美国国家公共电台 NPR The 30-Year Quest To Tame The 'Wily' Cancer Gene

 

RACHEL MARTIN, HOST:

This next story is about a line of cancer research that could potentially help a huge number of people, people like Michael Robertson.

MICHAEL ROBERTSON: I'd been having unidentified symptoms for a few months, but it was during a intense work period. I was drinking too much coffee, not sleeping enough. And so I kind of chalked it up to that.

MARTIN: But when this 41-year-old man finally made it to the doctor, he was diagnosed with stage 4 colorectal cancer. A genetic² mutation³ called RAS was at the core of his disease.

ROBERTSON: It didn't mean anything to me at the time. It was just - you know, another acronym⁴, another medical term.

MARTIN: It turns out RAS is the driving force in about 30 percent of all cancers, a million cancer deaths each year. And no drug can target this mutation - at least not yet. NPR's Richard Harris picks up the story.

RICHARD HARRIS, BYLINE⁵: RAS is the very first human cancer gene¹ ever discovered. It also turns out to be amazingly common.

FRANK MCCORMICK: It's a major player in lung cancer and the major driver of pancreatic cancer and also a major player in colon⁶ cancer and many other cancers as well.

HARRIS: Frank McCormick was working at a small biotech company in the San Francisco Bay Area back in the early 1980s when this cancer gene was identified. And he convinced his company to look for drugs and tests to combat it.

MCCORMICK: We took off from there and sort of got into the game and made a few early discoveries and fell in love with the whole project.

(LAUGHTER)

MCCORMICK: A long time ago.

HARRIS: The healthy RAS gene instructs the cell to make a protein that is basically an on/off switch that tells living cells when to start dividing.

MCCORMICK: But in cancer cells, the switch is basically defective⁷. So it's stuck in the on state most of the time.

HARRIS: So cells just keep on dividing and forming tumors. Given the gene's central role in cancer, many drug companies jumped into the fray⁸ to develop drugs to fix this broken switch, McCormick says.

MCCORMICK: People got into the drug discovery game very early for RAS. They tried and failed very early also. So (laughter) people moved away from RAS as a target.

ADRIENNE COX: It got the moniker on undruggable because we've been working on it for 35 years, and so far, we don't have a drug in the clinic that works.

HARRIS: Adrienne Cox at the University of North Carolina has also spent her entire career working on RAS. She says the failure to come up with a drug is not for lack of trying.

COX: It's because RAS is a wily beast. It's been described variously as a greasy⁹ ball, meaning there's no good pockets to stick a drug into.

HARRIS: That's how other targeted cancer drugs work. They jam up the works and kill the cancer cells. But drug companies couldn't find a drug that would stick to this greasy ball. Then, about four years ago, the then-head of the National Cancer Institute, Harold Varmus, decided¹⁰ to focus on RAS.

COX: So this started when Harold said, guys, this is embarrassing. You know, we don't have a drug. What's the problem here?

HARRIS: Varmus dedicated¹¹ about $10 million a year for a coordinated¹² effort to find drugs that will work against RAS. Cox is part of that effort, and so is Frank McCormick. In fact, McCormick leads the effort, which is run out of Cancer Institute labs in Frederick, Md.

Here, about 60 people are working together to home in on RAS.

Dwight Nissley leads me into a room where a robot is busy picking up plastic lab dishes and moving them from one instrument to the next.

DWIGHT NISSLEY: So this laboratory right here is a lab where we do a lot of the screening.

HARRIS: The scientists can screen as many as 100,000 compounds a week looking for potential drugs. One strategy is to find compounds that can stick to this greasy ball. Another idea is to prevent the on/off switch from latching¹⁴ onto the membrane¹⁵ where it needs to be in order to work. McCormick says that's a promising¹⁶ strategy.

MCCORMICK: Well, right now I'd say that's top of the list because we're actually making progress in that area and have some compounds which seem to be at least first step in a process towards doing that.

HARRIS: Some of the most promising ideas are coming from colleagues who are not part of the NCI initiative that McCormick is coordinating¹⁷.

MCCORMICK: So we are, in the big picture, a small piece of a big effort.

HARRIS: Scientists have found a particular mutant of RAS that drugs can latch¹³ onto, a mutant found commonly in lung cancer. Pharmaceutical¹⁸ companies are rushing to develop drugs based on that discovery. For the man with colorectal cancer, Michael Robertson, that day can't come soon enough. But Adrienne Cox says this will take time.

COX: The general public shouldn't go out and call their stockbrokers¹⁹ and think it's all over. But, you know, for those of us in the field for a long time, these are real advances.

HARRIS: And for Cox, it comes after 30 years of painfully slow progress.

COX: And so to see a real glimmer²⁰ of light at the end of the tunnel is pretty rewarding.

HARRIS: McCormick agrees with her.

MCCORMICK: I don't see any reason whatever to say this is not going to be cracked in the next few years. I'm sure it will be.

HARRIS: Now, these scientists are, by nature, optimists²¹. Otherwise, they wouldn't have kept at this very hard problem for decade upon decade. I asked McCormick if he felt like Captain Ahab obsessively²² pursuing Moby Dick.

Is this your white whale?

MCCORMICK: (Laughter) Not yet.

(LAUGHTER)

HARRIS: So I guess it is important to remember how that story ends.

MCCORMICK: Exactly.

(LAUGHTER)

HARRIS: Spoiler alert - Captain Ahab tracked down the white whale, but Moby Dick prevailed in the end.

Richard Harris, NPR News.

(SOUNDBITE OF REAL ESTATE'S "SATURDAY")

1 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。

2 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。

3 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。

4 acronym   

n.首字母简略词，简称

参考例句：

• That's a mouthful of an acronym for a very simple technology.对于一项非常简单的技术来说，这是一个很绕口的缩写词。
• TSDF is an acronym for Treatment, Storage and Disposal Facilities.TSDF是处理，储存和处置设施的一个缩写。

5 byline   

n.署名；v.署名

参考例句：

• His byline was absent as well.他的署名也不见了。
• We wish to thank the author of this article which carries no byline.我们要感谢这篇文章的那位没有署名的作者。

6 colon   

n.冒号，结肠，直肠

参考例句：

• Here,too,the colon must be followed by a dash.这里也是一样，应当在冒号后加破折号。
• The colon is the locus of a large concentration of bacteria.结肠是大浓度的细菌所在地。

7 defective   

adj.有毛病的，有问题的，有瑕疵的

参考例句：

• The firm had received bad publicity over a defective product. 该公司因为一件次品而受到媒体攻击。
• If the goods prove defective, the customer has the right to compensation. 如果货品证明有缺陷， 顾客有权索赔。

8 fray   

v.争吵；打斗；磨损，磨破；n.吵架；打斗

参考例句：

• Why should you get involved in their fray?你为什么要介入他们的争吵呢？
• Tempers began to fray in the hot weather.大热天脾气烦燥。

9 greasy   

adj. 多脂的，油脂的

参考例句：

• He bought a heavy-duty cleanser to clean his greasy oven.昨天他买了强力清洁剂来清洗油污的炉子。
• You loathe the smell of greasy food when you are seasick.当你晕船时，你会厌恶油腻的气味。

10 decided   

adj.决定了的，坚决的；明显的，明确的

参考例句：

• This gave them a decided advantage over their opponents.这使他们比对手具有明显的优势。
• There is a decided difference between British and Chinese way of greeting.英国人和中国人打招呼的方式有很明显的区别。

11 dedicated   

adj.一心一意的；献身的；热诚的

参考例句：

• He dedicated his life to the cause of education.他献身于教育事业。
• His whole energies are dedicated to improve the design.他的全部精力都放在改进这项设计上了。

12 coordinated   

adj.协调的

参考例句：

• The sound has to be coordinated with the picture. 声音必须和画面协调一致。
• The numerous existing statutes are complicated and poorly coordinated. 目前繁多的法令既十分复杂又缺乏快调。 来自英汉非文学 - 环境法 - 环境法

13 latch   

n.门闩，窗闩；弹簧锁

参考例句：

• She laid her hand on the latch of the door.她把手放在门闩上。
• The repairman installed an iron latch on the door.修理工在门上安了铁门闩。

14 latching   

n.闭塞；闭锁；关闭；闭塞装置v.理解( latch的现在分词 )；纠缠；用碰锁锁上（门等）；附着（在某物上）

参考例句：

• They have a reputation for latching onto all the latest crazes. 大家都知道他们对所有的最新时尚都有兴趣。 来自《简明英汉词典》
• Sometimes we should tolerate people's mistakes instead of latching on to them. 有的时候我们要能够容错，不要揪着对方的失误不放。 来自互联网

15 membrane   

n.薄膜，膜皮，羊皮纸

参考例句：

• A vibrating membrane in the ear helps to convey sounds to the brain.耳膜的振动帮助声音传送到大脑。
• A plastic membrane serves as selective diffusion barrier.一层塑料薄膜起着选择性渗透屏障的作用。

16 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。

17 coordinating   

v.使协调，使调和( coordinate的现在分词 )；协调；协同；成为同等

参考例句：

• He abolished the Operations Coordinating Board and the Planning Board. 他废除了行动协调委员会和计划委员会。 来自辞典例句
• He's coordinating the wedding, and then we're not going to invite him? 他是来协调婚礼的，难道我们不去请他？ 来自电影对白

18 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。

19 stockbrokers   

n.股票经纪人( stockbroker的名词复数 )

参考例句：

• Stockbrokers never more than now lack enthusiasm for the small client. 证券经济人在面对那些小客户时从未像现在这样缺乏激情。 来自互联网
• Today, I have expensive attorneys, accountants, real estate brokers and stockbrokers. 今天，我雇有身价昂贵的律师、会计师、房地产经纪人以及股票经纪人。 来自互联网

20 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。

21 optimists   

n.乐观主义者( optimist的名词复数 )

参考例句：

• Even optimists admit the outlook to be poor. 甚至乐观的人都认为前景不好。 来自《简明英汉词典》
• Optimists reckon house prices will move up with inflation this year. 乐观人士认为今年的房价将会随通货膨胀而上涨。 来自辞典例句

22 obsessively   

ad.着迷般地，过分地

参考例句：

• Peter was obsessively jealous and his behaviour was driving his wife away. 彼得过分嫉妒的举止令他的妻子想离他而去。
• He's rude to his friends and obsessively jealous. 他对他的朋友很无礼而且嫉妒心重。