Transcriber: H Maria Castro
Reviewer: Denise RQ Nine years ago, I found myself
in a doctor's office, contemplating the nature versus nurture debate
from a fresh perspective. You see, I had been trained
as a geneticist and had spent my career manipulating DNA and seeing the profound consequences
in a lab setting so I'd always put my money more on the nature,
or the genetic side of the debate. But, as my doctor revealed to me
that I was pregnant with identical twins, I realized that my convictions
were about to be put to the test. For starters, we had not budgeted
on two daycare bills at once. So I have half-jokingly started
to wonder what would be the consequences maybe, if we just sent one twin to daycare and maybe just kind of tuck the other one
in my office drawer during the workday. (Laughter) Despite their identical DNA,
I somehow doubted that things would turn out all that well
for the twin in the office drawer. (Laughter) Identical twins have had a profound impact on scientists' understanding
of nature and nurture. Studies on identical twins
who were separated at birth and raised in separate households
have helped us understand different traits that are
more affected by nature, or DNA, versus nurture, or the home environment. For example, some traits,
like IQ or criminal tendencies, are more affected by your DNA
than the house that you grew up in. On the other hand, other traits,
like depression in men, or your preference
for a particular political party, are more influenced
by your environment than by your genes. What about identical twins who are raised
in the same home environment? Their nature and their nurture
are almost the same. And yet, any parent
of identical twins, myself included, can quickly point out
differences in their children. One twin may have more of a preference
for certain types of foods, or may have more aptitude
for a certain sport or musical instrument. And sometimes, health differences
can arise in these children. For example,
there are reports of autism, or asthma, or bipolar disorder arising in one twin at a young age
while the other one remains unaffected. How do we explain these differences, given that the DNA
is the same in these children? And for the large part, their home
environment has been the same too. Well, it turns out that some
of these differences can be explained by a third, very powerful influence
on our lives, besides nature and nurture. This is epigenetics. I'm going to talk to you today
about what epigenetics is and how it impacts your life,
even if you're not an identical twin. Before we talk about epigenetics,
we need to consider our DNA and how it fits into our cells
because, believe it or not, of the 50 trillion
or so cells in your body, each one contains
about six linear feet of DNA. If we were to stretch it out, it would be
about as tall as a pretty tall man. So how in the world do we fit
that amount of genetic material into something the size
of a cell nucleus, which is 400,000 times smaller? Well, the answer is that we do it
by wrapping our DNA around clusters
of proteins called histones. You can think of histones
like molecular spools. There are about 30 million
of these spools in each of your cells. So this helps explain how you fit such a tremendous amount
of DNA into a small space. We call this combination
of histones and DNA, chromatin. While chromatin solves this tremendous packaging problem
that the cell has, it also presents a new one for the cell. This is one of DNA accessibility
because keep in mind that the functional units of DNA
are actually the genes encoded in it. These are the instructions for the cell. There are what tell the cell
what to do and who to become and yet, when these genes are tightly
compacted into a chromatin structure, the cell in unable to read them,
they might as well not even be there. This is where epigenetics comes in. 'Epi' meaning 'on top of'
and 'genetics', your 'genes', literally refers to a set of instructions that sits down on top
of our DNA and our histones. Epigenetic marks are small chemical tags
which sit down on our chromatin and can help instruct it
whether to compact or decompact. Those instructions can then affect how the cell reads the underlying genes
encoded in the DNA. So, to show this schematically, some Epigenetic marks, shown here
in red, can help condense chromatin. When they do this,
they obscure the underlying genes, preventing the cell
from being able to read them. They turn those genes off. Other Epigenetic marks,
shown here in green, can help decondense the chromatin. When they do this, the gene
becomes accessible to the cell, the cell is able
to read it and turn it on. These types of Epigenetic marks
are profoundly influential to our biology. Consider, for example, what is it that makes
our cells different from one another, what makes them
look and behave differently, what is it that makes
a muscle cell, for instance, look different from a neuron? After all, these cells contain
exactly the same DNA but it's their Epigenetic instructions
that help tell them which genes to turn on
and which ones to turn off. With those different genes at play,
these can become very different cells. You might be wondering
when does all this Epigenetic information get laid down on our chromatin? The answer is that much of it happens
during our embryonic development. Interestingly, when you
were first conceived, and you were just comprised of a few,
undifferentiated embryonic stem cells, which had the potential
to become any cell in your body, your chromatin didn't have
many Epigenetic marks on it. It was only as your cells began to divide and receive signals and information
from surrounding cells, that the Epigenetic marks
began to accumulate and then the genes began to get
turned off and turned on, and the muscle cell
became very different from the neuron. This brings me to a really
important point about epigenetics. Epigenetic marks
can be influenced by the environment. When I say environment,
I don't just mean the surrounding cells that tell a neuron to become a neuron. I also mean, the environment
outside of the developing embryo. So the food that the mom eats,
or the pre-natal vitamins that she takes, or the cigarettes that she smokes, or the stresses that she encounters
at home or at work, can all be transmitted as chemical signals through her bloodstream
to her developing fetus, where they can get laid down
as Epigenetic marks that affect the fetus' own genes
and long-term health. This has been shown
experimentally in mice. Mice contain a gene called agouti,
which makes them obese and yellow and susceptible to diseases,
like cancer and diabetes. This gene and these traits
can be passed down from generation to generation through DNA
so that an agouti mother will give rise to a fat, yellow,
disease-susceptible offspring, if that offspring
contains the agouti gene. Here's something interesting
about the agouti gene. It can be turned off, if silencing
Epigenetic marks accumulate around it. So, if a pregnant agouti mother
is fed a diet which is supplemented
with these silencing Epigenetic marks, those marks will be chemically transmitted
to the DNA of her embryo, where they'll accumulate
around that agouti gene and effectively turn it off. Her embryo will maintain those marks. So it will be born and grow up to be an adult mouse
that's thin, and brown, and healthy. Even though this mother
is genetically identical at the DNA level
to both sets of this offspring, you can see that the diet
that she consumed during her pregnancy can affect the health
and appearance of her offspring. This has, of course, implications
beyond the mouse world, because studies in humans have shown that women who don't eat well
during their pregnancy, who eat bad foods, will go on to have children who are more susceptible to developing
obesity and cardiovascular disease. Likewise, if women smoke
during their pregnancy, their children will grow up to have
a greater chance of developing asthma. These correlations between
maternal behavior during pregnancy and the long-term
health consequences for their offspring are thought to be linked by epigenetics, much as you've seen here
in the case of mice. Another important point
to make about epigenetics is that these types of marks
can be transmitted not only from a pregnant female
to her fetus but also from generation to generation if the marks are put down
on our sperm or eggs. So, if you're in the audience
and you're not pregnant, and you're not even thinking
about conceiving, think about this, because the lifestyle decisions
that you make today can still affect future generations. For example, a long-term study
was conducted in Sweden and England that showed that young boys
who overate or started smoking during their pre-pubescent years,
as their sperm was starting to develop, went on to have sons and grandsons
with significantly shorter lifespans. It's believed that the Epigenetic marks that were transmitted
by their diet and smoking decisions, affected the long-term health
of their future generations. This type of Epigenetic information,
of course, can also be passed through females to their daughters
and granddaughters, if the Epigenetic marks
are laid down on their eggs. The idea of transgenerational inheritance
of Epigenetic marks is still being debated and studied
in terms of humans, but I should add that in non-human organisms,
mice, flies, worms, there's mounting evidence
that this theory holds true. In fact, it's being shown in the lab
that over tens of generations, Epigenetic marks can be passed down. Another thing to know about epigenetics
is that they don't just affect us when we're a developing embryo, or when the sperm and egg
that conceived us were developing, they can also affect us after our birth. This is particularly relevant
as we think about our brains which continue to grow
and develop throughout our lives. Take this example from rats. Rats contain a gene called
the glucacorticoid receptor and this gene can be expressed, or read,
in a certain region of the rat's brain. When it is, it helps the rat
cope with stressful situations. So, the more receptor that the rat
has in this region of the brain, the better it will handle stress. There are studies that have shown
that interactions between a rat mother and her pups
during the first week of their life can have long-term consequences
for how much glucacorticoid receptor those pups will grow up
to have in their brains and therefore how well
they will handle stress. This is how this works. When rat pups are born,
their glucacorticoid receptor gene is surrounded by a number of these
silencing Epigenetic marks. This effectively turns the gene off. Yet, if a rat mother extensively
licks and grooms on her pups, basically takes good care of them,
during the first week of their life, those Epigenetic silencing marks
can be removed from the gene. This allows the glucacoid receptor gene
to turn back on, and it stays on in those pups' brains
throughout their lives. So they grow up to be
well-adjusted animals who deal well with stress. If a rat mother ignores her pups (Laughter) that glucacoid receptor gene will maintain
those silencing Epigenetic marks, they won't go away, and they'll stay in
those pups' brains throughout their lives. These rats will grow up to be
very anxious in stressful situations. This actually brings up a really
encouraging point about epigenetics in that Epigenetic marks are reversible. So, if you've been sitting in the audience cursing your parents and your grandparents for their poor lifestyle decisions,
or for the lack of licking and grooming (Laughter) that you've received
as a baby, take heart because scientists
are making terrific progress in designing drugs that can reverse
toxic Epigenetic marks to help combat certain diseases. This is especially looking promising
in the case of certain cancers which happen to be affected or turned on
by aberrant Epigenetic marks. This is how this can work. Our bodies have certain genes in them
called tumor-suppressor genes. The job of these genes is to protect cells
from becoming cancerous. But if too many silencing Epigenetic marks
start to accumulate around these genes, the genes get turned off, and they can no longer perform
their job of protecting the cell. So scientists have developed drugs
which have undergone FDA approval, and they're in a clinical setting,
which can target these silencing marks effectively removing them
from the tumor-suppressor genes and allowing these genes to go back
to their job of protecting the cell. Now think about it. This is a radical departure
from traditional cancer therapy. Historically, we've always
been focused on killing cancer cells. This, however, is taking the approach of
restoring cells to their original nature, reminding them
of what they're supposed to do. This type of therapeutic approach
is showing great promise in terms of other diseases as well,
besides cancer, diseases that are also similarly affected
by aberrant Epigenetic marks, like diabetes, and lupus, and asthma, and certain neurological disorders,
Huntington's and Alzheimer's diseases. I'm optimistic that this type of therapy
is going to hold great promise for our health in upcoming years, but I should caution that one
of the challenges as we go forward is figuring out how to target these drugs
toward toxic Epigenetic marks while leaving alone the beneficial ones
that help maintain our health. I want to conclude by emphasizing that there are things that we can do now
to positively influence our epigenome. It's not too late to start
eating healthier foods, foods that we already know
are good for us, like leafy vegetables, whole grains,
avoiding cigarettes, cocaine, stress all of which have been shown
experimentally to impact our epigenomes negatively. These are things that you can do to impact your genes
and your long-term health. And if that's not incentive enough, they can also impact the health
of your future children and grandchildren. I think this concept,
that we can positively impact our genes, is really profound and empowering because we've always worked
under the assumption that our genes are set in stone,
that they're beyond our influence. I want to end today
by challenging you, and myself, to take the opportunity
that we have before us to positively impact our long-term health by treating our epigenome kindly,
through healthy lifestyle decisions. Thank you. (Applause)
