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. The research around chimeric therapies 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, is considered rare. One could actually rebuke this assertion. 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 may 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: 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 protein are 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 DNA vaccines are the next generation of DNA vaccine advances to help protect or fight infectious diseases, cancer, and autoimmune conditions. Researchers were finding that naked DNA (meaning no proteins attached) induced humoral as well as cellular immune responses with high efficiency, such that their potency in human clinical trials was shown to be insufficient for protective immunity.
So, chimeric DNA vaccines are now being actively explored. The research is exploding, the combinations are endless, and findings can be difficult to explain in simple terms. At the most basic level, one study created a chimeric gene by putting Dengue virus on a Japanese encephalitis gene backbone. The results showed high neutralizing antibody titers with less Dengue virus infection-enhancing activity. In essence, by combining the DNAs from these two diseases, the researchers were able to produce a more effective vaccine against Dengue virus.
Another study took two copies of a DNA found on a tuberculosis protein and inserted them into another tuberculosis gene of another protein. Mice were given this vaccine after either a tuberculosis infection or a clinical multi-drug resistant tuberculosis isolate. Unfortunately, both groups of mice treated with this chimeric vaccine actually had accelerated mortality. According to the researchers of this study: “These findings are in contrast with previous results, which indicated that DNA vaccines expressing the individual antigens were either beneficial or at least not harmful. The results of the present study suggested that the ESAT-6 antigen is not suitable for inclusion in therapeutic vaccines.”
Other researchers are more cautious and argue the introduction of a foreign DNA actually disrupts a cell’s natural DNA sequence. Additionally, we do know what type of adverse reactions, if any, can occur with DNA vaccines. Regardless, research continues and science should prevail on this debate.
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 exciting and recently 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.
On January 26, 2017, the scientific journal, Cell, published a study on human-pig embryos – reigniting the ethical debate on interspecies chimeras. The ethical concerns are a heated topic that could potentially never be resolved. Nevertheless, the study was conducted and the 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.
It should be noted that scientists do distinguish the biological differences between hybrids and chimeras. 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).
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