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.

因為我仍然有一個正常的這種基因，

Because I still have one normal copy of this gene,

突變並不會影響我。

the mutation doesn't affect me.

但如果寶寶從雙親 遺傳到了這種突變，

But if a baby inherits this mutation from both parents,

如果兩個這種基因 都無法發揮正常功能，

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

就會造成泰薩氏症，

it results in Tay-Sachs,

這種疾病無法治癒，

an incurable disease

會漸漸讓中樞神經系統停擺，

that progressively shuts down the central nervous system

造成病人在五歲時就死亡。

and causes death by age five.

這種消息可能會讓 許多懷孕的女性極度慌張。

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

但，當我聽到這個關於 我自身生物學的震撼彈時，

But I knew something that helped keep me calm

因為我知道一件事， 讓我能保持冷靜。

when I heard this bombshell about my own biology.

我知道我的丈夫

I knew that my husband,

不像我有東歐猶太血統，

whose ancestry isn't Eastern European Jewish like mine,

因此他幾乎不可能

had a very low likelihood

同時也帶有泰薩氏症的突變基因。

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

所謂的異型合子指的是

While the frequency of heterozygotes,

一對基因中有一個正常

individuals who have one normal copy of the gene

另一個突變，

and one mutated copy,

在像我這種阿什肯納茲猶太裔身上

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

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,

我知道在阿什肯納茲族群當中 有異常高的泰薩氏症比率。

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

但，一直到我女兒出生的幾年後，

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

我在哈佛設計並教授 一場關於演化醫學的研討會時，

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

我才想到要問「為什麼？」

that I thought to ask,

並去尋找可能的答案。

and discovered a possible answer to,

天擇的演化過程

the question "why?"

通常會讓有害的突變消失。

The process of evolution by natural selection

所以，這個瑕疵的基因 怎麼能夠留存下來？

typically eliminates harmful mutations.

且為什麼在這個特定的族群中

So how did this defective gene persist at all?

發生的比率特別高？

And why is it found at such a high frequency

演化醫學的觀點能提供 很有價值的洞見，

within this particular population?

因為它在探究 「如何」及「為什麼」

The perspective of evolutionary medicine offers valuable insight,

人類過去的演化造成我們的身體

because it examines how and why

很難抵抗現今的疾病和其他問題。

humans' evolutionary past has left our bodies vulnerable

透過這樣的探究，可以發現

to diseases and other problems today.

天擇不一定會 讓我們的身體變得更好。

In doing so,

不見得。

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

但，我希望能用 我自己的故事來說明：

It can't necessarily.

了解你過去的演化有什麼意涵，

But as I hope to illustrate with my own story,

便能協助充實你的個人健康。

understanding the implications of your evolutionary past

當我開始從演化的觀點 研究泰薩氏症時，

can help enrich your personal health.

我偶然發現一個有趣的假設。

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

現今的阿什肯納茲猶太人具有

I came across an intriguing hypothesis.

泰薩氏症突變的比率高到不尋常，

The unusually high rate of the Tay-Sachs mutation

可能和過去這項突變

in Ashkenazi Jews today

帶給這個族群的優勢有關。

may relate to advantages the mutation gave this population

我相信在座有人在想：「抱歉，

in the past.

你剛剛的意思是 這種會造成疾病的突變

Now I'm sure some of you are thinking,

也有有益的效應？」

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

是的，沒錯。

had beneficial effects?"

當然我指的不是 遺傳到兩個突變基因

Yeah, I did.

且患有泰薩氏症的那些人。

Certainly not for individuals who inherited two copies of the mutation

但在某些情況下，像我這樣的人，

and had Tay-Sachs.

只有一個基因有缺陷的人，

But under certain circumstances,

可能在過去比較容易生存、繁殖，

people like me,

並將遺傳物質傳下去，

who had only one faulty gene copy,

包括那個突變的基因。

may have been more likely to survive, reproduce

在某些情況下異型合子會比較好，

and pass on their genetic material,

在座有人可能很熟悉這個想法。

including that mutated gene.

演化生物學家把這個現象稱為

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

「異型合子優勢」。

might sound familiar to some of you.

比如，它可以解釋

Evolutionary biologists call this phenomenon

為什麼鐮刀型紅血球貧血症

heterozygote advantage.

比較常出現在一些 非洲和亞洲人的族群中，

And it explains, for example,

或者祖先來自這些 熱帶地區的族群中。

why carriers of sickle cell anemia

在這些地理區域，

are more common among some African and Asian populations

瘧疾對健康是很重大的風險。

or those with ancestry from these tropical regions.

不過，造成瘧疾的寄生蟲

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

只能在正常、圓形的紅血球 細胞中完成它的生命循環。

The parasite that causes malaria, though,

鐮刀型紅血球細胞突變 能夠改變人類紅血球細胞的形狀，

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

進而保護人類，抵抗瘧疾。

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

有這種突變基因的人並不是

the sickle cell mutation confers protection against malaria.

比較不會被傳播瘧疾的蚊子叮咬，

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

但他們比較不會因為 被叮咬而生病或死亡。

by the mosquitoes that transmit the disease,

因此，有鐮刀型紅血球貧血症

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

反而是在瘧疾環境中 最好的遺傳選項。

Being a carrier for sickle cell anemia

這種人比較不會得到瘧疾，

is therefore the best possible genetic option

因為他們會製造 一些鐮刀型紅血球細胞，

in a malarial environment.

但他們也會製造 足夠的正常紅血球細胞，

Carriers are less susceptible to malaria,

所以他們不會受到鐮刀型 紅血球貧血症的負面影響。

because they make some sickled red blood cells,

在我的例子中，我身上的基因缺陷

but they make enough normal red blood cells

並不會保護我抵抗瘧疾。

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

但在阿什肯納茲族群中 泰薩氏症突變的比率

Now in my case,

高到不尋常的現象

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

可能是另一個異型合子優勢的例子。

But the unusual prevalence of the Tay-Sachs mutation

在這個例子中， 增強的是對結核病的抵抗力。

in Ashkenazi populations

點出泰薩氏症和結核病之間 可能有關聯的第一個暗示

may be another example of heterozygote advantage.

出現在 1970 年代，

In this case, increasing resistance to tuberculosis.

當時研究者公佈的資料顯示

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

美國的阿什肯納茲孩童 若在出生時就有泰薩氏症，

came in the 1970s,

他們在東歐出生的祖父母

when researchers published data

因為結核病而死的比率低得驚人。

showing that among the Eastern European-born grandparents

事實上，三百零六名祖父母中，

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

只有一名因結核病而死，

tuberculosis was an exceedingly rare cause of death.

但在二十世紀初期

In fact, only one out of these 306 grandparents

在東歐的大型城市中 結核病的致死率高達兩成。

had died of TB,

一方面，這些結果很讓人驚訝。

despite the fact that in the early 20th century,

大家公認

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

在歐洲，雖然猶太人和非猶太人

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

在這段時期得到 結核病的機率差不多，

People had already recognized

但非猶太人的死亡率卻是兩倍高。

that while Jews and non-Jews in Europe

但，假設這些阿什肯納茲祖父母

had been equally likely to contract TB during this time,

比較不可能死於結核病，

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

就是因為他們當中至少 有些人帶有泰薩氏症的基因，

But the hypothesis that these Ashkenazi grandparents

這個假設很新穎且引人注目。

had been less likely to die of TB

資料暗示，

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

阿什肯納茲猶太人中 泰薩氏症突變一直存在，

was novel and compelling.

這個現象的原因可能是

The data hinted

在流行結核病的環境中 帶有這種基因是有益處的。

that the persistence of the Tay-Sachs mutation

但可以注意到，

among Ashkenazi Jews

這種解釋只解開了拼圖的一部分。

might be explained by the benefits of being a carrier

即使泰薩氏症突變一直存在

in an environment where tuberculosis was prevalent.

是因為帶有這種基因 比較有機會生存、

You'll notice, though,

繁殖，再把遺傳物質傳下去，

that this explanation only fills in part of the puzzle.

那為什麼這種機制

Even if the Tay-Sachs mutation persisted

在阿什肯納茲人口中特別明顯？

because carriers were more likely to survive,

一個可能性是，東歐猶太人的基因

reproduce and pass on their genetic material,

和健康不僅受到地理的影響，

why did this resistance mechanism proliferate

還會受到歷史和文化因素的影響。

among the Ashkenazi population in particular?

在歷史上許多時點，

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

這個族群都被迫要住在擁擠

were affected not simply by geography

且衛生很差的都市猶太區。

but also by historical and cultural factors.

這些條件相當適合結核菌生長茁壯。

At various points in history

在這些環境中， 結核病是特別大的威脅，

this population was forced to live in crowded urban ghettos

沒有任何基因保護， 不帶有突變基因的人，

with poor sanitation.

更有可能會死亡。

Ideal conditions for the tuberculosis bacterium to thrive.

這種篩選效應

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

再加上阿什肯納茲人強烈偏好

those individuals who were not carriers of any genetic protection

只和同族群結婚生子，

would have been more likely to die.

就有可能放大帶有 突變基因者的相對數目，

This winnowing effect

促進對抗結核病的能力，

together with a strong cultural predilection

但不幸的副作用就是 泰薩氏症的發生率會增加。

for marrying and reproducing only within the Ashkenazi community,

1980 年代的研究支持這個想法。

would have amplified the relative frequency of carriers,

美國猶太人人口中

boosting TB resistance

這個族群帶有泰薩氏症 基因的人數最多，

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

他們追溯自己的世系到

Studies from the 1980s support this idea.

結核病發病率最高的歐洲國家。

The segment of the American Jewish population

在這些地方，因為結核病 而死的風險最高，

that had the highest frequency of Tay-Sachs carriers

因此帶有泰薩氏症 基因的益處也最大。

traced their descent

雖然我們不清楚 在 1970 或 1980 年代時

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

泰薩氏症突變基因到底 如何提供對抗結核病的保護，

The benefits of being a Tay-Sachs carrier were highest

近期有研究發現

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

突變如何增加細胞 對抗細菌的防禦能力。

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

所以，異型合子可以解釋

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

為什麼在某些族群中

recent work has identified

有問題的基因會大量延續下去。

how the mutation increases cellular defenses against the bacterium.

但，在協助我們了解人類健康上，

So heterozygote advantage can help explain

演化醫學的貢獻不只如此。

why problematic versions of genes persist at high frequencies

如先前所言，

in certain populations.

這個領域在挑戰我們認為

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

人類身體會隨時間變更好的觀念。

in helping us understand human health.

這個想法通常源自

As I mentioned earlier,

對演化功能的誤解。

this field challenges the notion

概括來說，

that our bodies should have gotten better over time.

有三個理由可以說明 為什麼人類的身體，

An idea that often stems from a misconception

包括你我的身體，

of how evolution works.

現今仍然很難抵抗疾病和其他問題。

In a nutshell,

天擇的速度很慢，

there are three basic reasons why human bodies,

天擇能做的改變有限，

including yours and mine,

且天擇的目標是繁殖成功率

remain vulnerable to diseases and other health problems today.

而非健康。

Natural selection acts slowly,

若想知道天擇影響 人類健康的步調有多緩慢，

there are limitations to the changes it can make

最明顯的地方

and it optimizes for reproductive success,

就是人類和傳染病病原體的關係。

not health.

我們和細菌及病毒 經常在做軍備競賽。

The way the pace of natural selection affects human health

我們的免疫系統持續演化， 限制細菌及病毒的感染力，

is probably most obvious

它們則持續發展新策略 來擊敗我們的防禦。

in people's relationship with infectious pathogens.

因為我們的壽命很長且繁殖緩慢，

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

人類這個物種明顯佔劣勢。

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

我們演化出一種對抗機制 所需要花的時間，

and they are continuously developing ways to outmaneuver our defenses.

病原體物種就已經 經過了數百萬個世代，

And our species is at a distinct disadvantage

有很充裕的時間演化，

due to our long lives and slow reproduction.

所以能夠持續 用我們的身體當作宿主。

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

天擇能做的改變有限是什麼意思？

a pathogenic species will go through millions of generations,

同樣可以用我的異型合子例子

giving it ample time to evolve,

來做說明。

so it can continue using our bodies as a host.

在抵抗結核病和瘧疾方面，

Now what does it mean that there are limitations

泰薩氏症和鐮刀型紅血球貧血症

to the changes natural selection can make?

突變的生理效應是很好的。

Again, my examples of heterozygote advantage

不過，在最極端的狀況， 它們會造成重大的問題。

offer a useful illustration.

這種脆弱的平衡

In terms of resisting TB and malaria,

強調出人類身體的天生限制，

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

以及演化過程一定得使用

are good.

既有的可得素材。

Taken to their extremes, though,

在許多例子中，改善生存 或繁殖能力的改變，

they cause significant problems.

在某種意義上， 可能會有一連串的效應，

This delicate balance highlights the constraints

帶有它們自己的風險。

inherent in the human body,

演化並不像是工程師從零開始，

and the fact that the evolutionary process

針對個別問題去創造解決方案。

must work with the materials already available.

演化完全是妥協。

In many instances,

還有一點也很重要，

a change that improves survival or reproduction

在考量到我們身體的弱點時，

in one sense

從演化的角度，

may have cascading effects that carry their own risk.

健康並不是最重要的貨幣。

Evolution isn't an engineer that starts from scratch

繁殖才是。

to create optimal solutions to individual problems.

判斷成功與否， 看的不是一個人有多健康，

Evolution is all about compromise.

或者壽命多長，

It's also important to remember,

而是這個人的基因 能複製多少份到下一代。

when considering our bodies' vulnerabilities,

這就說明了為什麼突變，

that from an evolutionary perspective,

比如造成另一種神經退化障礙

health isn't the most important currency.

亨丁頓舞蹈症的突變，

Reproduction is.

並沒有被天擇給淘汰。

Success is measured not by how healthy an individual is,

這類突變的有害效應

or by how long she lives,

通常要到一般的生育年齡 之後才會出現，

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

此時被影響的人也已經 把基因傳給下一代了。

This explains why a mutation

總的來說，

like the one that causes Huntington's disease,

生物醫學領域的焦點是在 「近因解釋」，

another degenerative neurological disorder,

並用它們來發展治療方法。

hasn't been eliminated by natural selection.

對於健康狀況的近因解釋

The mutation's detrimental effects

會考量立即性的因素：

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

現在這個人的體內有什麼現象

when affected individuals have already passed on their genes.

會造成某個特定問題。

As a whole,

以近視為例，

the biomedical community focuses on proximate explanations

通常是眼睛形狀改變的結果，

and uses them to shape treatment approaches.

很容易就用眼鏡來校正。

Proximate explanations for health conditions

但換成是我剛才討論的基因狀況，

consider the immediate factors:

近因解釋就只能提供全貌的一部分。

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

採用演化的視角，

that caused a particular problem.

更廣泛來思考我們一開始

Nearsightedness, for example,

為什麼會有這個問題——

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

演化醫學所謂的「終極觀點」——

and can be easily corrected with glasses.

讓我們能去洞察

But as with the genetic conditions I've discussed,

影響健康的非立即性因素。

a proximate explanation only provides part of the bigger picture.

這很重要，

Adopting an evolutionary perspective

因為從中可以找出一些方法

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

來將幫你自己或朋友家人 將風險降到最低。

to begin with --

在近視的例子中，

what evolutionary medicine calls the ultimate perspective --

有些研究指出，

can give us insight into nonimmediate factors

在某些族群中近視 更普遍的其中一個理由

that affect our health.

就是現今有很多人，

This is crucial,

包括在座的大部分人，

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