WEBVTT

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When I was approximately
nine weeks pregnant with my first child,

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I found out I'm a carrier
for a fatal genetic disorder

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called Tay-Sachs disease.

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What this means

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is that one of the two copies
of chromosome number 15

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that I have in each of my cells

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has a genetic mutation.

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Because I still have
one normal copy of this gene,

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the mutation doesn't affect me.

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But if a baby inherits this mutation
from both parents,

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if both copies of this particular gene
don't function properly,

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it results in Tay-Sachs,

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an incurable disease

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that progressively shuts down
the central nervous system

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and causes death by age five.

NOTE Paragraph

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For many pregnant women,
this news might produce a full-on panic.

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But I knew something
that helped keep me calm

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when I heard this bombshell
about my own biology.

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I knew that my husband,

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whose ancestry isn't Eastern
European Jewish like mine,

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had a very low likelihood

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of also being a carrier
for the Tay-Sachs mutation.

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While the frequency of heterozygotes,

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individuals who have
one normal copy of the gene

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and one mutated copy,

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is about one out of 27 people
among Jews of Ashkenazi descent, like me,

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in most populations,

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only one in about 300 people
carry the Tay-Sachs mutation.

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Thankfully, it turned out I was right
not to worry too much.

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My husband isn't a carrier

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and we now have two beautiful
and healthy children.

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As I said,

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because of my Jewish background,

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I was aware of the unusually high rate
of Tay-Sachs in the Ashkenazi population.

NOTE Paragraph

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But it wasn't until a few years
after my daughter was born

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when I created and taught a seminar
in evolutionary medicine at Harvard

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that I thought to ask,

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and discovered a possible answer to,

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the question "why?"

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The process of evolution
by natural selection

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typically eliminates harmful mutations.

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So how did this defective gene
persist at all?

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And why is it found
at such a high frequency

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within this particular population?

NOTE Paragraph

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The perspective of evolutionary medicine
offers valuable insight,

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because it examines how and why

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humans' evolutionary past
has left our bodies vulnerable

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to diseases and other problems today.

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In doing so,

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it demonstrates that natural selection
doesn't always make our bodies better.

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It can't necessarily.

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But as I hope to illustrate
with my own story,

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understanding the implications
of your evolutionary past

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can help enrich your personal health.

NOTE Paragraph

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When I started investigating Tay-Sachs
using an evolutionary perspective,

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I came across an intriguing hypothesis.

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The unusually high rate
of the Tay-Sachs mutation

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in Ashkenazi Jews today

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may relate to advantages
the mutation gave this population

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in the past.

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Now I'm sure some of you are thinking,

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"I'm sorry, did you just suggest
that this disease-causing mutation

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had beneficial effects?"

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Yeah, I did.

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Certainly not for individuals
who inherited two copies of the mutation

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and had Tay-Sachs.

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But under certain circumstances,

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people like me,

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who had only one faulty gene copy,

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may have been more likely
to survive, reproduce

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and pass on their genetic material.

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Including that mutated gene.

NOTE Paragraph

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This idea that there can be circumstances
in which heterozygotes are better off

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might sound familiar to some of you.

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Evolutionary biologists
call this phenomenon

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heterozygote advantage.

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And it explains, for example,

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why carriers of sickle cell anemia

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are more common among
some African and Asian populations

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or those with ancestry
from these tropical regions.

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In these geographic regions,
malaria poses significant risks to health.

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The parasite that causes malaria, though,

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can only complete its life cycle
in normal, round red blood cells.

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By changing the shape
of a person's red blood cells,

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the sickle cell mutation
confers protection against malaria.

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People with the mutation
aren't less likely to get bitten

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by the mosquitoes
that transmit the disease,

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but they are less likely to get sick
or die as a result.

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Being a carrier for sickle cell anemia

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is therefore the best
possible genetic option

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in a malarial environment.

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Carriers are less susceptible to malaria

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because they make some
sickled red blood cells,

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but they make enough
normal red blood cells

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that they aren't negatively affected
by sickle cell anemia.

NOTE Paragraph

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Now in my case,

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the defective gene I carry
won't protect me against malaria.

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But the unusually prevalence
of the Tay-Sachs mutation

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in Ashkenazi populations

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may be another example
of heterozygote advantage.

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In this case, increasing
resistance to tuberculosis.

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The first hint of a possible relationship
between Tay-Sachs and tuberculosis

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came in the 1970s,

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when researchers published data

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showing that among
the Eastern European-born grandparents

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of a sample of American Ashkenazi
children born with Tay-Sachs,

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tuberculosis was an exceedingly
rare cause of death.

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In fact, only one
out of these 306 grandparents

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had died of TB,

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despite the fact
that in the early 20th century,

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TB caused up to 20 percent of deaths
in large Eastern European cities.

NOTE Paragraph

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Now on the one hand,
these results weren't surprising.

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People had already recognized

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that while Jews and non-Jews in Europe

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had been equally likely
to contract TB during this time,

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the death rate among non-Jews
was twice as high.

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But the hypothesis
that these Ashkenazi grandparents

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had been less likely to die of TB

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specifically because at least some of them
were Tay-Sachs carriers

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was novel and compelling.

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The data hinted

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that the persistence
of the Tay-Sachs mutation

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among Ashkenazi Jews

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might be explained by the benefits
of being a carrier

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in an environment
where tuberculosis was prevalent.

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You'll notice, though,

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that this explanation
only fills in part of the puzzle.

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Even if the Tay-Sachs mutation persisted

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because carriers
were more likely to survive,

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reproduce and pass on
their genetic material,

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why did this resistance
mechanism proliferate

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among the Ashkenazi
population in particular?

NOTE Paragraph

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One possibility is that the genes
and health of Eastern European Jews

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were affected not simply by geography,

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but also by historical
and cultural factors.

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At various points in history

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this population was forced to live
in crowded urban ghettos

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with poor sanitation.

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Ideal conditions for the tuberculosis
bacterium to thrive.

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In these environments,
where TB posed an especially high threat,

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those individuals who were not carriers
of any genetic protection

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would have been more likely to die.

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This winnowing effect

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together with a strong
cultural predilection

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for marrying and reproducing
only within the Ashkenazi community,

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would have amplified
the relative frequency of carriers,

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boosting TB resistance,

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but increasing the incidence of Tay-Sachs
as an unfortunate side effect.

NOTE Paragraph

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Studies from the 1980s support this idea.

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The segment of the American
Jewish population

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that had the highest frequency
of Tay-Sachs carriers

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traced their descent

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to those European countries
where the incidence of TB was highest.

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The benefits of being
a Tay-Sachs carrier were highest

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in those places where the risk
of death due to TB was greatest.

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And while it was unclear
in the 1970s or '80s

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how exactly the Tay-Sachs mutation
offered protection against TB,

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recent work has identified

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how the mutation increases
cellular defenses against the bacterium.

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So heterozygote advantage can help explain

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why problematic versions of genes
persist at high frequencies

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in certain populations.

NOTE Paragraph

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But this is only one of the contributions
evolutionary medicine can make

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in helping us understand human health.

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As I mentioned earlier,

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this field challenges the notion

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that our bodies should have gotten
better over time.

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An idea that often stems
from a misconception

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of how evolution works.

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In a nutshell,

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there are three basic reasons
why human bodies,

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including yours and mine,

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remain vulnerable to diseases
and other health problems today.

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Natural selection acts slowly,

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there are limitations
to the changes it can make,

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and it optimizes for reproductive success,

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not health.

NOTE Paragraph

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The way the pace of natural selection
affects human health

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is probably most obvious

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in people's relationship
with infectious pathogens.

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We're in a constant arms race
with bacteria and viruses.

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Our immune system is continuously evolving
to limit their ability to infect,

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and they are continuously developing ways
to outmaneuver our defenses.

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And our species
is at a distinct disadvantage

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due to our long lives
and slow reproduction.

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In the time it takes us
to evolve one mechanism of resistance,

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a pathogenic species
will go through millions of generations,

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giving it ample time to evolve,

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so it can continue
using our bodies as a host.

NOTE Paragraph

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Now what does it mean
that there are limitations

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to the changes natural selection can make?

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Again, my examples
of heterozygote advantage

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offer a useful illustration.

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In terms of resisting TB and malaria,

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the physiological effects of the Tay-Sachs
and sickle cell anemia mutations

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are good.

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Taken to their extremes, though,

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they cause significant problems.

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This delicate balance
highlights the constraints

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inherent in the human body,

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and the fact that the evolutionary process

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must work with the materials
already available.

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In many instances,

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a change that improves
survival or reproduction

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in one sense

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may have cascading effects
that carry their own risk.

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Evolution isn't an engineer
that starts from scratch

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to create optimal solutions
to individual problems.

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Evolution is all about compromise.

NOTE Paragraph

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It's also important to remember,

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when considering
our bodies' vulnerabilities,

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that from an evolutionary perspective,

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health isn't the most important currency.

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Reproduction is.

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Success is measured
not by how healthy an individual is,

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or by how long she lives,

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but by how many copies of her genes
she passes to the next generation.

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This explains why a mutation

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like the one that causes
Huntington's disease --

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another degenerative
neurological disorder,

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hasn't been eliminated
by natural selection.

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The mutation's detrimental effects

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usually don't appear until after
the typical age of reproduction,

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when affected individuals
have already passed on their genes.

NOTE Paragraph

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As a whole,

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the biomedical community
focuses on proximate explanations,

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and uses them to shape
treatment approaches.

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Proximate explanations
for health conditions

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consider the immediate factors:

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What's going on inside
someone's body right now

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that caused a particular problem.

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Nearsightedness, for example,

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is usually the result of changes
to the shape of the eye,

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and can be easily corrected with glasses.

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But as with the genetic
conditions I've discussed,

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a proximate explanation
only provides part of the bigger picture.

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Adopting an evolutionary perspective

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to consider the broader question
of why do we have this problem

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to begin with --

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what evolutionary medicine calls
the ultimate perspective --

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can give us insight
into nonimmediate factors

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that affect our health.

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This is crucial,

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because it can suggest ways
by which you can mitigate your own risk

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or that of friends and family.

NOTE Paragraph

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In the case of nearsightedness,

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some research suggests

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that one reason it's becoming
more common in some populations

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is that many people today,

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including most of us in this room,

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spend far more time reading, writing

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and engaging with various types of screen

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than we do outside, interacting
with the world on a bigger scale.

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In evolutionary terms,
this is a recent change.

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For most of human evolutionary history,

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people used their vision
across a broader landscape,

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spending more time in activities
like hunting and gathering.

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The increase in recent years
in what's termed "near work,"

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focusing intensely on objects
directly in front of us

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for long periods of time,

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strains our eyes differently

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and affects the physical shape of the eye.

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When we put all these pieces together,

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this ultimate explanation
for nearsightedness --

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that environmental and behavioral change
impact the way we use our eyes --

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helps us better understand
the proximate cause.

NOTE Paragraph

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And an inescapable conclusion emerges --

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my mother was right,

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I probably should have spent
a little less time with my nose in a book.

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This is just one
of many possible examples.

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So the next time you or a loved one
are faced with a health challenge,

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whether it's obesity or diabetes,

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an autoimmune disorder,

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or a knee or back injury,

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I encourage you to think

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about what an ultimate
perspective can contribute.

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Understanding that your health

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is affected not just by what's going on
in your body right now,

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but also by your genetic inheritance,
culture and history,

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can help you make more informed decisions

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about predispositions,
risks and treatments.

NOTE Paragraph

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As for me,

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I won't claim that an evolutionary
medicine perspective

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has always directly
influenced my decisions,

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such as my choice of spouse.

00:14:37.403 --> 00:14:39.101
It turned out, though,

00:14:39.125 --> 00:14:41.545
that not following
the traditional practice

00:14:41.569 --> 00:14:43.958
of marrying within the Jewish community

00:14:43.982 --> 00:14:46.572
ultimately worked in my favor genetically,

00:14:46.596 --> 00:14:49.993
reducing the odds of me
having a baby with Tay-Sachs.

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It's a great example of why
not every set of Ashkenazi parents

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should hope that their daughter
marries "a nice Jewish boy."

NOTE Paragraph

00:14:57.386 --> 00:14:58.386
(Laughter)

00:14:58.410 --> 00:14:59.565
(Audience) Woo-hoo!

NOTE Paragraph

00:14:59.589 --> 00:15:01.339
More importantly, though,

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the experience of learning
about my own genes

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taught me to think differently
about health in the long run,

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and I hope sharing my story
inspires you to do the same.

NOTE Paragraph

00:15:11.849 --> 00:15:13.000
Thank you.

NOTE Paragraph

00:15:13.024 --> 00:15:14.500
(Applause)