后记 辨别身份
Sura-na Bheda Pramaana Sunaavo;
Bheda, Abheda, Pratham kara Jaano.
让我知道你可以辨别歌曲中的音符;
但是首先,让我看看你能否分辨
其中哪些音符可分
哪些不可分
——根据古典梵语诗歌创作的音乐作品
我的父亲用Abhed(身份)来表述基因“不可分割”的属性。而它的反义词Bhed却具有多重含义:“辨别”(动词形式)、“练习”、“决定”、“辨别”、“分割”以及“治愈”。Bhed与vidya(知识)和ved(医学)拥有相同的词根。此外,印度教经典“吠陀”(Vedas)也得名于相同的出处。它起源于古代印欧词语(uied),具有“了解”或“辨识”的含义。
众所周知,从事科研工作的人不可避免地会带有职业病,在对世界进行充分了解之前,我们必须将其分割成基因、原子以及比特等基本组成部分。我们不知道是否有其他方法可行,因此想要化零为整就必须先化整为零。
但是这种方法存在某种潜在的风险。一旦认识到人类这种生物体是由基因、环境以及基因—环境交互作用组成的,那么就会从根本上改变我们对于人类的定义。伯格对我说:“虽然任何理智的生物学家都会认为人类不过是个体基因的产物,但是我们对自身的感知将随着外源基因引入发生改变。”1即便是化零为整也无法令其再恢复到化整为零之前的原样。
就像梵语诗歌所述:
让我知道你可以辨别歌曲中的音符;
但是首先,让我看看你能否分辨
其中哪些音符可分
哪些不可分
※※※
现在人类遗传学还面临着三项艰巨的挑战,而它们均与辨别、分割和最终重建有关。其中第一项挑战就是辨别人类基因组中信息编码的确切本质。尽管人类基因组计划已经为后续工作奠定了基础,但是目前我们还面临着许多悬而未决的问题,例如,人类基因组中30亿个碱基对究竟“编码”了什么信息?基因组中的功能元件是什么?尽管基因组包含有21 000至24 000个蛋白质编码基因,但是其中分布的基因调节序列与DNA片段(内含子)将把基因分割成不同的区块。基因组中的信息可以构建成千上万的RNA分子,虽然它们无法被翻译成蛋白质,但是依然会在细胞生理过程中发挥多种作用。而我们曾经认为的那些“垃圾”DNA有可能编码了几百种未知的功能。此外,在细胞核的三维结构中,染色体在经过缠绕与折叠后可以通过相互接触发挥作用。
2013年,为了理解基因组中每个元件的作用,美国国立人类基因组研究所启动了一项庞大的国际合作计划,旨在创建一个涵盖全部人类基因组功能元件(染色体上任意具有编码或者指导功能的DNA序列)的目录。该项目被巧妙地命名为“DNA元件百科全书计划”(Encyclopedia of DNA Elements,ENC-O-DE),而它将对人类基因组序列中包含的全部信息进行交叉注释。
只要生物学家鉴定出这些功能“元件”,那么他们就将面对第二项挑战:理解这些元件在不同的时间与空间中交互作用的机制,以及它们对于人类胚胎发育、生理功能、解剖结构与生物体独有的属性与特征的影响。[1]然而令人感到尴尬的是,我们对于基因组知之甚少:人类对于自身基因及其功能的大部分认知均来自酵母菌、蠕虫、果蝇与小鼠中的相似基因。就像戴维·博特斯坦写的那样:“能够直接用于研究的人类基因屈指可数。”2新型基因组学的部分任务就是缩短小鼠与人类之间的差距,以便于在近似人体环境的背景下确定人类基因如何发挥功能。
如果该项目能够顺利实施,那么将为医学遗传学提供某些重要的帮助。人类基因组功能注释将有助于生物学家阐明疾病发生的新机制。虽然根据新型基因组元件与复杂疾病的内在联系就可以确定其最终原因,但是我们目前在该领域的研究仍旧一无所获,例如,遗传信息、行为暴露与随机因素的交互作用如何对高血压、精神分裂症、抑郁症、肥胖、癌症或心脏病产生影响。为了明确这些疾病的发病机制,我们需要首先在基因组中找到与它们关联的正确功能元件。
与此同时,了解这些关联亦可用于发现人类基因组的预测能力。2011年,心理学家埃里克·特克海默在一篇颇具影响力的综述中写道:“家族研究(双胞胎、兄弟姐妹、父母与子女以及被收养者)在经历了一个世纪的发展后终于建立起完整的谱系,而人们也逐渐打消了对于基因在解释全部人类差异(从病态到常态以及从生物到行为)时重要作用的质疑。”3然而尽管上述关联具有很强的说服力,但是特克海默笔下的“基因世界”要比预期的更加错综复杂。到目前为止,基因变化仅对那些导致表型发生显著改变的高外显率疾病具有强大的预测作用。由于我们很难对于多个基因变异形成的组合进行解读,因此根本无法确定某种特定基因的排列组合(基因型)在未来会产生何种特定结果(表型),而此类情况在结果受到多个基因支配的时候显得尤为突出。
但是随着新技术的应用,这种僵局将很快得到改观。现在让我们在脑海中虚拟一项思维实验。假设我们可以前瞻性(在不了解任何儿童未来的前提下)地对10万名儿童的基因组进行全面测序,然后针对每位儿童创建出包含全部变异与功能元件组合在内的数据库(这里所说的10万只是一种数量上的泛指,实验对象可以被扩展至任何数量的儿童)。现在假设我们已经获得了该队列儿童的“命运图谱”,并且将鉴定出的每种疾病与生理异常记录于平行的数据库中,那么我们或许可以将这种记录着个体全套表型(属性、特征、行为)的图谱称为人类“表型组”。接下来,假设某种计算引擎能够对来自遗传图谱或命运图谱的数据进行挖掘配对,那么我们就可以根据这些结果对于双方做出预测。尽管上述方法仍存在各种不确定性(甚至非常严重),但是10万份基因组与表型组图谱构成的数据集依然具有强大的说服力,它可以描绘出编码于基因组内部的人类命运本质。
这种命运图谱的特别之处就在于它不会受到疾病检测领域的局限,该方法还可以根据我们的需求在广度、深度以及详细程度上进行调整。目前命运图谱可能的应用范围包括低出生体重儿、学龄前学习障碍、青春期短暂躁动、青少年迷恋、婚姻、出柜、不孕症、中年危机、成瘾倾向、左眼白内障、早秃、抑郁、心脏病以及晚期卵巢癌或乳腺癌。虽然这种实验在过去简直无法想象,但是计算技术、数据存储与基因测序的协同作用将使其在未来成为可能。我们可以把它看作某种规模庞大的双胞胎实验(研究对象并不是双胞胎):该方法可以跨越时空对基因组与表型组进行匹配,然后通过计算创建出数以百万计的虚拟遗传“双胞胎”,而这些排列组合就能够被用于生命事件的注释。
由于通过基因组来预测疾病与命运的方法具有自身局限性,因此我们需要对于此类项目保持清醒的认识。“也许,”就像某位评论员所批评的那样,“遗传学解释的命运最终将脱离传统的病因学理论,它不仅无法完全呈现环境因素的作用,还会产生某些可怕的医学干预手段,而这种方法对于诠释人类命运根本没有任何作用。”4但是此类研究的意义在于它可以“摆脱”疾病的束缚,人们可以通过基因来理解个体发育与命运转归的变迁。如果能够将背景依赖或环境依赖的情况稀释或滤除,那么保留下来的就是深受基因影响的事件。总体而言,只要人群数量与计算能力达到一定程度,我们就可以确定并算出基因组拥有的全部预测能力。
※※※
相比之下,最后一项挑战的意义可能最为深远。就像根据人类基因组预测人类表型组的能力主要受限于计算技术的缺乏一样,定向改变基因组的能力也受制于生物学技术的短板。由于基因导入系统(病毒)存在效率低下、可靠性差甚至意外致死,所以我们几乎无法将外源基因定向导入至人类胚胎。
然而随着新技术的应用,这些障碍也将开始土崩瓦解。目前,“基因编辑”技术能够使遗传学家在精准改造基因组的同时保持高度的特异性。原则上来讲,我们可以通过定向方式在其他30亿对碱基不变的情况下让DNA中的某个碱基产生突变(这种技术就相当于某种编辑设备,当完成了扫描66卷《大英百科全书》的任务后,它可以在不影响其他内容的同时发现、擦除或改变某个单词)。在2010年至2014年间,我实验室的一位博士后研究员曾尝试采用标准基因传递病毒将某个明确的基因改变导入某个细胞系,但是最终收效甚微。2015年,当实验方法改为以CRISPR为基础的新型技术后,她只用了6个月的时间就在14个人类基因组中实现了14处基因改变,其中还包括了人类胚胎干细胞基因组,而这在过去完全是难以置信的丰功伟绩。全世界的遗传学家与基因治疗学家都在急不可耐地探索改变人类基因组的可能性,其实造成这种氛围的原因在某种程度上与生物技术的迅速发展密切相关。干细胞技术、细胞核移植、表观遗传修饰以及基因编辑方法的联合应用使得操纵人类基因组与转基因人类成为可能。
其实我们并不了解这些技术在实际应用中的保真性或效率到底如何。定向改变某个基因是否会引起基因组其他部分出现意外改变?某些基因是否比其他基因更容易“被编辑”呢?又是什么在调控基因的可塑性呢?我们不知道对于某个基因的定向改变是否会导致整个基因组发生失调。如果有些基因的作用就相当于道金斯所描述的“配方”,那么改变某个基因就可能对基因调控产生深远的影响,并且会产生类似蝴蝶效应的一系列下游结果。如果此类蝴蝶效应基因在基因组中屡见不鲜,那么它们将成为基因编辑技术的主要限制因素。基因的不连续性(遗传单位的离散性与自主性)也许只是某种幻觉:基因之间的内在联系可能比我们想象中的更为紧密。
但是首先,让我看看你能否分辨
其中哪些音符可分
哪些不可分
现在假设这些技术已经可以在某种环境下得到常规应用。女性在怀孕以后,每位父母都可以选择是否对子宫内的胎儿进行全基因组检测。如果发现胎儿携带有严重的致病突变,那么父母可以决定是否在孕早期终止妊娠,或是在经过全面遗传筛查后选择性地植入“正常”胎儿(我们将称其为全面胚胎植入前遗传学诊断,或c—PGD)。[2]
此外,基因组测序也可以鉴定出导致疾病倾向的复杂基因组合。假如携带此类可预测疾病倾向基因的孩子出生后,那么他们将在整个童年时代接受选择性干预措施。例如,对于某个具有遗传性肥胖倾向的孩子来说,他可能会在儿童时期接受体重变化监测、替代饮食治疗或使用激素、药物以及基因治疗进行代谢“重编程”。而具有注意力缺陷或多动症倾向的儿童可能会接受行为治疗或为其安排丰富多彩的教学活动。
如果疾病已经发生或出现进展,那么就应该使用基因疗法来治疗或者治愈患者。我们可以直接将矫正基因导入病变组织:例如,将功能性囊性纤维化基因雾化后注入患者的肺部即可使其恢复部分正常功能。而某位先天患有ADA缺乏症的女孩可以接受携带矫正基因的骨髓干细胞移植。对于较为复杂的遗传病来说,我们将采用基因诊断与基因治疗、药物治疗以及“环境疗法”相结合的手段。只要能够记录下导致某种癌症出现恶性增殖的突变,那么就可以对该肿瘤进行全面分析。这些突变将被用于鉴定引发细胞异常增殖的致病通路,而据此设计出的靶向治疗能够在保护正常细胞的同时精准地杀伤恶性细胞。
2015年,精神病学家理查德·弗里德曼(Richard Friedman)在《纽约时报》发表的文章中写道:“假设你是一名从战场上归来且患有创伤后应激障碍(post-traumatic stress disorder, PTSD)的士兵,那么只要通过简单的抽血化验来检测基因变异就可以了解你是否具有恐惧消退的能力……如果你携带降低恐惧消退能力的突变,那么治疗师就会明白可能需要增加暴露疗法的强度与疗程才能奏效。或者说,你可能需要接受暴露疗法以外的其他治疗方案,例如人际关系治疗或药物治疗。”5或许应该将消除表观遗传标记的药物与谈话治疗联合使用,细胞记忆的消除或许可以缓解历史记忆的负担。
除此之外,基因诊断与基因干预也将用于人类胚胎的筛查与矫正。如果能够在生殖细胞中鉴定出某些基因的“可干预”突变,那么父母就可以在受孕前选择基因手术来改变精子与卵子,或者从怀孕伊始就借助产前筛查来避免植入携带突变的胚胎。通过阳性选择、阴性选择或基因组修饰等方法,我们就能预先把导致严重疾病的基因变异从人类基因组中清除出去。
※※※
假如你已经仔细阅读了上述方案,那么就会发现科学奇迹背后隐藏的道德风险。对于癌症、精神分裂症以及囊性纤维化进行靶向治疗是医学发展的重要标志(尽管这些内容令人感到既遥远又陌生),但是个体干预并不能成为超越法律与道德底线的借口。如果这个世界由“预生存者”与“后人类”组成,那么他们不是接受了基因易损性的筛查就是改变了遗传倾向。随着人类疾病、痛苦、创伤、突变、虚弱与机会逐渐远去,我们的身份、怜悯、历史、变异、易感与选择也将渺无踪迹。[3]
1990年,当蠕虫遗传学家约翰·萨尔斯顿起草人类基因组计划的时候,他对智能生物“学会解读自身指令”导致的哲学困惑感到十分惊诧。不仅如此,这种困惑随着智能生物开始学习编写自身指令而变得愈发不可收拾。倘若基因与生物体可以相互决定对方的本质与命运,那么这种逻辑循环就可以形成闭环。一旦我们开始考虑把基因与命运画等号,就会不可避免地会将人类基因组当作昭昭天命。
※※※
当我们探望完莫尼准备离开加尔各答的时候,父亲还想在他童年住过的房子外面稍作停留,而他和兄弟们就在这里目睹了拉杰什遭受躁郁症的折磨。我们一路上默不作声,任由父亲的思绪沉浸在对往事的追忆里。我们将车停在哈亚特汗街狭窄的入口处,然后一起缓步走到小巷的尽头。那时大约是晚上6点,街边的房屋笼罩在昏暗的灯光下,潮湿的空气似乎预示着随时就要下雨。
“孟加拉历史上最重要的一件事情就是印巴分治。”父亲对我说道。他望着我们头顶上突出的阳台努力地回忆着以前邻居的名字:戈什(Ghosh)、塔卢克达尔(Talukdar)、穆克吉(Mukherjee)、查特吉(Chatterjee)以及森(Sen)。我注意到房屋之间密布着许多晾衣绳,也许落在身上的那些蒙蒙细雨就来自那些刚洗完的湿衣服。父亲说道:“印巴分治的结果关乎这座城市每个人的切身利益,而你的家园要么毁于这场灾难,要么就会成为别人的庇护所。”他指着我们头顶上那些窗口的柱廊喃喃自语道:“这里的每户人家都曾接纳过逃难的同胞。”尽管来自四面八方的人们彼此并不熟悉,但是大家在患难与共的过程中已经融为一体。
“当我们从巴里萨尔一路颠簸来到加尔各答的时候,虽然随身只携带了四个笨重的钢制行李箱与少量生活用品,但是内心已经开始憧憬未来的新生活。”我知道在那条街上生活的每个家庭都有自己的辛酸血泪史。似乎人们的各种差异都趋于平等,而这就像是冬天仅剩下植物根茎的花园。
对于许多像父亲一样的人来说,从孟加拉东部至西部的迁徙令他们的生活被彻底重置。让我们将时间恢复到元年,而历史也被割裂为分治之前(BP)与分治之后(AP)。印巴分治造成的灾难摧毁了原本和谐的生活:与父亲同时代的人们在不知不觉中就成了这项天然实验的牺牲品。只要时钟被重新归零,那么我们仿佛就可以回到人类的起点,然后近距离地观察生活、命运与选择的转归。在此过程中,父亲的感受可以用刻骨铭心来形容:一位兄弟(拉杰什)患上了躁郁症,而另一位兄弟(贾古)的现实生活也支离破碎。尽管祖母对于新生事物始终抱有谨小慎微的态度,但是我的父亲却从心底里喜欢尝试冒险。这些看似迥异的属性隐藏在每个人的体内,它们就像缩微人一样等待重获新生。
到底是什么力量或机制才能解释人类个体截然不同的命运与选择呢?人们在18世纪之前曾经把个体命运归结于神的旨意。其中印度教徒长期以来认为个体命运与其前世的因果报应密不可分(在印度教中,主神就像一位至高无上的道德税务会计师,他将根据既往投资的盈亏来清点与分配命运的优劣)。而基督教中的上帝也是恩威并施的化身,他既是桀骜不驯的运动员又是最终命运的裁判员。
19世纪与20世纪的医学发展为命运与选择提供了更为世俗化的概念。疾病或许是命运中最为常见的典型代表,我们可以通过规范的术语对其进行描述,它们不再是天谴神罚的愚昧无知,而是风险、暴露、体质、环境与行为共同作用的结果。与此同时,我们把选择理解为个体心理、经历、记忆、创伤与身世表达的一种方式。到了20世纪中期,身份、亲缘、气质与偏好(异性恋与同性恋或冲动与谨慎)越来越多地被描述为是心理冲动、个人历史与随机因素交互作用产生的现象,因此就诞生了涵盖命运与选择的流行病学。
在21世纪开始的前10年,我们开始学习使用另外一种语言来讲述因果,然后以此来构建某种全新的自我流行病学:我们开始从基因与基因组的角度来描述疾病、身份、亲缘、气质以及偏好,并且最终运用上述理论来诠释命运与选择。尽管基因作为反映人类本质与命运的唯一途径并非是遥不可及的天方夜谭,但是这种颇具争议的观点也让我们在面对历史与未来的时候谨言慎行:基因对于人类生存的影响要远比我们想象中的更为错综复杂与惊心动魄。当我们尝试去定向解读、改变与操纵基因组,并且获得改变未来命运与选择的能力时,上述观点也就变得愈发具有煽动性与破坏性。1919年,摩尔根曾经写道:“人类最终会了解自然的本质,而所谓的神秘莫测不过是场错觉罢了。”6随着科学技术的突飞猛进,我们当前正在把摩尔根的结论从了解自然扩展至领悟人性。
我的脑海中经常会出现贾古与拉杰什的身影,假设兄弟二人出生在距今50年到100年的未来,那么他们的生活轨迹又会是什么样子呢?我们能否根据遗传学易感性来治愈摧残他们生命的疾病呢?这种知识能否帮助他们恢复“正常”呢?如果答案是肯定的话,那么又会涉及何种道德、社会与生物危害呢?人们对于这种类型的知识是否会产生全新的理解与同情呢?还是说它们会成为新型歧视的核心内容?这种知识能被用来重新定义什么是“自然”吗?
但是“自然”到底是什么呢?我扪心自问。从一方面来说,它具有变异、突变、转换、无常、离散与流动的属性;而另一方面,它还表现出恒常、持久、完整与保真的特征。那么我们该如何辨别自然的身份呢?由于DNA本身就是一种自相矛盾的分子,因此它编码的生物体也是千奇百怪。我们原本想从遗传特征中总结出恒常的规律,但是却在不经意之间发现了变异(对立面)的奥秘,同时还认识到突变是保持人类本质的必要条件。我们体内的基因组正在努力维系着各种力量之间脆弱的平衡,其中就包括彼此互补的双螺旋结构、错综复杂的过去和未来以及挥之不去的欲望和记忆,而这也构成了世间万物最为人性的核心。因此如何科学管理就成为人类认知世界与明辨是非的终极挑战。
[1] 为了理解基因形成生物体的机制,我们不仅要了解基因,更要了解RNA、蛋白质以及表观标志物。未来的研究将能够揭示基因组、蛋白质变异体(蛋白质组)以及表观标志物(表观基因组)相互协调构建与维护人体的机制。
[2] 对于胎儿基因组进行全面检测在临床上被称为无创产前检测(Noninvasive Prenatal Testing , NIPT)。2014年,某家中国公司宣布已经完成了150 000例胎儿染色体的检测,而除此之外该公司还将该方法用于捕获单基因突变。虽然此类染色体异常(例如唐氏综合征)检测乍看起来与羊膜穿刺术的结果具有相同的保真性,但是它依然无法解决“假阳性”这个主要问题(也就是说,胎儿DNA检测认定的染色体异常结果与实际情况相反)。不过好在假阳性率将随着技术的发展大幅降低。
[3] 然而即便是看似简单明了的遗传筛查检测也会将我们卷入道德风险的困境。现在我们以弗里德曼筛查士兵中PTSD易感基因的设想为例。初看起来,这种方法似乎可以缓解他们经受的战争创伤:只要筛选出那些没有“恐惧消退”能力的士兵,然后对他们进行强化精神治疗或药物治疗就可以使其恢复正常。但是如果我们在部署任务之前就对士兵的PTSD风险进行筛查呢?这种做法真的有必要吗?我们真的想挑选出冷漠无情或是先天对于暴力无动于衷的士兵吗?我个人对于此类筛查持否定态度:失去“恐惧消退”制约的心态实际上是战争中应该避免的危险行为。
致谢
2010年5月,当《众病之王:癌症传》这部作品定稿之时,我从来没有想到自己会再次执笔撰写另外一部著作。虽然《众病之王:癌症传》带来的体力透支容易恢复,但是我的想象力几乎在写作过程中消耗殆尽。就在该书获得当年的《卫报》新人奖(Guardian First Book Prize)后,有一位评论家曾经埋怨应该将这部作品提名为“最佳图书奖”,而这种意外的惊喜让我彻底打消了内心的忧虑。《众病之王:癌症传》不仅是情节构思的创新更是人生角色的转换,我正是在它的启蒙下才逐步成长为一名作家的。
尽管《众病之王:癌症传》已经做到知无不尽,但是它并不能反映恶变之前的常态。如果把癌症这种“扭曲自我”比作《贝奥武甫》(Beowulf)中的魔鬼,那么是何种力量在维系正常的新陈代谢呢?于是我在探究常态、身份、变异与遗传奥秘的过程中创作了《基因传》,而这部作品其实可以被视为《众病之王:癌症传》的前传。1
虽然家庭与遗传的话题始终贯穿着人们的生活,但是市面上反映这些内容的书籍并不多见,因此我非常感谢大家在《基因传》创作中给予的鼎力支持。我的妻子萨拉·斯茨(Sarah Sze)是这部作品最忠实的读者与知音,同时女儿莉拉(Leela)与阿丽雅(Aria)每天都在提醒我她们在未来可能面临的风险。毋庸置疑,我的父亲塞布斯瓦尔(Sibeswar)与母亲谦达娜(Chandana)的经历也是这个故事的重要组成部分,而我的姐姐拉努(Ranu)与姐夫桑杰(Sanjay)为本书提供了道德指引。与此同时,我与朱迪(Judy)、施家铭(Chia-Ming Sze)、戴维·斯茨(David Sze)以及凯瑟琳·多诺霍(Kathleen Donohue)还就家庭与未来的话题展开过多次讨论。
接下来,我要感谢为本书提供慷慨建议的各位专家学者,正是在他们的帮助下《基因传》才能够确保内容准确无误,其中就包括保罗·伯格(遗传学与克隆)、戴维·博特斯坦(基因定位)、埃里克·兰德与罗伯特·沃特(人类基因组计划)、罗伯特·霍维茨与戴维·赫什(蠕虫生物学)、汤姆·马尼亚蒂斯(分子生物学)、肖恩·卡罗尔(进化与基因调控)、哈罗德·瓦默斯(癌症)、南希·西格尔(双胞胎研究)、因德尔·维尔马(基因治疗)、珍妮弗·杜德娜(基因编辑)、南希·韦克斯勒(人类基因图谱)、马库斯·费德曼(人类进化)、杰拉尔德·菲施巴赫(精神分裂症与自闭症)、戴维·艾利斯与蒂莫西·贝斯特(表观遗传学)、弗朗西斯·柯林斯(基因定位与人类基因组计划)、埃里克·托普尔(人类遗传学)与休·杰克曼(“金刚狼”,变种人)。
除此之外,阿肖克·拉伊(Ashok Rai)、内尔·布雷耶(Nell Breyer)、比尔·赫尔曼(Bill Helman)、高拉夫·马宗达(Gaurav Majumdar)、苏曼·施洛德卡(Suman Shirodkar)、梅鲁·戈哈尔(Meru Gokhale)、切克·萨卡尔(Chiki Sarkar)、戴维·布里施泰因(David Blistein)、阿兹拉·拉扎(Azra Raza)、切特纳·乔普拉(Chetna Chopra)与苏祖·巴塔恰里雅(Sujoy Bhattacharyya)在《基因传》初稿完成之后为本书提供了极其宝贵的意见。同时我在与丽莎·尤斯塔维奇(Lisa Yuskavage)、玛特威·莱文斯坦(Matvey Levenstein)、雷切尔·费因斯坦(Rachel Feinstein)以及约翰·柯林(John Currin)的交流中也获益匪浅。而尤斯塔维奇在她的作品(《双胞胎》)中引用了《基因传》与《医学的真相》的内容。布列塔尼·拉什(Brittany Rush)不仅耐心(出色)地完成了800余条参考文献的整理工作,并且还专心致志地投入到枯燥乏味的出版工作中;丹尼尔·勒德尔(Daniel Loedel)只用了一个周末的时间就确认文稿达到了预期目标。此外,米娅·克劳利—霍尔德(Mia Crowley-Hald)与安娜—索菲亚·瓦茨(Anna-Sophia Watts)在文字编辑过程中发挥了至关重要的作用,而凯特·洛伊德(Kate Lloyd)绝对是公关领域的天才。
本书的封面插图出自我的好友加布里埃尔·奥罗斯科(Gabriel Orozco),他独具匠心地通过大小不等的相切圆展现出整部作品的精华。我无法想象还有什么创意能够比这幅画面更适合《基因传》。
最后,我要由衷地感谢主编南·格雷厄姆(Nan Graham):你与斯图亚特·威廉姆斯(Stuart Williams)和萨拉·查尔方特(Sarah Chalfant)一起读完了那份68页的草稿,而萨拉当时只是通过两段文字介绍就敏锐地发现了这部作品的价值,你们不仅让《基因传》担当起时代的重任,还为它插上了腾飞的翅膀。
词汇表
等位基因(allele):基因的变异体或替代形式。等位基因通常由突变产生并且会造成表型变异。一个基因可以拥有多个等位基因。
级联反应(cascade):指在一系列连续事件中前面一种事件能激发后面一种事件的反应,其化学修饰为酶促反应以及放大效应。
中心法则或中心理论(central dogma, or central theory):在大多数生物体中,遗传信息只能从DNA(基因)传递给信使RNA,然后再从RNA传递给蛋白质。该理论在发展过程中已经过多次修改。其中逆转录病毒中的逆转录酶能以RNA为模板形成DNA。
染色质(chromatin):染色体的组成成分。由于最初是在进行细胞染色时发现的这种物质,因此人们就用chroma(颜色)对其命名。染色质中可能包含有DNA、RNA与蛋白质。
染色体(chromosome):这种由DNA与蛋白质组成的结构是细胞内储存遗传信息的载体。
DNA:脱氧核糖核酸,是所有细胞生物中携带遗传信息的化学物质。它在细胞中通常以两条配对互补链的形式出现。其中每条化学链都是由A、C、T与G四种碱基组成。基因携带的信息通过遗传“密码”的形式得到体现,而该序列在翻译成为蛋白质前先要经过RNA转录。
酶(enzyme):某种加速生物化学反应的蛋白质。
表观遗传学(epigenetics):在基因序列不变(例如A、C、T与G)的情况下,研究表型发生变异的遗传学分支学科。DNA化学修饰(例如甲基化)或DNA组装发生改变(例如组蛋白)是导致这种现象的常见原因。其中某些修饰具有可遗传性。
基因(gene):作为遗传物质的基本单位,基因通常由编码蛋白质或RNA链的DNA片段组成(在某些特殊情况下,基因可能以RNA的形式存在)。
基因组(genome):生物体携带的全套遗传信息。基因组包括蛋白质编码基因、非蛋白质编码基因、基因调节区域以及功能未知的DNA序列。
基因型(genotype):决定生物体物理、化学、生物与智力特征(见“表型”)的全部遗传信息。
突变(mutation):DNA的化学结构发生改变。突变既可以表现为沉默(也就是说这种变化不会对生物体的功能产生影响)也可以导致生物体的功能或结构出现变化。
细胞核(nucleus):这种膜包裹的细胞结构或细胞器存在于动物或植物细胞(不包括细菌细胞)中。动物细胞的染色体(与基因)就位于细胞核内。在动物细胞中,尽管大多数基因存在于细胞核内,但是线粒体亦可以携带少量基因。
细胞器(organelle):细胞中具有特殊功能的细胞亚单位。不同的细胞器通常被包裹在各自的膜结构中。例如线粒体是一种可以产生能量的细胞器。
外显率(penetrance):携带特定基因变异的生物体表现出相关性状或表型的百分比。在医学遗传学中,外显率是指导致个体出现某种疾病症状的基因型百分比。
表型(phenotype):个体在生物、物理与智力特征等方面的表现,例如皮肤颜色或眼睛颜色。此外,表型还包括某些复杂的特征,例如气质或性格。表型由基因、表观遗传改变、环境因素与随机概率共同决定。
蛋白质(protein):这种化学物质的核心结构由基因翻译的氨基酸链组成。蛋白质可以执行大部分细胞功能,其中就包括传递信号、提供结构支撑与加速生化反应。基因通常会为蛋白质“合成”提供蓝图。而加入磷酸、糖或脂质等小分子化合物可以对蛋白质进行化学修饰。
逆转录(reverse transcription):在逆转录酶的作用下,以RNA链作为模板合成DNA链的过程。逆转录酶存在于逆转录病毒中。
核糖体(ribosome):这种由蛋白质与RNA组成的细胞结构负责解码合成蛋白质所需的信使RNA。
RNA:核糖核酸,是一种执行多种细胞功能的化学物质,它可以作为“中介”信息将基因翻译成蛋白质。RNA由碱基(A、C、G与U)链与磷酸糖骨架结合而成。细胞中的RNA通常以单链形式存在(DNA通常为双链),但是在特殊情况下也会形成双链RNA。而以逆转录病毒为代表的生物体可以将RNA作为遗传信息的载体。
性状、显性性状与隐性性状(traits, dominant and recessive):性状是指生物体的物理或生物学特征。多个基因可以编码相同的性状,而单个基因亦可以编码不同的性状。显性性状是指显性与隐性等位基因同时存在时表现出的性状,而隐性性状指两个等位基因均为隐性时表现出的性状。此外,基因可以表现为共显性:在这种情况下,同时存在显性与隐性等位基因的生物体将表现为中间性状。
转录(transcription):以基因为模板生成RNA拷贝的过程。经过转录后,DNA中的遗传密码(ATG—CAC—GGG)就可产生RNA“拷贝”(AUG—CAC—GGG)。
转化(transformation):遗传物质在生物体之间的水平转移。一般来说,细菌无须繁殖即可通过传递遗传物质在生物体间交换遗传信息。
翻译(基因)【translation(of genes)】:核糖体将遗传信息由RNA信息转换为蛋白质的过程。在翻译过程中,由于RNA上的三联体密码(例如AUG)对应着某个氨基酸(例如蛋氨酸),因此一条RNA链就可以编码一条氨基酸链。
译者注记
我与穆克吉医生的作品结缘还要追溯至《众病之王:癌症传》。当时徐文老师介绍我与董正和刘利娴夫妇相识,席间董正提到中信出版集团刚刚上市了一本新书《众病之王:癌症传》,而我的主要研究方向恰好就聚焦在肿瘤领域。《众病之王:癌症传》的确是一部引人入胜的医学经典,从此我就对于穆克吉医生的作品有了某种期待。2016年5月,我得知穆克吉医生撰写的另一部力作《基因传》即将在美国问世,同时这本书的中译本也列入了中信出版集团的日程。其实我在正式接手《基因传》的翻译工作之前还是有些犹豫,毕竟本书许多内容涉及遗传学、生物学以及社会学等专业领域,因此如何再现本书的精髓是项非常艰巨的挑战。虽然我从未与穆克吉医生进行过沟通,但是同为医者的经历却令人感到默契。当本书译稿画上句号时,我深深感到发自内心的解脱。《基因传》不仅是一部翔实记述科学发展的历史,更是人类在21世纪面向未来的宣言。
我在此要感谢郭佳希博士、张雪博士、袁春旭、李雪、许林军在《基因传》初译稿整理过程中付出的辛勤努力。与此同时,徐文老师作为《基因传》的第一位读者对于译稿提出了许多真知灼见,而远在美国的姐姐马篱梅博士与姐夫俞从容博士为本书提供了专业指导。除此之外,徐珮雯、张薇以及范重君也帮助我一起在文字上精雕细琢。
《基因传》的顺利出版彰显了团队合作的重要性。我在此要感谢夏嘉老师自始至终的鼎力支持,而丁川老师引进的系列国外优秀作品堪称经典,同时王强老师带领的小伙伴们一直在争分夺秒,尤其是肖雪在审校过程中任劳任怨,当然还有最早合作的覃田甜老师以及那些默默无闻的编辑,是你们给了我足够的信任与时间去实现这个梦想。
最后,我要由衷感谢父亲与母亲将他们勤劳朴素的基因融入我的血脉,而宝妈与宝宝就是绘制靓丽蓝图的DNA!
注释
(引言)
1 An exact determination of the laws of heredity: W. Bateson, “Problems of Heredity as a Subject for Horticultural Investigation,” in A Century of Mendelism in Human Genetics, ed. Milo Keynes, A.W.F. Edwards, and Robert Peel (Boca Raton, FL: CRC Press, 2004), 153.
2 Human beings are ultimately nothing but carriers: Haruki Murakami, 1Q84 (London: Vintage, 2012), 231.
序言 骨肉同胞
1 The blood of your parents is not lost in you: Charles W. Eliot, The Harvard Classics: The Odyssey of Homer, ed. Charles W. Eliot (Danbury, CT: Grolier Enterprises, 1982), 49.
2 They fuck you up, your mum and dad: Philip Larkin, High Windows (New York: Far-rar, Straus and Giroux, 1974).
3 In 2012, several further studies: Maartje F. Aukes et al., “Familial clustering of schizo-phrenia, bipolar disorder, and major depressive disorder,” Genetics in Medicine 14, no. 3 (2012): 338–41; and Paul Lichtenstein et al., “Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: A population-based study,” Lancet 373, no. 9659 (2009): 234–39.
4 Three profoundly destabilizing: Atoms, Bytes and Genes: Public Resistance and Techno-Scientific Responses by Martin W. Bauer, Routledge Advances in Sociology (New York: Routledge, 2015).
5 “In the sum of the parts, there are only the parts”: Helen Vendler, Wallace Stevens: Words Chosen out of Desire (Cambridge, MA: Harvard University Press, 1984), 21.
6 “The whole organic world”: Hugo de Vries, Intracellular Pangenesis: Including a Paper on Fertilization and Hybridization (Chicago: Open Court, 1910), 13.
7 “Alchemy could not become chemistry until”: Arthur W. Gilbert, “The Science of Genetics,” Journal of Heredity 5, no. 6 (1914): 239.
8 “That the fundamental aspects of heredity”: Thomas Hunt Morgan, The Physical Basis of Heredity (Philadelphia: J. B. Lippincott, 1919), 14.
9 “the quest for eternal youth”: Jeff Lyon and Peter Gorner, Altered Fates: Gene Therapy and the Retooling of Human Life (New York: W. W. Norton, 1996), 9–10.
第一部分
1 This missing science of heredity: Herbert G. Wells, Mankind in the Making (Leipzig:Tauchnitz, 1903), 33.
2 jack: Yes, but you said yourself: Oscar Wilde, The Importance of Being Earnest (New York: Dover Publications, 1990), 117.
第一章 围墙花园
1 The students of heredity: G. K. Chesterton, Eugenics and Other Evils (London: Cas-sell, 1922), 66.
2 the Augustinians, fortunately, saw no conflict: Gareth B. Matthews, The Augustinian Tradition (Berkeley: University of California Press, 1999).
3 In October 1843, a young man from Silesia: Details of Mendel’s life and the Augustin-ian monastery are from several sources, including Gregor Mendel, Alain F. Corcos,and Floyd V. Monaghan, Gregor Mendel’s Experiments on Plant Hybrids: A Guided Study (New Brunswick, NJ: Rutgers University Press, 1993); Edward Edelson, Gregor Mendel: And the Roots of Genetics (New York: Oxford University Press, 1999); and Robin Marantz Henig, The Monk in the Garden: The Lost and Found Genius of Gregor Mendel, the Father of Genetics (Boston: Houghton Mifflin, 2000).
4 The tumult of 1848: Edward Berenson, Populist Religion and Left-Wing Politics in France, 1830–1852 (Princeton, NJ: Princeton University Press, 1984).
5 “Seized by an unconquerable timidity”: Henig, Monk in the Garden, 37.
6 he applied for a job to teach mathematics: Ibid., 38.
7 In the late spring of 1850, an eager Mendel: Harry Sootin, Gregor Mendel: Father of the Science of Genetics (New York: Random House Books for Young Readers, 1959).
8 On July 20, in the midst of an enervating heat wave: Henig, Monk in the Garden, 62.
9 On August 16, he appeared before his examiners: Ibid., 47.
10 In 1842, Doppler, a gaunt, acerbic: Jagdish Mehra and Helmut Rechenberg, The His-torical Development of Quantum Theory (New York: Springer-Verlag, 1982).
11 But in 1845, Doppler had loaded a train: Kendall F. Haven, 100 Greatest Science Dis-coveries of All Time (Westport, CT: Libraries Unlimited, 2007), 75–76.
12 But these categories, originally devised by the Swedish botanist: Margaret J. Anderson, Carl Linnaeus: Father of Classification (Springfield, NJ: Enslow Publishers, 1997).
13 “Not the true parent is the woman’s”: Aeschylus, The Greek Classics: Aeschylus — Seven Plays (n.p.: Special Edition Books, 2006), 240.
14 “She doth but nurse the seed”: Ibid.
15 from Indian or Babylonian geometers: Maor Eli, The Pythagorean Theorem: A 4,000-Year History (Princeton, NJ: Princeton University Press, 2007).
16 A century after Pythagoras’s death: Plato, The Republic, ed. and trans. Allan Bloom (New York: Basic Books, 1968).
17 In one of the most intriguing passages: Plato, The Republic (Edinburgh: Black & White Classics, 2014), 150.
18 “For when your guardians are ignorant”: Ibid.
19 The result, a compact treatise: Aristotle, Generation of Animals (Leiden: Brill Archive,1943).
20 “And from deformed”: Aristotle, History of Animals, Book VII, ed. and trans. D. M. Balme (Cambridge, MA: Harvard University Press, 1991).
21 “just as lame come to be from lame”: Ibid., 585b28–586a4.
22 “Men generate before they yet have certain characters”: Aristotle, The Complete Works of Aristotle: The Revised Oxford Translation, ed. Jonathan Barnes (Princeton, NJ: Princeton University Press, 1984), bk. 1, 1121.
23 A ristotle offered an alternative theory: Aristotle, The Works of Aristotle, ed. and trans. W..D. Ross (Chicago: Encyclop.dia Britannica, 1952), “Aristotle: Logic and Metaphysics.”
24 “[Just as] no material part comes from the carpenter”: Aristotle, Complete Works of Aristotle, 1134.
25 biologist Max Delbrück would joke that Aristotle: Daniel Novotny and Lukás Novák, Neo-Aristotelian Perspectives in Metaphysics (New York: Routledge, 2014), 94.
26 In the 1520s, the Swiss-German alchemist Paracelsus: Paracelsus, Paracelsus: Essential Readings, ed. and trans. Nicholas Godrick-Clarke (Wellingborough, Northampton-shire, England: Crucible, 1990).
27 “floating ..... in our First Parent’s loins”: Peter Hanns Reill, Vitalizing Nature in the Enlightenment (Berkeley: University of California Press, 2005), 160.
28 In 1694, Nicolaas Hartsoeker, the Dutch physicist: Nicolaas Hartsoeker, Essay de di-optrique (Paris: Jean Anisson, 1694).
29 “In nature there is no generation”: Matthew Cobb, “Reading and writing the book of nature: Jan Swammerdam (1637–1680),” Endeavour 24, no. 3 (2000): 122–28.
30 In 1768, the Berlin embryologist Caspar Wolff: Caspar Friedrich Wolff, “De forma-tione intestinorum praecipue,” Novi commentarii Academiae Scientiarum Imperialis Petropolitanae 12 (1768): 43–47. Wolff also wrote about essentialis corporis in 1759: Richard P. Aulie, “Caspar Friedrich Wolff and his ‘Theoria Generationis,’ 1759,” Jour-nal of the History of Medicine and Allied Sciences 16, no. 2 (1961): 124–44.
31 “The opposing views of today were in existence centuries ago”: Oscar Hertwig, The Bi-ological Problem of To-day: Preformation or Epigenesis? The Basis of a Theory of Or-ganic Development (London: Heinneman’s Scientific Handbook, 1896), 1.
第二章 “谜中之谜”
1 They mean to tell us all was rolling blind: Robert Frost, The Robert Frost Reader: Poetry and Prose, ed. Edward Connery Lathem and Lawrance Thompson (New York: Henry Holt, 2002).
2 Charles Darwin, boarded a ten-gun brig-sloop: Charles Darwin, The Autobiography of Charles Darwin, ed. Francis Darwin (Amherst, NY: Prometheus Books, 2000), 11.
3 He had tried, unsuccessfully, to study medicine: Jacob Goldstein, “Charles Darwin,Medical School Dropout,” Wall Street Journal, February 12, 2009, http://blogs.wsj.com/health/2009/02/12/charles-darwin-medical-school-dropout/.
4 Christ’s College in Cambridge: Darwin, Autobiography of Charles Darwin, 37.
5 Holed up in a room: Adrian J. Desmond and James R. Moore, Darwin (New York:Warner Books, 1991), 52.
6 John Henslow, the botanist and geologist: Duane Isely, One Hundred and One Bota-nists (Ames: Iowa State University, 1994), “John Stevens Henslow (1796–1861).”
7 The first, Natural Theology, published in 1802: William Paley, The Works of William Paley ..... Containing His Life, Moral and Political Philosophy, Evidences of Christian-ity, Natural Theology, Tracts, Horae Paulinae, Clergyman’s Companion, and Sermons, Printed Verbatim from the Original Editions. Complete in One Volume (Philadelphia:J.J. Woodward, 1836).
8 The second book, A Preliminary Discourse: John F. W. Herschel, A Preliminary Dis-course on the Study of Natural Philosophy. A Facsim. of the 1830 Ed. (New York: John-son Reprint, 1966).
9 “To ascend to the origin of things”: Ibid., 38.
10 “Battered relics of past ages”: Martin Gorst, Measuring Eternity: The Search for the Beginning of Time (New York: Broadway Books, 2002), 158.
11 “mystery of mysteries”: Charles Darwin, On the Origin of Species by Means of Natural Selection (London: Murray, 1859), 7.
12 dominated by so-called parson-naturalists: Patrick Armstrong, The English Parson-Naturalist: A Companionship between Science and Religion (Leominster, MA: Grace-wing, 2000), “Introducing the English Parson-Naturalist.”
13 In August 1831, two months after his graduation: John Henslow, “Darwin Correspon-dence Project,” Letter 105, https://www.darwinproject.ac.uk/letter/entry-105.
14 Th e Beagle lifted anchor on December 27, 1831: Darwin, Autobiography of Charles Darwin, “Voyage of the ‘Beagle.’.”
15 Charles Lyell’s Principles of Geology: Charles Lyell, Principles of Geology: Or, The Modern Changes of the Earth and Its Inhabitants Considered as Illustrative of Geol-ogy (New York: D. Appleton, 1872).
16 Lyell had argued (radically, for his time): Ibid., “Chapter 8: Difference in Texture of the Older and Newer Rocks.”
17 In September 1832, exploring the gray cliffs: Charles Darwin, Geological Observations on the Volcanic Islands and Parts of South America Visited during the Voyage of H.M.S. “Beagle” (New York: D. Appleton, 1896), 76–107.
18 The skull belonged to a megatherium: David Quammen, “Darwin’s first clues,” Na-tional Geographic 215, no. 2 (2009): 34–53.
19 In 1835, the ship left Lima: Charles Darwin, Charles Darwin’s Letters: A Selection, 1825–1859, ed. Frederick Burkhardt (Cambridge: University of Cambridge, 1996), “To J. S. Henslow 12 [August] 1835,” 46–47.
20 On October 20, Darwin returned to sea: G. T. Bettany and John Parker Anderson, Life of Charles Darwin (London: W. Scott, 1887), 47.
21 rather than all species radiating out: Duncan M. Porter and Peter W. Graham, Dar-win’s Sciences (Hoboken, NJ: Wiley-Blackwell, 2015), 62–63.
22 As an afterthought, he added, “I think”: Ibid., 62.
23 In the spring of 1838, as Darwin tore into a new journal: Timothy Shanahan, Th e Evolution of Darwinism: Selection, Adaptation, and Progress in Evolutionary Biology (Cambridge: Cambridge University Press, 2004), 296.
24 But the answer that came to him in October 1838: Barry G. Gale, “After Malthus: Dar-win Working on His Species Theory, 1838–1859” (PhD diss., University of Chicago, 1980).
25 In 1798, writing under a pseudonym, Malthus: Thomas Robert Malthus, An Essay on the Principle of Population (Chicago: Courier Corporation, 2007).
26 “sickly seasons, epidemics, pestilence and plague”: Arno Karlen, Man and Microbes: Disease and Plagues in History and Modern Times (New York: Putnam, 1995), 67.
27 “It at once struck me”: Charles Darwin, On the Origin of Species by Means of Natu-ral Selection, ed. Joseph Carroll (Peterborough, Canada: Broadview Press, 2003),438.
28 the phrase survival of the fittest was borrowed: Gregory Claeys, “The ‘Survival of the Fittest’ and the Origins of Social Darwinism,” Journal of the History of Ideas 61, no. 2 (2000): 223–40.
29 In 1844, he distilled the crucial parts: Charles Darwin, The Foundations of the Origin of Species, Two Essays Written in 1842 and 1844, ed. Francis Darwin (Cambridge: Cambridge University Press, 1909), “Essay of 1844.”
30 Alfred Russel Wallace, published a paper: Alfred R. Wallace, “XVIII. — On the law which has regulated the introduction of new species,” Annals and Magazine of Nat-ural History 16, no. 93 (1855): 184–96.
31 Wallace had been born to a middle-class family: Charles H. Smith and George Bec-caloni, Natural Selection and Beyond: The Intellectual Legacy of Alfred Russel Wallace (Oxford: Oxford University Press, 2008), 10.
32 but on the hard-back benches of the free library: Ibid., 69.
33 Like Darwin, Wallace had also embarked: Ibid., 12.
34 Wallace moved from the Amazon basin: Ibid., ix.
35 “The answer was clearly”: Benjamin Orange Flowers, “Alfred Russel Wallace,” Arena 36 (1906): 209.
36 In June 1858, Wallace sent Darwin a tentative draft: Alfred Russel Wallace, Alfred Rus-sel Wallace: Letters and Reminiscences, ed. James Marchant (New York: Arno Press, 1975), 118.
37 On July 1, 1858, Darwin’s and Wallace’s papers were read: Charles Darwin, The Cor-respondence of Charles Darwin, vol. 13, ed. Frederick Burkhardt, Duncan M. Porter, and Sheila Ann Dean, et al. (Cambridge: Cambridge University Press, 2003), 468.
38 The next May, the president of the society remarked: E. J. Browne, Charles Darwin: The Power of Place (New York: Alfred A. Knopf, 2002), 42.
39 “I heartily hope that my Book”: Charles Darwin, The Correspondence of Charles Dar-win, vol. 7, ed. Frederick Burkhardt and Sydney Smith (Cambridge: Cambridge Uni-versity Press, 1992), 357.
40 “All copies were sold [on the] first day”: Charles Darwin, The Life and Letters of Charles Darwin (London: John Murray, 1887), 70.
41 “The conclusions announced by Mr. Darwin are such”: “Reviews: Darwin’s Origins of Species,” Saturday Review of Politics, Literature, Science and Art 8 (December 24, 1859): 775–76.
42 “We imply that his work [is] one of the most important that”: Ibid.
43 “light will be thrown on the origin of man”: Charles Darwin, On the Origin of Species, ed. David Quammen (New York: Sterling, 2008), 51.
44 “intellectual husks”: Richard Owen, “Darwin on the Origin of Species,” Edinburgh Review 3 (1860): 487–532.
45 “One’s imagination must fill up very wide blanks”: Ibid.
第三章 “空中楼阁”
1 The “Very Wide Blank”: Darwin, Correspondence of Charles Darwin, Darwin’s letter to Asa Gray, September 5, 1857, https://www.darwinproject.ac.uk/letter/entry-2136.
2 Now, I wonder if: Alexander Wilford Hall, The Problem of Human Life: Embracing the “Evolution of Sound” and “Evolution Evolved,” with a Review of the Six Great Modern Scientists, Darwin, Huxley, Tyndall, Haeckel, Helmholtz, and Mayer (London: Hall & Company, 1880), 441.
3 In Lamarck’s view: Monroe W. Strickberger, Evolution (Boston: Jones & Bartlett, 1990), “The Lamarckian Heritage.”
4 “with a power proportional to the length of time”: Ibid., 24.
5 driving himself to the brink: James Schwartz, In Pursuit of the Gene: From Darwin to DNA (Cambridge, MA: Harvard University Press, 2008), 2.
6 minute particles containing hereditary information—gemmules: Ibid., 2–3.
7 blending inheritance — was already familiar: Brian Charlesworth and Deborah Charlesworth, “Darwin and genetics,” Genetics 183, no. 3 (2009): 757–66.
8 Darwin dubbed his theory pangenesis: Ibid., 759–60.
9 a new manuscript, The Variation of Animals: Charles Darwin, The Variation of Ani-mals and Plants under Domestication, vol. 2 (London: O. Judd, 1868).
10 “It is a rash and crude hypothesis”: Darwin, Correspondence of Charles Darwin, vol. 13, “Letter to T. H. Huxley,” 151.
11 “Pangenesis will be called a mad dream”: Charles Darwin, The Life and Letters of Charles Darwin: Including Autobiographical Chapter, vol. 2., ed. Francis Darwin (New York: Appleton, 1896), “C. Darwin to Asa Gray,” October 16, 1867, 256.
12 “The [variant] will be swamped”: Fleeming Jenkin, “The Origin of Species,” North British Review 47 (1867): 158.
13 There was no denying: In fairness to Darwin, he had sensed the problem in “blend-ing inheritance” even without Jenkin’s interjection. “If varieties be allowed freely to cross, such varieties will be constantly demolished...... any small tendency in them to vary will be constantly counteracted,” he wrote in his notes.
14 “Experiments in Plant Hybridization”: G. Mendel, “Versuche über Pflanzen-Hybriden,” Verhandlungen des naturforschenden Vereins Brno 4 (1866): 3–47 ( Jour-nal of the Royal Horticultural Society 26 [1901]: 1–32).
15 he made extensive handwritten notes on pages 50, 51, 53, and 54: David Galton, “Did Darwin read Mendel?” Quarterly Journal of Medicine 102, no. 8 (2009): 588, doi:10.1093/qjmed/hcp024.
第四章 他爱之花
1 “Flowers He Loved”: Edward Edelson, Gregor Mendel and the Roots of Genetics (New York: Oxford University Press, 1999), “Clemens Janetchek’s Poem Describing Men-del after His Death,” 75.
2 “We want only to disclose the [nature of] matter and its force”: Jiri Sekerak, “Gregor Mendel and the scientific milieu of his discovery,” ed. M. Kokowski (The Global and the Local: The History of Science and the Cultural Integration of Europe, Proceed-ings of the 2nd ICESHS, Cracow, Poland, September 6–9, 2006).
3 “The whole organic world is the result”: Hugo de Vries, Intracellular Pangenesis; In-cluding a Paper on Fertilization and Hybridization (Chicago: Open Court, 1910), “Mutual Independence of Hereditary Characters.”
4 Gregor Mendel decided to return to Vienna: Henig, Monk in the Garden, 60.
5 “remained constant without exception”: Eric C. R. Reeve, Encyclopedia of Genetics (London: Fitzroy Dearborn, 2001), 62.
6 Contrary to later belief: Mendel had several predecessors who had studied plant hy-brids just as intensively, except, perhaps, without Mendel’s immersion in numbers and quantification. In the 1820s, English botanists, such as T. A. Knight, John Goss, Alexander Seton, and William Herbert — attempting to breed more vigorous agri-cultural plants — had performed experiments with plant hybrids that were strikingly similar to Mendel’s. In France, Augustine Sageret’s work on melon hybrids was also similar to Mendel’s work. The most intensive work on plant hybrids immediately preceding Mendel was performed by the German botanist Josef K.lreuter, who had bred Nicotania hybrids. K.lreuter’s work was followed by the work of Karl von Gaertner and Charles Naudin in Paris. Darwin had actually read Sageret’s and Naudin’s stud-ies, both of which suggested the particulate quality of hereditary information, but Darwin had failed to appreciate their importance.
7 “the history of the evolution of organic forms”: Gregor Mendel, Experiments in Plant Hybridisation (New York: Cosimo, 2008),8.
8 By the late summer of 1857, the first hybrid peas: Henig, Monk in the Garden, 81. More details in “Chapter 7: First Harvest.”
9 “How small a thought it takes to fill”: Ludwig Wittgenstein, Culture and Value, trans. Peter Winch (Chicago: University of Chicago Press, 1984), 50e.
10 Mendel termed these overriding traits: Henig, Monk in the Garden, 86.
11 In some of these third-generation crosses: Ibid., 130.
12 “It requires indeed some courage”: Mendel, Experiments in Plant Hybridization, 8.
13 Mendel presented his paper: Henig, Monk in the Garden, “Chapter 11: Full Moon in February,” 133–47. A second portion of Mendel’s paper was read on March 8, 1865.
14 Mendel’s paper was published in: Mendel, “Experiments in Plant Hybridization,” www.mendelweb.org/Mendel.xhtml.
15 It is likely that he sent one to Darwin: Galton, “Did Darwin Read Mendel?” 587.
16 “one of the strangest silences in the history of biology”: Leslie Clarence Dunn, A Short History of Genetics: The Development of Some of the Main Lines of Thought, 1864–1939 (Ames: Iowa State University Press, 1991), 15.
17 “only empirical...... cannot be proved rational”: Gregor Mendel, “Gregor Mendel’s let-ters to Carl N.geli, 1866–1873,” Genetics 35, no. 5, pt. 2 (1950): 1.
18 “I knew that the results I obtained”: Allan Franklin et al., Ending the Mendel-Fisher Controversy (Pittsburgh, PA: University of Pittsburgh Press, 2008), 182.
19 “an isolated experiment might be doubly dangerous”: Mendel, “Letters to Carl N.geli,” April 18, 1867, 4.
20 In November 1873, Mendel wrote his last letter to N.geli: Ibid., November 18, 1867, 30–34.
21 “I feel truly unhappy that I have to neglect”: Gian A. Nogler, “The lesser-known Men-del: His experiments on Hieracium,” Genetics 172, no. 1 (2006): 1–6.
22 On January 6, 1884, Mendel died: Henig, Monk in the Garden, 170.
23 “Gentle, free-handed, and kindly...... Flowers he loved”: Edelson, Gregor Mendel, “Clemens Janetchek’s Poem Describing Mendel after His Death,” 75.
第五章 “名叫孟德尔”
1 The origin of species is a natural phenomenon: Lucius Moody Bristol, Social Adapta-tion: a Study in the Development of the Doctrine of Adaptation as a Theory of Social Progress (Cambridge, MA: Harvard University Press, 1915), 70.
2 The origin of species is an object of inquiry: Ibid.
3 The origin of species is an object of experimental investigation: Ibid.
4 In the summer of 1878: Peter W. van der Pas, “The correspondence of Hugo de Vries and Charles Darwin,” Janus 57: 173–213.
5 “margin was too small”: Mathias Engan, Multiple Precision Integer Arithmetic and Public Key Encryption (M. Engan, 2009), 16–17.
6 “In another work I shall discuss”: Charles Darwin, The Variation of Animals & Plants under Domestication, ed. Francis Darwin (London: John Murray, 1905), 5.
7 Darwin died in 1882: “Charles Darwin,” Famous Scientists, http://www.famousscientists.org/charles-darwin/.
8 In 1883, with rather grim determination: James Schwartz, In Pursuit of the Gene: From Darwin to DNA (Cambridge, MA: Harvard University Press, 2008), “Pangenes.”
9 Weismann called this hereditary material germplasm: August Weismann, William Newton Parker, and Harriet R.nnfeldt, The Germ-Plasm; a Theory of Heredity (New York: Scribner’s, 1893).
10 In a landmark paper written in 1897: Schwartz, In Pursuit of the Gene, 83.
11 He called these particles “pangenes”: Ida H. Stamhuis, Onno G. Meijer, and Erik J. A. Zevenhuizen, “Hugo de Vries on heredity, 1889–1903: Statistics, Mendelian laws, pangenes, mutations,” Isis (1999): 238–67.
12 “I know that you are studying hybrids”: Iris Sandler and Laurence Sandler, “A con-ceptual ambiguity that contributed to the neglect of Mendel’s paper,” History and Philosophy of the Life Sciences 7, no. 1 (1985): 9.
13 “Modesty is a virtue”: Edward J. Larson, Evolution: The Remarkable History of a Sci-entific Theory (New York: Modern Library, 2004).
14 That same year de Vries published his monumental study: Hans-J.rg Rheinberger, “Mendelian inheritance in Germany between 1900 and 1910. The case of Carl Cor-rens (1864–1933),” Comptes Rendus de l’Académie des Sciences — Series III — Sciences de la Vie 323, no. 12 (2000): 1089–96, doi:10.1016/s0764-4469(00)01267-1.
15 “I too still believed that I had found something new”: Url Lanham, Origins of Modern Biology (New York: Columbia University Press, 1968), 207.
16 “by a strange coincidence”: Carl Correns, “G. Mendel’s law concerning the behavior of progeny of varietal hybrids,” Genetics 35, no. 5 (1950): 33–41.
17 de Vries stumbled on an enormous, invasive: Schwartz, In Pursuit of the Gene, 111.
18 He called them mutants: Hugo de Vries, Th e Mutation Th eory, vol. 1 (Chicago: Open Court, 1909).
19 For William Bateson, the English biologist: John Williams Malone, It Doesn’t Take a Rocket Scientist: Great Amateurs of Science (Hoboken, NJ: Wiley, 2002), 23.
20 “We are in the presence of a new principle”: Schwartz, In Pursuit of the Gene, 112.
21 “I am writing to ask you”: Nicholas W. Gillham, “Sir Francis Galton and the birth of eugenics,” Annual Review of Genetics 35, no. 1 (2001): 83–101.
22 First, he independently confi rmed Mendel’s work: Other scientists, including Reginald Punnett and Lucien Cuenot, provided crucial experimental support for Mendel’s laws. In 1905, Punnett authored Mendelism, considered the first textbook of mod-ern genetics.
23 “His linen is foul. I daresay”: Alan Cock and Donald R. Forsdyke, Treasure Your Ex-ceptions: The Science and Life of William Bateson (Dordrecht: Springer Science & Business Media, 2008), 186.
24 Nicknamed “Mendel’s bulldog”: Ibid., “Mendel’s Bulldog (1902–1906),” 221–64.
25 “man’s outlook on the world”: William Bateson, “Problems of heredity as a subject for horticultural investigation,” Journal of the Royal Horticultural Society 25 (1900– 1901): 54.
26 “No single word in common use”: William Bateson and Beatrice (Durham) Bateson, William Bateson, F.R.S., Naturalist; His Essays & Addresses, Together with a Short Ac-count of His Life (Cambridge: Cambridge University Press, 1928), 93.
27 In 1905, still struggling for an alternative: Schwartz, In Pursuit of the Gene, 221.
28 “What will happen when . . . enlightenment actually comes to pass”: Bateson and Bate-son, William Bateson, F.R.S., 456.
第六章 优生学
1 Improved environment and education: Herbert Eugene Walter, Genetics: An Introduc-tion to the Study of Heredity (New York: Macmillan, 1938), 4.
2 Most Eugenists are Euphemists: G. K. Chesterton, Eugenics and Other Evils (London: Cassell, 1922), 12–13.
3 In 1883, one year after Charles Darwin’s death: Francis Galton, Inquiries into Human Faculty and Its Development (London: Macmillan, 1883).
4 “We greatly want a brief word to express”: Roswell H. Johnson, “Eugenics and So-Called Eugenics,” American Journal of Sociology 20, no. 1 (July 1914): 98–103, http:// www.jstor.org/stable/2762976.
5 “at least a neater word ..... than viriculture”: Ibid., 99.
6 “Believing, as I do, that human eugenics”: Galton, Inquiries into Human Faculty, 44.
7 A child prodigy, Galton: Dean Keith Simonton, Origins of Genius: Darwinian Perspec-tives on Creativity (New York: Oxford University Press, 1999), 110.
8 He tried studying medicine, but then switched: Nicholas W. Gillham, A Life of Sir Francis Galton: From African Exploration to the Birth of Eugenics (New York: Oxford University Press, 2001), 32–33.
9 “I saw enough of savage races”: Niall Ferguson, Civilization: The West and the Rest (Duisburg: Haniel-Stiftung, 2012), 176.
10 “initiated into an entirely new province of knowledge”: Francis Galton to C. R. Dar-win, December 9, 1859, https://www.darwinproject.ac.uk/letter/entry-2573.
11 Galton tried transfusing rabbits: Daniel J. Fairbanks, Relics of Eden: The Powerful Evi-dence of Evolution in Human DNA (Amherst, NY: Prometheus Books, 2007), 219.
12 “Man is born, grows up and dies”: Adolphe Quetelet, A Treatise on Man and the De-velopment of His Faculties: Now First Translated into English, trans. T. Smibert (New York: Cambridge University Press, 2013), 5.
13 He tabulated the chest breadth and height: Jerald Wallulis, The New Insecurity: The End of the Standard Job and Family (Albany: State University of New York Press, 1998), 41.
14 “Whenever you can”: Karl Pearson, The Life, Letters and Labours of Francis Galton (Cambridge: Cambridge University Press, 1914), 340.
15 “Keenness of Sight and Hearing”: Sam Goldstein, Jack A. Naglieri, and Dana Prin-ciotta, Handbook of Intelligence: Evolutionary Theory, Historical Perspective, and Cur-rent Concepts (New York: Springer, 2015), 100.
16 To marshal further evidence, Galton began: Gillham, Life of Sir Francis Galton, 156.
17 Galton published much of this data: Francis Galton, Hereditary Genius (London: Macmillan, 1892).
18 “You have made a convert”: Charles Darwin, More Letters of Charles Darwin: A Record of His Work in a Series of Hitherto Unpublished Letters, vol. 2 (New York:D.. Appleton, 1903), 41.
19 Galton called this the Ancestral Law of Heredity: John Simmons, The Scientific 100: A Ranking of the Most Influential Scientists, Past and Present (Secaucus, NJ: Carol Publishing Group, 1996), “Francis Dalton,” 441.
20 Basset Hound Club Rules, a compendium: Schwartz, In Pursuit of the Gene, 61.
21 Two prominent biologists: Ibid., 131.
22 But as Darbishire analyzed his own first-generation: Gillham, Life of Sir Francis Gal-ton, “The Mendelians Trump the Biometricians,” 303–23.
23 In the spring of 1905: Karl Pearson, Walter Frank Raphael Weldon, 1860–1906 (Cam-bridge: Cambridge University Press, 1906), 48–49.
24 trying...... to rework the data to fit Galtonian theory: Ibid., 49.
25 “To Weldon I owe the chief awakening of my life”: Schwartz, In Pursuit of the Gene,143.
26 “Each of us who now looks at his own patch”: William Bateson, Mendel’s Principles of Heredity: A Defence, ed. Gregor Mendel (Cambridge: Cambridge University Press, 1902), v.
27 “We have only touched the edge”: Ibid., 208.
28 “is second to no branch of science”: Ibid., ix.
29 Johannsen shortened the word to gene: Johan Henrik Wanscher, “The history of Wil-helm Johannsen’s genetical terms and concepts from the period 1903 to 1926,” Cen-taurus 19, no. 2 (1975): 125–47.
30 “Language is not only our servant”: Wilhelm Johannsen, “The genotype conception of heredity,” International Journal of Epidemiology 43, no. 4 (2014): 989–1000.
31 “The science of genetics is so new”: Arthur W. Gilbert, “The science of genetics,” Jour-nal of Heredity 5, no. 6 (1914): 235–44, http://archive.org/stream/journalofheredit 05amer/journalofh eredit05amer_djvu.txt.
32 “the technology of the industrial revolution confirmed”: Daniel J. Kevles, In the Name of Eugenics: Genetics and the Uses of Human Heredity (New York: Alfred A. Knopf, 1985), 3.
33 “forces which bring greatness to the social group”: Problems in Eugenics: First Interna-tional Eugenics Congress, 1912 (New York: Garland, 1984), 483.
34 In the spring of 1904, Galton presented his argument: Paul B. Rich, Race and Empire in British Politics (Cambridge: Cambridge University Press, 1986), 234.
35 “introduced into national consciousness, like a new religion”: Papers and Proceedings — First Annual Meeting — American Sociological Society, vol. 1 (Chicago: University of Chicago Press, 1906), 128.
36 “All creatures would agree that it was better”: Francis Galton, “Eugenics: Its definition, scope, and aims,” American Journal of Sociology 10, no. 1 (1904): 1–25.
37 “if unsuitable marriages from the eugenic point of view”: Andrew Norman, Charles Darwin: Destroyer of Myths (Barnsley, South Yorkshire: Pen and Sword, 2013), 242.
38 Henry Maudsley, the psychiatrist: Galton, “Eugenics,” comments by Maudsley,doi:10.1017/s0364009400001161.
39 “He had five brothers,” Maudsley noted: Ibid., 7.
40 “It is in the sterilization of failure”: Ibid., comments by H. G. Wells; and H. G. Wells and Patrick Parrinder, The War of the Worlds (London: Penguin Books, 2005).
41 “A pleasant sort o’ soft woman”: George Eliot, The Mill on the Floss (New York: Dodd, Mead, 1960), 12.
42 In 1911, Havelock Ellis, Galton’s colleague: Lucy Bland and Laura L. Doan, Sexology Uncensored: The Documents of Sexual Science (Chicago: University of Chicago Press, 1998), “The Problem of Race-Regeneration: Havelock Ellis (1911).”
43 On July 24, 1912: R. Pearl, “The First International Eugenics Congress,” Science 36, no. 926 (1912): 395–96, doi:10.1126/science.36.926.395.
44 Davenport’s 1911 book: Charles Benedict Davenport, Heredity in Relation to Eugen-ics (New York: Holt, 1911).
45 Van Wagenen suggested, and “they are totally”: First International Eugenics Congress, Problems in Eugenics (1912; repr., London: Forgotten Books, 2013), 464–65.
46 “We endeavor to keep track”: Ibid., 469.
第七章 “三代智障已经足够”
1 If we enable the weak and the deformed: Theodosius G. Dobzhansky, Heredity and the Nature of Man (New York: New American Library, 1966), 158.
2 And from deformed [parents] deformed [offspring]: Aristotle, History of Animals, Book VII, 6, 585b28–586a4.
3 In the spring of 1920, Emmett Adaline Buck: Many of the details of the Buck family story are from J. David Smith, The Sterilization of Carrie Buck (Liberty Corner, NJ: New Horizon Press, 1989).
4 Her husband, Frank Buck: Much of the information in this chapter is from Paul Lom-bardo, Three Generations, No Imbeciles: Eugenics, the Supreme Court, and Buck v. Bell (Baltimore: Johns Hopkins University Press, 2008).
5 A cursory mental examination: “Buck v. Bell,” Law Library, American Law and Legal Information, http://law.jrank.org/pages/2888/Buck-v-Bell-1927.xhtml.
6 Of these, an idiot was the easiest to classify: Mental Defectives and Epileptics in State Institutions: Admissions, Discharges, and Patient Population for State Institutions for Mental Defectives and Epileptics, vol. 3 (Washington, DC: US Government Printing Offi ce, 1937).
7 On January 23, 1924: “Carrie Buck Committed (January 23, 1924),” Encyclopedia Virginia, http://www.encyclopediavirginia.org/Carrie_Buck_Committed_January _23_1924.
8 On March 28, 1924: Ibid.
9 “Moron, Middle Grade”: Stephen Murdoch, IQ: A Smart History of a Failed Idea (Hoboken, NJ: John Wiley & Sons, 2007), 107.
10 Carrie Buck was asked to appear: Ibid., “Chapter 8: From Segregation to Steriliza-tion.”
11 On March 29, 1924, with Priddy’s help: “Period during which sterilization occurred,” Virginia Eugenics, doi:www.uvm.edu/~lkaelber/eugenics/VA/VA.xhtml.
12 “Do you care to say anything”: Lombardo, Three Generations, 107.
13 “A cross between”: Madison Grant, The Passing of the Great Race (New York: Scrib-ner’s, 1916).
14 “the menace of race deterioration”: Carl Campbell Brigham and Robert M. Yerkes, A Study of American Intelligence (Princeton, NJ: Princeton University Press, 1923), “Foreword.”
15 “The Eugenic ravens are croaking”: A. G. Cock and D. R. Forsdyke, Treasure Your Ex-ceptions: The Science and Life of William Bateson (New York: Springer, 2008), 437– 38n3.
16 “It is better for all the world”: Jerry Menikoff , Law and Bioethics: An Introduction (Washington, DC: Georgetown University Press, 2001), 41.
17 “Three generations of imbeciles is enough: Ibid. In 1927, the state of Indiana passed: Public Welfare in Indiana 68–75 (1907): 50. In 1907, a new law passed by the state legislature and signed by the governor of Indi-ana provided for the involuntary sterilization of “confirmed criminals, idiots, imbe-ciles and rapists.”
18 Although it was eventually found to be unconstitutional, this law is widely regarded as the first eugenics sterilization legislation passed in the world. In 1927, a revised law was implemented and before it was repealed in 1974, over 2,300 of the state’s most vulnerable citizens were involuntarily sterilized. In addition, In-diana established a state-funded Committee on Mental Defectives that carried out eugenic family studies in over twenty counties and was home to an active “better ba-bies” movement that encouraged scientific motherhood and infant hygiene as routes to human improvement. http://www.iupui.edu/~eugenics/.
19 Better Babies Contests: Laura L. Lovett, “Fitter Families for Future Firesides: Florence Sherbon and Popular Eugenics,” Public Historian 29, no. 3 (2007): 68–85.
20 “You should score 50% for heredity”: Charles Davenport to Mary T. Watts, June 17, 1922, Charles Davenport Papers, American Philosophical Society Archives, Phila-delphia, PA. Also see Mary Watts, “Fitter Families for Future Firesides,” Billboard 35, no. 50 (December 15, 1923): 230–31.
21 In 1927, a film called Are You Fit to Marry?: Martin S. Pernick and Diane B. Paul, The Black Stork: Eugenics and the Death of “Defective” Babies in American Medicine and Motion Pictures since 1915 (New York: Oxford University Press, 1996).
第二部分
1 “In the Sum of the Parts”: Wallace Stevens, The Collected Poems of Wallace Stevens (New York: Alfred A. Knopf, 2011), “On the Road Home,” 203–4.
2 It was when I said: Ibid.
第一章 “身份”
1 I am the family face: Thomas Hardy, The Collected Poems of Thomas Hardy (Ware, Hertfordshire, England: Wordsworth Poetry Library, 2002), “Heredity,” 204–5.
2 In 1907, when William Bateson visited: William Bateson, “Facts limiting the theory of heredity,” in Proceedings of the Seventh International Congress of Zoology, vol. 7 (Cambridge: Cambridge University Press Warehouse, 1912).
3 “Morgan is a blockhead”: Schwartz, In Pursuit of the Gene, 174.
4 “Cell biologists look; geneticists count; biochemists clean”: Arthur Kornberg, author interview, 1993.
5 “We are interested in heredity not primarily”: “Review: Mendelism up to date,” Jour-nal of Heredity 7, no 1 (1916): 17–23.
6 Walter Sutton, a grasshopper-collecting farm boy: David Ellyard, Who Discovered What When (Frenchs Forest, New South Wales, Australia: New Holland, 2005), “Walter Sutton and Theodore Boveri: Where Are the Genes?”
7 In 1905, using cells from the common mealworm: Stephen G. Brush, “Nettie M. Ste-vens and the Discovery of Sex Determination by Chromosome,” Isis 69, no. 2 (1978): 162–72.
8 The students called his laboratory the Fly Room: Ronald William Clark, The Survival of Charles Darwin: A Biography of a Man and an Idea (New York: Random House, 1984), 279.
9 He had visited Hugo de Vries’s: Russ Hodge, Genetic Engineering: Manipulating the Mechanisms of Life (New York: Facts On File, 2009), 42.
10 For Morgan, this genetic linkage: Thomas Hunt Morgan, The Mechanism of Mende-lian Heredity (New York: Holt, 1915), “Chapter 3: Linkage.”
11 genes had to be physically linked to each other: Morgan was exceptionally lucky in choosing fruit flies for his experiments, since flies have an unusually low number of chromosomes — just four. If flies had multiple chromosomes, linkage might have been much harder to prove.
12 It was a material thing: Thomas Hunt Morgan, “The Relation of Genetics to Physiol-ogy and Medicine,” Nobel Lecture (June 4, 1934), in Nobel Lectures, Physiology and Medicine, 1922–1941 (Amsterdam: Elsevier, 1965), 315.
13 The czarina of Russia, Alexandra: Daniel L. Hartl and Elizabeth W. Jones, Essential Genetics: A Genomics Perspective (Boston: Jones and Bartlett, 2002), 96–97.
14 Grigory Rasputin: Helen Rappaport, Queen Victoria: A Biographical Companion (Santa Barbara, CA: ABC-CLIO, 2003), “Hemophilia.”
15 Rasputin was poisoned: Andrew Cook, To Kill Rasputin: The Life and Death of Grigori Rasputin (Stroud, Gloucestershire: Tempus, 2005), “The End of the Road.”
16 On the evening of July 17, 1918: “Alexei Romanov,” History of Russia, http://historyof russia.org/alexei-romanov/.
17 In 2007, an archaeologist: “DNA Testing Ends Mystery Surrounding Czar Nicholas II Children,” Los Angeles Times, March 11, 2009.
第二章 真相与和解
1 All changed, changed utterly: William Butler Yeats, Easter, 1916 (London: Privately printed by Clement Shorter, 1916).
2 In 1909, a young mathematician: Eric C. R. Reeve and Isobel Black, Encyclopedia of Genetics (London: Fitzroy Dearborn, 2001), “Darwin and Mendel United: The Con-tributions of Fisher, Haldane and Wright up to 1932.”
3 In 1918, Fisher published: Ronald Fisher, “The Correlation between Relatives on the Supposition of Mendelian Inheritance,” Transactions of the Royal Society of Edin-burgh 52 (1918): 399–433.
4 Hugo de Vries had proposed that mutations: Hugo de Vries, The Mutation Theory; Ex-periments and Observations on the Origin of Species in the Vegetable Kingdom, trans. J. B. Farmer and A. D. Darbishire (Chicago: Open Court, 1909).
5 In the 1930s, Theodosius Dobzhansky: Robert E. Kohler, Lords of the Fly: Droso phila Genetics and the Experimental Life (Chicago: University of Chicago Press, 1994), “From Laboratory to Field: Evolutionary Genetics.”
6 In September 1943, Dobzhansky: Th. Dobzhansky, “Genetics of natural populations IX.Temporal changes in the composition of populations of Drosophila pseudoob-scura,” Genetics 28, no. 2 (1943): 162.
7 Dobzhansky could demonstrate it experimentally: Details of Dobzhansky’s exper-iments are sourced from Theodosius Dobzhansky, “Genetics of natural popula-tions XIV. A response of certain gene arrangements in the third chromosome of Droso phila pseudoobscura to natural selection,” Genetics 32, no. 2 (1947): 142; and S. Wright and T. Dobzhansky, “Genetics of natural populations; experimental repro-duction of some of the changes caused by natural selection in certain populations of Drosophila pseudoobscura,” Genetics 31 (March 1946): 125–56. Also see T. Dobzhan-sky, Studies on Hybrid Sterility. II. Localization of Sterility Factors in Drosophila Pseudoobscura Hybrids. Genetics (March 1, 1936) vol 21, 113–135.
第三章 转化
1 If you prefer an “academic life”: H. J. Muller, “The call of biology,” AIBS Bulletin 3, no. 4 (1953). Copy with handwritten notes, http://libgallery.cshl.edu/archive/files /c73e9703aa1b65ca3f4881b9a2465797.jpg.
2 We do deny that: Peter Pringle, The Murder of Nikolai Vavilov: The Story of Stalin’s Persecution of One of the Great Scientists of the Twentieth Century (Simon & Schus-ter, 2008), 209.
3 Grand Synthesis: Ernst Mayr and William B. Provine, The Evolutionary Synthesis: Per-spectives on the Unification of Biology (Cambridge, MA: Harvard University Press, 1980).
4 Transformation was discovered: William K. Purves, Life, the Science of Biology (Sun-derland, MA: Sinauer Associates, 2001), 214–15.
5 Griffith performed an experiment: Werner Karl Maas, Gene Action: A Historical Ac-count (Oxford: Oxford University Press, 2001), 59–60.
6 “this tiny man who ..... barely spoke above a whisper”: Alvin Coburn to Joshua Le-derberg, November 19, 1965, Rockefeller Archives, Sleepy Hollow, NY, http://www .rockarch.org/.
7 Griffith published his data: Fred Griffith, “The significance of pneumococcal types,” Journal of Hygiene 27, no. 2 (1928): 113–59.
8 In 1920, Hermann Muller: “Hermann J. Muller — biographical,” http://www.nobel prize.org/nobel_prizes/medicine/laureates/1946/muller-bio.xhtml.
9 accumulated mutations — dozens of them: H. J. Muller, “Artificial transmutation of the gene,” Science 22 (July 1927): 84–87.
10 In Darwin’s scheme: James F. Crow and Seymour Abrahamson, “Seventy years ago: Mutation becomes experimental,” Genetics 147, no. 4 (1997): 1491.
11 “There is no permanent status quo in nature”: Jack B. Bresler, Genetics and Society (Reading, MA: Addison-Wesley, 1973), 15.
12 struck him as frankly sinister: Kevles, In the Name of Eugenics, “A New Eugenics,” 251–68.
13 befriended the novelist and social activist Theodore Dreiser: Sam Kean, The Violinist’s Thumb: And Other Lost Tales of Love, War, and Genius, as Written by Our Genetic Code (Boston: Little, Brown, 2012), 33.
14 The FBI launched: William DeJong-Lambert, The Cold War Politics of Genetic Re-search: An Introduction to the Lysenko Affair (Dordrecht: Springer, 2012), 30.
第四章 没有生存价值的生命
1 He wanted to be God: Robert Jay Lifton, The Nazi Doctors: Medical Killing and the Psychology of Genocide (New York: Basic Books, 2000), 359.
2 A hereditarily ill person costs 50,000 reichsmarks: Susan Bachrach, “In the name of pub-lic health — Nazi racial hygiene,” New England Journal of Medicine 351 (2004): 417–19.
3 Nazism, the biologist Fritz Lenz once said: Erwin Baur, Eugen Fischer, and Fritz Lenz,Human Heredity (London: G. Allen & Unwin, 1931), 417.
4 Also used by Hess, Hitler’s deputy, the phrase was originally coined by Fritz Lenz as part of a review of Mein Kampf. had coined the phrase as early as 1895: Alfred Ploetz. Grundlinien Einer Rassen-Hygiene (Berlin: S. Fischer, 1895); and Sheila Faith Weiss, “The race hygiene move-ment in Germany,” Osiris 3 (1987): 193–236.
5 In 1914, Ploetz’s colleague Heinrich Poll: Heinrich Poll, “über Vererbung beim Menschen,” Die Grenzbotem 73 (1914): 308.
6 Kaiser Wilhelm Institute for Anthropology: Robert Wald Sussman, The Myth of Race: The Troubling Persistence of an Unscientific Idea (Cambridge, MA: Harvard Univer-sity Press, 2014), “Funding of the Nazis by American Institutes and Businesses,” 138.
7 Hitler, imprisoned for leading the Beer Hall Putsch: Harold Koenig, Dana King, and Verna B. Carson, Handbook of Religion and Health (Oxford: Oxford University Press, 2012), 294.
8 Sterilization Law: US Chief Counsel for the Prosecution of Axis Criminality, Nazi Conspiracy and Aggression, vol. 5 (Washington, DC: US Government Printing Of-fice, 1946), document 3067-PS, 880–83 (English translation accredited to Nurem-berg staff; edited by GHI staff).
9 Films such as Das Erbe: “Nazi Propaganda: Racial Science,” USHMM Collections Search, http://collections.ushmm.org/search/catalog/fv3857.
10 and Erbkrank: “1936—Rassenpolitisches Amt der NSDAP — Erbkrank,” Internet Archive, https://archive.org/details/1936-Rassenpolitisches-Amt-der-NSDAP-Erb krank.
11 in Leni Riefenstahl’s Olympia: Olympia, directed by Leni Riefenstahl, 1936.
12 In November 1933: ” Holocaust timeline,” History Place, http://www.historyplace .com/worldwar2/holocaust/timeline.xhtml.
13 In October 1935, the Nuremberg Laws: “Key dates: Nazi racial policy, 1935,” US Holocaust Memorial Museum, http://www.ushmm.org/outreach/en/article .php?ModuleId=10007696.
14 By 1934, nearly five thousand adults: “Forced sterilization,” US Holocaust Memorial Museum, http://www.ushmm.org/learn/students/learning-materials-and-resources /mentally-and-physically-handicapped-victims-of-the-nazi-era/forced-sterilization.
15 to euthanize their child, Gerhard: Christopher R. Browning and Jürgen Matth.us, Th e Origins of the Final Solution: The Evolution of Nazi Jewish Policy, September 1939– March 1942 (Lincoln: University of Nebraska, 2004), “Killing the Handicapped.”
16 Working with Karl Brandt: Ulf Schmidt, Karl Brandt: The Nazi Doctor, Medicine, and Power in the Third Reich (London: Hambledon Continuum, 2007).
17 No. 4 Tiergartenstrasse in Berlin: G.tz Aly, Peter Chroust, and Christian Pross, Cleansing the Fatherland, trans. Belinda Cooper (Baltimore: Johns Hopkins Uni-versity Press, 1994), “Chapter 2: Medicine against the Useless.”
18 The Sterilization Law had achieved: Roderick Stackelberg, The Routledge Companion to Nazi Germany (New York: Routledge, 2007), 303.
19 “banality of evil”: Hannah Arendt, Eichmann in Jerusalem: A Report on the Banality of Evil (New York: Viking, 1963).
20 In a rambling treatise entitled: Otmar Verschuer and Charles E. Weber, Racial Biol-ogy of the Jews (Reedy, WV: Liberty Bell Publishing, 1983).
21 First they came for the Socialists: J. Simkins, “Martin Niemoeller,” Spartacus Educa-tional Publishers, 2012, www. spartacus.schoolnet.co.uk/GERniemoller.htm.
22 Trofim Lysenko: Jacob Darwin Hamblin, Science in the Early Twentieth Century: An Encyclopedia (Santa Barbara, CA: ABC-CLIO, 2005), “Trofim Lysenko,” 188–89.
23 “gives one the feeling of a toothache”: David Joravsky, The Lysenko Affair (Chicago: Univer-sity of Chicago Press, 2010), 59. Also see Zhores A. Medvedev, Th eRise and Fall of T..D. Lysenko, trans. I. Michael Lerner (New York: Columbia University Press, 1969), 11–16.
24 The gene, he argued: T. Lysenko, Agrobiologia, 6th ed. (Moscow: Selkhozgiz, 1952), 602–6.
25 In 1940, Lysenko: “Trofim Denisovich Lysenko,” Encyclopaedia Britannica Online, http://www.britannica.com/biography/Trofim-Denisovich-Lysenko.
26 “I am nothing but dung now”: Pringle, Murder of Nikolai Vavilov, 278.
27 died a few weeks later: A number of Vavilov’s colleagues, including Karpechenko, Govorov, Levitsky, Kovalev, and Flayksberger, were also arrested. Lysenko’s influence virtually emptied the Soviet academy of all geneticists. Biology in the Soviet Union would be hobbled for decades.
28 Having coined the phrase: James Tabery, Beyond Versus: The Struggle to Understand the Interaction of Nature and Nurture (Cambridge, MA: MIT Press, 2014), 2.
29 In 1924, Hermann Werner Siemens: Hans-Walter Schmuhl, The Kaiser Wilhelm Insti-tute for Anthropology, Human Heredity, and Eugenics, 1927–1945: Crossing Boundar-ies (Dordrecht: Springer, 2008), “Twin Research.”
30 Between 1943 and 1945: Gerald L. Posner and John Ware, Mengele: The Complete Story (New York: McGraw-Hill, 1986).
31 “We were always sitting together — always nude”: Lifton, Nazi Doctors, 349.
32 In April 1933: Wolfgang Benz and Thomas Dunlap, A Concise History of the Third Reich (Berkeley: University of California Press, 2006), 142.
33 “Hitler may have ruined”: George Orwell, In Front of Your Nose, 1946–1950, ed. Sonia Orwell and Ian Angus (Boston: D. R. Godine, 2000), 11.
34 a lecture later published as: Erwin Schr.dinger, What Is Life?: The Physical Aspect of the Living Cell (Cambridge: Cambridge University Press, 1945).
第五章 “愚蠢的分子”
1 Never underestimate the power of ..... stupidity: Walter W. Moore Jr., Wise Sayings: For Your Thoughtful Consideration (Bloomington, IN: AuthorHouse, 2012), 89.
2 “The Fess”: “The Oswald T. Avery Collection: Biographical information,” National Institutes of Health, http://profiles.nlm.nih.gov/ps/retrieve/Narrative/CC/p-nid/35.
3 No one knew or understood the chemical structure: Robert C. Olby, The Path to the Double Helix: The Discovery of DNA (New York: Dover Publications, 1994), 107.
4 Swiss biochemist, Friedrich Miescher: George P. Sakalosky, Notio Nova: A New Idea (Pittsburgh, PA: Dorrance, 2014), 58.
5 extremely “unsophisticated” structure: Olby, Path to the Double Helix, 89.
6 “stupid molecule”: Garland Allen and Roy M. MacLeod, eds., Science, History and Social Activism: A Tribute to Everett Mendelsohn, vol. 228 (Dordrecht: Springer Sci-ence & Business Media, 2013), 92.
7 “structure-determining, supporting substance”: Olby, Path to the Double Helix, 107.
8 “primordial sea”: Richard Preston, Panic in Level 4: Cannibals, Killer Viruses, and Other Journeys to the Edge of Science (New York: Random House, 2009), 96.
9 “Who could have guessed it?”: Letter from Oswald T. Avery to Roy Avery, May 26, 1943, Oswald T. Avery Papers, Tennessee State Library and Archives.
10 Avery wanted to be doubly sure: Maclyn McCarty, The Transforming Principle: Dis-covering That Genes Are Made of DNA (New York: W. W. Norton, 1985), 159.
11 “cloth from which genes were cut”: Lyon and Gorner, Altered Fates, 42.
12 Oswald Avery’s paper on DNA was published: O. T. Avery, Colin M. MacLeod, and Maclyn McCarty, “Studies on the chemical nature of the substance inducing transfor-mation of pneumococcal types: Induction of transformation by a deoxyribonucleic acid fraction isolated from pneumococcus type III,” Journal of Experimental Medi-cine 79, no. 2 (1944): 137–58.
13 That year, an estimated 450,000 were gassed: US Holocaust Memorial Museum, “In-troduction to the Holocaust,” Holocaust Encyclopedia, http://www.ushmm.org/wlc /en/article.php?ModuleId=10005143.
14 In the early spring of 1945: Ibid.
15 The Eugenics Record Office: Steven A. Farber, “U.S. scientists’ role in the eugenics movement (1907–1939): A contemporary biologist’s perspective,” Zebrafish 5, no. 4 (2008): 243–45.
第六章 DNA双螺旋
1 One could not be a successful scientist: James D. Watson, The Double Helix: A Personal Account of the Discovery of the Structure of DNA (London: Weidenfeld & Nicolson, 1981), 13.
2 It is the molecule that has the glamour: Francis Crick, What Mad Pursuit: A Personal View of Scientific Discovery (New York: Basic Books, 1988), 67.
3 Science [would be] ruined: Donald W. Braben, Pioneering Research: A Risk Worth Taking (Hoboken, NJ: John Wiley & Sons, 2004), 85.
4 Among the early converts: Maurice Wilkins, Maurice Wilkins: The Third Man of the Double Helix: An Autobiography (Oxford: Oxford University Press, 2003).
5 Ernest Rutherford: Richard Reeves, A Force of Nature: The Frontier Genius of Ernest Rutherford (New York: W. W. Norton, 2008).
6 “Life ..... is a chemical incident”: Arthur M. Silverstein, Paul Ehrlich’s Receptor Immu-nology: The Magnificent Obsession (San Diego, CA: Academic, 2002), 2.
7 Wilkins found an X-ray diffraction machine: Maurice Wilkins, correspondence with Raymond Gosling on the early days of DNA research at King’s College, 1976, Mau-rice Wilkins Papers, King’s College London Archives.
8 It was, as one friend of Franklin’s: Letter of June 12, 1985, notes on Rosalind Frank-lin, Maurice Wilkins Papers, no. ad92d68f-4071-4415-8df2-dcfe041171fd.
9 the relationship soon froze into frank, glacial hostility: Daniel M. Fox, Marcia Mel-drum, and Ira Rezak, Nobel Laureates in Medicine or Physiology: A Biographical Dic-tionary (New York: Garland, 1990), 575.
10 She “barks often, doesn’t succeed in biting me”: James D. Watson, The Annotated and Illustrated Double Helix, ed. Alexander Gann and J. A. Witkowski (New York: Simon & Schuster, 2012), letter to Crick, 151.
11 “Now she’s trying to drown me”: Brenda Maddox, Rosalind Franklin: The Dark Lady of DNA (New York: HarperCollins, 2002), 164.
12 Franklin found most of her male colleagues “positively repulsive”: Watson, Annotated and Illustrated Double Helix, letter from Rosalind Franklin to Anne Sayre, March 1, 1952, 67.
13 It was not just sexism: Crick never believed that Franklin was affected by sexism. Unlike Watson, who eventually wrote a generous recapitulation of Franklin’s work highlighting the adversities that she had faced as a scientist, Crick maintained that Franklin was unaffected by the atmosphere at King’s. Franklin and Crick would eventually become close friends in the late 1950s; Crick and his wife were especially helpful to Franklin during her prolonged illness and in the months preceding her untimely death. Crick’s fondness for Franklin can be found in Crick, What Mad Pur-suit, 82–85.
14 passionate Marie Curie, with her chapped palms: “100 years ago: Marie Curie wins 2nd Nobel Prize,” Scientific American, October 28, 2011, http://www.scientific american.com/article/curie-marie-sklodowska-greatest-woman-scientist/.
15 ethereal Dorothy Hodgkin at Oxford: “Dorothy Crowfoot Hodgkin—biographical,” Nobelprize.org, http://www.nobelprize.org/nobel_prizes/chemistry/laureates/1964 /hodgkin-bio.xhtml.
16 an “affable looking housewife”: Athene Donald, “Dorothy Hodgkin and the year of crystallography,” Guardian, January 14, 2014.
17 ingenious apparatus that bubbled hydrogen: “The DNA riddle: King’s College, Lon-don, 1951–1953,” Rosalind Franklin Papers, http://profiles.nlm.nih.gov/ps/retrieve /Narrative/KR/p-nid/187.
18 J. D. Bernal, the crystallographer: J. D. Bernal, “Dr. Rosalind E. Franklin,” Nature 182 (1958): 154.
19 “shirttails flying, knees in the air”: Max F. Perutz, I Wish I’d Made You Angry Earlier: Essays on Science, Scientists, and Humanity (Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press, 1998), 70.
20 Wilkins showed little, if any, excitement: Watson Fuller, “For and against the helix,” Maurice Wilkins Papers, no. 00c0a9ed-e951-4761-955c-7490e0474575.
21 “Before Maurice’s talk”: Watson, Double Helix, 23.
22 “Maurice was English”: http://profi les.nlm.nih.gov/ps/access/SCBBKH.pdf.
23 “nothing about the X-ray diffraction”: Watson, Double Helix, 22.
24 “a complete flop”: Ibid., 18.
25 “The fact that I was unable”: Ibid., 24.
26 Watson had moved to Cambridge: Officially, Watson had moved to Cambridge to help Perutz and another scientist, John Kendrew, with their work on a protein called myoglobin. Watson then switched to the study of the structure of a virus called to-bacco mosaic virus, or TMV. But he was vastly more interested in DNA and soon abandoned all other projects to focus on DNA. Watson, Annotated and Illustrated Double Helix, 127.
27 “A youthful arrogance”: Crick, What Mad Pursuit, 64.
29 Pauling’s seminal paper: L. Pauling, R. B. Corey, and H. R. Branson, “The structure of proteins: Two hydrogen-bonded helical configurations of the polypeptide chain,” Proceedings of the National Academy of Sciences 37, no. 4 (1951): 205–11.
30 “product of common sense”: Watson, Annotated and Illustrated Double Helix, 44.
31 “like trying to determine the structure of a piano”: http://www.diracdelta.co.uk/science /source/c/r/crick%20francis/source.xhtml#.Vh8XlaJeGKI.
32 The experimental data would generate the models: Crick, What Mad Pursuit, 100–103. Crick always maintained that Franklin fully understood the importance of model building.
33 “How dare you interpret my data for me?”: Victor K. McElheny, Watson and DNA: Making a Scientific Revolution (Cambridge, MA: Perseus, 2003), 38.
34 “Big helix with several chains”: Alistair Moffat, The British: A Genetic Journey (Edin-burgh: Birlinn, 2014); and from Rosalind Franklin’s laboratory notebooks, dated 1951.
35 “Superficially, the X-ray data”: Watson, Annotated and Illustrated Double Helix, 73.
36 “check it with”: Ibid.
37 Wilkins, Franklin, and her student, Ray Gosling: Bill Seeds and Bruce Fraser accom-panied them on this visit.
38 As Gosling recalled, “Rosalind let rip”: Watson, Annotated and Illustrated Double Helix, 91.
39 “His mood”: Ibid., 92.
40 In the first weeks of January 1953: Linus Pauling and Robert B. Corey, “A proposed structure for the nucleic acids,” Proceedings of the National Academy of Sciences 39, no. 2 (1953): 84–97.
41 “V.Good. Wet Photo”: http://profi les.nlm.nih.gov/ps/access/KRBBJF.pdf.
42 “important biological objects come in pairs”: Watson, Double Helix, 184.
43 he would later write defensively: Anne Sayre, Rosalind Franklin & DNA (New York: W. W. Norton, 1975), 152.
44 “Suddenly I became aware”: Watson, Annotated and Illustrated Double Helix, 207.
45 “Upon his arrival”: Ibid., 208.
46 “winged into the Eagle”: Ibid., 209.
47 “We see it as a rather stubby double helix”: John Sulston and Georgina Ferry, The Common Thread: A Story of Science, Politics, Ethics, and the Human Genome (Wash-ington, DC: Joseph Henry Press, 2002), 3.
48 Maurice Wilkins came to take a look: Most likely on March 11 or 12, 1953. Crick in-formed Delbrück of the model on Thursday, March 12. Also see Watson Fuller, “Who said helix?” with related papers, Maurice Wilkins Papers, no. c065700f-b6d9-46cf -902a-b4f8e078338a.
49 “The model was standing high”: June 13, 1996, Maurice Wilkins Papers.
50 “I think you’re a couple of old rogues”: Letter from Maurice Wilkins to Francis Crick, March 18, 1953, Wellcome Library, Letter Reference no. 62b87535-040a-448c-9b73 -ff3a3767db91. http://wellcomelibrary.org/player/b20047198#?asi=0&ai=0&z=0.12 15%2C0.2046%2C0.5569%2C0.3498.
51 “I like the idea”: Fuller, “Who said helix?” with related papers.
52 “The positioning of the backbone”: Watson, Annotated and Illustrated Double Helix,222.
53 On April 25, 1953: J. D. Watson and F. H. C. Crick, “Molecular structure of nucleic acids: A structure for deoxyribose nucleic acid,” Nature 171 (1953): 737–38.
54 “the enigma of how the vast amount”: Fuller, “Who said helix?” with related papers.
第七章 “变化莫测的难解之谜”
1 In the protein molecule: “1957: Francis H. C. Crick (1916–2004) sets out the agenda of molecular biology,” Genome News Network, http://www.genomenewsnetwork.org /resources/timeline/1957_Crick.php.
2 In 1941: “1941: George W. Beadle (1903–1989) and Edward L. Tatum (1909–1975) show how genes direct the synthesis of enzymes that control metabolic processes,” Genome News Network, http://www.genomenewsnetwork.org/resources/timeline /1941_Beadle_Tatum.php.
3 a student of Thomas Morgan’s: Edward B. Lewis, “Thomas Hunt Morgan and his leg-acy,” Nobelprize.org, http://www.nobelprize.org/nobel_prizes/medicine/laureates /1933/morgan-article.xhtml.
4 the “action” of a gene: Frank Moore Colby et al., The New International Year Book: A Compendium of the World’s Progress, 1907–1965 (New York: Dodd, Mead, 1908), 786.
5 “A gene,” Beadle wrote in 1945: George Beadle, “Genetics and metabolism in Neuro-spora,” Physiological reviews 25, no. 4 (1945): 643–63.
6 “For over a year”: James D. Watson, Genes, Girls, and Gamow: After the Double Helix (New York: Alfred A. Knopf, 2002), 31.
7 “I am playing with complex organic”: http://scarc.library.oregonstate.edu/coll/pauling /dna/corr/sci9.001.43-gamow-lp-19531022-transcript.xhtml.
8 Gamow called it the RNA Tie Club: Ted Everson, The Gene: A Historical Perspective (Westport, CT: Greenwood, 2007), 89–91.
9 “It always had a rather ethereal existence”: “Francis Crick, George Gamow, and the RNA Tie Club,” Web of Stories. http://www.webofstories.com/play/francis.crick/84.
10 “Do or die, or don’t try”: Sam Kean, The Violinist’s Thumb: And Other Lost Tales of Love, War, and Genius, as Written by Our Genetic Code (New York: Little, Brown, 2012).
11 was required for the translation of DNA into proteins: Arthur Pardee and Monica Riley had also proposed a variant of this idea.
12 Is he in heaven, is he in hell?: Cynthia Brantley Johnson, The Scarlet Pimpernel (Simon & Schuster, 2004), 124.
13 “It’s the magnesium”: “Albert Lasker Award for Special Achievement in Medical Science: Sydney Brenner,” Lasker Foundation, http://www.laskerfoundation.org /awards/2000special.htm.
14 Like DNA, these RNA molecules were built: Two other scientists, Elliot Volkin and Lazarus Astrachan, had proposed an RNA intermediate for genes in 1956. The two seminal papers published by the Brenner/Jacob group and the Watson/Gilbert group in 1961 are: F. Gros et al., “Unstable ribonucleic acid revealed by pulse labeling of Escherichia coli,” Nature 190 (May 13, 1960): 581–85; and S. Brenner, F. Jacob, and M. Meselson, “An unstable intermediate carrying information from genes to ribo-somes for protein synthesis,” Nature 190 (May 13, 1960): 576–81.
15 “It seems likely...... that the precise sequence”: J. D. Watson and F. H. C. Crick, “Genetical implications of the structure of deoxyribonucleic acid,” Nature 171, no. 4361 (1953): 965.
16 In 1904, a single image: David P. Steensma, Robert A. Kyle, and Marc A. Shampo, “Walter Clement Noel — first patient described with sickle cell disease,” Mayo Clinic Proceedings 85, no. 10 (2010).
17 In 1951, working with Harvey Itano: “Key participants: Harvey A. Itano,” It’s in the Blood! A Documentary History of Linus Pauling, Hemoglobin, and Sickle Cell Anemia, http://scarc.library.oregonstate.edu/coll/pauling/blood/people/itano.xhtml.
第八章 基因的调控、复制与重组
1 It is absolutely necessary to find the origin: Quoted in Sean Carrol, Brave Genius: A Scientist, a Philosopher, and Their Daring Adventures from the French Resistance to the Nobel Prize (New York: Crown, 2013), 133.
2 “the properties implicit in genes”: Thomas Hunt Morgan, “The relation of genetics to physiology and medicine,” Scientific Monthly 41, no. 1 (1935): 315.
3 Jacques Monod, the French biologist: Agnes Ullmann, “Jacques Monod, 1910–1976: His life, his work and his commitments,” Research in Microbiology 161, no. 2 (2010): 68–73.
4 Pardee, Jacob, and Monod published: Arthur B. Pardee, Fran.ois Jacob, and Jacques Monod, “The genetic control and cytoplasmic expression of ‘inducibility’ in the synthe-sis of β=galactosidase by E. coli,” Journal of Molecular Biology 1, no. 2 (1959): 165–78.
5 “The genome contains”: Fran.ois Jacob and Jacques Monod, “Genetic regulatory mecha-nisms in the synthesis of proteins,” Journal of Molecular Biology 3, no. 3 (1961): 318–56.
6 1953 paper: Watson and Crick, “Molecular structure of nucleic acids,” 738.
7 “He called it DNA polymerase”: Arthur Kornberg, “Biologic synthesis of deoxyribo-nucleic acid,” Science 131, no. 3412 (1960): 1503–8.
8 “Five years ago”: Ibid.
第九章 基因与生命起源
1 In the beginning: Richard Dawkins, The Selfish Gene (Oxford: Oxford University Press, 1989), 12.
2 Am not I: Nicholas Marsh, William Blake: The Poems (Houndmills, Basingstoke, England: Palgrave, 2001), 56.
3 Lewis studied mutants: Many of these mutants had initially been created by Alfred Sturtevant and Calvin Bridges. Details of the mutants and the relevant genes can be found in Ed Lewis’s Nobel lecture, December 8, 1995.
4 “Is it sin”: Friedrich Max Müller, Memories: A Story of German Love (Chicago: A. C.McClurg, 1902), 20.
5 In Leo Lionni’s classic children’s book: Leo Lionni, Inch by Inch (New York: I. Obolen-sky, 1960).
6 “We propose to identify every cell in the worm”: James F. Crow and W. F. Dove, Per-spectives on Genetics: Anecdotal, Historical, and Critical Commentaries, 1987–1998 (Madison: University of Wisconsin Press, 2000), 176.
7 “like watching a bowl of hundreds of grapes”: Robert Horvitz, author interview, 2012.
8 “There is no history”: Ralph Waldo Emerson, The Journals and Miscellaneous Note-books of Ralph Waldo Emerson, vol. 7, ed. William H. Gilman (Cambridge, MA: Belknap Press of Harvard University Press, 1960), 202.
9 131 extra cells had somehow disappeared: Ning Yang and Ing Swie Goping, Apoptosis (San Rafael, CA: Morgan & Claypool Life Sciences, 2013), “C. elegans and Discovery of the Caspases.”
10 he called it apoptosis: John F. R. Kerr, Andrew H. Wyllie, and Alastair R. Currie, “Apoptosis: A basic biological phenomenon with wide-ranging implications in tis-sue kinetics,” British Journal of Cancer 26, no. 4 (1972): 239.
11 In another mutant, dead cells: This mutant was initially identified by Ed Hedgecock. Robert Horvitz, author interview, 2013.
12 Horvitz and Sulston discovered: J. E. Sulston and H. R. Horvitz, “Post-embryonic cell lineages of the nematode, Caenorhabditis elegans,” Developmental Biology 56. no. 1 (March 1977): 110–56. Also see Judith Kimble and David Hirsh, “The postembry-onic cell lineages of the hermaphrodite and male gonads in Caenorhabditis elegans,” Developmental Biology 70, no. 2 (1979): 396–417.
13 But even natural ambiguity: Judith Kimble, “Alterations in cell lineage following laser ablation of cells in the somatic gonad of Caenorhabditis elegans,” Developmental Bi-ology 87, no. 2 (1981): 286–300.
14 The British way, Brenner wrote: W. J. Gehring, Master Control Genes in Development and Evolution: The Homeobox Story (New Haven, CT: Yale University Press, 1998), 56.
15 began to study the effects of sharp perturbations on cell fates: The method had been pioneered by John White and John Sulston. Robert Horvitz, author interview, 2013.
16 As one scientist described it: Gary F. Marcus, The Birth of the Mind: How a Tiny Num-ber of Genes Creates the Complexities of Human Thought (New York: Basic Books, 2004), “Chapter 4: Aristotle’s Impetus.”
17 The geneticist Antoine Danchin: Antoine Danchin, The Delphic Boat: What Genomes Tell Us (Cambridge, MA: Harvard University Press, 2002).
18 Some genes, Dawkins suggests: Richard Dawkins, A Devil’s Chaplain: Reflections on Hope, Lies, Science, and Love (Boston: Houghton Mifflin, 2003), 105.
第三部分
1 Progress in science depends on new techniques: Sydney Brenner, “Life sentences: De-tective Rummage investigates,” Scientist — the Newspaper for the Science Professional 16, no. 16 (2002): 15.
2 If we are right ..... it is possible to induce: “DNA as the ‘stuff of genes’: The discovery of the transforming principle, 1940–1944,” Oswald T. Avery Collection, National Institutes of Health, http://profiles.nlm.nih.gov/ps/retrieve/Narrative/CC/p-nid/157.
第一章 “交叉互换”
1 A biochemist by training: Details of Paul Berg’s education and sabbatical are from the author’s interview with Paul Berg, 2013; and “The Paul Berg Papers,” Profiles in Science, National Library of Medicine, http://profiles.nlm.nih.gov/CD/.
2 a “piece of bad news wrapped in a protein coat”: M. B. Oldstone, “Rous-Whipple Award Lecture. Viruses and diseases of the twenty-first century,” American Journal of Pathology 143, no. 5 (1993): 1241.
3 Unlike many viruses, Berg learned: David A. Jackson, Robert H. Symons, and Paul Berg, “Biochemical method for inserting new genetic information into DNA of sim-ian virus 40: circular SV40 DNA molecules containing lambda phage genes and the galactose operon of Escherichia coli,” Proceedings of the National Academy of Sciences 69, no. 10 (1972): 2904–09.
4 Peter Lobban, had written a thesis: P. E. Lobban, “The generation of transducing phage in vitro,” (essay for third PhD examination, Stanford University, November 6, 1969).
5 Avery, after all, had boiled it: Oswald T. Avery, Colin M. MacLeod, and Maclyn McCarty. “Studies on the chemical nature of the substance inducing transformation of pneumococcal types: Induction of transformation by a desoxyribonucleic acid fraction isolated from pneumococcus type III,” Journal of Experimental Medicine 79, no. 2 (1944): 137–58.
6 “none of the individual procedures, manipulations, and reagents: P. Berg and J. E. Mertz, “Personal reflections on the origins and emergence of recombinant DNA technology,” Genetics 184, no. 1 (2010): 9–17, doi:10.1534/genetics.109.112144.
7 In the winter of 1970, Berg and David Jackson: Jackson, Symons, and Berg, “Bio-chemical method for inserting new genetic information into DNA of simian virus 40,” Proceedings of the National Academy of Sciences 69, no. 10 (1972): 2904–09.
8 In June 1971, Mertz traveled from Stanford: Kathi E. Hanna, ed., Biomedical politics (Washington, DC: National Academies Press, 1991), 266.
9 “You can stop splitting the atom”: Erwin Chargaff, “On the dangers of genetic med-dling,” Science 192, no. 4243 (1976): 938.
10 “My first reaction was: this was absurd”: “Reaction to Outrage over Recombinant DNA, Paul Berg.” DNA Learning Center, doi:https://www.dnalc.org/view/15017-Reaction -to-outrage-over-recombinant-DNA-Paul-Berg.xhtml.
11 Dulbecco had even offered to drink SV40: Shane Crotty, Ahead of the Curve: David Baltimore’s Life in Science (Berkeley: University of California Press, 2001), 95.
12 “In truth, I knew the risk was little”: Paul Berg, author interview, 2013.
13 “Janet really made the process vastly more efficient”: Ibid.
14 Boyer had arrived in San Francisco in the summer of ’66: Details of the story of Boyer and Cohen come from the following resources: John Archibald, One Plus One Equals One: Symbiosis and the Evolution of Complex Life (Oxford: Oxford University Press, 2014). Also see Stanley N. Cohen et al., “Construction of biologically functional bac-terial plasmids in vitro,” Proceedings of the National Academy of Sciences 70, no. 11 (1973): 3240–44.
15 Late that evening, Boyer: Details of this episode are from several sources including Stanley Falkow, “I’ll Have the Chopped Liver Please, Or How I Learned to Love the Clone,” ASM News 67, no. 11 (2001); Paul Berg, author interview, 2015; Jane Gitsch-ier, “Wonderful life: An interview with Herb Boyer,” PLOS Genetics (September 25, 2009).
第二章 现代音乐
1 Each generation needs a new music: Crick, What Mad Pursuit, 74.
2 People now made music from everything: Richard Powers, Orfeo: A Novel (New York: W. W. Norton, 2014), 330.
3 In the early 1950s, Sanger had solved: Frederick Sanger, “The arrangement of amino acids in proteins,” Advances in Protein Chemistry 7 (1951): 1–67.
4 Frederick Banting, and his medical student: Frederick Banting et al., “The effects of insulin on experimental hyperglycemia in rabbits,” American Journal of Physiology 62, no. 3 (1922).
5 In 1958, Sanger won the Nobel Prize: “The Nobel Prize in Chemistry 1958,” Nobel prize.org, http://www.nobelprize.org/nobel_prizes/chemistry/laureates/1958/.
6 his “lean years”: Frederick Sanger, Selected Papers of Frederick Sanger: With Com-entaries, vol. 1, ed. Margaret Dowding (Singapore: World Scientific, 1996), 11–12.
7 In the summer of 1962, Sanger moved: George G. Brownlee, Fred Sanger — Double Nobel Laureate: A Biography (Cambridge: Cambridge University Press, 2014), 20.
8 On February 24, 1977, Sanger used: F. Sanger et al., “Nucleotide sequence of bacte-riophage Φ174 DNA,” Nature 265, no. 5596 (1977): 687–95, doi:10.1038/265687a0.
9 “The sequence identifies many of the features”: Ibid.
10 In 1977, two scientists working independently: Sayeeda Zain et al., “Nucleotide se-quence analysis of the leader segments in a cloned copy of adenovirus 2 fiber mRNA,” Cell 16, no. 4 (1979): 851–61. Also see “Physiology or Medicine 1993—press release,” Nobelprize.org, http://www.nobelprize.org/nobel_prizes/medicine/laureates/1993 /press.xhtml.
11 The “arsenal of chemical manipulations”: Walter Sullivan, “Genetic decoders plumb-ing the deepest secrets of life processes,” New York Times, June 20, 1977.
12 “Genetic engineering...... implies deliberate”: Jean S. Medawar, Aristotle to Zoos: A Philo-sophical Dictionary of Biology (Cambridge, MA: Harvard University Press, 1985), 37–38.
13 “By learning to manipulate genes experimentally”: Paul Berg, author interview, Sep-tember 2015.
14 T cells sense the presence of invading cells: J. P Allison, B. W. McIntyre, and D..Bloch, “Tumor-specific antigen of murine T-lymphoma defined with monoclonal antibody,” Journal of Immunology 129 (1982): 2293–2300; K. Haskins et al, “The major his-tocompatibility complex-restricted antigen receptor on T cells: I. Isolation with a monoclonal antibody,” Journal of Experimental Medicine 157 (1983): 1149–69.
15 In 1970, David Baltimore and Howard Temin: “Physiology or Medicine 1975—Press Release,” Nobelprize.org. Nobel Media AB 2014. Web. 5 Aug 2015. http://www.nobel prize.org/nobel_prizes/medicine/laureates/1975/press.xhtml.
16 In 1984, this technique was deployed: S. M. Hedrick et al., “Isolation of cDNA clones encoding T cell-specific membrane-associated proteins,” Nature 308 (1984): 149–53; Y. Yanagi et al., “A human T cell-specific cDNA clone encodes a protein having ex-tensive homology to immunoglobulin chains,” Nature 308 (1984): 145–49.
17 “liberated by cloning”: Steve McKnight, “Pure genes, pure genius,” Cell 150, no. 6 (September 14, 2012): 1100–1102.
第三章 海边的爱因斯坦
1 I believe in the inalienable right: Sydney Brenner, “The influence of the press at the Asi-lomar Conference, 1975,” Web of Stories, http://www.webofstories.com/play/sydney .brenner/182;jsessionid=2c147f1c4222a58715e708eabd868e58.
2 In the summer of 1972: Crotty, Ahead of the Curve, 93.
3 “the beginning of a new era”: Herbert Gottweis, Governing Molecules: The Discursive Politics of Genetic Engineering in Europe and the United States (Cambridge, MA: MIT Press, 1998).
4 “Asilomar I,” as Berg would later call: Details of Berg’s account of Asilomar come from conversations and interviews with Paul Berg, 1993 and 2013; and Donald S. Fred-rickson, “Asilomar and recombinant DNA: The end of the beginning,” in Biomedical Politics, ed. Hanna, 258–92.
5 The Asilomar conference produced an important book: Alfred Hellman, Michael Neil Oxman, and Robert Pollack, Biohazards in Biological Research (Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press, 1973).
6 summer of 1973 when Boyer and Cohen: Cohen et al., “Construction of biologically functional bacterial plasmids,” 3240–44.
7 “ ‘safe’ viruses, plasmids and bacteria”: Crotty, Ahead of the Curve, 99.
8 “Well, if we had any guts at all”: Ibid.
9 “Don’t put toxin genes into E. coli”: “The moratorium letter regarding risky experi-ments, Paul Berg,” DNA Learning Center, https://www.dnalc.org/view/15021-The -moratorium-letter-regarding-risky-experiments-Paul-Berg.xhtml.
10 In 1974, the “Berg letter” ran: P. Berg et al., “Potential biohazards of recombinant DNA molecules,” Science 185 (1974): 3034. See also Proceedings of the National Acad-emy of Sciences 71 (July 1974): 2593–94.
11 “are specious”: Herb Boyer interview, 1994, by Sally Smith Hughes, UCSF Oral His-tory Program, Bancroft Library, University of California, Berkeley, http://content .cdlib.org/view?docId=kt5d5nb0zs&brand=calisphere&doc.view=entire_text.
12 On New Year’s Day 1974: John F. Morrow et al., “Replication and transcription of eukaryotic DNA in Escherichia coli,” Proceedings of the National Academy of Sciences 71, no. 5 (1974): 1743–47.
13 Asilomar II — one of the most unusual: Paul Berg et al., “Summary statement of the Asilomar Conference on recombinant DNA molecules,” Proceedings of the National Academy of Sciences 72, no. 6 (1975): 1981–84.
14 “You fucked the plasmid group”: Crotty, Ahead of the Curve, 107.
15 He was promptly accused of: Brenner, “The influence of the press.”
16 “Some people got sick of it all”: Crotty, Ahead of the Curve, 108.
17 “The new techniques, which permit”: Gottweis, Governing Molecules, 88.
18 To mitigate the risks, the document: Berg et al., “Summary statement of the Asilomar Conference,” 1981–84.
19 two-page letter written in August 1939: Albert Einstein, “Letter to Roosevelt, August 2, 1939,” Albert Einstein’s Letters to Franklin Delano Roosevelt, http://hypertext book.com/eworld/einstein.shtml#fi rst.
20 As Alan Waterman, the head: Attributed to Alan T. Waterman, in Lewis Branscomb, “Foreword,” Science, Technology, and Society, a Prospective Look: Summary and Con-clusions of the Bellagio Conference (Washington, DC: National Academy of Sciences, 1976).
21 Nixon, fed up with his scientific advisers: F. A. Long, “President Nixon’s 1973 Reor-ganization Plan No. 1,” Science and Public Affairs 29, no. 5 (1973): 5.
22 “was to demonstrate that scientists were capable”: Paul Berg, author interview, 2013.
23 “The public’s trust was undeniably increased”: Paul Berg, “Asilomar and recombinant DNA,” Nobelprize.org, http://www.nobelprize.org/nobel_prizes/chemistry/laureates /1980/berg-article.xhtml.
24 “Did the organizers and participants”: Ibid.
第四章 “克隆或死亡”
1 If you know the question: Herbert W. Boyer, “Recombinant DNA research at UCSF and commercial application at Genentech: Oral history transcript, 2001,” Online Archive of California, 124, http://www.oac.cdlib.org/search?style=oac4;titlesAZ=r ;idT=UCb11453293x.
2 Any sufficiently advanced technology: Arthur Charles Clark, Profiles of the Future: An Inquiry Into the Limits of the Possible (New York: Harper & Row, 1973).
3 “may completely change the pharmaceutical industry’s”: Doogab Yi, The Recombinant University: Genetic Engineering and the Emergence of Stanford Biotechnology (Chi-cago: University of Chicago Press, 2015), 2.
4 In May, the San Francisco Chronicle ran: “Getting Bacteria to Manufacture Genes,” San Francisco Chronicle, May 21, 1974.
5 Cohen also received: Roger Lewin, “A View of a Science Journalist,” in Recombinant DNA and Genetic Experimentation, ed. J. Morgan and W. J. Whelan (London: Elsevier, 2013), 273.
6 Cohen and Boyer filed a patent: “1972: First recombinant DNA,” Genome.gov, http:// www.genome.gov/25520302.
7 “to commercial ownership of the techniques for cloning all possible DNAs”: P. Berg and J. E. Mertz, “Personal reflections on the origins and emergence of recombinant DNA technology,” Genetics 184, no. 1 (2010): 9–17, doi:10.1534/genetics.109.112144.
8 Swanson came to see Boyer in January 1976: Sally Smith Hughes, Genentech: The Beginnings of Biotech (Chicago: University of Chicago Press, 2011), “Prologue.”
9 Boyer rejected Swanson’s suggestion of HerBob: Felda Hardymon and Tom Nicholas, “Kleiner-Perkins and Genentech: When venture capital met science,” Harvard Business School Case 813-102, October 2012, http://www.hbs.edu/faculty/Pages/item.aspx?num=43569.
10 In 1869, a Berlin medical student: A. Sakula, “Paul Langerhans (1847–1888): A cen-tenary tribute,” Journal of the Royal Society of Medicine 81, no. 7 (1988): 414.
11 Two decades later, two surgeons: J. v. Mering and Oskar Minkowski, “Diabetes mel-litus nach Pankreasexstirpation,” Naunyn-Schmiedeberg’s Archives of Pharmacology 26, no. 5 (1890): 371–87.
12 Ultimately, in 1921, Banting and Best: F. G. Banting et al., “Pancreatic extracts in the treat-ment of diabetes mellitus,” Canadian Medical Association Journal 12, no. 3 (1922): 141.
13 In 1953, after three more decades: Frederick Sanger and E. O. P. Thompson, “The amino-acid sequence in the glycyl chain of insulin. 1. The identification of lower peptides from partial hydrolysates,” Biochemical Journal 53, no. 3 (1953): 353.
14 To synthesize the somatostatin gene: Hughes, Genentech, 59–65.
15 “I thought about it all the time”: “Fierce Competition to Synthesize Insulin, David Goed-del,” DNA Learning Center, https://www.dnalc.org/view/15085-Fierce-competition -to-synthesize-insulin-David-Goeddel.xhtml.
16 “Gilbert was, as he had for many days past”: Hughes, Genentech, 93.
17 460 Point San Bruno Boulevard: Ibid., 78.
18 “You’d go through the back of Genentech’s door”: “Introductory materials,” First Chief Financial Officer at Genentech, 1978–1984, http://content.cdlib.org/view?docId=kt 8k40159r&brand=calisphere&doc.view=entire_text.
19 Gilbert recalled. The UCSF team: Hughes, Genentech, 93.
20 In the summer of 1978, Boyer learned: Payne Templeton, “Harvard group produces insulin from bacteria,” Harvard Crimson, July 18, 1978.
21 August 21, 1978, Goeddel joined: Hughes, Genentech, 91.
22 On October 26, 1982, the US Patent: “A history of firsts,” Genentech: Chronology, http://www.gene.com/media/company-information/chronology.
23 “effectively, the patent claimed”: Luigi Palombi, Gene Cartels: Biotech Patents in the Age of Free Trade (London: Edward Elgar Publishing, 2009), 264.
24 Many newspapers accusingly termed it: “History of AIDS up to 1986,” http://www .avert.org/history-aids-1986.htm.
25 In April, exactly two years: Gilbert C. White, “Hemophilia: An amazing 35-year jour-ney from the depths of HIV to the threshold of cure,” Transactions of the American Clinical and Climatological Association 121 (2010): 61.
26 90 percent would acquire HIV: “HIV/AIDS,” National Hemophilia Foundation,https://www.hemophilia.org/Bleeding-Disorders/Blood-Safety/HIV/AIDS.
27 Of the several million variants: John Overington, Bissan Al-Lazikani, and Andrew Hopkins, “How many drug targets are there?” Nature Reviews Drug Discovery 5 (De-cember 2006): 993–96, “Table 1 | Molecular targets of FDA-approved drugs,” http://www.nature.com/nrd/journal/v5/n12/fig_tab/nrd2199_T1.xhtml.
28 On October 14, 1980, Genentech sold: “Genentech: Historical stock info,” Gene.com,http://www.gene.com/about-us/investors/historical-stock-info.
29 In the summer of 2001, Genentech launched: Harold Evans, Gail Buckland, and David Lefer, They Made America: From the Steam Engine to the Search Engine — Two Cen-turies of Innovators (London: Hachette UK, 2009), “Hebert Boyer and Robert Swan-son: The biotech industry,” 420–31.
第四部分
1 Know then thyself: Alexander Pope, Essay on Man (Oxford: Clarendon Press, 1869).
2 Albany: How have you known: William Shakespeare and Jay L. Halio, The Tragedy of King Lear (Cambridge: Cambridge University Press, 1992), act 5, sc. 3.
第二章 诊所诞生
1 I start with the premise that: Lyon and Gorner, Altered Fates.
2 the New York Times published: John A. Osmundsen, “Biologist hopeful in solving secrets of heredity this year,” New York Times, February 2, 1962.
3 “The most important contribution to medicine”: Thomas Morgan, “The relation of genetics to physiology and medicine,” Nobel Lecture, June 4, 1934, Nobelprize.org, http://www.nobelprize.org/nobel_prizes/medicine/laureates/1933/morgan-lecture. html.
4 In 1947, Victor McKusick: “From ‘musical murmurs’ to medical genetics, 1945–1960,” Victor A. McKusick Papers, NIH, http://profiles.nlm.nih.gov/ps/retrieve/narrative /jq/p-nid/305.
5 McKusick described the case: Harold Jeghers, Victor A. McKusick, and Kermit H..Katz, “Generalized intestinal polyposis and melanin spots of the oral mucosa, lips and dig-its,” New England Journal of Medicine 241, no. 25 (1949): 993–1005, doi:10.1056 /nejm194912222412501.
6 In 1899, Archibald Garrod: Archibald E. Garrod, “A contribution to the study of al-kaptonuria,” Medico-chirurgical Transactions 82 (1899): 367.
7 “The phenomena of obesity”: Archibald E. Garrod, “The incidence of alkaptonuria: A study in chemical individuality,” Lancet 160, no. 4137 (1902): 1616–20, doi:10.1016 /s0140-6736(01)41972-6.
8 for decades, some medical historians: Harold Schwartz, Abraham Lincoln and the Marfan Syndrome (Chicago: American Medical Association, 1964).
9 By the mid-1980s, McKusick and his students: J. Amberger et al., “McKusick’s Online Mendelian Inheritance in Man,” Nucleic Acids Research 37 (2009): (database issue) D793–D796, fig. 1 and 2, doi:10.1093/nar/gkn665.
10 By the twelfth edition of his book: “Beyond the clinic: Genetic studies of the Amish and little people, 1960–1980s,” Victor A. McKusick Papers, NIH, http://profiles.nlm .nih.gov/ps/retrieve/narrative/jq/p-nid/307.
11 “The imperfect is our paradise”: Wallace Stevens, The Collected Poems of Wallace Ste-vens (New York: Alfred A. Knopf, 1954), “The Poems of Our Climate,” 193–94.
12 In November 1961: Fantastic Four #1 (New York: Marvel Comics, 1961), http://marvel .com/comics/issue/12894/fantastic_four_1961_1.
13 “a fantastic amount of radioactivity”: Stan Lee et al., Marvel Masterworks: The Amazing Spider-Man (New York: Marvel Publishing, 2009), “The Secrets of Spider-Man.”
14 the X-Men, launched in September 1963: Uncanny X-Men #1 (New York: Marvel Comics, 1963), http://marvel.com/comics/issue/12413/uncanny_x-men_1963_1.
15 in the spring of 1966: Alexandra Stern, Telling Genes: The Story of Genetic Counseling in America (Baltimore: Johns Hopkins University Press, 2012), 146.
16 Fetal cells from the amnion: Leo Sachs, David M. Serr, and Mathilde Danon, “Analy-sis of amniotic fluid cells for diagnosis of foetal sex,” British Medical Journal 2, no. 4996 (1956): 795.
17 On May 31, 1968: Carlo Valenti, “Cytogenetic diagnosis of down’s syndrome in utero,” Journal of the American Medical Association 207, no. 8 (1969): 1513, doi:10.1001 /jama.1969.03150210097018.
18 In September 1969: Details of McCorvey’s life are from Norma McCorvey with Andy Meisler, I Am Roe: My Life, Roe v. Wade, and Freedom of Choice (New York: Harper-Collins, 1994).
19 “with dirty instruments scattered around the room”: Ibid.
20 Blackmun wrote: Roe v. Wade, Legal Information Institute, https://www.law.cornell .edu/supremecourt/text/410/113.
21 “The individual’s [i.e., mother’s]”: Alexander M. Bickel, The Morality of Consent (New Haven: Yale University Press, 1975), 28.
22 control of the fetal genome to medicine: Jeffrey Toobin, “The people’s choice,” New Yorker, January 28, 2013, 19–20.
23 In some states: H. Hansen, “Brief reports decline of Down’s syndrome after abortion reform in New York State,” American Journal of Mental Deficiency 83, no. 2 (1978): 185–88.
24 By the mid-1970s: Daniel J. Kevles, In the Name of Eugenics: Genetics and the Uses of Human Heredity (New York: Alfred A. Knopf, 1985), 257.
25 “Tiny fault after tiny fault”: M. Susan Lindee, Moments of Truth in Genetic Medicine (Baltimore: Johns Hopkins University Press, 2005), 24.
26 McKusick published a new edition: V. A. McKusick and R. Claiborne, eds., Medical Genetics (New York: HP Publishing, 1973).
27 Joseph Dancis, the pediatrician, wrote: Ibid., Joseph Dancis, “The prenatal detection of hereditary defects,” 247.
28 In June 1969, a woman named Hetty Park: Mark Zhang, “Park v. Chessin (1977),” Th e Embryo Project Encyclopedia, January 31, 2014, https://embryo.asu.edu/pages/park -v-chessin-1977.
29 One commentator noted, “The court asserted”: Ibid.
第三章 “干预,干预,再干预”
1 After millennia in which most people: Gerald Leach, “Breeding Better People,” Ob-server, April 12, 1970.
2 No newborn should be declared human: Michelle Morgante, “DNA scientist Francis Crick dies at 88,” Miami Herald, July 29, 2004.
3 “The old eugenics was limited”: Lily E. Kay, The Molecular Vision of Life: Caltech, the Rockefeller Foundation, and the Rise of the New Biology (New York: Oxford Univer-sity Press, 1993), 276.
4 In 1980, Robert Graham: David Plotz, “Darwin’s Engineer,” Los Angeles Times, June 5, 2005, http://www.latimes.com/la-tm-spermbank23jun05-story.xhtml#page=1.
5 The physicist William Shockley: Joel N. Shurkin, Broken Genius: The Rise and Fall of William Shockley, Creator of the Electronic Age (London: Macmillan, 2006), 256.
6 “cruel, blundering and inefficient”: Kevles, In the Name of Eugenics, 263.
7 “moral obligation of the medical profession”: Departments of Labor and Health, Edu-cation, and Welfare Appropriations for 1967 (Washington, DC: Government Printing Office, 1966), 249.
8 “Near the end of his terms of office”: Victor McKusick, in Legal and Ethical Issues Raised by the Human Genome Project: Proceedings of the Conference in Houston, Texas, March 7–9, 1991, ed. Mark A. Rothstein (Houston: University of Houston, Health Law and Policy Institute, 1991).
9 “needle in a haystack”: Matthew R. Walker and Ralph Rapley, Route Maps in Gene Technology (Oxford: Blackwell Science, 1997), 144.
第四章 基因定位
1 Glory be to God for dappled things: W. H. Gardner, Gerard Manley Hopkins: Poems and Prose (Taipei: Shu lin, 1968), “Pied Beauty.”
2 We suddenly came upon two women: George Huntington, “Recollections of Hunting-ton’s chorea as I saw it at East Hampton, Long Island, during my boyhood,” Journal of Nervous and Mental Disease 37 (1910): 255–57.
3 In 1978, two geneticists: Robert M. Cook-Deegan, The Gene Wars: Science, Politics, and the Human Genome (New York: W. W. Norton, 1994), 38.
4 By studying Mormons in Utah: K. Kravitz et al., “Genetic linkage between hereditary hemochromatosis and HLA,” American Journal of Human Genetics 31, no. 5 (1979):601.
6 When Botstein and Davis had first discovered: David Botstein et al., “Construction of a genetic linkage map in man using restriction fragment length polymorphisms,” American Journal of Human Genetics 32, no. 3 (1980): 314.
7 The poet Louis MacNeice once wrote: Louis MacNeice, “Snow,” in The New Cambridge Bibliography of English Literature, vol. 3, ed. George Watson (Cambridge: Cambridge University Press, 1971).
8 “We can give you markers”: Victor K. McElheny, Drawing the Map of Life: Inside the Human Genome Project (New York: Basic Books, 2010), 29.
9 “We describe a new basis”: Botstein et al., “Construction of a genetic linkage map,” 314.
10 “like watching a giant puppet show”: N. Wexler, “Huntington’s Disease: Advocacy Driving Science,” Annual Review of Medicine, no. 63 (2012): 1–22.
11 life devolves into a “grim roulette”: N. S. Wexler, “Genetic ‘Russian Roulette’: The Expe-rience of Being At Risk for Huntington’s Disease,” in Genetic Counseling: Psychological Dimensions, ed. S. Kessler (New York, Academic Press, 1979).
12 “waiting game for the onset of symptoms”: “New discovery in fight against Hunting-ton’s disease,” NUI Galway, February 22, 2012, http://www.nuigalway.ie/about-us /news-and-events/news-archive/2012/february2012/new-discovery-in-fight -against-huntingtons-disease-1.xhtml.
13 “I don’t know the point where”: Gene Veritas, “At risk for Huntington’s disease,” Sep-tember 21, 2011, http://curehd.blogspot.com/2011_09_01_archive.xhtml.
14 Milton Wexler, Nancy’s father, a clinical psychologist: Details of the Wexler family story came from Alice Wexler, Mapping Fate: A Memoir of Family, Risk, and Genetic Research (Berkeley: University of California Press, 1995); Lyon and Gorner, Altered Fates; and “Makers profile: Nancy Wexler, neuropsychologist & president, Hereditary Disease Foundation,” MAKERS: The Largest Video Collection of Women’s Stories, http://www.makers.com/nancy-wexler.
15 “Each one of you has a one-in-two”: Ibid.
16 That year, Milton Wexler launched: “History of the HDF,” Hereditary Disease Foun-dation, http://hdfoundation.org/history-of-the-hdf/.
17 In one nursing home: Wexler, Nancy, “Life In The Lab” Los Angeles Times Magazine, February 10, 1991.
18 Leonore died on May 14, 1978: Associated Press, “Milton Wexler; Promoted Hun-tington’s Research,” Washington Post, March 23, 2007, http://www.washingtonpost .com/wp-dyn/content/article/2007/03/22/AR2007032202068.xhtml.
19 In October 1979: Wexler, Mapping Fate , 177.
20 “There have been a few times in my life”: Ibid., 178.
21 At first glance, a visitor to Barranquitas: Description of Barranquitas from “Nancy Wexler in Venezuela Huntington’s disease,” BBC, 2010, YouTube, https://www.you tube.com/watch?v=D6LbkTW8fDU.
22 When the Venezuelan neurologist Américo Negrette: M. S. Okun and N. Thommi, “Américo Negrette (1924 to 2003): Diagnosing Huntington disease in Venezuela,” Neurology 63, no. 2 (2004): 340–43, doi:10.1212/01.wnl.0000129827.16522.78.
23 In some parts: for data on prevalence, see http://www.cmmt.ubc.ca/research/ diseases/ huntingtons/HD_Prevalence.
24 two copies of the mutated Huntington’s disease gene — i.e., “homozygotes”: see “What Is a Homozygote?”, Nancy Wexler, Gene Hunter: The Story of Neuropsychologist Nancy Wexler, (Women’s Adventures in Science, Joseph Henry Press), October 30, 2006: 51.
25 “It was a clash of total bizarreness”: Jerry E. Bishop and Michael Waldholz, Genome: The Story of the Most Astonishing Scientific Adventure of Our Time (New York: Simon & Schuster, 1990), 82–86.
26 They assiduously collected: This pedigree would eventually grow to contain more than 18,000 individuals over 10 generations. All have descended from a common ancestor, a woman named Maria Concepión — a strangely apt name — who conceived the first family that carried the abnormal gene to these villages in the nineteenth century.
27 Here too the illness: The American family was not big enough to prove linkage, but the Venezuelan family was. By adding the two together, the scientists could prove the existence of a DNA marker traveling with HD. See Gusella JF, Wexler NS, Conneally PM, Naylor SL, Anderson MA, Tanzi RE, Watkins PC, Ottina K, Wallace MR, Sak-aguchi AY, Young AB, Shoulson I, Bonilla E, and Martin JB. “A Polymorphic DNA Marker Genetically Linked to Huntington’s Disease.” Nature, 1983 Nov 17–23; 306 (5940): 234–8.
28 In August 1983, Wexler, Gusella, and Conneally: James F. Gusella et al., “A polymor-phic DNA marker genetically linked to Huntington’s disease,” Nature 306, no. 5940 (1983): 234–38, doi:10.1038/306234a0.
29 The candidate gene had been found: Karl Kieburtz et al., “Trinucleotide repeat length and progression of illness in Huntington’s disease,” Journal of Medical Genetics 31, no. 11 (1994): 872–74.
30 “We’ve got it, we’ve got it”: Lyon and Gorner, Altered Fates, 424.
31 A remarkable feature of the inheritance: Nancy S. Wexler, “Venezuelan kindreds re-veal that genetic and environmental factors modulate Huntington’s disease age of onset,” Proceedings of the National Academy of Sciences 101, no. 10 (2004): 3498–503.
32 In 1857, a Swiss almanac: The Almanac of Children’s Songs and Games from Switzer-land (Leipzig: J. J. Weber, 1857).
33 “Inside the pericardium”: “The History of Cystic Fibrosis,” cysticfibrosismedicine .com, http://www.cfmedicine.com/history/earlyyears.htm.
34 In 1985, Lap-Chee Tsui: Lap-Chee Tsui et al., “Cystic fibrosis locus defined by a ge-netically linked polymorphic DNA marker,” Science 230, no. 4729 (1985): 1054–57.
35 By the spring of 1989, Collins: Wanda K. Lemna et al., “Mutation analysis for hetero-zygote detection and the prenatal diagnosis of cystic fibrosis,” New England Journal of Medicine 322, no. 5 (1990): 291–96.
36 Over the last decade: V. Scotet et al., “Impact of public health strategies on the birth prevalence of cystic fibrosis in Brittany, France,” Human Genetics 113, no. 3 (2003): 280–85.
37 In 1993, a New York hospital: D. Kronn, V. Jansen, and H. Ostrer, “Carrier screening for cystic fibrosis, Gaucher disease, and Tay-Sachs disease in the Ashkenazi Jewish population: The first 1,000 cases at New York University Medical Center, New York, NY,” Archives of Internal Medicine 158, no. 7 (1998): 777–81.
38 As the physicist and historian Evelyn Fox Keller: Elinor S. Shaffer, ed., The Third Cul-ture: Literature and Science, vol. 9 (Berlin: Walter de Gruyter, 1998), 21.
39 “a new horizon in the history of man”: Robert L. Sinsheimer, “The prospect for de-signed genetic change,” American Scientist 57, no. 1 (1969): 134–42.
40 “Some may smile and may feel”: Jay Katz, Alexander Morgan Capron, and Eleanor Swift Glass, Experimentation with Human Beings: The Authority of the Investigator, Subject, Professions, and State in the Human Experimentation Process (New York: Russell Sage Foundation, 1972), 488.
41 “no beliefs, no values, no institutions”: John Burdon Sanderson Haldane, Daedalus or Science and the Future (New York: E. P. Dutton, 1924), 48.
第五章 基因组时代
1 Our ability to read out this sequence: Sulston and Ferry, Common Thread, 264.
2 In 1977, when Fred Sanger had sequenced: Cook-Deegan, The Gene Wars, 62.
3 The human genome contains 3,095,677,412 base pairs: “OrganismView: Search or-ganisms and genomes,” CoGe: OrganismView, https://genomevolution.org/coge //organismview.pl?gid=7029.
4 BRCA1, was only identified in 1994: Yoshio Miki et al., “A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1,” Science 266, no. 5182 (1994):66–71.
5 such as chromosome jumping: F. Collins et al., “Construction of a general human chromosome jumping library, with application to cystic fibrosis,” Science 235, no. 4792 (1987): 1046–49, doi:10.1126/science.2950591.
6 “There was no shortage of exceptionally clever”: Mark Henderson, “Sir John Sulston and the Human Genome Project,” Wellcome Trust, May 3, 2011, http://genome.well come.ac.uk/doc_wtvm051500.xhtml.
7 “But even with the immense power”: Departments of Labor, Health and Human Ser-vices, Education, and Related Agencies Appropriations for 1996: Hearings before a Subcommittee of the Committee on Appropriations, House of Representatives, One Hundred Fourth Congress, First Session (Washington, DC: Government Printing Of-fice, 1995), http://catalog.hathitrust.org/Record/003483817.
8 in 1872, Hilário de Gouvêa, a Brazilian ophthalmologist: Alvaro N. A. Monteiro and Ricardo Waizbort, “The accidental cancer geneticist: Hilário de Gouvêa and heredi-tary retinoblastoma,” Cancer Biology & Therapy 6, no. 5 (2007): 811–13, doi:10.4161 /cbt.6.5.4420.
9 Vogelstein had already discovered that cancers: Bert Vogelstein and Kenneth W. Kinzler, “The multistep nature of cancer,” Trends in Genetics 9, no. 4 (1993): 138–41.
10 Schizophrenia, in particular, sparked a furor: Valrie Plaza, American Mass Murderers (Raleigh, NC: Lulu Press, 2015), “Chapter 57: James Oliver Huberty.”
11 NAS study found that identical twins possessed: “Schizophrenia in the National Academy of Sciences–National Research Council Twin Registry: A 16-year up-date,” American Journal of Psychiatry 140, no. 12 (1983): 1551–63, doi:10.1176/ ajp.140.12.1551.
12 An earlier study, published by: D. H. O’Rourke et al., “Refutation of the general single-locus model for the etiology of schizophrenia,” American Journal of Human Genetics 34, no. 4 (1982): 630.
13 For identical twins with the severest form: Peter McGuffin et al., “Twin concordance for operationally defined schizophrenia: Confirmation of familiality and heritabil-ity,” Archives of General Psychiatry 41, no. 6 (1984): 541–45.
14 Populist anxieties about genes, mental illness: James Q. Wilson and Richard J. Herrn-stein, Crime and Human Nature: The Definitive Study of the Causes of Crime (New York: Simon & Schuster, 1985).
15 “bad friends, bad neighborhoods, bad labels”: Matt DeLisi, “James Q. Wilson,” in Fift y Key Thinkers in Criminology, ed. Keith Hayward, Jayne Mooney, and Shadd Maruna (London: Routledge, 2010), 192–96.
16 another meeting of scientists was called to evaluate whether: Doug Struck, “The Sun (1837–1988),” Baltimore Sun, February 2, 1986, 79.
17 The most important technical breakthrough: Kary Mullis, “Nobel Lecture: The poly-merase chain reaction,” December 8, 1993, Nobelprize.org, http://www.nobelprize .org/nobel_prizes/chemistry/laureates/1993/mullis-lecture.xhtml.
18 To sequence all 3 billion base pairs: Sharyl J. Nass and Bruce Stillman, Large-Scale Biomedical Science: Exploring Strategies for Future Research (Washington, DC: Na-tional Academies Press, 2003), 33.
19 “The only way to give Rufus a life”: McElheny, Drawing the Map of Life, 65.
20 By 1989 after several: “About NHGRI: A Brief History and Timeline,” Genome.gov, http://www.genome.gov/10001763.
21 In January 1989, a twelve-member council: McElheny, Drawing the Map of Life, 89.
22 “We are initiating an unending study”: Ibid.
23 On January 28, 1983: J. David Smith, “Carrie Elizabeth Buck (1906–1983),” En-cyclopedia Virginia, http://www.encyclopediavirginia.org/Buck_Carrie_Elizabeth _1906–1983.
24 Vivian Dobbs — the child who: Ibid.
第六章 基因地理学家
1 So Geographers in Afric-maps: Jonathan Swift and Thomas Roscoe, The Works of Jonathan Swift, DD: With Copious Notes and Additions and a Memoir of the Author, vol. 1 (New York: Derby, 1859), 247–48.
2 More and more, the Human Genome Project: Justin Gillis, “Gene-mapping contro-versy escalates; Rockville firm says government officials seek to undercut its effort,” Washington Post, March 7, 2000.
3 Craig Venter, proposed a shortcut: L. Roberts, “Gambling on a Shortcut to Genome Sequencing,” Science 252, no. 5013 (1991): 1618–19.
4 In 1986, he had heard of: Lisa Yount, A to Z of Biologists (New York: Facts On File, 2003), 312.
5 “my future in a crate”: J. Craig Venter, A Life Decoded: My Genome, My Life (New York: Viking, 2007), 97.
6 the NIH technology transfer office contacted: R. Cook-Deegan and C. Heaney, “Pat-ents in genomics and human genetics,” Annual Review of Genomics and Human Ge-netics 11 (2010): 383–425, doi:10.1146/annurev-genom-082509-141811.
7 In 1984, Amgen had filed a patent: Edmund L. Andrews, “Patents; Unaddressed Question in Amgen Case,” New York Times, March 9, 1991.
8 “Patents (or so I had believed) are designed”: Sulston and Ferry, Common Thread, 87.
9 “It’s a quick and dirty land grab”: Pamela R. Winnick, A Jealous God: Science’s Cru-sade against Religion (Nashville, TN: Nelson Current, 2005), 225.
10 “Could you patent an elephant”: Eric Lander, author interview, 2015.
11 Walter Bodmer, the English geneticist, warned: L. Roberts, “Genome Patent Fight Erupts,” Science 254, no. 5029 (1991): 184–86.
12 Institute for Genomic Research: Venter, Life Decoded, 153.
13 Working with a new ally, Hamilton Smith: Hamilton O. Smith et al., “Frequency and distribution of DNA uptake signal sequences in the Haemophilus influenzae Rd ge-nome,” Science 269, no. 5223 (1995): 538–40.
14 “The final [paper] took forty drafts”: Venter, Life Decoded, 212.
15 “thrilled by the first glimpse”: Ibid., 219.
16 “What if you took a word”: Eric Lander, author interview, October 2015.
17 “The real challenge of the Human Genome Project”: Ibid.
18 TIGR had been set up: HGS was launched by William Haseltine, a former Harvard professor, who hoped to use genomics to discover novel drugs.
19 On May 12,1998,the Washington Post:Justin Gills and Rick Weiss," Private firm aims to beat government to gene map,"Washington Post,May 12,1998,http://www.washingtonpost.com/archive/politics/1998/05/12/private-firm-aims-to-beat-government-to-gene-map/bfd5a322-781e-4b71-b939-5e7e6a8ebbdb/.
20 In December 1998: “1998: Genome of roundworm C. elegans sequenced,” Genome .gov, http://www.genome.gov/25520394.
21 A gene called ceh-13, for instance: Borbála Tihanyi et al., “The C. elegans Hox gene ceh-13 regulates cell migration and fusion in a non-colinear way. Implications for the early evolution of Hox clusters,” BMC Developmental Biology 10, no. 78 (2010), doi:10.1186/1471-213X-10-78.
22 The C. elegans genome — published to universal: Science 282, no. 5396 (1998): 1945–2140.
23 its one-billionth human base pair: David Dickson and Colin Macilwain, “ ‘It’s a G’: The one-billionth nucleotide,” Nature 402, no. 6760 (1999): 331.
24 it had sequenced the genome of the fruit fly: Declan Butler, “Venter’s Drosophila ‘suc-cess’ set to boost human genome efforts,” Nature 401, no. 6755 (1999): 729–30.
25 In March 2000, Science published: “The Drosophila genome,” Science 287, no. 5461 (2000): 2105–364.
26 Of the 289 human genes known to be: David N. Cooper, Human Gene Evolution (Ox-ford: BIOS Scientific Publishers, 1999), 21.
27 177 genes: William K. Purves, Life: The Science of Biology (Sunderland, MA: Sinauer Associates, 2001), 262.
28 “a man like me”: Marsh, William Blake, 56.
29 “The lesson is that the complexity”: Quote from the director of the Berkeley Droso-phila Genome Project, Gerry Rubin, in Robert Sanders, “UC Berkeley collaboration with Celera Genomics concludes with publication of nearly complete sequence of the genome of the fruit fly,” press release, UC Berkeley, March 24, 2000, http://www .berkeley.edu/news/media/releases/2000/03/03-24-2000.xhtml.
30 “between a human and a nematode worm”: The Age of the Genome, BBC Radio 4, http://www.bbc.co.uk/programmes/b00ss2rk.
31 “Fix this!”: James Shreeve, The Genome War: How Craig Venter Tried to Capture the Code of Life and Save the World (New York: Alfred A. Knopf, 2004), 350.
32 That initial meeting in Ari Patrinos’s basement: For details of this story see ibid. Also see Venter, Life Decoded, 97.
33 At 10:19 a.m. on the morning of June 26: “June 2000 White House Event,” Genome .gov, https://www.genome.gov/10001356.
34 Clinton spoke first, comparing the map: “President Clinton, British Prime Minister Tony Blair deliver remarks on human genome milestone,” CNN.com Transcripts, June 26, 2000.
35 “My greatest success”: Shreeve, Genome War, 360.
36 Lander recruited yet another team of scientists: McElheny, Drawing the Map of Life, 163.
37 “In the history of scientific writing since the 1600s”: Eric Lander, author interview, Oc-tober 2015.
38 “genome tossed salad”: Shreeve, Genome War, 364.
第七章 人之书(共23卷)
1 It encodes about 20,687 genes in total: Details of the Human Genome Project come from “Human genome far more active than thought,” Wellcome Trust, Sanger In-stitute, September 5, 2012, http://www.sanger.ac.uk/about/press/2012/120905.xhtml; Venter, Life Decoded; and Committee on Mapping and Sequencing the Human Ge-nome, Mapping and Sequencing the Human Genome (Washington, DC: National Academy Press, 1988), http://www.nap.edu/read/1097/chapter/1.
第五部分
1 How nice it would be: Lewis Carroll, Alice in Wonderland (New York: W. W. Norton, 2013).
第一章 “不分彼此”
1 “So, We’s the Same”: Kathryn Stockett, The Help (New York: Amy Einhorn Books/ Putnam, 2009), 235.
2 We got to have a re-vote: “Who is blacker Charles Barkley or Snoop Dogg,” YouTube, January 19, 2010, https://www.youtube.com/watch?v=yHfX-11ZHXM.
3 What have I in common with Jews?: Franz Kafka, The Basic Kafka (New York: Pocket Books, 1979), 259.
4 This mirror writing can result: Everett Hughes, “The making of a physician: General statement of ideas and problems,” Human Organization 14, no. 4 (1955): 21–25.
5 “as absurd as defining the organs”: Allen Verhey, Nature and Altering It (Grand Rap-ids, MI: William B. Eerdmans, 2010), 19. Also see Matt Ridley, Genome: The Auto-biography of a Species In 23 Chapters (New York: Harper Collins, 1999), 54.
6 “Encoded in the DNA sequence are fundamental”: Committee on Mapping and Se-quencing, Mapping and Sequencing, 11.
7 “Had Mr. Darwin or his followers furnished”: Louis Agassiz, “On the origins of spe-cies,” American Journal of Science and Arts 30 (1860): 142–54.
8 In 1848, stone diggers in a limestone quarry: Douglas Palmer, Paul Pettitt, and Paul G. Bahn, Unearthing the Past: The Great Archaeological Discoveries That Have Changed History (Guilford, CT: Globe Pequot, 2005), 20.
9 “an early time in the evolution of man”: Popular Science Monthly 100 (1922).
10 Allan Wilson began to use genetic tools: Rebecca L. Cann, Mork Stoneking, and Allan C. Wilson, “Mitochondrial DNA and human evolution,” Nature 325 (1987): 31–36.
11 The genes lodged within mitochondria: See Chuan Ku et al., “Endosymbiotic origin and differential loss of eukaryotic genes,” Nature 524 (2015): 427–32.
12 First, when Wilson measured the overall diversity: Thomas D. Kocher et al., “Dy-namics of mitochondrial DNA evolution in animals: Amplification and sequencing with conserved primers,” Proceedings of the National Academy of Sciences 86, no. 16 (1989): 6196–200.
13 By 1991, Wilson could use his method: David M. Irwin, Thomas D. Kocher, and Allan C. Wilson, “Evolution of the cytochrome-b gene of mammals,” Journal of Molecular Evolution 32, no. 2 (1991): 128–44; Linda Vigilant et al., “African populations and the evolution of human mitochondrial DNA,” Science 253, no. 5027 (1991): 1503–7; and Anna Di Rienzo and Allan C. Wilson, “Branching pattern in the evolutionary tree for human mitochondrial DNA,” Proceedings of the National Academy of Sci-ences 88, no. 5 (1991): 1597–601.
14 In November 2008, a seminal study: Jun Z. Li et al., “Worldwide human relationships inferred from genome-wide patterns of variation,” Science 319, no. 5866 (2008): 1100–104.
15 “You get less and less variation”: John Roach, “Massive genetic study supports ‘out of Africa’ theory,” National Geographic News, February 21, 2008.
16 The oldest human populations: Lev A. Zhivotovsky, Noah A. Rosenberg, and Mar-cus W. Feldman, “Features of evolution and expansion of modern humans, inferred from genomewide microsatellite markers,” American Journal of Human Genetics 72, no. 5 (2003): 1171–86.
17 The “youngest” humans: Noah Rosenberg et al., “Genetic structure of human popula-tions,” Science 298, no. 5602 (2002): 2381–85. A map of human migrations can be found in L. L. Cavalli-Sforza and Marcus W. Feldman, “The application of molecular genetic approaches to the study of human evolution,” Nature Genetics 33 (2003): 266–75.
18 It is called the Out of Africa theory: For the origin of humans in Southern Africa, see Brenna M. Henn et al., “Hunter-gatherer genomic diversity suggests a southern Afri-can origin for modern humans,” Proceedings of the National Academy of Sciences 108, no. 13 (2011): 5154–62. Also see Brenna M. Henn, L. L. Cavalli-Sforza, and Marcus W. Feldman, “The great human expansion,” Proceedings of the National Academy of Sciences 109, no. 44 (2012): 17758–64.
19 “Sexual intercourse began”: Philip Larkin, “Annus Mirabilis,” High Windows.
20 “In terms of modern humans”: Christopher Stringer, “Rethinking ‘out of Africa,’ ” editorial, Edge, November 12, 2011, http://edge.org/conversation/rethinking-out-of -africa.
21 Others have proposed: H. C. Harpending et al., “Genetic traces of ancient demogra-phy,” Proceedings of the National Academy of Sciences 95 (1998): 1961–67; R. Gonser et al., “Microsatellite mutations and inferences about human demography,” Genetics 154 (2000): 1793–1807; A. M. Bowcock et al., “High resolution of human evolution-ary trees with polymorphic microsatellites,” Nature 368 (1994): 455–57; and C. Dib et al., “A comprehensive genetic map of the human genome based on 5,264 micro-satellites,” Nature 380 (1996): 152–54.
22 The most recent estimates suggest that: Anthony P. Polednak, Racial and Ethnic Dif-ferences in Disease (Oxford: Oxford University Press, 1989), 32–33.
23 As Marcus Feldman and Richard Lewontin put it: M. W. Feldman and R. C. Lewontin, “Race, ancestry, and medicine,” in Revisiting Race in a Genomic Age, ed. B. A. Koenig, S. S. Lee, and S. S. Richardson (New Brunswick, NJ: Rutgers University Press, 2008). Also see Li et al., “Worldwide human relationships inferred from genome-wide pat-terns of variation,” 1100–104.
24 In his monumental study on human genetics: L. Cavalli-Sforza, Paola Menozzi, and Alberto Piazza, The History and Geography of Human Genes (Princeton, NJ: Princeton University Press, 1994), 19.
25 “So, we’s the same”: Stockett, Help.
26 In 1994, the very year: Cavalli-Sforza, Menozzi, and Piazza, The History and Geography.
27 a very different kind of book about: Richard Herrnstein and Charles Murray, The Bell Curve (New York: Simon & Schuster, 1994).
28 “a flame-throwing treatise on class”: “The ‘Bell Curve’ agenda,” New York Times, Oc-tober 24, 1994.
29 his 1985 book, Crime and Human Nature: Wilson and Herrnstein. Crime and Human Nature.
30 In 1904, Charles Spearman, a British statistician: Charles Spearman, “ ‘General Intel-ligence,’ objectively determined and measured,” American Journal of Psychology 15, no. 2 (1904): 201–92.
31 Recognizing that this measurement varied with age: The concept of IQ was initially developed by William Stern, the German psychologist.
32 Developmental psychologists such as Louis Thurstone: Louis Leon Thurstone, “The absolute zero in intelligence measurement,” Psychological Review 35, no. 3 (1928): 175; and L. Thurstone, “Some primary abilities in visual thinking,” Proceedings of the American Philosophical Society (1950): 517–21. Also see Howard Gardner and Thomas Hatch, “Educational implications of the theory of multiple intelligences,” Educational Researcher 18, no. 8 (1989): 4–10.
33 Drawing heavily from an earlier article: Herrnstein and Murray, Bell Curve, 284.
34 In the 1950s, a series of reports: George A. Jervis, “The mental deficiencies,” Annals of the American Academy of Political and Social Science (1953): 25–33. Also see Otis Dudley Duncan, “Is the intelligence of the general population declining?” American Sociological Review 17, no. 4 (1952): 401–7.
35 They limited the tests to only those administered after 1960: The particular variables as-sessed by Murray and Herrnstein deserve mention. They wondered whether a deep dis-enchantment with tests and scores might pervade African-Americans, making them reluctant to engage with IQ tests. But subtle experiments to measure and excise any such “test disengagement” could not erase the 15-point difference. They considered the possi-bility that the tests were culturally biased (perhaps the most notorious example, borrowed from an SAT examination, asks students to consider the analogy “oarsmen:regatta.” It hardly takes an expert on language and culture to know that most inner-city children, black or white, might have little knowledge of what a regatta is, let alone what an oars-man does in one). Yet even after removing such culture-specific and class-specific items from the tests, Murray and Herrnstein wrote, a difference of 15-odd points remained.
36 In the 1990s, the psychologist Eric Turkheimer: Eric Turkheimer, “Consensus and controversy about IQ,” Contemporary Psychology 35, no. 5 (1990): 428–30. Also see Eric Turkheimer et al., “Socioeconomic status modifies heritability of IQ in young children,” Psychological Science 14, no. 6 (2003): 623–28.
37 In a blistering article written: Stephen Jay Gould, “Curve ball,” New Yorker, Novem-ber 28, 1994, 139–40.
38 The Harvard historian Orlando Patterson: Orlando Patterson, “For Whom the Bell Curves,” in The Bell Curve Wars: Race, Intelligence, and the Future of America, ed. Steven Fraser (New York: Basic Books, 1995).
39 black children do worse at tests: William Wright, Born That Way: Genes, Behavior, Personality (London: Routledge, 2013), 195.
40 a fact buried so inconspicuously: Herrnstein and Murray, Bell Curve, 300–305.
41 Sandra Scarr and Richard Weinberg in 1976: Sandra Scarr and Richard A. Weinberg, “Intellectual similarities within families of both adopted and biological children,” In-telligence 1, no. 2 (1977): 170–91.
42 “When nobody read”: Alison Gopnik, “To drug or not to drug,” Slate, February 22, 2010, http://www.slate.com/articles/arts/books/2010/02/to_drug_or_not_to _drug.2.xhtml.
第二章 遗传算法
1 For several decades, anthropology has participated: Paul Brodwin, “Genetics, identity, and the anthropology of essentialism,” Anthropological Quarterly 75, no. 2 (2002): 323–30.
2 “Sex is not inherited”: Frederick Augustus Rhodes, The Next Generation (Boston: R..G. Badger, 1915), 74.
3 “The egg, as far as sex is concerned”: Editorials, Journal of the American Medical As-sociation 41 (1903): 1579.
4 She termed it the sex chromosome: Nettie Maria Stevens, Studies in Spermatogenesis: A Comparative Study of the Heterochromosomes in Certain Species of Coleoptera, He-miptera and Lepidoptera, with Especial Reference to Sex Determination (Baltimore: Carnegie Institution of Washington, 1906).
5 “punk meets new romantic”: Kathleen M. Weston, Blue Skies and Bench Space: Ad-ventures in Cancer Research (Cold Spring Harbor, NY: Cold Spring Harbor Labora-tory Press, 2012), “Chapter 8: Walk This Way.”
6 In 1955, Gerald Swyer, an English endocrinologist: G. I. M. Swyer, “Male pseudoher-maphroditism: A hitherto undescribed form,” British Medical Journal 2, no. 4941 (1955): 709.
7 Page called the gene ZFY: Ansbert Schneider-G.dicke et al., “ZFX has a gene struc-ture similar to ZFY, the putative human sex determinant, and escapes X inactiva-tion,” Cell 57, no. 7 (1989): 1247–58.
8 intronless gene called SRY: Philippe Berta et al., “Genetic evidence equating SRY and the testis-determining factor,” Nature 348, no. 6300 (1990): 448–50.
9 the mice developed as anatomically male: Ibid.; John Gubbay et al., “A gene mapping to the sex-determining region of the mouse Y chromosome is a member of a novel fam-ily of embryonically expressed genes,” Nature 346 (1990): 245–50; Ralf J. J.ger et.al., “A human XY female with a frame shift mutation in the candidate testis- determining gene SRY gene,” Nature 348 (1990): 452–54; Peter Koopman et al., “Expression of a candidate sex-determining gene during mouse testis differentiation,” Nature 348 (1990): 450–52; Peter Koopman et al., “Male development of chromosomally female mice transgenic for SRY gene,” Nature 351 (1991): 117–21; and Andrew H. Sinclair et al., “A gene from the human sex-determining region encodes a protein with ho-mology to a conserved DNA-binding motif,” Nature 346 (1990): 240–44.
10 “I didn’t fit in well”: “IAmA young woman with Swyer syndrome (also called XY gonadal dysgenesis),” Reddit, 2011, https://www.reddit.com/r/IAmA/comments /e792p/iama_young_woman_with_swyer_syndrome_also_called/.
11 On the morning of May 5, 2004: Details of the story of David Reimer are from John Colapinto, As Nature Made Him: The Boy Who Was Raised as a Girl (New York: HarperCollins, 2000).
12 Based on Money’s advice, “Brenda”: John Money, A First Person History of Pediatric Psychoendocrinology (Dordrecht: Springer Science & Business Media, 2002), “Chap-ter 6: David and Goliath.”
13 “Gender identity is sufficiently incompletely”: Gerald N. Callahan, Between XX and XY (Chicago: Chicago Review Press, 2009), 129.
14 “my leather-and-lace look”: J. Michael Bostwick and Kari A. Martin, “A man’s brain in an ambiguous body: A case of mistaken gender identity,” American Journal of Psy-chiatry 164, no. 10 (2007): 1499–505.
15 “I feel like I have the brain of a man”: Ibid.
16 In 2005, a team of researchers at Columbia University: Heino F. L. Meyer-Bahlburg, “Gender identity outcome in female-raised 46,XY persons with penile agenesis, cloa-cal exstrophy of the bladder, or penile ablation,” Archives of Sexual Behavior 34, no. 4 (2005): 423–38.
17 “Is it really the case that all”: Otto Weininger, Sex and Character: An Investigation of Fundamental Principles (Bloomington: Indiana University Press, 2005), 2.
18 these animals might be anatomically female: Carey Reed, “Brain ‘gender’ more flexible than once believed, study finds,” PBS NewsHour, April 5, 2015, http://www.pbs.org /newshour/rundown/brain-gender-flexible-believed-study-finds/. Also see Bridget M. Nugent et al., “Brain feminization requires active repression of masculinization via DNA methylation,” Nature Neuroscience 18 (2015): 690–97.
第三章 最后一英里
1 Like sleeping dogs, unknown twins: Wright, Born That Way, 27.
2 “It is the consensus of many contemporary”: Sándor Lorand and Michael Balint, ed., Perversions: Psychodynamics and Therapy (New York: Random House, 1956; repr.,London: Ortolan Press, 1965), 75.
3 “The homosexual’s real enemy”: Bernard J. Oliver Jr., Sexual Deviation in American Society (New Haven, CT: New College and University Press, 1967), 146.
4 “close-binding and [sexually] intimate”: Irving Bieber, Homosexuality: A Psychoana-lytic Study (Lanham, MD: Jason Aronson, 1962), 52.
5 “a homosexual is a person”: Jack Drescher, Ariel Shidlo, and Michael Schroeder, Sex-ual Conversion Therapy: Ethical, Clinical and Research Perspectives (Boca Raton, FL:CRC Press, 2002), 33.
6 “homosexuality is more of a choice”: “The 1992 campaign: The vice president; Quayle contends homosexuality is a matter of choice, not biology,” New York Times, September 14, 1992, http://www.nytimes.com/1992/09/14/us/1992-campaign-vice-president -quayle-contends-homosexuality-matter-choice-not.xhtml.
7 In July 1993, the discovery of the: David Miller, “Introducing the ‘gay gene’: Media and scientific representations,” Public Understanding of Science 4, no. 3 (1995): 269–84, http://www.academia.edu/3172354/Introducing_the_Gay_Gene_Media_and _Scientific_Representations.
8 “What do we say of the woman”: C. Sarler, “Moral majority gets its genes all in a twist,” People, July 1993, 27.
9 The second book, Richard Lewontin’s: Richard C. Lewontin, Steven P. R. Rose, and Leon J. Kamin, Not in Our Genes: Biology, Ideology, and Human Nature (New York: Pantheon Books, 1984).
10 “There is no acceptable evidence that”: Ibid., 261.
11 In the 1980s, a professor of psychology: J. Michael Bailey and Richard C. Pillard, “A genetic study of male sexual orientation,” Archives of General Psychiatry 48, no. 12 (1991): 1089–96.
12 The brothers, who looked virtually identical: Frederick L. Whitam, Milton Diamond, and James Martin, “Homosexual orientation in twins: A report on 61 pairs and three triplet sets,” Archives of Sexual Behavior 22, no. 3 (1993): 187–206.
13 Protocol #92-C-0078 was launched: Dean Hamer, Science of Desire: The Gay Gene and the Biology of Behavior (New York: Simon & Schuster, 2011), 40.
14 “gay Roots project”: Ibid., 91–104.
15 “There were TV cameramen lined up”: “The ‘gay gene’ debate,” Frontline, PBS, http:// www.pbs.org/wgbh/pages/frontline/shows/assault/genetics/.
16 “science could be used to eradicate it”: Richard Horton, “Is homosexuality inherited?” Frontline, PBS, http://www.pbs.org/wgbh/pages/frontline/shows/assault/genetics /nyreview.xhtml.
17 “does identify a chromosomal region”: Timothy F. Murphy, Gay Science: The Ethics of Sexual Orientation Research (New York: Columbia University Press, 1997), 144.
18 Hamer was attacked left and right: M. Philip, “A review of Xq28 and the effect on ho-mosexuality,” Interdisciplinary Journal of Health Science 1 (2010): 44–48.
19 Since Hamer’s 1993 paper in Science: Dean H. Hamer et al., “A linkage between DNA markers on the X chromosome and male sexual orientation,” Science 261, no. 5119 (1993): 321–27.
20 In 2005, in perhaps the largest study: Brian S. Mustanski et al., “A genomewide scan of male sexual orientation,” Human Genetics 116, no. 4 (2005): 272–78.
21 In 2015, in yet another detailed analysis of 409: A. R. Sanders et al., “Genome-wide scan demonstrates significant linkage for male sexual orientation,” Psychological Medicine 45, no. 7 (2015): 1379–88.
22 One gene that sits: Elizabeth M. Wilson, “Androgen receptor molecular biology and po-tential targets in prostate cancer,” Therapeutic Advances in Urology 2, no. 3 (2010): 105–17.
23 In 1971, in a book titled: Macfarlane Burnet, Genes, Dreams and Realities (Dordrecht: Springer Science & Business Media, 1971), 170.
24 “An environmentalist view”: Nancy L. Segal, Born Together — Reared Apart: The Land-mark Minnesota Twin Study (Cambridge: Harvard University Press, 2012), 4.
25 “random access memory onto which”: Wright, Born That Way, viii.
26 “Whatever back-porch wisdom”: Ibid., vii.
27 Minnesota Study of Twins: Thomas J. Bouchard et al., “Sources of human psychologi-cal differences: The Minnesota study of twins reared apart,” Science 250, no. 4978 (1990): 223–28.
28 “Empathy, altruism, sense of equity”: Richard P. Ebstein et al., “Genetics of human social behavior,” Neuron 65, no. 6 (2010): 831–44.
29 “A surprisingly high genetic component”: Wright, Born That Way, 52.
30 Daphne Goodship and Barbara Herbert: Ibid., 63–67.
31 “Both drove Chevrolets”: Ibid., 28.
32 Two other women, also separated at birth: Ibid., 74.
33 oxford shirts with epaulets: Ibid., 70.
34 to describe the odd habit: squidging: Ibid., 65.
35 “door-knobs, needles and fishhooks”: Ibid., 80.
36 The most extreme novelty seekers, he discovered: Richard P. Ebstein et al., “Dopamine D4 receptor (D4DR) exon III polymorphism associated with the human personality trait of novelty seeking,” Nature Genetics 12, no. 1 (1996): 78–80.
37 Perhaps the subtle drive caused by: Luke J. Matthews and Paul M. Butler, “Novelty-seeking DRD4 polymorphisms are associated with human migration distance out-of-Africa after controlling for neutral population gene structure,” American Journal of Physical Anthropology 145, no. 3 (2011): 382–89.
38 “How nice it would be”: Lewis Carroll, Alice in Wonderland (New York: W. W. Norton, 2013).
39 Forty-three studies, performed: Eric Turkheimer, “Three laws of behavior genetics and what they mean,” Current Directions in Psychological Science 9, no. 5 (2000): 160–64; and E. Turkheimer and M. C. Waldron, “Nonshared environment: A theoretical, methodological, and quantitative review,” Psychological Bulletin 126 (2000): 78–108.
40 “unsystematic, idiosyncratic, serendipitous events”: Robert Plomin and Denise Dan-iels, “Why are children in the same family so different from one another?” Behav-ioral and Brain Sciences 10, no. 1 (1987): 1–16.
41 “a devil, a born devil”: William Shakespeare, The Tempest, act 4, scene 1.
第四章 冬日饥荒
1 Identical twins have exactly the same: Nessa Carey, The Epigenetics Revolution: How Modern Biology Is Rewriting Our Understanding of Genetics, Disease, and Inheritance (New York: Columbia University Press, 2012), 5.
2 Genes have had a glorious run in the 20th century: Evelyn Fox Keller, quoted in Mar-garet Lock and Vinh-Kim Nguyen, An Anthropology of Biomedicine (Hoboken, NJ:John Wiley & Sons, 2010).
3 When a songbird encounters a new: Erich D. Jarvis et al., “For whom the bird sings:Context-dependent gene expression,” Neuron 21, no. 4 (1998): 775–88.
4 In the 1950s, Conrad Waddington: Conrad Hal Waddington, The Strategy of the Genes: A Discussion of Some Aspects of Theoretical Biology (London: Allen & Unwin, 1957), ix, 262.
5 “only [consists of] a stomach”: Max Hastings, Armageddon: The Battle for Germany, 1944–1945 (New York: Alfred A. Knopf, 2004), 414.
6 In the 1980s, however: Bastiaan T. Heijmans et al., “Persistent epigenetic differences associated with prenatal exposure to famine in humans,” Proceedings of the National Academy of Sciences 105, no. 44 (2008): 17046–49.
7 “aptitude for doing things on a small scale”: John Gurdon, “Nuclear reprogramming in eggs,” Nature Medicine 15, no. 10 (2009): 1141–44.
8 In 1961, Gurdon began to test: J. B. Gurdon and H. R. Woodland, “The cytoplas-mic control of nuclear activity in animal development,” Biological Reviews 43, no. 2 (1968): 233–67.
9 It would lead, famously, to the cloning of Dolly: “Sir John B. Gurdon—facts,” Nobel prize.org, http://www.nobelprize.org/nobel_prizes/medicine/laureates/2012/gurdon -facts.xhtml.
10 the only other “observed case”: John Maynard Smith, interview in the Web of Stories. www.webofstories.com/play/john.maynard.smith/78.
11 Lyon found: in one cell: The Japanese scientist Susumu Ohno had hypothesized about X inactivation before the phenomenon was discovered.
12 simple organisms, such as yeast: K. Raghunathan et al., “Epigenetic inheritance un-coupled from sequence-specific recruitment,” Science 348 (April 3, 2015): 6230.
13 In his remarkable story “Funes the Memorious”: Jorge Luis Borges, Labyrinths, trans. James E. Irby (New York: New Directions, 1962), 59–66.
14 One of the four genes used by Yamanaka: K. Takahashi and S. Yamanaka, “Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors,” Cell 126, no. 4 (2006): 663–76. Also see M. Nakagawa et al., “Gen-eration of induced pluripotent stem cells without Myc from mouse and human fi-broblasts,” Nature Biotechnology 26, no. 1 (2008): 101–6.
15 “It sometimes seems as if curbing entropy”: James Gleick, The Information: A History, a Theory, a Flood (New York: Pantheon Books, 2011).
16 At Harvard, a soft-spoken biochemist: Itay Budin and Jack W. Szostak, “Expanding roles for diverse physical phenomena during the origin of life,” Annual Review of Biophysics 39 (2010): 245–63; and Alonso Ricardo and Jack W. Szostak, “Origin of life on Earth,” Scientific American 301, no. 3 (2009): 54–61.
17 followed the work of Stanley Miller: The original experiments were performed by Miller in conjunction with Harold Urey at the University of Chicago; John Suther-land, in Manchester, also performed key experiments.
18 Subsequent variations of the Miller experiment: Ricardo and Szostak, “Origin of life on Earth,” 54–61.
19 Szostak has demonstrated that such micelles: Jack W. Szostak, David P. Bartel, and P..Luigi Luisi, “Synthesizing life,” Nature 409, no. 6818 (2001): 387–90. Also see Mar-tin M. Hanczyc, Shelly M. Fujikawa, and Jack W. Szostak, “Experimental models of primitive cellular compartments: Encapsulation, growth, and division,” Science 302, no. 5645 (2003): 618–22.
20 “It is relatively easy to see how”: Ricardo and Szostak, “Origin of life on Earth,” 54–61.
第六部分
1 Those who promise us paradise on earth: Elias G. Carayannis and Ali Pirzadeh, Th e Knowledge of Culture and the Culture of Knowledge: Implications for Theory, Policy and Practice (London: Palgrave Macmillan, 2013), 90.
2 It’s only we humans: Tom Stoppard, The Coast of Utopia (New York: Grove Press, 2007), “Act Two, August 1852.”
第一章 未来的未来
1 Probably no DNA science is at once: Gina Smith, The Genomics Age: How DNA Tech-nology Is Transforming the Way We Live and Who We Are (New York: AMACOM, 2004).
2 Clear the air!: Thomas Stearns Eliot, Murder in the Cathedral (Boston: Houghton Mifflin Harcourt, 2014).
3 In 1974, barely three years after: Rudolf Jaenisch and Beatrice Mintz, “Simian virus 40 DNA sequences in DNA of healthy adult mice derived from preimplantation blas-tocysts injected with viral DNA,” Proceedings of the National Academy of Sciences 71, no. 4 (1974): 1250–54.
4 biologists stumbled on a critical discovery: M. J. Evans and M. H. Kaufman, “Estab-lishment in culture of pluripotential cells from mouse embryos,” Nature 292 (1981): 154–56.
5 “Nobody seems to be interested in my cells”: M. Capecchi, “The first transgenic mice: An interview with Mario Capecchi. Interview by Kristin Kain,” Disease Models & Mechanisms 1, no. 4–5 (2008): 197.
6 With ES cells, however, scientists: See for instance M. R. Capecchi, “High efficiency transformation by direct microinjection of DNA into cultured mammalian cells,” Cell 22 (1980): 479–88; and K. R. Thomas and M. R. Capecchi, “Site-directed mutagenesis by gene targeting in mouse embryo–derived stem cells,” Cell 51 (1987): 503–12.
7 You could choose to change the insulin gene: O. Smithies et al., “Insertion of DNA se-quences into the human chromosomal-globin locus by homologous re- combination,” Nature 317 (1985): 230–34.
8 The “watchmaker” of evolution, as Richard Dawkins: Richard Dawkins, The Blind Watchmaker: Why the Evidence of Evolution Reveals a Universe without Design (W..W..Norton, 1986).
9 They are the savants of the rodent world: Kiyohito Murai et al., “Nuclear receptor TLX stimulates hippocampal neurogenesis and enhances learning and memory in a transgenic mouse model,” Proceedings of the National Academy of Sciences 111, no. 25 (2014): 9115–20.
10 “It may be the field’s dirty little secret”: Karen Hopkin, “Ready, reset, go,” The Scientist, March 11, 2011, http://www.the-scientist.com/?articles.view/articleno/29550/title /ready—reset—go/.
11 In 1988, a two-year-old girl: Details of the story of Ashanti DeSilva are from W..French Anderson, “The best of times, the worst of times,” Science 288, no. 5466 (2000): 627; Lyon and Gorner, Altered Fates; and Nelson A. Wivel and W. French Anderson, “24: Human gene therapy: Public policy and regulatory issues,” Cold Spring Harbor Monograph Archive 36 (1999): 671–89.
12 “Mommy, you shouldn’t have had”: Lyon and Gorner, Altered Fates, 107.
13 The Bubble Boy, as David was called: “David Phillip Vetter (1971–1984),” American Experience, PBS, http://www.pbs.org/wgbh/amex/bubble/peopleevents/p_vetter.xhtml.
14 Richard Mulligan, a virologist and geneticist: Luigi Naldini et al., “In vivo gene deliv-ery and stable transduction of nondividing cells by a lentiviral vector,” Science 272, no. 5259 (1996): 263–67.
15 led by William French Anderson and Michael Blaese: “Hope for gene therapy,” Scien-tific American Frontiers, PBS, http://www.pbs.org/saf/1202/features/genetherapy.htm.
16 In the early 1980s, Anderson and Blaese: W. French Anderson et al., “Gene transfer and expression in nonhuman primates using retroviral vectors,” Cold Spring Harbor Symposia on Quantitative Biology 51 (1986): 1073–81.
17 “Nobody knows what may happen”: Lyon and Gorner, Altered Fates, 124.
18 Perhaps predictably, the RAC rejected the protocol outright: Lisa Yount, Modern Ge-netics: Engineering Life (New York: Infobase Publishing, 2006), 70.
19 “A cosmic moment has come and gone”: Lyon and Gorner, Altered Fates, 239.
20 “Jesus Christ himself could walk by”: Ibid., 240.
21 “It’s not a big improvement”: Ibid., 268.
22 At four, he had joyfully eaten: Barbara Sibbald, “Death but one unintended conse-quence of gene-therapy trial,” Canadian Medical Association Journal 164, no. 11 (2001): 1612.
23 In 1993, when Gelsinger was: For details of the Jesse Gelsinger story see Evelyn B. Kelly, Gene Therapy (Westport, CT: Greenwood Press, 2007); Lyon and Gorner, Altered Fates; and Sally Lehrman, “Virus treatment questioned after gene therapy death,” Nature 401, no. 6753 (1999): 517–18.
24 By noon, the procedure was done: James M. Wilson, “Lessons learned from the gene therapy trial for ornithine transcarbamylase deficiency,” Molecular Genetics and Me-tabolism 96, no. 4 (2009): 151–57.
25 “How could such a beautiful thing”: Paul Gelsinger, author interview, November 2014 and April 2015.
26 That Wilson had a financial stake in: Robin Fretwell Wilson, “Death of Jesse Gel-singer: New evidence of the influence of money and prestige in human research,” American Journal of Law and Medicine 36 (2010): 295.
27 In January 2000, when the FDA inspected: Sibbald, “Death but one unintended con-sequence,” 1612.
28 “The entire field of gene therapy”: Carl Zimmer, “Gene therapy emerges from disgrace to be the next big thing, again,” Wired, August 13, 2013.
29 “Gene therapy is not yet therapy”: Sheryl Gay Stolberg, “The biotech death of Jesse Gel-singer,” New York Times, November 27, 1999, http://www.nytimes.com/1999/11/28 /magazine/the-biotech-death-of-jesse-gelsinger.xhtml.
30 “cautionary tale of scientific overreach”: Zimmer, “Gene therapy emerges.”
第二章 基因诊断:“预生存者”
1 All that man is: W. B. Yeats, The Collected Poems of W. B. Yeats, ed. Richard Finneran (New York: Simon & Schuster, 1996), “Byzantium,” 248.
2 The anti-determinists want to say: Jim Kozubek, “The birth of ‘transhumans,’ ” Provi-dence (RI) Journal, September 29, 2013.
3 “Genetic tests,” as Eric Topol: Eric Topol, author interview, 2013.
4 Between 1978 and 1988, King added: Mary-Claire King, “Using pedigrees in the hunt for BRCA1,” DNA Learning Center, https://www.dnalc.org/view/15126-Using-pedigress -in-the-hunt-for-BRCA1-Mary-Claire-King.xhtml.
5 she had pinpointed it to a region: Jeff M. Hall et al., “Linkage of early-onset familial breast cancer to chromosome 17q21,” Science 250, no. 4988 (1990): 1684–89.
6 “Being comfortable with uncertainty”: Jane Gitschier, “Evidence is evidence: An in-terview with Mary-Claire King,” PLOS, September 26, 2013.
7 In 1998, Myriad was granted: E. Richard Gold and Julia Carbone, “Myriad Genetics: In the eye of the policy storm,” Genetics in Medicine 12 (2010): S39–S70.
8 “Some of these women [with BRCA1 mutations]”: Masha Gessen, Blood Matters: From BRCA1 to Designer Babies, How the World and I Found Ourselves in the Future of the Gene (Boston: Houghton Mifflin Harcourt, 2009), 8.
9 In 1908, the Swiss German psychiatrist: Eugen Bleuler and Carl Gustav Jung, “Kom-plexe und Krankheitsursachen bei Dementia praecox,” Zentralblatt für Nerven-heilkunde und Psychiatrie 31 (1908): 220–27.
10 In the 1970s, studies demonstrated: Susan Folstein and Michael Rutte, “Infantile au-tism: A genetic study of 21 twin pairs,” Journal of Child Psychology and Psychiatry 18, no. 4 (1977): 297–321.
11 “domineering, nagging and hostile mother”: Silvano Arieti and Eugene B. Brody, Adult Clinical Psychiatry (New York: Basic Books, 1974), 553.
12 National Book Award for science: “1975: Interpretation of Schizophrenia by Silvano Arieti,” National Book Award Winners: 1950–2014, National Book Foundation, http://www.nationalbook.org/nbawinners_category.xhtml#.vcnit7fxhom.
13 In 2013, an enormous study identified: Menachem Fromer et al., “De novo mutations in schizophrenia implicate synaptic networks,” Nature 506, no. 7487 (2014): 179–84.
14 108 genes (or rather genetic regions): Schizophrenia Working Group of the Psychiat-ric Genomics, Nature 511 (2014): 421–27.
16 “There are lots of ”: Benjamin Neale, quoted in Simon Makin, “Massive study reveals schizophrenia’s genetic roots: The largest-ever genetic study of mental illness reveals a complex set of factors,” Scientific American, November 1, 2014.
17 “We of the craft are all crazy”: Carey’s Library of Choice Literature, vol. 2 (Philadel-phia: E. L. Carey & A. Hart, 1836), 458.
18 In Touched with Fire, an authoritative: Kay Redfield Jamison, Touched with Fire (New York: Simon & Schuster, 1996).
19 Hans Asperger, the psychologist who first: Tony Attwood, The Complete Guide to As-perger’s Syndrome (London: Jessica Kingsley, 2006).
20 As Edvard Munch put it: Adrienne Sussman, “Mental illness and creativity: A neurologi-cal view of the ‘tortured artist,’ ” Stanford Journal of Neuroscience 1, no. 1 (2007): 21–24.
21 illness as the “night-side of life”: Susan Sontag, Illness as Metaphor and AIDS and Its Metaphors (New York: Macmillan, 2001).
22 Entitled “The Future of Genomic Medicine”: Details of the conference can be found in “The future of genomic medicine VI,” Scripps Translational Science Institute, http://www.slideshare.net/mdconferencefi nder/the-future-of-genomic-medicine -vi-23895019; Eryne Brown, “Gene mutation didn’t slow down high school senior,” Los Angeles Times, July 5, 2015, http://www.latimes.com/local/california/la-me-lilly -grossman-update-20150702-story.xhtml; and Konrad J. Karczewski, “The future of genomic medicine is here,” Genome Biology 14, no. 3 (2013): 304.
23 Alexis and Noah Beery: “Genome maps solve medical mystery for California twins,” National Public Radio broadcast, June 16, 2011.
24 Based on that genetic diagnosis: Matthew N. Bainbridge et al., “Whole-genome se-quencing for optimized patient management,” Science Translational Medicine 3, no. 87 (2011): 87re3.
25 That a mutation in the gene MECP2: Antonio M. Persico and Valerio Napolioni, “Autism genetics,” Behavioural Brain Research 251 (2013): 95–112; and Guillaume Huguet, Elodie Ey, and Thomas Bourgeron, “The genetic landscapes of autism spectrum disorders,” Annual Review of Genomics and Human Genetics 14 (2013): 191–213.
26 the eventual effects of these gene-environment: Albert H. C. Wong, Irving I. Gottes-man, and Arturas Petronis, “Phenotypic differences in genetically identical organ-isms: The epigenetic perspective,” Human Molecular Genetics 14, suppl. 1 (2005): R11–R18. Also see Nicholas J. Roberts et al., “The predictive capacity of personal genome sequencing,” Science Translational Medicine 4, no. 133 (2012): 133ra58.
27 an article in Nature magazine announced: Alan H. Handyside et al., “Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplifi-cation,” Nature 344, no. 6268 (1990): 768–70.
28 As the political theorist Desmond King puts it: D. King, “The state of eugenics,” New Statesman & Society 25 (1995): 25–26.
29 Take, for instance, a series of startlingly provocative: K. P. Lesch et al., “Association of anxiety-related traits with a polymorphism in the serotonergic transporter gene regulatory region,” Science 274 (1996): 1527–31.
30 the short allele has been associated with: Douglas F. Levinson, “The genetics of de-pression: A review,” Biological Psychiatry 60, no. 2 (2006): 84–92.
31 In 2010, a team of researchers launched: “Strong African American Families Pro-gram,” Blueprints for Healthy Youth Development, http://www.blueprintsprograms .com/evaluationAbstracts.php?pid=f76b2ea6b45eff 3bc8e4399145cc17a0601f5c8d.
32 Six hundred African-American families with early-adolescent: Gene H. Brody et al., “Prevention effects moderate the association of 5-HTTLPR and youth risk behavior initiation: Gene × environment hypotheses tested via a randomized prevention de-sign,” Child Development 80, no. 3 (2009): 645–61; and Gene H. Brody, Yi-fu Chen, and Steven R..H..Beach, “Differential susceptibility to prevention: GABAergic, dopa-minergic, and multilocus effects,” Journal of Child Psychology and Psychiatry 54, no. 8 (2013): 863–71.
33 Writing in the New York Times in 2014: Jay Belsky, “The downside of resilience,” New York Times, November 28, 2014.
34 “a technology of abnormal individuals”: Michel Foucault, Abnormal: Lectures at the Collège de France, 1974–1975, vol. 2 (New York: Macmillan, 2007).
第三章 基因治疗:后人类时代
1 There is in biology at the moment: “Biology’s Big Bang,” Economist, June 14, 2007.
2 a journalist visited James Watson at: Lyon and Gorner, Altered Fates, 537.
3 Jesse Gelsinger’s “biotech death”: Stolberg, “Biotech death of Jesse Gelsinger,” 136–40.
4 In 2014, a landmark study: Amit C. Nathwani et al., “Long-term safety and efficacy of factor IX gene therapy in hemophilia B,” New England Journal of Medicine 371, no. 21 (2014): 1994–2004.
5 In 1998, soon after Thomson’s paper: James A. Thomson et al., “Embryonic stem cell lines derived from human blastocysts,” Science 282, no. 5391 (1998): 1145–47.
6 President George W. Bush sharply restricted: Dorothy C. Wertz, “Embryo and stem cell research in the United States: History and politics,” Gene Therapy 9, no. 11 (2002): 674–78.
7 Doudna and Charpentier published their data: Martin Jinek et al., “A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity,” Science 337, no. 6096 (2012): 816–21.
8 this technique has exploded: Key contributors to the use of CRISPR/Cas9 in human cells include Feng Zhang (MIT) and George Church (Harvard). See, for instance,L.Cong et al., “Multiplex genome engineering using CRISPR/Cas systems,” Sci-ence 339, no. 6121 (2013): 819–23; and F. A. Ran, “Genome engineering using the CRISPR-Cas9 system,” Nature Protocols 11 (2013): 2281–308. Also see P. Mali et al., “RNA-Guided Human Genome Engineering via Cas9,” Science 339, no. 6121 (2013): 823–26.
9 In the winter of 2014, a team: Walfred W. C. Tang et al., “A unique gene regula-tory network resets the human germline epigenome for development,” Cell 161, no. 6 (2015): 1453–67; and “In a first, Weizmann Institute and Cambridge University scientists create human primordial germ cells,” Weizmann Institute of Science, De-cember 24, 2014, http://www.newswise.com/articles/in-a-first-weizmann-institute -and-cambridge-university-scientists-create-human-primordial-germ-cells.
10 Jennifer Doudna and David Baltimore: B. D. Baltimore et al., “A prudent path for-ward for genomic engineering and germline gene modification,” Science 348, no. 6230 (2015): 36–38; and Cormac Sheridan, “CRISPR germline editing reverberates through biotech industry,” Nature Biotechnology 33, no. 5 (2015): 431–32.
11 “It is very clear that people will try”: Nicholas Wade, “Scientists seek ban on method of editing the human genome,” New York Times, March 19, 2015.
12 “This reality means”: Francis Collins, Letter to the author, October 2015.
13 In the spring of 2015, a laboratory: David Cyranoski and Sara Reardon, “Chinese sci-entists genetically modify human embryos,” Nature (April 22, 2015).
14 The highest-ranking scientific journals: Chris Gyngell and Julian Savulescu, “The moral imperative to research editing embryos: The need to modify nature and science,” Ox-ford University, April 23, 2015, Blog.Practicalethics.Ox.Ac.Uk/2015/04/the-Moral-Imperative-to-Research-Editing-Embryos-the-Need-to-Modify-Nature-and-Science/.
15 the results were eventually published in: Puping Liang et al., “CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes,” Protein & Cell 6, no. 5 (2015): 1–10.
16 “planning to decrease the number of off-target”: Cyranoski and Reardon, “Chinese scientists genetically modify human embryos.”
17 “I don’t think China wants”: Didi Kristen Tatlow, “A scientific ethical divide between China and West,” New York Times, June 29, 2015.
后记 辨别身份
1 “No sane biologist believes”: Paul Berg, author interview, 1993.
2 “very few human genes”: David Botstein, letter to the author, October 2015.
3 In an influential review published in 2011: Eric Turkheimer, “Still missing,” Research in Human Development 8, nos. 3–4 (2011): 227–41.
4 “Perhaps,” as one observer complained: Peter Conrad, “A mirage of genes,” Sociology of Health & Illness 21, no. 2 (1999): 228–41.
5 “Imagine you are a soldier returning from war”: Richard A. Friedman, “The feel-good gene,” New York Times, March 6, 2015.
6 “[Nature] may, after all, be entirely approachable”: Morgan, Physical Basis of Heredity, 15.
致谢
1 “distorted version of our normal selves”: H.Varmus, Nobel lecture, 1989. http://www .nobelprize.org/nobel_prizes/medicine/laureates/1989/varmus-lecture.xhtml. For the paper describing the existence of endogenous proto-oncogenes in cells see D. Stehe-lin et al., “DNA related to the transforming genes of avian sarcoma viruses is pres-ent in normal DNA,” Nature 260, no. 5547 (1976): 170–73. Also see Harold Varmus to Dominique Stehelin, February 3, 1976, Harold Varmus Papers, National Library of Medicine Archives.
1694年,尼古拉斯·哈特苏克根据主观臆测勾勒出一幅蜷曲在精子中的缩微人画像。哈特苏克与同时代的许多生物学家一样崇尚“精源论”,而该理论认为形成胎儿的信息源自精子中的缩微人。
在欧洲中世纪时期,人们通常会根据“谱系树”来标记贵族家庭中的祖先与后代。这些谱系树被用来证明爵位与财产的归属或者是家族之间联姻的参考(部分减少了表兄妹之间近亲婚配的机会)。位于图片左上角的“基因”一词在这里是谱系或者血统的意思,直到几个世纪之后的1909年,基因这种遗传信息单位才被赋予现代意义。
查理·达尔文(70岁像)与他绘制的“生命之树”草图,该图显示所有生物体均源自某个相同的祖先(他在图片上方用怀疑的语气潦草地写着“我认为”)。达尔文进化论中的变异与自然选择需要基因理论的支持。仔细阅读达尔文进化论的读者可能会意识到,该理论仅在遗传微粒(不可分割且可以突变)能够在亲本与子代之间进行传递时才有意义。但由于达尔文从来没有拜读过格雷戈尔·孟德尔的文章,因此他也未能在有生之年对于进化论做出进一步的完善。
格雷戈尔·孟德尔手中的花朵可能摘自布尔诺(现位于捷克共和国)修道院花园中的某株豌豆。19世纪50年代到60年代,孟德尔通过实验开创性地证实了某些不可分割的信息微粒就是遗传信息的载体。孟德尔的论文(发表于1865年)被人们忽视了将近40年,而直到他的工作被重新发现后,生物学才跨入了新纪元。
弗朗西斯·高尔顿是英国数学家、生物学家与统计学家,他将个体数据制成“人体测量学卡片”,并且使用表格来反映身高、体重、容貌以及其他特征。高尔顿反对孟德尔的基因理论。他希望通过选择“最佳”的遗传性状与定向繁育后代来改良人种。高尔顿将这种借助遗传操作使人类获得解放的方法称为优生学,而这门学科随即沦为实现社会统治与政治野心的可怕工具。
1900年,威廉·贝特森“重新发现”了孟德尔的工作,而他本人也成为基因理论的忠实拥护者。1905年,贝特森首次使用“遗传学”这个词来描述遗传学研究。1909年,威廉·约翰森(左)在描述遗传单位的时候创造了“基因”一词。图为约翰森来到英国剑桥拜访贝特森时的合影,他们既是亲密的合作伙伴,也是基因理论的坚强捍卫者。
为了推行“种族卫生”计划,德国纳粹政府动用国家机器通过绝育、监禁与屠杀的方式进行种族清洗。他们通过双胞胎实验来证明遗传对于人类的影响,并且从肉体上清除那些携带有缺陷基因的男女老幼。更令人发指的是,纳粹分子还妄图使用“优生”手段来消灭犹太人、吉卜赛人、不同政见者以及同性恋者。上两图为纳粹科学家正在为双胞胎测量身高以及向新兵演示谱系图。
20世纪30年代,“健康婴儿大赛”被引入美国。医护人员正在对具有最佳遗传特征的儿童(均为白人)进行检查。这种比赛将最健康的婴儿作为基因选择的产物来展示,实际上被动支持了美国的优生学运动。
美国的《优生树》漫画主张“自我定向的人类进化”。其中医学、外科学、人类学与谱系学就相当于“树根”。优生学希望通过这些基本理论来选择更适合、更健康以及更聪明的人类。
20世纪30年代,卡丽·巴克与母亲艾玛·巴克被送至弗吉尼亚州立癫痫与智障收容所,而这里所有被认定为“弱智”的女性均需要接受绝育。这张照片摄于她们母女不经意的瞬间,其目的就是为了说明卡丽与艾玛彼此十分相似,并且以此作为她们具有“遗传性弱智”的证据。
20世纪20年代至30年代,托马斯·摩尔根在哥伦比亚大学与加州理工学院从事果蝇遗传领域的研究。他不仅证实了某些基因之间存在物理连接,而且还颇有先见之明地预测出这种单一的链状分子携带有遗传信息。最终,连锁定律被用于绘制人类基因图谱,并且为人类基因组计划奠定了基础。这张照片摄于摩尔根在加州理工学院的蝇室,他周围堆满了用于饲养蛆与果蝇的奶瓶。
20世纪50年代,罗莎琳德·富兰克林在伦敦国王学院使用显微镜观察研究结果。富兰克林在分析DNA结构的时候采用了X射线衍射成像技术,而她拍摄的51号照片是所有DNA晶体结构影像中最为完美的一张。尽管无法从照片中分辨出碱基A、C、T与G的方向,但是DNA的双螺旋结构已经一目了然。
1953年,沃森与克里克根据双股DNA链之间的碱基配对关系(A与T配对,G与C配对)证明了DNA为双螺旋结构。
20世纪50年代,维克多·马克库斯克在巴尔的摩创建了摩尔诊所,他在此对大量人类疾病相关基因进行了登记分类。马克库斯克发现数个不相干的基因突变决定了矮小症或侏儒症的表型。与之相反,单基因突变也可以导致患者出现各种不同的表型。
亨廷顿病(亨廷顿舞蹈症)是一种致死性的神经系统退行性疾病,患者身体会出现不自主的“舞蹈”动作或突然抽搐。由于南希·韦克斯勒的母亲与舅舅就患有此病,因此她义无反顾地投入到了寻找亨廷顿病基因的工作中。经过不懈努力,韦克斯勒在委内瑞拉发现了许多亨廷顿病患者,而他们体内的致病基因似乎均来源于同一位祖先。亨廷顿病是第一种通过现代基因定位技术确诊的单基因遗传病。
20世纪70年代,学生们在遗传会议现场举行抗议活动。由于无法忘却历史上德国纳粹政府推行优生学的暴行,因此人们非常担心基因测序、基因克隆与重组DNA等新技术会沦为创建“完美种族”的工具。图中标语出自希特勒:“我们将创造完美的种族。”
1975年,保罗·伯格、玛克辛·辛格与诺顿·津德在阿西洛马会议期间进行交流,与此同时悉尼·布伦纳在后面做记录。伯格等学者发现某类技术可以让杂交DNA分子(重组DNA)在细菌中大量扩增(基因克隆),于是他们建议在这种技术的风险得到充分评估前“暂停”某些重组DNA工作。
1976年,赫伯特·博耶(左)与罗伯特·斯旺森创建了通过基因工程生产药物的基因泰克公司。他们背后黑板上展现的是应用重组DNA技术生产胰岛素的方案,而斯旺森见证了首次大规模从细菌培养箱中生产出此类蛋白质的过程。
弗雷德里克·桑格正在检查DNA测序凝胶。桑格发明的DNA测序技术(也就是按照基因上碱基A、C、T与G的顺序读取)不仅彻底改变了我们对于基因的认识,而且还为人类基因组计划奠定了基础。
1999年,杰西·基辛格在去世前几个月于费城的光谱球馆前拍照留念。基辛格是世界上首批接受基因治疗的患者之一。研究人员通过病毒将矫正的突变基因注入其肝脏,但是基辛格随即就对病毒发生了超敏免疫反应,而他最终不幸因多器官功能衰竭死亡。基辛格“死于生物技术”的事实在全美引起了强烈反响,人们对于基因治疗临床试验的安全性表现出严重关切。
2000年6月26日,克雷格·文特尔(左)、克林顿总统(中)以及弗朗西斯·柯林斯在白宫宣布完成了人类基因组序列草图。(图片来源:AP / 东方IC)
2001年2月,《科学》杂志在封面上宣传了人类基因组序列草图。
尽管胎儿性别鉴定并不能改变人类基因组,但是这种方法还是在全球造成了极大的负面影响。历史上在亚洲部分地区,人们在通过羊膜穿刺对胎儿进行性别鉴定后会选择性地将女性胎儿流产,从而导致男女性别比例出现严重失衡,并且使人口与家庭结构发生前所未有的改变。
由于超级计算机可以快速精准地对遗传信息进行分析与注释,因此新型基因测序仪(位于那些灰箱样的柜子中)可以在几个月之内就完成人类基因组的测序。此类技术可以对多细胞胚胎或胎儿进行基因组测序,从而使胚胎植入前遗传学诊断与宫内诊断疾病成为现实。
珍妮弗·杜德娜(右)是加州大学伯克利分校研究RNA的生物学家,她与其他科学家一起正在研究某种可以实现基因定向突变的系统。尽管其安全性与保真性尚待进一步完善,但是该系统从理论上来讲能够用于“编辑”人类基因组。如果定向基因改变可以被导入精子、卵细胞或人类胚胎干细胞,那么这项技术就可以让人类的基因发生改变。
第三章 基因治疗:后人类时代这是最后一篇