The term cloning is used by scientists to describe many different processes that involve making duplicates of biological material. In most cases, isolated genes or cells are duplicated for scientific study, and no new animal results. The experiment that led to the cloning of Dolly the sheep in 1997 was different: It used a cloning technique called somatic cell nuclear transfer and resulted in an animal that was a genetic twin -- although delayed in time -- of an adult sheep. This technique can also be used to produce an embryo from which cells called embryonic stem (ES) cells could be extracted to use in research into potential therapies for a wide variety of diseases.
Thus, in the past five years, much of the scientific and ethical debate about somatic cell nuclear transfer has focused on its two potential applications: 1) for reproductive purposes, i.e., to produce a child, or 2) for producing a source of ES cells for research.
Cloning for Reproductive Purposes
The technique of transferring a nucleus from a somatic cell into an egg that produced Dolly was an extension of experiments that had been ongoing for over 40 years. In the simplest terms, the technique used to produce Dolly the sheep - somatic cell nuclear transplantation cloning - involves removing the nucleus of an egg and replacing it with the diploid nucleus of a somatic cell. Unlike sexual reproduction, during which a new organism is formed when the genetic material of the egg and sperm fuse, in nuclear transplantation cloning there is a single genetic "parent." This technique also differs from previous cloning techniques because it does not involve an existing embryo. Dolly is different because she is not genetically unique; when born she was genetically identical to an existing six-year-old ewe. Although the birth of Dolly was lauded as a success, in fact, the procedure has not been perfected and it is not yet clear whether Dolly will remain healthy or whether she is already experiencing subtle problems that might lead to serious diseases. Thus, the prospect of applying this technique in humans is troubling for scientific and safety reasons in addition to a variety of ethical reasons related to our ideas about the natural ordering of family and successive generations.
Scientific Uncertainties
Several important concerns remain about the science and safety of nuclear transfer cloning using adult cells as the source of nuclei. To date, five mammalian species -- sheep, cattle, pigs, goats, and mice -- have been used extensively in reproductive cloning studies. Data from these experiments illustrate the problems involved. Typically, very few cloning attempts are successful. Many cloned animals die in utero, even at late stages or soon after birth, and those that survive frequently exhibit severe birth defects. In addition, female animals carrying cloned fetuses may face serious risks, including death from cloning-related complications.
An additional concern focuses on whether cellular aging will affect the ability of somatic cell nuclei to program normal development. As somatic cells divide they proGREssively age, and there is normally a defined number of cell divisions that can occur before senescence. Thus, the health effects for the resulting liveborn, having been created with an "aged" nucleus, are unknown. Recently it was reported that Dolly has arthritis, although it is not yet clear whether the five-and-a-half-year-old sheep is suffering from the condition as a result of the cloning process. And, scientists in Tokyo have shown that cloned mice die significantly earlier than those that are naturally conceived, raising an additional concern that the mutations that accumulate in somatic cells might affect nuclear transfer efficiency and lead to cancer and other diseases in offspring. Researchers working with clones of a Holstein cow say genetic programming errors may explain why so many cloned animals die, either as fetuses or newborns.
Ethical Concerns
The announcement of Dolly sparked widespread speculation about a human child being created using somatic cell nuclear transfer. Much of the perceived fear that GREeted this announcement centered on the misperception that a child or many children could be produced who would be identical to an already existing person. This fear is based on the idea of "genetic determinism" -- that genes alone determine all aspects of an individual -- and reflects the belief that a person's genes bear a simple relationship to the physical and psychological traits that compose that individual. Although genes play an essential role in the formation of physical and behavioral characteristics, each individual is, in fact, the result of a complex interaction between his or her genes and the environment within which he or she develops. Nonetheless, many of the concerns about cloning have focused on issues related to "playing God," interfering with the natural order of life, and somehow robbing a future individual of the right to a unique identity.
Policy and Regulation
Several groups have concluded that reproductive cloning of human beings creates ethical and scientific risks that society should not tolerate. In 1997, the National Bioethics Advisory Commission recommended that it was morally unacceptable to attempt to create a child using somatic cell nuclear transfer cloning and suggested that a moratorium be imposed until safety of this technique could be assessed. The commission also cautioned against preempting the use of cloning technology for purposes unrelated to producing a liveborn child.
Similarly, in 2001 the National Academy of Sciences issued a report stating that the United States should ban human reproductive cloning aimed at creating a child because experience with reproductive cloning in animals suggests that the process would be dangerous for the woman, the fetus, and the newborn, and would likely fail. The report recommended that the proposed ban on human cloning should be reviewed within five years, but that it should be reconsidered "only if a new scientific review indicates that the procedures are likely to be safe and effective, and if a broad national dialogue on societal, religious and ethical issues suggests that reconsideration is warranted." The panel concluded that the scientific and medical considerations that justify a ban on human reproductive cloning at this time do not apply to nuclear transplantation to produce stem cells. Several other scientific and medical groups also have stated their opposition to the use of cloning for the purpose of producing a child.
Cloning for the Isolation of Human ES Cells
The cloning debate was reopened with a new twist late in 1998, when two scientific reports were published regarding the successful isolation of human stem cells. Stem cells are unique and essential cells found in animals that are capable of continually reproducing themselves and renewing tissue throughout an individual organism's life. ES cells are the most versatile of all stem cells because they are less differentiated, or committed, to a particular function than adult stem cells. These cells have offered hope of new cures to debilitating and even fatal illness. Recent studies in mice and other animals have shown that ES cells can reduce symptoms of Parkinson's disease in mouse models, and work in other animal models and disease areas seems promising.
In the 1998 reports, ES cells were derived from in vitro embryos six to seven days old destined to be discarded by couples undergoing infertility treatments, and embryonic germ (EG) cells were obtained from cadaveric fetal tissue following elective abortion. A third report, appearing in the New York Times, claimed that a Massachusetts biotechnology company had fused a human cell with an enucleated cow egg, creating a hybrid clone that failed to proGREss beyond an early stage of development. This announcement served as a reminder that ES cells also could be derived from embryos created through somatic cell nuclear transfer, or cloning. In fact, several scientists believed that deriving ES cells in this manner is the most promising approach to developing treatments because the condition of in vitro fertilization (IVF) embryos stored over time is questionable and this type of cloning could overcome graft-host responses if resulting therapies were developed from the recipient's own DNA.
Ethical Concerns
For those who believe that the embryo has the moral status of a person from the moment of conception, research or any other activity that would destroy it is wrong. For those who believe the human embryo deserves some measure of respect, but disaGREe that the respect due should equal that given to a fully formed human, it could be considered immoral not to use embryos that would otherwise be destroyed to develop potential cures for disease affecting millions of people. An additional concern related to public policy is whether federal funds should be used for research that some Americans find unethical.
Policy and Regulation
Since 1996, ConGREss has prohibited researchers from using federal funds for human embryo research. In 1999, DHHS announced that it intended to fund research on human ES cells derived from embryos remaining after infertility treatments. This decision was based on an interpretation "that human embryonic stem cells are not a human embryo within the statutory definition" because "the cells do not have the capacity to develop into a human being even if transferred to the uterus, thus their destruction in the course of research would not constitute the destruction of an embryo." DHHS did not intend to fund research using stem cells derived from embryos created through cloning, although such efforts would be legal in the private sector.
In July 2001, the House of Representatives voted 265 to 162 to make any human cloning a criminal offense, including cloning to create an embryo for derivation of stem cells rather than to produce a child. In August 2002, President Bush, contending with a DHHS decision made during the Clinton administration, stated in a prime-time television address that federal support would be provided for research using a limited number of stem cell colonies already in existence (derived from leftover IVF embryos). Current bills before ConGREss would ban all forms of cloning outright, prohibit cloning for reproductive purposes, and impose a moratorium on cloning to derive stem cells for research, or prohibit cloning for reproductive purposes while allowing cloning for therapeutic purposes to go forward. As of late June, the Senate has taken no action. President Bush's Bioethics Council is expected to recommend the prohibition of reproductive cloning and a moratorium on therapeutic cloning later this summer.
Prepared by Kathi E. Hanna, M.S., Ph.D., Science and Health Policy Consultant
因此，在过去的五年中，许多科学和伦理辩论，体细胞核转移的重点放在了两个潜在的应用前景： 1 ）为生殖目的，即产生一个孩子，或2 ）的生产来源的胚胎干细胞进行研究。
为生殖目的的克隆
技术转移的核心从体细胞变成一个鸡蛋生产多莉是一个扩展的实验已经进行了超过40年。在最简单的角度来看，技术用于生产多莉羊-体细胞核移植克隆-涉及消除核的卵子，代之以二倍体核体细胞。与有性繁殖，在此期间，一个新的生物体形成的遗传物质的卵和精子融合，核移植克隆技术有一个单一的遗传“父母。 ”这种技术也不同于以往的克隆技术，因为它不涉及现有的胚胎。多莉是不同的，因为她是没有的独特的基因，当她出生的基因完全相同现有6岁母羊。虽然多莉的诞生被称赞是一个成功的，事实上，该程序还没有完善和目前尚不清楚是否多莉将保持健康或她是否已经经历一个十分敏感的问题，可能导致严重的疾病。因此，展望这一技术的应用在人类令人不安的是科学和安全原因，除了各种各样的道德原因与我们的想法，自然有序的家庭和后代。
科学上的不确定性
有几个重要的问题仍然是关于科学和安全使用核转移克隆成年细胞的来源原子核。到目前为止， 5个哺乳动物物种-羊，牛，猪，羊，老鼠-已被广泛用于生殖性克隆研究。这些实验数据，说明所涉及的问题。一般来说，只有极少数的克隆尝试是成功的。许多克隆动物死在子宫内，甚至在后期或出生后不久，那些生存下来经常展览严重出生缺陷。此外，雌性动物进行克隆胎儿可能面临严重的风险，包括死亡的克隆有关的并发症。
另外一个关注的重点是否会影响细胞老化的能力，以体细胞核程序正常发展。体细胞分裂他们逐步年龄，而且通常是指一些细胞分裂前可能发生衰老。因此，对健康的影响的结果活，创造了一个“年龄”的核心，目前还无从知晓。最近据报道，多有关节炎，虽然目前尚不清楚是否五年半岁绵羊是痛苦的条件所造成的克隆过程。而且，科学家们在东京表明，克隆小鼠死于大大早于那些自然的设想，提高额外的关注，突变，积聚在体细胞可能影响核移植效率和导致癌症和其他疾病的后代。研究人员与克隆的荷斯坦奶牛说遗传编程错误也许可以解释为什么有那么多的克隆动物死亡，无论是作为胎儿或新生儿。
伦理问题
宣布多莉引发了广泛的猜测，人类的孩子正在建立利用体细胞核转移。大部分的担心，认为迎接本公告为中心的错误观念，儿童或许多儿童可以产生谁是相同的一个已经存在的人。这种担心是基于“的理念基因决定论” -即基因单独确定各方面的一个人-和反映，认为一个人的基因产生一种简单的关系，身体和心理特征撰写个人。虽然基因发挥重要作用，形成的生理和行为特征，每一个人，事实上，由于复杂的相互作用他或她的基因和环境，使他或她的发展。尽管如此，许多担心克隆集中相关的问题上“打神” ，干扰了自然秩序的生活，并以某种方式失去未来个人的权利，独特的个性。
政策与法规
几组得出结论认为，人的生殖性克隆的伦理和科学创造的风险，社会不应容忍。 1997年，国家生物伦理咨询委员会建议，这是道德上是不可接受的，试图建立一个儿童用体细胞核转移克隆，并建议暂停实施，直到安全这一技术可以评估。该委员会还警告不要抢占利用克隆技术的目的无关的生产活的孩子。
同样，在2001年美国国家科学院发表的一份报告指出，美国应当禁止人的生殖性克隆，旨在建立一个儿童因为生殖性克隆的经验表明，在动物中的进程将是危险的妇女，胎儿，和新生儿，并很可能会失败。该报告建议，提议禁止克隆人应在五年内完成审查，但它应该重新考虑“只有当一个新的科学审查表明，该程序很可能是安全有效的，如果一个广泛的民族对话的社会，宗教和道德问题，建议重新考虑是有道理的。 “小组的结论是，科学和医疗考虑的理由，禁止人的生殖性克隆在这个时候并不适用于核移植产生的干细胞。其他一些科学和医疗组也已表示反对使用克隆技术的目的是产生一个孩子。
克隆的分离人类ES细胞
克隆辩论是开放的新的转折在1998年末，当两个科学报告发表了关于成功分离人类干细胞。干细胞是唯一的和必不可少的细胞中发现的动物，有能力不断地复制自己，并重新组织整个个人有机体的生命。胚胎干细胞是最多才多艺的所有干细胞，因为它们是有区别的少，或承诺，某一特定功能比成人干细胞。这些细胞带来了希望的新疗法，以削弱甚至致命的疾病。最近的研究中的老鼠和其他动物已经表明， ES细胞可以减少症状的帕金森氏病的小鼠模型，并在其他动物模型和疾病领域似乎大有希望。
在1998年的报告中，胚胎干细胞来自胚胎在体外培养六至七天岁注定要被丢弃的夫妇接受不孕治疗，和胚胎生殖（例如）细胞取自尸体胎儿组织下列选任堕胎。第三份报告，出现在纽约时报称，马萨诸塞州的生物技术公司已融合人体细胞与牛的去核卵，形成混合克隆未能取得进展超出了初步的发展阶段。这一宣布是一个提醒人们，胚胎干细胞也可能产生胚胎产生的体细胞核转移或克隆。事实上，一些科学家认为，胚胎干细胞所产生的这种方式是最有希望的方式来处理，因为发展中国家的情况体外受精（试管婴儿）胚胎储存一段时间是值得怀疑和这种类型的克隆可以克服移植物抗宿主反应，如果造成疗法是从受援国自己的DNA 。
伦理问题
对于那些谁认为，胚胎的道德地位，一个人从受孕，研究或任何其他活动，会破坏它是错误的。对于那些谁相信人类胚胎应有一定程度的尊重，但不认为应该尊重平等，考虑到完全形成的人的，它可以被认为是不道德不使用胚胎，否则予以销毁发展潜力治愈疾病的影响数百万人死亡。额外的关注与公共政策是联邦基金应当用于研究，一些美国人发现不道德的。
政策与法规
自1996年以来，国会已禁止研究人员使用联邦基金对人类胚胎研究。 1999年， DHHS宣布，它打算基金研究人类胚胎干细胞来自胚胎的不孕症治疗后仍有剩余。这一决定是基于一种解释“说，人类胚胎干细胞并非人体胚胎内的法定定义” ，因为“细胞没有能力发展成为一个人，即使转移到子宫，从而使其破坏研究过程中不会构成破坏胚胎。 “ DHHS不打算基金研究利用干细胞来自胚胎克隆形成，尽管这种努力将是法律在私营部门。
2001年7月，众议院表决265至162作出任何克隆人的犯罪行为，包括克隆技术培养出胚胎用于干细胞的推导，而不是产生一个孩子。 2002年8月，美国总统布什，对立与DHHS决定在克林顿政府执政期间，在黄金时段电视讲话说，联邦政府将提供支持的研究使用数量有限的干细胞已经存在的殖民地（来源于剩余胚胎胚胎） 。目前在美国国会的法案，禁止一切形式的克隆彻底，禁止为生殖目的的克隆，并暂停克隆以获取干细胞进行研究，或禁止生殖性克隆的目的，同时允许克隆技术用于治疗目的的向前迈进。截至6月末，参议院已采取任何行动。布什总统的生物伦理委员会预计将建议禁止生殖性克隆和治疗性克隆暂停今年夏天晚些时候。
编写凯茜林大肠杆菌汉娜，硕士，博士，科学和卫生政策顾问
