Dieter Egli was just about to startgraduate school in 1998 when researchers first worked out how to derive humanembryonic stem cells. In the two decades since, the prolific cells have been afixture of his career. The biologist, now at Columbia University in New YorkCity, has used them to explore how DNA from adult cells can be reprogrammed toan embryonic state, and to tackle questions about the development and treatmentof diabetes. He has even helped to develop an entirely new form of humanembryonic stem cell that could simplify studies on what different human genesdo.

Dieter Egli在1998年即将开始研究生学习，那时研究人员第一次开始研究如何衍生人类胚胎干细胞。在此后的二十年里，多产细胞一直是他职业生涯的一部分。现在在纽约市哥伦比亚大学的生物学家已经利用它们来探索成年细胞中的DNA如何能够重新编辑为胚胎状态，解决有关糖尿病发展和治疗的问题。他甚至帮助开发了一种全新的人类胚胎干细胞，可以简化对不同人类基因的研究。

His wide-ranging research established himas a leader in embryonic stem-cell biology, a field challenged by restrictedfunding and an enthusiasm for competing technologies that don’t carry the sameethical baggage. Still, many say that human embryonic stem cells are now morerelevant than ever. “I am very excited about embryonic stem cells,” says Egli.“They will lead to unprecedented discoveries that will transform life. I haveno doubt about it.”

他的广泛研究使他成为胚胎干细胞生物学领域的领导者，这是一个受限制资金挑战的领域，具有对竞争技术的热情但是却没有道德包袱的领域。尽管如此，许多人认为人类胚胎干细胞现在比以往任何时候都更重要。 “我对胚胎干细胞感到非常兴奋，”Egli说。 “它们会引发前所未有的发现，这将改变我们的生活。我对此毫不怀疑。“

Embryonic stem (ES) cells provideunparallelled information on early development. Like astronomers looking backto the Big Bang for fundamental insight about the Universe, biologists rakeover the molecules inside these remarkable entities for clues as to how asingle original cell turns into trillions, with a dizzying array of forms andfunctions. Scientists have learnt how to turn the cells into dozens of mature celltypes representing various tissues and organs in the body. These are used totest drugs, to model disease and, increasingly, as therapies injected into thebody. Starting with an attempt to repair spinal-cord injuries in 2010, therehave been more than a dozen clinical trials of cells created from ES cells — totreat Parkinson’s disease and diabetes, among other conditions. Early resultssuggest that some approaches are working: a long-awaited report this week showsimproved vision in two people with age-related macular degeneration, a diseasethat destroys the sharpness of vision.

胚胎干（ES）细胞为早期发育提供了无与伦比的信息。就像天文学家回望宇宙大爆炸的基本见解一样，生物学家掠过这些非凡实体内部的分子，寻找单个原始细胞如何变成万亿的线索，并具有令人眼花缭乱的形式和功能。科学家们已经学会了如何将细胞转化为代表身体各种组织和器官的几十种成熟类型的细胞。这些用于测试药物，模拟疾病，并且越来越多地作为治疗机注射到体内。自2010年尝试修复脊髓损伤开始，已经有十几个胚胎干细胞产生的细胞的用于临床试验 - 治疗帕金森病和糖尿病等病症。早期的结果表明，一些方法正在发挥作用：本周期待已久的一份报告显示，两名年龄相关性黄斑变性患者的视力得到改善，这种疾病会破坏视力清晰度。

“In some ways, it’s not a surprise, because20 years ago we expected it,” says Egli, “but I’m still surprised that thispromise is becoming a reality.”

“从某些方面来说，这并不令人意外，因为20年前我们已经预测出它会出现，”Egli说，“但我仍然很惊讶这个承诺正在成为现实。

Tentative beginnings实验性的开始

In 1981, researchers managed to culturestem cells from mouse embryos. They soon recognized the research potential ofthese intriguing entities, which can both replicate themselves and be nudgedinto becoming any of the body’s 200-plus cell types. But that trick was noteasy to accomplish in primates. It took biologist James Thomson, at theUniversity of Wisconsin–Madison 14 years to achieve it in monkeys. Three yearslater, using donated embryos that had gone unused in fertility treatments,Thomson struck again, creating the world’s first human ES-cell line.

1981年，研究人员设法从小鼠胚胎培养干细胞。他们很快就认识到这些魅力无限的实体的研究潜力，它们既可以自我复制，又可以被纳入身体的200多种细胞类型中。但是这个窍门在灵长类动物中并不容易完成。威斯康星大学麦迪逊分校的生物学家詹姆斯汤姆森花了14年的时间在猴子身上实现这一目标。三年后，汤姆森再次使用未用于生育治疗的捐赠胚胎，创造了世界上第一个人类胚胎干细胞系.

Time to diversify随着时间发生多样化

Researchers are also trying to grow organs.Given the right signalling molecules and 3D environment, ES cells organizeinto complex tissues known as organoids, even in a dish. This capacity isimportant for researchers such as James Wells at Cincinnati Children’s Hospitalin Ohio, who is developing intestinal organoids for testing drugs, and perhapsone day for transplant.

研究人员也试图让它们长成器官。在正确的信号分子和3D环境下，胚胎干细胞即使在盘子里也能组织成复杂的组织，称为类固醇。这种能力对研究人员例如俄亥俄州辛辛那提儿童医院的詹姆斯韦尔斯，很重要，他正在开发用于测试药物的肠内类固醇，可能还有一天需要用于移植。

And new sources of ES cells have presentedother research tools for genetic disease. In 2004, for example, fertilitydoctors in Chicago started making ES-cell lines from embryos createdthrough in vitro fertilization that had been found to have agenetic defect, and thus were rejected for fertility treatments. This allowedthe team to create cellular models of thalassaemia, Huntington’s disease,Marfan’s syndrome, muscular dystrophy and other genetic conditions. In 2007,researchers used ES cells to pin down the molecular changes that lead tocognitive impairments seen in a heritable condition known as Fragile Xsyndrome.

胚胎干细胞的新来源也为其他遗传疾病提供了研究工具。例如，在2004年，芝加哥的生殖医生开始通过体外试管受精产生的胚胎制造胚胎干细胞系，该胚胎被发现具有遗传缺陷，因此被拒绝接受生育治疗。这使得该团队创建出地中海贫血，亨廷顿病，马凡氏综合征，肌营养不良和其他遗传病症的细胞模型。 2007年，研究人员利用胚胎干细胞来抑制导致认知障碍的分子变化，会出现在一种称为脆性X综合征的遗传性疾病中。

Cell revival细胞再生

Melton still has plans for the β-cells he’smade from ES cells. He hopes to transplant them into people with type 1diabetes to end, or at least reduce, their reliance on insulin injections. Thelast hurdle in the work is introducing the cells so that they are not destroyedby the immune system. Semma Therapeutics, a company that Melton founded inCambridge, aims to do this by ensconcing the cells in a pouch that would allownutrients in and insulin out, but would block access to immune cells. Heexpects to start clinical trials within three years. ViaCyte in San Diego,California, has just restarted a similar clinical trial it launched in 2014after redesigning its encapsulation technology. And other companies, such asNovo Nordisk in Denmark are starting up programmes for diabetes using cellsderived from ES cells.

梅尔顿对从胚胎干细胞制造β细胞依然有他的计划，他希望将它们移植到1型糖尿病患者身上，以终止或至少减少病人对胰岛素注射的依赖。这项工作中的最后一道障碍是细胞导入并不被免疫系统破坏。梅尔顿在剑桥创立的公司Semma Therapeutics的目标是通过将细胞放置在可使营养成分和胰岛素释放的小袋中，可以阻断对免疫细胞的接触。他预计会在三年内开始临床试验。加利福尼亚州圣迭戈的ViaCyte公司在重新设计了封装技术后，刚刚重启了类似2014年开展的临床试验。而其他公司，例如丹麦的诺和诺德公司正在利用胚胎干细胞衍生的细胞启动糖尿病项目。

In the clinical realm, many have assumedthat iPS cells would eventually win out over ES cells. One potential advantageis that they can produce cells and tissues with the same DNA as the patient andthus not cause an immune reaction when transplanted. But for most geneticdiseases, including type 1 diabetes, iPS cells created from a patient wouldcontain the mutation that causes the problem, and the cells would have to bemodified to confer any therapeutic benefit.

在临床领域，许多人认为诱导多能干细胞（iPS cells）最终会战胜胚胎干细胞，其中一个潜在的优点是iPS细胞可以产生具有与患者相同的DNA的细胞和组织，因此在移植时不会引起免疫反应。但对于大多数遗传性疾病，包括1型糖尿病，从患者产生的iPS细胞将含有导致该问题的突变，并且细胞必须被修改才能给治疗带来益处。

Pathway to promise通向承诺之路

ES-cell research still has room to grow, ifit can get past some hurdles. One big problem is that many cell types arechallenging to produce. Melton estimates that only about ten cell types createdso far are truly functional equivalents of normal human cells. And some withthe most far-reaching uses, such as eggs and sperm, are expected to remain achallenge for the foreseeable future.

胚胎干细胞研究如果能够克服一些障碍，仍然有增长空间，其中一个大问题是许多细胞类型都难以生产。梅尔顿估计，迄今为止产生的细胞中仅有约十种能具有真正等同于正常人类细胞的功能。而且一些最具影响力的用途，如鸡蛋和精子，预计在可预见的未来仍会是一个挑战。