【经济学人】你准备好怀孕了吗？|2016.10.22|第711期

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Infertility

不孕不育

Making sex cells from body cells

从体细胞中培育生殖细胞

An experiment on mice offers hope to infertile people

一个在老鼠身上做的实验给不孕不育的人带来了希望

Oct 22nd 2016 | From the print edition

2016年10月22日|摘自印刷版

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ISSUES of safety aside, the very idea of cloning people—of taking, say, a cell from the skin of a man or a woman and growing it into a new human being with exactly the same genes as its progenitor—is anathema to many. But what about taking such a cell and creating from it an egg or a sperm that can be used for in vitro fertilisation? That would enable infertile men and women, and gay couples, who wanted to raise children genetically related to both parents to do so, rather than relying on the assistance of an unrelated egg or sperm donor to start a family. 

将安全问题先放在一边，很多人对克隆人（可以将一个人的皮肤细胞培养成长为一个新的拥有与其完全相同基因的人类）都十分厌恶。但是从人体内取出一个细胞，把它培养成卵细胞或者精子细胞用于体外受精又该当何论？这将使不孕不育的夫妇，同性恋夫妇以及那些想要提高孩子的基因（与父母的基因息息相关）的夫妇们不需要借助不相关人捐献的卵细胞或者精子就孕育孩子。

In people, this is not yet possible. But Katsuhiko Hayashi and his colleagues at Kyushu University, in Fukuoka, Japan, have done the equivalent in mice. As they report this week in Nature, there are animals now scampering around cages in their laboratory whose maternal antecedents are egg cells derived not from the ovaries of their mothers, but from body cells (known as somatic cells), in this case from those mothers’ tails. Nor does it stop there. In the past, using a slightly different technique from the one that he describes this week, Dr Hayashi has bred mice using somatic-cell-derived sperm.

然而对人类来说，这个技术目前还不能实现。但是位于日本福冈的九州大学的Katsuhiko Hayashi教授和他的同事们已经在小鼠身上做了这样的实验。据他们这周发表在《自然》杂志上的文章所述，那些在他们实验室的笼子中奔跑的小鼠们的母体基因来自其母亲的体细胞（被称为体壁细胞）而不是卵巢卵细胞（这里采用的是母亲的尾巴上的细胞）。不止于此，Hayashi博士以前用过与这周技术稍微不同的技术，提取了自体细胞培育成精子，繁殖出了老鼠。

Both of these sorts of animals have gone on to breed successfully. So, not only are Dr Hayashi’s creations viable, they are fertile. Moreover, in principle—though he has not yet done so in practice—he could fertilise his somatic-cell-derived eggs with his somatic-cell-derived sperm to create an entirely somatic-cell-derived adult animal. He might even, if he so chose, be able to derive sperm and eggs from the same animal, for the processes do not require that the eggs be made from female cells and the sperm from those of males. That would create a mouse which had only one parent, yet was not a true clone of that parent because the sex cells which united to form it would both have undergone the internal genetic mixing that biologists call meiosis.

这两项技术培育而成的动物都成功地孕育了下一代。因此，Hayashi博士培育的生物很成功，并且还可以繁殖后代。除此之外，尽管他还没有实践过，但原则上来讲，可以利用体细胞培育的卵细胞和精子创造一个完全来源于体细胞的成年动物。如果这样选择，他也许能够只从同一个动物身上提取卵细胞和精子，而无需再从雌性动物体内提取卵细胞或从雄性动物体内提取精子，就可以进行繁殖。这样以来，就可以培育出父母只有一个的老鼠，并且这并不是其“父母”的克隆，因为它的合成性细胞经过了生物学家称之为减数分裂的内部遗传混合。

One step back, two steps forward

有时候只有退一步才能前进两步

Dr Hayashi and his colleagues do not create their eggs and sperm directly from somatic cells. First, those cells have to undergo an alchemical transformation to rejuvenate them into an ancestral form known as a pluripotent stem cell. Mature body cells (eggs and sperm included) derive from progenitors, known as stem cells, that have the power to divide, proliferate and eventually to turn into particular cellular components of a particular tissue. Pluripotent stem cells are, in turn, the ancestors of these tissue-forming stem cells.

Hayashi博士和他的同事们并不是直接用体细胞培育卵子和精子。首先，那些细胞必须经历一个类似炼金术的转化把细胞修复成原始多能干细胞。来源于本体、成熟的身体细胞（包括卵细胞和精子），被称为干细胞——这些干细胞可以分裂，繁殖并且最终成为特定组织的特定细胞成分。反过来，多功能干细胞是这些组织干细胞的原型。

In nature, pluripotent cells are restricted to embryos. The first students of cloning and its related arts had therefore to “harvest” them for their experiments—which created ethical dilemmas when the embryos involved were human. Such harvesting is no longer necessary. Instead, for mice, men and many other species, pluripotent cells can be made to order by taking an ordinary body cell and adding to it active copies of the four genes which encode the genetic switches that cause pluripotency.

在自然界中，多功能干细胞仅限于胚胎。克隆技术其相关的艺术的第一批学生可以把它们“收集”起来拿来实验——当所涉及到人类胚胎的时候就陷入了伦理困境。现在这样的“收集”不必要了。相反，对于小鼠，人类以及许多其他物种来说，多功能干细胞可以按需要来订做了：通过提取普通的身体细胞并给其添加四个带有多功能干细胞遗传开关的复制基因。

It was such “induced” pluripotent cells that formed Dr Hayashi’s starting-point. As he had discovered in his experiments creating sperm, judicious application of a molecule called bone morphogenetic protein 4 turns pluripotent cells into primordial germ cells—the type of stem cell ancestral to both sperm and eggs. Which of these a primordial germ cell goes on to become depends on the sex of the tissue it finds itself in. In those earlier experiments Dr Hayashi injected them into the testes of newly born mice, thus persuading them to become sperm when they underwent meiosis. This time he used ovarian tissue extracted from mouse fetuses to induce egg-forming meiosis.

这就是Hayashi博士“诱导型”多功能干细胞的出发点。正如他在培育精子实验中发现的一样，将骨形态发生4号蛋白将多功能细胞转化为原始生殖细胞（精子和卵子的干细胞的祖细胞类型）是一个明智的方法。原始的生殖细胞的究竟会长生什么取决于它所在组织的性别。在那些早期实验中Hayashi博士将它们注射到新生小鼠的睾丸中，它们进行减数分裂时就变成精子了。这一次他使用提取自小鼠胚胎的卵巢组织来诱导卵子进行减数分裂。

To keep track of this process, and to avoid confusion, Dr Hayashi took the cells used to make the eggs from a dark-eyed mouse. He then fertilised the eggs he had created in vitro with sperm from a pink-eyed male, and also implanted the resulting embryos into pink-eyed females. To everyone’s delight the pups born of this arrangement had dark eyes (see picture)—caused by a gene that could have come only from the tail-derived eggs. Furthermore, as had happened before with the somatic-cell-derived sperm, these pups developed normally into adults and were themselves able to reproduce.

为了跟踪记录此过程，避免混乱，Hayashi 博士提取了曾用来培育卵细胞的黑色眼睛老鼠的细胞。接下来，拿这个卵细胞与粉色眼睛老鼠的精子在体外结合，并且将这个胚胎植入粉色眼睛的母鼠体内。让所有人振奋的是，这种结合下出生的幼崽拥有黑色眼睛（如图）——这是只有来自尾部细胞衍生的卵子的基因才能做到的。此外，正如之前体细胞培育的精子一样，这些幼崽都能成年并且能够进行繁殖。

All this is a long way from enabling scientists to perform the same trick with people. First and foremost, using human embryonic tissue in any part of the process is out of the question for ethical reasons. That means someone needs to work out exactly which of the chemicals in testes and ovaries tell primordial germ cells whether to become eggs or sperm. Second, at the moment the process is extremely inefficient. Only 3.5% of Dr Hayashi’s tail-derived embryos grew into pups, compared with about 60% of embryos from normal eggs. Third, though mice have proved useful models for examining many questions of human medicine, mere models is all they are. A lot more research will be needed before anyone (or, at least, anyone with any ethical sensibility) tries something similar on a human being. If and when that day comes, though, the unwillingly childless around the world will be watching with great interest.（读者试译）

科学家们要想在人类身上施展这种魔术，还有很长的路要走。首先，从道德标准来看要想把人类的胚胎组织用于这一过程的任一环节都是不可能的。这意味他们需要精准地找出睾丸和卵巢中的哪种化学物质可以把原始生殖细胞培育成卵子或者精子。其次，目前这个过程的效率非常低。Hayashi博士的实验中，正常卵细胞培育的胚胎长成幼崽的几率为60%，而来源于尾部细胞的卵细胞培育的胚胎长成幼崽的几率只有3.5%。再次，尽管已经证实小鼠可以作为研究人类医学的许多问题时的有用的实验体，但也只是实验体而已。尽管，如果那一天到来了，那些不能生育的人们都会对此很感兴趣。（期待您的翻译，您可以将翻译留言到文章底部，第二天会有详细解析哦。）

This article appeared in the Print Edition with the headline: The ancestor’s tail

本文在印刷版的标题为：祖先的尾巴

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