文章來源：《經(jīng)濟(jì)學(xué)人》Jun 17th 2023 期 Science & technology 欄 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費(fèi)錢費(fèi)力的事情。如修復(fù)路面坑洼，資助警察和消防員，處理堆積如山的垃圾。在許多情況下，沒有預(yù)算來管理城市小貓。

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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.

其他小貓也會(huì)造成問題。據(jù)估計(jì)世界上有6億只家養(yǎng)貓，其中約有4.8億只是自由活動(dòng)的。流浪貓可能長(zhǎng)得不好看，它們之間可能會(huì)相互傳播疾病或傳染給人類。許多貓生活條件差且一生短暫。即使貓咪脫離困境，它們也會(huì)造成其他方面的問題--從老鼠到鳥類，有 60 多種動(dòng)物已被掠食性貓科動(dòng)物獵殺至滅絕。

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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.

解決貓相關(guān)的問題并不便宜。以色列的特拉維夫城擁有數(shù)萬只貓，每年僅在絕育計(jì)劃上就花費(fèi)了10多萬美元?，F(xiàn)在有個(gè)好消息，《自然通訊》上的一篇論文表明，單次注射是一種廉價(jià)、安全且持久的貓咪絕育方法。

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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.

所涉及的技術(shù)是基因療法，一般是通過改造病毒將基因攜帶到生物體內(nèi)，以產(chǎn)生一些額外的作用。基因療法在人類中蓬勃發(fā)展，截至今年2月，美國(guó)食品和藥物管理局已經(jīng)批準(zhǔn)了7種不同的基因療法。大多數(shù)是針對(duì)罕見的遺傳疾病，包括血友病B，因基因突變導(dǎo)致血液凝固問題。

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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.

哈佛大學(xué)的分子生物學(xué)家大衛(wèi).佩平意識(shí)到，同樣的技術(shù)也可以用于避孕。他的實(shí)驗(yàn)室正在研究一種鮮為人知的生殖激素，稱為AMH（抗繆勒管激素），這種激素是由哺乳動(dòng)物體內(nèi)未成熟卵細(xì)胞的卵泡產(chǎn)生的。卵泡在卵巢內(nèi)長(zhǎng)大，直至破裂，然后把其中的物質(zhì)釋放到輸卵管中并進(jìn)行潛在的受精。更成熟的卵泡產(chǎn)生AMH，以減緩留在卵巢中卵子的生長(zhǎng)速度。這種激素就像一個(gè)紅色交通燈，以確保成熟卵子的流動(dòng)不會(huì)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.

佩平博士得出結(jié)論，通過植入正確的基因，說服哺乳動(dòng)物產(chǎn)生高于正常量的AMH，可能會(huì)加強(qiáng)這種抑制信號(hào)并完全停止卵泡的生產(chǎn)。在嚙齒動(dòng)物身上取得初步成功后，他與辛辛那提動(dòng)植物園的比爾.斯旺森聯(lián)手合作，在貓身上做實(shí)驗(yàn)。

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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，研究人員給6只貓注射了一種無害病毒，該病毒含有貓科動(dòng)物 AMH 基因的合成物質(zhì)，并給3只對(duì)照貓只注射了無此基因的病毒。他們選擇的病毒能夠?qū)⒂行лd荷直接傳遞到貓的肌肉細(xì)胞中。這些細(xì)胞是理想的有兩個(gè)原因。首先，肌肉細(xì)胞處于完美的位置，可以將激素(如AMH)泵入血液，進(jìn)而泵入包括卵巢在內(nèi)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，在動(dòng)物的一生中，肌肉細(xì)胞既不會(huì)死亡，也不會(huì)一分為二。這確保了它們攜帶的新基因不會(huì)隨著時(shí)間的推移而消失——這是永久絕育的必要條件。這對(duì)于pepepin博士所使用的遞送機(jī)制尤其重要。雖然大多數(shù)動(dòng)物的基因都包含在細(xì)胞核內(nèi)的DNA鏈中，但AMH基因卻存在于細(xì)胞質(zhì)中。盡管它的位置不同尋常，但它仍然能夠指示細(xì)胞產(chǎn)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只貓--均以美國(guó)總統(tǒng)夫人的名字命名--然后在2年內(nèi)對(duì)它們的糞便進(jìn)行監(jiān)測(cè)，以便了解它們的生殖激素的水平。為了確保貓與糞便匹配無誤，研究人員給每只貓都喂食了不同顏色的染料，或者給少數(shù)獨(dú)特貓咪喂食了發(fā)光物。8個(gè)月后，重復(fù)操作，又過了20個(gè)月，將公貓引入實(shí)驗(yàn)生活區(qū)，以便評(píng)估母貓的繁殖情況。

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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.

盡管3只對(duì)照組的貓（米歇爾、南希和羅莎琳）成功排卵并懷孕，但注射了攜帶基因病毒的6只貓（貝蒂、多莉、杰奎琳、阿比蓋爾、芭芭拉和瑪麗）沒有排卵和懷孕。每只貓的AMH水平都比實(shí)驗(yàn)前高出1000倍。有4只貓甚至拒絕交配繁衍，而另外2只交配的貓也沒有懷孕。斯旺森博士總結(jié)道："這些貓無法繁衍后代。"

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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.

雖然貓和嚙齒動(dòng)物的機(jī)體運(yùn)作機(jī)制不相同，但高水平的AMH似乎對(duì)這兩個(gè)物種都有避孕作用。佩平博士希望AMH也能成為人類避孕的有用方法--盡管人類需要的是一種具有臨時(shí)避孕效果的藥片，而不是永久效果的注射劑。目前，最常見的激素避孕藥是混合型避孕藥，它含有雌激素和孕激素。激素使卵泡成熟，避孕藥就是限制這種激素的釋放，并使子宮入口處的粘液變稠，阻止精子通過。

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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體，不只是生殖系統(tǒng)才有。合成荷爾蒙也會(huì)影響全身受體。這是避孕藥產(chǎn)生許多副作用的原因之一，包括情緒波動(dòng)、惡心和頭痛。人類的 AMH 受體更具特異性，主要存在于生殖系統(tǒng)中。因此，但愿AMH避孕藥的副作用更少。