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 結(jié)腸

【2】chemotherapy 化療

居住在倫敦的退休公務(wù)員PETER LEY在2017年被診斷出患有結(jié)腸癌。切除腫瘤的手術(shù)很成功。但隨后的化療引起了嚴(yán)重的反應(yīng)，他需要住院兩周，并暫停癌癥治療。

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.

只要做個簡單的測試，所有這些都可以避免。這項測試檢測的是一種編碼一種叫做二氫嘧啶脫氫酶(簡稱DPD)的肝酶的基因。這種酶能分解幾種常見的抗癌藥物。沒有它，藥物的毒性水平會在體內(nèi)累積，有時會導(dǎo)致致命的后果。完全不能產(chǎn)生DPD的情況很少見，但已知的是DPD調(diào)控基因中有四種突變減少DPD的產(chǎn)生。事實證明，Ley先生有一個突變。

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 流行起來

【2】roll out 推出；開展

篩查這種“藥物基因”的想法正在醫(yī)生中流行起來。美國的幾家大醫(yī)院正在對他們的病人進(jìn)行十幾個或更多的測試。歐盟至少有7個成員國正在開展單獨的試點項目。英國國家醫(yī)療服務(wù)體系(NHS)正在對一些服用癌癥和艾滋病藥物的病人進(jìn)行篩查。3月29日，英國藥理學(xué)會(BPS)和皇家內(nèi)科醫(yī)師學(xué)會(RCP)在一份報告中建議將測試范圍擴(kuò)大到100種已知受藥物基因影響的處方開得最多的藥物中的40種藥物。該報告的作者認(rèn)為，這項檢測最早可能在2023年在英國國家醫(yī)療服務(wù)體系中推廣。

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 白種人的

【2】codeine 可待因[鴉片提取物，用于鎮(zhèn)痛或催眠]

【3】morphine 嗎啡

基因篩查有望帶來巨大的好處。突變可以以各種方式影響藥物，它決定藥片的療效、毒性、吸收和分解的程度。一些基因變異會同時影響幾種藥物，因為它們會改變廣泛使用的代謝途徑中的常見酶。英國的10萬基因組計劃顯示，幾乎99%的人攜帶至少一種藥物基因; 25%的人有四種。大約9%的白種人像Ley先生一樣患有DPD缺乏癥; 每200人中就有一人完全缺乏這種酶。大約8%的英國人無法從可待因中獲得止痛效果，因為他們?nèi)狈σ环N負(fù)責(zé)將可待因代謝成嗎啡的酶(他們將可待因代謝成其他對疼痛幾乎沒有影響的物質(zhì))。

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 總的來說

總的來說，科學(xué)家們已經(jīng)確定了大約120對這樣的藥物-基因?qū)?。荷蘭萊頓大學(xué)的藥理學(xué)家Henk-Jan Guchelaar說，其中大約一半是“可操作的”，這意味著改變劑量或更換藥物可以帶來更好的臨床結(jié)果。大多數(shù)人在他們生命的某個階段都會被開至少一種這些藥物。利物浦大學(xué)的藥理學(xué)家兼遺傳學(xué)家Munir Pirmohamed說，在英國，70歲以上的人至少有70%的幾率服用一種安全性或有效性受到基因影響的藥物。

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 （尤指為了增進(jìn)健康的）生活規(guī)則，養(yǎng)生之道，養(yǎng)生法

【2】trial-and-error 反復(fù)試驗，試錯法

目前，病人基因組和藥物療法之間的沖突是通過反復(fù)試驗處方來解決的。但這是耗時的，而且可能是有害的。如果一種藥物是針對高血壓或動脈阻塞的膽固醇水平開的，那么嘗試不同藥物的時間就意味著中風(fēng)、心臟病發(fā)作或器官損傷可能在這段時間發(fā)生。更明智的處方對整個醫(yī)療保健系統(tǒng)和個別患者都有好處。在英國，藥物不良反應(yīng)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，主要問題還是成本。在荷蘭，檢測50種藥物基因的費用大約是200歐元(217美元)。在英國，對40個這樣的基因進(jìn)行組合檢測需要花費100-150英鎊(130-195美元)。因此，在所有人群中進(jìn)行檢測將是極其昂貴的。今年晚些時候，當(dāng)2017年開始的一項研究PREPARE公布其結(jié)果時，人們將會看到一些關(guān)于這一成本是否值得的線索。該項目由Guchelaar博士領(lǐng)導(dǎo)，招募了來自7個歐洲國家的7000人來研究影響42種不同藥物的突變。一半的參與者接受了篩查，并拿到了列出標(biāo)記藥物的卡片。這些信息反過來又提供給醫(yī)生、藥劑師等人。Guchelaar博士和他的同事們正在分析，與未接受篩查的參與者相比，這種方法能減少多少藥物不良反應(yīng)，最重要的是，由此避免的醫(yī)療成本。

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 可觀地

這樣的成本效益分析對于證明政府或保險公司應(yīng)該為廣泛的基因檢測買單至關(guān)重要。然而，與此同時，醫(yī)生們已經(jīng)在考慮如何讓他們的錢花得最值。BPS和RCP研究建議了幾種擴(kuò)大藥物基因篩選的方法。一種是在第一次開出易感藥物的處方時檢測這些基因。另一種選擇是向超過一定年齡的人(也許是50歲)提供這種檢測(不過英國國家醫(yī)療服務(wù)體系也在考慮對所有新生兒進(jìn)行全面的基因篩查)。這可能會在他們以后的生活中得到豐厚的回報。