【每天一篇经济学人】Animal contraception 动物避孕（2023

文章来源：《经济学人》Jun 17th 2023 期 Science & technology 栏 Animal contraception

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Running a city can be an expensive business. There are potholes to fix, policemen and firefighters to fund, and mountains of refuse to collect. In many cases, the kitty is empty.

管理城市可能是一件费钱费力的事情。如修复路面坑洼，资助警察和消防员，处理堆积如山的垃圾。在许多情况下，没有预算来管理城市小猫。

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Other sorts of kitties cause problems, too. Some 480m of the world’s 600m domesticated cats are thought to be free-roaming. Strays can be unsightly and can spread diseases, either to each other or to people. Many endure short and uncomfortable lives. Even those that land on their feet can cause suffering elsewhere—more than 60 species of animals, ranging from mice to birds, have been hunted to extinction by predatory cats.

其他小猫也会造成问题。据估计世界上有6亿只家养猫，其中约有4.8亿只是自由活动的。流浪猫可能长得不好看，它们之间可能会相互传播疾病或传染给人类。许多猫生活条件差且一生短暂。即使猫咪脱离困境，它们也会造成其他方面的问题--从老鼠到鸟类，有 60 多种动物已被掠食性猫科动物猎杀至灭绝。

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Fixing the problem, as well as the cats, is not cheap. Tel Aviv, which has tens of thousands of the animals, has spent over $100,000 a year on neutering programmes alone. Now, though, a paper in Nature Communications suggests a single jab could offer a cheap, safe and long-lasting way to sterilise a cat.

解决猫相关的问题并不便宜。以色列的特拉维夫城拥有数万只猫，每年仅在绝育计划上就花费了10多万美元。现在有个好消息，《自然通讯》上的一篇论文表明，单次注射是一种廉价、安全且持久的猫咪绝育方法。

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The technology involved is gene therapy, in which a gene is carried into an organism’s body, usually by a modified virus, in order to fulfil some additional function. This has been gaining momentum in humans, with seven different gene therapies approved by America’s Food and Drug Administration as of this February. Most are designed to target rare genetic diseases, including haemophilia B, where mutation causes problems with blood clotting.

所涉及的技术是基因疗法，一般是通过改造病毒将基因携带到生物体内，以产生一些额外的作用。基因疗法在人类中蓬勃发展，截至今年2月，美国食品和药物管理局已经批准了7种不同的基因疗法。大多数是针对罕见的遗传疾病，包括血友病B，因基因突变导致血液凝固问题。

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David Pépin, a molecular biologist at Harvard University, came to realise the same techniques could also be used to induce contraception. His laboratory was investigating a lesser-known reproductive hormone called AMH (anti-müllerian hormone), which is produced by the follicles that house immature egg cells in mammals. These follicles grow inside the ovaries until they burst, releasing their cargo into the fallopian tubes and towards potential fertilisation. More mature follicles produce AMH in order to slow down the growth of those eggs remaining in the ovaries. The hormone acts as a red traffic light, as it were, to ensure the flow of maturing eggs is not too rapid.

哈佛大学的分子生物学家大卫.佩平意识到，同样的技术也可以用于避孕。他的实验室正在研究一种鲜为人知的生殖激素，称为AMH（抗缪勒管激素），这种激素是由哺乳动物体内未成熟卵细胞的卵泡产生的。卵泡在卵巢内长大，直至破裂，然后把其中的物质释放到输卵管中并进行潜在的受精。更成熟的卵泡产生AMH，以减缓留在卵巢中卵子的生长速度。这种激素就像一个红色交通灯，以确保成熟卵子的流动不会太快。

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Dr Pépin concluded that persuading a mammal to produce higher-than-usual amounts of AMH—by inserting the right type of gene—might strengthen this braking signal and halt follicle production altogether. After initial successes in rodents, he joined forces with Bill Swanson at the Cincinnati Zoo and Botanical Gardens to test the idea on cats.

佩平博士得出结论，通过植入正确的基因，说服哺乳动物产生高于正常量的AMH，可能会加强这种抑制信号并完全停止卵泡的生产。在啮齿动物身上取得初步成功后，他与辛辛那提动植物园的比尔.斯旺森联手合作，在猫身上做实验。

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In 2019 the researchers injected six cats with a harmless virus that contained a synthetic copy of a feline AMH gene, and three control cats with the virus alone. In 2019 the researchers injected six cats with a harmless virus that contained a synthetic copy of a feline AMH gene, and three control cats with the virus alone. The virus they chose was able to deliver its payload direct to the cats’ muscle cells. These cells are ideal for two reasons. First, muscle cells are perfectly placed to pump hormones such as AMH into the bloodstream and thence into organs across the body, including the ovaries.  

2019年，研究人员给6只猫注射了一种无害病毒，该病毒含有猫科动物 AMH 基因的合成物质，并给3只对照猫只注射了无此基因的病毒。他们选择的病毒能够将有效载荷直接传递到猫的肌肉细胞中。这些细胞是理想的有两个原因。首先，肌肉细胞处于完美的位置，可以将激素(如AMH)泵入血液，进而泵入包括卵巢在内的全身器官。

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Second, muscle cells neither die off nor split in two during an animal’s lifetime. That ensures the new genes they had been armed with would not disappear over time—essential for permanent sterilisation. This is particularly important for the delivery mechanism employed by Dr Pé­ pin. While most of an animal’s genes are contained in strands of DNA inside the nuclei of cells, the AMH gene floats around in the cellular cytoplasm. Despite its unorthodox location, it is still capable of instructing the cell to produce hormones.

其次，在动物的一生中，肌肉细胞既不会死亡，也不会一分为二。这确保了它们携带的新基因不会随着时间的推移而消失——这是永久绝育的必要条件。这对于pepepin博士所使用的递送机制尤其重要。虽然大多数动物的基因都包含在细胞核内的DNA链中，但AMH基因却存在于细胞质中。尽管它的位置不同寻常，但它仍然能够指示细胞产生激素。

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All nine cats—which were named after the wives of American presidents—then had their faeces monitored over the course of two years so that the levels of their reproductive hormones could be checked. In order to ensure the right cats were being matched to the right scat, each was fed food with a different coloured dye or, for a few fabulous individuals, glitter. After eight months, and then again after 20 months, male cats were introduced into the living quarters so that the females’ breeding patterns could be assessed.

所有9只猫--均以美国总统夫人的名字命名--然后在2年内对它们的粪便进行监测，以便了解它们的生殖激素的水平。为了确保猫与粪便匹配无误，研究人员给每只猫都喂食了不同颜色的染料，或者给少数独特猫咪喂食了发光物。8个月后，重复操作，又过了20个月，将公猫引入实验生活区，以便评估母猫的繁殖情况。

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Though the three control cats (Michelle, Nancy and Rosalyn) ovulated and got pregnant, the six injected with the gene-carrying virus (Betty, Dolly, Jacqueline, Abigail, Barbara and Mary) did not. Each had levels of AMH up to a thousand times higher than before they were treated. Four refused to even try to breed, and the two that were still receptive to the idea had no pregnancies. “These cats are not able to reproduce,” concludes Dr Swanson.

尽管3只对照组的猫（米歇尔、南希和罗莎琳）成功排卵并怀孕，但注射了携带基因病毒的6只猫（贝蒂、多莉、杰奎琳、阿比盖尔、芭芭拉和玛丽）没有排卵和怀孕。每只猫的AMH水平都比实验前高出1000倍。有4只猫甚至拒绝交配繁衍，而另外2只交配的猫也没有怀孕。斯旺森博士总结道："这些猫无法繁衍后代。"

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While the precise mechanisms in cats and rodents are not identical, high levels of AMH seem to have a contraceptive effect in both species. Dr Pépin hopes AMH could become a useful target in human contraception too—though as a pill with temporary effects rather than a permanent injection. Presently, the most common kind of hormonal contraception is the combined pill, which contains oestrogen and progesterone. These limit the release of hormones which cause follicles to ripen, and thicken the mucus at the entrance of the womb, preventing the passage of sperm.

虽然猫和啮齿动物的机体运作机制不相同，但高水平的AMH似乎对这两个物种都有避孕作用。佩平博士希望AMH也能成为人类避孕的有用方法--尽管人类需要的是一种具有临时避孕效果的药片，而不是永久效果的注射剂。目前，最常见的激素避孕药是混合型避孕药，它含有雌激素和孕激素。激素使卵泡成熟，避孕药就是限制这种激素的释放，并使子宫入口处的粘液变稠，阻止精子通过。

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But there are oestrogen and progesterone receptors all over the body, not just in the reproductive system. Synthetic hormones affect those as well. That is one reason for the pill’s many side-effects, including mood swings, nausea and headaches. AMH receptors in humans are much more specific, being found mostly in the reproductive system. The hope is that a contraceptive that targets AMH may therefore be one with many fewer side-effects.

但全身都有雌激素和孕激素受体，不只是生殖系统才有。合成荷尔蒙也会影响全身受体。这是避孕药产生许多副作用的原因之一，包括情绪波动、恶心和头痛。人类的 AMH 受体更具特异性，主要存在于生殖系统中。因此，但愿AMH避孕药的副作用更少。