Amy 阿尔法医学英语 3天前
新生儿的诞生会给一个家庭带来幸福和快乐，但也会让一个原本可以幸福快乐的家变得痛苦不堪。根据医学统计，每年出生的新生儿中，约有2%-3%罹患先天性疾病，这是造成婴幼儿长期卧病、残障，甚至夭折的主要原因之一。在先天性疾病诊疗方面的进步无疑给这些被痛苦缠绕的家庭带来一丝希望的曙光。
这次分享的这篇经济学人文章告诉我们先天性疾病的研究可以怎样帮助患者更好地生活甚至康复，怎样促进生活中的常见病如骨质疏松、心脏病等治疗手段的改进。
https://www.economist.com/technology-quarterly/2020/03/12/congenital-diseases-reveal-a-lot-about-human-biology
文章的开头描述了一个令人心碎的画面：Nizar医生的儿子们患有一种先天性疾病。当医生对他们进行疼痛测量时，这几个小孩子问疼痛量表上的笑脸符号代表什么含义，因为他们不知道没有疼痛的生活是什么样的。
When a clinician（临床医师） showed Dr Nizar’s sons a pain chart, they asked her what the smiley face at one end of the scale meant. The boys do not know, Dr Nizar says, what it is like to live without pain.
Pain chart就是衡量患者疼痛强度的疼痛量表：
https://www.prohealth.com/library/what-the-pain-scale-really-means-34982
可以说，这些患有严重先天性疾病的患者面临的是无处可逃的处境：
People with serious congenital diseases have no escape or respite; their symptoms are inescapable.
Congenital意思是“先天的”。它表示两个方面的“先天”，一种是病症方面的先天的，如congenital heart disease 先天性心脏病，congenital abnormalities 先天性畸形；另一种是性格、品性方面先天的，如He's a congenital liar. 相当于He's a liar by nature. 他是一个生*爱性**说谎的人。
Respite指的是从困难或不快的境遇中得到暂时的缓解、休息（a short break or escape from sth. difficult or unpleasant），或是指在完成一项艰巨痛苦的任务前所获得的短暂的喘息（a short delay allowed before sth difficult or unpleasant must be done）。例如：
The drug brought a brief respite from the pain. 药物暂时缓解了疼痛。
She continued to work without respite. 她连续工作,没有休息。
Their teacher was away, so they had a day's respite before their essays were due. 老师不在，所以他们在完成论文前有一天短暂的休息。
基因病，尤其是罕见基因病的诊断是一件既耗时又耗力的事情。有从事相关领域的人员称这个过程就像是诊断中的“奥德赛”，需要对致病的原因进行假设，然后检测，再排除，然后再提出假设，循环往复直到找到真正的病因。
Those who deal with rare genetic diseases talk of the “diagnostic odyssey”. This is the process of repeatedly suggesting a cause for a rare disease, testing, ruling out（排除） and suggesting again.
https://penlighten.com/short-summary-of-odyssey
Odyssey是荷马创作的一篇希腊史诗，讲述的是特洛伊战争后，奥德修斯Odysseus经历了漫长而艰辛的十年辗转回到家园的故事，因此odyssey现在常用来形容“艰苦的跋涉；漫长而充满风险的历程（a long exciting journey on which a lot of things happen）”。这里用来形容罕见遗传病的诊断过程是再形象不过的了。
例如：
The film follows one man's odyssey to find the mother from whom he was separated at birth. 这部影片讲述了一名男子寻找生下自己后就失散的母亲的漫长曲折的历程。
The march to Travnik was the final stretch of a 16-hour odyssey. 去特拉夫尼克的这段路是长达16小时艰险旅行的最后一程。
a spiritual odyssey 精神探索
the emotional odyssey 情感历程
an odyssey of self-discovery 自我探索的历程
https://www.pcgamer.com/assassins-creed-odyssey-celebrates-its-anniversary-with-a-5-week-epic-event/
好在基因组检测（genomic testing）为罕见病的诊断提供了便利。即使有些基因疾病还未找到治愈之法，知道它的原因所在和确切性质也依然非常重要的，而且越早知道越好，这对于后续对该疾病的治疗和护理方法的正确选择有指导性的作用。
In Britain and many other rich countries, genomic testing（基因组检测） has the length of the odyssey down to months or even weeks, says Dr Caulfield. This matters because, even when genetic diseases cannot be cured, knowing the precise nature of the defect often matters—and the earlier it is known, the better. When a Mexican clinic for children with birth defects had 60 of its patients sequenced, subsequent changes in diagnosis led to revisions in the care given to almost half of them.
这里补充一个基因组检测（genomic testing）和基因检测（genetic testing）的不同之处：基因组检测是对一个人的全部基因进行检查，而非只对某个特异基因或特定的基因组进行观察。
这一段中有一个关于“降低/减少至……”的说法，可以代替常用的reduce sth. to…： have sth. down to…
知道详细具体的致病原因对于该疾病的治疗和护理方法的正确选择有指导性的作用。应对方法正确，结果常常会给人带来意想不到的惊喜。这一段列举了两个关于在正确诊断病因的条件下，选择具有针对性的治疗和护理方案从而帮助患者正常生活的例子：
Sometimes the correct care has dramatic results. Jessica was four years old when sequencing showed that the disease affecting her movement and development stemmed from a misprint in a gene called SLC2A1. This meant her cells did not make enough of a protein that transports sugar into the brain, thus leaving it chronically（长期地） underpowered. Giving Jessica a carefully tailored low-carbohydrate diet（低碳水饮食） activated an alternative way of getting calories to her brain. Another situation in which knowledge gives huge power is Brown-Vialetto-Van Laere disease（BVVL综合征）, a rare form of motor-neurone（运动神经元） disease that strikes in childhood. Faults in the genes SLC52A2 and SLC52A3 reduce the body’s stocks of a protein that transports riboflavin (vitamin B2，核黄素/维生素B2) from the gut into the blood stream. High doses of riboflavin can provide great benefits to many such patients—but they will not get them if they do not know they need them.
Stem from sth. 是一个固定词组，意思是“起源于……；根源是……”，用于引出原因、起因。大家在写作中表示因果关系时可以用动词词组stem from来代替because, for, as等连词，可以使文章的表达更加多样。
Tailor作名词时是裁缝的意思，作动词时是“专门制作、订做”，则tailored意思是就是“量身定制的”，近义词是形容词bespoke，后文会出现。
例如：Special programmes of study are tailored to the needs of specific groups. 制订特殊课程,以满足特定群体的需要。
当灾难或疾病作strike（及物/不及物都可）的主语时，表示某种灾难或疾病突然爆发，产生危害，如：The disease has struck the whole community, sometimes wiping out whole families. 疾病袭击整个社区，有时整个家族都无一生还。
They predict that a large earthquake will strike the east coast before the end of the decade. 他们预测这十年内东海岸就会发生一场大地震。
Gut这个词有很多意思，在文中指“消化道；内脏”。当gut做肠道或内脏讲时，有三个俗语非常的形象：①spill one’s guts，把肠子都掏出来，也就是“告密；把所知和盘托出；倾诉心里话”。② work/slog one’s guts out，形容“拼命工作”，颇有呕心沥血、肝脑涂地之感。③hate sb’s guts，恨某人的内脏，顾名思义，就是“恨之入骨”。
Gut还有两个意思值得关注，一个是guts勇气（s不能丢），做某事需要很大的勇气可以说成it takes the guts to do sth. 另一个是gut直觉（单数名词，不能加s）,如gut reaction 本能反应；对于某事有种直觉可以说成I have a gut feeling that…
https://www.bulletproof.com/gut-health/gut-health-microbiome/
基因病诊断方面取得的进步不仅可以造福罕见病的患者，还可以给常见疾病的治疗带来启发：
SOST基因突变影响了硬骨素（一种对骨形成活动起抑制作用的蛋白）的表达，从而导致骨的过度增生，这是硬化性骨化症和van Buchem病的致病原因。这为骨质疏松症的治疗带来了启发，也许通过药物来抑制硬骨素，就可以促进骨骼的生长：
Studies of two rare genetic disorders in which bones grow too eagerly, sclerosteosis（硬化性骨化症） and van Buchem’s disease, revealed that both involved mutations in SOST, a gene that describes a protein now called sclerostin（硬骨素；骨硬化蛋白）. When expressed in bone-building cells, sclerostin turned out to suppress bone growth—hence the bone overgrowth problems when the gene is faulty. This opened up the possibility that patients without enough bone growth might benefit from a drug that inhibited（抑制） sclerostin. That has led to the development of antibodies against sclerostin as a new strategy for treating osteoporosis（骨质疏松症）. Van Buchem’s disease is almost as rare as Jansen’s; but in ageing populations osteoporosis is a public-health scourge（祸害）.
这一段中有几个与骨骼相关的医学词汇：sclerosteosis 硬化性骨化症; osteoporosis 骨质疏松症。这两个词看起来难记，其实只要掌握了当中的词根词缀，你就能轻松辨别并记住这两个单词。
先来看看这两个单词中相同的部分：
Osteo- 即“bone”，表示“骨头”；
-osis 表示“疾病”。
再来看看各自不同的部分：
Sclero- 表示“硬；硬化”；
Por- 即单词“pore”，表示“小孔”。
对红斑性肢痛症的研究促进了新型止痛药的研发，PCSK9基因突变导致的心脏病为一种新型降胆固醇药物的问世带来了启发：
Similarly, studies of a Chinese family with a rare form of erythromelalgia（红斑性肢痛症）, which causes burning pain and redness in the feet, are driving the development of new painkillers（止痛药）. Studies of the faulty PCSK9 gene found in families with a genetic disorder that gives them poor coronary（心脏的；冠状动脉的） health inspired a whole class of new anti-cholesterol drugs（降胆固醇药物） that are more effective than statins（他汀类药物）.
那些存在基因突变但是仍然健康或病程缓慢的病人，他们身上或许有保护他们免遭疾病侵害的基因，这可能有助于为其他患者带来新的治疗方法：
A wrinkle on this approach is to find people with disease-causing mutations who stay healthy, or whose disease progresses slowly. These people contain genes that may protect them from harm, which might be useful in creating new therapies for others. Maze Therapeutics, based in San Francisco, is looking for “genetic modifiers” that alter the course of conditions like ALS (also known as Lou Gehrig’s disease肌萎缩侧索硬化，“渐冻人” ). This disease is normally fatal within a couple of years. But in some sufferers, such as the late（已故的） physicist Stephen Hawking, it develops much more slowly.
https://heho.com.tw/archives/38469
尽管人们对于这些罕见遗传病致病机制的了解相比以前而言已经有了长足的进步，但是相应的治疗手段和药物还是相对落后。一是因为市场小（患病的只有几十或几百人），二是因为需要针对不同的病因定制药物，使其既要作用于目标蛋白质，又不能误伤其它正常工作的蛋白，难度系数很高。
Yet as humanity’s knowledge of disease mechanisms has grown dramatically through the study of rare inherited diseases, the development of treatments for those diseases themselves has failed to keep pace. Conditions that blight lives by the dozen or hundred are not big markets.
Blight在这里作及物动词，相当于damage，意思是“损害；困扰”，例如：
His career has been blighted by injuries.
他的事业不断受到伤病的困扰。
an area blighted by unemployment
饱受失业之苦的地区
Many hope that various new technologies could drastically reduce the costs of bespoke（定制的） treatments for at least some congenital diseases. Most drugs today work by targeting a protein—either one of the body’s proteins that is misbehaving, or a protein in a pathogen that is achieving its goals all too well. The drug has to be tailored to the shape and activity of the protein it targets, while not messing up the workings of other inoffensive proteins that are doing vital work. That isn’t easy.
如今大多数投入使用的治疗基因病的药物是通过靶向一种有缺陷的蛋白质来实现的，但是可不可以研发出一种药物来阻止问题蛋白的生成呢？
What, though, if you could stop a problematic protein from being made in the first place? For a cell to make a protein, it first needs to make a copy of the gene sequence that describes that protein. This copy is called a messenger RNA（信使RNA）, or mRNA. If you know the sequence of the gene, it is easy to work out the sequence of its mRNA, and from that design a short strand of DNA that, by dint of（通过；凭借） its own sequence, will stick to that mRNA, thus rendering it useless (see diagram).
https://www.economist.com/technology-quarterly/2020/03/12/congenital-diseases-reveal-a-lot-about-human-biology
这种通过与信使RNA结合从而阻止靶标基因翻译的“神器”就是反义寡核苷酸（antisense oligonucleotides），一种短的单链DNA分子。它的DNA序列与特定的靶标RNA序列互补，结合后可通过各种不同的机制影响靶标基因的表达，从而导致问题蛋白质生成失败。反义寡核苷酸药物已经用于治疗一些基因病。
Such DNA-based saboteurs are called “antisense oligonucleotides” (ASOs). They are now being used to treat various faulty-gene diseases, including a particular form of spinal muscular atrophy (SMA，脊髓性肌肉萎缩症), some types of Duchenne muscular dystrophy（杜兴氏肌肉营养不良症） and familial hypercholesterolemia（家族性高胆固醇血症）—the disease that led to the design of new anti-cholesterol drugs. There are trials under way to see if an ASO can slow the progression of Huntington’s disease, a lethal（致命的） degenerative（变性的） disease which affects from five to 10 people per 100,000.
Saboteur意思是为防止敌方利用或着为表示抗议而故意破坏设施的人（-eur在法语中表示“人”，和英语中的-er作用类似）。文中用saboteur来比喻破坏问题蛋白质生成的反义寡核苷酸。
拓展一下，sabotage指的是为防止敌人利用或表示抗议而对设备、交通等进行蓄意破坏的行为，既可作名词也可作及物动词，如：an act of economic / military / industrial sabotage 经济/军事/工业破坏活动；Protesters failed to sabotage the peace talks. 抗议者未能破坏和平谈判。
sabotage和saboteur这两个词的由来很有趣。在中世纪，只有贵族才有钱购买皮鞋，普通老百姓买不起皮鞋，因此发明了造价便宜但同样防潮保暖的木鞋。这种木鞋在法语中叫做sabot。现在法国几乎看不到穿这种木鞋的人，但在中世纪时期，法国老百姓几乎人人都穿着sabot。在资本主义发展初期阶段，当工人和工厂管理层发生矛盾时，往往会偷偷把脚上的木鞋sabot脱下来扔进机器里来破坏机器，从而衍生了saboteur和sabotage这两个英文单词。
https://www.collinsdictionary.com/zh/dictionary/english/sabot
反义寡核苷酸药物对于罕见病患者来说是福音，它大大降低了针对特定疾病定制药物的难度。一旦确定了生成蛋白质的基因序列，相应的反义寡核苷酸在一年内就可以合成，而且可以用于治疗某一患者特有的疾病。
Antisense drugs are particularly exciting to patients with rare congenital diseases because they can be easily tailored. Once the sequence of the gene for the protein at fault is established, an ASO can be ready in under a year, says Art Krieg, the boss of Checkmate Pharmaceuticals, a biotech company. The fact that ASOs are based on sequences means that they can be “programmed” to inhibit the synthesis of a wide range of proteins. An ASO can also be designed and used to treat a disease unique to a single patient—what doctors call an n-of-1 trial（单病例随机对照实验）.
后台回复“congenital diseases”可获得原文。
引文节选自：
https://www.economist.com/technology-quarterly/2020/03/12/congenital-diseases-reveal-a-lot-about-human-biology
图片来源：
https://www.economist.com/technology-quarterly/2020/03/12/congenital-diseases-reveal-a-lot-about-human-biology
https://www.prohealth.com/library/what-the-pain-scale-really-means-34982
https://penlighten.com/short-summary-of-odyssey
https://www.pcgamer.com/assassins-creed-odyssey-celebrates-its-anniversary-with-a-5-week-epic-event/
https://www.bulletproof.com/gut-health/gut-health-microbiome/
https://heho.com.tw/archives/38469
https://www.collinsdictionary.com/zh/dictionary/english/sabot
参考资料：
http://www.cbdio.com/BigData/2018-08/07/content_5789920.htm
https://baike.baidu.com/item/%E5%85%88%E5%A4%A9%E6%80%A7%E7%96%BE%E7%97%85
https://www.dana-farber.org/for-patients-and-families/becoming-a-patient/international-patients/chinese/inspiration/%E4%BB%80%E4%B9%88%E6%98%AF%E5%9F%BA%E5%9B%A0%E7%BB%84%E6%A3%80%E6%B5%8B%EF%BC%88genomic-testing%EF%BC%89-/
http://www.xml-data.org/GUSS/html/89d488ca-9096-4c96-8754-8d3b5c0ca70f.htm
https://www.sciencedirect.com/topics/neuroscience/antisense-oligonucleotide
https://zh.wikipedia.org/wiki/%E5%8F%8D%E4%B9%89%E5%AF%A1%E6%A0%B8%E8%8B%B7%E9%85%B8
AlphaMedEnglish
供稿：Amy
编辑：西瓜籽
审核：TS
