This is a reflection on the proposed new legal regulation on the phenomenon of transgenderism, which introduces aspects in the legal, social, educational and moral spheres that merit an assessment.

We shall analyze some of them that I believe are of particular interest, proposing arguments from the scientific evidence that may illustrate the subject with some objectivity.

“Sex assigned at birth”

The preamble already uses this terminology, common in the context of gender ideology, which underlies the content of the entire bill. Biological sex, to which the term “assigned at birth” seems to refer, is not the one accorded to each individual at the time of their birth, but the one they possess from the moment of their conception, i.e., since they commenced their journey as a human being. Thus, the chromosomally-determined sexual identity, which results from the chromosomal crossing over that occurs after fertilization, forms a sexed male or female identity from the earliest evolutionary stages of the embryo. This biological identity, which can in fact be known in the very early stages of pregnancy by determining the karyotype of the embryo’s cells, remains unchanged during the life of the individual. Incidentally, not only are the X and Y chromosomes involved in defining the sexed nature of the individual, but today we know that other chromosomes are also involved in the process of phenotypic differentiation that accompanies the individual throughout their life.

Genetic basis of sexual dimorphism

Sex is genetically determined in the individual even before the embryo is exposed to different levels of hormones, such as testosterone or estrogens. Specifically, of the 23 pairs of chromosomes of the human species, the XX or XY pair determines sex. This depends on the sperm that fertilizes the egg, which can provide an X or Y chromosome, which will form the XX or XY pair, together with the chromosome provided by the mother, which is always the X chromosome.  Additionally, the SRY gene in region 1 of the short arm of the Y chromosome determines the process of masculinization in the seventh week of gestation and the Tfm gene, located on the X chromosome, encodes the receptor for the male hormones. The ODF region on the X chromosome also favors the development of the ovary and inhibits that of the testis.

In embryonic development, the activation of certain sexed genes leads to the silencing of their counterparts of the other sex. Thus, the H19 gene is silenced on the paternal chromosome while the Igf2 gene is silenced on the maternal one.

But there is yet more genetic control. Not only are the X and Y chromosomes involved in sexual differentiation, but the gene encoding the synthesis of anti-Müllerian hormone by the Sertoli cells of the testis is on the short arm of chromosome 19 and the Gadd45g gene, which is on chromosome 9, is also critical in masculinization, and interacts with the SRY gene (Johnen et al., 2013).

When does sexual differentiation begin in the individual?

Sexual differences can be evidenced in the early embryo and in its preimplantation phase, i.e., in the first 15 days of life, where the hormonal influence of the environment has not yet manifested. From the first cell divisions of the zygote in the preimplantation phase, it can be observed that the male and female embryos follow different pathways. Thus, for example, glucose consumption levels are significantly different in the male and female, with growth rates and morphologies also different, even at such an early stage of embryonic development (Gardner, Larman, & Thouas, 2010).

After birth, and before the environment can tilt the balance toward one or another sexual behavior, it appears that there is an innate predisposition to sex-differentiated social behavior in humans. Such behavior is independent of the environment and education received. “Male infants show a stronger interest in the physical-mechanical mobile while female infants showed a stronger interest in the face. The results of this research clearly demonstrate that sex differences are in part biological in origin” (Connellan, Baron-Cohen, Wheelwright, Batkia, & Ahluwalia, 2000).

Hormones and sexual differentiation

Both in later embryonic development and after birth, hormone levels are decisive in the progression of sexual differentiation already determined from genetics. The maternal hormones will influence this progression, but so too will those of the individual themselves, which, as well as the receptors of these hormones, will be configured according to their genetic program. For example, estradiol, which is synthesized in the hippocampus and prefrontal cortex of our brain, is a modulator of the cognitive processes of learning and memory and also of mood, social behavior and various psychiatric disorders (Luine, 2014). Similarly, high testosterone levels reduce the expression of the enzyme DNA methyltransferase. This causes a decrease in DNA methylation (epigenetic mechanism), allowing the expression of genes related to masculinization (Nugent et al., 2015).

Environment and sexual differentiation

That said, an influence of the “molecular environment”, i.e., hormones, drugs, toxins, etc. on the progression of masculinization or feminization during pregnancy cannot be excluded. However, in no case is it a “sexual definition towards the male or female”, but interference to a variable degree in the progression of the already genetically established definition.

We could say that the different degrees of genetic expression, together with the biochemical environment of the fetus, may mark degrees of intensity in the processes of masculinization or feminization, but not interchanges between one or other state that, as we have said, has been determined from the chromosomal crossing over.

Finally, the possibility that the genome could undergo epigenetic changes caused by stimuli from the environment to such an extent that they were able to modify sexual behavior has been proposed as a possible explanation for this conduct, but to date, there is no scientific evidence to justify it per se.

Disorders of Sexual Development: Are there more than two sexes?

Recent research raises the possibility of considering the sexed reality not as a binary entity (male and female), but as a spectrum at whose boundaries the male and the female would be situated, and that would harbor a whole gradient of intersex states, in which there would be no clear identification with any of the “extremes”, male and female (Ainsworth, 2015).

The author bases her argument on the existence of so-called Disorders of Sex Development (DSD), which consist of the manifestation of abnormalities in the genotypic and phenotypic constitution that cause certain individuals to present either ambiguous genitalia, or virilizing traits in women or feminizing traits in men. Their origin is usually defects in certain genes that can disrupt both the anatomical structure of the genitals and external sexual characteristics, as well as endocrine function and fertility.

In my opinion, the author draws conclusions inconsistent with the evidence from the data she provides. Considering that the existence of genetic anomalies (some known and others not) responsible for alterations in the establishment of the male and female sex in some individuals would justify redefining the sexes, adding a whole spectrum of variants or possibilities that would traverse the space between male and female, would mean raising the exception to the status of norm.

The anomalies that the author collects and details in her article as DSD are still anomalies, something very different from the physiological manifestation that, in a state of homeostasis, the individuals of the human species present in the form of males or females.

The actual frequency of intersex states (males with female sexual structures and vice versa) is extremely low, more than 100 times lower than that indicated in this article, as stated by other authors (Sax, 2002). We are talking about rare exceptions to the norm marked by nature.

Furthermore, the article overlooks the reality that the male and female sexual makeup pursues the biological end of procreation; therefore, it confers fertility on both sexes, ensuring perpetuation of the species. However, “intersex” states, as defined by the author, are generally sterile, precisely because they are phenotypic manifestations of genetic errors that compromise the normal development of anatomical structures and biochemical, endocrine or neurological processes.

Finally, premature intervention is rightly criticized in the case of individuals with genital malformation that causes intersex or ambiguous genitalia, and who, in many cases, are operated early after birth to establish them as males or females, depending on the possibilities of surgical reconstruction towards the male or female morphology. They often ignore the subject’s own perception — which occurs in a more established way at the age of 13 at the earliest — or their genetic makeup, which will determine the endocrine, neurological and biochemical balance in sexual maturity.

People with DSD should be treated with the prudence, intensity and efficacy that their dignity requires. However, the existence of these disorders should not be confused with the existence of an “intersex mosaic”, but as exceptions to the rule of binary male and female sexuality, specific to the human species.

Transgenderism: What does it mean to try to reverse biological sex?

In fact, attempts to reverse this biological state, based on hormonal or surgical therapies, will not change the genetic basis responsible for the processes of differentiation towards one or other sex.

Therefore, in our opinion, it is based on a fundamental error: the biological sex of each individual is not the one assigned at birth, but the one resulting from their genetic makeup, which will manifest in their phenotype.

The difference is critical: a trait assigned externally on the basis of multiple conditions can be modified without further problems when the conditions change. This is what this bill seems to be proposing. But if this trait does not respond to an external assignment but to an internal constitution, trying to reverse or modify it would involve modifying the very nature of the individual.

Moreover, the phenotypic identification of biological sex is not based exclusively, as the bill states, on the visual appreciation of the external genital organs. The sexed condition can be evidenced in multiple facets of an individual’s organic constitution, which include the anatomical, but also the physiological, endocrine, neurological, biochemical, immune aspects, etc.

What is said about biological sex (“assigned at birth”) should be qualified when talking about psychological sex, which is susceptible to change or modification, according to multiple factors. The American Academy of Psychiatry refers to “gender dysphoria” when the biological sex does not coincide with the psychological sex, i.e., with the subjective perception of the genetically determined male or female state.

What does the new law propose in these cases?

The current legal system already recognizes the existence of the Transgender Act, establishing guarantees for non-discrimination of the persons involved in any of the personal, social, labor, educational, health fields, etc. The possibility of changing legal identity from one sex to the other is even contemplated.

So what is the interest of the current bill? It seems to be about going further in some areas. I shall highlight some of them.

The possibility of migrating from one gender to another, i.e., trying to match the sexual phenotype (its physical manifestation) with the psychological or self-perceived sex, is allowed, but the possibility of making the journey in the opposite direction is not accepted. Any attempt to ensure that the transgender person’s subjective psychological perception, which does not coincide with the constitutive biological sexual reality, converges with the latter, is prohibited.

Indeed, there is no scientific or anthropological explanation that justifies making the journey in one direction and not the other, especially when gender dysphoria processes can be transient and time-limited in many cases, specifically when sexual maturation has not been completed, as is the case with childhood, pre-adolescence, and puberty.

Furthermore, the clinical intervention aimed at modifying the secondary sexual characteristics is a very important entity. The endocrine balance of the individual, which is genetically determined, must be modified in a sustained way over time in order to artificially reverse the hormone-dependent physical manifestations, whose natural tendency will not be reversed but merely repressed during administration of the treatment.

A similar argument can be made about the consequences of surgical interventions aimed at mutilating (“exeresis”) or modifying (“reconstruction”) the physical constitution of the person in order to assimilate it to their psychological perception of their gender, which is discordant with the phenotypic one.

Many of these interventions have associated non-reversible side effects, which are leading many people who have embarked on the transition process and subsequently regretted it to find that they are unable to recover their previous state, not only at an anatomical level, but also at the neuroendocrine one. This is the subject of increasingly frequent lawsuits.

Proposition or imposition?

The importance of the proposed measures for the individual and, therefore, for society, demands absolute respect for individual freedoms. Both individuals affected by transgenderism, as well as their parents or guardians in the event that they are minors, should have all the information at the time of decision-making. This should include not only that offered by gender ideologists, which underlies this legislative norm, but also by those who adopt diametrically opposed anthropological positions, considering sex not as a fluid, indefinite or changing reality, but as constituting the personal being.

Attempting to impose the dissemination and acceptance at all levels of gender postulates as “normalized” and, in a way, undisputed, is interference in the field of individual freedoms that is unacceptable in an advanced society.

Needless to say, measures aimed at guaranteeing respect for the rights and dignity of the human being in all circumstances, which are already implemented in our legal framework, are not only appropriate, but necessary.

But imposing a single mindset, especially when, as in this case, it is so far removed from scientific evidence and from certain anthropological postulates different from those of gender ideology, would be a setback for everyone, those who think one thing or the opposite, even for those who do not think.

Julio Tudela

Bioethics Observatory – Institute of Life Sciences

Catholic University of Valencia

 

References

Ainsworth, C. (2015). Sex redefined. Nature, 518(7538), 288-91.

Connellan, J., Baron-Cohen, S., Wheelwright, S., Batkia, A., & Ahluwalia, J. (2000). Sex differences in human neonatal social perception. Infant Behavior and Development, 23(1), 113-8.

Gardner, D., Larman, M., & Thouas, G. (2010). Sex-related physiology of the preimplantation embryo. Molecular Human Reproduction, 16(8), 539-47.

Johnen, H., González-Silva, L., Carramolino, L., Flores, J., Torres, M., & Salvador, J. (2013). Gadd45g Is Essential for Primary Sex Determination, Male Fertility and Testis Development. Plos One, 8(3), 2-8.

Luine, V. (2014). Estradiol and cognitive function: past, present and future. Hormones and Behavior, 66(4), 602-18.

Nugent, B., Wright, C., Shetty, A., Hodes, G., Lenz, K., Mahurkar, A., & Mccarthy, M. (2015). Brain feminization requires active repression of masculinization via DNA methylation. Nature Neuroscience, 18(5), 690-7.

Sax, L. (2002). How common is intersex? A response to Anne Fausto-Sterling. The Journal of Sex Research, 39(3), 174.

 

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