>> from our studios in new york city, this is "charlie rose." charlie: >> in all these discussions we are going to come back and forth. four regions are important. the prefrontal cortex is , the amygdala and hypothalamus. the prefrontal cortex is involved in executive function and decision-making and what we call character formation. defects in the prefrontal cortex can lead to an increase in aggression. the ventral stratum is also four kinds of aggression.

the amygdala is the orchestrator of the emotion positive and , negative. it influences the hypothalamus. the hypothalamus has many functions but we will focus on its role in aggression and sexuality. >> we are basic neuroscientists in my lab, and we want to understand some of the most fundamental questions about aggression. how is aggression, a revolutionary ancient behavior, throughout the animal kingdom how is that hardwired into the , brain? where is aggression in the brain? we have studied this problem in flies and mice and we're particularly interested in the relationship between the parts of the brain that control aggression and those that control mating or sexual behavior. as you know mating and , aggression are closely related behaviors. in nature you often find that periods of aggression are at their highest when animals are mating.

these behaviors reinforce each other. at the same time, they are mutually exclusive. a male will direct mating towards a female of the species , aggression towards another male. there's a paradox. how can these behaviors be mutually exclusive but also reinforce each other in some way? we have begun by trying to pinpoint the neurons that control aggressive behavior and we have started by looking in a very evolutionarily ancient region of the brain, which eric brought up, called the hypothalamus. we began by trying to measure the electrical activity of cells that were active during aggression or mating, in a tiny region of the hypothalamus. we found something quite surprising. within this very small region of the brain we found a mixture of neurons, some of which were active, turned on when the animals were fighting, this was done in males, some of which were turned on when the animals were mating with a female, and

interestingly some of these were , active during both fighting and mating, 25% of them overlap. that was an interesting observation, a correlation, and we really wanted to understand the function of these neurons. we began by using very modern techniques now called opto genetics to activate and inhibit these neurons. we can pinpoint this activation with a high level of accuracy, directly to specific cells in the brain active during aggressive -- aggression, and turn them on and off with a time resolution of milliseconds. i'm going to show you a video of what happens to a male mouse when you activate these aggression neurons in the brain. before the video, some of your viewers might find the image of it disturbing, but we are not hurting the mouse. these are all protocols that have been approved by our institutional animal use and

care committee and nih approved. you will see the mouse in a cage with an inanimate object. when the light comes on we are stimulating these aggression neurons in the mouse. we can actually trigger the mouse to attack a rubber glove. if there were another mouse there he would attack the other mouse as well. we wanted to ask, are these neurons necessary for normal aggression? mice will normally fight for -- with each other, for example if you introduce an intruder mouse into the cage where a male mouse lives, very shortly thereafter the resident mouse will attack the intruder. he does not like somebody impinging on his territory. we ask if we shut these neurons off, can we stop a fight dead in its tracks? as the next video will show you, it's possible to do that. these mice are fighting naturally. when the light comes on we inhibit these neurons and the fight stops. we will show you that again in slow motion.

the mice are fighting and suddenly the light comes on, we stopped the attack dead in its tracks. charlie: i don't understand how neurons know how to respond to light. do this iswe genetically implant in these neurons in the brain, a protein that comes from a light-sensitive algae. that protein makes an ion channel through the membrane of the neuron that turns the neurons on, only when light activates the channel. we can convert these neurons into light-sensitive neurons. that shows us the neurons are necessary and sufficient for aggression. >> there are different kinds of one's, those that activate the neurons and those that shut off. we can do either. we discovered, as we were manipulating, the conditions for

turning these neurons on very surprising. you needed high intensity stimulation to activate aggression but low intensity stimulation would promote mounting behavior. the mouse would try to meet with whatever other mouse was in the cage with low intensity stimulation, whether it was a male mouse, female mouse, it would try to mount. we could actually switch the behavior of the same animal from attempted mounting to a mixture of mounting and attack just by increasing the intensity of light. that tells us that in this tiny region of the brain there is a mixture of neurons controlling both the mating instinct and the fighting instinct, and perhaps that will account or may account for the tension between the sex drive and the aggressive drive. charlie: it's extraordinary. >> it is extraordinary. it also sort of explains why aggression can lead to sexual aggression. it really is an amazing set of findings. >> a lot of people think

aggression is more prevalent in people with mental illness. the fact is mental illness on his own does not increase the rate of aggression. it is more likely to occur in individuals with issues of substance abuse and dependence, and especially prior history of aggression. everyone gets very concerned when mass shootings happen. this person must be mentally unfit. those are very individual situations. when you look across large epidemiological studies, that does not pan out. there are multiple forms of aggression. there is socially sanctioned aggression, such as fighting in war, medically induced aggression. a medical condition makes more -- makes one more irritable. but the two big ones will be impulsive aggression and premeditated aggression. impulsive aggression is not exactly spontaneous. people get or perceive a threat or frustration and their , threshold to blowup is very low.

they just blowup or display a temper touch or more physical -- temper tantrum or physical aggression. premeditated aggression, which can happen in anybody, is taught already thought through. the people most likely to do that is psychopaths, maybe 1% of the population. but people have intermittent explosive disorder, which is more like 3% or 5% to 6%. that is much more the case as far as that is concerned. those important distinctions to put forth, because we have an idea of how to treat impulsive aggression. we are not quite sure how to treat premeditated aggression. we will say something more about that. charlie: what did we see at the neurobiological level? >> people with aggression is similar to what we're hearing at this table. the doctor talked about 4% of boys being chronically aggressive.

that is about how many ied's you have out there. we also see the same sort of thing biologically pretty see problems with serotonin function, where serotonin function is diminished. we see evidence of heightened other neurotransmitters that will facilitate aggression. we see problems in the frontal area of the brain. when we present to these individuals, pictures of individuals who are angry or threatening, the amygdala will overact to that stimulus compared to healthy volunteers. that also correlates with how aggressive these people have been over the course of their lives. an important thing going along with this is serotonin and the amygdala really have to do with the tendency to be aggressive. what makes you aggressive in the here and now has to do with how you interpret social signals. people that are aggressive -- it may very well be because they had been aggressive as a child

tend to have problems of social internation processing. they don't take in enough information about what's going on and they make a hostile inference as to what the other people is doing. you can have a situation where the threshold may be high or low , and where you are coming into to day is you are primed think somebody brushed up against you or is looking at you funny, is threatening or frustrating to you. you have a serotonin system in the frontal lobe that is not working so well. brakes are bad, high accelerator, you will have a crash. >> charlie and i did a program on depression. one of the key things is treatment of depression often is designed to increase the level of serotonin. is there a increased incidence of this kind of aggression and people who are depressed and have low levels of serotonin? >> not necessarily. the early studies i did were interesting in that. we saw this problem in

individuals who did not have a primary mood disorder. and what we think is going on is their brain systems involved in activation are not working well. they will make a suicide attempt when they are severely depressed because that is the arousal going on. when you have low serotonin, it is bad breaks. charlie: we talked about certain individuals who cannot control their impulses. >> yes m.l. has been talking , about people in a hospital context. what we do is we work with people at the street level were violent psychopaths, even killers. charlie: what the psychopath mean? >> an individual who lacks conscience, remorse, guilt. because of that lack of normal emotional feelings, there are no areas. they do outrageous things. -- there are no barriers. they do outrageous things. there stimulation seekers, their impulsive. >> there are two types.

there is the cold, calculating, callused type. then you have the antisocial lifestyle, doing horrible things to other people. we have been studying their brains using brain imaging to look to see what part of the brain may not be working right, what part may be physically different. what we find in normal people is that their prefrontal cortex is working well, as you see there, in the green. this is where we brain scanned murderers in the next slide. what we see our murderers who are impulsive, they do not plan the murders they are hot-blooded , in terms of their homicide. and what we see on the left is poorer functioning in that frontal region of the brain. why is it that that part of the brain can predispose to aggression? it is a part of the brain involved in checking on impulsive behavior. we all get angry at times. what stops us lashing out? we have a good frontal cortex that is working well to regulate

and control our aggressive behavior. those are hot-blooded murderers, but what about the cold-blooded murderers? when we brain scan them, they had pretty good frontal functioning, which makes sense because these are killers who premeditate their homicide. they are planning ahead. they had the wherewithal to do that. the interesting question becomes, what is it then that is producing them to be violent in a predatory fashion? let's turn to the next slide. we will look at another brain region. this is the amygdala on the left. you can see where it is located in the brain. when we study cold-blooded offenders, psychopaths, they have a physical shrinkage in the amygdala. it is reduced in size by 18%. on the right, you can see the areas within the amygdala

colored in blue that are actually physically deformed. the amygdala is important in generating emotions. if there is a shrinkage, that will reduce fear. what stops a lot of us breaking the law of the lands, we are frightened about the punishments we would get if we were caught. but if you lack that fear, you are more likely to commit offenses in a cold-blooded fashion. there's more to it than that. on the left you can see where it is located in the brain. another brain region. on the right, you can see there's greater activity in psychopaths when they are anticipating rewards. we have the idea that psychopaths are reward driven. they want the goods, just like an addiction.

charlie: there is stimulation to the brain? >> the idea is the anticipation reward is part of the brain, firing up a lot more. maybe that is why psychopaths are more likely to pursue rewards and gains that they want. they have the drive to do that. and they don't have the emotional amygdala to hold them back in a way to give them anticipatory fear. that would normally result. >> this is a spectacular series of findings. when i was a medical student, none of these imaging techniques were available. you had very little insight of what was going on and the living brain of people. we now have insight into the biological substratum of different kinds of aggressive syndromes. this is just the beginning, how much we have learned, different categories, impulsive versus premeditated, different categories.

charlie: even affecting the size of the amygdala. the question is, because of your reference to imaging, can you look at imaging and decide it is most likely to be aggressively violent? >> it's a great question. we are beginning to get clues about who may be more likely to be violent in the future. myself and colleagues brain scanned males in the community. those individuals with a smaller volume to the amygdala were more cold-blooded. so to speak. they were four times more likely to commit a violent act in the next three years. that is prediction over and above prior history of violence, prior history of psychopathy. it not perfect by any manner, but we are beginning to get value used by imaging to try to understand who are at risk for becoming the next generation of future offenders. charlie: are we seeing this kind of research used in trials, in criminal trials?

>> the key question here is if a psychopath is -- what is causing that amygdala shrinkage? it could be genetic. it could be how the brain develops. we also know that trauma reduces the size of the amygdala in children. neglect reduces the size of the amygdala. for whatever reason, i don't think psychopaths ask to be born with an amygdala three sizes too small. if that brain empowerment -- impairment predisposes them, alters them, doing the terrible things they do, the fascinating question is to what extent do we , hold them fully responsible for their actions? >> this is not dna evidence. this is not like saying, i am responsible, david is not definitively. this is a probabilistic statement, and that is imperfect in front of the law. >> absolutely. >> i think as techniques get

better, and not only the amygdala the amygdala is , associated with abnormality, danger is associated with another abnormality, we will be in a better position. ♪

>> human parents, this behavior is essential for the proper development of the child heard .

in addition, parenting is one of the strongest and most enduring social bonds in human societies . remarkably, parental behavior is wildly conservative in the animal kingdom. in mammals, females lactate and therefore they take primary responsibility of parental care. as you can see in this slide, female chimpanzee is watching over the first child. females are very flagrantly maternal, not only in mammals but also some species of birds, reptiles and insects. what about the fathers? the contribution of males in parenting is very variable. in some species, for example in the silverback monkey and gorilla playing with his infants, in some species males are paternal, they nurture their young. in some other species, males attack the children and sometimes kill them.

i am a neurobiologist. my group used a laboratory mouse to try to understand basic biology of parenting behavior. we would like to identify the brain areas that are involved in driving parental behavior and we would like to understand how these brain areas are regulated, in order to have animals that are parenting and some animals that are neglecting their infants. in females, mothers as well as non-mothers are spontaneously maternal. which means that when they are put in the presence of pups they , will spontaneously build a nest, they will retrieve them they will groom them, and huddle , with them for long periods. in contrast, males are infanticidile. they will readily attack pups and kill them. however, males that have access to the females become paternal three weeks after meeting with a

mating with a female which corresponds exactly to the , gestation time in mice. in other words, males who become fathers also become paternal. we took advantage of these extremely interesting paradigm and differences in behavior between males and females and infanticidal males to try to understand what are the brain role. what are the neurons that drive parental behavior? in the first set of experiment we identified a specific set of cells in the hypothalamus that are activated during parental behavior. we then ask all these neurons, required for the parental drive. in a subsequent experiments, we ablated these neurons in parental males and females. surprisingly and remarkably, now these animals neglect their

infants or attack them. these experiments suggest these near runs are required for -- a neurons are required for parental behavior. in the next experiments, we ask whether the activity of these neurons was sufficient to create parental behavior. took aggressive males and artificially stimulated these nurturing neurons. amazingly, these aggressive males stopped attacking the cubs and they groomed their infants. what this experiment says is the activity of these neurons is sufficient to drive parental care. in another experiment, we identified a set of cells in a different area of the hypothalamus that is activated when aggressive males attack their infants. we call these the parental neglect neurons. in another experiment, we activate these neurons in females and found these females, instead of caring for their infants, now neglect or attack them.

so what over all these experiments suggest is that the brain has two components. a set of cells in the hypothalamus that drive parental behavior, and another set of cells that drive parental neglect. these very excited by results, because it opens new opportunity to understand the behavior, parental and possibly why some animals are parental and some are neglecting or attacking these infants. parental behavior is widely conserved among animals. also raises the possibility that the function and regulation of the cells is widely conserved across the animal kingdom. charlie: one question before we go to suzanne. how do you stimulate the neuron's to make the aggressive males more nurturing?

catherine: we use modern methods in neuroscience called opto genetics, that are able to shine light on neurons that have been genetically modified and have an ion channel that is light activated. in other words we drive the , activity of genetically defined population of neurons. >> there is been fascinating work done by teams understanding the evolution of parenting behavior and of bonding between males and females. in both there is a very nice , system where some species are polygamists and some are monogamous. excellente vole is an example of the monogamous system, where males and females form these long time pair bonds and both are nurturing towards their young. what has been found in this system is that not only are the higher levels of oxytocin, but

in the males there is a similar hormone produced by the hypothalamus which seems to be important in determining both paternal behavior and pair bonding behavior. in the monogamous species there are more receptors and higher levels. we have oxytocin in females which seems to be important in driving pair bonds and maternal behavior. and in males, the other that plays a similar role in driving pair bonds and -- >> by insulin. and young, they did a fascinating series of experiments determining how oxytocin impact some female maternal behavior and for males, paired bonding and paternal behavior. charlie: is it monogamy that produces the higher levels of oxytocin or is it higher levels of oxytocin that produce monogamy? susanne: oxytocin is primarily involved with maternal behavior.

the other is associated with monogamy. some of the same teams who worked on how vasopressin relates to pair bonding and paternal behavior in both has also shown you can take both species that are not monogamous essin and make them switched to be monogamous. and add vasopressin and that changes their behavior. what is it about human biology that is both similar and different to other primates is what drives our research. one of the things very remarkable that humans is we have a very large rain and exceptionally long juvenile and infancy periods. because we are born so helpless and so unable to take care of ourselves, parenting becomes exceptionally important. human babies are totally defenseless and even throughout

their juvenile period they need much more investment by their parents than similar species that are closely related to us. i think that tells us that in humans particularly understanding the role of , parenting behavior and the biology of behavior is very important. charlie: what is the effect on children who are deprived of nurturing? >> we know that children are exposed to a continuum of care. as you can see here this infant , and mother are having a wonderful conversation. the mother is clearly in love with this baby. this is what we want to see in all infants and mothers. but under conditions of profound deprivation all of that is , missing. we have a pair of twins in -- interacting. but now we have institutional care. notice the sheer number of babies in institutions, the lack of caregivers. as you look through here, there is one in the back. you can see there is a very low investment in these children unlike the videos we saw in the

, beginning. this lack of social interaction, we think, plays a fundamental role in building the brain. what we started to observe was in the study, what happens to the developing brain and kids growing up in institutional care. we formed a manipulation in which we saw a large number of children abandon the institutions in romania. after studying extensively some , were placed in high quality foster care and some remained in the institution. i want to show you a video of what a child at the age of two looks like. this is on an outing with a bunch of kids from an institution. if you notice, the girl was rolling over, she is 22 months of age, her iq is below 50 at this time. she's been in the institution close to the time of birth. the other little girl is rocking. off camera there are other kids rocking. that stereotype rocking is characteristic of kids who grow up in institutions. the question becomes, what happens to the brain?

in the next slide i will see the beginning of the journey. the first thing we did is recorded deep rains electrical activity -- brains electrical activity by simply placing sensors on top of the head. the billions of neurons in the brain generate electrical activity we can pick up. from that activity, for the power the brain is producing, how much electrical activity is there, we can color code that. that indicates more or less power. on the right side you see an image of a never institutionalized brain. look at it from the top down. the distribution of electrical activity is portrayed here to reflect much more brain activity in red sitting over the frontal lobe. you looked on the left panel, that is the institutionalized group. the kids in the institution are drastically underpowered. we can use the analogy, instead of a 100 watt light bulb it is 40 watts. at that point we were very concerned and we got, what is

going on, what is producing less activity? when the children were 8 to 10 be performed at a resonance imaging to look at the detailed anatomy of the brain. on the right is an m.r.i. scan. we are showing gray matter. gray matter represents the cell bodies, appendages of neurons. does the computations and calculations of the brain. whereas white matter does any occasions. white matter shows a whitish, and gray matter shows up grayish. on the far right you see the amount of gray matter in the never institutionalized. these are the children who grew up in families in bucharest, romania. but if you look at the children who have been institutionalized on the far left, it is dramatically reduced. they show less brain matter as do the kids we put in foster care. this is showing us that the brain has mu less gray matter by a function of being in an institution. in the next slide we show the same reduction in white matter.

what is scary is thiss almost suggesting we note that there is a smaller brain as a function of being in an institution. dr. kandel: the reason this is so important is before chuck did these studies ople knew that , deprivation or lack of parental and -- involvement was d for cognitive development. they did not know that affected the brain directly. but this is the first evidence showing dramatic changes charlie: would ibe different if there was some kind of tivity with the kids in institutions, a much more collegiality that was produced from outside? >> yes. in a moment we will talk about what happens when you put kids in families. your question is, can you improve an institution. dr. kanl: charlie is asking another question, does it have to bearents, can it be substitutes. >> we know it has to be the investment the caregivers make who care about that chd. it doesn't have to be the parents. what goes on in institutions is

you don't have that. is it as sile as you can feel the sense of, your brain will develop if you can feel there is conct that somebody knows who you are and recognizes you? >> precisely. there is a social interaction that is stimulating brain developnt. he lack of social teraction kids t in an institution who , got cognitive and linguistic imulation but no caregiving, they would jusbe as poorly off as the kids we s. thquestion is how much recovery is there. in ts study we placed lf of the kids into foer care, high ality foster care. at t beginning of thisideo -- we will see that little girl en she is 22 months of age, iq below 50 in an institution. ypical motor behavior. this is her interacting with her foster care mother.

this is merely 8 months of foster care. now aboutip, she is four years of age, she has spent half her life in foster care. look at that interaction she's having. this is the same little girl we saw in the beginning it was crawling backwards, rolling over, had barely any language and now her iq is in the 80's. there is tremendous recovery that can occur by placing children into a family. but, it seems to be regulated by a critical period. placement before the age of around 2 years of age leads to much better outcomes. placement after two years of age leads to much less desirable outcomes. on the next slide we can show the eeg. on the right is the brain of the never institutionalized child. more red means more activity. left side is institutionalized child. in the next slide we see the critical period. now, the brain that is left at the institution after age 2, it looks identical to the institutionalized brain.

the child is in a family but not until they were older than 2. in the next slide you can see now the children placed before 2 that look activity just like the kids who have never been in an institution. we see this in other domains as well. we see this inflection point and development, removal from an institution and placed into a good family before 2 leads to much better outcomes than children placed after 2. charlie: timing is everything. if you don't have it, it puts a ceiling on how much you can produce. >> exactly. the window of opportunity for brain plasticity is reduced. ♪

dr. kandel: what we can bring to bear on this subject is not only a deep discussion about the sociological and psychological issues are, but what the logical underpinnings of that is. when we begin to speak about the biological underpinnings we want to distinguish as you already implied, two different concepts. anatomical sex and gender identity. anatomical sex is a body parts associated with sexuality and reproduction. gender identity is a more subtle complex image that is a sense of oneself as a male, female, or something else. let's begin with anatomical sex. it is determined by our genes. genes are ancient chromosomes

and we have 23 pairs of chromosomes. we get half from our father, and the other from our mother. mes.f these are called otoso 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 quite different than the others. they have a very important function in determining sex. let's begin with the y chromosome and see how that determines the sex of the man. we are born with an undifferentiated gonad that can move in either direction. it either can develop into testes or ovaries. if there is a y chromosome there that has a region in it which is called the sex determining region of y, that contains a gene that activates the

differentiation of the undifferentiated gonads into the testes. if that y gene is not there, you have an xx, female gonad develop. each of those has profound consequences. male look at the differentiation. the testes develop within the first seven weeks in utero. if the testes matures as a result of the sex determining region of y, the testes releases a massive amount of testosterone comparable to the level you have at puberty in the adult. that is responsible for giving you the male body form, the brain characteristic of mail -- male functioning, as well as having actions and basically every aspect of your being. if the sex determining region of y is not there, you have xx, you have development of

the ovary. the ovary secretes estrogen and progesterone and it gives you the female body form and changes in the brain. these are extremely important changes. that is the easy part here this part. this is the anatomical part. the more subtle part is the gender identity. charlie: tell me the experience you went through. share with us as much as you can about what led up to your decision, how you carried forward and the impact it has had on your life. >> share, i think in many ways my experience is probably typical for other transgender people. i was four or five years old when i first started to have strong feelings that i felt more like a boy. i was born as a girl, barbara. i felt like a boy, i played with boys. i preferred boys toys. i remember dreadfully wishing i could be in the cub scouts and boy scouts. every halloween i would dress up as an army man or football player.

it seemed normal to me, i felt like a boy. as i got into middle school, early teen years, i did start to feel more and more uncomfortable with this. i did not feel i should have breasts. i did not feel comfortable at all wearing dresses, makeup, jewelry. it became increasingly uncomfortable when i got into high school. i started to be teased more by kids. i had a lot of confusion about my gender and i felt very ashamed of it. i never spoke with friends or family about it once. charlie: no one? >> no. i felt very ashamed and very confused. this was in the days before the internet, so there wasn't a lot of information about this tort -- sort of thing. as i got into my 20's, i was doing well in my career, i was doing medical and research training, but i was increasingly uncomfortable and like many trans people i started to think about suicide.

i never actually attempted, but i thought about it a lot. this is a picture of me back when i was barbara. i think i was 30. i was a bridesmaid at my little sister's wedding. i remember vividly just the agony that i felt, the discomfort, putting on that dress, wearing jewelry, wearing makeup. after 30 years i still remember that. i did complete my training and begin a job at stanford 20 years ago at the age of 40. about two years into that i developed breast cancer. i was still very confused about my gender identity, but i knew i did not like to have breasts and so when the doctor said he needed to do a mastectomy to remove the cancer, which was fortunately picked up early and i was cured of, i said, while you are there, please take off the other breast. [laughter] he was quite horrified by this.

he was the first one i shared my feelings with perhaps, but since cancer runs in my family, he did agree to move the other breast. i just can't tell you how therapeutic that was. i felt so relieved to have those breasts removed. i recognized that was a different response then my mom had when she saw this -- when she had a mastectomy. she saw this as a huge load to the -- blow to her femininity. then the doctor began to talk to me about reconstructing my breasts. i was horrified, there is no way you are putting these back on me. it occurred to me that there was something different about my gender. a year later i was reading the "san francisco chronicle" when i read a several page article about the life of james green. open elite female to male transgender person in the bay area. i realized for the first time in my life that there were other people who experienced the same sorts of gender confusion, there were other people like me and i might be transgender. i went to see a sex change pioneer at stanford and he ran a

gender clinic. after they evaluated me they told me that i thought i was transgender and they offered me the possibility of changing my sex, which was immediately irresistible to me and very quickly within weeks i decided to change sex. i had already had the upper surgery. the mastectomies. i did not want lower surgery, so all that was needed was to take testosterone. you can see the effects it has had on me. it is powerful stuff. when of the most surprising things about the testosterone was that to my great surprise it became harder for me to cry. male to females report that it becomes much easier for them to cry. that was perhaps surprising. the main experience i had was i felt after i changed sex, it's hard to describe the intense

relief i felt. like this weight lifted off my back and i have been so much happier since. i've never had another suicidal thought. at the time i decided to do this, i had been a scientist at stanford for several years. this was 20 years ago. i was very worried it would alter my career. but i have to say everybody, all my colleagues and friends and family were immediately supportive, and i have been very fortunate to have my career continue and to have lots of wonderful students and so forth. >> i want to show you a powerful example of identical twins. in this case, one of the male twins -- we have proven that these twins are indeed absolutely identical and born male -- one of them at age 3 started to say everything about being a girl. if there was any issue that came

up, she turned it into an issue of gender. she did some of those things we consider hallmarks, preferring to where female underwear and female pajamas, etc. by the age of 7, 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 9 to 10 years of age. charlie: what grade? >> fourth-grade. what i want to point out, that is if i switched all the attachments to them, the earrings, the clothes, hair style, shoes, you could

basically switch one for the other. the fact of the matter is that kids with their clothes on our are virtually interchangeable pre-puberty. actually, there are model levels -- their hormonal levels at this particular point are interchangeable. everything happens really at puberty. here they are at age 14. because it is so difficult to live in a gender different from your biologic sex, when you have a toxic effects of your genetically hormone driven puberty, which would basically make twin sister look exactly like twin brother. and you can see that she looks still almost like a 9 or 10 year old. 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 was receiving and that some of us make, but during fetal life, especially in the mid trimester, the level of testosterone in the fetus rises to a level close to the full adult range. and then it falls, and then there's another blip right after birth, second puberty. then things go completely dormant. in fact, if they did not go dormant, we would have a whole bunch of pubertal looking fifth-graders running around. because everything is suppressed. dr. kandel: when we are thinking about possible causes for transgender, wouldn't it be possible that some aberration in testosterone secretion or estrogen secretion during

intrauterine development or shortly thereafter might be one of the contributing factors. >> it is certainly possible. it's a very dynamic stage. we still don't know what that second bump is after birth, or what role it plays, or whether boys without testes or otherwise normal show any differences because of that. the problem is that when we went -- want to look at a hormone, we have to be able to get it out and measure it. you can't get it out of the brain. the other problem is sometimes it isn't the hormone level that is important, but the affinity of the receptor for the hormone. it's very difficult to measure such things. reallydel: it is a defining, biological problem, to see what is the biological underpinning of transgender identity.

it is so important because kids who are in the wrong sex, there are incidents of suicide attempt is very serious. >> it's one of the highest risks of any. dr. kandel: this is really something we need to understand. >> in the pubertal process, the whole system reawakens again, the system that had been awakened in utero suddenly comes back. hypothalamic hormones hitting the pituitary cause the release of other hormones that strike the ovary or the testes and cause the release of what we call the sex steroid hormones, which are testosterone and estrogen mainly. those things produce the differences between the body of the male and the female associated with puberty. we have been able to probably since the 1980's we have been able to 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 that it's completely reversible. look how revealing this is. the twin sister affirms a female identity and the puberty blocks for two years, two years to get more time for counseling without the pressure of body change. that is important for it if we are going to get her estrogen, that will have permanent effects. look at what would happen to her if she had not been given this blockade. she would look exactly like twin brother. he's in early puberty for a 14-year-old. 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.

while at the same time having her male hormones blocked. with that, our patients don't need breast surgery when they feminize because it is so effective. she is now entering junior high school, as is her brother. she's fabulous. this past october the dutch, who taught us, reported that first follow-up of the patients, 55 of whom whose puberty was blocked and for whom sex steroids related switched in the manner of the twin sister the dutch , group had surgery at 18, at which point their gender dysphoria, total uncomfortableness with their gender disappeared. the dutch found that the kids treated this way are psycho socially functioning as well or better than the control group of non-transgender kids they are being compared to.

charlie: a powerful argument for surgery? >> a powerful argument for available surgery at the right time for the right people. dr. kandel: also, one of the nice things about the dutch approach is it delays puberty. once puberty sets in, you have physical changes that make it much more difficult to reverse. so you prevent those physical changes of the other sex occurring. in addition to the biological changes it delays, it allows the child to think through whether this is the quest they want to be on. some people say i'm in the wrong body, i want to be a man when they are a woman, but change their mind after a few months. i think this is the wrong -- they think it is the wrong course. this delay allows not only the physiological process to be handled in a more satisfactory way, but the psychological evaluation to see whether this is the way the kid actually feels or if this is a temporary decision in their minds.

>> the dutch gave me their protocol in 2006, and we started using it in boston children's hospital, at which time we were the only major medical center to do so, but not that many years since 2006 and over 40 programs now are doing it. it is becoming the standard of care. ♪

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>> it is tuesday, the 29th of september. this is "trending business." ♪ yvonne: here is what we are watching for you this morning. down nearly 30% in hong kong following similar fall in london and new york. the one-time star has lost more than three quarters of its value since march. falling commodities and worries about china send asia stocks towards their worst close in nearly three years. japan is at its lowest since

february. the yen holds its gains. and wider world is the more car companies may be swept up in the airbag scandal. tesla, mercedes, and vw are among a number that have been contacted by regulators. let us know what you think of today's top stories by following me on twitter. do not forget to include the #trendingbusiness. it is an ugly day for regional markets. mining traitor glencore fell to record lows in new york, london, and now here in hong kong. juliette saly has been monitoring. >> quite a lot of selling coming through. we saw that they fall in london and new york. in open on hong kong, glencore shells -- shares falling by about