TG Medical: " It's All in Our Genes, Isn't it?"

As Published in TG Forum & The Pinnacle
By Cerise Richards, M.D.

We hear so much today about the advances in genetics and the mapping of the entire human genome, that we wonder if this new science will help us understand why we are Transgendered. A few fragmentary steps have been taken to examine the behavior and brains of transsexuals, but it is unlikely to happen since we are so well closeted that there won't be enough of us to study to come to any TG conclusions. It is the hope of a new field of Behavioral genetics that some answers can be gained for the GLBT community that will lead to a unified theory of why gender plays such a large role in our lives. Just the concept that behaviors can be inherited on a molecular basis in our chromosomes is only a decade old. But we have known for a century that we can breed cows for physical qualities and dogs for behavioral qualities that we admire. So, why not humans in this Brave New World?

It was only a little over a century ago, after the publication of the works of Darwin, that his brother in-law, Sir Francis Galton, was to study heredity and human behavior systematically. It was shortly after his death that the term "genetics" appeared referring to the study of heredity. At the beginning of the 1900's, Eugenic (true-birth) Movements in Britain, then America  and finally Nazi Germany were initiated to breed humans for desired characteristics like intelligence, civility and even blonde hair. But nothing turned out as planned. With the rise of Sigmund Freud and the behaviorists, nurture and environmental factors held sway for about 50 years. With the discovery of hormones and molecular cell biology, these chemicals were found to influence some of our sexual and social behaviors as aggression and sexual capacity. The century old argument of Nature vs. Nurture was enjoined and depending on the year, one or the other was considered more important. But this argument is now being reframed as Nature Via Nurture, where each has influence on the other. I shall try and explain how the environment changes your genes and how your genes shape your environment.

Some basic cell biology is necessary before we start or you may skip this paragraph. The nucleus of all human cells contains 23 paired chromosomes composed of DNA in the form of a double helix as described by Watson and Crick. The last set of chromosomes is the sex chromosome, paired as XY (male) or XX (female) or any combination from one to four resulting in intersexed people. The chromosomal DNA is composed of paired nucleotide bases, Adenine, Thymine, Guanine and Cytosine strung in long chained pairs (A-T & G-C) of varying lengths composed of 50 to 200 million base pairs. These function as the memory of the cell for producing the proteins which guide our dividing cells from birth to death. Each chromosome contains many genes of specific lengths of DNA which produce specific proteins for specific functions depending on the alphabet sequence in which they are arranged, like ATTGGCCA or GATTACA, (like the movie).  Now in nature a long part of a chromosome can be broken (deletions) or moved to the wrong chromosome (translocations) resulting in birth defects. But on a molecular level the alphabet sequence can be changed by only a few letters resulting in major developmental problems, which can be passed from generation to generation. Viruses, carcinogens and heavy metals can do this easily. Only 2% of the entire genome is known to be functional for coding proteins, but only 50% of known genes have been associated with a specific function to date. 99.9% of all people have the same nucleotide base sequences, 95-98% of which can be found in our closest relative the chimp. Oh! there is so much to be learned in this Brave New World.

When looking for the cause and effects of genes most of our current knowledge has come from physical abnormalities caused by a single gene defect as described in TG MEDICAL: Middlesex: A Generational Secret. By analyzing the relatives of people with the same physical abnormality, it has been possible to type their DNA and see the common gene defect. A few of the intersex abnormalities appear to be associated with a single gene defect.  In gene therapy, newly transformed genes have been inserted into a defective white blood cell's DNA, grown in vitro and reinserted into the blood stream, where they continue to reproduce and provide immunity to patients, who would otherwise die at an early age from multiple infections. But most of our bodily functions appear to be related to multiple polymorphic genes, which are always changing by either being switched on or off by other genes. Behavioral changes such as schizophrenia or bipolar states appear to have multiple genes associated with them. No single gene determines a particular behavior. Behaviors are complex traits involving multiple genes that are affected by a variety of factors in our environment, which harks back to Darwin's natural selection theories of "survival of the fittest and most sexually capable."

Now to what is known about gender in behavioral genetics. In 1991 Dr. J. Michael Bailey published a study of homosexual identical twins, homosexual fraternal twins and adopted brothers of homosexuals. He found a strong link for the hereditability of homosexual siblings of 52%, 22% and 11% for each respective group. This was again repeated in later studies with the brothers and sisters of homosexuals. The observation that male homosexuals usually have more gay brothers than gay sisters, whereas lesbians have more gay sisters than gay brothers, suggested that family factors are at least partially distinct in men compared to women. Did being raised in the same familial environment contribute in some way?  Then specific areas of the brain associated with gender identification were found to be twice as large in heterosexual men than women or homosexual men. And finally a gene on the X chromosome was identified as Xq28 in 64% of homosexual siblings and thought to be responsible for homosexuality with a 99% confidence limit. Since then Bailey has been the Darling of the gay community who recently nominated him for a Lambda Literary Award for his recent book on Transsexuals. This work has been roundly criticized as being Junk Science with theories of Autogynephilia viewed as racist by the Southern Poverty Law Center. Bailey is currently under investigation by Northwestern University for his research and extracurricular activities.  But this adoption of "naturalistic fatalism" by the Gay community is a double-edged sword. "Yes, I can't help it that I'm gay, it's in my genes." But that will not stop the so called Evangelists, who want to treat this known genetic "disease" or use gene therapy to stop this "moral abomination". Because it is natural, it is not necessarily "morally good" in their eyes. Can the "Marriage Amendment" be the first eugenic step to keep homosexuals from producing and raising homosexual children?  It's genetic, Isn't it?  Thankfully, the American Psychiatric Association has removed Homosexuality as a Mental Disorder from the DSM-IV, but we are still there under Gender Identity Disorder until the next revision in 2006.

Now as far as Transsexuals are concerned Zhou and Gooren in 1995 found that the volume of the central subdivision of the bed nucleus of the stria terminalis (BSTc) of the hypothalamus, a brain area that is essential for sexual behavior, is larger in men than in women. They also found a female-sized BSTc in male-to-female transsexuals. The size of the BSTc was not influenced by sex hormones in adulthood and was independent of sexual orientation. Furthermore, the size of BSTc of heterosexual men and homosexual men did not differ. Ref: OMIM 600952. There is also a study showing Transsexualism occurring in families.  So do genes form our brains. Sure they do, but brains have neuroplasticity. They are constantly forming new neurons and connections as we learn, are affected by our environment and by the hormones we ingest. So how do genes affect our sexual identity. We are just beginning to understand that the most important sexual organ in our body may be our brain.

In birds, it has been shown that parts of the brain direct sexual plumage and mating behaviors irrespective of hormonal bathing. In humans, it appears that the SRY gene on the Y chromosome, which switches on the SOX9 gene, is all that is necessary to become masculinized long before the testes produce any hormones. The SOX9 gene then directs other polygenes to switch on and off causing the production of internal sexual organs and hormones. If one of the paired SOX9 genes is not working, then a female will be born with a Y chromosome.. It appears that the SRY gene is expressed in the brains of male mammals weeks before testes develop, but we do not know how it functions in the brain as of yet.  Studies of non-hormonal influences on sexuality are at an early stage, but researchers are now looking at gene sequences on the Y chromosomes of MTF Transsexuals to ascertain if their strong desire to transition is genetic. The answers are just on the Horizon. Stay Tuned!

Best of Luck in Your New Future,

Cerise Richards, M.D.