A Biotech Founder Makes the Moral Case for Gene-Editing Human Embryos

一位生物科技创始人提出基因编辑人类胚胎的道德论据

When the Chinese scientist He Jiankui announced in 2018 that he had created the first gene-edited babies, the experiment was widely condemned as reckless and premature. It ended with He in prison. 2018年，中国科学家贺建奎宣布他创造了首批基因编辑婴儿，这一实验被广泛谴责为鲁莽且操之过急。最终，贺建奎被判入狱。

But that hasn’t stopped the push for gene-edited human embryos, with biotech entrepreneur Cathy Tie arguing that doing so isn’t just urgent—it’s a “moral imperative.” 但这并没有阻止人们对基因编辑人类胚胎的推动，生物科技企业家凯西·泰（Cathy Tie）认为，这样做不仅紧迫，而且是一种“道德上的当务之急”。

Tie is the 30-year-old founder of Origin Genomics, a company that launched in March with plans to bring gene-edited embryos to IVF clinics. In a new commentary published in the journal Trends in Genetics, she argues for public funding and new regulatory pathways to advance gene-edited babies and eventually move into clinical use. 泰现年30岁，是Origin Genomics公司的创始人。该公司于今年3月成立，计划将基因编辑胚胎引入体外受精（IVF）诊所。在《遗传学趋势》（Trends in Genetics）期刊发表的一篇新评论中，她主张通过公共资金和新的监管途径来推进基因编辑婴儿的研究，并最终将其投入临床使用。

But questions remain about what evidence researchers will need to determine whether gene-edited embryos are safe enough to attempt a human pregnancy—and what risks might remain for the resulting children. 然而，研究人员需要什么样的证据来确定基因编辑胚胎是否足够安全以进行人类妊娠，以及由此出生的孩子可能面临哪些风险，这些问题依然存在。

“There are cautionary tales of first human trials where there was really no flashing red light, and people died,” says Hank Greely, a law professor and director of the Center for Law and the Biosciences at Stanford University. 斯坦福大学法学教授兼法律与生物科学中心主任汉克·格里利（Hank Greely）表示：“早期的首次人体试验中存在一些警示案例，当时并没有明显的危险信号，但人们还是因此丧生了。”

So-called germ-line gene editing involves modifying cells involved in human reproduction, like embryos. Any changes made could be passed on to future generations. That could mean, for example, correcting a devastating genetic mutation for good. But accidental DNA edits elsewhere, known as “off-target effects,” could introduce new health risks that could also be passed down. Those high stakes are part of why dozens of countries have banned gene-editing of human embryos intended for pregnancy. 所谓的生殖系基因编辑涉及修改参与人类生殖的细胞，例如胚胎。所做的任何改变都可能遗传给后代。例如，这意味着可以彻底纠正某种毁灭性的基因突变。但其他部位意外的DNA编辑（即“脱靶效应”）可能会引入新的健康风险，这些风险也可能被遗传下去。这种高风险正是数十个国家禁止对旨在妊娠的人类胚胎进行基因编辑的部分原因。

People at risk of passing a genetic disease on to their children can use IVF combined with genetic screening to identify disease-free embryos before transfer to the womb. Critics of embryo editing argue that screening tools make the need for it very small. Gene-editing embryos, Greely says, would be helping “a fraction of a fraction of a fraction.” 有将遗传病传给子女风险的人，可以使用体外受精（IVF）结合基因筛查，在植入子宫前识别出无疾病的胚胎。胚胎编辑的批评者认为，筛查工具使得基因编辑的需求变得非常小。格里利表示，基因编辑胚胎所能帮助的只是“极小比例中的极小比例”。

The drawback of the current approach is that IVF is inefficient; viable embryos can be hard to come by, even for people without an inherited disease risk. Ian Watts and Cheyenne Ziegler, for example, underwent three rounds of IVF in their attempt to have children that do not carry the genetic variant responsible for Watts’ Charcot-Marie-Tooth disease, a degenerative neurological disorder that impacts fine motor skills and mobility. With any IVF cycle, eggs regularly don’t fertilize, and those that do often stall in development or have chromosomal abnormalities. Adding additional screening for disease means that some viable embryos also don’t make the cut. 当前方法的缺点是IVF效率低下；即使对于没有遗传病风险的人来说，获得可存活的胚胎也很困难。例如，伊恩·瓦茨（Ian Watts）和夏安·齐格勒（Cheyenne Ziegler）进行了三轮IVF，试图生育不携带导致瓦茨患有腓骨肌萎缩症（Charcot-Marie-Tooth disease，一种影响精细运动技能和行动能力的退行性神经系统疾病）基因变异的孩子。在任何IVF周期中，卵子经常无法受精，而受精的卵子也常在发育中停滞或出现染色体异常。增加额外的疾病筛查意味着一些原本可存活的胚胎也会被淘汰。

In Watts and Ziegler’s case, three rounds of IVF have produced eight chromosomally normal embryos, but only three without Watts’ variant. Those three embryos are likely not enough to give the couple the three or four children they hope to have one day. 在瓦茨和齐格勒的案例中，三轮IVF产生了八个染色体正常的胚胎，但只有三个不携带瓦茨的致病变异。这三个胚胎很可能不足以让这对夫妇实现他们未来生育三到四个孩子的愿望。

“The choices currently available are either not having children or doing lots of IVF,” says Watts, a 36-year-old engineer in Long Beach, California. Gene editing could give people like him more chances at a future family. It could also help couples in the extremely rare situation where every embryo would inherit a disease-causing mutation, such as partners who each have two copies of a harmful variant. “目前可行的选择要么是不生孩子，要么是进行大量的IVF，”加利福尼亚州长滩市36岁的工程师瓦茨说。基因编辑可以给像他这样的人更多组建未来家庭的机会。它还可以帮助那些处于极端罕见情况下的夫妇，即每个胚胎都会遗传到致病突变的情况，例如双方都携带两份有害变异的伴侣。

“We’re here to treat these diseases, not just exclude embryos and call it a day,” says Tie, a former Thiel fellow who’s alluded to herself as “biotech Barbie.” “我们的目的是治疗这些疾病，而不仅仅是剔除胚胎就了事，”泰说。她曾是泰尔研究员（Thiel fellow），并曾自称为“生物科技芭比”。

The invention of CRISPR raised the possibility of gene-edited babies more than a decade ago, and newer forms of gene editing offer increasing precision. In June, researchers at Columbia University revealed that they had edited early-stage human embryos using a technique called base editing with incredible accuracy. Tie cites this work in her commentary, arguing that precision editing is now well within reach. CRISPR的发明在十多年前就提出了基因编辑婴儿的可能性，而更新形式的基因编辑提供了更高的精确度。今年6月，哥伦比亚大学的研究人员透露，他们使用一种称为“碱基编辑”的技术，以惊人的准确度编辑了早期人类胚胎。泰在她的评论中引用了这项工作，认为精确编辑现在已触手可及。

If medicine can safely and effectively prevent a disease, she writes, deciding whether to use that treatment should be part of a patient’s reproductive choice. “The obligation of medicine is not only to avoid causing harm but also to prevent avoidable suffering when effective interventions exist,” she writes. Tie says, though, the technology shouldn’t to enhance traits such as intelligence. 她写道，如果医学能够安全有效地预防某种疾病，那么决定是否使用这种治疗方法应该成为患者生殖选择的一部分。“医学的义务不仅是避免造成伤害，而且是在存在有效干预措施时，防止可避免的痛苦，”她写道。不过，泰表示，这项技术不应用于增强智力等特征。

And people seem to want the choice: A European survey released in July found that more people supported than opposed human embryo editing. 人们似乎也想要这种选择：7月份发布的一项欧洲调查发现，支持人类胚胎编辑的人数多于反对的人数。

Tie says that New York City–based Origin is currently working on “optimizing” base- and prime-editing tools on human embryos that IVF patients have donated for research. (The company is currently only testing it in human embryonic stem cell lines.) She expects the company to have significant data in the coming months showing that its embryo-editing tools are safe and efficient. Tie’s first human embryo-editing company, Manhattan Genomics, abruptly shuttered this year after operating for only a few months. 泰表示，总部位于纽约市的Origin公司目前正致力于在IVF患者捐赠用于研究的人类胚胎上“优化”碱基编辑和先导编辑工具。（该公司目前仅在人类胚胎干细胞系中进行测试。）她预计公司在未来几个月内将获得重要数据，证明其胚胎编辑工具是安全且高效的。泰的第一家人类胚胎编辑公司Manhattan Genomics在运营仅几个月后，于今年突然倒闭。

But while the Columbia work demonstrated that precise genetic changes to human embryos are possible, the researchers didn’t correct disease-causing mutations. Some of the editing tools they developed also resulted in unwanted and inconsistent genomic changes, leading them to conclude in a paper published this month that “undesirable consequences” meant the technology was not ready for clinical use. 尽管哥伦比亚大学的研究证明了对人类胚胎进行精确的基因改变是可能的，但研究人员并没有纠正致病突变。他们开发的一些编辑工具也导致了不必要的和不一致的基因组改变，这使他们在本月发表的一篇论文中得出结论：“不良后果”意味着该技术尚未准备好用于临床。

Variability also means that one editor working doesn’t establish that another will be safe. 变异性也意味着，一种编辑工具的成功并不能证明另一种工具就是安全的。

“Each and every mutation will therefore be a new medicine,” says Dieter Egli, who led the Columbia work. On top of the added technical challenges, that could make embryo-editing especially time-consuming and expensive to develop. “因此，每一个突变都将成为一种新的药物，”领导哥伦比亚大学这项研究的迪特尔·埃格利（Dieter Egli）说。除了增加的技术挑战外，这可能会使胚胎编辑的开发变得特别耗时且昂贵。

Tie is clear that she does not think embryo editing is ready for human patients, but she argues it’s close enough that it’s time to address the legal and funding barriers that stand in the way of developing it for use in US clinics. Federal funding for human embryo research is currently legally restricted, and the Food and Drug Administration is… 泰明确表示，她认为胚胎编辑尚未准备好用于人类患者，但她认为它已经足够接近，现在是时候解决阻碍其在美国诊所开发和使用的法律和资金障碍了。目前，联邦政府对人类胚胎研究的资助受到法律限制，而美国食品药品监督管理局（FDA）正在……