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children develop their own autonomy and decision-making capacity. This is based on the assumption that, except under rare circumstances, parents have the most to lose or gain from a decision and will ultimately make decisions that reflects the future values and beliefs of their children. According to this assumption, it could be assumed that parents are the most appropriate decision makers for their future children as well. However, there are anecdotal reports of children and adults who disagree with the medical decisions made by a parent during pregnancy or early childhood, such as when death was a possible outcome. There are also published patient stories by individuals who feel that they would not wish to change or remove their own medical condition if given the choice and individuals who disagree with medical decisions made by their parents during childhood.
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on Human Gene
Editing in December 2015 the collaboration of scientists issued the first international guidelines on genetic research. These guidelines allow for the pre-clinical research into the editing of genetic sequences in human cells granted the embryos are not used to implant pregnancy. Genetic alteration of somatic cells for therapeutic proposes was also considered an ethically acceptable field of research in part due to the lack of ability of somatic cells to transfer genetic material to subsequent generations. However citing the lack of social consensus, and the risk of inaccurate gene editing the conference called for restraint on any germline modifications on implanted embryos intended for pregnancy.
206: to edit single-celled, non-viable embryos to see the effectiveness of this technique. This attempt was rather unsuccessful; only a small fraction of the embryos successfully incorporated the new genetic material and many of the embryos contained a large number of random mutations. The non-viable embryos that were used contained an extra set of chromosomes, which may have been problematic. In 2016, another similar study was performed in China which also used non-viable embryos with extra sets of chromosomes. This study showed very similar results to the first; but there weren't successful integrations of the desired gene, and the majority of the attempts failed, or produced undesirable mutations.
248:(gRNA). Cas9 acts as a pair of âmolecular scissorsâ that can cut the DNA at a specific location in the genome so that DNA can be added or removed. The guide RNA is a piece of RNA with complementary bases to those at the target location, so that it will only bind there and no other regions of the genome. The Cas9 follows the guide RNA to the same location in the DNA sequence and makes a cut across both strands of the DNA. At this stage, the cell recognizes that the DNA is damaged and tries to repair it. Scientists can use the DNA repair machinery to introduce changes to one or more genes in the genome of a cell of interest.
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be short because his parents are very short. Editing the embryo of boy 1 to make him of average height would be a therapeutic germline edit, while editing the embryo of boy 2 to be of average height would be a non-therapeutic germline edit. In both cases with no editing of the boys' genomes they would both grow up to be very short, which would decrease their wellbeing in life. Likewise editing both of the boys' genomes would allow them to grow up to be of average height. In this scenario, editing for the same phenotype for being of average height falls under both therapeutic and non-therapeutic germline engineering.
327:". The concept of a "designer baby" is that its entire genetic composition could be selected for. In an extreme case, people would be able to effectively create the offspring that they want, with a genotype of their choosing. Not only does human germline engineering allow for the selection of specific traits, but it also allows for enhancement of these traits. Using human germline editing for selection and enhancement is currently very heavily scrutinized, and the main driving force behind the movement of trying to ban human germline engineering.
256:. This could be used to eliminate certain diseases in humans, or at least significantly decrease a disease's frequency until it eventually disappears over generations. Cancer survivors theoretically would be able to have their genes modified by the CRISPR/Cas9 so that certain diseases or mutations will not be passed down to their offspring. This could possibly eliminate cancer predispositions in humans. Researchers hope that they can use the system in the future to treat currently incurable diseases by altering the genome altogether.
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subject. Because RNA processes differ between bacteria and mammalian cells, scientists have had difficulties coding for mRNA's translated data without the interference of RNA. Studies have been done using the Cas9 nuclease that uses a single guide RNA to allow for larger knockout regions in mice, and this was successful. Altering the genetic sequence of mammals is also widely debated, and this creates a difficult FDA regulation standard for such studies.
191:, which then mature into genetically modified eggs and sperm. For safety, ethical, and social reasons, there is broad agreement among the scientific community and the public that germline editing for reproduction is a red line that should not be crossed at this point in time. There are differing public sentiments, however, on whether it may be performed in the future depending on whether the intent would be therapeutic or non-therapeutic.
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773:'s Council on Ethical and Judicial Affairs stated that "genetic interventions to enhance traits should be considered permissible only in severely restricted situations: (1) clear and meaningful benefits to the fetus or child; (2) no trade-off with other characteristics or traits; and (3) equal access to the genetic technology, irrespective of income or other socioeconomic characteristics."
25:
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statement on
November 28, calling on scientists to improve self-discipline and self-regulation, and to abide by corresponding ethical principles, laws, and regulations. Finally, the Chinese Academy of Medical Sciences published a correspondence in The Lancet, stating that they are âopposed to any clinical operation of human embryo genome editing for reproductive purposes."
398:, Paul Bergfrom along with others across the globe published a call for a framework that does not foreclose any outcome but includes a voluntary pledge by nations along with a coordinating body to monitor the application of pledged nations in a moratorium on human germline editing with an attempt to reach social consensus before moving forward into further research.
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810:, according to which âcouples (or single reproducers) should select the child, of the possible children they could have, who is expected to have the best life, or at least as good a life as the others, based on the relevant, available informationâ. Some ethicists argue that the principle of procreative beneficence would justify or even require
217:. In May 2019, lawyers in China reported, in light of the purported creation by He Jiankui of the first gene-edited humans, the drafting of regulations that anyone manipulating the human genome by gene-editing techniques, like CRISPR, would be held responsible for any related adverse consequences.
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the mutants recovered from strokes more quickly and had improved motor and cognitive functions following traumatic brain injury. The later study, in the 21 February issue of Cell, also included an analysis of 68 stroke patients who had one copy of CCR5 with the HIV resistance mutation; it concluded they had improved recovery, too.
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which also increased their muscle mass. This showed that muscle mass could be increased with germline editing, which is likely applicable to humans because humans also have the myostatin gene to regulate muscle growth. Human germline engineering may then result in intentionally increased muscle mass, with applications such as
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normal CCR5, she is expected to have no protection from HIV. Nana, according to the data He presented in a slide at an international genome-editing summit held in
November 2018 in Hong Kong, China, had bases added to one CCR5 copy and deleted from the other, which likely would cripple both genes and provide HIV resistance.
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There is distinction in some country policies, including but not limited to official regulation and legislation, between human germline engineering for reproductive use and for laboratory research. As of
October 2020, there are 96 countries that have policies involving the use of germline engineering
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further argues that âold-fashioned sexual reproduction is itself an untested genetic experimentâ, often compromising a child's wellbeing and pro-social capacities even if the child grows in a healthy environment. According to Pearce, âthe question of comes down to an analysis of risk-reward ratios â
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One issue related to human genome editing relates to the impact of the technology on future individuals whose genes are modified without their consent. Clinical ethics accepts the idea that parents are, almost always, the most appropriate surrogate medical decision makers for their children until the
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in the embryos occurred preferentially through alternative pathways. In the end only 4 of the 54 zygotes carried the intended genetic information, and even then the successfully edited embryos were mosaics containing the preferential genetic code and the mutation. The conclusion of the scientists was
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On the night of
November 26, 122 Chinese scientists issued a statement strongly condemning He's action as unethical. They stated that while CRISPR-Cas is not a new technology, it involves serious off-target risks and associated ethical considerations, and so should not be used to produce gene-altered
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He added the genes for the CRISPR machinery almost immediately after each embryo was created through in vitro fertilization, but several researchers who closely studied the slide caution that it may have done its editing after Nana's embryo was already past the one-cell stage. That means she could be
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The lack of clear international regulation has led to researchers across the globe attempting to create an international framework of ethical guidelines. Current framework lacks the requisite treaties among nations to create a mechanism for international enforcement. At the first
International Summit
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There is also debate on if there can be a defined distinction between therapeutic and non-therapeutic germline editing. An example would be if two embryos are predicted to grow up to be very short in height. Boy 1 will be short because of a mutation in his Human Growth
Hormone gene, while boy 2 will
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A relevant issue concerns âoff target effectsâ, large genomes may contain identical or homologous DNA sequences, and the enzyme complex CRISPR/Cas9 may unintentionally cleave these DNA sequences causing mutations that may lead to cell death. The mutations can cause important genes to be turned on or
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has a right to remain genetically unmodified, that parents hold the right to genetically modify their offspring, and that every child has the right to be born free of preventable diseases. For parents, genetic engineering could be seen as another child enhancement technique to add to diet, exercise,
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People inherit two copies of CCR5, one from each parent. He chose the gene as a target because he knew that about 1% of
Northern European populations are born with both copies missing 32 base pairs, resulting in a truncated protein that does not reach the cell surface. These people, known as CCR5Î32
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and implanted into five surrogates, resulting in 16 piglets. It was found that only specific mutations to the myostatin signal peptide resulted in increased muscle mass in the piglets mainly due to an increase in muscle fibers. A similar animal study created a knockout in the myostatin gene in mice,
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The other ethical concern is the potential for âdesigner babiesâ, or the creation of humans with "perfect", or "desirable" traits. There is a debate as to if this is morally acceptable as well. Such debate ranges from the ethical obligation to use safe and efficient technology to prevent disease to
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Aside from the primary HIV concerns, the gene edits may have inadvertently altered cognitive function. Researchers showed in 2016 that knocking out one or both CCR5s in mice enhances their memory and cognition. A subsequent study that crippled CCR5 in mice found that, compared with control animals,
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A major concern has been that He
Jiankui's attempts to cripple CCR5, the gene for a protein on immune cells that HIV uses to infect the cells, also made âoff-targetâ changes elsewhere in the girls' genomes. Those changes could cause cancer or other problems. He contends that the babies have no such
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female participants are HIV-negative. The participants' sperm was âwashed offâ to get rid of HIV and then injected into eggs collected from the female participants. By using clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9, a gene editing technique, they disabled a gene called
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Several religious positions have been published with regards to human germline engineering. According to them, many see germline modification as being more moral than the alternative, which would be either discarding of the embryo, or birth of a diseased human. The main conditions when it comes to
758:, a group of scientists urged a worldwide moratorium on clinical use of gene editing technologies to edit the human genome in a way that can be inherited. In April 2015, researchers reported results of basic research to edit the DNA of non-viable human embryos using CRISPR, creating controversy.
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funds to engage in research regarding human germline modification. In April 2015, a research team published an experiment in which they used CRISPR to edit a gene that is associated with blood disease in non-living human embryos. This experiment was unsuccessful, but gene editing tools are used in
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Although the CRISPR/Cas9 can be used in humans, it is more commonly used by scientists in other animal models or cell culture systems, including in experiments to learn more about genes that could be involved in human diseases. Clinical trials are being conducted on somatic cells, but CRISPR could
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Reproductive use of human germline engineering involves implanting the edited embryo to be born. 70 countries currently explicitly prohibit the use of human germline engineering for use in reproduction, while 5 countries prohibit it for reproduction with exceptions. No countries permit the use of
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There remains debate on if the permissibility of human germline engineering for reproduction is dependent on the use, being either a therapeutic or non-therapeutic application. In a survey by the UK's Royal
Society, 76% of participants in the UK supported therapeutic human germline engineering to
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posted a statement declaring their opposition to any clinical use of genome editing on human embryos, noting that âthe theory is not reliable, the technology is deficient, the risks are uncontrollable, and ethics and regulations prohibit the actionâ. The Chinese Academy of Engineering released a
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technology to correct a single mistaken amino acid successfully in 16 out of 18 attempts in a human embryo. The unusual level of precision was achieved by the use of a base editor (BE) system which was constructed by fusing the deaminase to the dCas9 protein. The BE system efficiently edits the
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and homology-directed repair response with high accuracy and precision. Double-strand breaks at the mutant paternal allele were repaired using the homologous wild-type gene. By modifying the cell cycle stage at which the DSB was induced, they were able to avoid mosaicism, which had been seen in
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In the embryos, He's team designed CRISPR to cut CCR5 at the base pair at one end of the natural deletion. The error-prone cell-repair mechanism, which CRISPR depends on to finish knocking out genes, then deleted 15 base pairs in one of Lulu's copies of the gene, but none in the other. With one
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He explained the details of his experiment in his address at the Hong Kong conference. He and his team had recruited eight couples through an HIV volunteer group named Baihualin (BHL) China League (one couple later withdrew from the research). All the male participants are HIV-positive, and all
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Scientists using the CRISPR/Cas9 system to modify genetic materials have run into issues when it comes to mammalian alterations due to the complex diploid cells. Studies have been done in microorganisms regarding loss of function genetic screening and some studies have been done using mice as a
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Ma H, Marti-Gutierrez N, Park SW, Wu J, Lee Y, Suzuki K, Koski A, Ji D, Hayama T, Ahmed R, Darby H, Van Dyken C, Li Y, Kang E, Park AR, Kim D, Kim ST, Gong J, Gu Y, Xu X, Battaglia D, Krieg SA, Lee DM, Wu DH, Wolf DP, Heitner SB, Belmonte JC, Amato P, Kim JS, Kaul S, Mitalipov S (August 2017).
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Another ethical concern pertains to potential unequal distribution of benefits, even in the case of genome editing being inexpensive. For example, corporations may be able to take unfair advantage of patent law or other ways of restricting access to genome editing and thereby may increase the
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is could effectively be used as a gene-editing tool in human 2PN zygotes, which could lead potentially pregnancy viable if implanted. The scientists used injection of Cas9 protein complexed with the relevant sgRNAs and homology donors into human embryos. The scientists found homologous
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The first known publication of research into human germline editing was by a group of Chinese scientists in April 2015 in the Journal "Protein and Cell". The scientists used tripronuclear (3PN) zygotes, zygotes fertilized by two sperm and therefore non-viable, to investigate
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signal peptide. Myostatin is a negative regulator of muscle growth, so through mutating the signal peptide regions of the gene, muscle growth could be promoted in the experimental pigs. The Myostatin genes in 955 pig embryos were mutated at several locations with
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gene without evidence of unintended mutations. The scientists concluded that the technique may be used for the correction of mutations in human embryos. The claims of this study were however pushed back on by critics who argued the evidence was overall
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There are concerns that the introduction of desirable traits in a certain part of the population (instead of the entire population) could cause economic inequalities (âpositionalâ good). However, this is not the case if a same desirable trait would be
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Gonzalez-Cadavid, Nestor F.; Taylor, Wayne E.; Yarasheski, Kevin; Sinha-Hikim, Indrani; Ma, Kun; Ezzat, Shereen; Shen, Ruoqing; Lalani, Rukhsana; Asa, Sylvia; Mamita, Mohamad; Nair, Gouri; Arver, Stefan; Bhasin, Shalender (1998-12-08).
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prevent or correct disease, however for non-therapeutic edits such as enhancing intelligence or altering eye or hair color in embryos, there was only 40% and 31% support, respectively. There was a similar result in a study at the
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in the embryos, aiming to close the protein doorway that allows HIV to enter a cell and make the subjects immune to the HIV virus. The process led to at least one successful pregnancy and the birth of the twin baby girls,
462:, a Chinese researcher of the Southern University of Science and Technology, released a video on YouTube announcing that he and his colleagues have âcreatedâ the world's first genetically altered babies, Lulu and Nana.
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Human germline engineering is a widely debated topic, and in more than 40 countries, it is formally outlawed. While there is no current legislation explicitly prohibiting germline engineering in the United States, the
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In June 2018, a group of scientists published and article in "Nature" journal indicating a potential link for edited cells having increased potential turn cancerous. The scientists reported that genome editing by
1919:
Li, Ruiqiang; Zeng, Wu; Ma, Miao; Wei, Zixuan; Liu, Hongbo; Liu, Xiaofeng; Wang, Min; Shi, Xuan; Zeng, Jianhua; Yang, Linfang; Mo, Delin; Liu, Xiaohong; Chen, Yaosheng; He, Zuyong (February 2020).
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babies. They described He's experiment as âcrazyâ and âa huge blow to the global reputation and development of Chinese scienceâ. The Scientific Ethics Committee of the Academic Divisions of the
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Alanis-Lobato, Gregorio; Zohren, Jasmin; McCarthy, Afshan; Fogarty, Norah M. E.; Kubikova, Nada; Hardman, Emily; Greco, Maria; Wells, Dagan; Turner, James M. A.; Niakan, Kathy K. (June 2021).
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was highly inefficient and did not do so in a majority of the trials. Problems arose such as off target cleavage and the competitive recombination of the endogenous delta-globin with the
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National Academies of Sciences, Engineering, and Medicine. 2017. Human Genome Editing: Science, Ethics, and Governance. Washington, DC: The National Academies Press. doi: 10.17226/24623.
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Other scientists and philosophers have noted that the issue of the lack of prior consent applies as well to individuals born via traditional sexual reproduction. Philosopher
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gave support to human genome editing in 2017 once answers have been found to safety and efficiency problems "but only for serious conditions under stringent oversight." The
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mutations would result in copies of the gene which do not possess any mutations, effectively curing the disease. If the germline could be edited, this normal copy of the
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Tang L, Zeng Y, Du H, Gong M, Peng J, Zhang B, Lei M, Zhao F, Wang W, Li X, Liu J (June 2017). "CRISPR/Cas9-mediated gene editing in human zygotes using Cas9 protein".
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RodrĂguez-RodrĂguez, Diana Raquel; RamĂrez-SolĂs, Ramiro; Garza-Elizondo, Mario Alberto; Garza-RodrĂguez, MarĂa De Lourdes; Barrera-Saldaña, Hugo Alberto (April 2019).
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2011:
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In March 2017, a group of Chinese scientists claimed to have edited three normal viable human embryos out of six total in the experiment. The study showed that
852:, Colombia, where students as well as professors generally agreed that therapeutic genome editing is acceptable, while non-therapeutic genome editing is not.
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The biologists writing in Science support continuing laboratory research with the technique, and few if any scientists believe it is ready for clinical use.
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Human germline engineering could be used to heritably cure genetic disorders and other diseases, and to give specific traits to human babies. For example,
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Another use would be to cure genetic disorders. In the first study published regarding human germline engineering, the researchers attempted to edit the
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whether or not it is morally and ethically acceptable lie within the intent of the modification, and the conditions in which the engineering is done.
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gene (which codes for a protein on the surface of white blood cells, targeted by the HIV virus) that deactivates the expression of CCR5, conferring
382:, scientists have continued discussion on the best possible mechanism for enforcement of an international framework. On March 13, 2019 researchers
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Wivel, Nelson A.; Walters, LeRoy (22 October 1993). "Germ-Line Gene Modification and Disease Prevention: Some Medical and Ethical Perspectives".
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education, training, cosmetics, and plastic surgery. Another theorist claims that moral concerns limit but do not prohibit germline engineering.
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Haapaniemi E, Botla S, Persson J, Schmierer B, Taipale J (July 2018). "CRISPR-Cas9 genome editing induces a p53-mediated DNA damage response".
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use, where edited cells will not be implanted to be born. 19 countries currently explicitly prohibit any use of human germline engineering for
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mutation in both somatic cells and germline cells. The study is noted for its relative precision which is a departure from past results of
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induced DNA damage response and the cell cycle stopped. The study was conducted in human retinal pigment epithelial cells, and the use of
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Liang P, Xu Y, Zhang X, Ding C, Huang R, Zhang Z, Lv J, Xie X, Chen Y, Li Y, Sun Y, Bai Y, Songyang Z, Ma W, Zhou C, Huang J (May 2015).
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In general, CRISPR-Cas9 is one of the most effective gene-editing technique to date. The CRISPR-Cas9 system consists of an enzyme called
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using these new tools, and such concerns have continued as technology progressed. In March 2015, with the advent of new techniques like
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With the international outcry in response to the first recorded case of human germ line edited embryos being implanted by researcher
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Using germline editing for reproduction is prohibited by law in more than 70 countries and by a binding international treaty of the
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2966:"Ethical issues related to prenatal genetic testing. The Council on Ethical and Judicial Affairs, American Medical Association".
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Powell R, Buchanan A (February 2011). "Breaking evolution's chains: the prospect of deliberate genetic modification in humans".
187: of an individual is edited in such a way that the change is heritable. This is achieved by altering the genes of the
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In November 2018, a group of Chinese scientists published research in the journal "Molecular Therapy" detailing their use of
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In a 2019 animal study with Liang Guang Small Spotted pigs, increased muscle mass was achieved with precise editing of the
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Roco MC, Bainbridge WS (2002). "Converging Technologies for Improving Human Performance: Integrating From the Nanoscale".
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Smith KR, Chan S, Harris J (October 2012). "Human germline genetic modification: scientific and bioethical perspectives".
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inequalities. There are already disputes in the courts where CRISPR-Cas9 patents and access issues are being negotiated.
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earlier similar studies, in cleaving embryos and achieve a large percentage of homozygous embryos carrying the wild-type
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1921:"Precise editing of myostatin signal peptide by CRISPR/Cas9 increases the muscle mass of Liang Guang Small Spotted pigs"
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530:-mediated gene editing in human cells, something that had never been attempted before. The scientists found that while
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As early in the history of biotechnology as 1990, there have been scientists opposed to attempts to modify the human
2685:"Correction of the Marfan Syndrome Pathogenic FBN1 Mutation by Base Editing in Human Cells and Heterozygous Embryos"
1475:"Edición genómica heredable: un estudio exploratorio desde la perspectiva del principio bioético de la beneficencia"
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a genetic âmosaicâ who has some unaffected cells with normal CCR5âand ultimately might have no protection from HIV.
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2028:"Organization of the human myostatin gene and expression in healthy men and HIV-infected men with muscle wasting"
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Countries that explicitly prohibit (with exceptions) the use of human germline engineering for reproduction are:
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Katz G, Pitts PJ (November 2017). "Implications of CRISPR-Based Germline Engineering for Cancer Survivors".
3243:"Potential impact of human mitochondrial replacement on global policy regarding germline gene modification"
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On 25 November 2018, two days before the Second International Summit on Human Genome Editing in Hong Kong,
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targeted C to T or G to A without the use of a donor and without DBS formation. The study focused on the
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Cohen IG, Adashi EY (August 2016). "SCIENCE AND REGULATION. The FDA is prohibited from going germline".
2005:
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Cyranoski, David; Reardon, Sara (22 April 2015). "Chinese scientists genetically modify human embryos".
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to edit out a mutation responsible for congenital heart disease. The study looked at heterozygous
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announced on December 18, 2018 plans to convene an intentional committee on clinical germline editing.
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Savulescu, Julian (October 2001). "Procreative Beneficence: Why We Should Select the Best Children".
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3337:"Genome engineering through CRISPR/Cas9 technology in the human germline and pluripotent stem cells"
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213: created the first human genetically edited babies, known by their pseudonyms,
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Vassena, R.; Heindryckx, B.; Peco, R.; Pennings, G.; Raya, A.; Sermon, K.; Veiga, A. (June 2016).
1745:"Genome editing: A perspective on the application of CRISPR/Cas9 to study human diseases (Review)"
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Ormond KE, Mortlock DP, Scholes DT, Bombard Y, Brody LC, Faucett WA, et al. (August 2017).
198:. However, in November 2015, a group of Chinese scientists used the gene-editing technique
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Countries that explicitly prohibit any use of human germline engineering for reproduction are:
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280:). One proposal is to genetically modify human embryos to give the CCR5 Î32 allele to people.
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off-target mutations, although some scientists are skeptical of the evidence offered so far.
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Zeng Y, Li J, Li G, Huang S, Yu W, Zhang Y, Chen D, Chen J, Liu J, Huang X (November 2018).
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Ranisch, Robert (2 December 2017). "Germline Genome Editing and the Functions of Consent".
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Playing God?: Human Genetic Engineering and the Rationalization of Public Bioethical Debate
587:. The scientists also noted the limitations of their study and called for further research.
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Countries that explicitly prohibit (with exceptions) the use of germline engineering for
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The Center for Health Ethics, University of Missouri School of Medicine. 25 April 2013.
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off, such as genetic anti-cancer mechanisms, that could speed up disease exasperation.
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and our basic ethical values, themselves shaped by our evolutionary past.â Bioethicist
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Baylis F, Robert JS (2004). "The inevitability of genetic enhancement technologies".
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666:. The study provides proof positive for the corrective value of gene therapy for the
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Design and Destiny: Jewish and Christian Perspectives on Human Germline Modification
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The Declaration of Inuyama: Human Genome Mapping, Genetic Screening and Gene Therapy
2669:
2533:
Ma H, Marti-Gutierrez N, Park SW, Wu J, Lee Y, Suzuki K, et al. (August 2017).
2519:
1866:
1832:
1539:
Baylis, Françoise; Darnovsky, Marcy; Hasson, Katie; Krahn, Timothy M. (2020-10-01).
3877:
3708:"Human genetic enhancement might soon be possible â but where do we draw the line?"
3625:
3185:
Allhoff, Fritz (2005). "Germ-Line Genetic Enhancement and Rawlsian Primary Goods".
1372:
1280:
1264:
1154:
1098:
713:
3765:"Ethical Issues of Using CRISPR Technologies for Research on Military Enhancement"
3305:
2900:
Committee on Human Gene Editing: Scientific, Medical, and Ethical Considerations.
3749:
3633:
2757:
1975:
3849:
3841:
3576:
2700:
2366:
1272:
1126:
1114:
1050:
1046:
492:
441:
for information on how to properly incorporate it into this article's main text.
383:
341:
3259:
3242:
3122:
2291:
2266:
1936:
1711:
297:, which can be fatal. Perfect editing of the genome in patients who have these
3780:
3486:
Daws, Steven (6 October 2017). "Procreative Beneficence in the CRISPR World".
3163:
2793:
2780:
2643:
2503:
2458:
1858:
1232:
1094:
1042:
938:
554:
led to unexpected mutation. The results of the study indicated that repair of
459:
391:
379:
210:
188:
3882:
Life at the Speed of Light: From the Double Helix to the Dawn of Digital Life
3788:
3674:
2979:
2880:
2053:
2044:
1944:
1816:
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1566:
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that further effort was needed in to improve the precision and efficiency of
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3415:
3353:
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2210:
2155:
1491:
1022:
886:
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331:
245:
3796:
3692:
3649:"Frequent loss of heterozygosity in CRISPR-Cas9âedited early human embryos"
3617:
3423:
3362:
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3084:
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2120:
1952:
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1632:
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1448:
120:
3561:
3208:
2987:
2071:
1991:
1541:"Human Germline and Heritable Genome Editing: The Global Policy Landscape"
1186:
Laboratory research use involves human germline engineering restricted to
592:
In August 2017, a group of scientists from Oregon published an article in
3727:"Being human: The ethics, law, and scientific progress of genome editing"
3499:
3041:
1348:
1311:
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1188:
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1078:
1070:
1026:
914:
751:
320:
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2583:
2559:
2534:
1895:
New Horizons in Medical Anthropology: Essays in Honour of Charles Leslie
1647:
1623:
1598:
1416:
640:
inhibition might increase efficiency of human germline editing and that
3388:
2601:. If this is an intentional citation to a such a paper, please replace
1665:. If this is an intentional citation to a such a paper, please replace
1432:
1336:
1316:
1296:
1276:
1248:
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1236:
1220:
1216:
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1201:
Countries that explicitly prohibit any use of germline engineering for
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1038:
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998:
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898:
894:
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878:
3269:
3824:
Evolving Ourselves: How Unnatural Selection is Changing Life on Earth
2085:
Lanphier E, Urnov F, Haecker SE, Werner M, Smolenski J (March 2015).
1387:
1344:
1309:
Countries that explicitly permit the use of germline engineering for
1304:
1268:
1244:
1228:
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1138:
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1102:
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1074:
1062:
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1002:
978:
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Ethical claims about germline engineering include beliefs that every
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671:
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597:
571:
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527:
231:
199:
184:
16:
Process of editing the human genome so that the changes are inherited
3608:
3591:
2414:"Amid uproar, Chinese scientist defends creating gene-edited babies"
2345:"Amid uproar, Chinese scientist defends creating gene-edited babies"
2111:
2086:
2841:"Chinese Scientists Edit Genes of Human Embryos, Raising Concerns"
2443:"CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes"
1340:
1328:
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1168:
1118:
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930:
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781:
289:
gene which codes for the human ÎČ-globin protein. Mutations in the
3379:(2017). "The Reproductive Revolution". In Vinding, Magnus (ed.).
2781:"US science advisers outline path to genetically modified babies"
1417:"Using the therapy and enhancement distinction in law and policy"
323:
modifications to humans which would result in what are known as "
1332:
1066:
994:
542:, the efficiency of homologous recombination directed repair of
480:
467:
276:. HIV/AIDS carries a large disease burden and is incurable (see
269:
241:
235:
203:
319:
The non-therapeutic use of human germline engineering would be
3846:
Hacking Darwin: Genetic Engineering and the Future of Humanity
682:
641:
637:
633:
577:
556:
550:
544:
535:
415:
285:
114:
59:
18:
2187:"Genetic screens in human cells using the CRISPR-Cas9 system"
2908:. National Academy of Sciences; National Academy of Medicine
1198:
use, while 4 prohibit it with exceptions, and 11 permit it.
495:, appear healthy and are highly resistant to HIV infection.
3516:
Redesigning Humans: Choosing Our Genes, Changing Our Future
2810:"Scientists Seek Ban on Method of Editing the Human Genome"
2535:"Correction of a pathogenic gene mutation in human embryos"
1599:"Correction of a pathogenic gene mutation in human embryos"
2389:"He Jiankui Fired in Wake of CRISPR Babies Investigation"
636:
pathway. The conclusion of the study would suggest that
2902:"Human Genome Editing: Science, Ethics, and Governance"
2243:"On Human Gene Editing: International Summit Statement"
1974:
Professor, Apostolos Stergioulas, Ph D. (2021-02-04).
2869:"Human Gene Editing Receives Science Panel's Support"
606:
mutation in human embryos. The study claimed precise
827:
seeing some actual benefit in genetic disabilities.
632:led to a selection against cells with a functional
3857:
644:function would need to be watched when developing
3592:"A slippery slope to human germline modification"
3439:"Procreative Beneficence and Genetic Enhancement"
2393:GEN - Genetic Engineering and Biotechnology News
305:genes could be passed on to future generations.
3653:Proceedings of the National Academy of Sciences
2032:Proceedings of the National Academy of Sciences
1805:Therapeutic Innovation & Regulatory Science
79:for grammar, style, cohesion, tone, or spelling
2942:"Scientists OK genetically engineering babies"
2436:
2434:
874:human germline engineering for reproduction.
8:
3763:Greene, Marsha; Master, Zubin (2018-09-01).
2926:: CS1 maint: multiple names: authors list (
2267:"Germline gene-editing research needs rules"
2010:: CS1 maint: multiple names: authors list (
1749:International Journal of Molecular Medicine
746:Designer baby § Ethical_considerations
53:Learn how and when to remove these messages
3725:Newson, Ainsley; Wrigley, Anthony (2016).
2615:|...|intentional=yes}}
1679:|...|intentional=yes}}
712:. Please do not remove this message until
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2110:
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1719:
1622:
1556:
1490:
732:Learn how and when to remove this message
168:Learn how and when to remove this message
103:Learn how and when to remove this message
708:Relevant discussion may be found on the
596:journal detailing the successful use of
145:of all important aspects of the article.
3859:"Special Issue: Human Germline Editing"
3822:Enriquez, Juan; Gullans, Steve (2015).
1473:Caro-Romero, Henry David (2020-06-09).
1404:
3030:The Journal of Medicine and Philosophy
2919:
2003:
483:has on the memory function the brain.
370:Lack of clear international regulation
355:Consolidated Appropriation Act of 2016
252:make it possible to modify the DNA of
141:Please consider expanding the lead to
3236:
3234:
3123:Gene Therapy and Genetic Engineering.
1468:
1466:
1410:
1408:
833:introduced over the entire population
575:recombination-mediated alteration in
7:
3381:Can Biotechnology Abolish Suffering?
1878:
1876:
1844:
1842:
1798:
1796:
1534:
1532:
1530:
1528:
1526:
1524:
1522:
1520:
1518:
430:This section should include only a
3187:Kennedy Institute of Ethics Journal
2343:Begley, Sharon (28 November 2018).
843:Therapeutic and non-therapeutic use
406:He Jiankui controversy and research
2779:Reardon, Sara (14 February 2017).
1700:American Journal of Human Genetics
806:in turn proposes the principle of
209:In November 2018, researcher
14:
3706:Johnson, Tess (3 December 2019).
3446:KRITERION - Journal of Philosophy
3294:The American Journal of Bioethics
183:is the process by which the
34:This article has multiple issues.
3144:Journal of Nanoparticle Research
3077:10.1111/j.1467-8519.2004.00376.x
2087:"Don't edit the human germ line"
1892:Lock M, Nichter M (2003-09-02).
822:Unequal distribution of benefits
687:
420:
119:
64:
23:
3247:Reproductive Biomedicine Online
3102:. University of Chicago Press.
2492:Molecular Genetics and Genomics
2185:Wang, Tim; et al. (2014).
1696:"Human Germline Genome Editing"
662:mutation that is causative for
133:may be too short to adequately
42:or discuss these issues on the
3590:Darnovsky, Marcy (July 2013).
1479:Revista Colombiana de Bioética
268:has a genetic mutation in the
143:provide an accessible overview
1:
3769:Journal of Bioethical Inquiry
3519:. Houghton Mifflin Harcourt.
3306:10.1080/15265161.2017.1388875
2574:(This paper currently has an
1976:"Gene doping in modern sport"
1638:(This paper currently has an
534:could effectively cleave the
479:has discovered an impact the
439:Knowledge (XXG):Summary style
400:The World Health Organization
3001:Cole-Turner, Ronald (2008).
2758:10.1016/j.arcmed.2012.09.003
2746:Archives of Medical Research
1415:McGee, Andrew (2019-10-15).
771:American Medical Association
767:National Academy of Medicine
763:National Academy of Sciences
761:A committee of the American
293:gene result in the disorder
2968:Archives of Family Medicine
2701:10.1016/j.ymthe.2018.08.007
1980:Journal Biology of Exercise
714:conditions to do so are met
513:Chinese Academy of Sciences
434:summary of another article.
3944:
3826:. One World Publications.
3260:10.1016/j.rbmo.2014.04.001
2839:Kolata G (23 April 2015).
2292:10.1038/d41586-019-00788-5
2247:www8.nationalacademies.org
1937:10.1007/s11248-020-00188-w
1712:10.1016/j.ajhg.2017.06.012
1378:Germinal choice technology
743:
520:Major studies of influence
409:
312:
229:
181:Human germline engineering
3781:10.1007/s11673-018-9865-6
3731:AQ - Australian Quarterly
3341:Human Reproduction Update
2974:(7): 633â642. July 1994.
2794:10.1038/nature.2017.21474
2644:10.1038/s41591-018-0049-z
2504:10.1007/s00438-017-1299-z
2459:10.1007/s13238-015-0153-5
2277:(7747): 145. March 2019.
1859:10.1038/nature.2015.17378
1383:Human genetic enhancement
1368:Human genetic engineering
679:Ethical and moral debates
254:spermatogonial stem cells
2980:10.1001/archfami.3.7.633
2808:Wade N (19 March 2015).
2045:10.1073/pnas.95.25.14938
1817:10.1177/2168479017723401
1558:10.1089/crispr.2020.0082
278:Epidemiology of HIV/AIDS
274:innate resistance to HIV
3666:10.1073/pnas.2004832117
3554:10.1126/science.8211180
3513:Stock, Gregory (2003).
3458:10.1515/krt-2018-320105
3416:10.1111/1467-8519.00251
3241:Ishii T (August 2014).
3164:10.1023/A:1021152023349
3128:3 December 2013 at the
2867:Harmon A (2017-02-14).
2211:10.1126/science.1246981
2156:10.1126/science.aag2960
1492:10.18270/rcb.v15i1.2732
835:(similar to vaccines).
808:procreative beneficence
244:and a special piece of
215:Lulu and Nana
3928:2010s in biotechnology
3923:Biotechnology in China
1761:10.3892/ijmm.2019.4112
907:Bosnia and Herzegovina
396:Emmanuelle Charpentier
3437:Veit, Walter (2018).
3354:10.1093/humupd/dmw005
3209:10.1353/ken.2005.0007
2948:. Reuters. 2017-02-14
2906:nationalacademies.org
2787:: nature.2017.21474.
2613:expression of concern
2607:|...}}
2605:expression of concern
2576:expression of concern
1992:10.4127/jbe.2009.0021
1853:: nature.2015.17378.
1677:expression of concern
1671:|...}}
1669:expression of concern
1640:expression of concern
860:Current global policy
812:genetically enhancing
3500:10.7916/vib.v3i.6031
3475:on October 23, 2021.
2363:"ć€çèŽșć»șć„çäșșç蜚èżčïŒæŻè°ç»äșä»ćæ°"
2325:on February 22, 2019
2315:"WHO | Gene editing"
1177:United Arab Emirates
850:University of Bogota
3659:(22): e2004832117.
3488:Voices in Bioethics
3156:2002JNR.....4..281R
2584:10.1038/nature23305
2560:10.1038/nature23305
2551:2017Natur.548..413M
2283:2019Natur.567..145.
2203:2014Sci...343...80W
2148:2016Sci...353..545C
2103:2015Natur.519..410L
2038:(25): 14938â14943.
1925:Transgenic Research
1648:10.1038/nature23305
1624:10.1038/nature23305
1615:2017Natur.548..413M
1182:Laboratory research
701:of this section is
3884:. United Kingdom:
3848:. Naperville, IL:
3042:10.1093/jmp/jhq057
2873:The New York Times
2846:The New York Times
2815:The New York Times
2447:Protein & Cell
2369:. 27 November 2018
1545:The CRISPR Journal
1433:10.1111/bioe.12662
433:
266:The Berlin Patient
83:You can assist by
3548:(5133): 533â538.
3109:978-0-226-22262-2
2695:(11): 2631â2637.
2689:Molecular Therapy
2545:(7668): 413â419.
1609:(7668): 413â419.
742:
741:
734:
456:
455:
431:
412:He Jiankui affair
348:State of research
196:Council of Europe
178:
177:
170:
160:
159:
113:
112:
105:
57:
3935:
3899:
3873:
3861:
3853:
3837:
3809:
3808:
3760:
3754:
3753:
3722:
3716:
3715:
3712:The Conversation
3703:
3697:
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3686:
3668:
3644:
3638:
3637:
3611:
3587:
3581:
3580:
3537:
3531:
3530:
3510:
3504:
3503:
3483:
3477:
3476:
3474:
3468:. Archived from
3443:
3434:
3428:
3427:
3410:(5â6): 413â426.
3399:
3393:
3392:
3373:
3367:
3366:
3356:
3332:
3326:
3325:
3289:
3283:
3282:
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3229:
3228:
3202:
3182:
3176:
3175:
3139:
3133:
3120:
3114:
3113:
3098:Evans J (2002).
3095:
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3060:
3054:
3053:
3025:
3019:
3018:
2998:
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2991:
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2953:
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2915:
2913:
2897:
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2888:
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2864:
2858:
2857:
2855:
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2836:
2830:
2829:
2824:
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2805:
2799:
2798:
2796:
2776:
2770:
2769:
2741:
2735:
2729:
2723:
2722:
2712:
2680:
2674:
2673:
2655:
2627:
2621:
2620:
2618:
2616:
2608:
2597:Retraction Watch
2572:
2562:
2530:
2524:
2523:
2487:
2481:
2480:
2470:
2438:
2429:
2428:
2426:
2425:
2410:
2404:
2403:
2401:
2400:
2385:
2379:
2378:
2376:
2374:
2359:
2353:
2352:
2340:
2334:
2333:
2331:
2330:
2321:. Archived from
2311:
2305:
2304:
2294:
2263:
2257:
2256:
2254:
2253:
2239:
2233:
2232:
2222:
2182:
2176:
2175:
2131:
2125:
2124:
2114:
2082:
2076:
2075:
2065:
2047:
2022:
2016:
2015:
2009:
2001:
1999:
1998:
1971:
1965:
1964:
1916:
1910:
1909:
1889:
1883:
1880:
1871:
1870:
1846:
1837:
1836:
1800:
1791:
1790:
1780:
1755:(4): 1559â1574.
1740:
1734:
1733:
1723:
1691:
1685:
1684:
1682:
1680:
1672:
1661:Retraction Watch
1636:
1626:
1593:
1587:
1586:
1560:
1536:
1513:
1512:
1494:
1470:
1461:
1460:
1412:
869:Reproductive use
865:in human cells.
814:one's children.
804:Julian Savulescu
737:
730:
726:
723:
717:
691:
690:
683:
451:
448:
442:
424:
423:
416:
388:Françoise Baylis
357:bans the use of
260:Conceivable uses
173:
166:
155:
152:
146:
123:
115:
108:
101:
97:
94:
88:
68:
67:
60:
49:
27:
26:
19:
3943:
3942:
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3936:
3934:
3933:
3932:
3903:
3902:
3896:
3876:
3856:
3840:
3834:
3821:
3818:
3816:Further reading
3813:
3812:
3762:
3761:
3757:
3724:
3723:
3719:
3705:
3704:
3700:
3646:
3645:
3641:
3609:10.1038/499127a
3589:
3588:
3584:
3539:
3538:
3534:
3527:
3512:
3511:
3507:
3485:
3484:
3480:
3472:
3441:
3436:
3435:
3431:
3401:
3400:
3396:
3375:
3374:
3370:
3334:
3333:
3329:
3291:
3290:
3286:
3240:
3239:
3232:
3184:
3183:
3179:
3141:
3140:
3136:
3130:Wayback Machine
3121:
3117:
3110:
3097:
3096:
3092:
3062:
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2999:
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2778:
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2773:
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2730:
2726:
2682:
2681:
2677:
2632:Nature Medicine
2629:
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2624:
2610:
2602:
2600:
2573:
2532:
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2265:
2264:
2260:
2251:
2249:
2241:
2240:
2236:
2184:
2183:
2179:
2142:(6299): 545â6.
2133:
2132:
2128:
2112:10.1038/519410a
2097:(7544): 410â1.
2084:
2083:
2079:
2024:
2023:
2019:
2002:
1996:
1994:
1973:
1972:
1968:
1918:
1917:
1913:
1906:
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1874:
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1471:
1464:
1414:
1413:
1406:
1401:
1364:
1184:
1059:North Macedonia
871:
862:
845:
824:
791:
748:
738:
727:
721:
718:
707:
692:
688:
681:
664:Marfan syndrome
536:ÎČ-globin gene (
522:
477:Alcino J. Silva
452:
446:
443:
436:
425:
421:
414:
408:
372:
350:
325:designer babies
317:
311:
309:Designer babies
262:
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3918:Genome editing
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3895:978-0143125907
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3833:978-1780748412
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3775:(3): 327â335.
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3526:978-0618340835
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3368:
3347:(4): 411â419.
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3284:
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3200:10.1.1.566.171
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3150:(4): 281â295.
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3090:
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2993:
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2800:
2771:
2752:(7): 491â513.
2736:
2724:
2675:
2638:(7): 927â930.
2622:
2525:
2498:(3): 525â533.
2482:
2453:(5): 363â372.
2430:
2405:
2380:
2365:(in Chinese).
2354:
2335:
2306:
2258:
2234:
2197:(6166): 80â4.
2177:
2126:
2077:
2017:
1966:
1931:(1): 149â163.
1911:
1904:
1884:
1872:
1838:
1811:(6): 672â682.
1792:
1735:
1706:(2): 167â176.
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951:Czech Republic
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648:based therapy.
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410:Main article:
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295:ÎČ-thalassaemia
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137:the key points
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3878:Venter, Craig
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3377:Pearce, David
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3300:(12): 27â29.
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3014:9780262533010
3010:
3007:. MIT Press.
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1905:9781134471287
1901:
1898:. Routledge.
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1393:Designer Baby
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1357:United States
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631:
627:
622:
621:
618:unpersuasive.
616:
615:
609:
605:
604:
599:
595:
591:
590:
586:
585:
580:
579:
573:
569:
568:
565:gene editing.
564:
559:
558:
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547:
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541:
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533:
529:
524:
523:
519:
517:
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500:
496:
494:
488:
484:
482:
478:
475:. Researcher
474:
473:Lulu and Nana
469:
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315:Designer baby
308:
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138:
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107:
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96:
86:
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73:This article
71:
62:
61:
56:
54:
47:
46:
41:
40:
35:
30:
21:
20:
3881:
3869:
3863:
3845:
3842:Metzl, Jamie
3823:
3772:
3768:
3758:
3734:
3730:
3720:
3711:
3701:
3656:
3652:
3642:
3599:
3595:
3585:
3545:
3541:
3535:
3515:
3508:
3491:
3487:
3481:
3470:the original
3449:
3445:
3432:
3407:
3403:
3397:
3380:
3371:
3344:
3340:
3330:
3297:
3293:
3287:
3253:(2): 150â5.
3250:
3246:
3193:(1): 39â56.
3190:
3186:
3180:
3147:
3143:
3137:
3118:
3099:
3093:
3068:
3064:
3058:
3033:
3029:
3023:
3003:
2996:
2971:
2967:
2961:
2950:. Retrieved
2945:
2936:
2910:. Retrieved
2905:
2895:
2884:. Retrieved
2872:
2862:
2850:. Retrieved
2844:
2834:
2826:
2819:. Retrieved
2813:
2803:
2784:
2774:
2749:
2745:
2739:
2727:
2692:
2688:
2678:
2653:10138/303675
2635:
2631:
2625:
2611:{{
2603:{{
2596:
2594:,
2542:
2538:
2528:
2495:
2491:
2485:
2450:
2446:
2422:. Retrieved
2420:. 2018-11-28
2417:
2408:
2397:. Retrieved
2395:. 2019-01-21
2392:
2383:
2371:. Retrieved
2357:
2348:
2338:
2327:. Retrieved
2323:the original
2318:
2309:
2274:
2270:
2261:
2250:. Retrieved
2246:
2237:
2194:
2190:
2180:
2139:
2135:
2129:
2094:
2090:
2080:
2035:
2031:
2020:
2006:cite journal
1995:. Retrieved
1983:
1979:
1969:
1928:
1924:
1914:
1894:
1887:
1850:
1808:
1804:
1752:
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1738:
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1675:{{
1667:{{
1660:
1658:,
1606:
1602:
1591:
1548:
1544:
1482:
1478:
1427:(1): 70â80.
1424:
1420:
1373:Gene therapy
1310:
1308:
1286:
1284:
1265:Saudi Arabia
1202:
1200:
1193:
1187:
1185:
1158:
1099:Saudi Arabia
876:
872:
863:
854:
846:
837:
829:
825:
816:
799:David Pearce
796:
792:
779:
775:
760:
749:
728:
722:October 2020
719:
697:
667:
659:
612:
601:
593:
582:
576:
555:
549:
543:
537:
509:
505:
501:
497:
489:
485:
464:
457:
444:
429:
377:
373:
364:
354:
351:
329:
318:
302:
298:
290:
284:
282:
263:
250:
239:
208:
193:
180:
179:
164:
148:
132:
130:lead section
99:
90:
77:copy editing
75:may require
74:
50:
43:
37:
36:Please help
33:
3850:Sourcebooks
3071:(1): 1â26.
3036:(1): 6â27.
2912:21 February
2578:, see
2373:28 November
2367:sina.com.cn
1642:, see
1273:Switzerland
1127:Switzerland
1115:South Korea
1051:New Zealand
1047:Netherlands
672:CRISPR/Cas9
655:CRISPR/Cas9
646:CRISPR/Cas9
626:CRISPR/Cas9
608:CRISPR/Cas9
572:CRISPR/Cas9
563:CRISPR/Cas9
532:CRISPR/Cas9
528:CRISPR/Cas9
493:homozygotes
384:Eric Lander
342:gene doping
226:CRISPR-Cas9
151:August 2023
3907:Categories
3872:(1). 2020.
3750:2046113711
3743:A441491350
3737:(1): 3â8.
3634:1415758114
3389:B075MV9KS2
3270:2115/56864
2952:2017-02-17
2886:2017-02-17
2734:. cioms.ch
2424:2019-04-18
2399:2019-04-18
2329:2019-04-18
2252:2019-04-18
1997:2022-12-06
1399:References
1355:, and the
1279:, and the
1233:Costa Rica
1175:, and the
1153:, and the
1095:San Marino
1043:Montenegro
939:Costa Rica
744:See also:
699:neutrality
460:He Jiankui
392:Feng Zhang
380:He Jiankui
221:Techniques
211:He Jiankui
189:germ cells
85:editing it
39:improve it
3865:Bioethics
3789:1872-4353
3675:0027-8424
3577:213545041
3570:A14296431
3466:149244361
3452:: 75â92.
3404:Bioethics
3195:CiteSeerX
3172:136290217
3065:Bioethics
2881:0362-4331
2349:STAT News
2172:206651381
2054:0027-8424
1961:255111445
1945:0962-8819
1769:1791-244X
1583:225053656
1567:2573-1599
1509:225804689
1501:2590-9452
1457:204738693
1441:0269-9702
1421:Bioethics
1315:use are:
1291:use are:
1207:use are:
1023:Lithuania
887:Australia
883:Argentina
710:talk page
481:CCR5 gene
447:July 2023
332:myostatin
246:guide RNA
135:summarize
93:July 2023
45:talk page
3913:Genetics
3880:(2014).
3844:(2020).
3805:49640190
3797:29968018
3746:ProQuest
3693:34050011
3630:ProQuest
3618:23846625
3573:ProQuest
3424:12058767
3363:26932460
3322:10117287
3314:29148947
3279:24832374
3225:14432440
3217:15881795
3126:Archived
3085:15168695
3050:21228084
2922:cite web
2852:24 April
2821:20 March
2766:23072719
2719:30166242
2670:47018050
2662:29892067
2592:28783728
2569:28783728
2520:16358211
2512:28251317
2477:25894090
2301:30867612
2229:24336569
2164:27493171
2121:25810189
1953:31927726
1867:87604469
1833:13658866
1825:30227096
1787:30816503
1730:28777929
1656:28783728
1633:28783728
1575:33095042
1449:31617223
1362:See also
1349:Thailand
1312:in vitro
1293:Colombia
1288:in vitro
1261:Pakistan
1253:Malaysia
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