The biology of gender, from DNA to the brain | Karissa Sanbonmatsu

So what does it mean to be a woman? We all have XX chromosomes, right? Actually, that’s not true. Some women are mosaics. They have a mix of chromosome types
with X, with XY or with XXX. If it’s not just
about our chromosomes, then what is being a woman about? Being feminine? Getting married? Having kids? You don’t have to look far
to find fantastic exceptions to these rules, but we all share something
that makes us women. Maybe that something is in our brains. You might have heard theories
from last century about how men are better
at math than women because they have bigger brains. These theories have been debunked. The average man has a brain
about three times smaller than the average elephant, but that doesn’t mean the average man is three times
dumber than an elephant … or does it? (Laughter) There’s a new wave
of female neuroscientists that are finding important differences
between female and male brains in neuron connectivity, in brain structure, in brain activity. They’re finding that the brain
is like a patchwork mosaic — a mixture. Women have mostly female patches
and a few male patches. With all this new data,
what does it mean to be a woman? This is something that I’ve been
thinking about almost my entire life. When people learn that I’m a woman
who happens to be transgender, they always ask, “How do you know you’re a woman?” As a scientist, I’m searching
for a biological basis of gender. I want to understand what makes me me. New discoveries
at the front edge of science are shedding light
on the biomarkers that define gender. My colleagues and I in genetics,
neuroscience, physiology and psychology, we’re trying to figure out
exactly how gender works. These vastly different fields
share a common connection — epigenetics. In epigenetics,
we’re studying how DNA activity can actually radically
and permanently change, even though the sequence stays the same. DNA is the long, string-like molecule
that winds up inside our cells. There’s so much DNA that it actually gets tangled
into these knot-like things — we’ll just call them knots. So external factors change
how those DNA knots are formed. You can think of it like this: inside our cells, there’s different
contraptions building things, connecting circuits, doing all the things they need
to make life happen. Here’s one that’s sort of reading
the DNA and making RNA. And then this one is carrying
a huge sac of neurotransmitters from one end of the brain cell to the other. Don’t they get hazard pay
for this kind of work? (Laughter) This one is an entire molecular factory — some say it’s the secret to life. It’s call the ribosome. I’ve been studying this since 2001. One of the stunning
things about our cells is that the components inside them
are actually biodegradable. They dissolve, and then they’re rebuilt each day, kind of like a traveling carnival where the rides are taken down
and then rebuilt every single day. A big difference between our cells
and the traveling carnival is that in the carnival, there are skilled craftsmen
that rebuild the rides each day. In our cells, there are
no such skilled craftsmen, only dumb builder machines that build whatever’s
written in the plans, no matter what those plans say. Those plans are the DNA. The instructions for every
nook and cranny inside our cells. If everything in, say,
our brain cells dissolves almost every day, then how can the brain remember
anything past one day? That’s where DNA comes in. DNA is one of the those things
that does not dissolve. But for DNA to remember
that something happened, it has to change somehow. We know the change
can’t be in the sequence; if it changed sequence all the time, then we might be growing like, a new ear
or a new eyeball every single day. (Laughter) So, instead it changes shape, and that’s where those DNA knots come in. You can think of them like DNA memory. When something big
in our life happens, like a traumatic childhood event, stress hormones flood our brain. The stress hormones
don’t affect the sequence of DNA, but they do change the shape. They affect that part of DNA with the instructions for molecular
machines that reduce stress. That piece of DNA
gets wound up into a knot, and now the dumb builder machines
can’t read the plans they need to build the machines that reduce stress. That’s a mouthful, but it’s
what’s happening on the microscale. On the macroscale, you practically lose
the ability to deal with stress, and that’s bad. And that’s how DNA can remember
what happens in the past. This is what I think
was happening to me when I first started my gender transition. I knew I was a woman on the inside, and I wore women’s clothes on the outside, but everyone saw me as a man in a dress. I felt like no matter
how many things I try, no one would ever
really see me as a woman. In science, your credibility
is everything, and people were
snickering in the hallways, giving me stares, looks of disgust — afraid to be near me. I remember my first big talk
after transition. It was in Italy. I’d given prestigious talks before, but this one, I was terrified. I looked out into the audience, and the whispers started — the stares, the smirks, the chuckles. To this day, I still have social anxiety
around my experience eight years ago. I lost hope. Don’t worry,
I’ve had therapy so I’m OK — I’m OK now. (Laughter) (Cheers) (Applause) But I felt enough is enough: I’m a scientist, I have a doctorate in astrophysics, I’ve published in the top journals, in wave-particle interactions,
space physics, nucleic acid biochemistry. I’ve actually been trained
to get to the bottom of things, so — (Laughter) I went online — (Applause) So I went online, and I found
fascinating research papers. I learned that these DNA knot things
are not always bad. Actually, the knotting and unknotting — it’s like a complicated computer language. It programs our bodies
with exquisite precision. So when we get pregnant, our fertilized eggs grow
into newborn babies. This process requires
thousands of DNA decisions to happen. Should an embryo cell become a blood cell? A heart cell? A brain cell? And the decisions happen
at different times during pregnancy. Some in the first trimester,
some in the second trimester and some in the third trimester. To truly understand
DNA decision-making, we need to see the process
of knot formation in atomic detail. Even the most powerful
microscopes can’t see this. What if we tried
to simulate these on a computer? For that we’d need
a million computers to do that. That’s exactly what we have
at Los Alamos Labs — a million computers
connected in a giant warehouse. So here we’re showing the DNA
making up an entire gene folded into very specific shapes of knots. For the first time, my team has simulated
an entire gene of DNA — the largest biomolecular simulation
performed to date. For the first time, we’re beginning
to understand the unsolved problem of how hormones trigger
the formation of these knots. DNA knot formation
can be seen beautifully in calico cats. The decision between orange and black happens early on in the womb, so that orange-and-black patchy pattern, it’s an exact readout of what happened when that cat was
just a tiny little kitten embryo inside her mom’s womb. And the patchy pattern actually happens
in our brains and in cancer. It’s directly related to intellectual
disability and breast cancer. These DNA decisions
also happen in other parts of the body. It turns out that the precursor genitals
transform into either female or male during the first trimester of pregnancy. The precursor brains, on the other hand, transform into female or male
during the second trimester of pregnancy. So the current working model is that a unique mix in my mom’s womb caused the precursor genitals
to transform one way, but the precursor brain
to transform the other way. Most of epigenetic research has really focused
on stress, anxiety, depression — kind of a downer, kind of bad things. (Laughter) But nowadays — the latest stuff — people are looking at relaxation. Can that have a positive
effect on your DNA? Right now we’re missing
key data from mice models. We know that mice relax, but could they meditate
like the Dalai Lama? Achieve enlightenment? Could they move stones with their mind
like Jedi Master Yoda? (Yoda voice): Hm, a Jedi mouse
must feel the force flow, hm. (Laughter) (Applause) I wonder if the support I’ve had
since that talk back in Italy has tried to unwind my DNA. Having a great circle of friends,
supportive parents and being in a loving relationship has actually given me strength
and hope to help others. At work I wear a rainbow bracelet. Sometimes it raises eyebrows,
but it also raises awareness. There’s so many transgender people — especially women of color — that are just one demeaning comment
away from taking their own lives. Forty percent of us attempt suicide. If you’re listening and you feel
like you have no other option, try to call a friend, go online or try to get
in a support group. If you’re a woman who’s not transgender
but you know pain of isolation, of sexual assault — reach out. So what does it mean to be a woman? The latest research is showing that female and male brains
do develop differently in the womb, possibly giving us females
this innate sense of being a woman. On the other hand, maybe it’s our shared sense
of commonality that makes us women. We come in so many different
shapes and sizes that asking what it means to be a woman
may not be the right question. It’s like asking a calico cat
what it means to be a calico cat. Maybe becoming a woman
means accepting ourselves for who we really are and acknowledging the same in each other. I see you. And you’ve just seen me. (Applause and cheers)

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