1997. Also here, a group of scientists norman spack of bostons Childrens Hospital, Catherine Dulac of harvard university, Melissa Hines of the university of cambridge, and janet hyde of the university of wisconsin at madison. Im pleased to have all of them here and to begin this conversation with my colleague eric kandel. What are we going to talk about . Eric we will talk about gender identity and the biology of the brain. This is a marvelous topic and i like it particularly because it shows how Brain Science can be liberating in our life. As we understand the biology of our own gender identity better and become more comfortable with ourselves to become more empathic to somebody elses gender identity, we can understand it at age 9, 10, a person says i am in the wrong body. We really can sympathize with them and understand what is going on. But, this is not only an interesting topic, it is an unbelievably timely topic. When we began talking about this six months ago, it was not on the radar screen. We were ahead of our time. But now, you cannot pick up an issue of the New York Times or vanity fair without having a discussion of gender identity. Charlie 17 Million People watched the diane sawyer interview. Eric what we can bring to bear is not a deep discussion of psychological issues, but what the biological issues are. When we begin to talk about the biology, we want to distinguish two different kind of concepts. Anatomical sex and gender identity. Anatomical sex is the body parts associated with sexuality and reproduction. Gender identity is a sense of ones self is a male, female or something else. Anatomical sex is determined not surprisingly by our genes. Genes are ancient chromosomes and we have 23 pairs of chromosomes. Half from our father and from our mother. 22 of these are called autosomes. The difference between the fathers and mothers contributions are real but modest. The sex chromosomes, the difference is quite profound. Women are xx and men are xy. The chromosomes are really quite different than the autosomes. They had a very important function in determining sex. Lets begin with a y chromosome and see how that determines the sex of the male. They are born with a gonad that could develop into testes or ovaries. If there is a y chromosome there, it has a region in it which is called the sex determining region of y. That contains the gene that activates the differentiation of the undifferentiated gonad into the tests. If that gene is not there, you have a female gonads develop. Each of those have profound consequences. Lets look at the male testes. The testes developed within the first seven weeks in utero. It it matures, the testes releases a massive amount of testosterone comparable to the level you have in puberty. That is responsible for giving you the male body form, the brain characters of male functioning and every aspect of your being. If the region of y is not there, you have development of the ovaries. The ovaries secrete estrogen and it gives you the female body form and gives you changes in the brain. Clearly, these are extremely important changes and thats the easy part. This is the anatomical part. The more elaborate part is the gender identity. That is why we have brought together this spectacular group of people to talk about that. As you pointed out, ben is a longterm colleague. He is a major scientist in my field, in Brain Science. Hes chairman at stanford. Member of the National Academy of science and a transgender person. He made a decision in his 40s to undergo a bodily change. He can tell us what it was like before when he felt he was in the wrong body and how we feel about. He can also people knew him as a scientist before he went under this change they can describe him interacting as a woman and now as a man. Norman is one of the pioneers in the United States of pediatric and her chronology and can people make a decision whether or not they should go one with their idea that they are in the wrong body. He has adopted a european strategy and applied it into the United States. People can think through what they actually want to do and make the decisions in an intelligent fashion. Once puberty forms it is a more radical procedure than before. We have catherine with us, an old friend. She is interested in how sexes are presented in the brain and she founded that in the male mouse there is a representation of the female. This is not a completely out idea. Freud suggested we are all bisexual and that is one aspect of the sexuality matures and the other one remains. You pointed this out there are men with female components and women with mail components even in adult life. We have melissa with us who is interested in how kids differ boys and girls in the games they play and interacting with each other. She is interested in how hormonal levels affect a child playing the games they get involved with. We have janet hyde. She is interested in seeing what are the differences in cognitive capabilities between men and women in computer science, mathematics and engineering. Her data suggests that there is very little difference between them. As i have gotten to know janet and little better, i think that is incorrect it. The more i speak with her she majored in mathematics i have come to the conclusion that women are very much into mathematics, engineering and computer science. We have a fantastic program. Charlie let me begin with ben. Tell me the experience he went through. Share with us about what led up to your decision, how you carried forward and the impact it has had on your life. Ben i think my experience is pretty typical for other transgender people. I think i was only about five years old when i had strong feelings that i felt more like a boy and i was born as a girl barbara. I played with little boys, i preferred boys toys. I remember wishing i could be in the cub scouts and boy scouts. Every halloween, i would dress up as a football player. I felt like a boy. As i got into middle school, i did start to feel more and more uncomfortable with it. I did not feel i should have breasts. I do not feel comfortable wearing dresses, makeup, jewelry. It became increasingly uncomfortable when i got into high school. I started to be teased more by kids. I just had a lot of confusion about my gender and i felt very ashamed. I never spoke with friends or family about it at all once. Charlie no one . Ben i felt very ashamed and confused. It was the days before the internet so there was not a lot of information about this sort of thing. As i got into my 20s, i was doing well. I was doing well in my career. I was doing medical training and research training. I was increasingly uncomfortable. Like many trans people, i started to think about suicide. I thought about it a lot. This is a picture of me back when i was barbara. I was 30 at that point and a bridesmaid at my Little Sisters wedding. I could still remember vividly just the agony that i felt, the discomfort putting on that dress, wearing jewelry and makeup. I still remember that. Anyway, i did complete my training and begin my job at stanford. Two years into that, i developed breast cancer. I was very confused about my gender identity, but i knew i did not like to have breasts. When the doctor said he had to do a mastectomy, i said while he were there, please take off the other breast. He was quite horrified by this. He did agree to remove the other breast. I cannot tell you how therapeutic that was. I felt so relieved to have those breasts relieved. I recognized it was a different response my mom had. She thought it was a very huge blow to her femininity. After the surgery, the doctors talk to me about reconstructing my breasts. I was absolutely horrified. It occurred to me that there was Something Different about my gender. It was only about a year later i was reading several pages about the life of james green, an openly female to male transgender person. I realized there were other people that had gender confusion. Other people like me. I went to see a sex change pioneer at stanford. He ran a gender clinic. After the evaluated me, they told me they thought i was transgender and offered me the possibility of changing my sex. It was irresistible to me. Within weeks, i decided to change sex. I already had the upper surgery. I just needed testosterone. You can obviously see the effects it has had on me. It is powerful stuff. One of the interesting things about the testosterone is it became harder for me to cry. Male to females report it becomes easier for them to cry. That was perhaps a surprising experience. I think the main experience i had was i just felt after i changed sex it is hard to describe the intense relief i had. Like this intense weight off my back. I have been so much happier. I have never had another suicidal thought. At the time, i had been a scientist at stanford for several years, i was very worried that changing sex could alter my career. This was 20 years ago. Everybody, all of my colleagues and friends and family were supportive and i have been fortunate to have my career continue and have lots of wonderful students and support. I guess the other thing i would like to say is i think the other surprise after changing my sex is i found living as a man has changed how people react to me. I can tell you a story about an experience that happened surely after a change sex. I was invited to give a seminar about my research at m. I. T. And one of my friends told me after i gave the seminar that one of his colleagues was talking to him about the seminar. He said ben barres is somewhat better than his sisters barbara. [laughter] ben i think that experience points out something that all of us trans people we have lived life as both genders. We have shared in intense anger at the different ways society treats men and women simply based on their gender. I think in general i think we would all say in general society men are competent until proven otherwise and women are considered incompetent. It is incredibly unfair barriers for women in science. That im am trying to promote some of my time to help one in. Him and charlie listening to that story, i assume it may be typical in terms of somebody questioning to looking for solutions and the experience of the reaction after you have changed. What does this say about gender identity . Norman i wish we knew more, charlie. We certainly know it when we see it. I want to show you a very powerful example of two identical twins who, in this case, one of the male twins we have proven these twins are indeed absolutely identical and born male. One of them at age three started to say everything about being a girl. In fact, if there was any issue that came up, she turned it into an issue of gender. She did some of those things that we consider hallmarks like preferring to wear female underwear and pajamas, etc. And by the age of seven, the family decided with the help of a counselor to change her name to a female name and to have the child assume a female role. Here is twin sister with twin brother at the age of just about nine to 10 years. So, they are in fourth grade. What i want to point out is if i switch all the attachments to them, the earrings, the clothing, the hairstyle, the shoes, you could basically switch one for the other. The fact of the matter is that kids with their clothing on are virtually interchangeable prepuberty. Their hormonal levels are virtually at that point interchangeable. Everything happens really at puberty. Here they are at age 14. Now, because it is so difficult to live in a gender different from your biologic sex, when you have the toxic effects of your genetically hormone driven puberty which would make twin sister looked exactly like twin brother. You can see that he looks still almost like a nine or 10yearold and there is a good reason for it. She has had her puberty suppressed. The next slide shows the level of sex hormones across the human lifespan. Look at the blue line which is the male level of testosterone the hormone that ben was receiving and some of us make. But, during fetal life especially in the mid trimester, the level of testosterone in a fetus rises to a level close to the full adult range. Then it falls and then theres another blip up after birth, a kind of second are pretty. Then things go completely dormant. If they did not go dormant, we would have a whole bunch of puberty looking fifthgraders looking running around because everything is suppressed. Eric when we are thinking about possible causes for transgender, ben and i spoke about this before, wouldnt it be possible there is some kind of aberration in testosterone secretion during development or shortly thereafter . Norman it is certainly possible. It is a very dynamic stage. We still dont know what that second bump is after birth or what role it plays or whether boys are born without testes and show any differences because of that. The problem, eric, is that when we want to look at hormone we want to measure it. You cannot get it out of the brain. The other problem is sometimes it is not the hormone level that is important but the affinity of the receptor for them and it is very difficult to measure such things. Eric it is a very fascinating problem. To see what is the biological underpinning of entity. It is so important because kids who were in the wrong sex, their incidence of suicide attempts is serious. Norman it is one of the highest risks of any. Eric it is something we need to understand. Norman in the puberty process this system reawakens again. The system that has been awakened in utero comes back in which hormones hitting the pituitary causes the release of other hormones that strike the ovary or testes and cause the release of testosterone of estrogen mainly. Those produced the differences between the body of the male and female which is associated with puberty. So, we have been able to, since 1980, block the release of the hormone from the hypothalamus to the pituitary. Once you do that so far upstream, everything downstream goes down to zero. We have a record of this medication being completely successful in shutting them down until the appropriate time and also the fact it is completely reversible. Look how revealing this is because the twin sister affirms the female identity and the puberty blocks two years to get more time for counseling without measure of body change. That is very important because if we are going to give her estrogen, that will have permanent effects. Take a look at what will happen to her if she was not given the blockade. She would look exactly like twin brother. He is in early puberty, but so would she have been because they are identical. Here are the twins at age 17. At age 14, just after that picture was taken, she began estrogen. At the same time having her male hormones blocked. With that, our patients do not need breast surgery when they feminize because it is so effective. She is now entering junior year of high school in that picture. She is absolutely fabulous. This past october, the dutch reported the first followup of the patients 55 whose puberty was blocked and sex steroids were switched. The dutch group had surgery at 18 and which point their total uncomfortableness with their gender disappears. The dutch found that the kids treated this way were psycho socially functioning as well or better than the nongroup. The dutch gave me their protocol in 2006. We started using it in boston Childrens Hospital at which time we were the only Major Medical center to do so, but we are not that many years since 2006 and over 40 programs now. So, it is now becoming standardized care. Charlie let me turn to catherine and talk about whether this is wired. Catherine as weve just heard from ben and norman, humans have a strong sense of their gender entity and this is a critical component to our individual identity as humans. In humans, males and females display clear differences in behaviors. Mostly but not exclusively related to sexual and social behaviors. For example, males and females have a very distinct sexual and aggressive displays and we see in the previous episode that mothers of females are maternal and males are attacking the pups. How are these differences established and maintained . The basic mechanisms in which the brain controls the gender specific behavior cannot be studied experimentally in humans. Instead, my laboratory is using the mouse as a model system. Mice display clear gender specific behaviors. The mechanisms by which the brain controls gender specific behavior in the mouse can be studied using all the model tools of modern neuroscience. Scientifical behaviors particular sexual, aggressive and parental behavior, are extremely maintained across different animal species. That suggests the brain control of those behaviors is also very maintained. In contrast, the signals that trigger these behaviors are usually extremely specific of a given species. For example, in the species of birds called the american flicker, there is only one sign that matters to trigger gender specific behavior and that is the black mustache on the face of the male. So, if you remove the black mustache from the face of the male, then the other males will attempt to copulate with the male because they will assume it is a female. If you paint a mustache on the face of a female, the other males will attack it because they will assume it is a male. I have a mustache, im a male. I dont, im a female. In contrast, we use a very specific set of factors called pheromones. Humans are particularly a fact that has been exploited very much by the pornography industry. Once we know the signals that trigger gender specific behavior, we can look into the brain. How was the brain processing these signals and establishing these gender specific behaviors . As we have heard from norman, in young males, there is very important release of testosterone and this release of testosterone has been shown to be essential to masculinize the brain. In males, testosterone is essential to establishing and maintaining the very specific set of certain underlying male specific behaviors. Females organize their brand in a different way in order to control female specific behaviors. We have performed a number of genetic experiments that show that the situation is a little more complex. The experiment we did is actually very simple. We looked at thermo detection which is indicated by this little cross on the structure of the brain. This animal is insensitive to sex specific cues. When we look at their behavior we saw something surprising. In grey is female, in black is male. The female is mounting the male which is a very male specific sexual display. This female is displaying the male specific behavior. This male strangely instead of attacking pups is now retreating an infant and bringing it to the nest the male has. This mouse is displaying female specific parental behavior. So, what do we learn . What we learned is that the brain of both males and females contain the right presentation of male and female behaviors. The male is repressed by pheromonal system. The female specific circuit is repressed. What is happening is the repression of the opposite brain, opposite sex behavior circuit no longer exists and therefore the female is able to display both male specific behavior and female specific behavior. Similarly, the male can display both female and male specific behavior. Eric i think this is so beautiful because it provides the way we can begin thinking and exploring Transgender Identity if we have the circuits. You can see how it can contribute to wanting to be another gender. I think this is very profound. Catherine exactly, as eric mentioned, this shows the brain of males and females are similar. And specific hormonal and genetic regulation leads to the predominate but not exclusive display of the behaviors of given sex. This is extremely important because animals occasionally need to display the behavior of the other sex. We have seen in the previous episode that males are occasionally ok to display parental behaviors. In many species, females are using mounting as a sign of dominance. The brain has been shown to be bisexual in fish, in reptiles more recently and now in mice. We think this ability to have the both presentations of the male and female brain could be totally relevant to gender identity. Charlie let me turn to melissa and talk about defining gender identity and Sexual Orientation and gender behavior. Melissa i study the role of testosterone and human development. We studied genetic conditions that cause people to have either higher or lower levels of testosterone during Prenatal Development than would otherwise be the case. From those people, evidence suggests testosterone in human also influences gender development, including gender identity. To start, it is useful to put this into context to expand our understanding of the dimensions of gender related behavior. We have talked about anatomical sex and gender identity which is our sense of self as male or female or something else. Also, people have Sexual Orientation and this is separate to gender identity. It refers to our erotic interest in male, females, both or neither. Finally, there is a third class of peter called gender role behavior. These other characteristics that differ on the average. Some are different from others. Some of the biggest ones are seen in childhood toy preferences. The next image shows the sex difference in height and we are all familiar with this. Males tend to be taller than females but there is some overlap. The males are the blue and the females are the orange. The overlap would be the people that you would not know their gender by knowing their height. The next image shows these gender differences in play, play with toys like vehicles or boys toys or dolls, are similar in size to the sex different height. Finally, we see the gender difference in identifying with the male gender. We can see this gender difference is even bigger and there is almost no overlap between males and females, but there are some people who are in the other distribution. These include people who want to change their gender. How does this come to be . We have talked about these sex differences in testosterone, some of which occur very early in life. This corresponds to a period very Rapid Brain Development so it provides an opportunity for hormones to program the brain in ways that might have enduring influences across the lifespan including gender identification. The next image shows data about women who have had very high level of testosterone before birth. About 2 of women who had very high testosterone, in adulthood decide to live is men. It is hundreds of times more than would otherwise do so. This has increased many times over by being exposed to high testosterone prenatally. The next image shows men. In this case xy individuals who are actually xy females because their cells cannot respond to testosterone. They have testes, they are producing testosterone, but because their sales cannot respond, they look like girls. Almost 99. 9 of them want to live as women. Eric it is so profound because although we dont know the vast majority of cases what causes the desire to change sex, here we find one concrete biological explanation. It is clearly a biological factor and with time we will be able to identify the significant number of other ones. I think having one example is good. Melissa when i began this work, people thought these different interests in boys and girls were completely socially determined but it turns out these are altered by prenatal testosterone exposure. The next slide shows the toy choices of girls and boys in general versus those exposed to testosterone before birth. Boys spent most of their time playing with toys like vehicles. Girls spent most of their time playing with toys like dolls. The girls exposed to testosterone prenatally or in between. They spend about half their time playing with toys that boys normally choose and about 30 of their time playing with toys that girls normally choose. These are different dimensions of behavior. The influence on gender identity is less powerful, it appears then the influence of testosterone on childhood play. That leaves a lot of unidentified factors that contribute to gender identity outcomes. Finally, this is not just testosterone acting on the brain before birth, but also children who have high levels of testosterone engage in different behaviors and this has a feedback aspect on their brain developed. This becomes an increasing mechanism where their behavior is increasingly masculinized as they go through life. Charlie thank you. Janet, talk about cognitive abilities and performance. Janet we have lots of stereotypes in our culture that there are gender differences and abilities. People believe that boys are better at math and girls and women are better at verbal skills and boys are better at spatial performance. What does the real data show . We are at distributions for male and female performance, blue for male and orange for females. You see the most recent data shows that girls are tied with boys in mathematic performance. Many people find this surprising but i have data for millions of people showing this. In regards to verbal performance, you can see there is a female advantage but it is tiny. You can hardly see it. These are very subtle, slight differences. For spatial performance, the difference is a little larger favoring males. I will show you one spatial performance that involves the ability to rotate threedimensional objects. Other kinds of spatial performance do not show this quite a larger difference. You need this spatial ability if you need to be an engineer or architect or if you want navigate around new york city. We get this gender difference in spatial performance in the absence of the spatial curriculum in the school. We teach kids lots of verbal skills and mathematical skills. We dont teach them spatial skills. These are completely trainable. Some School Districts are getting the message and starting to institute these programs. If we want to do something to foster women getting into areas like engineering where they are very underrepresented, instituting a spatial curriculum might really do a lot to help. I also want to emphasize the importance of cultural context in shaping these gender differences. This is the percentage of phds awarded to women in the u. S. By decade beginning in the 1890s. It turns out, i did not know this, it turns out even in the 1890s, 11 of the phds were going to women. You can see it inches up in the 1930s and the percentage plummets in the 1950s. Only 5 of the phds are going to limit. It has been inching up ever since. Today, 31 of the phds in mathematics are going to women. Why didnt plummet in the 50s . The men came home from the war and the women were delighted to see them. They went to the suburbs and had lots of babies. There is not one single biological force that causes women to be good enough to get a phd. It has much more to do with cultural context. It is findings like these that led me to propose the principle of gender similarities. Men and female are similar in most biological performances. You saw math performances which is stereotyped. There are performances for women in those careers. This map shows the gender similarity type is. We have the overlapping distributions. You can see there is huge overlap in which males and females are similar. Let me look at psychological disorders because for some disorders we do get very lopsided gender ratios. On the left part of this graph you can see two disorders were many more men are affected. Alcoholism and autism. The blue bar is the preponderance of males. That is not to say we dont have women alcoholics or girls with autism, but it is a preponderance of males. On the right, you can see depression and the eating disorder of anorexia it is a preponderance of women shown in the orange bars. We do have these lopsided gender ratios. We wonder why those are. My research has been on gender differences and depression. The gender difference in depression is not present in childhood, but it begins to emerge between 15 and 16 years of age as you can see the orange bar is going up. It widens between 15 and 18 years of age. Gender differences in depression emerges in adolescence. We need to understand why the gender different emerges in adolescence. We have a few genes that have been identified that have to do with depression. It may have to do with pubertal hormones. It may have to do with other factors such as the media emphasis on hyper skinny models. Boys have the advantage because they are adding muscle, and that is the way the models look. That may be a factor. We also know that there is plenty of Sexual Harassment in the schools. We live in a pick and choose world. Choose choose choose. But at bedtime . Why settle for this . Enter sleep number dont miss the final days of the lowest prices of the season. Sleepiq technology tells you how well you slept and what adjustments you can make. You like the bed soft. Hes more hardcore. So your sleep goes from good to great to wow only at a sleep number store. Dont miss the final days of the lowest prices of the season. Save 300 to 700 on selected mattress sets. Ends sunday know better sleep with sleep number. Charlie let me go back to this idea of how society is responding because we know from the cover of vanity fair, we know Time Magazine did a cover story which i am told is the secondbiggest selling Time Magazine cover story that year with the one exception of the pope. Transgender is right behind the pope. Ben it is unfortunate society often sees transgender to be a Mental Illness or an immoral choice. Transgender people are still denied basic human rights, often subject to violence. In some states, transgender people can still be fired just for being transgender. As we heard today, the brain has innate circuits that determine our gender identity. To be transgender is not a choice i made, but it is how i was born. I should mention something we have not really brought out yet, there is a Broad Spectrum of transgender people. Some of them prefer not to change sex or even to be identified as male or female. For some of us, there is a compelling innate need to change sex. 40 of us attempt suicide. I think by helping transgender teens to avoid this agony, the dutch pioneers are great. This is not gender identity expression by in large. This is almost always a gender roleplay which is normal for children. Now, of children who are fairly persistent in their cross gender play, but are prepubertal, only about 20 to want to be transgender. 80 are not going to be transgender. What i would say to parents is that if your child is getting close to puberty or worse is already in puberty and is showing this kind of behavior, particularly underwear wearing and saying im the wrong gender etc. , then you need to get help for that child fast. That maybe calling your pediatrician and asking for a gender specialist to meet with your child because a child who is, according to the dutch and us, a child who holds on to the belief that they are in the wrong body on the outset of puberty it is like pinocchio becoming a donkey they will take their life. These are the kids who are the real deal. Charlie over the series of three years, you and i found a range of things we have traced to the brain and understood. In some cases, what we understood about what was taking place inside the brain was large and some small. Where do you put this in terms of understanding what is going on . Eric i think we are in the very early stages of understanding. This discussion points out there is a biology. It is a challenging problem. But, our understanding is very modest. We talked about this before. Many times people have asked how long it will take until we have a satisfactory understanding of the brain. It will take a century. We have made a lot of progress in the last few years that we are long way. Catherine gender identity is so essential to who we are and our ability to be happy. We have a duty to provide some kind of explanation. It is not all black and white. Ben differences are not disorders. Im proud to be transgender. I think it has different innovations and perspectives. The real question is why society persists in insisting that male brains are better brains which we have heard tonight is definitely not the case. Eric one thing that is interesting to see is as you function in a way that you are comfortable with does it increase your creativity . Ben i released a lot of Mental Energy that was devoted to confusion. I would say yes. I have felt much happier and productive as a person. Charlie what percentage of people go under anatomical change . Norman we are in a state of flux on an operation that could cost a lot of money. The reason i say that is because Insurance Companies are waking up to the idea that this is a medical condition. That it is entitled to be billable for surgical and medical aspects of their care can be covered by insurance. It is going to change everything. Up until now, people had to save up to have the surgery. It starts from the top down. First, you have to not make it as a Mental Illness. You have to define it as a physical problem which it is. Hiding it as being gay was, what freed up people starting to see gay people is not having a psychiatric illness. It was having it removed from the manual of Mental Illnesses. We will see. The colleges that are selfinsured, maybe even the college you went to, his paid by people. If i am going over to some of them and seeing them. Charlie i thank each of you very much for coming. There is enormous interest, as you can see in the publications, and also the conversation that is taking place. This subject was introduced in terms of a Television Program somebody came up to me and identified themselves as transgender. But, they said that to me that the fact it has gained so much attention made all the difference in their life. They felt not so isolated and not so different. They felt like they had been in identified so they can have an appreciation of where they stood and what their options were. What are we doing next time . Eric we will continue to discuss child development. What are the consequences of growing up under different circumstances . How does it affect the Cognitive Development of children and is it passed on from generation to generation . Charlie thank you. Thank all of you. And thank you. We will see you next time. 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