Nature or nurture? The role of epigenetics


[Music]>>JEFF STOWELL: How many of you have heard
of epigenetics before? How many of you have not heard of epigenetics? OK, about half of
you. First of all, this is a photo that I took in one of the Smithsonian museums
that a human evolution exhibit and you can sit down and, and find out what you would
have looked like as a Neanderthal man so that’s me actually on the right there.
Now, one of the pervasive questions in psychology is the nature-nurture debate, right? You know,
where you born this way like Lady Gaga you know or did you, you
know was it the home you were raised in that causes development? And let me first emphasize
and you, you probably understand it’s the original question has
really should never have been is it nature or nurture ah because clearly you can’t
have one without the other. And the real question was can differences between people,
ok, the variability among a trait or characteristic can it be explained, uh, to what extent can
it be explained by genetics versus your environment? And of course
they do the twin studies and family studies and, and you can get some estimate of the
heritability, uh, of a characteristic. So your height and weight,
uh, do have a strong genetic component to them. Um, what religion you are probably very
little genetic contribution to that. Although I do remember a study that
found that your attitudes on, uh, life issues seems to carry some genetic component, you
know, on euthanasia or abortion issues. And even your tendency to like thrilling
roller coaster rides ok, to some extent. So, yeah you can probably find some genetic influence
on just about any behavior. Um, here’s a question, a nature-nurture
question. The pose of a champion, ok, is that an innate behavior that the puffed up chest,
the arms raised, ok, that that signifies victory over a, over a competitor.
Ah you know and how did we come to know that? So, this is certainly not a definitive study
but ah they looked at blind ath- wrestlers, ok, who have presumably been
blind from birth or at least early on. And they found that after, after winning a wrestling
match that the winner took the victory pose ok as, as Michael Phelps here
in this picture. And when they lost they had kind of the dejected pose, right, the slumped
over look. So, maybe, you know, that has some genetic inheritance in that
behavior. So, we like to come up with numbers, right,
that tell us just how much a characteristic is inherited and heritability is a measure
between zero and one. One is perfect, uh, genetic inheritance, zero is
absolutely none. And you know we like to look at things like intelligence and we find that
some studies suggest inheritance of up to point seven for IQ, whatever that
measures, ok, uh, that would suggest there is a strong genetic component and maybe some
of you have heard the story of the Jim twins, ok, how many of you have heard
the Jim twins study, OK? Most of you, look it up if you haven’t. Um amazing similarity
in their, uh, physical characteristics they are identical twins that
were separated shortly after birth. Ah but where the vacationed, type of car they drove,
the names of women that they married and divorced and then married again.
And, uh, their children and so forth. So raises some you know this is really important and
interesting component of our field. So let’s just talk just briefly about the
hard core genetics and we know that chromosomes – we have 23 pairs of them in humans. They
have segments upon which we label them genes, ah which are simply codes of DNA
which are made up of you know base pair nucleotides, ah DNA. Ah wound up in this ah helical model.
Ah what did one chromosome say to the other chromosome? Do
these genes make me look fat? [Laughter.] So, you know, and we know that dominant recessive
principle, and just basic Mendelian genetics. That’s probably what you are familiar with
and probably even most of your students. We all have high school biology
and we learn about those round and wrinkled peas. And maybe you’ve heard um about Lamarckian
evolution and how that is different than uh I guess regular evolution,
[laughs]. Ah does anyone is anyone familiar with Lamarckian evolution that would like
to explain it? Steve.>>STEVE JONES: Was this the one where Lamarck
said that giraffes got taller because they needed to be taller to eat and so because
they needed they stretched their necks more and that’s what made them taller
and then therefore their offspring were therefore more tall taller or something?>>STOWELL: Precisely, ok, he believed that
the use and/or disuse of characteristics influenced those characteristics in the offspring. So
for example if you worked out and got big muscles then uh your offspring
would have more be more likely to have the same physique of muscles. Maybe you’ve heard
this in popular culture, well we keep taking out our wisdom teeth ‘cause
we don’t use them, in the future, people will be born without them, right? Ok is that
true? No, the only way that that will ever be true is if people who are born without
wisdom teeth reproduce more than people who are born with wisdom teeth. Ok so it just
so happens that of my children who are old enough to know ah none of them
have wisdom teeth ok. I did my wife only had two and so we are lucking out on some, uh,
oral surgery bills right. Um, so anyway I’m doing my part for human evolution
right? [Laughter.] Or that um because maybe we don’t use our
little toe then someday we will be born without an ex- the fifth toe right. This is the idea
this is kind of like popular culture. Well we know, uh, from Mendelian
genetics that that can’t be true. Uh, giraffes won’t have children or offspring with longer
necks simply because they stretched theirs. Ok, that makes no sense,
right, you know? How would that be encoded in the genes that get passed on? Well you
know the real reason why giraffes have long necks don’t you? Oh no. Well it’s
because their heads are so far away from their bodies. That’s why they have long necks.
Connect them. Well, Lamarckian evolution was you know, those
were the days of past and there was no functional explanation for how that could occur. Well, epigenetics is overturning pretty much
everything that we know about, uh, the nature nurture debate. And, in fact, in some ways
is a return to Lamarckian evolution. Which may, which may surprise you.
How can that be? [Clears throat.] Epigenetics, the word literally
means above genetics. Or above the gene code. Ah we have the DNA sequence we have done the
Human Genome Project, we have some idea of the 25,000 or so genes that,
that humans carry. Um their chromosomes. But epi- means above. And it essentially means
a modification of which genes get turned on or off, and surprisingly it
is our exposure to the environment that turns genes on or off. Now, that may be no big surprise to you except
that these epigenetic changes, if they occur in the sex cells, can be transmitted to the
offspring. Wow. What are epigenetic changes? Well, once again, they
are changes in the expression of which genes get turned on or off depending on, uh, exposure
to things in your diet ok or in the environment. And the way that these changes
take place is note in this, uh, winding of the DNA strands around these proteins called
histones. And [clears throat] they can be wound so tightly around these
proteins that there are certain segments of the DNA code that can be inaccessible for
transcription, ok, so that they can never produce the proteins that they code
for. Simply because of the physical covering ok in the winding of this DNA strand around
these histone proteins. That’s one way, that’s one epigenetic mechanism. Is
simply by affecting the shape of the histone proteins, then affecting which genes can be
exposed physically to be trans, transcribed or not, ok. Maybe more importantly, ok, is another mechanism
which is not shown on this slide but it is later. Which is that on the DNA sequence itself
you can have a methyl group which is nothing more than a CH3 group, you
know, carbon and three, three hydrogen ions attached. You can put a methyl group on a
sequence of DNA code which will either allow that gene to be transcribed or
not, ok. Somebody, sounds like somebody is conference calling, ok. So let me ah let me talk about one study and
then maybe give you some a few other possibilities of how epigenetic changes may influence ah
behavior. Ok ah this was a study with mice, and these were I think these
were male mice … um, I believe these were male mice, ok. And they did a classical conditioning
paradigm with these male fathers in which they paired a cherry scent
or odor with shock. And as you might expect this odor became a conditioned stimulus that
elicited fear, ok, in these animals. Then they breed these fearful fathers
ok with female rat er mouse. And they measured the offsprings’ reaction to this novel odor,
they’ve never smelled this cherry scent before. And how do the offspring
react? The offspring demonstrate a greater sensitivity to this chemical if their father
prior to conception had been classically conditioned to fear it. Now isn’t
that amazing? Ok. Because they’ve got the same DNA sequence as other offspring from
non-conditioned fathers. Ok. Same code for this olfactory receptor, ok. But
what differed was the methylation of that gene code for the receptor. And they found
that the offspring of those who had been exposed to the fearful ah condition, well,
whose fathers had been exposed to the fear condition that there was I think it was less
methylation of this DNA sequence which lead to an overexpression of the olfactory
receptor that this chemical bound to, ok. Yes?>>PARTICIPANT: Can you just explain what methylation
is?>>STOWELL: It’s the binding of a methyl
group onto the DNA sequence, and I, I don’t know e- exactly where it binds, but it’s
– a methyl group is just a CH3 chemical formula: carbon ion – carbon atom and three
hydrogens. It just sticks on and, uh, we’ll see in a little video I’m gonna show you
–>>PARTICIPANTS: [Unclear].>>STOWELL: Yeah it – yes, onto the DNA.
Now, the other thing that’s interesting – this is a reversible process, ok, and
it probably depends on your diet, and not only what the father had been exposed to prior
to conception, but what the mother had been exposed to prior to – or – to conception,
or during pregnancy. So, let me, uh – yeah, is there another –>>PARTICIPANT 1: Is it ok if I – oh wait
–>>PARTICIPANT 2: No, go ahead.>>PARTICIPANT 1: Um, so, if we take some supposition
a little farther based on the study, I mean obviously, you know, it’s not causal, but
correlational, I mean, so we don’t [unclear] –>>STOWELL: Well this is –>>PARTICIPANT 1: This is causal.>>STOWELL: This is a pretty good design. I
mean, it’s an experimental design, you s- you selectively breed some who are feared,
others who are not, and then look at the offspring, and look at the receptor and
its methylation.>>PARTICIPANT: So, if you take that situation
and apply it to human beings of, like, being raised in a very stressful environment, for
example, in poverty, in conflict, in war, even if – I mean, it could
alter the genetic sequence expression if two of those people who are in that community
mate and have offspring, they’re gonna be more susceptible to stressors in
their environment than those who aren’t raised like that.>>STOWELL: Possibly.>>PARTICIPANT: Possibly.>>STOWELL: So, let me tell you –>>PARTICIPANT: – possibly even more –>>STOWELL: I’m probably going to mess up
on some of the details of this study, but it was in um Sweden, and they looked at, there
was a famine. Uh and during that period of famine individuals who were I think
prepubescent ok they looked at that age and found that their offspring, ok, were more
susceptible and I think independent measures were cardiovascular disease and maybe
diabetes, ok, with some health related outcome. They found a difference, but it was only carried
among I think the paternal line in one case and then there was
another disease that was carried only through the maternal line, but it depended on their
experience when they were young, ok, which influenced their posterity. Now
how long are these epigenetic changes transmitted across generations, we don’t know yet, really.
Um but it seems we know at least in animals it can be perpetuated through
at least one generation. And I think it was, there was a second generation that they also
did, and found that it perpetuated. But maybe these are reversible, ok, by things
that we do later in our lives. Ok, so I’m going to show you a video. So this is a narrated
slide show, that shows how, um, these mice who agouti mice that are a
model for diabetes and the gene for diabetes also, uh, in some way influences their coat
color. So their color of their fur is an indicator of their essentially susceptibility
to diabetes. But it’s influenced by epigenetic, uh, changes. [Video: “Hi, I’m Doctor Dana Dulenoy,
a postdoctoral research fellow in the laboratory of Randy Gertle at Duke University. In our
laboratory, we study epigenetic gene regulation, or how environmental exposures
interact with the epigenome to affect long term health and disease.” “So today I’d like to introduce you to
two agouti mice, and as you can see, the yellow mouse is quite obese and she is also prone
to diabetes and cancer. But on the other hand, the brown mouse remains slender
and lean, and also has a lower risk of developing disease. But what’s really amazing about
these two mice are that they are genetically identical. They are two identical
twin sisters from the same mother. So, what makes them look so different?” “Well it turns out there is a second genome
called the epigenome. Epigenome literally means in addition to or above the genome.
And while the recently completed human genome project identified approximately 25,000
genes, these genes still need instructions for what to do and when to do it and where
to do it. And that is where the epigenome comes into play.” “A useful analogy is to think of the epigenome
as the software that directs the genomic hardware of a computer. All of our cells contain the
same DNA in genes. But it is the epigenome that decides how these genes
are expressed and determines how a cell becomes a heart cell, a liver cell, or even a hair
cell.” “Epingenetics consists of molecular switches
and markers, such as DNA methylation that help control gene regulation in which a core
set of atoms, called a methyl group, attaches to DNA and shuts down genes.
And as you can see, the red balls here are attaching to the DNA and turning off the gene.” “So back to the agouti sisters. In the yellow
obese mouse, the agouti gene is un-methylated and turned on all the time. While in the brown
mouse, the gene is completely methylated and shut down. There
are also other mice that appear mottled in which half of the cells are methylated and
shut down and the other half are un- methylated and turned on. And these mice appear
to be yellow and brown. So the coat colors of these agouti mice acts like a sensor for
the amount of DNA methylation present.” “We use the agouti mice to study how maternal
nutrients and environmental factors affect the epigenome. Specifically, we wanted to
know whether a mom’s exposure to a contaminant found everywhere in the environment
can alter the fetal epigenome and eventually the long term fate of her offspring.” “In this study, pregnant mothers were exposed
to a common chemical found in certain plastics. This chemical is called Bisphenol A, of BPA
for short. And it’s present in many commonly used products, including
food and beverage containers, baby bottles, dental sealants, and the lining of food cans.
Um about four years ago the CDC studied approximately four hundred people
and in ninety-five percent of these four hundred people they measured detectible levels of
Bisphenol A.” “And when we fed the pregnant mothers, the
mice, BPA, we noticed that the number of offspring with the yellow obese coat color increased
dramatically. And we also saw that maternal exposure to this chemical decreased
the methylation in the offspring, and turned this agouti gene on when it is supposed to
be off.” “So we started a second study in which pregnant
mothers were exposed to BPA plus nutritional supplementation, such as methyl donors like
folic acid. Or, um, genocine, which is a common ingredient found in soy
products. The level of soy that we provided was similar to what a person who eats a high
soy diet or an individual living in Asia might eat. And once we did this, we observed
that the offspring were no longer predominantly yellow and more obese. And that there were
more offspring with the slender brown phenotype. This indicates that
maternal nutrient supplementation can counteract the negative effects of exposure to that chemical.” “The traditional thinking about human health
and disease is that it is affected by genetics and the environment. And whenever identical
twins have different disease status, this was often attributed to the environment
or different behavioral choices such as smoking status. But with epigenetic gene regulation,
we can see that we can no longer say whether genetics or the
environment have a bigger impact. Because it may be not only what you were exposed to
but what your mother and potentially grandparents were exposed to as well. And
maybe even your father.” “These studies with the agouti mice so us
that we can no longer say whether genetics or the environment have a greater impact on
our health. Because the two are inexplicitly linked through the epigenome.
This work suggests in the future that we may be able to protect individuals from negative
epigenetic profiles either by modifying the diet or developing drugs that
can affect epigenomic profiles although we’re several years away from doing this.”>>STOWELL So what did you learn? [Background noise]>>PARTICIPANT: So when you look at the the
two mice, genetically, if you looked at them, if you did a test, genetically they would
look identical, correct?>>STOWELL: The DNA sequence would be the same.>>PARTICIPANT: And this is not considered
to be a copying or deletion error, this is a suppression of a section.>>STOWELL: Yep.>>PARTICIPANT: I’m a little confused when
you talk about the methyl group, you said the methyl group are proteins themselves or
do proteins cause a methyl group?>>STOWELL: The methyl group is just a chemical
group, a carbon atom, three hydrogen ion- atoms that bind onto the DNA sequence, so
I’m not exactly sure what they are binding to, but it’s not a protein. So no.>>PARTICIPANT: [unclear]>>STOWELL: There’s, there’s two different
mechanisms, one is the histone proteins which the strands wrap around, and those can influence
the exposure of the gene sequences to be expressed or not. But the
methyl group is a separate epigenetic mechanism that can either turn on or off genes when
it binds.>>PARTICIPANT: Are they supposed to be there,
or are they saying it’s the environment that inserts those to mess up the code, like
do we normally have methyl groups binding?>>STOWELL: Um, no.>>PARTICIPANT: OK>>STOWELL: And my understanding is that at
certain developmental sequences it essentially clears the methyl groups off->>PARTICIPANT: OK>>STOWELL: -And then maybe further experience
seems to add them back in?>>PARTICIPANT: So it’s not something that’s
normally supposed to do be there for the process.>>STOWELL: Well, I don’t know, what do you
mean by, I mean just by being exposed to our environment we’re going to have methyl groups.>>PARTICIPANT: I guess I’m saying normal…>>STOWELL: The default setting->>PARTICIPANT: OK>>STOWELL: is I don’t think there’s supposed
to be methyl groups there.>>PARTICIPANT: So do we have a question about
breastfeeding versus not breastfeeding?>>STOWELL: Oh yeah, this raises questions
about everything again. Right, it’s like well does smoking when you are a teenager,
does that have influence on your posterity? Ah, I even saw headlines about
maybe being bullied, you know, as a child influencing it. And now we’re starting to
see that it’s not just what the mother is exposed to, maybe even during pregnancy, but
what the father was exposed to. And there was another study, I can’t remember, I think
it was mice or rats, the father’s epigenetic changes were transferred to their
daughters, that led to obesity or diabetes, I mean, it’s raising a whole lot of new
possibilities.>>PARTICIPANT 1: So you can’t really…>>PARTICIPANT 2: OK, so epigenetics now, my
students brought up this point a few times, and I always giggle because I thought it was
funny, that the reason why a lot of Chinese people are getting taller is that
they like to play basketball now. And I’m like, OK, that’s an interesting take on
the situation that you know basketball [unclear] players are taller and they are
jumping more and that’s- And so, it’s one of those I can’t prove them wrong now
with epigenetics I’m like I think there’s more to it than that, diets have changed over
the past few years and genetics and so does the nature versus nurture, you know, again
is it what you eat or is it what’s genetically been passed down, how tall were
your parents, how tall are you, but society as a whole has been getting taller over, um,
hundreds of years. So, environment versus, so that can be linked to epigenetics.>>STOWELL: Yeah, I probably wouldn’t say
that playing basketball->>PARTICIPANT: I know, that’s a long stretch,
but->>STOWELL: Long stretch, but->>PARTICIPANT: There are other factors involved,
but who am I to cross that one off part of it. People are jumping more, trying to do
things that taller people need to do.>>STOWELL: This is, this is new,>>PARITCIPANTS: It’s very fascinating->>PARITCIPANTS: [unclear]>>STOWELL: You know, genetics is gonna, is
gonna set the bounds on you to some extent, you know. I wanted to be six foot but I am
actually 5’10” and a half, ok so, no matter how much I wanted to I just don’t
think I was going to make it. Yeah what other questions do you have about epigenetics? I
may not be able to answer them.>>PARITICPANT: Well if a behavior then is
attributed to the fact that was this process in the genes if the mice had diabetes, and
you had to say if it was nature versus nurture, it’s both, or?>>STOWELL: Oh yeah, I never say it was just
one or the other. Always, it’s always->>PARTICIPANT: Or even the fact that the genes
[yeah] were handed down [yeah] so it’s both>>STOWELL: Yeah, absolutely. It’s not and
it never should have been nature or nurture [right right], you know, it’s really to
what extent. Now, it’s just complicated. Yes?>>PARTICIPANT: [Unclear…] but do you think
if they test the offspring rats for fear of other stimuluses? So like where they specifically
more fearful of the odor or where they just more inclined to be fearful?>>STOWELL: I believe they tested them on other
odors but I can’t remember. I’m sorry. But, somebody could google it, look it up.
Yes?>>PARTICIPANT: Do you have something that
you use to help your students understand heritability?>>OTHER PARTICIPANTS: Yeah, it’s so complicated.>>PARTICIPANT: The idea that it’s more within
a group versus individuals.>>STOWELL: Right, um, I tend I don’t talk
a lot about the number heritability other than I try to just emphasize it’s look it’s
the individual differences, ok, among a group, ok, how well can those differences
be explained by genetics. And it’s not to say that you know 70% of my intelligence was
inherited. Eh, that’s not quite what I mean by that. But I don’t have any particular
way that I, I help with that. So. I don’t know someone can think of a good way, and
let me know. Alright, so to summarize um epigenetic mechanisms,
ok, things that influence, ok, the outcome here. Things that occur during development,
environmental chemicals, drugs, aging, diet. This show a methyl group,
the black carbon and three white hydrogen atoms stuck onto the DNA sequence. This shows
the winding around the histone proteins, which can be altered by these things
binding to a portion of the histone protein, but in terms of the health endpoints, this
has implications for cancer, autoimmunity, mental disorders, diabetes,
um, obesity. It’s->>PARTICIPANT: How about autism? Have you
seen any studies on that, I mean, given the geometric progression of it?>>STOWELL: I haven’t. No.>PARTICIPANT: Could this explain potentially
why we see things increasing, like ADHD, or why there are shifts in population?>>STOWELL: Ah, there’s a lot of possible
explanations for those increases so, I’m sure somebody will latch onto it. This will
be, you know, whatever explains everything in the future. Right? So, I don’t
know. Ok, so it’s not nature or nurture. But think
about the choices you are making now, how they can influence your posterity. Ok. Maybe
a little more accountability for our behavior, that it’s, ah it’s just
me right, well, no maybe it’s me and my children and grandchildren and what we’re
doing here. Yes, Steve?>>JONES: I did look up that paper and I can
only see the abstract but it does say that the second- next two generations had an increased
odor sensitivity to that conditioned odor but not to other odors.>>STOWELL: But not to others, yeah.>>JONES: So it was that specific odor that
they were conditioned.>>STOWELL: Yeah, so, they did test other odors.>>PARTICIPANT: What was the year of the study?>>JONES: Um, um, December 2013 I think. [Oh
wow] And I just, literally just used the first perennial olfactory experiences and it was
the first thing that came up.>>PARTICIPANT: Thank you.>>JONES: Sure>>PARTICIPANT: So now we have more to feel
guilty about as if it being – [unclear]>>STOWELL: Yeah, you know, it’s like, it
is your fault as a parent. You know, it really is your fault. But don’t tell your kids
that. [Laughter] They’ll blame it on you one way or the other
you know, they’ll blame it on you. But maybe you can say but yes, it’s in your power
to change, right? You can be better than I was.

5 thoughts on “Nature or nurture? The role of epigenetics

  1. maybe people at a disadvantage due to epigenetics is for a reason, perhaps when they are at a advantage they cause mayhem and destruction "Middle East, Africa". Ive seen it first hand here in Detroit, minorities with power and influence, cause more destruction then a thug with a gun. Maybe we should continue keeping them at a disadvantage for benefit of all mankind

  2. Has anybody ever heard of the dark ages???? that the centuries of hordes of "minorities" ravished the world with conquest and destruction, not until the enlightened "light" people stood up against them and allowed basic human freedoms to flourish

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