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)