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独眼羊的奇特案例 – Tien Nguyen – 译学馆
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独眼羊的奇特案例 - Tien Nguyen

The strange case of the cyclops sheep - Tien Nguyen

在1950年 一群爱达荷的农场工人
In the 1950s, a group of ranchers in Idaho
困惑地发现他们的绵羊产下一种畸形羊羔
were baffled when their sheep gave birth to lambs with a singular deformity.
一种神秘的独眼羊
Mystified by these cyclops sheep,
他们叫来了美国农业部的科学家
they called in scientists from the U.S. Department of Agriculture to investigate.
这些科学家先设想了这些母羊在怀孕期间
The researchers hypothesized that the pregnant ewes
吃了会造成先天缺陷的毒植物
had snacked on poisonous birth defect-causing plants.
他们收集当地的植物并将样本喂给小白鼠
They collected the local flora and fed samples to lab rats,
但没有什么效果
but struggled to replicate the effect.
于是他们决定近距离观察这些绵羊
So they decided to directly observe the sheep
其中一位科学家甚至和它们一起住了三年
with one scientist even living with the herd for three summers.
经过了十年的不懈努力 科学家们终于发现了罪魁祸首
After a decade of trial and error, the scientists finally found the culprit,
野生的玉米百合花
wild corn lilies.
该百合含有一种有六个连接环的活跃分子
The lilies contained an active molecule with six connected rings
这种分子被命名为环巴胺 取自独眼羊的名字
that they named cyclopamine in reference to the cyclops sheep.
虽然他们并不知道环巴胺造成畸变的细节
They didn’t know exactly how cyclopamine caused the defect
但是告诉农场工人们清理掉这些花
but told ranchers to steer clear.
一个由菲利普 比奇教授带领的生物小队
It took about four decades before a team of biologists,
花费了40年的时间
led by Professor Philip Beachy,
偶然发现了答案
stumbled upon the answer.
他的实验室当时在研究一种下至老鼠上至人类
His lab was studying a specific gene found in many species,
都存在的特殊基因
from mice to humans,
——Hh基因
called the hedgehog gene.
该名字是两位因此获得诺贝尔的科学家取的
It was named by two scientists, who later shared the Noble Prize for their work,
因为他们在果蝇身上发现了这个在突变的基因
who found that mutating this gene in fruit flies
使得果蝇长满了酷似刺猬的毛刺
produced pointy spikes like a hedgehog.
比奇和他的同事尝试通过转基因
Beachy and his colleagues performed genetic modifications
来消去老鼠身上的Hh基因
to turn off the hedgehog genes in mice.
却导致了老鼠在成长中
This resulted in severe defects in the development
它们的大脑 组织和眼睛产生了严重畸变
of their brains, organs, and eyes
正如你所见 独眼老鼠
or, rather, eye.
在查阅书籍后 比奇无意间发现了独眼羊的照片
Then while perusing a textbook, Beachy came across photos of the cyclops sheep
并且意识到困扰了科学家近40年的东西
and realized what had eluded scientists for four decades.
肯定是这东西恶性入侵了Hh基因
Something must have gone awry involving the hedgehog gene.
让我们回头看看
Let’s take a step back.
基因拥有告诉细胞在何时该做什么的指令
Genes contain instructions that tell cells what to do and when to do it,
并且通过蛋白质来传达指令
and they communicate their directives using proteins.
而Hh基因则告诉细胞释放一种所谓的Hh蛋白
The hedgehog gene itself tells cells to release a so-called hedgehog protein,
——一种有着一系列复杂细胞信号的蛋白
which kicks off a complex series of cellular signals.
来看看它是如何在正常健康的发育中工作的
Here’s how it works in normal healthy development.
Hh蛋白会进入一种叫做Ptc的蛋白
Hedgehog protein latches on to a protein called patched.
来抑制 或者阻碍Ptc蛋白的工作
That inhibits, or holds, patched back,
而允许一种名为Smo的蛋白质来自由发信号给细胞
allowing another protein called smoothened to freely signal the cells,
告诉它们该去哪和该变成何种组织
telling them where to go and what kind of tissues to become.
环巴胺 通过可口的玉米百合花的形式进入
Cyclopamine, say in the form of a delicious corn lily,
并堵塞Smo来中断通道传输
interrupts this pathway by binding onto smoothened.
这使得Smo无法发送信号
That locks smoothened up so that it’s unable to send the signals
来使大脑分成两部分
needed to mold the brain into two hemispheres,
亦或是分成5个指头和两只眼睛
and form fingers or separate eyes.
所以即使Hh蛋白仍然在做
So even though the hedgehog protein is still doing its job
激活Smo蛋白的工作
of keeping the way clear for smoothened,
但环巴胺通过其化学信息破坏了Smo
cyclopamine blocks smoothened from passing along its chemical message.
这样就解决了困扰科学家的独眼羊问题
That settled the science behind the one-eyed sheep,
而比奇团队却抓住了其他
but Beachy and his team caught the glimmer
更有用的联系的灵感
of another more beneficial connection.
他们记录了Smo蛋白不受控制的行为
They noted that uncontrolled activation of the smoothened protein
并且和人类的临床医学联系起来
was associated with a human syndrome.
比如基底细胞痣综合征 并且可以使人们有把握预测癌症
It’s known as Basal Cell Nevus Syndrome, and it predisposes people to certain cancers.
这些科学家们提出
The scientists proposed
可以把被环巴胺附着的Smo蛋白的能力用于
putting cyclopamine’s smoothened binding powers to good use
治疗这些癌症中去
as a treatment for these cancers,
只要患者没有怀孕就行
as long as the patient wasn’t pregnant.
不幸的是 研究者们最后发现环巴胺
Unfortunately, researchers eventually found that cyclopamine
只能造成坏的影响
causes negative side effects,
它的化学性质使它很难被使用
and its chemical properties make it difficult to work with.
不过他们也的确发现了一个功能近似但无害的相关分子
But they did discover that closely related molecules are safe and effective,
并在2012年和2015年分别投入使用制作抗皮肤癌的药
and two of these drugs were approved in 2012 and 2015 as skin cancer medicines.
农夫们第一次看到这些独眼羊时
When those farmers first saw the cyclops sheep,
他们本可以将其归于基因突变即可
they could have chalked it up to a freak genetic mutation and walked away.
然而 他们却决定通过医学来调查这个神奇的事
Instead, their decision to investigate turned a mystery into medicine
展现了事情有时并非像其表面上那么简单
showing that sometimes there’s more than meets the eye.

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视频概述

讲诉了美国的一个农场发现了独眼羊,之后因此发现抗癌药物的故事。

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视频来源

https://www.youtube.com/watch?v=Fzz-Pblbvqw

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