美国国家公共电台 NPR Drugs That Work In Mice Often Fail When Tried In People

 

RACHEL MARTIN, HOST:

We're going to talk now about how scientists test new drugs. A lot of the drugs made for humans are tested first on mice or other lab animals, although one of the big problems is that most drugs that work in mice don't work in people, leading to major disappointments and increasing the cost of developing new drugs. Scientists know that animals are unreliable stand-ins for humans, but they use them anyway. Today in Your Health, NPR's Richard Harris looks at efforts to avoid this particular pitfall¹.

RICHARD HARRIS, BYLINE²: When scientists first started using animals in research over a century ago, the animals were not seen simply as little, furry³ people. Todd Preuss at Emory University says people studying rats were trying to learn about rats, at least at the start.

TODD PREUSS: As this process went on, people stopped seeing them as specialized⁴ animals and started seeing them more and more as prototypical mammals.

HARRIS: The generic⁵ mammal - scientist started inferring things more broadly about mammals just from studying rats.

PREUSS: The people who were selling these things - it wasn't strictly⁶ a financial interest. They really believed that you could do almost anything that you could learn about almost any feature of human organization - that you could cure almost any human disease by studying these animals.

HARRIS: That was a dangerous assumption. Rodents⁷ have been on their own evolutionary⁸ trajectory⁹ distinct from ours for perhaps a hundred million years, so it should come as no surprise that a drug that works in a mouse won't necessarily work in a person. Even so, Preuss says, there's tremendous momentum¹⁰ to keep using animals as human substitutes. Entire scientific communities are built up around rats, mice and other animals.

PREUSS: Once these communities exist, then you have an infrastructure¹¹ of knowledge - how to raise the animals, how to keep them healthy. You have companies that spring up to provide you with specialized equipment to study these animals.

HARRIS: Chances are, people studying the same disease you are used the same animal models. Journals and funding agencies actually expect it.

PREUSS: So there's a whole institution that develops.

HARRIS: And it's hard to break that culture.

You can get a glimpse of this by passing through a facility that's devoted¹² to the care and feeding of mice. Attendants roll supply carts through fluorescent-lit hallways past row after row of doors at an expansive mouse facility on the Stanford University campus.

(SOUNDBITE OF DOOR CLOSING)

JOE GARNER¹³: I just got lost. Perhaps this way.

HARRIS: Joe Garner, a behavioral scientist at Stanford, guides me through the labyrinth¹⁴. We go into a windowless room stacked floor to ceiling with seemingly identical plastic cages full of mice. He says mouse researchers in one facility often have trouble repeating the exact same experiment done somewhere else. And that's because, despite outward appearances, there is a huge amount of variation.

GARNER: When people talk about this being a standardized¹⁵ environment, it just isn't. Right? There's the effect of the bedding. There's the effect of the diet, which may well be changing.

HARRIS: Mice on the top shelf have a different experience from those tucked away in the shadows at the bottom. And that difference can skew an experiment.

GARNER: This rack and that rack are different.

HARRIS: For decades, scientists have been operating under the assumption that they can control all these variables in order to get consistent results. Garner says it hasn't worked, and he argues it doesn't even make sense.

GARNER: So imagine that you were doing a human drug trial. And you said to the FDA - OK, I'm going to do this trial in 43-year-old white males in one small town in California, where everybody lives in identical ranch¹⁶ homes. They all have identical, monotonous¹⁷ diets that never change. Their thermostats¹⁸ are all set to the same temperature, which is too cold and they can't change it. Oh - and you all have the same grandfather.

HARRIS: The FDA would laugh that off as an insane setup.

GARNER: But that's exactly what we do in animals, right. We try and control everything we can possibly think of, and as a result, we learn absolutely nothing.

HARRIS: Garner and some like-minded colleagues argue that research based on mice would be more reliable if it was set up more like experiments in humans, recognizing that variation is inevitable¹⁹ and designing to embrace it rather than ignore it.

GARNER: Maybe we need to stop thinking of animals as these little, fairy test tubes that can be controlled or even should be controlled. And that instead, maybe we should think about them as patients.

HARRIS: That could solve some of the problems with animals but by no means all. Dr. Gregory Petsko at the Weill Cornell medical school studies Alzheimer's and other neurological disorders²⁰. And he says scientists make far too many assumptions about the underlying²¹ biology of disease when creating animal models of those illnesses.

GREGORY PETSKO: And it's probably only when you get to try your treatments in people that you're really going to have any idea how right those assumptions were.

HARRIS: So do you think the field is being led astray by relying so heavily on animal models?

PETSKO: Yes, I do. I believe it's been led astray for many years by relying so heavily on animal models. Now, that's not as much of a criticism of the people who develop those models and use them as it sounds.

HARRIS: It was the best they could do at the time, he says.

PETSKO: What I am saying is, at some point, you have to know when to cut your losses. You have to say, OK, this took us as far as it could take us quite some time ago.

HARRIS: For neurological diseases, Petsko says, scientists might learn more from studying human cells than whole animals. Animals are still useful for studying the safety of potential new treatments. But beyond that, he says, don't count on them.

I asked Todd Preuss from Emory if he also thought that the problems of drug development and understanding disease are due to overreliance on animals.

PREUSS: I think it's a big problem. I think that we have means to resolve that, though.

HARRIS: That requires breaking from the scientific mindset that has built up over the decades.

PREUSS: You have to think outside of the model box.

HARRIS: Mice and rats aren't simplified humans. Scientists should stop thinking that they are.

PREUSS: There's just a lot more that we can learn about humans from studying animals, by the way they're different from us as well as the ways in which they're similar.

HARRIS: And that gets back to his earlier observation. Scientists need to break out of a culture that is hampering²² progress. That's tough to do right now in a world where science funding is on the chopping block. Many scientists are reluctant to take a risk that could jeopardize²³ their careers. Richard Harris, NPR News.

(SOUNDBITE OF KOLOTO'S "PRIMER")

MARTIN: Richard did some of the reporting for this story while researching his book, titled "Rigor²⁴ Mortis."

1 pitfall   

n.隐患，易犯的错误；陷阱，圈套

参考例句：

• The wolf was caught in a pitfall.那只狼是利用陷阱捉到的。
• The biggest potential pitfall may not be technical but budgetary.最大的潜在陷阱可能不是技术问题，而是预算。

2 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。

3 furry   

adj.毛皮的；似毛皮的；毛皮制的

参考例句：

• This furry material will make a warm coat for the winter.这件毛皮料在冬天会是一件保暖的大衣。
• Mugsy is a big furry brown dog,who wiggles when she is happy.马格斯是一只棕色大长毛狗，当她高兴得时候她会摇尾巴。

4 specialized   

adj.专门的，专业化的

参考例句：

• There are many specialized agencies in the United Nations.联合国有许多专门机构。
• These tools are very specialized.这些是专用工具。

5 generic   

adj.一般的，普通的，共有的

参考例句：

• I usually buy generic clothes instead of name brands.我通常买普通的衣服，不买名牌。
• The generic woman appears to have an extraordinary faculty for swallowing the individual.一般妇女在婚后似乎有特别突出的抑制个性的能力。

6 strictly   

adv.严厉地，严格地；严密地

参考例句：

• His doctor is dieting him strictly.他的医生严格规定他的饮食。
• The guests were seated strictly in order of precedence.客人严格按照地位高低就座。

7 rodents   

n.啮齿目动物( rodent的名词复数 )

参考例句：

• Rodents carry diseases and are generally regarded as pests. 啮齿目动物传播疾病，常被当作害虫对待。 来自《简明英汉词典》
• Some wild rodents in Africa also harbor the virus. 在非洲，有些野生啮齿动物也是储毒者。 来自辞典例句

8 evolutionary   

adj.进化的；演化的，演变的；[生]进化论的

参考例句：

• Life has its own evolutionary process.生命有其自身的进化过程。
• These are fascinating questions to be resolved by the evolutionary studies of plants.这些十分吸引人的问题将在研究植物进化过程中得以解决。

9 trajectory   

n.弹道，轨道

参考例句：

• It is not difficult to sketch the subsequent trajectory.很容易描绘出它们最终的轨迹。
• The path followed by a projectile is called its trajectory.抛物体所循的路径称为它的轨道。

10 momentum   

n.动力，冲力，势头；动量

参考例句：

• We exploit the energy and momentum conservation laws in this way.我们就是这样利用能量和动量守恒定律的。
• The law of momentum conservation could supplant Newton's third law.动量守恒定律可以取代牛顿第三定律。

11 infrastructure   

n.下部构造，下部组织，基础结构，基础设施

参考例句：

• We should step up the development of infrastructure for research.加强科学基础设施建设。
• We should strengthen cultural infrastructure and boost various types of popular culture.加强文化基础设施建设，发展各类群众文化。

12 devoted   

adj.忠诚的，忠实的，热心的，献身于...的

参考例句：

• He devoted his life to the educational cause of the motherland.他为祖国的教育事业贡献了一生。
• We devoted a lengthy and full discussion to this topic.我们对这个题目进行了长时间的充分讨论。

13 garner   

v.收藏；取得

参考例句：

• He has garnered extensive support for his proposals.他的提议得到了广泛的支持。
• Squirrels garner nuts for the winter.松鼠为过冬储存松果。

14 labyrinth   

n.迷宫；难解的事物；迷路

参考例句：

• He wandered through the labyrinth of the alleyways.他在迷宫似的小巷中闲逛。
• The human mind is a labyrinth.人的心灵是一座迷宫。

15 standardized   

adj.标准化的

参考例句：

• We use standardized tests to measure scholastic achievement. 我们用标准化考试来衡量学生的学业成绩。
• The parts of an automobile are standardized. 汽车零件是标准化了的。

16 ranch   

n.大牧场，大农场

参考例句：

• He went to work on a ranch.他去一个大农场干活。
• The ranch is in the middle of a large plateau.该牧场位于一个辽阔高原的中部。

17 monotonous   

adj.单调的，一成不变的，使人厌倦的

参考例句：

• She thought life in the small town was monotonous.她觉得小镇上的生活单调而乏味。
• His articles are fixed in form and monotonous in content.他的文章千篇一律，一个调调儿。

18 thermostats   

n.恒温（调节）器( thermostat的名词复数 )

参考例句：

• This is the basic operating principle of many thermostats. 这是许多恒温箱的基本工作原理。 来自辞典例句
• Thermostats can be used to regulate the temperature of a room. 恒温器可用来调节室内温度。 来自辞典例句

19 inevitable   

adj.不可避免的，必然发生的

参考例句：

• Mary was wearing her inevitable large hat.玛丽戴着她总是戴的那顶大帽子。
• The defeat had inevitable consequences for British policy.战败对英国政策不可避免地产生了影响。

20 disorders   

n.混乱( disorder的名词复数 )；凌乱；骚乱；（身心、机能）失调

参考例句：

• Reports of anorexia and other eating disorders are on the increase. 据报告，厌食症和其他饮食方面的功能紊乱发生率正在不断增长。 来自《简明英汉词典》
• The announcement led to violent civil disorders. 这项宣布引起剧烈的骚乱。 来自《简明英汉词典》

21 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。

22 hampering   

妨碍，束缚，限制( hamper的现在分词 )

参考例句：

• So fraud on cows and development aid is seriously hampering growth. 因此在牛问题上和发展补助上的诈骗严重阻碍了发展。
• Short-termism, carbon-trading, disputing the science-are hampering the implementation of direct economically-led objectives. 短效主义，出售二氧化碳，进行科学辩论，这些都不利于实现以经济为主导的直接目标。

23 jeopardize   

vt.危及，损害

参考例句：

• Overworking can jeopardize your health.工作过量可能会危及你的健康。
• If you are rude to the boss it may jeopardize your chances of success.如果你对上司无礼，那就可能断送你成功的机会。

24 rigor   

n.严酷，严格，严厉

参考例句：

• Their analysis lacks rigor.他们的分析缺乏严谨性。||The crime will be treated with the full rigor of the law.这一罪行会严格依法审理。