Chemical Messengers and Brain Builders: Unlocking the Secrets of Hormones and Genes

Hello, and welcome to So Curious, a podcast from the Franklin Institute.

We're your hosts.

I'm the Bull Bey. Yeah.

Yeah. And I'm Kirsten Michelle Cills.

Just kidding. I'm Kirsten.

And I'm the Bull Bey.

And this season is all about mental

health, the science behind it, the factors that impact it, and much, much more.

Yeah.

And in this episode, we're exploring how things in our body, like hormones and

genetics, can affect our mental health and disposition.

We're first going to talk to Dr.

Randi Hutter Epstein, a medical writer who quite literally wrote the book on the

history of how hormones were discovered by the scientific community.

Yeah and then we're going to chat with Dr.

Michael Gandal about his lab's research

into how genetics can help us better understand mental health disorders.

But before we get into all that, Kirsten,

what do you know about hormones and genetics?

Jesus Christ.

I know hormones are okay.

When I think of hormones, I think of them affecting your brain.

And people love to be like, oh, that girl

is being really moody because she's hormonal.

But then also, I know hormones are just like something that everybody has, right?

Yeah. I feel like the entire time you were

describing it, it sounded like you were describing teenagers.

That's what it sounded like to me.

Okay, well, then I guess let's chat with

someone who actually understands hormones better than we do.

Dr. Randi Hutter.

Epstein. Welcome to the show.

Introduce yourself and tell us what you do.

Hi, I am an MD, and I write about

medicine, and I also teach medical writing to undergrads at Yale College and to

graduate students at Columbia Journalism School.

And I'm the writer in residence at Yale School of Medicine.

And I'd say that my writing really looks

at the intersections of science and society.

So how things going on in society and

culture influence what doctors do, what scientists do, and then vice versa?

What their research how their research

influences the way we think about health and disease?

Yeah, that sounds like a study of a relationship, hopefully a good one.

Sometimes yes, sometimes not.

But isn't that what all relationships kind of are?

We won't go there.

Yeah, right.

That was last season.

You're so right.

So you wrote a book called Aroused the

History of Hormones and How They Control Just about everything.

Can you explain what that title means? Sure.

I'm going to go back in time a bit.

discovered the way that hormones work, we didn't have a name.

They just discovered these chemicals in the body that aroused the pituitary.

They aroused the adrenal glands.

They did all these arousing things in the body, these internal chemicals.

They knew that they were onto something big and they needed a name for it.

So this was 19 five.

And they did actually what doctors like to do.

They like highfalutin names.

So they went to two of their friends who are Cambridge University professors in

classics and said, what's a Greek word that means to arouse?

And again, we're talking arousing, the pituitary, the pancreas, all those really

exciting things that we all think about when we think about arousal.

And their Cambridge University friends

said, how about something along the lines of hormone, which is to arouse and Greek.

So they gave a talk at the Royal Society, the two British scientists.

They explained this new theory of how the

body works and they sort of said, almost aside, hormones, as we shall call them.

And that's how we got the name Hormone.

I'd like to say that they were at a

meeting and all the doctors were like, yes, love this idea.

Now we have a name.

But a lot of times people don't agree and they want to get their thing in.

So one of the doctors at the meeting said, not a good name.

How about autocoid, which means like internal cure or internal drug?

And that's kind of cool. We could see that.

That's 19 five.

More than 100 years later, when I'm finishing my book and I needed a title, I

turned to a friend of mine, just the way these Hormone guys did.

They turned to their smart friend and I turned to my smart friend Abby Ellen, who

is a prolific writer and wrote this book called Duped.

But her real claim to fame is she's great at name.

She named a haagendas ice cream flavor.

She named Carmel sutra.

No, if you can name Carmel Sutra, you can come up with a name for my book.

You can do anything.

I emailed Abby and I'm like, I need a name.

I can't call it hormone.

So she said, well, what does hormone mean?

And I said, well, the word comes from the word aroused.

And she said, well, that's your title.

And then I came up with this title and everyone loved it.

Some people thought it was misleading, but I don't think I'm misleading people.

It's the way you perceive the word.

I mean, you're aroused when you get out of

bed in the morning, if you're arousing to wake up.

Could you give us the exact science definition of what is a hornmon?

Break it down just in layman terms and all that good stuff.

Hormones.

I like to think of it as your internal WiFi.

And what makes hormones so exciting is they are teeny tiny bits, like

nanodroplets of chemicals that are released from a gland, let's say the

pituitary gland, which is in your brain or your testes or your ovaries.

They're droplets of chemicals that reach specific targets.

So nowadays, because we have WiFi and emails, it's like, no big deal.

But think back when we used to think that everything in the body traveled along

nerves, like you're working in a factory and you just hand it to the next person.

These widgets, the concept that a little chemical could come out of your brain and

then reach your testes and not anywhere else.

That was remarkable.

So that's why I think of it as like your internal WiFi.

And honestly, I don't really understand

WiFi, and I don't understand email or technology.

But I do know that when I send an email, if I write it to a friend, that email is

going to flow through cyberspace and I hope only goes to that friend.

And so that's what we think of hormones as chemicals.

Doctors like to say travel a distance, and

when they say distance, they mean like head to testes, head to ovary.

That's what makes hormones so remarkable.

Your book spores all the bizarre turns

that were taken while researching hormones.

What are your favorite stories from the book?

Gosh, I have a lot of favorite stories.

I love the story of growth hormone, in a sense, because it talks about the hubris

of doctors and what desperate parents would do.

And then I also read about oxytocin, which, you know, is the love hormone and

like where we sort of exaggerated those claims.

getting vasectomies for their mental health.

I love how this is starting already.

I just want to repeat that right now.

We do not think that men should be getting

vasectomies to boost their egos and their mental health and their urine output.

know that was a thing that men cared about.

And they're a libido.

Obviously that has to do with it went up.

So right now we think vasectomies are for

people that do not want to worry about impregnating someone else.

We don't think of them as mental health boosters.

patients to seek out a treatment that might not be proven.

And also sometimes how we base science on assumptions that might not be accurate.

So where do we get this from?

He was a preeminent neuroscientist who

studied a lot about hormones and the psyche.

He did a study on two rats and gave them

vasectomies to see how it affected their moods and behavior.

Because of two assumptions.

One was right, one was wrong.

One thing he thought correctly was that

cells near the sperm duct secrete some kind of male hormone.

Today we do not like to think of testosterone as the male hormone.

Women have it too.

It wasn't even named yet.

But he thought there was something potent being secreted near the sperm ducts.

He was right. People didn't really believe that.

Here's what he was wrong about.

He thought when you blocked cells in an

area of the body, the cells around it would proliferate like weeds.

Like if you plucked a flower out of a

garden, weeds would come in and proliferate.

So he thought, oh, if I do something to

block something near these producing cells, we'll just have more of them.

One, he was wrong on that, and two, this

is just based on his idea of what a male hormone juice would be.

His assumption, right?

Huge assumption.

So he did this wonderful study and I don't think you have to be a statistician to

realize that two male rats is not a large sample size.

He gave them vasectomies.

I don't know how he judged their libido, but he claimed to think that these two

little vasectomized rats just seemed healthier than ever.

and lost his libido and right after the surgery, he never felt better.

So from there, word got out and this

doctor who created this idea of vasectomies, his last name was Steineak.

His name was Eugene Steiner.

It was called Steinecking.

You didn't say, I'm having a vasectomy to boost my libido.

You said, I want to be Steineact.

Freud was Steineact, the famous poet.

Yates was Steineact this was going on in Europe, but American men heard about it

and they were lining up begging for vasectomies.

Steineact, baby. Wow.

Exactly. Yeah.

Hashtag, Steineact me.

If you want it to stay fertile, you could just do one side.

I mean, to me it's fascinating because it

proves, one, the power of placebo, two, what men will do if someone says, I

have something that's going to boost your libido and make you feel better.

And three, how sometimes things take off.

There were doctors at the time in the

1920s saying there's no science, but that's really hard to push back against

men lining up and saying, my libido is great.

Yeah. This is, first of all, blowing my mind.

So what are people most surprised about in

something like, oh, I didn't know that was controlled by hormones?

I think to me, one of the big issues in

hormones, a few things that I think it's misunderstood and it's kind of hard to

wipe out of our brain imaging of this is we tend to think of hormones in silos.

Like if you think of horses on a

racetrack, there's the growth hormone track for growing and there's the estrogen

one, which we mistakenly always think makes you the female thing.

And men have estrogen, the testosterone

one, and we think of them all in their own separate tracks.

But honestly, you should think cobweb in your head, not like race tracks.

They all interact with each other and now

we're learning that they interact with our immune system.

So how you fiddle with your hormones is going to fiddle with your immune system

and vice versa, how your immune system is going to affect your hormones.

And then the other really shocking thing

that has come out recently is all this talk of the microbiome.

We all hear about our gut bacteria and all

these teeny little microbes that are living within us.

There's more of them than there are of us.

They interact with our hormone system and they may be secreting hormones.

So all of that complicates the picture.

The other thing, which isn't new, but I think is just fascinating.

And what does that mean?

That means that hormones aren't just metabolism and growth and sex drive.

They're your yearnings and desires.

And I don't mean like just sexual desires, but hunger, appetite.

So it's so much more complex and it's so much more fascinating.

And it kind of does make us realize that we are our chemistry.

There's all this thing of like, control your hormones, control your chemistry.

But if we are our chemistry, where's that?

It's more circular than just getting on top of things and controlling them.

Yeah. I was actually going to throw in there

this great philosopher, Ludicrous and Nate Dog.

They once said, control your hormones and keep your drawers on.

And I was like, does that suggest that we

actually can control our hormones or are we controlled by them?

And you mentioned that circular dynamic.

Where does our influence exist in that circle?

I think that enters into some weird philosophical thing.

I mean, in some ways it's philosophical, in some ways it's easy.

So the philosophical side is like, is our

influence, though, of what we're trying to do?

Is that our hormones telling us to do that?

So where does that start?

On the other hand, there are people that have documented low levels of certain

hormones, either from a tumor or disease or for whatever reason, and we now can.

Thanks to endocrinology advances, we now

have ways to help people that have low hormones.

For instance, a pituitary gland.

The pituitary sends out so many signals.

100 years ago, if you had a defective or

non working pituitary, it wouldn't kill you, but you would never mature.

You'd never go through puberty, you'd never grow napa days.

And I met someone who was born with a non functioning pituitary.

He was like this brainiac dynamic kid, and

his doctors were able to diagnose it early on and give him the growth hormone he

needs, the testosterone he needs, not pumping him up to be a superman.

He did seem super special when I met him,

but just making sure, like, he went through puberty, he grew.

There's actually some amazing advances where we can keep people feeling healthy.

I mean, we take insulin for granted that we have that.

That's a hormone that's keeping diabetics alive.

Yeah. Since we are doing mental health, that is

the name of the game for this season three.

How do you think our understanding of

hormones has changed how we understand mental health today?

I think what we need to understand is that we're not going to say this chemical is a

little low and I'm going to give it to you.

And this is why you're feeling depressed, because of this hormone.

I even think we still tend to think, oh, women are hormonal before their periods

because their estrogen is this or progesterone is that.

I think it's oversimplified.

Women going through fertility are put on massive doses of these hormones yeah.

That can really trigger depression and make them feel differently.

So we know there's receptors in the brain for estrogen, progesterone, all these

hormones, but that's very different from going to someone and having them measure

your hormones from those levels that snapshot.

They can't say like, oh, you're depressed

because of this, and we're going to treat it that way.

One of the things that we're also finding is it may not be your exact level.

You don't want to get like, a fitbit of

hormones to compare your levels to your friends.

It may be the swings.

So you may have a certain level of estrogen in you and then it menopause.

When it slams down and plummets, it's that change.

It's that plummet that makes you feel different, not the actual level of it.

You've researched the history of hormones, so what does the future look like?

I think that the neuroendocrinologist that I speak to and these people are so smart,

and I've actually recently talked to Neuro Gastroenterologists.

I think that there's a lot of scientists

out there that are breaking out of their traditional silos and really looking at

this mind body interplay in ways we hadn't before used to be.

Let's learn as much as we can about this hormone.

And it was also so binary about what women were like and what men were like.

And I think now we're really trying to

understand how our hormones, how the nerves in our gut, the nervous system, how

our immune system, how they all interact with each other.

Dr.

Epstein randi, thank you so much for being here.

Seriously, we really appreciate all of this.

This was very informative. This was an awesome conversation.

Yeah, it was so awesome to talk to you. Thank you.

Thank you so much to Dr.

Randy Hunter Epstein for coming on to the show and speaking with us.

Yeah.

Who knew the history of something like hormones would be that wild?

Hey, Bey.

So do you ever wonder whether this planet is even going to exist in 30 years?

I do.

Mhm.It can be overwhelming to think about

how to deal with some of the biggest problems we're facing.

Our friends over at the Franklin Institute

talked to some of the sharpest minds working in science and technology, though,

docuseries from the Franklin Institute at fi.edu.

Nice.

We've looked at the history of hormones,

but now let's look at the future of genetics.

Bey, what do you know about genetics?

Well, there is this historical group called the X Men.

And somewhere in there they talk about genes and mutation.

And that might be the limit of what I know about genes.

I was going to say the only thing I know

about genes is I remember when I was in high school, I had this friend, he was a

photographer, Peter Parker, and he got bit by the spider.

There you go. And it was the craziest thing.

All his jeans got rewritten and he was shooting webs.

And was just walking on walls.

In any case, hopefully our next conversation will bring it down to earth.

Yeah.

And if we get the courage to ask that to a professional, then we will.

But I'm going to try to seem professional.

I won't ask about spiderman unless it comes up organically.

Let's welcome Dr.

Michael Gandal to so curious, can you introduce yourself and what you do?

Sure.

Well, thank you for inviting me to come talk with you guys.

I'm Michael Gandal.

I'm the Hetznecker Associate Professor of Psychiatry at the University of

Pennsylvania and I run a developmental brain genetics and genomics research lab

at Penn and at the Children's Hospital of Philadelphia.

Nice.

Just so we could have an idea going forward.

And for the audience, can you explain what genes actually are?

Yes let us know. What's the working definition?

That's a great question.

So we all have inside of every cell in our

body, 23 chromosomes that are comprised of 3 billion base pairs of DNA.

That's A's, T's, G's and C's that we all inherit from our mom and our dad.

And every single cell inside the nucleus has two copies of each of these.

And these are the instruction manual for what makes us a person, what makes us

tick, and what makes our bodies and cells do what they do and how we develop.

As it relates to your research, how would you define mental health?

So I'm trained as a psychiatrist.

I went to medical school and did clinical training in adult psychiatry.

And so I treat patients who have various mental health conditions.

And mental health are sort of constellations of symptoms that people

experience that kind of go together that can cause some impairment in how somebody

might be able to think or feel or function in the real world.

And the symptoms kind of go together in

certain patterns and we give them names, things like depression, anxiety, or autism

spectrum disorder, which is what we're studying for the most part.

And they are sort of characterized by these groups of symptoms.

But it actually is a really hard thing to

define because the symptoms are kind of subjective and it's not like you can go to

the doctor and get a blood test or you can go to get a brain scan and it says.

You have. This exact thing

Right.

And so that's what makes, I think it particularly hard to study some of these

disorders and mental health conditions that we do.

What conditions does your work focus on?

So my lab and my research mostly focuses on the neurodevelopmental side.

So that means brain development.

So different conditions that occur within

the first, say, two or three decades of life.

So I mentioned autism being one of them,

which is something that happens very early in life.

But we also study things like

schizophrenia, which is another mental health condition, which doesn't really

begin to show symptoms, often until 18 to 20 to 30.

But we now appreciate that it has a lot of roots in early brain development, whether

it's during fetal brain development or early childhood.

Okay

Wow and so you direct a developmental let's see if I can get this right.

A developmental neurogenomics research

laboratory, the Gandal lab, is that correct?

That is correct. And then can you tell us about it?

What does your research look like?

What's your day to day?

Yeah, so we are really interested in understanding how these different

disorders come about and really trying to translate symptoms into biology and

understand the basic biology of neuropsychiatric disorders.

And the way that we do this is to leverage genetics as kind of a foothold.

So, as I mentioned before, it's often very hard to define or to really systematically

understand what these disorders are that are characterized by various symptoms, to

how people are thinking or feeling or behaving.

It's very hard to quantify it.

But one thing that we do know, and we've known now for several decades, is that if

one person in a family has some kind of pattern of symptoms related to mental

health, other people in the family likely have something similar.

This tells us that these conditions are heritable, which means that there are

certain genetic factors that are shared between members of the same family that

are likely contributing to these different symptoms.

And so my lab, that's sort of the guiding foothold that we try to use to understand

biology and what do we do on a day to day basis is that we rely a lot on two things.

One is human brain samples.

We actually are very fortunate to be able

to get access to hundreds to thousands of post mortem human brain tissue.

Wow I was going to say, how do you get that?

Yeah. wow! How do you find that at?

Wow, that's not lying around. Well, hopefully not.

Yeah, right. It's not.

Which is one thing that makes it very

tricky to study brain disorders, is that you can't just go in and take a biopsy.

You can't just take a piece of somebody's brain.

And so we have to rely on brain banks and post mortem brain tissue and basically

relying on individuals in the community who recognize the importance of this type

of work and are willing to say, if my loved one passes away for some reason and

they had a certain condition, that they'll donate it to different brain banks.

And organizations like the Autism Tissue program or the autism brain net, which is

actually where we get a lot of our brain tissue samples from.

And that really helps us to understand and

develop better insights and biological understanding for things like autism is

extremely important for the work that we do.

Do you see in the future?

Because like you said, you can't just do a blood test and find out if somebody is

going to be predispositioned right, to have a condition.

But do you think that there will be?

Like I'm thinking about so I have cystic fibrosis genetic disease and it was a

nightmare getting diagnosed because especially in the mid 90s when I was born,

so it took forever because there's so many possible mutations.

Do you think that there is going to be or hopefully the ability to actually take

blood one day and be able to spot those disorders?

Yes and no is the simple answer.

We are definitely gaining a much greater appreciation for the genetic causes of

various mental health conditions like autism.

And at the very extreme end of the

distribution, you do have these forms of autism where if somebody has a genetic

variant, they're very likely to have the disorder.

And that's something that you could

potentially test for somewhat along the lines of what we do now in prenatal

screening, for example, for some other developmental conditions.

But those tend to be very rare.

The vast majority, I think, of the genetic

risk or genetic load is not nearly as deterministic.

It's again, kind of a bunch of shades of gray.

And so I don't think we'll ever necessarily be able to say yes or no, but

I think we'll be able to think of it more along the lines of predicting risk.

Like the genetics will say you're at a two fold increased risk or a fourfold

increased risk based on this pattern compared to general population.

Now, you talked about this already, but can you talk a little bit more about the

relationship between genes and mental health?

How does genes impact mental health and vice versa?

How does mental health impact genetics?

Yeah, that's a really interesting and loaded question.

The way that we know that genes impact mental health, it kind of goes back to

this idea that if a person in a family has symptoms of a mental health condition,

more people in the extended family likely have similar symptoms.

And we can actually take measurements of

how related everyone is in a family or in a large population and how similar the

symptoms, say, of schizophrenia or autism or depression or whatever.

And then we can actually use that to calculate a number that tells you sort of

how genetic or how heritable this condition is between zero and one.

How much does genes impact these symptoms?

And so for autism and and schizophrenia, the two main disorders that I study, it's

somewhere between 70 and 80% in the population is being driven by genetics.

Now, we don't know what the individual genes are yet, but we know, sort of in

aggregate, you take all of the genetic material or all the genetics together, and

it contributes about 70% to 80% in the population.

Wow.

I want to ask this what ideas around genetics and mental health do you wish

were more widely understood by the general public?

Two things, I think, that we need to

understand that a lot of these disorders do have roots in genetics.

And I think that in some cases, that can

actually be very liberating to people to kind of, for example, know that it's not

necessarily their fault if somebody in their family or a kid begins to struggle

with some of these issues, because it's not something they necessarily did.

It's just something that these genetic factors that we all have within ourselves,

and it sort of helps take some of the pressure off, I think, a little bit, or

that the parents especially put on themselves.

I really appreciate that.

I just want to kind of focus on that for a second, because I think carrying around

guilt and shame really makes it difficult to tackle some of these things.

And that's not just like somebody saying

that emotionally, you're talking about scientifically, it's just not your fault.

It's just not necessarily something we did.

YeahExactly.

And I'll give you a very concrete example

of this that I think also hits close to home.

So there was a study many years ago that

looked at pregnant women who were taking certain medications during pregnancy and

what the outcomes were in the kids that were born from those pregnant moms.

There's been many flavors of these types

of studies that have been done along the years, but the two medicines that have

been looked at one was the SSRI medication, which is a commonly used

medicine that we prescribe for things like anxiety and depression.

And then the other one was

Tylenolacetameenophen, which is a commonly used pain medicine.

And both of those are thought to be pretty

safe to use, actually, during pregnancy, although you should always consult with

your own doctor about individual medication decisions.

But what the initial studies found was that there were elevated rates of things

like autism and ADHD in the kids when moms took those medicines.

What those studies, though, failed to account for was the fact that there's

genetic reasons that moms may be taking medicines for these conditions.

So maybe mom has a little bit more of a genetic predisposition for anxiety or

depression or something like that, and then is on the medicine, and then we'll

pass those genes on to their kid, and then maybe the kid will have some symptoms.

And so it's actually nothing to do with

the medicine causing some exposure, but it's really just tracking the genetics.

And when you control for the genetics,

almost all of these associations really get substantially reduced.

And I think that there are a lot.

Of moms out there who maybe took some

Tylenol during pregnancy and then had a kid who had struggles and then blamed

himself for that decision because these studies come out.

And really what the genetics I think is

showing is that these things matter a lot less than we think they do.

Interesting. And so my last question for you then,

Michael, is what does the future of your research look like?

We are, I think, at a very exciting time right now in genetics in general and brain

genetics, where every day there's a new, bigger study of trying to identify these

genetic risk factors for these disorders coming together.

Very large biobanks, they call them, are

really huge studies and I think it's very exciting because we're starting to get a

foothold on what these genetic factors are.

And I'm really excited now to take it to

the next level or the next stage, which is to then build an understanding of what

these variants in genes are doing altogether and be able to start making

predictions about treatments or therapies or things that we can do to help people in

a more specific way based on what their genetics are.

And in some very rare cases, this may be something like gene therapy almost type of

approaches where if there's a really rare mutation that somebody might have that we

know is fully associated with the disorder, that one could potentially go in

and actually try to edit that out or correct that specific change.

Or probably on the more common side, which

is just really predicting which medicines somebody might respond to, or even

predicting new medicines based on genetics that might work.

And I'm really excited about that era, what we call this precision medicine.

And I think we're getting very close to

being able to do this now and really begin to translate all this knowledge that we

have, but actually make a difference in people's lives.

Awesome. Hell yeah.

Thank you so much to both Dr.

Gandal and Dr.

Hutter Epstein  for coming on the show.

We really did learn so so somuch.

And make sure you tune in next week to learn even more.

This time, all about how medications are used to treat mental health conditions and

what medications might look like for the future.

What is it about this person that says

this is the right drug or this is the wrong drug?

All that and more on the next episode of So Curious.

And don't forget to subscribe to this podcast wherever you listen.

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And I'm Kirsten Michelle CillsOh, yeah. And I'm the bull Bey.