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  • I would like to talk with you about sex and disease,

    我想跟大家談談性別和疾病

  • but perhaps not what you're thinking.

    但可能跟你想的不太一樣

  • So, now that I've gotten your attention,

    現在,我吸引到各位的注意了

  • I'd like to tell you about something that's really fundamental.

    我想告訴大家一些很根本的事情

  • I'd like to tell you about a connection between sex

    我想告訴大家性別和疾病

  • and disease that is very critical,

    之間很重要的關聯

  • but a connection between sex and disease

    但是性別和疾病之間的關聯

  • that has gone largely unnoticed and unexplored

    一直嚴重被忽視也未被發覺

  • even within the scientific community.

    即使是在科學界

  • So, to get things under way,

    在開始之前

  • let me open with three observations

    我先提出三項觀察結果

  • that I think you may find a little surprising and startling.

    我想各位會覺得有些驚訝且吃驚

  • First of all, human genome, we have a problem.

    首先,人類基因,我們有個問題

  • Second, men and women are not equal.

    第二,男性和女性並不平等

  • I'll pause there --

    暫停一下──

  • And third, that the study of disease is flawed.

    第三,疾病研究是有瑕疵的

  • So, let's explore each of these in turn.

    我們現在來依序探究這些項目

  • Across the course of time,

    過去以來

  • scientists, no matter how brilliant they are,

    不管科學家們有多聰明

  • have gotten things wrong in a big way.

    都嚴重地搞錯了一些事

  • For a long time, we thought that the Earth was flat,

    有很長一段時間,我們都相信地球是平坦的

  • and we thought that the sun revolved around the Earth.

    也認為太陽繞著地球運行

  • Well, in this time of the human genome revolution,

    而這次的人類基因革命

  • it turns out that we're missing something

    事實證明我們的確遺漏了一些

  • that is of critical importance.

    非常重要的東西

  • And to understand what's that all about,

    為了瞭解這些

  • I need to ask you to return with me to the beginning

    我希望各位和我一起回到

  • where each of us began.

    我們的起點

  • So, here it is, the moment of conception, egg meets sperm!

    這就是受精的時刻,卵子遇上精子!

  • All the cells of your body --

    所有構成身體的細胞──

  • your lung cells, your liver cells, your skin cells,

    你的肺細胞、肝細胞、皮膚細胞

  • all the cells of your body ultimately derived from this one founding cell,

    所有組成身體的細胞最初都是從這個細胞分裂而來

  • the fertilized egg.

    也就是受精卵

  • So, the fertilized egg divides to become two cells,

    受精卵分裂成兩個細胞

  • those two divide to become four, and eight, and so on --

    兩個細胞分裂成四個,然後是八個,以此類推

  • until your entire body consisting of --

    直到你全身上下

  • on the order of 10 trillion cells has been assembled,

    被10兆個細胞組合起來

  • and what is most amazing is that within the nucleus

    而最奇妙的是

  • of each of those 10 trillion cells that make up your body,

    在10兆個組成你的細胞的細胞核中

  • within each of those cells,

    每個細胞內

  • you carry the same 23 pairs of chromosomes.

    都有23對相同的染色體

  • And those 23 pairs of chromosomes,

    而這23對染色體

  • carry all of the DNA,

    攜帶有所有的DNA

  • all of the hereditary material,

    所有的遺傳物質

  • all of the hereditary information

    所有的遺傳資訊

  • with which your cells, and tissues, and organs in your body execute their functions.

    是你體內每個細胞、組織和器官執行功能的地方

  • So, let's look at those 23 pairs of chromosomes in more detail.

    我們現在來更仔細的看這23對染色體

  • It turns out, that of the 23 pairs,

    結果是這23對中

  • 22 pairs are absolutely identical

    有22對完全相同

  • and shared between men and women.

    而且男性和女性都有

  • And here they're shown --

    如圖所示

  • The differences arise in the 23rd pair,

    不同之處在於第23對

  • which in females is a beautifully matched pair of X chromosomes,

    女性擁有一對完美對稱的X染色體

  • but in males, that 23rd matched pair

    但男性的第23對染色體

  • is replaced by a mismatched pair, an XY pair.

    是不對稱的XY染色體

  • And let's look in more detail at that mismatched XY pair --

    現在來更仔細的看看不相配的XY染色體

  • Here they are --

    就是這個

  • to the left, the stately and grand X chromosome --

    左邊的是高貴雄偉的X染色體

  • (Laughter) Why do you laugh?

    (笑聲)你們為什麼在笑?

  • To its right, the diminutive and demure Y chromosome, with its head down.

    右邊的,是嬌小端莊的Y染色體,頭部向下

  • Now, if truth be known,

    說實話

  • I've spent the entirety of my career at Whitehead Institute

    我奉獻了我的職業生涯在懷特海德研究所

  • defending the honor of the Y chromosome -- (Laughter)

    捍衛Y染色體的光榮──(笑聲)

  • In the face of innumerable insults to its character and its future prospect.

    儘管有無數個對於它的特性和前途的侮辱

  • Even to this day, it is thought by physicians and most scientists around the world,

    直至今日,全球大部分的醫師和科學家還是認為

  • that the function of the Y chromosome

    Y染色體的功能

  • is restricted to the cells of the reproductive tract.

    只侷限於生殖道的細胞

  • And in fact, this idea that the cells of the reproductive tract

    事實上,認為生殖道細胞

  • are the only place where the Y functions,

    是Y染色體唯一有功用的地方的想法

  • has led, in turn, to the notion

    反而讓我們注意到

  • that the genomes of men and women are,

    男性和女性的基因

  • apart from the reproductive tract,

    除了生殖道以外

  • functionally, maybe even morally equivalent.

    在功能上是道德上相等的

  • And so, in fact, it has been said many times

    所以,事實上,大家常常說

  • that apart from the reproductive tract and even disregarding that for a moment,

    除了生殖道以外,甚至忽略這個部分不看

  • it is been said many times,

    大家常常說

  • that our genomes are all 99.9% identical,

    我們的基因是99.9%相同的

  • from one person to the next.

    每個人都一樣

  • This idea that we're 99.9% identical has gained great traction

    認為每個人都是99.9%相同的概念受到廣大支持

  • and for a number of reasons --

    而理由也很多──

  • It's very appealing to say that we are all 99.9% identical --

    每個人都是99.9%相同的說法很吸引人──

  • It's so appealing that this idea

    這個說法吸引了

  • was seized upon by President Bill Clinton

    比爾柯林頓總統的注意

  • in his 2000 State of the Union address --

    他在2000年的國情咨文演說中都利用了這個概念──

  • when he stated that, "This fall, at the White House...

    他表示:「今年秋天,有一位

  • we had a distinguished scientist visiting,

    傑出的科學家造訪白宮

  • an expert in this work on the human genome,

    他是人類基因科學的專家

  • and he said that we are all, regardless of race,

    他說人類的基因

  • genetically 99.9% the same."

    都是 99.9%相同的,不分種族。」

  • Wow -- it turns out that this idea is even correct --

    哇──事實證明這個想法是正確的

  • as long as, the two individuals being compared are both men.

    只要兩個被比較的個體都是男性

  • It's also correct, if the two individuals being compared are both women.

    如果兩個被比較的個體都是女性,這樣也是正確的

  • However, if you compare the genome of a man

    然而,如果你比較男性的基因

  • with the genome of a woman,

    和女性的基因

  • you'll find that they are actually only 98.5% identical.

    你會發現其實基因只有98.5%相同

  • In other words, the genetic difference between a man and a woman

    換句話說,男性與女性之間的基因差異

  • is 15 times the genetic difference

    是兩位男性與兩位女性之間的

  • between two men or between two women.

    基因差異的15倍

  • Let us consider, for example, the case of Bill and Hillary -- (Laughter)

    現在讓我們以比爾和希拉蕊作為比較案例(笑聲)

  • So, it turns out that Bill is as genetically similar to Hillary,

    事實證明比爾和希拉蕊之間的基因相似度

  • as he is to a male chimpanzee. (Laughter)

    等同於和雄性黑猩猩的基因相似度(笑聲)

  • But, human genome, we have a problem --

    但是人類基因,現在有個問題

  • In the human genome era in which we're living,

    在我們生活的人類基因體時代

  • this fundamental difference between males and females,

    男性與女性之間的基本差異

  • has been overlooked.

    一直被忽略

  • Instead, we have been operating

    取而代之的是,我們一直

  • with a unisex vision of the human genome.

    將人類基因視為男女相同的

  • And so -- in fact, men and women are not equal in their genomes --

    所以事實上,男性和女性在基因上是不平等的

  • as I just explained,

    如我所解釋

  • and, as I want to go on to explain now --

    也如我接下來要解釋的

  • men and women are also not equal in the face of disease.

    男性和女性在面對疾病時,也是不平等的

  • Now, what do I mean by that?

    這是什麼意思?

  • And what are its consequences

    這會造成什麼後果

  • and what are the implications for health care?

    這對醫療保健又有什麼意義?

  • I will cite a number of examples to illustrate what I have in mind.

    我會援引許多例子來闡述我的想法

  • We'll take the case of Rheumatoid Arthritis --

    先談談類風濕性關節炎的案例

  • For every man with Rheumatoid Arthritis,

    罹患類風濕性關節炎的男女比

  • there are 2 to 3 women who are affected with this disorder.

    是1位男性比2.5位女性

  • Now, is Rheumatoid Arthritis a disease of the reproductive tract?

    類風濕性關節炎是生殖道疾病嗎?

  • No.

    不是

  • Is there any obvious anatomic difference between men and women

    男性與女性之間是否有解剖學上的顯著差異

  • to account for this dramatic difference

    能解釋為何罹患類風濕性關節炎的機率

  • in the incidence of Rheumatoid Arthritis, its higher incidence in women?

    有這麼大的差異,而且女性罹患的機率較高?

  • There is no simple, anatomic explanation to be had.

    並沒有簡單的、解剖學上的解釋能說明

  • Let's flip the tables now and consider Autism Spectrum Disorders.

    先不管這個,來看看自閉譜系疾患

  • For every girl with an Autism Spectrum Disorder

    自閉譜系疾患的男女比

  • the most recent numbers suggest,

    以最近的數據來看

  • that there are about 5 boys with such a disorder.

    是1位女性比5位男性

  • Why is that the case?

    為何如此?

  • Let's flip the table yet again --

    我們同樣先跳過

  • Lupus - a long term, autoimmune disorder

    狼瘡──長期的自體免疫疾病

  • with devastating consequences that can result in death,

    破壞力非常強,可能會導致死亡

  • for every man who is suffering from Lupus,

    罹患狼瘡的男女比

  • there are 6 women who is suffering from this disorder.

    是1位男性比6位女性

  • And so, for a whole host of disorders

    所以,有許多

  • that occur outside the reproductive tract

    不是發生在生殖道的疾病

  • we see that the incidence or prevalence

    我們發現男性與女性之間

  • in men and women can differ dramatically.

    罹患或感染疾病的機率差異非常大

  • And even in the case when a disease occurs

    甚至在男性和女性

  • in both men and women,

    都罹患疾病的案例中

  • that disorder can be much more severe

    某一個性別的疾病症狀

  • or have more severe consequences

    或疾病造成的後果

  • in one sex than the other.

    都會比另一個性別嚴重

  • Let's consider here the case of Dilated Cardiomyopathy.

    再來看擴張型心肌症的案例

  • Dilated Cardiomyopathy is a condition

    擴張型心肌症就是

  • where the wall of the heart thins,

    心臟壁變薄

  • and the heart balloons dangerously --

    導致心臟危險地膨脹

  • and sometimes, with devastating consequences.

    有時候會造成毀壞性的後果

  • What I'm going to show you here is the survival curve,

    現在展示的是存活曲線圖

  • the death curve, if you will,

    你可以稱它為死亡曲線

  • for women who have Dilated Cardiomyopathy

    這是因為有特定基因瑕疵

  • due to a very specific genetic defect --

    而罹患擴張型心肌症的女性

  • It turns out that men can also get Dilated Cardiomyopathy

    事實證明,男性可能也會因為相同的

  • as a result of this same specific genetic defect,

    特定基因缺陷,而罹患擴張型心肌症

  • but if they do, they tend to die at a much younger age.

    但如果男性得到這個病,他們很可能會更早過世

  • Why is this the case?

    為什麼會這樣?

  • Well, so I asked my colleagues --

    我問了我的同事

  • When I travel around, I ask my colleagues in biomedical research --

    當我旅行各地時,我詢問了研究生物醫學的同事

  • Why is it, that for so many disorders,

    為什麼這些疾病的

  • the incidence of disease or the severity of disease

    發生機率或嚴重程度

  • differs so dramatically between men and women?

    在男性和女性之間的差距這麼大?

  • Why is this the case?

    為什麼會這樣?

  • And the answer, that I almost invariably get is --

    而我得到的答案通常是──

  • "I don't have a clue."

    「我毫無頭緒。」

  • Now, this is a big question --

    這是個大問題

  • this is a big, big question --

    非常大的問題

  • Whenever I press harder on my colleagues and say,

    每當我窮追不捨的詢問我的同事:

  • What do you think might be going on?

    「你覺得可能是怎麼一回事?」

  • The answer that I receive, most frequently is,

    我最常得到的答案是

  • "Well, maybe it's the sex hormones."

    「這個嘛,也許是性荷爾蒙。」

  • How could it be that we are in such a place in the research world,

    為什麼我們身處在充滿研究的世界上

  • in this, human genetics era

    在這個人類基因體時代

  • when the answers are so shallow?

    得到的答案卻是如此膚淺?

  • Well, it turns out that the human genetics revolution

    事實證明人類基因革命

  • has delivered us, has provided us with a set of tools

    傳達、提供了我們一組工具

  • with which we can ask the question --

    讓我們得以發問──

  • Why is one man at a higher or a lower risk than another man

    為什麼一個男人罹患某個特定疾病的風險

  • of suffering from a particular disease?

    比另一個男人高或低?

  • Similarly, we have the tools with which to ask the question --

    同樣的,我們也有工具可以發問──

  • Why is one woman at a higher or a lower risk than another woman

    為什麼一個女人罹患某個特定疾病的風險

  • of suffering from a particular disease?

    比另一個女人高或低?

  • But, as unbelievable as it may seem,

    但是,令人難以置信的是

  • we have no genetic toolkit to ask the question,

    我們沒有基因工具箱可以發問

  • Why are men, as a group, at a higher or lower risk

    為什麼男性群體罹患某個特定疾病的風險

  • of [suffering from] a particular disease, than women, as a group?

    比女性群體高或低?

  • This is a big, big question

    這是很大的問題

  • and to this point, we have had no answers,

    而直到現在,我們仍沒有答案

  • no systematic way of proceeding.

    也沒有系統性的方法能著手處理

  • But perhaps, just perhaps --

    但也許,只是也許──

  • the answer has been staring at us in the face all along.

    答案其實一直在我們眼前

  • Because, of course, the individuals who are prone to Autism,

    因為,理所當然的,容易得到自閉症的人

  • and who tend to suffer more severely at an early age

    以及容易在年輕時罹患嚴重的

  • from Dilated Cardiomyopathy,

    擴張型心肌病的人

  • those individuals are men and they are XY.

    這些人是男性,擁有XY染色體

  • And those individuals who disproportionately

    而那些不成比例的

  • suffer from Lups and Rheumatoid Arthritis, and a host of other diseases,

    飽受狼瘡及類風濕關節炎,還有許多疾病所苦的人

  • are women and they are XX.

    都是女性,擁有XX染色體

  • Of course, being XY versus XX is the most fundamental difference,

    理所當然的,XY和XX染色體的相對

  • between males and females.

    是男性與女性最基礎的差別

  • But, the whole biomedical research enterprise

    但是整個生物醫學研究界

  • has been operating for decades under the assumption

    好幾十年以來,都在這個假設下進行操作

  • that the Y chromosome is operating

    就是假設Y染色體

  • only within the cells of the reproductive tract

    只在生殖道的細胞內運作

  • or, to frame it another way,

    或是,換一種說法

  • that the Y chromosome matters only in our nether parts.

    Y染色體只在我們的下半身作用

  • And, as an extension,

    延伸來看

  • the notion has been held firm

    數十年來,整個生物醫學研究界

  • throughout the biomedical research enterprise for decades,

    都堅持這個觀念

  • that all the differences between the sexes

    認為不同性別之間的

  • outside the reproductive tract,

    生殖道以外的差別

  • including differences in disease susceptibility

    包括非生殖道疾病的

  • outside the reproductive tract,

    發生率的差異

  • the notion has been that all such differences

    這個觀念認為這些差異

  • must stem from sex hormones

    一定是生殖器官製造的

  • that are produced by the reproductive organs.

    性荷爾蒙造成的

  • But it turns out that in recent years,

    但事實證明,最近幾年

  • my laboratory at the Whitehead Institute has discovered

    我在懷特海德研究所的實驗室發現

  • that the Y chromosome is functioning

    Y染色體的作用

  • not just in the reproductive organs

    不僅限於生殖道器官

  • but actually, throughout the body.

    而是貫通整個身體

  • So that all the cells of your body --

    所以你身體中所有的細胞

  • the skin cells, the cells of your liver,

    皮膚細胞、肝細胞

  • and of your heart, and even of your ear,

    和你的心臟細胞,甚至你的耳朵

  • those cells know, at a fundamental molecular level,

    這些細胞在基本分子的層級中

  • whether they are XX or XY.

    都知道它們是XX或XY細胞

  • And the question that I want to put before you is,

    我希望各位思考的問題是

  • "Does this matter?"

    「這很重要嗎?」

  • Does it matter outside the reproductive tract?

    這在生殖道之外的部位重要嗎?

  • And I would like to suggest that it does matter,

    而我想說的是,這很重要

  • and it suggests a path forward towards a better health care.

    而且這會指引我們一條更好的醫療保健之路

  • But how serious is the problem? Am I making this up?

    但這個問題有多嚴重?這是我編造的嗎?

  • Is the research enterprise really unaware of this reality?

    研究界真的沒有察覺這項事實嗎?

  • Well, if I go to visit my research colleagues around the world

    如果我去拜訪我在世界各地做研究的同事

  • working in universities, in medical centers, in pharmaceutical companies --

    不論他們在大學、醫學中心或製藥公司──

  • If I got to ask colleagues around the world

    如果我能夠問問在世界各地

  • who are studying human cells, as shown here --

    研究人類細胞的同事,如圖所示──

  • If I ask them, "Are you studying XX cells or XY cells?"

    如果我問他們:「你在研究XX細胞或XY細胞嗎?」

  • The answer I get, almost always is -- "I don't know."

    我得到的答案總是──「我不知道。」

  • Well, if you don't know whether if you're studying XX or XY cells --

    如果你不知道自己是否在研究XX或XY細胞

  • How could you possibly be taking account of this most fundamental difference

    你怎麼能考慮到男性和女性的細胞、

  • between male and female cells, tissues, organs and bodies?

    組織、器官和身體之間這個最根本的差別?

  • And so -- it is the case that a great deal of the researchs being conducted today

    所以,現在有很多研究被引導

  • with an eye towards understanding the cause of disease,

    他們著眼於了解疾病的成因

  • and identifying possible cures and treatments for disease,

    釐清能夠治療疾病的方式

  • is failing to account for this most fundamental difference

    卻沒有考慮到這個男性與女性之間

  • between men and women.