An evolutionary perspective on human health and disease Lara Durgavich
Transcriber: Ivana Korom
Reviewer: Krystian Aparta
When I was approximately
nine weeks pregnant with my first child,
I found out I’m a carrier
for a fatal genetic disorder
called Tay-Sachs disease.
What this means
is that one of the two copies
of chromosome number 15
that I have in each of my cells
has a genetic mutation.
Because I still have
one normal copy of this gene,
the mutation doesn’t affect me.
But if a baby inherits this mutation
from both parents,
if both copies of this particular gene
don’t function properly,
it results in Tay-Sachs,
an incurable disease
that progressively shuts down
the central nervous system
and causes death by age five.
For many pregnant women,
this news might produce a full-on panic.
But I knew something
that helped keep me calm
when I heard this bombshell
about my own biology.
I knew that my husband,
whose ancestry isn’t Eastern
European Jewish like mine,
had a very low likelihood
of also being a carrier
for the Tay-Sachs mutation.
While the frequency of heterozygotes,
individuals who have
one normal copy of the gene
and one mutated copy,
is about one out of 27 people
among Jews of Ashkenazi descent, like me,
in most populations,
only one in about 300 people
carry the Tay-Sachs mutation.
Thankfully, it turned out I was right
not to worry too much.
My husband isn’t a carrier,
and we now have two beautiful
and healthy children.
As I said,
because of my Jewish background,
I was aware of the unusually high rate
of Tay-Sachs in the Ashkenazi population.
But it wasn’t until a few years
after my daughter was born
when I created and taught a seminar
in evolutionary medicine at Harvard,
that I thought to ask,
and discovered a possible answer to,
the question “why?”
The process of evolution
by natural selection
typically eliminates harmful mutations.
So how did this defective gene
persist at all?
And why is it found
at such a high frequency
within this particular population?
The perspective of evolutionary medicine
offers valuable insight,
because it examines how and why
humans' evolutionary past
has left our bodies vulnerable
to diseases and other problems today.
In doing so,
it demonstrates that natural selection
doesn’t always make our bodies better.
It can’t necessarily.
But as I hope to illustrate
with my own story,
understanding the implications
of your evolutionary past
can help enrich your personal health.
When I started investigating Tay-Sachs
using an evolutionary perspective,
I came across an intriguing hypothesis.
The unusually high rate
of the Tay-Sachs mutation
in Ashkenazi Jews today
may relate to advantages
the mutation gave this population
in the past.
Now I’m sure some of you are thinking,
“I’m sorry, did you just suggest
that this disease-causing mutation
had beneficial effects?”
Yeah, I did.
Certainly not for individuals
who inherited two copies of the mutation
and had Tay-Sachs.
But under certain circumstances,
people like me,
who had only one faulty gene copy,
may have been more likely
to survive, reproduce
and pass on their genetic material,
including that mutated gene.
This idea that there can be circumstances
in which heterozygotes are better off
might sound familiar to some of you.
Evolutionary biologists
call this phenomenon
heterozygote advantage.
And it explains, for example,
why carriers of sickle cell anemia
are more common among
some African and Asian populations
or those with ancestry
from these tropical regions.
In these geographic regions,
malaria poses significant risks to health.
The parasite that causes malaria, though,
can only complete its life cycle
in normal, round red blood cells.
By changing the shape
of a person’s red blood cells,
the sickle cell mutation
confers protection against malaria.
People with the mutation
aren’t less likely to get bitten
by the mosquitoes
that transmit the disease,
but they are less likely to get sick
or die as a result.
Being a carrier for sickle cell anemia
is therefore the best
possible genetic option
in a malarial environment.
Carriers are less susceptible to malaria,
because they make some
sickled red blood cells,
but they make enough
normal red blood cells
that they aren’t negatively affected
by sickle cell anemia.
Now in my case,
the defective gene I carry
won’t protect me against malaria.
But the unusual prevalence
of the Tay-Sachs mutation
in Ashkenazi populations
may be another example
of heterozygote advantage.
In this case, increasing
resistance to tuberculosis.
The first hint of a possible relationship
between Tay-Sachs and tuberculosis
came in the 1970s,
when researchers published data
showing that among
the Eastern European-born grandparents
of a sample of American Ashkenazi
children born with Tay-Sachs,
tuberculosis was an exceedingly
rare cause of death.
In fact, only one
out of these 306 grandparents
had died of TB,
despite the fact
that in the early 20th century,
TB caused up to 20 percent of deaths
in large Eastern European cities.
Now on the one hand,
these results weren’t surprising.
People had already recognized
that while Jews and non-Jews in Europe
had been equally likely
to contract TB during this time,
the death rate among non-Jews
was twice as high.
But the hypothesis
that these Ashkenazi grandparents
had been less likely to die of TB
specifically because at least some of them
were Tay-Sachs carriers
was novel and compelling.
The data hinted
that the persistence
of the Tay-Sachs mutation
among Ashkenazi Jews
might be explained by the benefits
of being a carrier
in an environment
where tuberculosis was prevalent.
You’ll notice, though,
that this explanation
only fills in part of the puzzle.
Even if the Tay-Sachs mutation persisted
because carriers
were more likely to survive,
reproduce and pass on
their genetic material,
why did this resistance
mechanism proliferate
among the Ashkenazi
population in particular?
One possibility is that the genes
and health of Eastern European Jews
were affected not simply by geography
but also by historical
and cultural factors.
At various points in history
this population was forced to live
in crowded urban ghettos
with poor sanitation.
Ideal conditions for the tuberculosis
bacterium to thrive.
In these environments,
where TB posed an especially high threat,
those individuals who were not carriers
of any genetic protection
would have been more likely to die.
This winnowing effect
together with a strong
cultural predilection
for marrying and reproducing
only within the Ashkenazi community,
would have amplified
the relative frequency of carriers,
boosting TB resistance
but increasing the incidence of Tay-Sachs
as an unfortunate side effect.
Studies from the 1980s support this idea.
The segment of the American
Jewish population
that had the highest frequency
of Tay-Sachs carriers
traced their descent
to those European countries
where the incidence of TB was highest.
The benefits of being
a Tay-Sachs carrier were highest
in those places where the risk
of death due to TB was greatest.
And while it was unclear
in the 1970s or ’80s
how exactly the Tay-Sachs mutation
offered protection against TB,
recent work has identified
how the mutation increases
cellular defenses against the bacterium.
So heterozygote advantage can help explain
why problematic versions of genes
persist at high frequencies
in certain populations.
But this is only one of the contributions
evolutionary medicine can make
in helping us understand human health.
As I mentioned earlier,
this field challenges the notion
that our bodies should have gotten
better over time.
An idea that often stems
from a misconception
of how evolution works.
In a nutshell,
there are three basic reasons
why human bodies,
including yours and mine,
remain vulnerable to diseases
and other health problems today.
Natural selection acts slowly,
there are limitations
to the changes it can make
and it optimizes for reproductive success,
not health.
The way the pace of natural selection
affects human health
is probably most obvious
in people’s relationship
with infectious pathogens.
We’re in a constant arms race
with bacteria and viruses.
Our immune system is continuously evolving
to limit their ability to infect,
and they are continuously developing ways
to outmaneuver our defenses.
And our species
is at a distinct disadvantage
due to our long lives
and slow reproduction.
In the time it takes us
to evolve one mechanism of resistance,
a pathogenic species
will go through millions of generations,
giving it ample time to evolve,
so it can continue
using our bodies as a host.
Now what does it mean
that there are limitations
to the changes natural selection can make?
Again, my examples
of heterozygote advantage
offer a useful illustration.
In terms of resisting TB and malaria,
the physiological effects of the Tay-Sachs
and sickle cell anemia mutations
are good.
Taken to their extremes, though,
they cause significant problems.
This delicate balance
highlights the constraints
inherent in the human body,
and the fact that the evolutionary process
must work with the materials
already available.
In many instances,
a change that improves
survival or reproduction
in one sense
may have cascading effects
that carry their own risk.
Evolution isn’t an engineer
that starts from scratch
to create optimal solutions
to individual problems.
Evolution is all about compromise.
It’s also important to remember,
when considering
our bodies' vulnerabilities,
that from an evolutionary perspective,
health isn’t the most important currency.
Reproduction is.
Success is measured
not by how healthy an individual is,
or by how long she lives,
but by how many copies of her genes
she passes to the next generation.
This explains why a mutation
like the one that causes
Huntington’s disease,
another degenerative
neurological disorder,
hasn’t been eliminated
by natural selection.
The mutation’s detrimental effects
usually don’t appear until after
the typical age of reproduction,
when affected individuals
have already passed on their genes.
As a whole,
the biomedical community
focuses on proximate explanations
and uses them to shape
treatment approaches.
Proximate explanations
for health conditions
consider the immediate factors:
What’s going on inside
someone’s body right now
that caused a particular problem.
Nearsightedness, for example,
is usually the result of changes
to the shape of the eye
and can be easily corrected with glasses.
But as with the genetic
conditions I’ve discussed,
a proximate explanation
only provides part of the bigger picture.
Adopting an evolutionary perspective
to consider the broader question
of why do we have this problem
to begin with –
what evolutionary medicine calls
the ultimate perspective –
can give us insight
into nonimmediate factors
that affect our health.
This is crucial,
because it can suggest ways
by which you can mitigate your own risk
or that of friends and family.
In the case of nearsightedness,
some research suggests
that one reason it’s becoming
more common in some populations
is that many people today,
including most of us in this room,
spend far more time reading, writing
and engaging with various types of screen
than we do outside, interacting
with the world on a bigger scale.
In evolutionary terms,
this is a recent change.
For most of human evolutionary history,
people used their vision
across a broader landscape,
spending more time in activities
like hunting and gathering.
The increase in recent years
in what’s termed “near work,”
focusing intensely on objects
directly in front of us
for long periods of time,
strains our eyes differently
and affects the physical shape of the eye.
When we put all these pieces together,
this ultimate explanation
for nearsightedness –
that environmental and behavioral change
impact the way we use our eyes –
helps us better understand
the proximate cause.
And an inescapable conclusion emerges –
my mother was right,
I probably should have spent
a little less time with my nose in a book.
This is just one
of many possible examples.
So the next time you or a loved one
are faced with a health challenge,
whether it’s obesity or diabetes,
an autoimmune disorder,
or a knee or back injury,
I encourage you to think
about what an ultimate
perspective can contribute.
Understanding that your health
is affected not just by what’s going on
in your body right now,
but also by your genetic inheritance,
culture and history,
can help you make more informed decisions
about predispositions,
risks and treatments.
As for me,
I won’t claim that an evolutionary
medicine perspective
has always directly
influenced my decisions,
such as my choice of spouse.
It turned out, though,
that not following
the traditional practice
of marrying within the Jewish community
ultimately worked in my favor genetically,
reducing the odds of me
having a baby with Tay-Sachs.
It’s a great example of why
not every set of Ashkenazi parents
should hope that their daughter
marries “a nice Jewish boy.”
(Laughter)
(Audience) Woo-hoo!
More importantly, though,
the experience of learning
about my own genes
taught me to think differently
about health in the long run,
and I hope sharing my story
inspires you to do the same.
Thank you.
(Applause)