Chimera. The word’s unusual origin stems from Greek mythology and refers to a fire-breathing she-monster that has a lion’s head, a goat’s body, and a serpent’s tail. Nowadays, scientists and medical professionals apply the word chimera more broadly. Chimeric therapies research is exploding, complicated, vast and controversial.
Individuals Who Are Chimeras
By definition, a chimera is a single organism that contains at least two distinct sets of DNA. Each DNA code could create separate organisms. Oftentimes, one set of DNA is found in the blood and the other set in the tissues.
One form of chimerism, fraternal twin absorption in the womb, where the fetal tissue is absorbed by the other twin, placenta or the mother, is a rare condition. This gives the appearance of a “vanishing twin.” Chimeras are usually not visibly different, unless there is a developmental anomaly in one of cell lines. Heterochromia, the condition of having two distinct eye colors, quite common in certain dog breeds, could be a result of chimerism, melanin concentration in the eye or another genetic condition called mosaicism. Essentially, you could be a chimera and not even know it until thorough genetic testing is done.
The same applies to dogs and cats. If you search the internet for “chimera dog” or “chimera cat”, you may be surprised by the headlines stating, “Mixed Breed Dog with Unusual Coat Might Be a Chimera.” This may be true, but it could lead one to assume that all mixed breed dogs and cats are chimeras. Remember, a dog or cat would have had to absorb a twin in utero in this instance. So, a mixed breed dog or cat could or could not be a chimera – the same applies with a full-bred dog or cat.
Two other known forms of chimerism can occur and are recognized at this time: in bone marrow transplant recipients and fetal microchimerism.
Bone marrow transplants are commonly used to treat leukemia, one type of blood cell cancer. A recipient’s bone marrow – that is destroyed through radiation or chemotherapy – is replaced with healthier bone marrow from a species-matched donor. Red blood cells are then produced by the bone marrow’s “mother” stem cells. So, a recipient will have all blood cells that are genetically identical to those of the donor for life or a mix of his blood cells and that of the donor.
Fetal microchimerism is another condition whereby cells from a fetus travel into a woman’s bloodstream and to her other organs. It is unknown how long the cells will last in the body and the situation is likely case-specific. One research study involved analyzing the brains of women who had passed away between the ages of 32 and 101 – 63 percent had traces of male DNA from fetal cells in their brains; the oldest of these microchimeric women was 94 years of age.
A 2013 study banked whole blood from female Golden Retrievers who had had at least one male in their litters from three months to eight years before the whole blood collection. It turned out, that 36% of the mothers had positive Y-chromosome bands. Further, there was no correlation between the time of blood analysis after the litter and Y-chromosome band intensity.
Chimeric Vaccines
There are several applications of chimeric vaccines. One such application is a chimeric protein which is created by joining together several proteins to form a single hybrid protein. To make a chimeric protein, the DNA sequences that encode the desired segments to be included are “recombined” into a piece of DNA referred to as a “recombinant”.
One example is a Lyme Disease vaccine for dogs. It is currently marketed as a chimeric protein vaccine to protect dogs from a broader spectrum of the outer surface proteins that the bacteria, Borrelia burgdorferi, may produce in the body.
Prior to this vaccine, many of the Lyme Disease vaccines only protected against outer surface protein A (OspA) and possibly one outer surface protein C (OspC). So, this vaccine contains not only protection against OspA, but also a chimera of OspC. The chimeric OspC component consists of seven OspC types that have been demonstrated to stimulate antibody production in mammals.
Chimeric Treatment for Cancer
In addition to bone marrow transplants and the ongoing research into DNA cancer vaccines, Chimeric Antigen Receptor (CAR) T-Cell Therapy is an approved type of cancer immunotherapy. CAR refers to genetically engineered molecules manufactured in a laboratory, hence the reason why the word chimeric is applicable here. The process uses the T- cells of the individual who has cancer.
- White blood cells and T-cells are separated from the rest of a patient’s blood via a process called leukapheresis. The blood is then returned to the patient’s body.
- The T-cells are sent to a laboratory.
- The laboratory engineers and increases the amount of active T-cells that can then find and kill cancer cells.
- After approximately one to two weeks and a round of chemotherapy, the T-cells are reintroduced to the patient’s bloodstream.
- Once inside the body, the CAR T-cells identify the cancer cells with the target antigens and kill them. CAR T-cells also may remain in the blood for some time to help prevent the cancer cells from returning.
Does this turn someone into a chimera like bone marrow transplants? Technically, no, because the genetic DNA of another person is not taking over that of the patient. However, researchers may use the word “chimerism” to refer to the presence of cells from a third-party source to indicate the persistence of the CAR T-cells and absence of rejection.
Chimeric Species
The scientific journal, Cell, published a study on human-pig embryos – reigniting the ethical debate on interspecies chimeras. These ethical concerns are a heated topic that could potentially never be resolved. Nevertheless, the study results were fascinating.
In this study, the researchers wanted to see about growing transplantable human tissues and organs to address the worldwide shortage of organs. So, they injected human stem cells into pig embryos to create a chimera. The embryo was then implanted into a sow for up to one month. Of the 2,075 implanted embryos, only 186 continued to develop up to the 28-day stage. Interestingly, signs indicated that the human cells were functioning – albeit as a tiny fraction of the total tissue – within the human-pig chimera.
Please note that scientists distinguish the biological differences between chimeras and hybrids. A cell from a chimera contains the genetic material of either one parent species or the other. While each cell from a hybrid animal, such as a mule, contains genetic material from both parent species (donkey and mare).
References
Axiak-Bechtel, Sandra, et al. “Y-Chromosome DNA Is Present in the Blood of Female Dogs Suggesting the Presence of Fetal Microchimerism.” PLoS ONE, vol. 8, no. 7, 8 July 2013. http://doi.org/10.1371/journal.pone.0068114.
Bolhassani, Azam, and Sima Rafati Yazdi. “DNA Immunization as an Efficient Strategy for Vaccination.” Avicenna Journal of Medical Biotechnology, vol. 1., no. 2, 2009, pp.71–88, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3558129/.
Boklage, Charles. “Embryogenesis of Chimeras, Twins and Anterior Midline Asymmetries.” Human Reproduction, vol. 21, no. 3, 1 Mar. 2006, pp. 579–591, http://doi.org/10.1093/humrep/dei370.
Chimeric Antigen Receptor (CAR) T-Cell Therapy, Leukemia & Lymphoma Society, https://www.lls.org/treatment/types-treatment/immunotherapy/chimeric-antigen-receptor-car-t-cell-therapy.
Kenderian, Saad, et al. “Chimeric Antigen Receptor T Cells and Hematopoietic Cell Transplantation: How Not to Put the CART Before the Horse.” Biology of Blood and Marrow Transplantation, vol. 23, no. 2, Feb. 2017, pp. 235–246, https://pmc.ncbi.nlm.nih.gov/articles/PMC5237606/.
Pandya, Aanshi et al. “The future of cancer immunotherapy: DNA vaccines leading the way.” Medical Oncology (Northwood, London, England) vol. 40,7 200. 9 Jun. 2023, doi:10.1007/s12032-023-02060-3, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10251337/.
Rettner, Rachael. “3 Human Chimeras That Already Exist.” Scientific American, 8 Aug. 2016, http://www.scientificamerican.com/article/3-human-chimeras-that-already-exist/.
“VANGUARD CrLyme.” Zoetis US, https://www.zoetisus.com/products/dogs/vanguard/vanguard-crlyme.
Wu, Jun, et al. “Interspecies Chimerism with Mammalian Pluripotent Stem Cells.” Cell, vol. 168, no. 3, 26 Jan. 2017, pp. 473–486, https://pubmed.ncbi.nlm.nih.gov/28129541/.
Originally Posted: October 21, 2018; Updated: September 15, 2024