbit cells to human skills cells resulting in the supposed first human-hybrid of this kind to be produced. Though, the hybrid produced was promptly destroyed in a few days after extraction of the live stem cells. The process of doing this is simple: genetic material is removed from an animal ovum followed by the insertion of human DNA thus resulting in the production of a single zygote having animal-human origins in what could be the cheapest way yet to produce human stem cells for research purposes.

A sheep-goat chimera "geep" (source: www.ansci.wisc.edu)

While geeps, chimeric mice and human-infused mice pioneer the stem cell research; they are only allowed to do so due to their rooted animal nature. They lack the concept of individuality and do not possess any human-like behavior that would result in ethical and moral disagreements. Chimerism studies lie on the fine line between ethical and unethical. Several questions arise on the field : Will scientists cross a fine line between humans and animals if a chimera having a subsequent percentage of DNA of both human and animal was ever to be produced? Will this breach ethical and moral boundaries? And if yes, who will define the boundaries for the studies to be conducted? Should true human-animal chimeras ever be created? How far will these studies go?

 

Heart transplants use porcine valves, researchers have produced pigs with human blood and sheep with partial animal organs. The possibilities of studies on chimeras are known to be endless and without any regulation, they could easily get out of hand resulting in creations far beyond our control. Like any technology of the past chimera research could be a double-edged sword that could either provide a great benefit or inflict great pain on humanity.  

 


Works Cited

  • fauzishaikh125155553001478983376
    fauzia bi

    Chimerism seems to be a big challenge to genetics and DNA fingerprinting technique, which is considered a solution to all genetic and paternity issues. But DNA fingerprinting isn't useful in the case of chimerism. Very Interesting.