0:00:01.119,0:00:05.151
When I was approximately[br]nine weeks pregnant with my first child,

0:00:05.175,0:00:08.651
I found out I'm a carrier[br]for a fatal genetic disorder

0:00:08.675,0:00:10.341
called Tay-Sachs disease.

0:00:11.101,0:00:12.291
What this means

0:00:12.315,0:00:16.204
is that one of the two copies[br]of chromosome number 15,

0:00:16.228,0:00:18.141
that I have in each of my cells,

0:00:18.165,0:00:19.807
has a genetic mutation.

0:00:20.458,0:00:23.490
Because I still have[br]one normal copy of this gene

0:00:23.514,0:00:25.580
the mutation doesn't affect me.

0:00:26.063,0:00:29.904
But if a baby inherits this mutation[br]from both parents,

0:00:29.928,0:00:34.237
if both copies of this particular gene[br]don't function properly,

0:00:34.261,0:00:36.061
it results in Tay-Sachs,

0:00:36.085,0:00:37.934
an incurable disease

0:00:37.958,0:00:40.704
that progressively shuts down[br]the central nervous system

0:00:40.728,0:00:43.116
and causes death by age five.

0:00:44.570,0:00:46.109
For many pregnant women

0:00:46.133,0:00:48.800
this news might produce a full-on panic.

0:00:49.125,0:00:51.478
But I knew something[br]that helped keep me calm

0:00:51.502,0:00:54.625
when I heard this bombshell[br]about my own biology.

0:00:54.944,0:00:56.365
I knew that my husband,

0:00:56.389,0:01:00.087
whose ancestry isn't Eastern[br]European Jewish like mine,

0:01:00.111,0:01:01.770
had a very low likelihood

0:01:01.794,0:01:05.110
of also being a carrier[br]for the Tay-Sachs mutation.

0:01:05.569,0:01:07.863
While the frequency of heterozygotes,

0:01:07.887,0:01:10.656
individuals who have[br]one normal copy of the gene

0:01:10.680,0:01:12.347
and one mutated copy,

0:01:12.371,0:01:15.037
is about one out of 27 people

0:01:15.061,0:01:18.355
among Jews of Ashkenazi descent, like me,

0:01:18.379,0:01:20.013
in most populations,

0:01:20.037,0:01:24.275
only one in about 300 people[br]carry the Tay-Sachs mutation.

0:01:25.125,0:01:28.363
Thankfully, it turned out I was right[br]not to worry too much.

0:01:28.387,0:01:30.117
My husband isn't a carrier

0:01:30.141,0:01:33.324
and we now have two beautiful[br]and healthy children.

0:01:35.602,0:01:36.753
As I said,

0:01:36.777,0:01:38.308
because of my Jewish background,

0:01:38.332,0:01:43.498
I was aware of the unusually high rate[br]of Tay-Sachs in the Ashkenazi population.

0:01:43.522,0:01:47.141
But it wasn't until a few years[br]after my daughter was born

0:01:47.165,0:01:51.212
when I created and taught a seminar[br]in evolutionary medicine at Harvard

0:01:51.236,0:01:52.831
that I thought to ask,

0:01:52.855,0:01:55.220
and discovered a possible answer to,

0:01:55.244,0:01:56.894
the question "why?"

0:01:57.252,0:01:59.743
The process of evolution[br]by natural selection

0:01:59.767,0:02:02.429
typically eliminates harmful mutations.

0:02:02.776,0:02:06.329
So how did this defective gene[br]persist at all?

0:02:06.353,0:02:09.408
And why is it found[br]at such a high frequency

0:02:09.432,0:02:11.699
within this particular population?

0:02:13.059,0:02:17.093
The perspective of evolutionary medicine[br]offers valuable insight,

0:02:17.117,0:02:19.522
because it examines how and why

0:02:19.546,0:02:23.442
humans' evolutionary past[br]has left our bodies vulnerable

0:02:23.466,0:02:26.057
to diseases and other problems today.

0:02:26.716,0:02:28.057
In doing so,

0:02:28.081,0:02:29.930
it demonstrates that natural selection

0:02:29.954,0:02:32.272
doesn't always make our bodies better.

0:02:32.296,0:02:34.025
It can't necessarily.

0:02:34.597,0:02:37.394
But as I hope to illustrate[br]with my own story,

0:02:37.418,0:02:40.934
understanding the implications[br]of your evolutionary past

0:02:40.958,0:02:43.839
can help enrich your personal health.

0:02:45.148,0:02:49.076
When I started investigating Tay-Sachs[br]using an evolutionary perspective,

0:02:49.100,0:02:52.012
I came across an intriguing hypothesis.

0:02:52.401,0:02:55.338
The unusually high rate[br]of the Tay-Sachs mutation

0:02:55.362,0:02:57.704
in Ashkenazi Jews today

0:02:57.728,0:03:01.561
may relate to advantages[br]the mutation gave this population

0:03:01.585,0:03:02.735
in the past.

0:03:03.665,0:03:05.506
Now I'm sure some of you are thinking,

0:03:05.530,0:03:09.498
"I'm sorry, did you just suggest[br]that this disease-causing mutation

0:03:09.522,0:03:11.728
had beneficial effects?"

0:03:11.752,0:03:13.149
Yeah, I did.

0:03:13.173,0:03:16.824
Certainly not for individuals[br]who inherited two copies of the mutation

0:03:16.848,0:03:18.466
and had Tay-Sachs.

0:03:18.847,0:03:20.769
But under certain circumstances,

0:03:20.793,0:03:21.959
people like me,

0:03:21.983,0:03:25.107
who had only one faulty gene copy,

0:03:25.131,0:03:29.004
may have been more likely[br]to survive, reproduce

0:03:29.028,0:03:31.258
and pass on their genetic material.

0:03:31.282,0:03:33.249
Including that mutated gene.

0:03:34.631,0:03:38.012
This idea that there can be circumstances

0:03:38.036,0:03:40.425
in which heterozygotes are better off

0:03:40.449,0:03:42.774
might sound familiar to some of you.

0:03:43.076,0:03:45.966
Evolutionary biologists[br]call this phenomenon

0:03:45.990,0:03:48.260
heterozygote advantage.

0:03:48.284,0:03:50.879
And it explains, for example,

0:03:50.903,0:03:52.895
why carriers of sickle cell anemia

0:03:52.919,0:03:56.942
are more common among some African[br]and Asian populations

0:03:56.966,0:04:00.101
or those with ancestry[br]from these tropical regions.

0:04:00.768,0:04:02.530
In these geographic regions,

0:04:02.554,0:04:05.791
malaria poses significant risks to health.

0:04:06.546,0:04:09.164
The parasite that causes malaria though

0:04:09.188,0:04:11.514
can only complete its life cycle

0:04:11.538,0:04:14.688
in normal, round red blood cells.

0:04:15.493,0:04:18.548
By changing the shape[br]of a person's red blood cells,

0:04:18.572,0:04:20.127
the sickle cell mutation

0:04:20.151,0:04:23.119
confers protection against malaria.

0:04:23.659,0:04:26.521
People with the mutation[br]aren't less likely to get bitten

0:04:26.545,0:04:29.045
by the mosquitoes[br]that transmit the disease,

0:04:29.069,0:04:32.704
but they are less likely to get sick[br]or die as a result.

0:04:33.450,0:04:36.204
Being a carrier for sickle cell anemia

0:04:36.228,0:04:39.109
is therefore the best[br]possible genetic option

0:04:39.133,0:04:40.866
in a malarial environment.

0:04:41.276,0:04:43.654
Carriers are less susceptible to malaria

0:04:43.678,0:04:46.640
because they make some[br]sickled red blood cells,

0:04:46.664,0:04:49.514
but they make enough[br]normal red blood cells

0:04:49.538,0:04:53.156
that they aren't negatively affected[br]by sickle cell anemia.

0:04:55.292,0:04:56.450
Now in my case,

0:04:56.474,0:05:00.450
the defective gene I carry[br]won't protect me against malaria.

0:05:01.196,0:05:04.903
But the unusually prevalence[br]of the Tay-Sachs mutation

0:05:04.927,0:05:06.799
in Ashkenazi populations

0:05:06.823,0:05:10.755
may be another example[br]of heterozygote advantage.

0:05:10.779,0:05:14.311
In this case, increasing[br]resistance to tuberculosis.

0:05:15.915,0:05:18.581
The first hint of a possible relationship

0:05:18.605,0:05:20.478
between Tay-Sachs and tuberculosis

0:05:20.502,0:05:22.458
came in the 1970s,

0:05:22.482,0:05:23.973
when researchers published data

0:05:23.997,0:05:27.029
showing that among the Eastern[br]European-born grandparents

0:05:27.053,0:05:31.200
of a sample of American Ashkenazi[br]children born with Tay-Sachs

0:05:31.224,0:05:35.018
tuberculosis was an exceedingly[br]rare cause of death.

0:05:35.042,0:05:39.153
In fact, only one[br]out of these 306 grandparents

0:05:39.177,0:05:40.597
had died of TB.

0:05:41.043,0:05:44.177
Despite the fact[br]that in the early 20th century

0:05:44.201,0:05:46.797
TB caused up to 20 percent of deaths

0:05:46.821,0:05:49.021
in large Eastern European cities.

0:05:50.483,0:05:53.158
Now on the one hand,[br]these results weren't surprising.

0:05:53.182,0:05:54.912
People had already recognized

0:05:54.936,0:05:57.403
that while Jews and non-Jews in Europe

0:05:57.427,0:06:01.149
had been equally likely[br]to contract TB during this time,

0:06:01.173,0:06:04.791
the death rate among non-Jews[br]was twice as high.

0:06:05.657,0:06:08.831
But the hypothesis[br]that these Ashkenazi grandparents

0:06:08.855,0:06:11.387
had been less likely to die of TB

0:06:11.411,0:06:16.005
specifically because at least some of them[br]were Tay-Sachs carriers,

0:06:16.029,0:06:17.949
was novel and compelling.

0:06:18.545,0:06:19.696
The data hinted

0:06:19.720,0:06:21.886
that the persistence[br]of the Tay-Sachs mutation

0:06:21.910,0:06:23.616
among Ashkenazi Jews

0:06:23.640,0:06:27.237
might be explained by the benefits[br]of being a carrier

0:06:27.261,0:06:30.840
in an environment[br]where tuberculosis was prevalent.

0:06:32.135,0:06:33.491
You'll notice though

0:06:33.515,0:06:37.213
that this explanation[br]only fills in part of the puzzle.

0:06:37.803,0:06:40.983
Even if the Tay-Sachs mutation persisted

0:06:41.007,0:06:43.572
because carriers[br]were more likely to survive,

0:06:43.596,0:06:46.771
reproduce and pass on[br]their genetic material,

0:06:46.795,0:06:49.443
why did this resistance[br]mechanism proliferate

0:06:49.467,0:06:52.534
among the Ashkenazi[br]population in particular?

0:06:53.626,0:06:58.745
One possibility is that the genes[br]and health of Eastern European Jews

0:06:58.769,0:07:01.516
were affected not simply by geography,

0:07:01.540,0:07:04.905
but also by historical[br]and cultural factors.

0:07:05.588,0:07:07.302
At various points in history

0:07:07.326,0:07:10.910
this population was forced to live[br]in crowded urban ghettos

0:07:10.934,0:07:12.334
with poor sanitation.

0:07:12.688,0:07:16.704
Ideal conditions for the tuberculosis[br]bacterium to thrive.

0:07:17.284,0:07:18.572
In these environments,

0:07:18.596,0:07:21.823
where TB posed an especially high threat,

0:07:21.847,0:07:26.649
those individuals who were not carriers[br]of any genetic protection

0:07:26.673,0:07:29.006
would have been more likely to die.

0:07:29.482,0:07:31.529
This winnowing effect

0:07:31.553,0:07:34.522
together with a strong[br]cultural predilection

0:07:34.546,0:07:38.879
for marrying and reproducing[br]only within the Ashkenazi community,

0:07:38.903,0:07:42.625
would have amplified[br]the relative frequency of carriers,

0:07:42.649,0:07:44.609
boosting TB resistance,

0:07:44.633,0:07:49.426
but increasing the incidence of Tay-Sachs[br]as an unfortunate side effect.

0:07:50.403,0:07:53.154
Studies from the 1980s support this idea.

0:07:53.713,0:07:56.334
The segment of the American[br]Jewish population

0:07:56.358,0:07:59.498
that had the highest frequency[br]of Tay-Sachs carriers

0:07:59.522,0:08:01.038
traced their descent

0:08:01.062,0:08:05.098
to those European countries[br]where the incidence of TB was highest.

0:08:05.678,0:08:09.280
The benefits of being[br]a Tay-Sachs carrier were highest

0:08:09.304,0:08:13.090
in those places where the risk[br]of death due to TB was greatest.

0:08:13.561,0:08:16.743
And while it was unclear[br]in the 1970s or '80s

0:08:16.767,0:08:21.950
how exactly the Tay-Sachs mutation[br]offered protection against TB,

0:08:21.974,0:08:23.761
recent work has identified

0:08:23.785,0:08:28.148
how the mutation increases[br]cellular defenses against the bacteria.

0:08:29.315,0:08:32.625
So heterozygote advantage can help explain

0:08:32.649,0:08:36.395
why problematic versions of genes[br]persist at high frequencies

0:08:36.419,0:08:37.952
in certain populations.

0:08:38.482,0:08:41.933
But this is only one of the contributions[br]evolutionary medicine can make

0:08:41.957,0:08:44.106
in helping Gus understand human health.

0:08:44.686,0:08:46.051
As I mentioned earlier,

0:08:46.075,0:08:48.003
this field challenges the notion

0:08:48.027,0:08:51.051
that our bodies should have gotten[br]better over time.

0:08:51.075,0:08:54.173
An idea that often stems[br]from a misconception

0:08:54.197,0:08:56.347
of how evolution works.

0:08:57.363,0:08:58.537
In a nutshell,

0:08:58.561,0:09:01.228
there are three basic reasons[br]why human bodies,

0:09:01.252,0:09:03.236
including yours and mine,

0:09:03.260,0:09:06.942
remain vulnerable to diseases[br]and other health problems today.

0:09:07.379,0:09:09.561
Natural selection acts slowly,

0:09:09.585,0:09:12.291
there are limitations[br]to the changes it can make,

0:09:12.315,0:09:15.450
and it optimizes for reproductive success,

0:09:15.474,0:09:17.109
not health.

0:09:18.641,0:09:21.799
The way the pace of natural selection[br]affects human health

0:09:21.823,0:09:23.537
is probably most obvious

0:09:23.561,0:09:26.934
in people's relationship[br]with infectious pathogens.

0:09:26.958,0:09:31.287
We're in a constant arms race[br]with bacteria and viruses.

0:09:31.311,0:09:33.906
Our immune system is continuously evolving

0:09:33.930,0:09:36.184
to limit their ability to infect

0:09:36.208,0:09:40.776
and they are continuously developing ways[br]to outmaneuver our defenses.

0:09:40.800,0:09:43.815
And our species[br]is at a distinct disadvantage

0:09:43.839,0:09:46.839
due to our long lives[br]and slow reproduction.

0:09:47.419,0:09:52.011
In the time it takes us[br]to evolve one mechanism of resistance,

0:09:52.035,0:09:56.138
a pathogenic species will go through[br]millions of generations,

0:09:56.162,0:09:58.051
giving it ample time to evolve,

0:09:58.075,0:10:00.840
so it can continue[br]using our bodies as a host.

0:10:02.481,0:10:04.751
Now what does it mean[br]that there are limitations

0:10:04.775,0:10:07.100
to the changes natural selection can make?

0:10:07.124,0:10:09.965
Again, my examples[br]of heterozygote advantage

0:10:09.989,0:10:11.856
offer a useful illustration.

0:10:12.506,0:10:15.371
In terms of resisting TB and malaria,

0:10:15.395,0:10:19.989
the physiological effects of the Tay-Sachs[br]and sickle cell anemia mutations

0:10:20.013,0:10:21.385
are good.

0:10:21.871,0:10:23.434
Taken to their extremes though,

0:10:23.458,0:10:25.759
they cause significant problems.

0:10:26.339,0:10:29.458
This delicate balance[br]highlights the constraints

0:10:29.482,0:10:31.456
inherent in the human body.

0:10:31.480,0:10:34.170
And the fact that the evolutionary process

0:10:34.194,0:10:36.932
must work with the materials[br]already available.

0:10:37.298,0:10:38.583
In many instances

0:10:38.607,0:10:40.910
a change that improves[br]survival or reproduction

0:10:40.934,0:10:42.101
in one sense,

0:10:42.125,0:10:45.449
may have cascading effects[br]that carry their own risk.

0:10:45.990,0:10:49.290
Evolution isn't an engineer[br]that starts from scratch

0:10:49.314,0:10:52.593
to create optimal solutions[br]to individual problems.

0:10:53.077,0:10:55.783
Evolution is all about compromise.

0:10:57.188,0:10:58.736
It's also important to remember

0:10:58.760,0:11:01.069
when considering[br]our bodies' vulnerabilities

0:11:01.093,0:11:03.276
that from an evolutionary perspective,

0:11:03.300,0:11:05.839
health isn't the most important currency.

0:11:05.863,0:11:07.568
Reproduction is.

0:11:07.592,0:11:11.727
Success is measured[br]not by how healthy an individual is,

0:11:11.751,0:11:13.601
or by how long she lives,

0:11:13.625,0:11:17.570
but by how many copies of her genes[br]she passes to the next generation.

0:11:18.331,0:11:19.833
This explains why a mutation

0:11:19.857,0:11:22.386
like the one that causes[br]Huntington's disease,

0:11:22.410,0:11:25.085
another degenerative[br]neurological disorder,

0:11:25.109,0:11:28.338
hasn't been eliminated[br]by natural selection.

0:11:28.362,0:11:30.125
The mutation's detrimental effects

0:11:30.149,0:11:34.561
usually don't appear until after[br]the typical age of reproduction,

0:11:34.585,0:11:38.101
when affected individuals[br]have already passed on their genes.

0:11:38.855,0:11:40.030
As a whole,

0:11:40.054,0:11:43.744
the biomedical community[br]focuses on proximate explanations,

0:11:43.768,0:11:46.529
and uses them to shape[br]treatment approaches.

0:11:46.942,0:11:49.586
Proximate explanations[br]for health conditions

0:11:49.610,0:11:51.751
consider the immediate factors:

0:11:51.775,0:11:54.704
What's going on inside[br]someone's body right now

0:11:54.728,0:11:56.861
that cause a particular problem.

0:11:57.196,0:11:58.934
Nearsightedness, for example,

0:11:58.958,0:12:02.268
is usually the result of changes[br]to the shape of the eye,

0:12:02.292,0:12:05.025
and can be easily corrected with glasses.

0:12:06.061,0:12:09.188
But as with the genetic[br]conditions I've discussed,

0:12:09.212,0:12:13.267
a proximate explanation only provides[br]part of the bigger picture.

0:12:13.776,0:12:16.323
Adopting an evolutionary perspective

0:12:16.347,0:12:20.608
to consider the broader question[br]of why do we have this problem

0:12:20.632,0:12:22.212
to begin with,

0:12:22.236,0:12:26.340
what evolutionary medicine calls[br]the ultimate perspective,

0:12:26.364,0:12:29.277
can give us insight[br]into nonimmediate factors

0:12:29.301,0:12:30.835
that affect our health.

0:12:31.158,0:12:32.309
This is crucial

0:12:32.333,0:12:36.396
because it can suggest ways[br]by which you can mitigate your own risk

0:12:36.420,0:12:38.261
or that of friends and family.

0:12:39.571,0:12:41.269
In the case of nearsightedness,

0:12:41.293,0:12:43.039
some research suggests

0:12:43.063,0:12:46.355
that one reason it's becoming[br]ore common in some populations

0:12:46.379,0:12:48.283
is that many people today,

0:12:48.307,0:12:50.529
including most of us in this room,

0:12:50.553,0:12:53.968
spend far more time reading, writing,

0:12:53.992,0:12:56.513
and engaging with various types of screen

0:12:56.537,0:13:00.577
than we do outside, interacting[br]with the world on a bigger scale.

0:13:01.331,0:13:04.664
In evolutionary terms,[br]this is a recent change.

0:13:05.061,0:13:07.466
For most of human evolutionary history

0:13:07.490,0:13:10.815
people used their vision[br]across a broader landscape,

0:13:10.839,0:13:14.259
spending more time in activities[br]like hunting and gathering.

0:13:14.839,0:13:19.418
The increase in recent years[br]in what's termed "near work,"

0:13:19.442,0:13:22.443
focusing intensely on objects[br]directly in front of us

0:13:22.467,0:13:24.315
for long periods of time,

0:13:24.339,0:13:26.379
strains our eyes differently

0:13:26.403,0:13:28.926
and affects the physical shape of the eye.

0:13:29.736,0:13:32.077
When we put all these pieces together,

0:13:32.101,0:13:35.403
this ultimate explanation[br]for nearsightedness,

0:13:35.427,0:13:40.458
that environmental and behavioral change[br]impact the way we use our eyes,

0:13:40.482,0:13:43.426
helps us better understand[br]the proximate cause.

0:13:43.736,0:13:46.474
And an inescapable conclusion emerges.

0:13:47.029,0:13:48.363
My mother was right,

0:13:48.387,0:13:52.243
I probably should have spent[br]a little less time with my nose in a book.

0:13:53.156,0:13:55.705
This is just one[br]of many possible examples.

0:13:56.047,0:14:00.190
So the next time you or a loved one[br]are faced with a health challenge,

0:14:00.214,0:14:02.317
whether it's obesity or diabetes,

0:14:02.341,0:14:04.023
an autoimmune disorder,

0:14:04.047,0:14:05.888
or a knee or back injury,

0:14:05.912,0:14:07.157
I encourage you to think

0:14:07.181,0:14:09.974
about what an ultimate[br]perspective can contribute.

0:14:10.553,0:14:12.847
Understanding that your health

0:14:12.871,0:14:16.919
is affected not just by what's going on[br]in your body right now,

0:14:16.943,0:14:19.213
but also by your genetic inheritance,

0:14:19.237,0:14:21.237
culture and history,

0:14:21.261,0:14:23.895
can help you make more informed decisions

0:14:23.919,0:14:27.255
about predispositions,[br]risks and treatments.

0:14:28.489,0:14:29.663
As for me,

0:14:29.687,0:14:32.323
I won't claim that an evolutionary[br]medicine perspective

0:14:32.347,0:14:35.116
has always directly[br]influenced my decisions,

0:14:35.140,0:14:37.007
such as my choice of spouse.

0:14:37.403,0:14:39.101
It turned out though

0:14:39.125,0:14:41.545
that not following[br]the traditional practice

0:14:41.569,0:14:43.958
of marrying within the Jewish community

0:14:43.982,0:14:46.572
ultimately worked in my favor genetically,

0:14:46.596,0:14:49.993
reducing the odds of me[br]having a baby with Tay-Sachs.

0:14:50.469,0:14:54.199
It's a great example of why[br]not every set of Ashkenazi parents

0:14:54.223,0:14:57.362
should hope that their daughter[br]marries "a nice Jewish boy."

0:14:57.386,0:14:59.029
(Laughter)

0:14:59.053,0:15:01.339
More importantly though,

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the experience of learning[br]about my own genes

0:15:04.325,0:15:07.920
taught me to think differently[br]about health in the long run,

0:15:07.944,0:15:11.507
and I hope sharing my story[br]inspires you to do the same.

0:15:11.849,0:15:13.000
Thank you.

0:15:13.024,0:15:14.500
(Applause)