An evolutionary perspective on human health and disease | Lara Durgavich

Transcriber: Ivana Korom Reviewer: Krystian Aparta

譯者: Lilian Chiu 審譯者: Helen Chang

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

當我懷第一胎大約九週的時候，

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

我發現我帶有泰薩氏症的隱性基因，

called Tay-Sachs disease.

一種致命的遺傳性疾病。

What this means

意思就是說，

is that one of the two copies of chromosome number 15

我每個細胞中的兩條十五號染色體

that I have in each of my cells

其中有一條發生了基因突變。

has a genetic mutation.

Because I still have one normal copy of this gene,

因為我仍然有一個正常的這種基因，

the mutation doesn't affect me.

突變並不會影響我。

But if a baby inherits this mutation from both parents,

但如果寶寶從雙親 遺傳到了這種突變，

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

如果兩個這種基因 都無法發揮正常功能，

it results in Tay-Sachs,

就會造成泰薩氏症，

an incurable disease

這種疾病無法治癒，

that progressively shuts down the central nervous system

會漸漸讓中樞神經系統停擺，

and causes death by age five.

造成病人在五歲時就死亡。

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

這種消息可能會讓 許多懷孕的女性極度慌張。

But I knew something that helped keep me calm

但，當我聽到這個關於 我自身生物學的震撼彈時，

when I heard this bombshell about my own biology.

因為我知道一件事， 讓我能保持冷靜。

I knew that my husband,

我知道我的丈夫

whose ancestry isn't Eastern European Jewish like mine,

不像我有東歐猶太血統，

had a very low likelihood

因此他幾乎不可能

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

同時也帶有泰薩氏症的突變基因。

While the frequency of heterozygotes,

所謂的異型合子指的是

individuals who have one normal copy of the gene

一對基因中有一個正常

and one mutated copy,

另一個突變，

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

在像我這種阿什肯納茲猶太裔身上

發生的頻率約為二十七分之一，

in most populations,

在大部分的人口中，

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

只有三百分之一的人 帶有突變的泰薩氏症基因。

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

謝天謝地，結果的確是 不需要我太擔心。

My husband isn't a carrier,

我先生沒有突變基因，

and we now have two beautiful and healthy children.

現在我們育有兩個健康的好孩子。

As I said,

如我所言，因為我的猶太背景，

because of my Jewish background,

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

我知道在阿什肯納茲族群當中 有異常高的泰薩氏症比率。

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

但，一直到我女兒出生的幾年後，

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

我在哈佛設計並教授 一場關於演化醫學的研討會時，

that I thought to ask,

我才想到要問「為什麼？」

and discovered a possible answer to,

並去尋找可能的答案。

the question "why?"

The process of evolution by natural selection

天擇的演化過程

typically eliminates harmful mutations.

通常會讓有害的突變消失。

So how did this defective gene persist at all?

所以，這個瑕疵的基因 怎麼能夠留存下來？

And why is it found at such a high frequency

且為什麼在這個特定的族群中

within this particular population?

發生的比率特別高？

The perspective of evolutionary medicine offers valuable insight,

演化醫學的觀點能提供 很有價值的洞見，

because it examines how and why

因為它在探究 「如何」及「為什麼」

humans' evolutionary past has left our bodies vulnerable

人類過去的演化造成我們的身體

很難抵抗現今的疾病和其他問題。

to diseases and other problems today.

In doing so,

透過這樣的探究，可以發現

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

天擇不一定會 讓我們的身體變得更好。

It can't necessarily.

不見得。

But as I hope to illustrate with my own story,

但，我希望能用 我自己的故事來說明：

understanding the implications of your evolutionary past

了解你過去的演化有什麼意涵，

can help enrich your personal health.

便能協助充實你的個人健康。

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

當我開始從演化的觀點 研究泰薩氏症時，

I came across an intriguing hypothesis.

我偶然發現一個有趣的假設。

The unusually high rate of the Tay-Sachs mutation

現今的阿什肯納茲猶太人具有

泰薩氏症突變的比率高到不尋常，

in Ashkenazi Jews today

may relate to advantages the mutation gave this population

可能和過去這項突變

帶給這個族群的優勢有關。

in the past.

Now I'm sure some of you are thinking,

我相信在座有人在想：「抱歉，

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

你剛剛的意思是 這種會造成疾病的突變

had beneficial effects?"

也有有益的效應？」

Yeah, I did.

是的，沒錯。

Certainly not for individuals who inherited two copies of the mutation

當然我指的不是 遺傳到兩個突變基因

and had Tay-Sachs.

且患有泰薩氏症的那些人。

But under certain circumstances,

但在某些情況下，像我這樣的人，

people like me,

who had only one faulty gene copy,

只有一個基因有缺陷的人，

may have been more likely to survive, reproduce

可能在過去比較容易生存、繁殖，

and pass on their genetic material,

並將遺傳物質傳下去，

including that mutated gene.

包括那個突變的基因。

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

在某些情況下異型合子會比較好，

might sound familiar to some of you.

在座有人可能很熟悉這個想法。

Evolutionary biologists call this phenomenon

演化生物學家把這個現象稱為

heterozygote advantage.

「異型合子優勢」。

And it explains, for example,

比如，它可以解釋

why carriers of sickle cell anemia

為什麼鐮刀型紅血球貧血症

are more common among some African and Asian populations

比較常出現在一些 非洲和亞洲人的族群中，

or those with ancestry from these tropical regions.

或者祖先來自這些 熱帶地區的族群中。

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

在這些地理區域，

瘧疾對健康是很重大的風險。

The parasite that causes malaria, though,

不過，造成瘧疾的寄生蟲

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

只能在正常、圓形的紅血球 細胞中完成它的生命循環。

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

鐮刀型紅血球細胞突變 能夠改變人類紅血球細胞的形狀，

the sickle cell mutation confers protection against malaria.

進而保護人類，抵抗瘧疾。

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

有這種突變基因的人並不是

by the mosquitoes that transmit the disease,

比較不會被傳播瘧疾的蚊子叮咬，

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

但他們比較不會因為 被叮咬而生病或死亡。

Being a carrier for sickle cell anemia

因此，有鐮刀型紅血球貧血症

is therefore the best possible genetic option

反而是在瘧疾環境中 最好的遺傳選項。

in a malarial environment.

Carriers are less susceptible to malaria,

這種人比較不會得到瘧疾，

because they make some sickled red blood cells,

因為他們會製造 一些鐮刀型紅血球細胞，

but they make enough normal red blood cells

但他們也會製造 足夠的正常紅血球細胞，

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

所以他們不會受到鐮刀型 紅血球貧血症的負面影響。

Now in my case,

在我的例子中，我身上的基因缺陷

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

並不會保護我抵抗瘧疾。

But the unusual prevalence of the Tay-Sachs mutation

但在阿什肯納茲族群中 泰薩氏症突變的比率

in Ashkenazi populations

高到不尋常的現象

may be another example of heterozygote advantage.

可能是另一個異型合子優勢的例子。

In this case, increasing resistance to tuberculosis.

在這個例子中， 增強的是對結核病的抵抗力。

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

點出泰薩氏症和結核病之間 可能有關聯的第一個暗示

came in the 1970s,

出現在 1970 年代，

when researchers published data

當時研究者公佈的資料顯示

showing that among the Eastern European-born grandparents

美國的阿什肯納茲孩童 若在出生時就有泰薩氏症，

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

他們在東歐出生的祖父母

tuberculosis was an exceedingly rare cause of death.

因為結核病而死的比率低得驚人。

In fact, only one out of these 306 grandparents

事實上，三百零六名祖父母中，

只有一名因結核病而死，

had died of TB,

despite the fact that in the early 20th century,

但在二十世紀初期

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

在東歐的大型城市中 結核病的致死率高達兩成。

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

一方面，這些結果很讓人驚訝。

People had already recognized

大家公認

that while Jews and non-Jews in Europe

在歐洲，雖然猶太人和非猶太人

had been equally likely to contract TB during this time,

在這段時期得到 結核病的機率差不多，

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

但非猶太人的死亡率卻是兩倍高。

But the hypothesis that these Ashkenazi grandparents

但，假設這些阿什肯納茲祖父母

had been less likely to die of TB

比較不可能死於結核病，

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

就是因為他們當中至少 有些人帶有泰薩氏症的基因，

was novel and compelling.

這個假設很新穎且引人注目。

The data hinted

資料暗示，

that the persistence of the Tay-Sachs mutation

阿什肯納茲猶太人中 泰薩氏症突變一直存在，

among Ashkenazi Jews

might be explained by the benefits of being a carrier

這個現象的原因可能是

在流行結核病的環境中 帶有這種基因是有益處的。

in an environment where tuberculosis was prevalent.

You'll notice, though,

但可以注意到，

that this explanation only fills in part of the puzzle.

這種解釋只解開了拼圖的一部分。

Even if the Tay-Sachs mutation persisted

即使泰薩氏症突變一直存在

because carriers were more likely to survive,

是因為帶有這種基因 比較有機會生存、

reproduce and pass on their genetic material,

繁殖，再把遺傳物質傳下去，

why did this resistance mechanism proliferate

那為什麼這種機制

在阿什肯納茲人口中特別明顯？

among the Ashkenazi population in particular?

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

一個可能性是，東歐猶太人的基因

和健康不僅受到地理的影響，

were affected not simply by geography

but also by historical and cultural factors.

還會受到歷史和文化因素的影響。

At various points in history

在歷史上許多時點，

this population was forced to live in crowded urban ghettos

這個族群都被迫要住在擁擠

with poor sanitation.

且衛生很差的都市猶太區。

Ideal conditions for the tuberculosis bacterium to thrive.

這些條件相當適合結核菌生長茁壯。

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

在這些環境中， 結核病是特別大的威脅，

those individuals who were not carriers of any genetic protection

沒有任何基因保護， 不帶有突變基因的人，

would have been more likely to die.

更有可能會死亡。

This winnowing effect

這種篩選效應

together with a strong cultural predilection

再加上阿什肯納茲人強烈偏好

for marrying and reproducing only within the Ashkenazi community,

只和同族群結婚生子，

would have amplified the relative frequency of carriers,

就有可能放大帶有 突變基因者的相對數目，

boosting TB resistance

促進對抗結核病的能力，

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

但不幸的副作用就是 泰薩氏症的發生率會增加。

Studies from the 1980s support this idea.

1980 年代的研究支持這個想法。

The segment of the American Jewish population

美國猶太人人口中

這個族群帶有泰薩氏症 基因的人數最多，

that had the highest frequency of Tay-Sachs carriers

traced their descent

他們追溯自己的世系到

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

結核病發病率最高的歐洲國家。

The benefits of being a Tay-Sachs carrier were highest

在這些地方，因為結核病 而死的風險最高，

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

因此帶有泰薩氏症 基因的益處也最大。

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

雖然我們不清楚 在 1970 或 1980 年代時

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

泰薩氏症突變基因到底 如何提供對抗結核病的保護，

recent work has identified

近期有研究發現

how the mutation increases cellular defenses against the bacterium.

突變如何增加細胞 對抗細菌的防禦能力。

So heterozygote advantage can help explain

所以，異型合子可以解釋

why problematic versions of genes persist at high frequencies

為什麼在某些族群中

有問題的基因會大量延續下去。

in certain populations.

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

但，在協助我們了解人類健康上，

in helping us understand human health.

演化醫學的貢獻不只如此。

As I mentioned earlier,

如先前所言，

this field challenges the notion

這個領域在挑戰我們認為

that our bodies should have gotten better over time.

人類身體會隨時間變更好的觀念。

An idea that often stems from a misconception

這個想法通常源自

對演化功能的誤解。

of how evolution works.

In a nutshell,

概括來說，

there are three basic reasons why human bodies,

有三個理由可以說明 為什麼人類的身體，

including yours and mine,

包括你我的身體，

remain vulnerable to diseases and other health problems today.

現今仍然很難抵抗疾病和其他問題。

Natural selection acts slowly,

天擇的速度很慢，

there are limitations to the changes it can make

天擇能做的改變有限，

and it optimizes for reproductive success,

且天擇的目標是繁殖成功率

not health.

而非健康。

The way the pace of natural selection affects human health

若想知道天擇影響 人類健康的步調有多緩慢，

is probably most obvious

最明顯的地方

in people's relationship with infectious pathogens.

就是人類和傳染病病原體的關係。

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

我們和細菌及病毒 經常在做軍備競賽。

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

我們的免疫系統持續演化， 限制細菌及病毒的感染力，

and they are continuously developing ways to outmaneuver our defenses.

它們則持續發展新策略 來擊敗我們的防禦。

And our species is at a distinct disadvantage

因為我們的壽命很長且繁殖緩慢，

due to our long lives and slow reproduction.

人類這個物種明顯佔劣勢。

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

我們演化出一種對抗機制 所需要花的時間，

a pathogenic species will go through millions of generations,

病原體物種就已經 經過了數百萬個世代，

giving it ample time to evolve,

有很充裕的時間演化，

so it can continue using our bodies as a host.

所以能夠持續 用我們的身體當作宿主。

Now what does it mean that there are limitations

天擇能做的改變有限是什麼意思？

to the changes natural selection can make?

Again, my examples of heterozygote advantage

同樣可以用我的異型合子例子

offer a useful illustration.

來做說明。

In terms of resisting TB and malaria,

在抵抗結核病和瘧疾方面，

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

泰薩氏症和鐮刀型紅血球貧血症

突變的生理效應是很好的。

are good.

Taken to their extremes, though,

不過，在最極端的狀況， 它們會造成重大的問題。

they cause significant problems.

This delicate balance highlights the constraints

這種脆弱的平衡

強調出人類身體的天生限制，

inherent in the human body,

and the fact that the evolutionary process

以及演化過程一定得使用

must work with the materials already available.

既有的可得素材。

In many instances,

在許多例子中，改善生存 或繁殖能力的改變，

a change that improves survival or reproduction

in one sense

在某種意義上， 可能會有一連串的效應，

may have cascading effects that carry their own risk.

帶有它們自己的風險。

Evolution isn't an engineer that starts from scratch

演化並不像是工程師從零開始，

to create optimal solutions to individual problems.

針對個別問題去創造解決方案。

Evolution is all about compromise.

演化完全是妥協。

It's also important to remember,

還有一點也很重要，

when considering our bodies' vulnerabilities,

在考量到我們身體的弱點時，

that from an evolutionary perspective,

從演化的角度，

health isn't the most important currency.

健康並不是最重要的貨幣。

Reproduction is.

繁殖才是。

Success is measured not by how healthy an individual is,

判斷成功與否， 看的不是一個人有多健康，

or by how long she lives,

或者壽命多長，

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

而是這個人的基因 能複製多少份到下一代。

This explains why a mutation

這就說明了為什麼突變，

like the one that causes Huntington's disease,

比如造成另一種神經退化障礙

another degenerative neurological disorder,

亨丁頓舞蹈症的突變，

hasn't been eliminated by natural selection.

並沒有被天擇給淘汰。

The mutation's detrimental effects

這類突變的有害效應

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

通常要到一般的生育年齡 之後才會出現，

when affected individuals have already passed on their genes.

此時被影響的人也已經 把基因傳給下一代了。

As a whole,

總的來說，

the biomedical community focuses on proximate explanations

生物醫學領域的焦點是在 「近因解釋」，

and uses them to shape treatment approaches.

並用它們來發展治療方法。

Proximate explanations for health conditions

對於健康狀況的近因解釋

consider the immediate factors:

會考量立即性的因素：

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

現在這個人的體內有什麼現象

that caused a particular problem.

會造成某個特定問題。

Nearsightedness, for example,

以近視為例，

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

通常是眼睛形狀改變的結果，

and can be easily corrected with glasses.

很容易就用眼鏡來校正。

But as with the genetic conditions I've discussed,

但換成是我剛才討論的基因狀況，

a proximate explanation only provides part of the bigger picture.

近因解釋就只能提供全貌的一部分。

Adopting an evolutionary perspective

採用演化的視角，

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

更廣泛來思考我們一開始

為什麼會有這個問題——

to begin with --

what evolutionary medicine calls the ultimate perspective --

演化醫學所謂的「終極觀點」——

can give us insight into nonimmediate factors

讓我們能去洞察

影響健康的非立即性因素。

that affect our health.

This is crucial,

這很重要，

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

因為從中可以找出一些方法

來將幫你自己或朋友家人 將風險降到最低。

or that of friends and family.

In the case of nearsightedness,

在近視的例子中，

some research suggests

有些研究指出，

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

在某些族群中近視 更普遍的其中一個理由

is that many people today,

就是現今有很多人，

including most of us in this room,

包括在座的大部分人，

spend far more time reading, writing

花在閱讀、書寫，

和接觸各種螢幕的時間，

and engaging with various types of screen

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

遠多於我們花在外面， 和更大的世界互動的時間。

In evolutionary terms, this is a recent change.

在演化方面，這算是近期的改變。

For most of human evolutionary history,

人類演化史上大部分的時間，

people used their vision across a broader landscape,

人們都把視力用在更廣大的地景上，

spending more time in activities like hunting and gathering.

花更多時間從事 如打獵和採集等活動。

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

近年來，所謂的「近距離工作」增加，

focusing intensely on objects directly in front of us

聚焦在我們面前的物品上，

for long periods of time,

且持續很長的時間，

strains our eyes differently

用不同的方式讓眼睛疲憊，

and affects the physical shape of the eye.

影響眼睛的實體形狀。

When we put all these pieces together,

當我們把所有這些拼圖拼起來，

this ultimate explanation for nearsightedness --

這個近視的終極解釋——

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

即：環境和行為的改變影響了 我們使用眼睛的方式——

helps us better understand the proximate cause.

能協助我們更了解近因。

And an inescapable conclusion emerges --

而必然的結論就浮現了——

my mother was right,

我母親是對的——

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

我應該少花點時間埋頭讀書。

This is just one of many possible examples.

這只是許多可能例子中的一個。

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

下次，當你或你親愛的人 面臨健康上的難題時，

whether it's obesity or diabetes,

不論是肥胖或糖尿病、

an autoimmune disorder,

自體免疫疾病，

or a knee or back injury,

或膝蓋或背部受傷，

I encourage you to think

我都鼓勵你去想想 最終觀點能提供什麼見解。

about what an ultimate perspective can contribute.

Understanding that your health

若你能知道你的健康

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

不僅會受到你的身體現狀所影響，

but also by your genetic inheritance, culture and history,

也會受到基因遺傳、 文化、歷史的影響，

can help you make more informed decisions

也許你就能根據更多資訊來做出

about predispositions, risks and treatments.

和體質、風險，及治療相關的決策。

As for me,

至於我，

I won't claim that an evolutionary medicine perspective

我不會宣稱演化醫學觀點

has always directly influenced my decisions,

向來都會直接影響我的決策，

such as my choice of spouse.

比如我對配偶的選擇。

It turned out, though,

不過，結果發現，

that not following the traditional practice

不遵循傳統做法

of marrying within the Jewish community

嫁給猶太族群的人，

ultimately worked in my favor genetically,

最終反而在基因方面對我有好處，

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

減少我生出泰薩氏症寶寶的機率。

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

這是個很好的例子， 說明為什麼阿什肯納茲父母

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

不應該希望他們的女兒 嫁給「一個猶太好男孩」。

(Laughter)

（笑聲）（觀眾歡呼）

(Audience) Woo-hoo!

More importantly, though,

不過，更重要的是，

the experience of learning about my own genes

了解我自己基因的這段經歷

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

教導我如何用不同的方式 看待長期的健康，

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

希望藉由分享我的故事， 也能鼓舞大家這麼做。

Thank you.

謝謝。

(Applause)

（掌聲）