An evolutionary perspective on human health and disease | Lara Durgavich

Transcriber: Ivana Korom Reviewer: Krystian Aparta

翻译人员: Wanting Zhong 校对人员: Yanyan Hong

When I was approximately nine weeks pregnant with my first child,

在我怀上第一个孩子约九周的时候，

I found out I'm a carrier for a fatal genetic disorder

我发现我是一种 致命性遗传疾病的携带者，

called Tay-Sachs disease.

这种病叫做 “泰伊-萨克斯 二氏病” （Tay-Sachs）。

What this means

这意味着

is that one of the two copies of chromosome number 15

在我的所有细胞中，

that I have in each of my cells

每对 15 号染色体中的一条

has a genetic mutation.

都携带了一个基因突变。

Because I still have one normal copy of this gene,

因为我的另一条染色体上 还有这个基因的正常副本，

the mutation doesn't affect me.

所以这个突变并未影响我。

But if a baby inherits this mutation from both parents,

但如果婴儿从父母双方 遗传了这个突变，

if both copies of this particular gene don't function properly,

如果两个这种基因 都无法发挥正常功能，

it results in Tay-Sachs,

就会导致泰伊-萨克斯二氏病，

an incurable disease

这是一种无法治愈的疾病，

that progressively shuts down the central nervous system

会逐步关闭中枢神经系统，

and causes death by age five.

并导致患儿在五岁前死亡。

For many pregnant women, this news might produce a full-on panic.

对于很多孕妇， 这个消息可能会造成极大恐慌。

But I knew something that helped keep me calm

但当我听到关于我自身 生理的这个爆炸性消息时，

when I heard this bombshell about my own biology.

我知道的某件事情让我保持冷静。

I knew that my husband,

因为我的丈夫和我不同，

whose ancestry isn't Eastern European Jewish like mine,

他不像我有东欧犹太血统，

had a very low likelihood

因此他也携带 “泰伊-萨克斯” 突变

of also being a carrier for the Tay-Sachs mutation.

的几率非常低。

While the frequency of heterozygotes,

所谓杂合子指的是

individuals who have one normal copy of the gene

一对基因中有一个正常，

and one mutated copy,

另一个突变，

is about one out of 27 people among Jews of Ashkenazi descent, like me,

在像我这样的阿什肯纳兹犹太裔中，

发生的概率大约是 27 分之一，

in most populations,

但在大多数人群中，

only one in about 300 people carry the Tay-Sachs mutation.

300 多个人中才会有一个 携带泰伊-萨克斯基因突变。

Thankfully, it turned out I was right not to worry too much.

谢天谢地，事实证明 我是对的，无须太担心。

My husband isn't a carrier,

我的丈夫不是携带者，

and we now have two beautiful and healthy children.

而现在我们有两个健康可爱的孩子。

As I said,

正如我所说的，

because of my Jewish background,

因为我的犹太背景，

I was aware of the unusually high rate of Tay-Sachs in the Ashkenazi population.

我很清楚阿什肯纳兹犹太裔中 泰伊-萨克斯病的风险异常高，

But it wasn't until a few years after my daughter was born

但直到我女儿出生几年后，

when I created and taught a seminar in evolutionary medicine at Harvard,

直到我在哈佛创立并教授 一门进化医学的研讨课，

that I thought to ask,

那时我才想提问 “为什么？”

and discovered a possible answer to,

并发现了一个可能的答案。

the question "why?"

The process of evolution by natural selection

自然选择的演化过程

typically eliminates harmful mutations.

通常会淘汰有害的突变。

So how did this defective gene persist at all?

那么，这个有缺陷的基因 是如何保留至今的呢?

And why is it found at such a high frequency

为什么它在这个特定人群当中

within this particular population?

发生的频率如此之高？

The perspective of evolutionary medicine offers valuable insight,

进化医学的观点 提供了有价值的见解，

because it examines how and why

因为它在探究人类的进化历史

humans' evolutionary past has left our bodies vulnerable

如何及为什么会让我们的身体

to diseases and other problems today.

在面对当今的疾病 和其他问题时如此脆弱。

In doing so,

通过这些研究，

it demonstrates that natural selection doesn't always make our bodies better.

表明了自然选择并不会 总是让我们的身体变好。

It can't necessarily.

它不见得会。

But as I hope to illustrate with my own story,

但我希望能用我自己的故事来说明，

understanding the implications of your evolutionary past

了解你的进化历史的影响

can help enrich your personal health.

可以有助于改善你的个人健康。

When I started investigating Tay-Sachs using an evolutionary perspective,

当我开始从进化的角度 研究泰伊-萨克斯病时，

I came across an intriguing hypothesis.

我发现了一个有趣的假设。

The unusually high rate of the Tay-Sachs mutation

泰伊-萨克斯基因突变

在今天的阿什肯纳兹 犹太人中发生率异常之高，

in Ashkenazi Jews today

may relate to advantages the mutation gave this population

可能与过去这个突变 为这个种群带来的好处有关。

in the past.

Now I'm sure some of you are thinking,

我相信你们中的一些人会心想，

"I'm sorry, did you just suggest that this disease-causing mutation

“不好意思，你刚才难道想说， 这种会导致疾病的基因突变

had beneficial effects?"

还能有好处？”

Yeah, I did.

没错，就是这个意思。

Certainly not for individuals who inherited two copies of the mutation

对于那些遗传了两个突变副本、

and had Tay-Sachs.

得了泰伊-萨克斯病的人来说， 当然没有好处。

But under certain circumstances,

但在某些情况下，

people like me,

像我这样

who had only one faulty gene copy,

只有一个错误的基因副本的人，

may have been more likely to survive, reproduce

可能更容易生存、繁殖，

and pass on their genetic material,

并传递他们的遗传物质，

including that mutated gene.

其中包括那个突变的基因。

This idea that there can be circumstances in which heterozygotes are better off

此观点认为，在某些情况下， 杂合子会出落得更好。

might sound familiar to some of you.

听起来可能有些耳熟。

Evolutionary biologists call this phenomenon

进化生物学家将这种现象称为

heterozygote advantage.

“杂合子优势”。

And it explains, for example,

它能够解释，例如，

why carriers of sickle cell anemia

为什么镰状细胞性贫血的携带者

are more common among some African and Asian populations

在一些非洲和亚洲人群中，

or those with ancestry from these tropical regions.

或是祖先来自这些热带 地区的人群中更为常见。

In these geographic regions, malaria poses significant risks to health.

在这些地理区域， 疟疾对健康构成重大威胁。

The parasite that causes malaria, though,

但是导致疟疾的寄生虫

can only complete its life cycle in normal, round red blood cells.

只能在正常的圆形红细胞中 完成其生命周期。

By changing the shape of a person's red blood cells,

通过改变人体红细胞的形状，

the sickle cell mutation confers protection against malaria.

镰状细胞的突变 能够保护人类，抵抗疟疾。

People with the mutation aren't less likely to get bitten

带有这种突变的人仍有同等几率

by the mosquitoes that transmit the disease,

被传播疟疾的蚊子叮咬，

but they are less likely to get sick or die as a result.

但他们因此患病或死亡的几率却更低。

Being a carrier for sickle cell anemia

因此，在疟疾肆虐的环境中，

is therefore the best possible genetic option

携带镰状细胞性贫血

in a malarial environment.

是最好的遗传选项。

Carriers are less susceptible to malaria,

携带者不太容易感染疟疾，

because they make some sickled red blood cells,

因为他们会产生一些镰状红细胞，

but they make enough normal red blood cells

但也能生成足够的正常红细胞，

that they aren't negatively affected by sickle cell anemia.

这样就不会受到 镰状细胞性贫血的负面影响。

Now in my case,

在我的例子中，

the defective gene I carry won't protect me against malaria.

我携带的缺陷基因 不能保护我免受疟疾的侵害。

But the unusual prevalence of the Tay-Sachs mutation

但是泰伊-萨克斯突变

in Ashkenazi populations

在阿什肯纳兹犹太人群中的异常流行

may be another example of heterozygote advantage.

可能是另一个杂合子优势的案例。

In this case, increasing resistance to tuberculosis.

在这个例子里， 则是增加了对肺结核的抵抗力。

The first hint of a possible relationship between Tay-Sachs and tuberculosis

泰伊-萨克斯突变和肺结核之间 可能存在联系的第一个迹象

came in the 1970s,

出现在 20 世纪 70 年代，

when researchers published data

当时研究人员分析了一个

showing that among the Eastern European-born grandparents

先天患有泰伊-萨克斯病的 美籍阿什肯纳兹犹太儿童样本，

of a sample of American Ashkenazi children born with Tay-Sachs,

数据显示，他们东欧出身的祖父母中，

tuberculosis was an exceedingly rare cause of death.

结核病是一种极其罕见的死亡原因。

In fact, only one out of these 306 grandparents

事实上，306 位祖父母中只有一位

had died of TB,

死于肺结核，

despite the fact that in the early 20th century,

尽管在 20 世纪早期，

TB caused up to 20 percent of deaths in large Eastern European cities.

在东欧的大城市里， 结核病导致了超过 20% 的死因。

Now on the one hand, these results weren't surprising.

一方面，这些结果并不出乎意料。

People had already recognized

人们已经认识到，

that while Jews and non-Jews in Europe

虽说当时欧洲的犹太人和非犹太人

had been equally likely to contract TB during this time,

感染肺结核的可能性是相同的，

the death rate among non-Jews was twice as high.

非犹太人的死亡率 却是犹太人的两倍。

But the hypothesis that these Ashkenazi grandparents

但是这个假设指出， 这些德系犹太人祖父母

had been less likely to die of TB

死于结核病的几率 更低的具体原因在于

specifically because at least some of them were Tay-Sachs carriers

他们中至少有一部分 是泰伊-萨克斯携带者，

was novel and compelling.

这个假说非常新颖且有力。

The data hinted

这些数据暗示了

that the persistence of the Tay-Sachs mutation

泰伊-萨克斯突变

among Ashkenazi Jews

在德系犹太人当中持续存在，

might be explained by the benefits of being a carrier

也许是因为在结核病流行的环境中，

in an environment where tuberculosis was prevalent.

携带这种基因是有益处的。

You'll notice, though,

不过，你会注意到，

that this explanation only fills in part of the puzzle.

这种解释只解答了部分谜团。

Even if the Tay-Sachs mutation persisted

即使泰伊-萨克斯突变持续存在

because carriers were more likely to survive,

是因为携带者更有可能存活下来，

reproduce and pass on their genetic material,

繁殖并传承他们的遗传物质，

why did this resistance mechanism proliferate

为什么这种抵抗机制 只在阿什肯纳兹犹太人中

among the Ashkenazi population in particular?

得以扩增？

One possibility is that the genes and health of Eastern European Jews

一种可能性是东欧 犹太人的基因和健康

were affected not simply by geography

不只是受地理因素的影响，

but also by historical and cultural factors.

还受到历史文化因素的影响。

At various points in history

在不同的历史时期，

this population was forced to live in crowded urban ghettos

这些人被迫住在拥挤的城市贫民窟，

with poor sanitation.

这些地方卫生条件恶劣，

Ideal conditions for the tuberculosis bacterium to thrive.

正是结核杆菌生长的理想温床。

In these environments, where TB posed an especially high threat,

在这些结核病构成了 特别高威胁的环境中，

those individuals who were not carriers of any genetic protection

那些没有携带任何基因保护的个人

would have been more likely to die.

更有可能死亡。

This winnowing effect

这个风选效应

together with a strong cultural predilection

再加上阿什肯纳兹犹太人 只和同族人结婚生子的

for marrying and reproducing only within the Ashkenazi community,

强烈文化偏好，

would have amplified the relative frequency of carriers,

这会扩大携带者的相对频率，

boosting TB resistance

提高对肺结核的抵抗力，

but increasing the incidence of Tay-Sachs as an unfortunate side effect.

但不幸的副作用就是 泰伊-萨克斯病的发病率会增加。

Studies from the 1980s support this idea.

20 世纪 80 年代的研究 证实了这一观点。

The segment of the American Jewish population

美籍犹太人中

that had the highest frequency of Tay-Sachs carriers

泰伊-萨克斯携带频率最高的人群，

traced their descent

能把他们的血统追溯到

to those European countries where the incidence of TB was highest.

那些结核病发病率最高的欧洲国家。

The benefits of being a Tay-Sachs carrier were highest

在那些死于结核病 的风险最大的地方，

in those places where the risk of death due to TB was greatest.

身为泰伊-萨克斯 携带者的好处也越大。

And while it was unclear in the 1970s or '80s

虽然在七八十年代还不清楚

how exactly the Tay-Sachs mutation offered protection against TB,

泰伊-萨克斯突变 究竟是如何预防结核病的，

recent work has identified

最近的研究发现了

how the mutation increases cellular defenses against the bacterium.

这个突变能如何增加 细胞对结核菌的防御。

So heterozygote advantage can help explain

因此杂合子优势有助于解释

why problematic versions of genes persist at high frequencies

为什么有问题的基因在特定人群中

仍高频率地持续存在。

in certain populations.

But this is only one of the contributions evolutionary medicine can make

但这只是进化医学 为帮助我们了解人类健康

in helping us understand human health.

所能做出的贡献之一。

As I mentioned earlier,

如之前所说，

this field challenges the notion

这个领域挑战了

“人类的身体应当越变越好” 的观念。

that our bodies should have gotten better over time.

An idea that often stems from a misconception

这个想法通常源于

对进化的误解。

of how evolution works.

In a nutshell,

简而言之，

there are three basic reasons why human bodies,

有三个基本原因导致了

including yours and mine,

包括你我的身体，

remain vulnerable to diseases and other health problems today.

现今仍然容易受到疾病 和其他健康问题的困扰。

Natural selection acts slowly,

自然选择的过程是缓慢的；

there are limitations to the changes it can make

它所能做的改变是有限的；

and it optimizes for reproductive success,

它优化的是繁殖成功率，

not health.

而不是健康。

The way the pace of natural selection affects human health

自然选择的速度 影响人类健康的方式

is probably most obvious

在人类与传染性病原体的关系中

in people's relationship with infectious pathogens.

可能是最明显的。

We're in a constant arms race with bacteria and viruses.

我们一直在与细菌和病毒 进行军备竞赛。

Our immune system is continuously evolving to limit their ability to infect,

我们的免疫系统不断进化， 以限制它们的感染能力，

and they are continuously developing ways to outmaneuver our defenses.

而它们则在不断开发各种方法 以突破我们的防线。

And our species is at a distinct disadvantage

而我们人类处于明显的劣势，

due to our long lives and slow reproduction.

因为我们的寿命长，繁殖慢。

In the time it takes us to evolve one mechanism of resistance,

在我们进化出一种抗性机制的时间里，

a pathogenic species will go through millions of generations,

一个致病物种早已经历了数百万代，

giving it ample time to evolve,

给它提供了足够的时间来进化，

so it can continue using our bodies as a host.

使得它可以继续 把我们的身体当做宿主。

Now what does it mean that there are limitations

那么，自然选择能做出的改变有限

to the changes natural selection can make?

又是什么意思呢？

Again, my examples of heterozygote advantage

同样，我举出的杂合子优势的例子

offer a useful illustration.

能提供有用的佐证。

In terms of resisting TB and malaria,

在抵御结核病和疟疾方面，

the physiological effects of the Tay-Sachs and sickle cell anemia mutations

泰伊-萨克斯

和镰状细胞性贫血突变的生理效果

are good.

是有利的。

Taken to their extremes, though,

但是，当这些突变走了极端，

they cause significant problems.

就会导致严重的问题。

This delicate balance highlights the constraints

这个微妙的平衡

突显了人体自身的局限，

inherent in the human body,

and the fact that the evolutionary process

也说明了演化的过程

must work with the materials already available.

必须利用现有的素材。

In many instances,

在很多情况下，

a change that improves survival or reproduction

一个能在某方面

in one sense

改善生存或繁衍的变化，

may have cascading effects that carry their own risk.

却会衍生出一连串有风险的效应。

Evolution isn't an engineer that starts from scratch

进化并不像是工程师从零开始，

to create optimal solutions to individual problems.

针对个别问题创造最优解法。

Evolution is all about compromise.

进化全是关乎妥协。

It's also important to remember,

我们还需谨记，

when considering our bodies' vulnerabilities,

在考虑到我们身体的弱点时，

that from an evolutionary perspective,

从进化的角度看来，

health isn't the most important currency.

健康并不是最重要的通货。

Reproduction is.

繁殖才是。

Success is measured not by how healthy an individual is,

成功的标尺并非个体有多健康，

or by how long she lives,

或者能活多久，

but by how many copies of her genes she passes to the next generation.

而是能向下一代传递多少份基因。

This explains why a mutation

这解释了为什么某个基因突变，

like the one that causes Huntington's disease,

例如导致另一种神经退化障碍

another degenerative neurological disorder,

亨丁顿舞蹈症的突变，

hasn't been eliminated by natural selection.

并没有被自然选择淘汰。

The mutation's detrimental effects

这个突变的毁灭性效果

usually don't appear until after the typical age of reproduction,

通常在育龄之后才开始浮现，

when affected individuals have already passed on their genes.

这时患者已经 把他们的基因遗传下去了。

As a whole,

总体来说，

the biomedical community focuses on proximate explanations

生物医学领域的焦点 在于 “近因解释” ，

and uses them to shape treatment approaches.

并利用它们打造治疗方案。

Proximate explanations for health conditions

健康问题的近因解释

consider the immediate factors:

会考虑到直接因素：

What's going on inside someone's body right now

某人身体内此时此刻 正在发生什么事情

that caused a particular problem.

导致了某个特定问题。

Nearsightedness, for example,

比如说，近视

is usually the result of changes to the shape of the eye

通常是因为眼球形状发生了改变，

and can be easily corrected with glasses.

可以用眼镜轻松地矫正。

But as with the genetic conditions I've discussed,

但与我讨论的遗传病症如出一辙，

a proximate explanation only provides part of the bigger picture.

近因解释只涵盖了全貌的一部分。

Adopting an evolutionary perspective

采取进化的视角

to consider the broader question of why do we have this problem

去更广泛地思考我们一开始

to begin with --

为什么会有这个问题——

what evolutionary medicine calls the ultimate perspective --

也是进化医学所说的 “终极因” ——

can give us insight into nonimmediate factors

能让我们洞察

影响健康的非直接因素。

that affect our health.

This is crucial,

这是至关重要的，

because it can suggest ways by which you can mitigate your own risk

因为从中可以找出一些方法 来帮助你自己或是家人朋友

or that of friends and family.

将健康风险降低。

In the case of nearsightedness,

在近视的例子里，

some research suggests

有部分研究表明

that one reason it's becoming more common in some populations

近视在某些人群中 变得更普遍的原因之一

is that many people today,

是现在的很多人，

including most of us in this room,

包括这个房间内的大多数人，

spend far more time reading, writing

花更多时间读写

and engaging with various types of screen

以及接触各式屏幕，

than we do outside, interacting with the world on a bigger scale.

而不是在户外 和更广阔的的世界互动。

In evolutionary terms, this is a recent change.

以进化的角度来看， 这是最近才发生的变化。

For most of human evolutionary history,

人类进化史的大部分时间里，

people used their vision across a broader landscape,

人们的视力都用在了 更广阔的的景观中，

spending more time in activities like hunting and gathering.

花更多时间进行 狩猎与采集这样的活动。

The increase in recent years in what's termed "near work,"

近年来，“近距离用眼工作” 的增加

focusing intensely on objects directly in front of us

让我们对面前的近物

进行长时间、高强度的聚焦，

for long periods of time,

strains our eyes differently

以不同的方式让我们用眼疲劳，

and affects the physical shape of the eye.

影响了眼球的物理形状。

When we put all these pieces together,

当我们把这些信息串联在一起，

this ultimate explanation for nearsightedness --

就能得出近视的 “终极因” 解释——

that environmental and behavioral change impact the way we use our eyes --

环境和行为的变化 影响了我们的用眼方式——

helps us better understand the proximate cause.

这个解释能帮助我们 更好地理解近因。

And an inescapable conclusion emerges --

随之浮现的是一个无可避免的结论——

my mother was right,

我妈妈是对的，

I probably should have spent a little less time with my nose in a book.

我或许应该少花点时间埋头看书。

This is just one of many possible examples.

这只是许许多多例子中的一个。

So the next time you or a loved one are faced with a health challenge,

下一次你或者你心爱的人 面临健康挑战的时候，

whether it's obesity or diabetes,

无论是肥胖症、糖尿病，

an autoimmune disorder,

自身免疫疾病，

or a knee or back injury,

还是膝盖或腰背受伤，

I encourage you to think

我鼓励你想想

about what an ultimate perspective can contribute.

一个终极因的角度能提供什么帮助。

Understanding that your health

你的健康

is affected not just by what's going on in your body right now,

不仅受到你身体此刻的状况影响，

but also by your genetic inheritance, culture and history,

同时也受到你的遗传、 文化和历史影响，

can help you make more informed decisions

理解这一点能帮助你在考虑 遗传基因、风险和治疗时，

about predispositions, risks and treatments.

做出更加明智的决定。

As for me,

对于我来说，

I won't claim that an evolutionary medicine perspective

我并不会声称进化医学的角度

has always directly influenced my decisions,

总会直接影响我的决定，

such as my choice of spouse.

比如说，我对配偶的选择。

It turned out, though,

但结果是，

that not following the traditional practice

我没有遵从

在犹太人群体内结婚的传统，

of marrying within the Jewish community

ultimately worked in my favor genetically,

最终在遗传方面对我有利，

reducing the odds of me having a baby with Tay-Sachs.

减少了我的孩子患上 泰伊-萨克斯病的几率。

It's a great example of why not every set of Ashkenazi parents

这个绝佳的例子也说明了，

为什么并不是 每对阿什肯纳齐犹太父母

should hope that their daughter marries "a nice Jewish boy."

都应希望他们的女儿 嫁给 “一个犹太好男孩” 。

(Laughter)

（笑声）

(Audience) Woo-hoo!

（观众）诶嘿！

More importantly, though,

但更重要的是， 了解我自己基因的经历

the experience of learning about my own genes

taught me to think differently about health in the long run,

教会我以不同的方式 长远地思考健康问题，

and I hope sharing my story inspires you to do the same.

我希望通过分享我的故事， 也能启发各位这么做。

Thank you.

谢谢。

(Applause)

（掌声）