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基因工程将会永久改变一切——CRISPR技术 – 译学馆
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基因工程将会永久改变一切——CRISPR技术

Genetic Engineering Will Change Everything Forever – CRISPR

试着想象:你穿越回80年代 有人告诉你
Imagine you were alive back in the 1980’s and were told
电子计算机将统治一切
the computers would soon take over everything.
从购物到约会 再到股票市场
>From shopping to dating and the stock market.
数十亿人将被一种“网”连接起来
That billions of people would be connected via a kind of web.
人们将拥有比超级计算机
That you would own a handheld device
更加强大的掌上设备
orders of magnitude more powerful than supercomputers.
听起来很荒谬 但之后统统成为现实
It would seem absurd but then all of it happened.
科学幻想逐渐成真 可人们并不在意
Science fiction became our reality that we don’t even think about it
今天 我们在基因工程领域遇到了相似的情况
We’re at a similar point today with genetic engineering.
且听我细细道来
So let’s talk about it.
基因工程源自何方? 我们现在走到了那一步?
Where it came from? What we’re doing right now?
还有近期研究领域的突破 将永远改变我们的生活方式
And about a recent breakthrough that will change how we live
和对 “正常” 的定义
and what we perceive as “normal” forever.
在过去的几千年里 人类早已通过选择性培育对生命进行改造
Humans have been engineering life for thousands of years, through selective breeding.
我们对动植物有用的特征进行强化
We strengthened useful traits and plants and animals.
我们对此驾轻就熟 却不知其所以然
We became very good at this but never truly understood how it works.
直到我们发现了生命的密码: 脱氧核糖核酸 即DNA
Until we discovered the code of life: deoxyribonucleic acid, DNA,
这是一种复杂的分子 引导所有生命的发育
a complex molecule the guide of the growth, development function
机能运作和繁衍
and reproduction of everything alive.
其分子结构中隐藏着编码信息
Information is encoded in the structure of the molecule.
四种核苷酸配对 形成携带指令的编码
Four nucleotides are paired and make up a code that carries instructions.
更改指令 你就改变了携带此DNA的生命体
Change the instructions and you change the being carrying it.
发现DNA之后 人们一直在尝试对其进行修改
As soon as DNA was discovered people try to tinker with it.
二十世纪60年代 科学家通过辐射轰击植物
In the 1960’s, scientists bombarded plants with radiation
来引发随机的基因变异
to cause random mutations in the genetic code.
目的是凭运气得到有用的植物
The idea was to get a useful plant variation by pure chance.
这法子偶尔真能起作用
Sometimes, it actually worked too.
70年代 科学家向细菌 植物和动物注射DNA片段
In the 70’s, scientists inserted DNA snippets into bacteria, plants and animals
进行改良后以开展研究 或应用在医药和农业领域。 有时也只是好玩而已
to study and modify them for research, medicine, agriculture and for fun.
首例基因改良动物出生于1974年
The earliest genetically modified animal was born in 1974,
使得老鼠成为该领域研究的标准工具 拯救了数以百万的生命
making mice a standard tool for research, saving millions of lives.
80年代 研究进入了商业化阶段
In the 80’s, we got commercial.
首例专利被授予一种 能吸收石油的基因改造微生物
The first patent was given for a microbe engineered to absorb oil.
今天 我们能通过基因工程改造的生命 制造多种化学物质
Today, we produce many chemicals by means of engineered life
比如 挽救生命的凝固因子 生长荷尔蒙以及胰岛素
like life-saving clotting factors, growth hormones and insulin;
在此之前 我们只能从动物器官中提取
all things we had to harvest from the organs of animals before that.
第一种在实验室进行改造的食物于1994年上市:Flavr Savr番茄
The first food modified in the lab went on sale in 1994: the Flavr Savr tomato,
这种番茄保质期更长
a tomato given a much longer shelf-life
系通过加入一种抑制腐化酶生成的基因得以实现
via an extra gene that suppresses the build-up of a rotting enzyme.
但是 基因改良食品和围绕它们的争议需要拍专门的视频来说明
But GM food and the controversy surrounding them deserve a video of their own.
上世纪90年代 我们开始涉足人类基因工程领域
In the 1990’s there was also a brief foray into human engineering.
为治疗不孕不育 科学家培育出携带
To treat maternal infertility, babies were made
来自三个人的基因信息的婴儿
that carry genetic information from three humans
它们因此成为第一批拥有三名基因父母的人类
making them the first humans ever to have three genetic parents.
现在 已经出现了超级肌肉猪 能快速生长的大马哈鱼
Today there are super muscled pigs, fast-growing salmon,
无毛鸡和透明青蛙
featherless chickens and see-through frogs.
有趣的是 我们使生物在黑暗中发光
On the fun side, we made things glow in the dark.
荧光斑马鱼只要区区十美元
Fluorescent zebrafish are available for as little as ten dollars.
这些成就让人振奋 但最近我们又有了新的突破
All of this is already very impressive but until recently,
基因编译十分昂贵 繁杂 且消耗时间
gene editing was extremely expensive, complicated and took a long time to do.
但随着一项革命性新技术的出现 情况得以改变:
This has now changed with a revolutionary new technology now entering the stage:
基因编组技术 CRISPR(Clustered regularly interspaced short palindromic repeats)
CRISPR.
一夜之间 基因工程的成本降低了99%
Overnight, the costs of engineering have shrunk by 99%.
原来需要一年时间完成的实验 如今只需几个星期
Instead of a year, it takes a few weeks to conduct experiments
基本上有实验室的人就能完成
and basically everybody with a lab can do it.
要理解基因编组技术带来的技术革命并不容易
It’s hard to get across how big a technical revolution CRISPR is.
但该技术确有永远改变人类的潜质
It literally has the potential to change humanity forever.
为什么这项革命性技术突然出现?其原理又是什么?
Why did this sudden revolution happen and how does it work?
自生命诞生之日起 细菌与病毒的斗争从未停息
Bacteria and viruses have been fighting since the dawn of life.
“噬菌体”猎杀细菌
So-called bacteriophages, or phages, hunt bacteria.
海洋里的噬菌体每天消灭40%的细菌
In the ocean, phages kill 40% of them every single day.
噬菌体通过向细菌注射自己的基因编码
Phages do this by inserting their own genetic code into the bacteria
达到控制细菌 将其改造成工厂的目的
and taking them over to use them as factories.
细菌试图反抗 但大多数情况下以失败告终
The bacteria try to resist, but fail most of the time
原因在于它们的保护工具十分脆弱
because their protection tools are too weak.
但细菌偶尔能幸免于难
But sometimes, bacteria survive the attack.
之后就能启动它们所拥有的 最有效的反病毒系统
Only if they do so can they activate their most effective antivirus system.
它们把病毒的一段DNA储存在
They save a part of the virus DNA in
自己的基因编码中 收录在称为CRISPR的DNA库里
their own genetic code in a DNA archive called CRISPR.
病毒DNA被安全地存储起来以备后用
Here it’s stored safely until it’s needed.
当病毒再次进犯 细菌便迅速从DNA库中制作一段核糖核酸(RNA)复制体
When the virus attacks again, the bacterium quickly makes an RNA copy
并配备秘密武器 一种名为Cas9的蛋白质
from the DNA archive and arms a secret weapon, a protein called Cas9.
这种蛋白质开始扫描细菌内部 通过将找到的每段DNA和库里的样本进行比较
The protein now scans the bacterium’s inside for signs of the virus invader by
来甄别入侵的病毒
comparing every bit of DNA it finds to the sample from the archive.
当找到完全吻合的DNA
When it finds a 100-percent perfect match
它便启动并切除病毒DNA 使其失效
it’s activated and cuts out the virus DNA making it useless,
保护细菌免受攻击
protecting the bacterium against the attack.
需要特别指出的是 Cas9非常精准 可称得上是DNA外科医生
What’s special is that Cas9 is very precise, almost like a DNA surgeon.
当科学家们弄明白CRISPR系统是可编程的 技术革命便由此开始
The revolution began when scientists figured out that the CRISPR system is programmable.
你可以向它提供拟修改的DNA副本
You can just give it a copy of DNA you want to modify
然后把它植入活体细胞
and put the system into a living cell.
如果说过去的基因操纵技术像地图
If the old techniques of genetic manipulation were like a map,
CRISPR就是全球定位系统
CRISPR is like a GPS system.
除了精准 廉价和易操作
Aside from being precise cheap and easy,
该系统提供了编辑活体细胞的能力 可以任意添加或删除基因
CRISPR offers the ability to edit live cells, to switch genes on and off
可以甄别并研究特定的DNA序列
and target and study particular DNA sequences.
它适用于所有细胞:微生物 植物 动物或者人类
It also works for every type of cell: microorganisms, plants, animals or humans.
虽然CRISPR是科学界的革命性发现
But despite the revolution CRISPR is for science,
但它还只是第一代工具
it’s still just a first generation tool.
此时此刻 更多更精准的工具正在被制造出来并得以应用
More precise tools are already being created and used as we speak.
2015年 科学家们在实验室运用CRISPR 切除病人体内的活体细胞病毒
In 2015, scientists use CRISPR to cut the HIV virus out of living cells
证明此方法可行
from patients in the lab, proving that it was possible.
一年后 他们开始了更大规模的项目
Only about a year later they carried out a larger scale project
这次的实验对象 是身体细胞几乎充满HIV病毒的老鼠
with rats that had the HIV virus in basically all of their body cells.
仅仅通过向老鼠尾部注射CRISPR
By simply injecting CRISPR into the rats tails,
他们身体细胞里超过50%的病毒被清除了
they were able to remove more than 50% of the virus from cells all over the body.
在未来几十年中 CRSIPR疗法也许能治愈HIV及其他逆转录酶病毒
In a few decades, a CRISPR therapy might cure HIV and other retroviruses.
可用此方法清除隐藏在人类DNA中的病毒 如疱疹
Viruses that hide inside human DNA like herpes could be eradicated this way.
CRISPR可以战胜我们最危险的敌人之一: 癌症
CRISPR could also defeat one of our worst enemies: cancer.
当细胞拒绝死亡并大量繁殖
Cancer occurs when cells refused to die and keep multiplying
躲过免疫系统 癌症就出现了
while concealing themselves from the immune system.
CRISPR让我们可以编辑免疫细胞
CRISPR gives us the means to edit your immune cells
使其更好地对抗癌症
and make them better cancer hunters.
最终 要治愈癌症可能只需注射几针
Getting rid of cancer might eventually mean getting just a couple of injections
从实验室里改造过的
of a few thousand of your own cells that have been engineered in the lab
你自己的几千个细胞
to heal you for good.
2016年初 美国批准了首例CRISPR
The first clinical trial for a CRISPR cancer treatment on human patients was
在人类病患身上的临床应用
approved in early 2016 in the US.
不到一个月之后 中国科学家发表声明
Not even a month later, Chinese scientists announced that
称将在2016年8月 使用以CRISPR系统改造的免疫细胞
they would treat lung cancer patients with immune cells
治疗肺癌病人
modified by CRISPR in August 2016.
一切都进入了快车道
Things are picking up pace quickly.
接下来是基因疾病。它们种类繁多
And then there are genetic diseases. There are thousands of them and they range
有的仅仅让人心绪不宁 有的则带来长期的折磨
from merely annoying to deadly or entail decades of suffering.
有了CRISPR这种强有力的工具 我们也许能结束这一切
With a powerful tool like CRISPR, we may be able to end this.
人体DNA中一个单独的错误字节 就能引发超过3000种基因疾病
Over 3,000 genetic diseases are caused by a single incorrect letter in your DNA.
我们已开始着手打造升级版Cas9
We are already building a modified version of Cas9 that is made to
以纠正单独的字节 修复细胞内的疾病
change just a single letter, fixing the disease in the cell.
之后十到二十年里 我们也许能一劳永逸地治愈上千种疾病
In a decade or two we could possibly cure thousands of diseases forever.
但所有这些医学应用有一个共同点:
But all of these medical applications have one thing in common:
它们只针对个体且随之消亡
they are limited to the individual and die with them,
除非把它们加入繁殖细胞或处于初期的胚胎
except if you use them on reproductive cells or very early embryos.
但CRISPR有能力而且可能将起到更大的作用:
But CRISPR can and probably will be used for much more:
改良人类 定制婴儿 并可能逐渐但不可逆地
the creation of modified humans, designer babies and will mean gradual but
改变人类基因库
irreversible changes to the human gene pool.
编辑人类胚胎染色体组的技术业已存在
The means to edit the genome of a human embryo already exists,
只是目前仍不成熟
though the technology is still in its early stages.
但已经有过两次尝试:2015年和2016年 中国科学家
But it has already been attempted twice: in 2015 and 2016, Chinese scientists
使用人类胚胎进行实验 并在第二次尝试时取得阶段性成功
experimented with human embryos and were partially successful on their second attempt.
此举展示了我们在胚胎基因改造中 面临的巨大挑战
They showed the enormous challenges we still face in gene editing embryos
但同时 科学家们也在奋力攻克难关
but also that scientists are working on solving them.
就像70年代的电子计算机: 之后还会有更好的
This is like the computer in the 70’s: there will be better computers.
不论你个人对基因改造持何种看法 它都会对你产生影响
Regardless of your personal take on genetic engineering, it will affect you.
改良人类可能会改变全人类的染色体组
Modified humans could alter the genome of our entire species because their
因为他们的改良特征将传给儿女
engineered traits will be passed on to that children and could spread over
并世代相传 逐渐改变人类基因库
generations slowly modifying the whole gene pool of humanity.
开端是缓慢的: 第一批定制婴儿不会有过多改变
It will start slowly: the first designer babies will not be overly designed,
最有可能创造它们的原因是
it’s most likely that they will be created to
清除致命的家族基因疾病
eliminate a deadly genetic disease running in a family.
随着技术进步升级 越来越多的人也许会
As the technology progresses and gets more refined, more and more people may argue
争辩不使用基因改良技术有违道德 因为这迫使儿童
that not using genetic modification is unethical, because it condemns children
遭受本可避免的病痛以及死亡 且不向其提供治疗的手段
to preventable suffering and death and denies them to cure.
而只要第一例定制婴儿诞生 一扇门自此打开
But as soon as the first engineered kid is born, a door is opened
再无法关闭
that can’t be closed anymore.
早期 人们不会对虚荣特征有太多的关注 但随着基因改良
Early on, vanity traits will mostly be left alone, but as genetic modification
愈发大众化 而且我们对人类基因编码的知识日益增进
becomes more accepted and our knowledge of our genetic code enhances,
诱惑将逐渐增长
the temptation will grow.
如果你给予后代免疫奥森海默症的能力
If you make your offspring immune to Alzheimer,
为何不加入强化新陈代谢?
why not also give them an enhanced metabolism?
再来个完美视力?高大健硕的体格如何?
Why not throw in perfect eyesight? How about height or muscular structure?
浓密的秀发? 超级智力不来一发?
Full hair? How about giving your child the gift of extraordinary intelligence?
数百万个体的单独选择叠加起来
Huge changes are made as a result of the personal decisions
就能引发巨大改变
of millions of individuals that accumulate.
这就是滑坡谬误(译注:一种逻辑谬论,即不合理地使用连串的因果关系,将“可能性”转化为“必然性”,以达到某种意欲之结论。 引自知乎用户 王阿蛮)
This is a slippery slope.
基因改良人类可能成为新的标准
Modified humans could become the new standard,
但随着基因改造愈发普遍 以及相关知识的增长
but as engineering becomes more normal and our knowledge improves,
我们也许能解决人类生存的最大风险因素: 衰老
we could solve the single biggest mortality risk factor: aging.
今天全球死亡的15万人中 有三分之二将死于衰老引发的症状
Two-thirds of the 150,000 people who die today will die of age-related causes.
目前 我们认为衰老是自身损害的积累造成的
Currently we think aging is caused by the accumulation of damage to ourselves,
比如DNA断裂 以及修复系统随时间推移逐渐失效
like DNA breaks and the system’s responsible for fixing those wearing off over time.
但也有直接影响衰老的基因。通过基因改造
But there are also genes that directly affect aging. A combination of genetic
和其他疗法能够终止或减缓衰老 以至返老还童
engineering and other therapy could stop or slow down aging, maybe even reverse it.
我们知道自然界存在对衰老免疫的动物
We know from nature that there are animals immune to aging.
也许能从它们那借一些基因
Maybe we could even borrow a few genes for ourselves.
部分科学家甚至认为生理的衰老
Some scientists even think biological aging
可以被最终消除
could be something that eventually just stops being a thing.
我们还是会死亡
We would still die at some point,
但不是90岁的时候死在医院
but instead of doing so in hospitals at age 90,
我们也许能和家人朋友共同生活几千年
we might be able to spend a few thousand years with our loved ones.
对此的研究尚在起步阶段
Research into this is in its infancy,
很多科学家有理由对终结衰老这一概念持怀疑态度
and many scientists are rightly skeptical about the end of aging.
挑战前所未见 成功也许无望
The challenges are enormous, and maybe it is unachievable.
但今天的人们也许能成为首批
But it is conceivable that people alive today might be the first
因抗衰老疗法受益的人群
to profit from effective anti aging therapy.
我们需要做的就是想办法说服某个聪明的亿万富翁
All we might need is for someone to convince a smart billionaire
将此作为下一个辄需解决的难题
to make it their next problem to solve.
从更长远的角度看 我们的确能依赖基因改造人
On a bigger scale we certainly could solve many problems
解决很多问题
by having a modified population.
他们也许能更好地消化该能量食物
Engineered humans might be better equipped to cope with high-energy food,
清除肥胖症等文明带来的疾病
eliminating many diseases of civilization like obesity.
拥有储存着潜在威胁数据库的改良免疫系统
In possession of a modified immune system with a library of potential threat,
我们也许能对目前纠缠着人类的大部分疾病免疫
we might become immune to most diseases that haunt us today.
如果将目光放的更长远一些 我们能把人类改造成
Even further into the future we could engineer humans to be equipped for
适合长时间宇宙旅行 并适应其他星球的不同环境
extended space travel and cope with different conditions on other planets,
这对于我们在这个荒蛮宇宙中的生存 具有重大的意义
which would be extremely helpful in keeping us alive in our hostile universe.
但我们仍将面对几大难题。有技术的 也有道德领域的
Still a few major challenges await us. Some technological, some ethical.
诸位看官可能对我们将要创造的世界深感不安和恐惧
Many of you watching will feel uncomfortable and fear that we will create a world
我们将不接受“非完美”的人类 并根据自己的健康的理解
in which we will reject non-perfect humans and preselect features and qualities
提前选择身体特征和品质
based on our idea of what’s healthy.
事实上 我们已经这样做了
The thing is we are already living in this world.
在世界上许多地方 孕妇接受对胎儿
Tests for dozens of genetic diseases or complications
有关基因疾病和并发症的测试已成为常态
have become standard for pregnant women in much of the world.
通常来说 仅仅怀疑胎儿有基因缺陷 就会导致妊娠中止
Often, the mere suspicion of a genetic defect can lead to the end of pregnancy.
以唐氏综合症为例:这是最普遍的基因缺陷之一
Take Down Syndrome for example: one of the most common genetic defects.
在欧洲 如检测到此症状 近92%的妊娠都被中止(译吐槽:生物课本上的那位兄弟 谢天谢地你父母不是欧洲人)
In Europe, about 92% of all pregnancies where it’s detected are terminated.
中止妊娠是非常私人的选择
The decision to terminate pregnancy is incredibly personal, but
但认识到我们一直在根据身体条件
it’s important to acknowledge the reality that we are preselecting humans
对人类进行预选非常重要
based on medical conditions.
不要假装这种情况会改变
There is also no use in pretending this will change,
因此 我们在推进该技术进步的时候 必须小心审慎
so we have to act carefully and respectfully as we advance the technology
而且保证有愈来愈多的选项
and can make more and more selections.
但所有这些都无法很快实现:
But none of this will happen soon:
即便强大如CRISPR的工具 也非万无一失
as powerful as CRISPR is, and it is, it’s not infallible yet.
还存在错误编辑 以及未知的误差
Wrong edit still happen as well as unknown errors
这些都可能在不为人知的情况下 出现在DNA的任意位置
that could occur anywhere in the DNA and might go unnoticed.
基因编辑可能如愿成功消除某种疾病
The gene edit might achieve the desired result
但同时也可能引起不良变化
disabling a disease, but also might accidentally trigger unwanted changes.
目前 我们的知识不足以了解基因的复杂内在关联
We just don’t know enough yet about the complex interplay of our genes
无法避免未知结果的出现
to avoid unpredictable consequences.
随着首例人体实验的展开 我们应主要关注
Working on accuracy and monitoring methods is a major concern
提高精确度并严密检验实验方法
as the first human trials begin.
同时 我们讨论了可能出现的美好未来
And since we’ve discussed a possible positive future,
也有堕入黑暗面的可能
there are darker visions too.
试着想想 如果朝鲜开始基因改造会发生什么
Imagine what a state like North Korea could do if they embraced genetic engineering.
国家会不会对民众强制进行基因改造 以巩固统治?
Could a state cement its rule forever by forcing gene editing on their subjects?
又有什么能阻止集权国家
What would stop a totalitarian regime
组建由基因改造的超级士兵组成的军队?
from engineering an army of modified super soldiers?
这在理论上是可行的。
It is doable in theory.
类似的场景距我们还很遥远
Scenarios like this one are far far off into the future,
只是可能性不大
if they ever become possible at all.
但类似的基因改造在理论上的证据 如今业已存在
But the basic proof of concept for genetic engineering like this already exists today.
技术的力量就是如此强大
The technology really is that powerful.
诚然 这是禁止基因改造
While this might be a tempting reason
和相关研究的绝佳借口
to ban genetic editing and related research,
但肯定是个错误
that would certainly be a mistake.
禁止人类基因工程只会导致这项科学
Banning human genetic engineering would only lead to the science wandering off
投入我们不认同国家或组织的怀抱
to a place with jurisdiction and rules that we are uncomfortable with.
只有积极参与 我们才能保证未来的研究
Only by participating can we make sure that further research is guided by caution,
在谨慎 理性 合规 透明等理念指导下进行
reason, oversight and transparency.
觉得不舒服吗?
Do you feel uncomfortable now?
我们中的大多数都对此持怀疑态度
Most of us have something wrong with them.
在不久的将来 我们还会被允许存活于世吗?
In the future that lies ahead of us, would we have been allowed to exist?
这项技术的确有点吓人
The technology is certainly a bit scary,
但我们能获得很多好处 而且基因工程
but we have a lot to gain and genetic engineering might
可能只是宇宙中 智能种族在自然进化中的一步
just be a step in the natural evolution of intelligent species in the universe.
我们也许能终结疾病
We might end disease,
也许能将寿命延长几个世纪 然后踏上星际之旅
we could extend our life expectancy by centuries and travel to the stars.
当谈及这些话题 不要固步自封
There’s no need to think small when it comes to this topic.
无论你对基因工程持何观点 未来都将如期而至
Whatever your opinion on genetic engineering, the future is approaching no matter what.
曾经的疯狂科学幻想 如今将成为我们新的现实
What has been insane science fiction is about to become our new reality,
机遇与挑战并存的现实
a reality full of opportunities and challenges.
因为有你在parteon.com上的捐助 我们的视频短片才得以成真
Videos like this would not be possible without your donations on patreon.com
如果你想帮忙阐释复杂理论 或者
If you want to support in explaining complicated stuff and maybe get your own
获得专属“鸟标” 都可通过此网站。如果想了解更多CRISPR知识
bird in return you can do so here. If you want to learn more about CRISPR, we put
我们把素材和更多阅读材料放在说明里。日后还将退出更多关于
the sources and further reading in the description. More videos about the whole
完整话题的讨论区。如果想获得有关问题的通知
topic area will follow. If you want to be notified when it happens,
可以在此关注我们
you can follow us here.
英文字幕由Amara.org社区提供
Subtitles by the Amara.org community

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