字幕列表 影片播放 已審核 字幕已審核 列印所有字幕 列印翻譯字幕 列印英文字幕 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.