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TSS特别报道:处于停滞中的克隆学是否会重新复苏?

TSS EXCLUSIVE: Is cloning – a relatively, dormant scientific field – due for a resurgence?

by A’liya Spinner

“克隆”一词通常会让人想到科幻小说中的反乌托邦和遥远的未来,但它其实是是一个自然发生的过程,与自然概念本身一样古老。单细胞微生物是地球上第一个已知的生命实体,约37亿年前出现在温暖的原始海洋中。这些古老的生命体通过自我克隆进行自我复制,这种无性生殖形式仍然由这些微生物的后代进行:原核生物(单细胞生物,如细菌)和更大更复杂的生命体(如植物、真菌和动物,包括人)体内的单个细胞。

The word “cloning” typically brings to mind science-fiction dystopias and far-off futures, but “cloning” is a naturally-occurring process as old as the idea of nature itself. Single-celled microbes, the first known instance of life on planet Earth, appeared in warm, primordial soup about 3.7 billion years ago. These ancient lifeforms replicated themselves by self-cloning— an asexual form of reproduction still performed by the descendants of those microbes: prokaryotes (single-cellular organisms like bacteria) and the individual cells in the bodies of much larger and complex lifeforms like plants, fungi, and animals— including human beings.

在我们体内,单个细胞的小规模克隆不断发生。这种情况也发生在实验室里;20世纪80年代,美国生物化学家卡里·穆利斯发明了一种称为多聚酶链式反应(PCR)的方法,科学家可以快速复制DNA片段,产生数十亿份所需序列的拷贝。通过PCR进行的克隆,彻底改变了法医学和基因检测,将小样本转化为大培养群进行研究和鉴定。

Cloning on a small, single-cellular scale is happening constantly inside our bodies. It happens in laboratories, too; in the 1980s, American biochemist Kary Mullis invented a process known as Polymerase Chain Reaction (PCR), which allows scientists to rapidly duplicate segments of DNA, producing billions of copies of the desired sequence. Cloning through PCR revolutionized forensics and genetic testing, turning small samples into large cultures for study and identification.

但当提到克隆时,人们想到的并不只是发生在科幻小说中的细胞复制或PCR:而是生殖性克隆。生殖性克隆是将一个基因复制到先前存在的多细胞有机体上,或者创造一个生物的精确副本。类似的事情也发生在自然界:例如,任何能生同卵双胞胎的物种,都有机会产生自然发生的多细胞“克隆体”。但是,在实验室里应用这个未来主义的想法的历史比大多数人所知道的要丰富得多。人工生殖克隆可追溯到20世纪,当时德国胚胎学家汉斯·斯佩曼(Hans Spemann)将蝾螈胚胎“变为孪生”(split),并因此获得诺贝尔奖。克隆蝌蚪的罗伯特·布里格斯和托马斯·金于1952年发明了第二种克隆方法,称为“细胞核移植”,即将遗传密码从细胞转移到未受精的胚胎。这一过程在1958年被复制到用肠细胞克隆青蛙,之后,在1996年,被用于一只名叫多利的人尽皆知的母羊。

But when cloning is mentioned, it isn’t cellular replication or PCR that people envision taking place in a science-fiction setting: it’s reproductive cloning. Reproductive cloning is the production of a genetic duplicate to a preexisting, multicellular organism, or creating an exact copy of a living thing. Something similar happens in nature: any species that can give birth to identical twins, for instance, has the chance to produce naturally-occuring, multicellular “clones”. But even the laboratory application of this futuristic-sounding idea has a much richer history than most people know. Artificial reproductive cloning dates back to the 1900s, when German embryologist Hans Spemann “twinned”, or split, a salamander embryo, for which he won a Nobel Prize. A second method of cloning known as “nuclear transfer”, wherein genetic code is transferred from a cell to an unfertilized embryo, was developed in 1952 by Robert Briggs and Thomas J. King, who cloned tadpoles. This process was replicated to clone frogs using intestinal cells in 1958, and then, perhaps most famously, a female sheep named Dolly in 1996.

多利证明了以前被认为是不可能的事情:成年哺乳动物可以被克隆,也许包括人类。但是,生殖性克隆并没有探索这一发展,也没有继续建立在一百多年的进步之上,而是似乎停滞不前。这是一个久经考验的过程,但如今却只在推测性的虚构中进行探索。但这是为什么?为什么多利羊放缓了整个新兴科学领域的进展,是否有一天这个领域会恢复以往的速度?

Dolly proved what was previously thought to be impossible: adult mammals can be cloned, including, perhaps, human beings. But rather than exploring this development or continuing to build on over a hundred years of progress, reproductive cloning seemed to come to a standstill, explored only in speculative fiction despite being a tried and proven process. But why was that? Why did Dolly the sheep slow the progress of an entire emergent scientific field, and might it someday resume?

克隆人类的艰难历程
It’s Harder For Humans

造成这种停滞的第一个原因在于克隆科学本身——克隆人类比克隆蝾螈和青蛙困难得多。许多人不知道,多莉的诞生其实是凑巧发生的事情,它是由成年细胞的对照组出生的,而实验本身则专注于胚胎和胎儿细胞。多莉的出生仅仅是多莉的出生,不管是不是意外,都不意味着她的成功很容易被复制——在整个实验过程中,她是唯一成功出生的个体,实验涉及277个细胞融合,29个人工胚胎,13个植入代孕母亲体内。在多利之后,克隆绵羊的尝试产生了患有危及生命的疾病或极度残疾的羔羊,这是克隆方法不完善的常见副作用。伊恩·威尔穆特是多莉的创造者之一,也是科学家,他在不久之后就制造出了这些有缺陷的复制品,他称这是一种“令人痛苦的”景象,并且不鼓励对人类胚胎进行实验,因为这可能会导致畸形出生和流产。

The first reason for this stagnation lies in the science of cloning itself— cloning humans is much more difficult than salamanders and frogs. Unknown to many, the creation of Dolly was actually a happy accident, born from the control group of adult cells, while the experiment itself focused on embryonic and fetal cells. And just because Dolly was born, accident or not, does not mean that her success was easily replicable— she was the only viable birth throughout the course of the experiment, which involved 277 cell fusions, 29 created embryos, and 13 implantations into surrogate mothers. Attempts to clone sheep that followed Dolly produced lambs with life-threatening diseases or extreme disabilities, a common side effect to the imperfections of the cloning method. Ian Wilmut, one of Dolly’s creators and the scientist who shortly thereafter produced these deficient copies, called it a “distressing” sight and discouraged experimentation with human embryos due to likelihood of abnormal births and lost pregnancies.

但成功克隆所需的大量试验并不是唯一的障碍;实验证明,灵长类动物(如人类)比其他哺乳动物更难克隆。自从多利成功以来,科学家们一直希望克隆猴子,为生物医学研究和灵长类疾病的研究提供宝贵的实验室标本。然而,尽管其他哺乳动物(如猫和牛)在这段时间内利用1997年首创的体细胞核移植(SCNT)方法取得了越来越大的成功,但直到2018年,克隆的灵长类动物才成功健康出生(产生了一对克隆猕猴)。这要归功于技术的进步和新的探索性克隆技术。开发出创造灵长类动物活胎所需的替代方法的科学家认为,这一过程可以重复进行,以有效地克隆人类——尽管极低的体外成功率仍然是一个障碍。

That may not always be the case in the future, however. Since the triumph of the 2018 macaque twins, the field of mammalian cloning has declared several important breakthroughs. In summer of 2020, the cause for oversized placentas in SCNT-cloned mammals was discovered after almost twenty years of research and mystery. Oversized placentas cause myriad issues during fetal development, but after correcting for this (the culprit was an overexpression of microRNA in clone genome) the number of successful pregnancies and births doubled.

波士顿儿童医院干细胞研究员张毅博士最近发现了另一项突破;从中衍生出克隆的成年细胞原本已专门化为身体中的特定细胞(例如作为皮肤或肝脏的一部分),并因此“关闭”了某些基因。植入卵子可以激活其中的许多基因,但只有几个小时的可操作时间,之后胚胎将开始发育,此时许多关键的基因仍然无法激活,最终导致克隆体的死亡。然而,几年前,张博士发现了一种化学物质,当遗传物质添加到卵子中时,它有助于更快地释放被阻断的基因。在老鼠身上测试时,化学修饰的卵子成功率为10%,相比之下,对照组只有1%的成功率。几年后,张的团队测试了人类女性志愿者的卵子;如果没有这种化学物质,就没有卵子成功地开始发育,而那些有这种化学物质的女性中有四分之一的卵子能够发育成功。张博士的团队从未将克隆人类胚胎作为实验目的;他们的目标是开发出从有需要的成年人身上克隆干细胞的方法,以合理的价格为病人创造基因相同的组织。但就算他不打算利用自己的突破性成果克隆人,也不意味着另一位企业家科学家不会这么做。

Another recent breakthrough was discovered by Dr. Yi Zhang, a stem-cell researcher at Boston Children’s Hospital; adult cells, from which clones are derived, have already specialized to a specific purpose in the body (such as being a part of the skin or liver), and have thus “shut down” certain genes. Implantation into an egg can reactivate many of these genes, but there are only a few hours to do so before the embryo begins developing with many crucial genes still unavailable, resulting in the demise of the clone. Several years ago, however, Zhang discovered a chemical that, when added to the egg, helps release the blocked genes much faster. Tested on mice, the chemically-modified eggs succeeded 10% of the time, compared to a dismal 1% rate of unaltered trials. A few years later, Zhang’s team tested the eggs of volunteer human women; without the chemical, no eggs successfully began development, whereas a quarter of those with the chemical did. Zhang’s team never implanted the embryos in hopes of making human babies; their goal was to develop ways to clone stem cells from adults in need, creating genetically identical tissues for sick people at a reasonable price. But even though he isn’t planning on using his breakthrough for human cloning doesn’t mean another entrepreneurial scientist won’t.

随着哺乳动物和灵长类克隆技术的最新进展,克隆人的问题很有可能回到科学和公众辩论的前沿。也许过去几十年的平静岁月对于将技术、发现和技术发展到生殖性克隆人可行的水平是真正必要的。如果这是真的,我们可能很快就会看到宠物克隆市场的需求会大大增加;但生殖性克隆的故事除了科学之外还有另一面——伦理、道德和激烈的辩论。

With the recent advances in mammal and primate cloning technology, it’s more than possible that the issue of human cloning will be brought back to the forefront of science and public debate. Perhaps the quiet years of the past few decades were truly necessary to advance techniques, discoveries, and technology to the level where reproductive human cloning was feasible. If this is true, we may soon see a much stronger demand for human clones evolving from the pet-cloning market; but there’s another side to the story of reproductive cloning beyond just the science— that of ethics, morality, and fierce debate.

社会僵局
Social Stalemate

对一些人来说,克隆的想法在他们的脑海中很少出现。但对其他人,尤其是那些积极参与生物体复制的科学家来说,克隆人是一个有争议的、令人关注的、敏感的课题。许多从事克隆研究的研究人员——包括张毅博士——在口头上反对利用生殖性克隆来创造活人。“没有一个社会能接受这一点,”张博士说,并评论了哺乳动物克隆带来的胚胎失败和错误怀孕的极端成本。张博士只打算利用克隆技术生产出与捐赠者具有相同遗传密码的胚胎干细胞,但由于诱导多能干细胞的日益成功,这种技术可能会在几年后被淘汰。诱导多能干细胞来源于成年人的细胞,在实验室条件下已恢复到非特定状态,使其与胚胎干细胞一样具有多功能性。鉴于诱导多能干细胞的制造比克隆胚胎要简单,在未来几年内,它们将有可能取代对胚胎干细胞的医学需求,从而减少对克隆人类胚胎的需求。

For some, the idea of cloning occupies very little space or worry in their mind. For others— especially those scientists actively involved in the duplication of living organisms— human cloning is a contentious, concerning, and touchy subject. Many researchers engaged in the study of cloning— including Dr. Yi Zhang— vocally discourage the use of reproductive cloning to create living human beings. “No society could accept this,” Zhang has said, commenting on the extreme cost of failed embryos and faulty pregnancies that comes with mammalian cloning. Zhang intends only to use cloning to produce embryonic stem cells with the same genetic code as their donors, a process that, only a few years after its discovery, may be becoming obsolete due to the rising success of induced pluripotent cells— cells derived from an adult’s cells that have been reverted back into an unspecialized state in a laboratory setting, making them as versatile as embryonic stem cells. Given that induced pluripotent cells are less complicated to create than cloned embryos, they will likely replace the medical need for embryonic stem cells in the coming years, diminishing the need for cloned human embryos.

但是克隆人呢?我们会不会看到孩子出生时是已故亲人的基因克隆体,或者是一位杰出科学家或世界领袖的人工创造的继任者?道德上的困境将在此同时发生。对一些人,尤其是像全美生命联盟这样的著名的保守宗教团体来说,所有形式的克隆人体组织,甚至胚胎克隆,都应该被禁止。相比不那么保守的部分福音派不鼓励创造克隆人,因为他们担心克隆人会导致人类生活的商品化,这是大多数主要宗教团体,特别是穆斯林伦理学家和民间领袖的共同观点,对他们来说,克隆人既是轻浮的行为,也是对上帝至高无上地位的侵犯。

But what about cloned humans? Will we ever see children born who are genetic clones of a deceased loved one, or the artificially-created successor to a brilliant scientist or world leader? Here, most of all, is where ethic and moral dilemmas seem to take place. To some— especially prominent and staunchly conservative religious groups like the All American Life League— all forms of cloning human tissue, even embryonic cloning, should be banned. A less severe Evangelical perspective discourages the creation of human clones for fear that it could lead to the commodification of human life, an opinion shared by most major religious groups, especially Muslim ethicists and civil leaders, to whom human cloning is both frivolous and an infringement on the supremacy of God.

对“更高权力”的冒犯和不尊重是这些反对克隆者的一种共识,他们的次要论点——认为克隆人是不负责任的行为,更能得到世俗社会的认同。简单来说,大多数人,尤其是那些致力于研究有可能应用于创造活生生的人类复制品的科学家,并不认为克隆是值得的。尽管最近在提高胎儿的生存能力方面取得了进展,但植入克隆胚胎对父母和孩子来说仍然是极其危险的,最终的结果——即使是成功妊娠——也不会是“原始胚胎”的完全复制品;一个人的个性、才能和行为不仅取决于他们的能力基因构成,但也取决于他们成长的环境,他们在一生中形成的互动和关系,以及他们所经历的独特经历。

While offense or disrespect to a higher power is consistent with and principal to the spiritual perspective surrounding cloning, their secondary arguments— especially regarding the frivolous or irresponsible nature of copying humans— are shared with the secular community. Simply put, most people, especially those scientists working on advancements that could potentially be applicable to the creation of living, human copies, don’t believe cloning is worth it. Despite recent progress in improving feta; viability, implanting cloned embryos can still be incredibly dangerous for both the parent and the child, and the end result— even in the case of a successful pregnancy— will not be an exact replica of the “original”; the personality, talent, and behavior of a person is dependent not only on their genetic makeup, but also on the environment in which they’re raised, the interactions and relationships they forge throughout life, and the unique experiences they undergo.

如今,大多数心理学家都认为,基因和环境因素共同作用,使我们成为真正的自己,而且这两者不易分离;因此,克隆人无法保证被克隆个体拥有理想的人格特征或才能。有悲伤的父母想要完美地复制他们失去的孩子,或者有人希望通过抚养一位著名作家或诺贝尔化学奖获得者的克隆人来作为培养成功后代的赌注,但他们不太可能得偿所愿,他们会看到一个新的人——有自己的愿望、行为,和身份-只是和原来的那个人有着相同的基因组成。我们很容易看出那些可能选择追求克隆的人的那种不切实际的(最终是失败的)期望将如何导致人类生存和个性的商品化,以及克隆人在一个可能遭到排斥的社会中生活质量的降低。归根结底,无论宗教信仰或对克隆的复杂性是否熟悉,似乎大多数人都不认为克隆是现代科学进步在伦理上或可行的应用。

Today, most psychologists agree that genetic and environmental factors work together to turn us into who we are, and cannot be easily separated; therefore, desirable personality traits or talents cannot be guaranteed in a clone. Grieving parents wanting to perfectly replicate their lost child or families hoping to hedge their bets for successful progeny by raising the clone of an acclaimed author or Nobel Prize winning chemist are unlikely to get what they expect, but rather a new person— with their own aspirations, behaviors, and identity— that is identical to the original in genetic makeup only. It’s easy to see how the unrealistic (and, eventually, disappointed) expectations of those who might choose to pursue cloning will lead to the commodification of human existence and individuality, as well as a lower quality of life for clones in a society where they will likely be ostracized. Ultimately, regardless of religious affiliation or familiarity with the intricacies of cloning, it seems as though most people do not see cloning as an ethical or viable application of modern scientific progress.

克隆会成为常态吗?
Will Cloning Ever Become Common?

《侏罗纪公园》和《加塔卡》等的电影暗示,人类注定要不负责任地利用科学进步,但真的是这样吗?纵观当今世界,30年来人类克隆的停滞似乎不太可能很快结束,更不用说开始以无法控制的速度发展了。随着技术的进步,一些国家正在采取先发制人的立法行动来禁止克隆。30多个国家禁止一切形式的克隆,15个国家禁止生殖性克隆,但允许治疗性(胚胎)克隆,尽管包括美国在内的许多国家尚未通过联邦法律,概述哪些研究或实践可以在私人实验室进行,哪些不可以在私人实验室进行。尽管如此,许多美国政治家(甚至前总统)都表示支持在全球范围内普遍禁止一切形式的人体组织克隆。其他国际组织,包括联合国、非洲联盟和阿拉伯联盟已经讨论了一项多国条约的问题,并可能有朝一日共同努力通过全球立法,使世界对一套共同的理想负责。

Movies like Jurassic Park and Gattaca imply that humanity is doomed to use scientific advancements irresponsibly, but is that really the case? Looking at the state of the world now, it seems unlikely that the thirty-year stagnation of human cloning is going to end anytime soon, let alone begin to develop at an uncontrollable pace. As technology progresses, some countries are taking preemptive legislative action to ban cloning. Over thirty countries prohibit all forms of cloning and fifteen countries ban reproductive cloning but allow therapeutic (embryonic) cloning, although many, including the United States, have yet to pass federal laws outlining what research or practices may or may not be conducted in private laboratories. Despite this, many American politicians (and even prior presidents) have expressed support for a global and universal ban on all forms of cloning of human tissue. Other international organizations, including the United Nations, African Union, and Arab Leagues have discussed the issue of a multinational treaty, and may someday collaboratively attempt to pass global legislation, and to hold the world accountable to a common set of ideals.

尽管将某些科学学科定为非法并不一定会阻止顽固的科学家继续他们的研究(以哥白尼和伽利略为例),但它确实使获得资金和公众支持变得更加困难,尤其是在克隆这样一个资源密集且容易失败的领域。今天,即使没有在全球范围内禁止生殖性克隆,世界上大多数国家已经出于各种难以争辩的原因坚决反对复制人类的想法;即使科学触手可及,创造心爱宠物和珍贵家畜的基因复制品的做法也越来越普遍,走路、说话的克隆人不太可能比那些虚构猜测更有趣了。

Although making particular scientific disciplines illegal does not necessarily discourage stubborn scientists from continuing their research (consider Copernicus and Galileo), it does make it significantly more difficult to gain funding and public support, especially for such a resource-heavy and failure-prone field as cloning. Today, even without a global ban on reproductive cloning, the majority of the world is already firmly against the idea of replicating human beings for a variety of reasons that are difficult to dispute; even with the science at the fingertips and the increasingly common practice of creating genetic duplicates of beloved pets and valuable livestock, it’s unlikely that walking, talking clones are ever going to be more than fun— and purely fictional— speculation.

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