每天一篇经济学人 | Personalised medicine 定制化药...

Peter ley, a retired civil servant who lives in London, was diagnosed with colon cancer in 2017. An operation to remove the tumour was successful. But the chemotherapy that followed caused a severe reaction that required a two-week hospital stay and a pause in his cancer treatment.

【1】colon 结肠

【2】chemotherapy 化疗

居住在伦敦的退休公务员PETER LEY在2017年被诊断出患有结肠癌。切除肿瘤的手术很成功。但随后的化疗引起了严重的反应，他需要住院两周，并暂停癌症治疗。

All that could have been avoided had a simple test been done. The test examines a gene that encodes a liver enzyme called dihydropyrimidine dehydrogenase (or DPD for short). The enzyme breaks down several common cancer drugs. Without it, toxic levels of the drugs build up in the body, sometimes with fatal results. A complete inability to make DPD is rare, but there are four mutations in the DPD-regulating gene that are known to reduce its production. As it turned out, Mr Ley had one of them.

只要做个简单的测试，所有这些都可以避免。这项测试检测的是一种编码一种叫做二氢嘧啶脱氢酶(简称DPD)的肝酶的基因。这种酶能分解几种常见的抗癌药物。没有它，药物的毒性水平会在体内累积，有时会导致致命的后果。完全不能产生DPD的情况很少见，但已知的是DPD调控基因中有四种突变减少DPD的产生。事实证明，Ley先生有一个突变。

Screening for such “pharmacogenes” is an idea that is catching on among doctors. Several big hospitals in America are testing their patients for a dozen or more of them. Separate pilot projects are under way in at least seven of the European Union’s member states. Britain’s National Health Service (NHS) is doing screening tests for some patients being prescribed cancer and HIV drugs. A report on March 29th by the British Pharmacological Society (BPS) and the Royal College of Physicians (RCP) proposed widening that testing to cover the 40 drugs among the 100 most-prescribed that are known to be affected by pharmacogenes. The report’s authors reckon testing could feasibly be rolled out across the NHS as soon as 2023.

【1】catch on 流行起来

【2】roll out 推出；开展

筛查这种“药物基因”的想法正在医生中流行起来。美国的几家大医院正在对他们的病人进行十几个或更多的测试。欧盟至少有7个成员国正在开展单独的试点项目。英国国家医疗服务体系(NHS)正在对一些服用癌症和艾滋病药物的病人进行筛查。3月29日，英国药理学会(BPS)和皇家内科医师学会(RCP)在一份报告中建议将测试范围扩大到100种已知受药物基因影响的处方开得最多的药物中的40种药物。该报告的作者认为，这项检测最早可能在2023年在英国国家医疗服务体系中推广。

Genetic screening promises big benefits. Mutations can affect drugs in all sorts of ways, determining a pill’s efficacy, toxicity, how well it is absorbed, and how well it is broken down. Some genetic variants affect several drugs at once, because they alter common enzymes in widely used metabolic pathways. Britain’s 100,000 Genomes project has shown that almost 99% of people carry at least one pharmacogene; 25% have four. About 9% of Caucasian people have, like Mr Ley, DPD deficiency; one in 200 lack the enzyme completely. Roughly 8% of Britain’s population get little pain relief from codeine, because they lack an enzyme responsible for metabolising the drug into morphine (they instead metabolise it into other substances that have little influence on pain).

【1】Caucasian 白种人的

【2】codeine 可待因[鸦片提取物，用于镇痛或催眠]

【3】morphine 吗啡

基因筛查有望带来巨大的好处。突变可以以各种方式影响药物，它决定药片的疗效、毒性、吸收和分解的程度。一些基因变异会同时影响几种药物，因为它们会改变广泛使用的代谢途径中的常见酶。英国的10万基因组计划显示，几乎99%的人携带至少一种药物基因; 25%的人有四种。大约9%的白种人像Ley先生一样患有DPD缺乏症; 每200人中就有一人完全缺乏这种酶。大约8%的英国人无法从可待因中获得止痛效果，因为他们缺乏一种负责将可待因代谢成吗啡的酶(他们将可待因代谢成其他对疼痛几乎没有影响的物质)。

All told, scientists have identified about 120 such drug-gene pairs so far. Roughly half of them are “actionable”, says Henk-Jan Guchelaar, a pharmacologist at the University of Leiden in the Netherlands—meaning that changing the dose or replacing the drug can lead to a better clinical outcome. And most people will be prescribed at least one of those drugs at some point in their lives. In Britain people over the age of 70 have around 70% chance of taking at least one drug whose safety or efficacy is compromised by their genes, says Munir Pirmohamed, a pharmacologist and geneticist at the University of Liverpool.

【1】All told 总的来说

总的来说，科学家们已经确定了大约120对这样的药物-基因对。荷兰莱顿大学的药理学家Henk-Jan Guchelaar说，其中大约一半是“可操作的”，这意味着改变剂量或更换药物可以带来更好的临床结果。大多数人在他们生命的某个阶段都会被开至少一种这些药物。利物浦大学的药理学家兼遗传学家Munir Pirmohamed说，在英国，70岁以上的人至少有70%的几率服用一种安全性或有效性受到基因影响的药物。

Currently, clashes between a patient’s genome and his drug regimen are dealt with by trial-and-error prescribing. But that is time-consuming, and may be harmful. If a drug is being prescribed for high blood pressure or artery-clogging levels of cholesterol, time spent trying different drugs means time in which a stroke, heart attack or organ damage may occur. And cleverer prescribing would have benefits for the health-care system overall, as well as for individual patients. Adverse drug reactions account for 6.5% of hospital admissions in Britain.

【1】regimen （尤指为了增进健康的）生活规则，养生之道，养生法

【2】trial-and-error 反复试验，试错法

目前，病人基因组和药物疗法之间的冲突是通过反复试验处方来解决的。但这是耗时的，而且可能是有害的。如果一种药物是针对高血压或动脉阻塞的胆固醇水平开的，那么尝试不同药物的时间就意味着中风、心脏病发作或器官损伤可能在这段时间发生。更明智的处方对整个医疗保健系统和个别患者都有好处。在英国，药物不良反应占住院病人的6.5%。

The chief issue, as ever, is cost. In the Netherlands a test for 50 pharmacogenes costs about €200 ($217). In Britain a panel test for 40 such genes costs £100-150 ($130-195). Carrying out testing on an entire population would, therefore, be extremely expensive. Some light on whether it is worth the cost will be shone later this year when PREPARE, a study that began in 2017, publishes its results. The project, which is led by Dr Guchelaar, recruited 7,000 people across seven European countries for a study of mutations affecting 42 different drugs. Half the participants were screened, and given cards listing the drugs flagged up. That information, in turn, was made available to doctors, pharmacists and the like. Dr Guchelaar and his colleagues are analysing how much this reduces adverse drug reactions compared with the unscreened participants—and, crucially, the health-care costs averted as a result.

一如既往，主要问题还是成本。在荷兰，检测50种药物基因的费用大约是200欧元(217美元)。在英国，对40个这样的基因进行组合检测需要花费100-150英镑(130-195美元)。因此，在所有人群中进行检测将是极其昂贵的。今年晚些时候，当2017年开始的一项研究PREPARE公布其结果时，人们将会看到一些关于这一成本是否值得的线索。该项目由Guchelaar博士领导，招募了来自7个欧洲国家的7000人来研究影响42种不同药物的突变。一半的参与者接受了筛查，并拿到了列出标记药物的卡片。这些信息反过来又提供给医生、药剂师等人。Guchelaar博士和他的同事们正在分析，与未接受筛查的参与者相比，这种方法能减少多少药物不良反应，最重要的是，由此避免的医疗成本。

Such cost-benefit analyses will be vital in making the argument that governments or insurance firms should pay for widespread genetic testing. In the meantime, though, doctors are already pondering ways to get the most bang for their buck. The BPS and RCP study suggests several ways to expand pharmacogene screening. One is to test for the genes the first time a drug known to be susceptible is prescribed. Another option is to offer that test to everyone over a certain age, perhaps 50—though the NHS is also pondering the idea of comprehensive genetic screening for all newborn babies. That could pay off handsomely later in their lives. 

【1】handsomely 可观地

这样的成本效益分析对于证明政府或保险公司应该为广泛的基因检测买单至关重要。然而，与此同时，医生们已经在考虑如何让他们的钱花得最值。BPS和RCP研究建议了几种扩大药物基因筛选的方法。一种是在第一次开出易感药物的处方时检测这些基因。另一种选择是向超过一定年龄的人(也许是50岁)提供这种检测(不过英国国家医疗服务体系也在考虑对所有新生儿进行全面的基因筛查)。这可能会在他们以后的生活中得到丰厚的回报。