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)