An evolutionary perspective on human health and disease

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 unusually 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 bacteria.

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 Gus 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 cause 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
ore 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)

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)