In the laboratories of mother nature, strange experiments are taking place: twins absorb each other right in the womb, the mother is not a mother to her children, and siblings merge into a single organism in order to survive. Geneticists have been catching up with nature for a hundred years, but to this day they have not been able to surpass it. So, we have chimerism
A resident of the United States, Lydia Fairchild, was in for an unpleasant surprise when, after her divorce, she applied for social benefits. Her husband had to confirm paternity by DNA analysis - and the latter showed that it was Lydia who was not the mother of two common children (and at the same time the third, with whom she was pregnant at that time). At first, it was suggested that the cause was a tissue transplant or blood transfusion, but neither the woman nor the children were exposed.
The state has filed a fraud lawsuit. Mrs. Fairchild's attorney saved the situation - he provided the court with an article from the New England Journal of Medicine:
52-year-old Boston teacher Karen Keegan required a kidney transplant. Three of her sons agreed to be donors, but genetic analysis showed that two of them are not relatives of their own mother! Research has established a lot of interesting facts: in particular, it turned out that Karen had a twin sister, who at the early phase of embryonic development merged with the surviving embryo. The Boston teacher turned out to be a chimera - a creature in whose body tissues with different sets of genes are present, without interfering with each other.
In the precedent with Mrs. Fairchild, everything turned out to be even more complicated - the DNA of Lydia's children proved only a relationship with their grandmother, Mrs. Fairchild's mother. It was possible to figure it out only thanks to the analysis of the hair, and the hair on the woman's head and pubis contained different genetic material. Mrs. Fairchild came out dry, and her story in 2006 was devoted to the program "My twin in me".
About forty cases of chimerism have been officially recorded, but in fact there are many more. With a high probability, the famous maniac Chikatilo, whose blood group and sperm data did not match, was a chimera. Sometimes chimerism accidentally pops up during attempts at in vitro fertilization or artificial insemination: scientists from Germany described a patient in whom 99% of the cells in the body contained the female chromosome set XX and 1% - male, XY. As it turned out, her twin brother died at birth, but his cells lived in his sister's body.
And these are just cases reported to the general medical community.
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Paws, wings and tail
The term "chimera" is taken from Greek mythology - it is a "composite" monster with the body of a goat, the head of a lion, a snake's tail, etc. It was generated by ugly monsters - a half-woman-half-snake Echidna and the giant Typhon, but, according to one of the versions, it was killed by Bellerophon. In biology, a chimera, as already mentioned, is a creature with heterogeneous genetic material that coexists in one organism. The term was first introduced in 1907 by the German botanist Hans Winkler, who called the plants obtained as a result of grafting nightshade on a tomato stalk chimeras. Another botanist, Erwin Baur, explained the nature of the phenomenon. And the first "compound" animal was constructed in 1984 - an artificial "mosaic" of a sheep and a goat, a cub of four parents, some of whose cells contained the sheep's genome, and some - the goat's.
Chimerism in plants is the result of natural mutations or grafts, when a branch of a plant of one species is added to the trunk of another. Luther Burbank's experiments with the famous Russet Burbank, a potato variety that now accounts for up to 50% of the potato crop in the United States of America, seedless plums and pineapple-scented quince were mostly the creation of Frankenstein in the plant world.
The famous Michurin did the same, who thoroughly studied how the rootstock (a young plant on which someone else's cutting is planted) affects the yield, viability and other properties of the scion. The "graft versus host" reaction, due to which organ transplants in humans and animals are so dangerous, is in general unusual for plants. The only difficulty is that green chimeras, as a rule, do not pass on their qualities by inheritance, they have to be propagated vegetatively.
Chimerism in mammals can result from several processes, both natural and artificial. The first is the so-called tetragametic chimerism, when two eggs merge together, each of which is fertilized with its own sperm, or two embryos in the early stages of development, as a result of which different organs or cells of such an organism contain a different chromosome set. The "swallowed twin" stories are a typical example of such chimerism.
The second is microchimerism … The baby's cells can enter the mother's circulatory system and take root in her tissues (fetal microchimerism). For example, the immune cells of the fetus can (at least for several years) cure the mother of rheumatoid arthritis, help restore the heart muscle after developing heart failure during pregnancy, or increase the mother's resistance to cancer. Conversely, the mother's cells cross the placental barrier to the fetus (maternal microchimerism). Not without his help, the system of innate immunity is formed: the immune system of the fetus is "trained" to resist diseases, to which the mother has developed immunity. The flip side of this coin is that a child in the womb can become a victim of her own diseases. In particular, such an autoimmune disease,like neonatal lupus, often occurs in children whose mothers have systemic lupus erythematosus.
The third variant of natural chimerism is "twin", when due to the fusion of blood vessels, heterozygous twins transfer their cells to each other (not with the same cells, as in homozygous ones, but with different gene sets, like in siblings). This is how the above-mentioned patient from Germany became a chimera.
The next variant of chimerism is post-transplantation, when, after a blood transfusion or organ transplant, the human body's own cells coexist with the donor's cells. It is very rare, but it happens that the donor's cells are completely "incorporated" into the recipient's body - for example, a few years ago, after a liver transplant, an Australian girl's blood group changed forever.
The last option is a bone marrow transplant, in which doctors make every effort to make a chimera out of the patient and make the transplanted cells work instead of the host's.
The patient's own bone marrow is killed with radiation and special drugs, donor hematopoietic cells are injected in its place and wait. If the tests reveal donor chimerism, everyone is happy, the process is underway, and if we manage to cope with the transplant rejection, there is a chance of recovery. But the return of "native" cells means a quick relapse of the disease.
Laboratory chimeras
The history of chimeric embryos began with the gobies of Dr. Ray Owen and the chickens of Dr. Peter Brian Medawar, thanks to which the mechanism of chimerization was developed.
Calves and Chickens Owen was the first to notice that in twin calves cells with heterogeneous genetic material coexist perfectly in the body, and the reason for this is the fusion of blood vessels. And Dr. Medavar first spliced chicken eggs with sawn-out "windows", then experimented with introducing duck cell cultures into chicken embryos, then began to connect the circulatory systems of chicken embryos, and finally formulated the term "immunological tolerance" - the body's readiness to accept foreign cells. He was the first to transplant the embryos of mice from one pure line of embryonic cells to another, and then transplanted skin flaps to the surviving chimeras to demonstrate that the transplanted biomaterials retain the properties of their native organism and are not rejected at the same time. Scientists in Chicago and Liverpool have engineered chimeras of wood and domestic mice in laboratories, injecting additional genetic material into embryos at the blastocyst stage.
The mice turned out to be quite viable: more active than domestic mice, but less active than forest mice. In Russia, chicken chimeras were successfully raised - white leghorns with red rhodeland tails.
Toy men
Another option for creating chimeras is the introduction of human DNA into an animal's egg. The genetic material of cybrids - cell hybrids - is almost completely human, they receive only mitochondrial DNA from the animal. True, attempts to bring hybrid embryos to the birth of chimeras at the modern level of science are doomed to failure; besides, human cloning and, moreover, the creation of human-animal chimeras are legally prohibited in all developed countries. And there is no point in such complex experiments. Several dozen cybrid embryos, created for purely research purposes, were destroyed a few days after the start of egg division.
Doctors and homunculi
It took scientists about twenty years (since the first successful operation of Dr. Thomas) to learn how to select donors and recipients that are compatible with human leukocyte antigens - proteins, the mismatch of which triggers a cascade of molecular reactions leading to transplant rejection, and to combat rejection with the help of drugs. suppressing immunity. By 1990, about 4,000 bone marrow transplants were performed - fewer than nowadays performed in a year. Now the five-year survival rate (in fact - recovery) for acute leukemia is 65%. Accordingly, it became possible to observe the unexpected effects of chimerism.
Both doctors and relatives of patients have long been ready for the fact that after transplantation the blood group, Rh factor and hair structure may change - but this is by no means all.
The fact that a bone marrow transplant can even cure AIDS is an accidental discovery, the luck of German doctors. It is known that about 1% of Europeans are resistant to HIV. A 42-year-old American, with both lymphoma and AIDS, underwent a bone marrow transplant to treat one of his diseases. And unexpectedly for everyone (including doctors) he was healed of both - his donor turned out to be a carrier of a mutation that provides resistance to the virus, and transferred it to the recipient along with the bone marrow.
Know-how of the XXI century - developments in intrauterine cell therapy. Blood stem cells are injected into a fetus suffering from immunodeficiency, thalassemia, granulocytosis - and theoretically the child should be born healthy. In practice, it was possible to achieve an effect only in fetuses with immunodeficiency; in all other cases, even with minimal chimerism, the disease did not recede. Experiments on complex therapy are being actively carried out on animals: first, the immunity of the fetus is turned off, and then the transplant is carried out. But experiments on humans are still far away.
Chimerism for good
Medicine put the possibilities of chimerism at its service even before this phenomenon was studied in its entirety. In 1940, the first attempt was made to transplant his brother's bone marrow to a patient with aplastic anemia. In 1958, six Yugoslav physicists who were injured in an accident at a nuclear power plant were treated with a bone marrow transplant in Paris, five of them survived. In 1957, in the United States, Dr. Edward Thomas succeeded (after total body irradiation) to achieve graft engraftment in two children with leukemia. The children soon died, and 10 years later, out of 417 transplants performed by Thomas, only three were successful. In 1968, a completely successful transplant was carried out: a child with severe immunodeficiency was injected with the bone marrow of his brother. The patient recoveredbecoming a chimera - instead of its own cells, blood in the body produced "brotherly" ones. And Edward Thomas in 1990 received the Nobel Prize in Medicine.
"Popular Mechanics # 2 2012"