【经济学人】实验小鼠是否太过干净？丨2017.3.23丨总第849期

THE hygiene hypothesis posits that certain diseases—notably asthma, eczema and type-1 diabetes—which are becoming more common than they once were, are caused in part by modern environments being too clean. The diseases in question result from misfunctions of the immune system. The hygiene hypothesis suggests such misfunctions are the result of children’s immune systems being unable to learn, by appropriate exposure to viruses, bacteria, fungi and parasitic worms, how to respond properly.

卫生假说认为某些疾病的形成，尤其是越来越常见的哮喘、湿疹、1型糖尿病，部分原因是现在的环境太过干净。所谈论到的疾病的起因是免疫系统的功能障碍。卫生假说认为，因为儿童的免疫系统无法通过接触适量的病毒、细菌、真菌和寄生虫来学习如何恰当地应对各种情况，最终导致免疫系统出现障碍。

• hygiene hypothesis：n.卫生假说

• asthm：n.哮喘

• eczema：n.湿疹

• fungi：n.真菌

• parasitic worms：n.寄生虫

If modern human homes are unnaturally clean, though, they are as nothing compared with the facilities in which experimental mice are housed. Those are practically sterile. That led Lili Tao and Tiffany Reese, two researchers at the University of Texas Southwestern Medical Centre, in Dallas, to wonder if such mice would display extreme versions of the predictions of the hygiene hypothesis.

虽然现代人类的住所及其干净，却也无法与侍养实验小鼠的环境相比，它们居住的环境近乎无菌。这引发了达拉斯德州西南医学中心的两位研究人员Lili Tao和Tiffany Reese去研究这些老鼠在卫生假说预测上是否会表现出极端的状况。

• Dallas：n.达拉斯（地名）

This would matter, because mice are often used in medical experiments on the assumption that their reactions are similar enough to those of human beings for them to act as stand-ins. Conversely, laboratories’ spotlessness might also mean mice are sometimes too healthy to act as useful models for disease. As they explain in Trends in Immunology, Dr Tao and Dr Reese therefore combed the scientific literature to look for both phenomena.

这很重要，因为一般都假设老鼠的对药物的反应与人类的反应基本相同，故经常作为人类的替身，被用于医学实验。但是，干净清洁的实验室意味着小鼠过于健康，因此小鼠有时甚至都不适合作为研究疾病的有效模型。正如他们在《免疫学趋势》杂志中所说的，为了找到这两种现象，Tao博士和Reese博士搜查了所有的科学文献。

• stand-ins：n.替代品

A nice example which the two researchers found of the hygiene hypothesis at work is that stopping laboratory mice being infected with murine cytomegalovirus, which is common in their wild kin, damages their immune response to a host of other pathogens, bacterial as well as viral. Mice so infected will survive subsequent exposure to otherwise-lethal doses of Listeria monocytogenes (a soil- and food-borne bacterium) and Yersinia pestis (the bacterium that causes plague). These mice are also better able than others to handle retrovirus infections. And the effects on them of multiple sclerosis—an illness the underlying cause of which is suspected to be an inappropriate immune response—are reduced.

两位研究人员在研究中发现的一个关于卫生假说的恰当例子就是，避免实验小鼠感染在野生亲缘常见的鼠巨细胞病毒，这种病毒（包括细菌和病毒）会损害它们对许多其他病原体的免疫反应。被感染的小鼠放在致死剂量的单核细胞增多性李斯特氏菌(土壤和食源性细菌)和鼠疫耶尔森菌(引起鼠疫的细菌)中也能存活。这些小鼠也比其他小鼠更能够抵抗逆转录病毒感染，而且减小了多发性硬化（该病的根本原因被认为是不恰当免疫反应）对它们的影响。

• murine cytomegalovirus：n.小鼠巨细胞病毒

• Listeria monocytogenes：n.单核细胞增多性李斯特氏菌

• Yersinia pestis：n.鼠疫耶尔森菌

• plague：n.鼠疫

• multiple sclerosis：n.多发性硬化

鼠疫耶尔森菌

On the other hand, early infection with a different common pathogen, Yersinia pseudotuberculosis, affects murine immune systems in a way that leaves mice more open to subsequent attack, rather than less so—the reverse of the hygiene hypothesis. By unknown means, such infection permanently diverts immune cells called dendritic cells from their normal homes in lymph nodes and to the wall of the gut, where they cause sustained inflammation. Similarly, early exposure to certain herpes viruses, also common in the wild, can result in latent infections that cause no perceptible symptoms unless a kind of parasitic worm called a helminth also turns up. That reactivates the infection. Anyone attempting to mimic human worm infestations using mice should be aware of this.

另一方面，早期感染另一种常见的致病原假结核耶尔森菌，通过影响感染鼠类免疫系统使它们之后更易被攻击，而不是减少小鼠被攻击的次数，这与卫生假说相悖。这种感染会通过一些我们现在未知的途径，将一种叫树突细胞的免疫细胞从正常的淋巴结永久地转移到肠壁上，造成持续的炎症反应。同样，早期接触了某些在野外很常见的某些疱疹病毒，可导致无症状的潜伏性感染，这种感染病毒在感染了一种叫蠕虫的寄生虫之后，才会被激活，这是任何想要利用小鼠模仿人类寄生虫感染的研究者应该知道的。

• helminth：n.蠕虫（寄生虫的一种）
  

• Yersinia pseudotuberculosis：n.假结核耶尔森菌

• dendritic cells：n.树突细胞

Those studying vaccines, too, need to be aware of the confounding effects of hygiene. Laboratory-bred mice have fewer memory T-cells than those brought up in the outside world. Memory T-cells are the parts of the immune-system that remember prior infections, thus enabling a rapid response if the agent which caused that infection is encountered again. Generating such T-cell memories is a vaccine’s job.

研究疫苗的专家也需要注意卫生的混杂效应。实验室侍养的小鼠的记忆T细胞比在外界生长的小鼠要少。“期待您的翻译，将您的理解留言在文章下方留言处，第二天将会有长难句解析哟~。”疫苗的研究就是为了生产这样的记忆T细胞。

记忆T细胞

Moreover, an experiment done by Dr Reese herself showed that exposing young mice to human pathogens, such as herpes and influenza viruses, altered their subsequent responses to vaccines for other diseases. Animals so exposed produce fewer antibodies against a yellow-fever vaccine than do pathogen-free mice.

另外，Reese博士自己做的一个实验表明，将幼鼠暴露于人类病原如疱疹病毒和流感病毒中后，能改变它们随后对其他疾病疫苗的免疫反应。这些小鼠所产生的能抵抗黄热病疫苗的抗体数量要比无病原体的小鼠少。

• yellow-fever:n.黄热病
  

• Herpes:n.疱疹病毒

As is often the case with these sorts of preliminary literature reviews, the outcome is a grab-bag of intriguing results, rather than a coherent hypothesis or prescription for action. But the evidence Dr Tao and Dr Reese have assembled suggests there is something going on here that needs investigating.It seems to be a classic example of the law of unintended consequences. The point of raising mice hygienically is to eliminate as many uncontrolled factors from an experiment as possible. That hygiene itself might be such a factor has not, until now, crossed people’s minds.

在这些初步的文献综述中，结果通常是混杂而有趣的，而不是一个连贯的假设或行为的指示，这是常有的事。但是Tao博士和Reese博士收集的证据表明，有些东西仍需要继续研究。这似乎是一个经典的例子，有着意想不到的结果。卫生地饲养小鼠的目的是尽可能消除实验中的不可控因素。而卫生本身可能就是一个影响因素，到目前为止还尚未出现在人们的思考范围中。

• grab-bag:n.摸彩袋，碰运气

How to respond is unclear. Running trials twice, with “dirty” and “clean” mice, could be one approach. Another might be to agree on a set of bugs to which early exposure is permitted. What this work does show, though, is that in research, cleanliness is not necessarily next to godliness.

如何解决这个问题目前还太清楚。用“脏”小鼠和“干净”小鼠分别做一次实验也许是个方法。另一种方法可能是允许小鼠早期暴露在正常环境中，尽管这些是表现在研究上，但也体现了清洁并不一定次于圣洁这一事实。

• 注：Cleanliness is next to godliness清洁是仅次于圣洁第二重要的事

翻译 ▍hua外音，冰兰

审核 ▍云图

编辑 ▍hua外音