Chimerism

This article reviews the history and present state of research on the creation of human--animal hybrids and chimeras. The idea has been present in culture since ancient times and was picked up by scientists a long time before breakthroughs in DNA were made.
Scientifi c experiments in the fi eld of chimerization and hybridization are a continuation of thought experiments expressed in a variety of cultural texts and artefacts throughout 208 Magdalena Kozhevnikova
the history of mankind. The author reviews the scientific implementation of this ancient idea – from simple transplants between different species and different sexes to xenotransplantation
and further on to genetic engineering.
Today’s development of individual stem cells therapies and the production of new medicines and healthcare products are claimed to be the goal of such research, yet in the future, “upgrades” (enhancement) of people with animal genes and the transfer of selected biological characteristics to the human species will become realistic possibilities.
Due to the unpredictable consequences of such research, both concerning individuals and humankind, such a prospect raises serious concern among scientists. As a result, questions appear regarding the potential threat to humankind, which in turn calls for the revision of the concept and development of a new vision of who “man” is in this age of
biotechnology.

The lack of a biological basis for conditions such as gender dysphoria (GD) or transgenderism has caused much stress over the years among social and scientific factions alike.  The classical theory of hormone differentiation points to gonadal hormone levels as the cause of sexual differentiation throughout the body.  However, many studies have not only cast doubt on this theory but supported the genetic theory of differentiation—that the sexually dimorphic areas of the body—in particular the brain—differentiate due to direction by genetic information on sex chromosomes.  Two genes in particular have been implicated in this process: SRY and Z.  Additional studies have implicated certain areas of the brain as the most likely candidates for determining gender-specific behavior and therefore responsible for sex discordances when sexually differentiated in opposition to the individual’s primary physical sex characteristics.  This paper presents possible methodology for how these sex discordances could arise, specifically pointing to dual-gender tetragametic chimerism or other possibilities such as chromosomal nondisjunction or translocation between the X and Y chromosomes, resulting in mislocation of either the SRY or Z gene among the DNA of individual cells, thus leading to a discordance between sexually dimorphic areas of the brain including the BSTc and the presumed sex of the individual.  This research, by tying theories of the prevalence of chromosomal abnormalities to research surrounding sexually dimorphic areas of the brain and their influence on gender identity has the potential to cast light on an issue that has as of yet been kept in scientific and social darkness.

A large number of autoimmune diseases (ADs) are more prevalent in women. The more frequent the AD and the later it appears, the more women are affected. Many ideas mainly based on hormonal and genetic factors that influence the autoimmune systems of females and males differently, have been proposed to explain this predominance. These hypotheses have gained credence mostly because

Imagine being told by a doctor that a twin, one you never knew you had, exists inside you. It is well known that fraternal twins arise from two fertilized eggs that develop into nonidentical siblings. Less well known is that these two zygotes sometimes overlap and fuse so completely as to develop into one body with two distinct sets of DNA, a phenomenon called tetragametic chimerism (Tippett 1983). We explore how this rare occurrence exposes complex links between understandings of DNA, human subjectivity, and definitions of motherhood. We focus on cases in the United States of two chimeric women, Lydia and Karen, who were subjected to genetic tests for parentage and subsequently deemed by medical authorities not to be the mothers of their children. The stories of these two women offer opportunities to investigate how definitions of motherhood are constructed, legitimized, and contested by and through science.

I present literature evidence that suggests that human chimerism may be quite common, occurring in between 5% and 15% of people. Chimerism has been believed to be rare because it usually presents without visible phenotype. In addition to the documented occurrence of dual gender macro-chimeras with true hermaphrodite phenotype, there are reports of the occurrence of other natural human macro-chimeras. The literature reviewed in this paper suggests that such macrochimerism is much more common than usually appreciated. Chimerism occurs in a patchy manner, with male cells outgrowing female in macro-chimerism causing the majority to be phenotypically male. The literature also suggests that the sex of nervous system tissue is the primary determinant in higher animals of sexual attraction.  From this, the existence of human macro-chimeras in which large proportions of cells are male and female is predicted to have a correlation with homosexuality and transgender self-identification because in many such cases, the central nervous system, or crucial parts of it, will be of one sex and the gonads and body form will be of the opposite sex. I describe experiments to further calarify this hypothesis, which can also have potential benefit beyond this specific question.

Although improvements in conventional treatment have enhanced the prognosis of thalassaemia, stem cell transplantation remains the only cure. Over the last 2 decades, progress in preventive strategies, effective control of transplant related complications and development of new preparative regimens, have considerably improved the results of transplants from HLA-identical siblings. Currently class 1, class 2 and class 3 patients receiving bone marrow transplantation (BMT) from an HLA-identical related donor have 87, 85 and 80% of probability of thalassaemia-free survival. The results of transplant in adult patients treated with current protocols are less successful. This study reports experience with BMT for thalassaemia.

Abstract. The chimaera is female and has two children. Her blood contains 99% group 0, type AcP: BA, Pep-A: 8–2 and 1% group A2B, type AcP:RA, Pep-A: 1 red cells. H-, A- and B-transferase activities were demonstrated in her serum. The level of the H enzyme activity is low but is at the lower end of the normal range for group 0 persons. The levels of the A and B enzymes are also low but are higher than expected in a person with 1% A2B red cells in the blood. The levels of the A and B enzymes indicate that tissues other than the chimaera's haemopoietic tissue carry her genetically A2B cell line and are contributing the corresponding transferases to her plasma. Gross patchy skin pigmentation is present on the upper part of her body. The chimaera has evidently inherited two dissimilar germ nuclei from each parent.

Ibridazione, Totem e Chimere. Alcune considerazioni sulla mostruosità e sull'ibridazione.
Lavoro sviluppato nell'ambito del corso di Antropologia dell'Immagine del mondo greco di Elisabetta Villari.

La cultura occidentale, affonda le radici del proprio razionalismo nella cultura della Grecia antica e la Grecia antica affonda a sua volta le proprie radici culturali nel mito, nella genealogia degli dei, nella tradizione della cosmogonia come metafora di diversi enti e forze che interagendo tra loro hanno creato il mondo e l'universo; gli dei e le storie ad essi connesse incarnavano la personalizzazione e divinizzazione delle forze naturali, metafore antropomorfe o zoomorfe degli istinti primari, delle virtù e dei vizi universali o delle forze naturali manifeste con cui gli esseri umani da sempre si confrontano. Un pantheon di divinità dalle caratteristiche umane, simboli e animali ad essi associati deve la  propria esistenza nel modo di osservare dell'uomo la natura simbolica del mondo.

The author starts from stating the counterintuitive nature of chimerical beings, including both types of Greek horse-men – resp. centaurs and satyrs. One source referring at once to two (or more) different classification categories, on one hand, draws extra attention as a semantic anomaly, and on the other, makes a recipient to believe in additional meaningfulness and ‘alienness’ of a chimera, provoking a feeling close to a religious one. Any counterintuitive chimera is good when alongside a semantic aporia, crucial for giving the message a higher communicative status, it offers some additional semantic link that allows the recipient a possibility to pass over this aporia – usually through a reference to some other culture code, by means of which the opposed notions could be in some way put together. For the horse-men such link is to be found in culture practices having rather strict social and gender connotations – namely, in the practices going together with the pre-adult male statuses. Early centaur imagery shows us not a body of a stallion with a male torso, but a full male figure with the genitals clearly defined – combined with a croup of a mare with no less clearly defined lack of male genitals. The mythoi dealing with centaurs work out characteristics emphasizing, on one hand, the hypertrophied male features and, on the other hand, the features incompatible with a (high male) citizen status. Satyrs embody the same set of characteristics with the accents put in other way, presumably referring to other genre frames and/or imagery-producing contexts.

For decades, it has been widely accepted that the heart is a terminally differentiated organ that is unable to regenerate. Studies of recipients of hearts donated by other humans have shed light on the regenerative potential of the human heart. Investigators have been able to trace the Y chromosome by fluorescence in situ hybridization or polymerase chain reaction, or both,

Severe combined immunodeficiency (SCID) represents a group of rare, sometimes fatal, congenital disorders in which there is a combined absence of T-lymphocyte and B-lymphocyte function. Children with SCID die within two years of age, if untreated. The effective treatment for SCID is a hematopoietic stem cell transplantation (HSCT). It has been repeatedly described that in peripheral blood of infants with SCID maternal T cells can be found. Here we report a case of blood chimerism in a one-year-old boy with SCID.

The main function of hemoglobin (Hb) is to transport oxygen in the circulation. It is among the most highly studied proteins due to its roles in physiology and disease, and most of our understanding derives from comparative research. There is great diversity in Hb gene evolution in placental mammals, mostly in the repertoire and regulation of the β-globin subunits. Dogs are an ideal model in which to study Hb genes because: 1) they are members of Laurasiatheria, our closest relatives outside of Euarchontoglires (including primates, rodents and rabbits), 2) dog breeds are isolated populations with their own Hb-associated genetics and diseases, and 3) their high level of health care allows for development of biomedical investigation and translation. We established that dogs have a complement of five α and five β-globin genes, all of which can be detected as spliced mRNA in adults. Strikingly, HBD, the allegedly-unnecessary adult β-globin protein in humans, is the primary adult β-globi...

Post-hematopoietic stem cell transplantation (HSCT) chimerism monitoring is important to assess relapse and therapeutic intervention. The purpose of our study is to compare two methods variable number tandem repeats (VNTR) vs. quantitative real- time polymerase chain reaction (qPCR) in terms of determining chimerism. 127 (peripheral blood n=112, bone marrow n=15) samples were simultaneously tested by VNTR using APO-B, D1S80, D1S111, D17S30, gene loci SRY and ZP3 and qPCR using 34 assays (CA001-CA034) that are designed to a bi-allelic insertion/deletion (indel) polymorphism in the human genome. Samples were separated in three subsets: total WBC, T-cell and Myeloid cells. Extraction of DNA was performed then quantified. We analyzed column statistics, paired t-test and regression analysis for both methods. There was complete correlation between the two methods. The simplicity and rapidity of the test results from the qPCR method is more efficient and accurate to assess chimerism.

In seinem Buch Wir sind nie modern gewesen behauptet Bruno Latour, das moderne Denken gründe auf dem Prinzip der kritischen Differenzierung: Es sei durchdrungen von einem Denkstil der Reinigung. Selbst in den Fällen, in denen die Existenz von Hybriden anerkannt wird, betrachtet das moderne Denken diese »als Mischung zweier reiner Formen« – ja, die modernen Erklärungen bestehen darin, »die Mischwesen aufzuspalten«.
Sobald wir »unsere Aufmerksamkeit dagegen gleichzeitig auf die Arbeit der Reinigung und der Hybridisierung richten, hören wir sofort auf, gänzlich modern zu sein«. Die Figur, in der sich dieser noch-nicht-moderne oder nicht-mehr-moderne Denkstil am Prägnantesten manifestiert, ist die Chimäre: »Vorn ein Löwe und hinten ein Drache und Ziege in der Mitte«, wie es in Homers Ilias heißt – aber natürlich haben auch Zentauren – vorne Mensch, hinten Pferd – den Charakter von Chimären. Wenn ich es recht sehe, dann genügt der Hybriditätsbegriff allein nicht aus, um derartige chimärische Konfigurationen zu beschreiben. Diese zeichnen sich – so meine These – dadurch aus, dass sie Hybridität als spezifischen Modus des Kompositorischen repräsentieren, nämlich als konzeptionelles cut and paste im Sinne der Aufpfropfung.

A 12-year-old male with pre-B-cell acute lymphoblastic leukemia with cryptic BCR/ABL rearrangement underwent sex-mismatched allogeneic bone marrow transplantation (allo-BMT). Contradictory results were provided by various chimerism analyses 3 months later. Y-chromosome-specific quantitative polymerase chain reaction and sex chromosome-specific interphase fluorescence in situ hybridization (i-FISH) showed complete donor chimerism. Analysis of autosomal short tandem repeats (A-STR), BCR/ABL i-FISH test, and X-STR haplotype indicated relapse. Metaphase-FISH and combined BCR/ABL and sex chromosome-specific i-FISH patterns revealed loss of the Y-chromosome and duplication of the X-chromosome in the host cells. Sex chromosome changes after allo-BMT can cause significant difficulties in chimerism analysis. Pediatr Blood Cancer. 2010;55:1239–1242. © 2010 Wiley-Liss, Inc.

Male microchimerism, the presence of a small number of male cells, in women has been attributed to prior pregnancies. However, male microchimerism has also been reported in women with only daughters, in nulliparous women and prepubertal girls suggesting that other sources of male microchimerism must exist. The aim of the present study was to examine the presence of male microchimerism in a cohort of healthy nulliparous Danish girls aged 10-15 y using DNA extracted from cells from whole blood (buffy coats) and report the association with potential sources of male cells. A total of 154 girls were studied of which 21 (13.6%) tested positive for male microchimerism. There was a tendency that girls were more likely to test positive for male microchimerism if their mothers previously had received transfusion, had given birth to a son or had had a spontaneous abortion. Furthermore, the oldest girls were more likely to test positive for male microchimerism. However, less than half of microc...