经济学人107:克雅氏病 攻破屏障

 　　Science and Technology Creutzfeldt-Jakob disease Breaking down the barrier

　　科技 克雅氏病 攻破屏障

　　A glimmer¹ of hope for a drug that treats disease caused by prions

　　药物治疗朊病毒感染疾病的一线希望

　　THE epidemic² of mad-cow disease in people that some forecast in the 1990s has not, fortunately, come to pass.

　　时至今日，疯牛病没有像上世纪90年代的某些预言说的那样在人群中流行，真是幸运。

　　But Creutzfeldt-Jakob disease (CJD), to give its proper name, is still a nasty illness that humanity would be better off without.

　　这种严重损害人类性情的疾病的准确名称叫克雅氏病（CJD），治疗起来仍然棘手。

　　It is also a strange illness.

　　克雅氏病是一种奇怪的疾病。

　　CJD and a handful of similar neurological conditions are caused by the misfolding of a particular protein that is found in the membranes³ of certain nerve cells.

　　该病以及类似的一些神经症状是由于某种神经细胞的细胞膜上的一个特殊蛋白发生错误折叠所致。

　　The strangeness is that the misfolded protein, known as a prion, somehow catalyses other molecules⁵ of the protein to misfold in the same way. The result is a chain reaction in which more and more protein ends up as prions.

　　这种错误折叠的蛋白称为朊病毒，令人奇怪的是它可以催化其他蛋白分子发生相同的错误折叠，这个链式反应使越来越多的蛋白质变成朊病毒。

　　Nerve cells containing the prions stop working. The sufferer endures memory loss, personality changes and spontaneous, jerky bodily movements.

　　含有朊病毒的神经细胞失去正常功能，罹患者出现记忆减退、人格改变和自发的躯体急速抽动等症状，最后患者死亡。

　　Eventually, the disease kills him.

　　所以，能够治疗CJD的药物将大受青睐。

　　A drug to treat CJD would therefore be welcome. And chemicals that seem either to prevent the misfolding, or to help the body clear away misfolded molecules, do, indeed, exist. The problem is turning at least one of those chemicals into an effective medicine.

　　能阻止分子错误折叠或帮助机体清除错误折叠分子的化学药品似乎确实存在，困难在于如何用至少一种这样的化学药品进行有效治疗。

　　Adam Renslo of the University of California, San Francisco, and his colleagues (who include Stanley Prusiner, the Nobel laureate who discovered prions) have been trying to do so.

　　旧金山加利福尼亚大学的Adam Renslo与其同事（包括因发现朊病毒获得诺贝尔奖的Stanley Prusiner）一直在进行将化学药品用于治疗CJD的尝试，

　　The chemicals they have lighted on are called aminothiazoles. These are quite effective in reducing the prion levels of cultured nerve cells.

　　他们感兴趣的化学药品叫做氨噻唑，它能有效降低体外培养的神经细胞内的朊病毒水平。

　　Testing aminothiazoles in Petri dishes is, however, rather different from testing them on living animals.

　　但是，检验发现氨噻唑在活动物体内的作用与在体外培养细胞中的作用大不相同。

　　A natural barrier exists between the bloodstream and the brain, to protect it from harmful chemicals. This barrier interprets many putative⁶ drugs, including aminothiazoles, as harmful, and thus keeps them out.

　　生理状态下，血流与脑之间存在着一个屏障，使脑避免接触有害物质，可能有效的许多药物包括氨噻唑也被这个屏障当作有害物质阻挡在脑外。

　　And if a molecule⁴ cannot cross the barrier, it will not make an effective neurological treatment.

　　不能通过屏障进入脑的分子当然就无法完成有效的神经治疗。

　　Dr Renslo and his colleagues have therefore been analysing and modifying the chemical structure of aminothiazoles to see if this can enable them to cross the blood-brain barrier.

　　为此，Renslo博士与其同事已经在分析并尝试修饰氨噻唑的分子结构，以使之能通过血脑屏障。

　　As they report in the Journal of Medicinal Chemistry, they think they have now pulled off the trick.

　　根据他们在药物化学杂志的报道，他们已经找到了突破口。

　　They did it by removing groups of atoms called hydrogen-bond donors⁷ from the original molecules and adding a ring of carbon and hydrogen atoms.

　　他们移除氨噻唑分子上一组提供氢键的原子，并加上一个碳氢环。

　　That made the aminothiazoles look more like cholesterol—which despite its malign⁸ everyday reputation is an important component⁹ of brains and routinely crosses the blood-brain barrier.

　　修饰后的氨噻唑分子看起来更像胆固醇分子。尽管胆固醇整天被认为是个对人体有害的物质，但它却是脑的重要成分，是通过血脑屏障的常客。

　　It worked. When Dr Renslo fed mice a diet containing the improved aminothiazoles, he found that the most promising¹⁰ of them accumulated in the brain in concentrations nearly 25 times higher than those required to clear prions from cultured cells.

　　成功了！Renslo博士给小鼠喂食含有改进后的氨噻唑的饮食后，发现这些最有希望的分子在小鼠的脑内聚集，其浓度达到清除体外培养细胞内朊病毒所需浓度的25倍。

　　The molecular¹¹ changes did not, though, seem to change the aminothiazoles' prion-killing attributes.

　　氨噻唑分子的改变似乎并没有改变其杀灭朊病毒的特性。

　　When tested in Petri dishes, the new molecules were as good as their precursors¹².

　　在培养皿实验中，修饰后的分子与其前体一样有效。

　　More importantly, preliminary results suggest they are effective at extending the lives of prion-infected mice. Such mice lived for 100 days longer when treated with the new molecules than they did when untreated.

　　更重要的是，初步的实验结果提示这些分子能有效延长朊病毒感染小鼠的寿命，用这些新分子治疗的小鼠比不治疗的小鼠多存活100天。

　　That is a significant fraction of the two to three years a healthy laboratory mouse might be expected to survive if it is not experimented on.

　　考虑到实验室中未受试的健康小鼠的预期寿命是2到3年，染毒小鼠获得延长的这部分存活期显得很显著了。

　　Trials in mice are, of course, just the beginning.

　　当然，用小鼠进行的试验只是个开始。

　　But breaching¹³ the blood-brain barrier in this way is a crucial step, and one that might be generalised to potential treatments for other brain diseases—Alzheimer's, for example.

　　但药物以这种方式突破血脑屏障确实是个关键步骤，在此基础上，人们还可能找到治疗阿尔茨海默尔病这样的其他脑部疾病的良方。

　　If that came to pass, this small step on the journey of drug discovery might come to be seen, in retrospect¹⁴, as a giant leap.

　　在达到那些目标之后，回过头来看，实现药物通过屏障的这一小步将被视为一个巨大的跨步

1 glimmer   

v.发出闪烁的微光；n.微光，微弱的闪光

参考例句：

• I looked at her and felt a glimmer of hope.我注视她，感到了一线希望。
• A glimmer of amusement showed in her eyes.她的眼中露出一丝笑意。

2 epidemic   

n.流行病；盛行；adj.流行性的，流传极广的

参考例句：

• That kind of epidemic disease has long been stamped out.那种传染病早已绝迹。
• The authorities tried to localise the epidemic.当局试图把流行病限制在局部范围。

3 membranes   

n.（动物或植物体内的）薄膜( membrane的名词复数 )；隔膜；（可起防水、防风等作用的）膜状物

参考例句：

• The waste material is placed in cells with permeable membranes. 废液置于有渗透膜的槽中。 来自辞典例句
• The sarcoplasmic reticulum is a system of intracellular membranes. 肌浆网属于细胞内膜系统。 来自辞典例句

4 molecule   

n.分子，克分子

参考例句：

• A molecule of water is made up of two atoms of hygrogen and one atom of oxygen.一个水分子是由P妈̬f婘̬ 妈̬成的。
• This gives us the structural formula of the molecule.这种方式给出了分子的结构式。

5 molecules   

分子( molecule的名词复数 )

参考例句：

• The structure of molecules can be seen under an electron microscope. 分子的结构可在电子显微镜下观察到。
• Inside the reactor the large molecules are cracked into smaller molecules. 在反应堆里，大分子裂变为小分子。

6 putative   

adj.假定的

参考例句：

• There have been many attempts to track down the putative Loch Ness monster.人们为追踪假定存在的尼斯湖水怪做了许多努力。
• He is the putative father of this child.他是这孩子的推定的父亲。

7 donors   

n.捐赠者( donor的名词复数 )；献血者；捐血者；器官捐献者

参考例句：

• Please email us to be removed from our active list of blood donors. 假如你想把自己的名字从献血联系人名单中删去，请给我们发电子邮件。
• About half this amount comes from individual donors and bequests. 这笔钱大约有一半来自个人捐赠及遗赠。 来自《简明英汉词典》

8 malign   

adj.有害的；恶性的；恶意的；v.诽谤，诬蔑

参考例句：

• It was easy to see why the cartoonists regularly portrayed him as a malign cherub.难怪漫画家总是把他画成一个邪恶的小天使。
• She likes to malign innocent persons.她爱诋毁那些清白的人。

9 component   

n.组成部分，成分，元件；adj.组成的，合成的

参考例句：

• Each component is carefully checked before assembly.每个零件在装配前都经过仔细检查。
• Blade and handle are the component parts of a knife.刀身和刀柄是一把刀的组成部分。

10 promising   

adj.有希望的，有前途的

参考例句：

• The results of the experiments are very promising.实验的结果充满了希望。
• We're trying to bring along one or two promising young swimmers.我们正设法培养出一两名有前途的年轻游泳选手。

11 molecular   

adj.分子的；克分子的

参考例句：

• The research will provide direct insight into molecular mechanisms.这项研究将使人能够直接地了解分子的机理。
• For the pressure to become zero, molecular bombardment must cease.当压强趋近于零时，分子的碰撞就停止了。

12 precursors   

n.先驱( precursor的名词复数 )；先行者；先兆；初期形式

参考例句：

• Phenyl (or polyphenyl) substituted epoxides serve as excellent precursors to phenyl (or diphenyl) carbenes. 某些苯代（或多苯）环氧乙烷是制取带苯环（或二苯）碳烯的极好原料。 来自辞典例句
• Note the presence of megakaryocytes, erythroid islands, and granulocytic precursors. 可见巨核细胞，红细胞岛和粒细胞前体细胞。 来自互联网

13 breaching   

攻破( breach的过去式 )； 破坏，违反

参考例句：

• The company was prosecuted for breaching the Health and Safety Act. 这家公司被控违反《卫生安全条例》。
• Third, an agency can abuse its discretion by breaching certain principles of judge-made law. 第三，行政机关会因违反某些法官制定的法律原则而构成滥用自由裁量权。

14 retrospect   

n.回顾，追溯；v.回顾，回想，追溯

参考例句：

• One's school life seems happier in retrospect than in reality.学校生活回忆起来显得比实际上要快乐。
• In retrospect,it's easy to see why we were wrong.回顾过去就很容易明白我们的错处了。