CARL ZIMMER2026年6月5日研究人员修改了影响血液中低密度脂蛋白胆固醇和血红蛋白水平的基因。 Claude Cortier/Science SourceScientists at Columbia University have edited the DNA of early human embryos with unprecedented accuracy, an achievement that could open the way to babies engineered with particular characteristics.哥伦比亚大学科学家以前所未有的精确度编辑了早期人类胚胎的DNA，这一成果可能为培育具有特定特征的“定制婴儿”打开大门。The prospect has fueled controversy for years. On the one hand, the technology might one day enable parents to safely repair disease-causing mutations in embryos. But it might also be used to select desired traits — a practice that some ethicists have argued is nothing short of eugenics.这一前景多年来一直存有争议。一方面，该技术未来可能让父母安全修复胚胎中导致疾病的突变；但另一方面，它也可能被用于选择理想特征，一些伦理学家认为这种做法无异于优生学。Dieter Egli, a geneticist at Columbia University who led the research, called for a public conversation about the pros and cons of altering embryonic DNA. “As a scientist, you can provide the data for discussion, but then essentially there you stop and let others take over,” he said.领导这项研究的哥伦比亚大学遗传学家迪特尔·埃利呼吁就修改胚胎DNA的利弊展开公众讨论。“作为科学家，我可以提供讨论所需的数据，但之后基本上就该停下来，让其他人接手，”他说。With a newer technology called base editing, Dr. Egli and his colleagues were able to meticulously replace individual genetic letters in sequences of DNA without causing the damage often observed with an earlier form of gene editing, CRISPR.埃利及其同事使用一种被称为碱基编辑的新技术对DNA序列中的单个遗传字母进行精确替换，不会造成早期基因编辑技术CRISPR常有的那种损伤。Dr. Egli cautioned that the research left unanswered many questions about harmful side effects. “We’re not saying this is going to be used tomorrow in the clinics,” he said.埃利警告称，该研究仍有很多关于有害副作用的问题尚未解答。“我们并不是说这项技术明天就能用于临床，”他说。Dr. Egli and his colleagues posted their study online. The research is under review for publication in a scientific journal.埃利及其同事已将研究论文发布在网上。该研究目前正在接受科学期刊的同行评审。The possibility of editing the DNA of human embryos became a matter of serious debate more than a decade ago, after the invention of CRISPR.编辑人类胚胎DNA的可能性在CRISPR技术发明十多年前就已成为严肃辩论的话题。In 2012, scientists discovered how to create customized molecules that could snip out a targeted segment of DNA. CRISPR quickly became a standard tool for scientists — a cheap, easy way to discover how genes function by tweaking the genome.2012年，科学家发现可以制造定制分子来切除DNA中特定的片段。CRISPR迅速成为科学家的标准工具——一种廉价、简便的通过修改基因组来研究基因功能的方法。A number of medical companies sprang up, seeking to use the technology to treat hereditary diseases. In 2023, the Food and Drug Administration approved a CRISPR-based treatment for sickle cell anemia.多家医疗公司应运而生，试图利用该技术治疗遗传性疾病。2023年，美国食品和药物管理局批准了一种基于CRISPR的疗法，用于治疗镰状细胞贫血。But scientists knew it was not perfect. In some cells, CRISPR molecules failed to find their targets in DNA, or sometimes snipped out the wrong genetic bits.但科学家们知道它并不完美。在某些细胞中，CRISPR分子无法找到目标DNA，有时还会切错遗传片段。Those concerns did not stop a Chinese scientist, He Jiankui, from using CRISPR to alter the DNA of human embryos in 2018.这些担忧并未阻止中国科学家贺建奎在2018年使用CRISPR修改人类胚胎DNA。Dr. He later said his goal was to give children a genetic resistance to H.I.V. infection. But experts condemned his work as reckless, and Chinese authorities imprisoned him for three years.贺建奎后来表示，他的目标是让儿童获得对HIV感染的遗传抵抗力。但专家谴责他的工作过于鲁莽，中国当局判处他三年监禁。Dr. He’s experiment led to three “healthy, beautiful babies,” he claimed in a January interview with The New York Times. But the status of the children has never been independently evaluated.贺建奎声称他的实验诞生了三个“健康、漂亮的婴儿”，他在今年1月接受《纽约时报》采访时如此表示。但这些儿童的状况从未经过独立评估。贺建奎去年秋天在北京的家中。此前，他因制造了基因编辑婴儿入狱服刑三年。 Chang W. Lee/The New York TimesIn 2020, Dr. Egli and his colleagues carried out an experiment to see how CRISPR behaves in human embryos.2020年，埃利及其同事进行了一项实验，观察CRISPR在人类胚胎中的表现。They obtained donated sperm from men with a mutation in a gene called EYS causing hereditary blindness. The researchers used the sperm to fertilize healthy eggs, producing human embryos with one working copy of EYS and one defective copy. The researchers used CRISPR to cut out the mutant region of EYS.他们从携带EYS基因突变（会导致遗传性失明）的男性那里获得捐赠精子，用这些精子使健康卵子受精，产生具有一个正常EYS拷贝和一个缺陷拷贝的人类胚胎。研究人员使用CRISPR切除EYS的突变区域。Previous studies suggested that the embryo might repair the gene by using the healthy version as a guide. Only some embryos did so, ending up with two working copies of EYS.先前研究表明，胚胎可能会以健康版本为模板修复该基因。但只有部分胚胎成功，最终拥有两个正常EYS拷贝。But the repair failed in about half of them. Some chopped off long stretches of DNA. Some destroyed the entire chromosome on which the EYS gene is located.但约一半胚胎修复失败。有些切除了大段DNA，有些则破坏了EYS基因所在的整个染色体。“It had absolutely catastrophic consequences,” Dr. Egli said.“后果绝对是灾难性的，”埃利说。Many scientists and bioethicists saw these results as further evidence that editing human embryos was far too risky to even consider — at least, for the time being.许多科学家和生物伦理学家认为，这些结果进一步证明编辑人类胚胎风险极高，至少在目前不值得考虑。But in 2016, David Liu, a geneticist at Harvard University, and colleagues combined one of the CRISPR molecules with other compounds to create base editing, a new method for editing genes. Rather than chop out a segment of DNA, base editors made a tiny nick in one strand. They could then guide the cell to fix the mutation.但在2016年，哈佛大学遗传学家刘如谦(David Liu)及其同事将CRISPR分子与其他化合物结合，创造了碱基编辑技术。这是一种新的基因编辑方法。它不再切除DNA片段，而是在其中一条链上制造一个微小的切口，然后引导细胞修复突变。Base editing has proved to be often superior to earlier CRISPR methods. Last year, a baby was cured of a potentially lethal genetic disorder after receiving a customized set of base editing molecules.碱基编辑已被证明往往优于早期的CRISPR方法。去年，在接受定制碱基编辑分子治疗后，一名患有可能致命的遗传疾病的婴儿被治愈。Dr. Egli decided to try it on human embryos.埃利决定在人类胚胎上尝试这项技术。For the new experiments, he and his colleagues set out to alter two genes. One, called PCSK9, can carry mutations that raise levels of LDL in the blood — and the risk of heart disease. The other gene, HBG, directs hemoglobin production in fetuses.在这项新实验中，他和同事试图修改两个基因。一个是PCSK9基因，其突变会导致血液中LDL（低密度脂蛋白）水平升高，从而增加心脏病风险。另一个是HBG基因，负责胎儿期血红蛋白的产生。Dr. Egli and his colleagues delivered their base editors into fertilized eggs and into two-cell embryos donated by parents. The researchers didn’t find any of the extensive damage associated with CRISPR.埃利及其同事将碱基编辑器导入受精卵和父母捐赠的双细胞期胚胎。研究人员没有发现与CRISPR相关的大范围损伤。哥伦比亚大学遗传学家迪特尔·埃利是该研究负责人。 Roy Rochlin/Getty ImagesInstead, the researchers were able to successfully change both the PCSK9 and HBG genes. In some experiments, they simultaneously changed both genes in the same embryo.相反，研究人员成功修改了PCSK9和HBG两个基因。在部分实验中，他们在同一个胚胎中同时修改了两个基因。But the edits were still not perfect. Sometimes the base editing molecules failed to find their target DNA. As a result, some cells in the embryos retained the original versions of the genes, while others were altered.但编辑仍不完美。有时碱基编辑分子无法找到目标DNA，导致胚胎中部分细胞保留原始基因版本，部分细胞被修改。Those embryos became genetic mixtures, so-called mosaics. Having cells with different versions of the same gene could have led to medical problems had the embryos developed into babies.这些胚胎成为基因混合体，即所谓的“镶嵌”(mosaics)。如果胚胎发育成婴儿，不同细胞拥有不同基因版本可能导致医疗问题。Despite those failures, the new results were strong enough that Dr. Paula Amato, a fertility expert at Oregon Health & Science University who was not involved in the study, thought the method was “promising.”尽管存在这些失败，未参与该研究的俄勒冈健康与科学大学生育专家葆拉·阿马托博士仍认为该方法“很有前景”。Still, she said it would be important to examine the final results when they’re published in a journal.不过她表示，待论文正式发表后，仔细审阅最终结果非常重要。Ana Iltis, a bioethicist at Wake Forest University, worried that assessing the safety of base-edited embryos will require far more scrutiny than simply looking for damaged chromosomes.维克森林大学生物伦理学家安娜·伊尔蒂斯认为，要评估碱基编辑胚胎的安全性，单纯检查染色体损伤是远远不够的。“It is possible that some of the potentially harmful effects would not be evident until after birth,” she warned.“有些潜在有害影响可能要到出生后才会显现，”她警告说。Nathan Treff, the chief clinical officer of Nucleus Genomics and a co-author of the new study, said that the ability to fix disease-causing mutations in embryos could be a boon to those using I.V.F., allowing them to implant embryos that they otherwise would have discarded.Nucleus Genomics首席临床官、新研究合著者内森·特雷夫博士表示，能够修复胚胎中致病突变的技术对接受体外受精的人来说可能是一大福音，让他们能够植入原本会被丢弃的胚胎。“There’s still work to do before getting to that point, but this research gets us closer,” Dr. Treff said.“要达到那个阶段还有很多工作要做，但这项研究让我们离目标更近了，”特雷夫说。Nucleus Genomics will support the next stage of Dr. Egli’s research. (The federal government does not fund studies on human embryos for research purposes.)Nucleus Genomics将支持埃利研究的下一阶段。（联邦政府不资助以研究为目的人类胚胎研究。）Some upcoming studies will look for ways to avoid mosaic embryos. The researchers will also test base editing on embryos that contain about 100 cells. Fertility clinics typically freeze and test embryos at that stage.即将进行的研究将寻找避免镶嵌胚胎的方法。研究人员还将在包含约100个细胞的胚胎上测试碱基编辑。生育诊所通常会在这个阶段冷冻和检测胚胎。Nucleus Genomics, founded in 2021, screens I.V.F. embryos for thousands of genetic disorders. The company also makes predictions about an embryo’s risks for conditions such as heart disease and diabetes. And it looks at genes linked to traits such as height and intelligence.成立于2021年的Nucleus Genomics可筛查IVF胚胎数千种遗传疾病。该公司还会预测胚胎患心脏病、糖尿病等疾病的风险，并查看与身高、智力等特征相关的基因。一家试管婴儿诊所内，装有捐赠精子的皮氏培养皿。科学家们表示，如果能修复胚胎中致病的突变，就能有更多胚胎得以植入，而不是被废弃。 Jackie Molloy for The New York TimesIn November, the firm stirred controversy when it plastered ads on New York City subways telling commuters to “have your best baby.” Geneticists have criticized the predictions Nucleus Genomics makes for traits, such as IQ, as having low accuracy.去年11月，该公司在纽约地铁投放广告，告诉通勤者“生出你最好的宝宝”，引发争议。遗传学家批评Nucleus Genomics对智商等特征的预测准确性较低。And critics have accused the company of promoting a biotech spin on eugenics — a charge the company rejects.批评者指责该公司在推广一种生物技术版的优生学——公司对此予以否认。“We see ourselves as a natural pathway for eventually bringing technologies like this into clinical care as part of a broader genetics platform — a full ‘Genetic Optimization’ stack,” Kaitlyn Gallacher, head of communications at Nucleus Genomics, wrote in an email.Nucleus Genomics传播主管凯特琳·加拉赫在邮件中写道：“我们将自己视为最终将此类技术引入临床护理的自然途径，这是一个更广泛的遗传学平台——完整的‘遗传优化’体系。”Fyodor Urnov, a geneticist at the University of California, Berkeley, who was not involved in the study, said the results were in line with earlier studies of base editing in living cells.未参与该研究的加州大学伯克利分校遗传学家费奥多尔·乌尔诺夫表示，这些结果与此前在活细胞中进行碱基编辑的研究一致。But the prospect of using the method on embryos was both novel and risky, Dr. Urnov said. In regular I.V.F., embryos are screened for genetic abnormalities. That made much more sense, he argued, than resorting to a new technique with so many open questions.但他认为，将该方法用于胚胎的可能性具有新意，但也充满风险。他主张，在常规IVF中筛查胚胎遗传异常的做法更合理，而不是采用一项仍有许多未知风险的新技术。“Do we do what we’ve done safely and effectively 15 million times since 1978, or do we instead try something that we can never truly de-risk, and where the risks are clear?” he asked.“我们是继续做自1978年以来已经安全有效地做了1500万次的事，还是去尝试一种我们永远无法完全排除风险、且风险已然清晰的技术？”他问道。Dr. Urnov speculated that the new method, once perfected, would appeal to people who don’t merely want to address inherited diseases, but to enhance traits by engineering embryos.乌尔诺夫推测，一旦这项新技术完善，它将吸引那些不仅想解决遗传疾病，还想通过胚胎改造来提升特征的人。“What they are really doing is providing the ‘baby improvers’ with a how-to manual for forays beyond the ethical pale,” Dr. Urnov wrote in an email.“他们真正做的是为‘婴儿改进者’提供一本越过伦理底线的教程，”乌尔诺夫在邮件中写道。Whether anyone could actually alter babies in this way is not yet settled, though. Many human traits are influenced by hundreds, or thousands, of genes.不过，目前尚不确定是否真的有人能以这种方式改变婴儿。因为许多人类特征受数百甚至数千个基因影响。Dr. Egli noted that the more genes in a single embryo that scientists try to rewrite, the higher the risk that they will fail.埃利指出，科学家在单个胚胎中试图修改的基因越多，失败风险就越高。“I think you can probably combine three or four, maybe even five, but I think there’s a limit,” he said. “Where that limit is remains to be determined.”“我认为大概可以组合三到四个，也许五个，但肯定存在极限，”他说。“这个极限在哪里，还有待确定。”Carl Zimmer为时报报道科学新闻，并撰写“Origins“专栏。翻译：经雷点击查看本文英文版。