财富杂志 AI如何让老药新用?(5)

Parlaying genomics and technology into pharmaceutical¹ success is something Cohen has done before.

利用基因组学和技术取得制药成功是科恩以前做过的事情。

He was a cofounder of Millennium² Pharmaceuticals³, a U.S. oncology-drug maker⁴ that helped develop the multiple-myeloma treatment Velcade.

他曾是美国肿瘤药物制造商千禧制药公司的联合创始人，该公司曾帮助研发了一款治疗多发性骨髓瘤的药物Velcade。

Cohen is bullish that Pharnext can be successful with A.I., but he is also aware of the technology's limitations.

科恩看好Pharnext可以与AI取得成功，但他也意识到了这项技术的局限性。

Google's -AlphaZero, an A.I. program, was able to beat the world's human masters at the Chinese strategy game Go, without using any prior human knowledge.

谷歌的AI程序AlphaZero，能够在不使用任何先验人类知识的情况下，在中国围棋策略游戏中击败世界上的人类大师。

But as Cohen points out, Go has a finite set of rules, which AlphaZero knew completely.

但正如科恩所指出的，围棋有一套有限的规则，AlphaZero完全清楚这些规则。

In biology, thanks in part to pleiotropy, the rules are not fully⁵ known—and may never be.

在生物学中，由于基因多效性的原因，其规则还未被完全了解——并且可能永远都不会被了解。

But thoughtfully designed A.I. has enabled Pharnext to build models around the rules that are known and make choices accordingly.

但经过精心设计的AI让Pharnext能够围绕已知的规则构建模型，并据此做出选择。

Out of the universe of 10,000 known drugs, the company's discovery model takes in an assortment⁶ of 2,000 that are both out of patent and "marketed"—

在一万种已知药物中，该公司的发现模型包含了2000种既已过了专利期又已“上市”的药物——

that is, already judged both therapeutically⁷ effective and safe enough to be sold to the public.

即被判定有疗效且足够安全，可以对公众进行销售。

To develop its CMT drug, Pharnext first spent about a year assembling its network model for the disease—

为了研发其CMT药物，Pharnext首先花了大约一年的时间来组装这种疾病的网络模型——

a framework comparable to GNS's Parkinson's map, showing how nervous and muscular problems "cascade⁸" from the relevant gene⁹ mutation¹⁰.

一种能够与GNS的帕金森地图相媲美的框架，呈现的是神经和肌肉问题是如何“级联”相关基因突变的。

Based on this mechanism¹¹, the computer model arrived at a short list of 57 candidate drugs that addressed various points in the cascade.

基于这种机制，计算机模型得到了57种候选药物的简短列表，这些候选药物针对着级联中的各个点。

Pharnext tested those drugs one by one in vitro, generating a shorter list of 22 to be tested in mice,

Pharnext对这些药物逐一进行了体外测试，生成了一份更短的清单，其中22种将在老鼠身上进行测试，

which finally yielded the three-drug combination that went to human clinical trials.

最终产生了三种药物的组合，并进行了人体临床试验。

The recent positive Phase III results confirmed that the PXT3003 cocktail¹² is acting¹³ at various points in the cascade.

近期第三期阳性结果证实了，PXT3003药物组合正在作用于级联中的各个点上。

Without the A.I. model, many more years of preclinical testing would have been required beyond the three years it took Pharnext, says Cohen.

科恩表示，没有了AI模型，除了Pharnext所花费的三年时间，可能还需要更多时间来进行临床前测试。

"With 2,000 drugs to start with, I could produce all possible combinations, a billion possibilities" to test in vitro.

“根据一开始的两千种药物，我可以制造出所有可能的组合，一百万种可能”来进行体外测试。

That's a recipe for countless¹⁴ false positives and dead ends—years of frustration¹⁵, for now forestalled¹⁶.

这就是无数假阳性和死胡同的秘诀——多年的失望，现在该先发制人了。

Pharnext's shares, which trade on the Paris stock exchange, have more than doubled since October's Phase III results announcement.

自10月第三阶段结果宣布以来，在巴黎股票交易所交易的Pharnext股票已上涨逾一倍。

The company has spent about 120 million euros ($135 million) over the past decade on research and development—a very modest figure by pharma standards.

在过去的十年里，该公司在研发上花费了大约1.2亿欧元（即1.35亿美元）——以制药行业的标准来衡量，这是一个非常合理的数字。

It has never made a profit, but analysts¹⁷ estimate that if PXT3003 reaches the market, revenue—9 million euros in 2018—could soar starting in 2020.

该公司从未实现过盈利，但分析师估计，如果PXT3003上市，该公司的收入——2018年为900万欧元——将从2020年开始猛增。

(GNS Healthcare is privately¹⁸ held and does not disclose spending or revenue.)

（GNS Healthcare是一家私营企业，并且没有披露支出或收入。）

Beyond possible victories for investors¹⁹, the advances at Pharnext and GNS point the way to A.I.'s growing up—and pharmacology along with it.

除了可能为投资者带来收益，Pharnext和GNS的进步也为AI的发展指明了道路——药理学也随之而生。

The ability to reason about causality, and to explore counterfactual questions, is a threshold that users of artificial intelligence have long sought to cross.

推理因果关系，以及探究反设事实问题的能力，是AI用户长期以来一直寻求跨越的一道门槛。

The computer models at these startups are making a foray in that direction as they manage and tame a bewildering number of variables.

随着它们管理并驯服了大量令人眼花缭乱的变量，这些初创公司的计算机模型正朝着这个方向进军。

Even the underlying²⁰ definition of disease may evolve. As scientists are learning, these definitions have been overly simplistic.

疾病的基本定义也可能进化。随着科学家的不断了解，这些定义被过度简化了。

A study in the journal Bioinformatics last year noted²¹ that attempts to treat tumors

去年《Bioinformatics》期刊上的一项研究指出，

are hampered²² by the fact that genetic²³ mutations in cancer are "fundamentally heterogeneous":

治疗肿瘤的尝试受到了这样一个事实的阻碍，即癌症的基因突变“从根本上是异质性的”：

What appears as one disease, or class of disease, in fact contains few commonalities and many differences from patient to patient.

表现为一种疾病或一类疾病的物质，实际上几乎没有共性，并且病人之间也有许多不同之处。

As it becomes clear that what's happening in any body differs sharply from the "on/off" model of one gene turning on a set of symptoms,

我们越来越清楚，在任何身体中发生的情况都与一个基因启动一系列症状的“开启/关闭”模式截然不同，

technology can help drug developers wrestle²⁴ with the complexity²⁵.

技术能够帮助药物研发者全力解决这种复杂性。

Last, but hardly least, these A.I.-driven efforts offer a glimmer²⁶ of economic hope.

最后但同样重要的是，这些由AI驱动的努力带来了一丝经济希望。

In an era in which the cost of drug development is a daunting²⁷ obstacle,

在当今时代，药物研发成本是一个令人生畏的障碍，

smart algorithms may someday enable medical stakeholders to derive²⁸ more value from the trillions of dollars that have already been spent on drug research.

聪明的算法将来可能会让医疗利益相关者从已经花费在药物研究上的数万亿美元中获得更多的价值。

In theory, with repurposing, "you don't need to design new drugs," Cohen avers²⁹. "My feeling is that with 50 drugs, we can treat everything."

理论上，有了再利用，“你就不需要设计新药物了，”科恩断言。“我觉得有了这50种药物，我们可以治愈一切。”

That would mean changing yet another definition: the meaning of "discovery."

这将意味着改变另一个定义：“发现”的含义。

1 pharmaceutical   

adj.药学的，药物的；药用的，药剂师的

参考例句：

• She has donated money to establish a pharmaceutical laboratory.她捐款成立了一个药剂实验室。
• We are engaged in a legal tussle with a large pharmaceutical company.我们正同一家大制药公司闹法律纠纷。

2 millennium   

n.一千年，千禧年；太平盛世

参考例句：

• The whole world was counting down to the new millennium.全世界都在倒计时迎接新千年的到来。
• We waited as the clock ticked away the last few seconds of the old millennium.我们静候着时钟滴答走过千年的最后几秒钟。

3 pharmaceuticals   

n.医药品；药物( pharmaceutical的名词复数 )

参考例句：

• the development of new pharmaceuticals 新药的开发
• The companies are pouring trillions of yen into biotechnology research,especially for pharmaceuticals and new seeds. 这些公司将大量资金投入生物工艺学研究，尤其是药品和新种子方面。 来自《简明英汉词典》

4 maker   

n.制造者，制造商

参考例句：

• He is a trouble maker，You must be distant with him.他是个捣蛋鬼，你不要跟他在一起。
• A cabinet maker must be a master craftsman.家具木工必须是技艺高超的手艺人。

5 fully   

adv.完全地，全部地，彻底地；充分地

参考例句：

• The doctor asked me to breathe in,then to breathe out fully.医生让我先吸气，然后全部呼出。
• They soon became fully integrated into the local community.他们很快就完全融入了当地人的圈子。

6 assortment   

n.分类，各色俱备之物，聚集

参考例句：

• This shop has a good assortment of goods to choose from.该店各色货物俱全，任君选择。
• She was wearing an odd assortment of clothes.她穿着奇装异服。

7 therapeutically   

[医]adv.在治疗上

参考例句：

• A lead compound will have some property considered therapeutically useful. 一种先导化合物应具有治疗作用的特性。 来自互联网
• Drugs causing fibrinolysis have been utilized therapeutically. 纤维蛋白溶解药物已被用于临床治疗。 来自互联网

8 cascade   

n.小瀑布，喷流；层叠；vi.成瀑布落下

参考例句：

• She watched the magnificent waterfall cascade down the mountainside.她看着壮观的瀑布从山坡上倾泻而下。
• Her hair fell over her shoulders in a cascade of curls.她的卷发像瀑布一样垂在肩上。

9 gene   

n.遗传因子，基因

参考例句：

• A single gene may have many effects.单一基因可能具有很多种效应。
• The targeting of gene therapy has been paid close attention.其中基因治疗的靶向性是值得密切关注的问题之一。

10 mutation   

n.变化，变异，转变

参考例句：

• People who have this mutation need less sleep than others.有这种突变的人需要的睡眠比其他人少。
• So far the discussion has centered entirely around mutation in the strict sense.到目前为止，严格来讲，讨论完全集中于围绕突变问题上。

11 mechanism   

n.机械装置；机构，结构

参考例句：

• The bones and muscles are parts of the mechanism of the body.骨骼和肌肉是人体的组成部件。
• The mechanism of the machine is very complicated.这台机器的结构是非常复杂的。

12 cocktail   

n.鸡尾酒；餐前开胃小吃；混合物

参考例句：

• We invited some foreign friends for a cocktail party.我们邀请了一些外国朋友参加鸡尾酒会。
• At a cocktail party in Hollywood,I was introduced to Charlie Chaplin.在好莱坞的一次鸡尾酒会上，人家把我介绍给查理·卓别林。

13 acting   

n.演戏，行为，假装；adj.代理的，临时的，演出用的

参考例句：

• Ignore her,she's just acting.别理她，她只是假装的。
• During the seventies,her acting career was in eclipse.在七十年代，她的表演生涯黯然失色。

14 countless   

adj.无数的，多得不计其数的

参考例句：

• In the war countless innocent people lost their lives.在这场战争中无数无辜的人丧失了性命。
• I've told you countless times.我已经告诉你无数遍了。

15 frustration   

n.挫折，失败，失效，落空

参考例句：

• He had to fight back tears of frustration.他不得不强忍住失意的泪水。
• He beat his hands on the steering wheel in frustration.他沮丧地用手打了几下方向盘。

16 forestalled   

v.先发制人，预先阻止( forestall的过去式和过去分词 )

参考例句：

• She forestalled their attempt. 她先发制人，阻止了他们的企图。 来自《简明英汉词典》
• I had my objection all prepared, but Stephens forestalled me. 我已做好准备要提出反对意见，不料斯蒂芬斯却抢先了一步。 来自辞典例句

17 analysts   

分析家，化验员( analyst的名词复数 )

参考例句：

• City analysts forecast huge profits this year. 伦敦金融分析家预测今年的利润非常丰厚。
• I was impressed by the high calibre of the researchers and analysts. 研究人员和分析人员的高素质给我留下了深刻印象。

18 privately   

adv.以私人的身份，悄悄地，私下地

参考例句：

• Some ministers admit privately that unemployment could continue to rise.一些部长私下承认失业率可能继续升高。
• The man privately admits that his motive is profits.那人私下承认他的动机是为了牟利。

19 investors   

n.投资者，出资者( investor的名词复数 )

参考例句：

• a con man who bilked investors out of millions of dollars 诈取投资者几百万元的骗子
• a cash bonanza for investors 投资者的赚钱机会

20 underlying   

adj.在下面的，含蓄的，潜在的

参考例句：

• The underlying theme of the novel is very serious.小说隐含的主题是十分严肃的。
• This word has its underlying meaning.这个单词有它潜在的含义。

21 noted   

adj.著名的，知名的

参考例句：

• The local hotel is noted for its good table.当地的那家酒店以餐食精美而著称。
• Jim is noted for arriving late for work.吉姆上班迟到出了名。

22 hampered   

妨碍，束缚，限制( hamper的过去式和过去分词 )

参考例句：

• The search was hampered by appalling weather conditions. 恶劣的天气妨碍了搜寻工作。
• So thought every harassed, hampered, respectable boy in St. Petersburg. 圣彼德堡镇的那些受折磨、受拘束的体面孩子们个个都是这么想的。

23 genetic   

adj.遗传的，遗传学的

参考例句：

• It's very difficult to treat genetic diseases.遗传性疾病治疗起来很困难。
• Each daughter cell can receive a full complement of the genetic information.每个子细胞可以收到遗传信息的一个完全补偿物。

24 wrestle   

vi.摔跤，角力；搏斗；全力对付

参考例句：

• He taught his little brother how to wrestle.他教他小弟弟如何摔跤。
• We have to wrestle with difficulties.我们必须同困难作斗争。

25 complexity   

n.复杂(性)，复杂的事物

参考例句：

• Only now did he understand the full complexity of the problem.直到现在他才明白这一问题的全部复杂性。
• The complexity of the road map puzzled me.错综复杂的公路图把我搞糊涂了。

26 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。

27 daunting   

adj.使人畏缩的

参考例句：

• They were faced with the daunting task of restoring the house.他们面临着修复房子的艰巨任务。
• Starting a new job can be a daunting prospect.开始一项新工作有时会让人望而却步。

28 derive   

v.取得；导出；引申；来自；源自；出自

参考例句：

• We derive our sustenance from the land.我们从土地获取食物。
• We shall derive much benefit from reading good novels.我们将从优秀小说中获得很大好处。

29 avers   

v.断言( aver的第三人称单数 )；证实；证明…属实；作为事实提出

参考例句：

• He avers that chaos will erupt if he loses. 他断言，如果他失败将会爆发动乱。 来自辞典例句
• He avers he will not attend the meeting. 他断言不会参加那个会议。 来自互联网