https://www.economist.com/science-and-technology/2021/05/20/rna-good-for-vaccines-can-also-be-used-as-a-pesticide

A new approach to debugging
除虫有新招

RNA, good for vaccines, can also be used as a pesticide

用于疫苗的 RNA 也可用作杀虫剂

RIBONUCLEIC ACID (RNA), once little-known outside biological circles, has recently become the molecule de nos jours. The reason is its role in covid-19 vaccines. The RNA molecules in these encode spike, a coronavirus protein. So, when the protein-making machinery of a body cell encounters such RNA, spike is what it makes. That lets a vaccine-recipient’s immune system learn to recognise a crucial part of the enemy before the real thing turns up.

核糖核酸(RNA)过去在生物圈之外鲜为人知,近来却成了「这个时代的分子」。这是因为它在新冠疫苗中扮演的角色。新冠疫苗中的 RNA 分子会编码一种冠状病毒刺突蛋白,因此当人体细胞的蛋白合成机制遇到这样的 RNA,就会制造刺突。这让疫苗受种者的免疫系统在真正的敌人出现之前,学会识别它的关键特征。

Helping to make proteins is not, however, RNA’s only job. Among many other things it is central to a process called RNA interference, which prevents, rather than facilitates, the manufacture of specific proteins. RNAi, as this activity is called for short, has also been investigated medically. It has been approved for use against four genetic diseases and is under investigation for the treatment of more than a dozen others. That is good. Some biologists, though, think RNAi may have an important non-medical use as well, as a precisely targeted, environmentally friendly pesticide.

然而,帮助合成蛋白质并不是 RNA 唯一的工作。它的许多其他工作之一是在一个叫作 RNA 干扰的过程中起到的核心作用。RNA 干扰是阻止、而不是帮助特定蛋白质的生成。这一过程简称为 RNAi。人们也对它进行了医学上的研究。它已经被批准用来治疗四种遗传病,还有其他十多种疾病的治疗也在研究中。这是件好事。不过,一些生物学家认为,RNAi 可能还有一个重要的非医学用途,即用作一种精准靶向、对环境无害的杀虫剂。

The theory is simple. Identify a protein crucial to the survival of the pest in question. Tailor a specific interfering RNA molecule to sabotage production of that protein. Deliver it into the bodies of the pests. Then wait for them all to die. In practice, of course, things are more complicated. Delivery mechanisms have to be designed and regulatory hoops jumped through. But until recently, the biggest obstacle was cost. Life-saving medicines can be expensive. Pesticides must be cheap. One effect of all the medical RNA work, however, has been to bring down the cost of making the stuff. As Michael Helmstetter, the boss of RNAissance Ag, a firm in Kansas which is developing RNA-based pesticides, observes,“a gram of RNA cost $100,000 when we started. By 2014 it was $100 a gram. Now it’s a dollar a gram.”

它的原理很简单。找到对相关害虫的存活至关重要的一种蛋白质。制作专门的 RNA 干扰分子来破坏这种蛋白质的生成。把它送入害虫体内。然后等待害虫通通死掉。当然,实际操作起来会更复杂。必须设计好药物输送机制,还要通过重重监管。但直到最近,最大的障碍还是成本。救命药可以昂贵,而杀虫剂必须便宜。但 RNA 的医学研究带来的好处之一是降低了这种物质的生产成本。堪萨斯州的 RNAissance Ag 公司正在研发基于 RNA 的杀虫剂,其老板迈克尔・海姆斯泰特(Michael Helmstetter)说:「公司刚启动时 RNA 的价格是 10 万美元一克。到 2014 年是 100 美元一克。现在是一美元一克。」

Running interference 积极干扰

Top of the list of potential beneficiaries are honeybees. These semi-domesticated insects, important not only for their eponymous product, but also as pollinators, are plagued by Varroa destructor, a mite a couple of millimetres across (pictured above, on the head of a pupating bee). Varroa mites live by attaching themselves to, and feeding on, bees. This weakens or kills the hosts and also spreads viruses around a hive. Some suspect Varroa plays a role in colony-collapse disorder, a mysterious phenomenon in which most of a hive’s workers desert for no apparent reason.

蜜蜂可能是最大的受益者。这些半驯养的昆虫之所以重要,不仅是因为它们生产蜂蜜,还因为它们传播花粉。但它们常常受到狄斯瓦螨(以下简称瓦螨)的侵扰。瓦螨是一种只有几毫米大的螨虫(如上图所示,贴附在一只正在化蛹的蜜蜂头上)。瓦螨靠附着在蜜蜂身上并吸食蜜蜂体液为生。这会让蜜蜂衰弱或者死亡,并且在蜂房周围传播病毒。一些人怀疑瓦螨与蜂群崩溃综合症有关,这是一种导致大部分工蜂原因不明地弃巢而去的神秘现象。

Beekeepers have tried all sorts of ways of attacking Varroa mites. Some place plastic strips laced with amitraz, a pesticide reckoned particularly effective against mites, at the entrances to hives. Others vaporise oxalic acid, which has a similar reputation, and pump it into the hive. Others still run breeding programmes, selecting for bees that resist infestation. None has succeeded in solving the Varroa problem. At best, these approaches keep the mites’numbers just below the threshold of crisis.

养蜂人尝试了各种办法来对付瓦螨。一些人在蜂房入口处放置加有双甲脒的塑料条,双甲脒是公认的高效杀螨剂。一些人把同样被认为有很好杀螨效果的草酸汽化后注入蜂房。另一些人仍在开展育种项目,选育抗螨蜂种。但他们都没能成功解决瓦螨问题。这些方法充其量也只是把瓦螨的数量刚刚控制在危机爆发的临界值以下。

GreenLight Biosciences, a company in Boston, wants to help. It has bought from Bayer, a German pharmaceutical and life-science firm, the rights to an experimental Varroa pesticide based on RNAi. Andrey Zarur, GreenLight’s boss, hopes this will succeed where other methods fail because it attacks the mite in a way mere chemical interventions cannot.

波士顿一家名为 GreenLight Biosciences 的公司想出份力。它从德国制药和生命科学公司拜耳那里买下了一种基于 RNAi 的试验性瓦螨杀虫剂的所有权。GreenLight 的老板安德烈・扎鲁(Andrey Zarur)希望它会在其他方法都挫败之时取得成功,因为它对付瓦螨的方法是单凭化学干预无法做到的。

Varroa’s lifecycle starts when a pregnant female mite crawls alongside a bee larva developing inside one of the nursery cells in a hive’s honeycomb. While the larva is growing, this mite just sits there. But once it turns into a pupa she springs into action and lays her eggs on it. Mites and bee then mature in unison over the next few days, and when the adult bee emerges from the cell, the mites attached to it spread around the hive to repeat their trick with future generations.

当待产卵的雌螨和在蜂房的巢室里成长的蜜蜂幼虫一起爬行时,瓦螨的生命周期便开始了。在蜜蜂幼虫生长的过程中,雌螨只是静待在那里。但一旦蜜蜂幼虫变成蛹,雌螨就开始行动起来,在蜂蛹上产卵。在接下来的几天里,瓦螨会和蜜蜂一起发育成熟,当蜜蜂成虫从巢室里出来时,附着在它身上的瓦螨就会在蜂房周围四散开来,以后一代接一代地重复这种伎俩。

That the mites spend so much time hidden in the honeycomb makes them hard to attack. And this is where GreenLight hopes its RNA will win through. In field trials in the state of Georgia the firm’s operatives are feeding Varroa-destroying RNA to the bees themselves—mixing it in sugar water which the workers drink and make honey from. This lays a biotechnological trap for the mites by lacing any honey in their birthplace with the stuff. By lowering the cost of RNA production and so allowing much more of it to be used, Mr Zarur thinks he can deliver more RNA to the mites, succeeding where Bayer and others did not.

瓦螨在巢房里蛰伏的时间很长,这让它们很难对付。这也是 GreenLight 希望自己的 RNA 能取得突破的地方。在乔治亚州的田野试验中,GreenLight 的技术人员把能杀灭瓦螨的 RNA 掺在工蜂食用以及酿造蜂蜜用的糖水中喂给蜜蜂。如此这般在瓦螨出生地的所有蜂蜜中加入这种 RNA,就为瓦螨设下了一个生物技术陷阱。扎鲁认为,如果能降低 RNA 的生产成本,并由此大幅提高 RNA 的用量,他就能更多地给瓦螨投喂 RNA,从而做成拜耳和其他公司没有做成的事。

Varroa mites are not, though, the only pests in GreenLight’s crosshairs. It also has its sights trained on Colorado potato beetles, which can devastate crops if not controlled. In their case the RNA is simply sprayed onto an infested field and the beetles munch it up. And, though it is cagey about the details, the firm says it has 13 other hostile organisms under investigation, too. These include the fall armyworm, a moth caterpillar that chomps through everything from tobacco to oranges, and the caterpillars of the diamondback moth, the world’s worst pest of brassicas, a group which includes cabbages, cauliflowers, broccoli, Brussels sprouts and oilseed rape. Nor is the RNAi approach limited to attacking animals. In principle, any organism is susceptible to it. GreenLight’s target list therefore also includes crop-damaging fungi such as Botrytis, Fusarium and powdery mildew.

不过,瓦螨并不是 GreenLight 瞄上的唯一害虫。它还盯上了科罗拉多马铃薯甲虫,这种甲虫如果不加以控制,会对庄稼造成毁灭性破坏。他们的做法是直接把 RNA 喷洒到受甲虫入侵的田地里,让甲虫吃掉。尽管对细节讳莫如深,但 GreenLight 表示,它还在对其他 13 种有害生物开展研究,其中包括草地贪夜蛾的幼虫,它从烟草到柑橘无所不吃;还有小菜蛾的毛虫,这是世界上对包括卷心菜、花椰菜、西兰花、抱子甘蓝和油菜在内的芥属植物危害最大的害虫。另外,RNAi 方法也不是只能用来对付动物。原则上,所有生物体都容易受到它的影响。因此,GreenLight 的目标清单里还包括葡萄孢菌、镰刀菌和白粉菌等对作物有害的真菌。

Cell game 细胞游戏

Not surprisingly, GreenLight has rivals in its quest to develop RNA pesticides. At least two other American companies are working on them as well. RNAissance Ag, Dr Helmstetter’s firm, is gunning for the potato beetle and the fall armyworm. AgroSpheres, in Charlottesville, Virginia, is going after Diamondback moths. All three enterprises think they can make RNA cheaply enough for it to be sprayed onto fields. But they do so in different ways.

毫不出奇,GreenLight 在研发 RNA 杀虫剂的过程中遇到了竞争对手。至少还有两家美国公司也在致力于研发这种杀虫剂。海姆斯泰特的公司 RNAissance Ag 正在竭力对付马铃薯甲虫和草地贪夜蛾。位于弗吉尼亚州的夏洛茨维尔市(Charlottesville)的 AgroSpheres 正在想办法消灭小菜蛾。这三家企业都认为自己能生产足够便宜的 RNA,用于田间喷洒灭虫。但它们的方法有所不同。

GreenLight employs a process called cell-free biology, which is more akin to chemistry than conventional biotechnology. Eliminating the need to coddle fussy micro-organisms, says Mr Zarur, simplifies and cheapens things dramatically. But the more traditional approach taken by RNAissance and AgroSpheres, of growing their RNA molecules inside modified bacteria, offers advantages, too. Packaging the RNA in bacterial cells in this way protects the molecules. It also allows the companies’biotechnologists to add features to the cell walls, such as stickiness that stops them slipping off the leaves of plants.

GreenLight 采用的方法叫作无细胞生物学,它更类似于化学而不是传统的生物技术。扎鲁说,无需悉心培养娇贵的微生物这一点极大地简化了过程并降低了成本。而 RNAissance 和 AgroSpheres 采用了更传统的方法——在经基因改造的细菌中培育 RNA 分子。这也自有优势。这种方法将 RNA 包裹进菌细胞,可以起到保护 RNA 分子的作用。它还可以让这两家公司的生物技术专家在细胞壁上做文章,比如增加粘性,防止它们从植物叶片上滑落。

Spraying RNA onto crops is not, however, the only way to get it into pests. Though it has abandoned its honeybee technology, Bayer is developing a genetically modified maize which produces RNA that kills beetle larvae called corn rootworms. A group at the University of Florida is taking a similar approach to the insects known as psyllids that spread a bacterium which causes citrus-greening disease, a serious threat to orange groves.

然而,在作物上喷洒 RNA 并不是让它进入害虫体内的唯一方法。虽然拜耳已经放弃了蜜蜂技术,但它正在研发一种转基因玉米,这种玉米产生的 RNA 可以杀死一种叫作玉米根虫的甲虫幼虫。佛罗里达大学的一个研究团队正在尝试采用类似的方法对付一种叫作木虱的昆虫。木虱传播的细菌会引发柑橘黄龙病,对柑橘园是严重的威胁。

RNA spraying has advantages, though. A farmer can use it on existing crops, rather than having to replant with transgenic versions. The regulations are Less onerous than for the creation of transgenic organisms. And in Europe, where transgenic crops are banned in many places, governments seem open to RNA-based pesticides.

不过,RNA 喷洒有其优势。农民可以在现有作物上喷洒 RNA,而不必改种转基因作物。且与创造转基因生物相比,相关法规也没那么繁琐。欧洲很多地方都禁止转基因作物,各国政府似乎对基于 RNA 的杀虫剂持开放态度。

Andreas Vilcinskas, an entomologist at the Fraunhofer Institute’s campus in Giessen, Germany, who is working with GreenLight, says the German government now supports their development. It has good reason to. In 2018 the European Union banned the outdoor use of three types of neonicotinoids, a popular class of pesticides. Since then, Germany, France and Poland have all had to reverse this ban on an emergency basis after aphids spread like wildfire. Ironically, neonicotinoids were banned to help bees. Promoting RNA as a pesticide might thus, as it were, kill many bugs with one stone.

德国弗劳恩霍夫应用研究促进协会(Fraunhofer Institute)吉森(Giessen)园区的昆虫学家安德里亚斯・维尔钦斯卡斯(Andreas Vilcinskas)正在与 GreenLight 合作,他说他们的研究现在得到了德国政府的支持。德国政府有充分的理由这么做。2018 年,欧盟禁止在户外使用当时被广泛应用的三种新烟碱类杀虫剂。从那以后,蚜虫如野火般迅速蔓延,德国、法国和波兰不得不又紧急撤销了这道禁令。讽刺的是,禁止新烟碱类杀虫剂的初衷是为了保护蜜蜂。因此,将 RNA 作为杀虫剂来推广,可说是一箭双雕

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我们应该学会去理解别人的观点,不仅仅是服从和被告知。

我们应该学会去理解别人的观点,不仅仅是服从和被告知。
我们应该学会去理解别人的观点,不仅仅是服从和被告知。
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