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  • 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,