人造DNA的最极端的可能性
日期:2019-01-15 15:28

(单词翻译:单击)

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All life, every living thing ever, has been built according to the information in DNA.
所有的生命,每一个生命体,都是根据脱氧核糖核酸(DNA)中的信息建造的。
What does that mean? Well, it means that just as the English language is made up of alphabetic letters that,
这是什么意思?就像英语语言由字母组成,
when combined into words, allow me to tell you the story I'm going to tell you today,
当组合成单词的时候,我就可以将我今天要说的故事了,
DNA is made up of genetic letters that, when combined into genes, allow cells to produce proteins,
DNA是由基因字母组成,结合成基因,让细胞产生蛋白质,
strings of amino acids that fold up into complex structures that perform the functions that allow a cell to do what it does, to tell its stories.
氨基酸组成具有复杂结构和功能的细胞,发挥作用,讲述它的故事。
The English alphabet has 26 letters, and the genetic alphabet has four.
英文有26个字母,基因字母有4个。
They're pretty famous. Maybe you've heard of them.
他们非常出名。你们或许听说过。
They are often just referred to as G, C, A and T.
他们通常被称为G,C,A和T。
But it's remarkable that all the diversity of life is the result of four genetic letters.
令人惊叹的是,生命的所有多样性都是这四个基因字母的结果。
Imagine what it would be like if the English alphabet had four letters.
设想一下如果英文只有4个字母会是什么样。
What sort of stories would you be able to tell?
你能说出怎样的故事?
What if the genetic alphabet had more letters?
如果基因字母不止4个呢?
Would life with more letters be able to tell different stories, maybe even more interesting ones?
是不是有更多字母的生命,会讲述不同的、更有趣的故事呢?
In 1999, my lab at the Scripps Research Institute in La Jolla, California started working on this question
1999年,我在加利福尼亚州拉霍亚斯克里普斯研究所的实验室开始研究这个问题,
with the goal of creating living organisms with DNA made up of a six-letter genetic alphabet,
目的是创造一个由6个基因字母组成的DNA生物体,
the four natural letters plus two additional new man-made letters.
4个自然基因字母加2个新的人造基因字母。
Such an organism would be the first radically altered form of life ever created.
这样的生物体将是有史以来第一个彻底改变的生命形式。
It would be a semisynthetic form of life that stores more information than life ever has before.
这将是一种半合成的生命体,存储比之前更多的信息。
It would be able to make new proteins,
它能够制造新的蛋白质,
proteins built from more than the 20 normal amino acids that are usually used to build proteins.
蛋白质由超过20种常用氨基酸构成。
What sort of stories could that life tell?
这又是怎样的生命故事呢?
With the power of synthetic chemistry and molecular biology and just under 20 years of work,
凭借合成化学和分子生物学的力量及近20年的努力,
we created bacteria with six-letter DNA. Let me tell you how we did it.
我们用6种字母的DNA创造了细菌。让我给你们讲讲我们是怎么做到的。
All you have to remember from your high school biology is that the four natural letters pair together to form two base pairs.
你从高中生物当中知道,四个自然基因字母组合在一起形成两个碱基对。
G pairs with C and A pairs with T, so to create our new letters,
G与C配对,A和和T配对,为了创建我们的新基因,
we synthesized hundreds of new candidates, new candidate letters,
我们合成了数百个新的候选基因字母,
and examined their abilities to selectively pair with each other.
选择性地配对来检测他们的功能。
And after about 15 years of work, we found two that paired together really well, at least in a test tube.
在15年的尝试之后,我们发现有两个配对很好,通过试管配对。
They have complicated names, but let's just call them X and Y.
他们的名称很复杂,我们简称为X和Y。
The next thing we needed to do was find a way to get X and Y into cells,
接下来我们要尝试着将X和Y加入细胞中,
and eventually we found that a protein that does something similar in algae worked in our bacteria.
最终我们发现,在藻类起类似作用的蛋白质,在我们的细菌中起差不多的作用。
So the final thing that we needed to do was to show that with X and Y provided,
最后我们需要做的就是,用X和Y表示出来,
cells could grow and divide and hold on to X and Y in their DNA.
细胞可以生长、分裂并保持DNA中的X和Y。
Everything we had done up to then took longer than I had hoped -- I am actually a really impatient person
这一切工作耗费的时间比我们预期长很多,我其实很没耐心,
but this, the most important step, worked faster than I dreamed, basically immediately.
但是最关键的一步完成的很快,我做梦都没想到,立马完成。
On a weekend in 2014, a graduate student in my lab grew bacteria with six-letter DNA.
2014年的一个周末,实验室的一名研究生用6个基因字母的DNA培养出细菌。
Let me take the opportunity to introduce you to them right now.
让我借此机会向你们介绍一下。
This is an actual picture of them. These are the first semisynthetic organisms.
这是他们的真实照片。这是第一个半合成生物。
So bacteria with six-letter DNA, that's really cool, right?
这就是六个基因字母的DNA,很厉害,对吧?
Well, maybe some of you are still wondering why.
也许大家还有点不清楚。
So let me tell you a little bit more about some of our motivations, both conceptual and practical.
我给大家介绍一下我们研究的意识动机和实践动机。
Conceptually, people have thought about life,
意识上,人们总在思考生命,
what it is, what makes it different from things that are not alive, since people have had thoughts.
从有思想开始就在思考,什么是生命,生命体和非生命体有什么区别。
Many have interpreted life as being perfect, and this was taken as evidence of a creator.
很多人认为生命是完美的,是造物者的象征。
Living things are different because a god breathed life into them.
生命体十分不同,因为上帝注入了生命。
Others have sought a more scientific explanation,
其他人寻求更科学的解释,
but I think it's fair to say that they still consider the molecules of life to be special.
但我认为生命细胞与众不同这一说法合理。
I mean, evolution has been optimizing them for billions of years, right?
我的意思是,生物进化已经优化了数十亿年,不是吗?
Whatever perspective you take, it would seem pretty impossible for chemists to come in
无论你支持什么观点,化学家们似乎都不能
and build new parts that function within and alongside the natural molecules of life without somehow really screwing everything up.
进入生命自然分子内部或边缘并建立新的成分,他们会搞砸一切。
But just how perfectly created or evolved are we? Just how special are the molecules of life?
但是人类创造或进化到底多完美?生命体细胞究竟多特殊?
These questions have been impossible to even ask, because we've had nothing to compare life to.
这些问题无法回答,因为生命无法用来比较。
Now for the first time, our work suggests that maybe the molecules of life aren't that special.
现在,我们的工作第一次表明生命细胞并没有那么特别。
Maybe life as we know it isn't the only way it could be.
也许生命并不是只有我们知道的这一种方式。
Maybe we're not the only solution, maybe not even the best solution, just a solution.
也许我们不是唯一的解决方案。也许也算不上最好的解决方法,只是一个方法而已。
These questions address fundamental issues about life, but maybe they seem a little esoteric.
这些问题是生命的基本问题,虽然似乎有点深奥。
So what about practical motivations?
那实践动机呢?
Well, we want to explore what sort of new stories life with an expanded vocabulary could tell,
我们想要探索扩大词汇量的生命,能讲述什么样的新故事,
and remember, stories here are the proteins that a cell produces and the functions they have.
记住,故事就是细胞产生的蛋白质及具备的功能。
So what sort of new proteins with new types of functions could our semisynthetic organisms make and maybe even use?
合成体生命体会制造和使用怎么的具有新型功能的新蛋白质?
Well, we have a couple of things in mind.
我们有几点想法。
The first is to get the cells to make proteins for us, for our use.
首先让细胞生产蛋白质,为我们所用。
Proteins are being used today for an increasingly broad range of different applications,
今天蛋白质的使用越来越广泛和多样化,
from materials that protect soldiers from injury to devices that detect dangerous compounds,
从保护士兵受伤的材料,到检测危险化合物的设备,
but at least to me, the most exciting application is protein drugs.
但对我来说,最令人激动的是蛋白质药物。
Despite being relatively new, protein drugs have already revolutionized medicine, and, for example, insulin is a protein.
尽管蛋白质药物相对较新,但它已经使医学发生了革命性的变化,例如,胰岛素就是一种蛋白质。
You've probably heard of it, and it's manufactured as a drug that has completely changed how we treat diabetes.
你可能听说过胰岛素作为药物彻底改变了糖尿病的治疗方式。
But the problem is that proteins are really hard to make and the only practical way to get them is to get cells to make them for you.
问题是蛋白质很难制造,唯一的方法是是让细胞生产蛋白质。
So of course, with natural cells, you can only get them to make proteins with the natural amino acids,
当然,天然细胞只能与天然氨基酸一起生产蛋白质,
and so the properties those proteins can have, the applications they could be developed for,
这样蛋白质的特性和开发利用,
must be limited by the nature of those amino acids that the protein's built from.
受限于构建蛋白质的天然氨基酸特性。

人造DNA的最极端的可能性

So here they are, the 20 normal amino acids that are strung together to make a protein,
因此20种常规氨基酸串在一起制成蛋白质,
and I think you can see, they're not that different-looking.
我想你们能看到,他们看起来区别不大。
They don't bring that many different functions. They don't make that many different functions available.
他们没有太多的不同功能。没有提供那么多不同功能。
Compare that with the small molecules that synthetic chemists make as drugs.
将其与合成化学家制造的小分子药物进行比较。
Now, they're much simpler than proteins, but they're routinely built from a much broader range of diverse things.
它们比蛋白质简单得多,但是他们通常是由各种各样的东西构建的。
Don't worry about the molecular details, but I think you can see how different they are.
不必担心分子细节,你会发现它们有很大不同。
And in fact, it's their differences that make them great drugs to treat different diseases.
事实上,正是它们的差异使它们成为治疗不同疾病的伟大药物。
So it's really provocative to wonder what sort of new protein drugs you could develop if you could build proteins from more diverse things.
那么,如果从更多的事物构建蛋白质,会开发出哪些新型蛋白质药物呢?
So can we get our semisynthetic organism to make proteins that include new and different amino acids,
我们能否让合成生命体制造蛋白质,包含新的和不同的氨基酸,
maybe amino acids selected to confer the protein with some desired property or function?
或者选择一些具备所需特性和功能的氨基酸?
For example, many proteins just aren't stable when you inject them into people.
举个例子,很多蛋白质注入人体后不稳定。
They are rapidly degraded or eliminated, and this stops them from being drugs.
它们迅速降解或消失,无法成为药品。
What if we could make proteins with new amino acids with things attached to them that protect them from their environment,
如果我们能够制造新的蛋白质,含有保护它们不受环境影响、
that protect them from being degraded or eliminated, so that they could be better drugs?
不会降解或消失的氨基酸,使它们成为更好的药物呢?
Could we make proteins with little fingers attached that specifically grab on to other molecules?
我们能否在蛋白质上装上小指,专门勾住其他的分子?
Many small molecules failed during development as drugs
很多小分子在药物开发中失败,
because they just weren't specific enough to find their target in the complex environment of the human body.
因为它们的特异性无法在复杂的人体中找到它们的目标。
So could we take those molecules and make them parts of new amino acids that,
我们能否让这些分子组成新的氨基酸,
when incorporated into a protein, are guided by that protein to their target?
掺入蛋白质,找到它们的目标?
I started a biotech company called Synthorx.
我创办了Synthorx生物技术公司,
Synthorx stands for synthetic organism with an X added at the end because that's what you do with biotech companies.
Synthorx代表合成生物体,最后的X正是生物科技公司要做的。
Synthorx is working closely with my lab,
Synthorx与我的实验室合作密切,
and they're interested in a protein that recognizes a certain receptor on the surface of human cells.
他们正在研究识别人体细胞表面某种受体的蛋白质。
But the problem is that it also recognizes another receptor on the surface of those same cells, and that makes it toxic.
但问题是它还能识别同类细胞表面的另一种受体,这使它具有毒性。
So could we produce a variant of that protein where the part that interacts with that second bad receptor is shielded,
我们能否制造出一种蛋白质变体,挡住蛋白质与第二种有害受体交互部分,
blocked by something like a big umbrella so that the protein only interacts with that first good receptor?
像一把大伞一样挡住,这样蛋白质只能与第一种受体交互?
Doing that would be really difficult or impossible to do with the normal amino acids,
常规氨基酸很难或根本不可能做到,
but not with amino acids that are specifically designed for that purpose.
但专门为此而设计的氨基酸则不然。
So getting our semisynthetic cells to act as little factories to produce better protein drugs isn't the only potentially really interesting application,
因此,让我们的半合成细胞作为小工厂来生产更好的蛋白质药物,不是唯一可能真正有趣的应用,
because remember, it's the proteins that allow cells to do what they do.
因为,蛋白质决定细胞功能。
So if we have cells that make new proteins with new functions, could we get them to do things that natural cells can't do?
如果我们具有新功能细胞,我们能否让它完成天然细胞无法完成的任务?
For example, could we develop semisynthetic organisms that when injected into a person,
比如说,我们是否可以开发半合成生物,注入人体,
seek out cancer cells and only when they find them, secrete a toxic protein that kills them?
寻找癌细胞,找到之后分泌出杀死癌细胞的有毒蛋白质?
Could we create bacteria that eat different kinds of oil, maybe to clean up an oil spill?
我们能否创造出吃各种油的细菌,来清理漏油?
These are just a couple of the types of stories that we're going to see if life with an expanded vocabulary can tell.
这些只是我们将要看到的几种类型的故事,如果基因字母增加的话。
So, sounds great, right? Injecting semisynthetic organisms into people,
听起来不错,对吧?向人体注射半合成生物,
dumping millions and millions of gallons of our bacteria into the ocean or out on your favorite beach?
将数百万加仑的细菌导入海洋或者放在你最喜欢的沙滩?
Oh, wait a minute, actually it sounds really scary. This dinosaur is really scary.
稍等,实际上听起来很吓人。这种想法真的很吓人。
But here's the catch: our semisynthetic organisms in order to survive, need to be fed the chemical precursors of X and Y.
但关键是:我们的半合成生物为了存活,需要喂食X和Y两种化学前体细胞。
X and Y are completely different than anything that exists in nature.
X和Y与自然界其他东西完全不同。
Cells just don't have them or the ability to make them.
细胞根本没有也不可能制造它们。
So when we prepare them, when we grow them up in the controlled environment of the lab,
当我们准备它们的时候,当我们在实验室的受控环境中培养它们的时候,
we can feed them lots of the unnatural food.
我们可以喂它们很多非天然食物。
Then, when we deploy them in a person or out on a beach where they no longer have access that special food,
当我们注入人体或者放置沙滩上,它们无法获得这些特殊食物,
they can grow for a little bit, they can survive for a little,
它们能够成长一点,存活一小段时间,
maybe just long enough to perform some intended function, but then they start to run out of the food.
也许有可以完成一些预期的功能的时间,但之后它们就开始耗尽食物。
They start to starve. They starve to death and they just disappear.
它们开始挨饿。最后饿死了,消失了。
So not only could we get life to tell new stories, we get to tell life when and where to tell those stories.
我们不仅有生命可以讲故事,我们也可以告诉生命何时何地去讲故事。
At the beginning of this talk I told you that
演讲开始时,我告诉大家,
we reported in 2014 the creation of semisynthetic organisms that store more information, X and Y, in their DNA.
在2014年我们报道了半合成生物的产生,他们的DNA中存储了更多的信息,X和Y。
But all the motivations that we just talked about require cells to use X and Y to make proteins, so we started working on that.
但是我们刚刚谈到我们需要细胞使用X和Y来制造蛋白质,所以我们开始研究。
Within a couple years, we showed that the cells could take DNA with X and Y and copy it into RNA, the working copy of DNA.
在几年内,我们发现细胞可以用含有X和Y的DNA,并复制给DNA的工作副本RNA。
And late last year, we showed that they could then use X and Y to make proteins.
去年年底,我们发现它们可以利用X和Y来制造蛋白质。
Here they are, the stars of the show, the first fully-functional semisynthetic organisms.
就是它们,我的演讲主题,它们是一个功能齐全的半合成生物。
These cells are green because they're making a protein that glows green.
这些细胞是绿色的,因为他们会产生一种发绿光的蛋白质。
It's a pretty famous protein, actually, from jellyfish that a lot of people use in its natural form because it's easy to see that you made it.
这是很有名的水母蛋白质,很多人直接使用因为能看出来它是怎么来的。
But within every one of these proteins, there's a new amino acid that natural life can't build proteins with.
但是在这些蛋白质中,每一种蛋白质都含有自然生命无法构建的新氨基酸。
Every living cell, every living cell ever, has made every one of its proteins using a four-letter genetic alphabet.
每个活细胞,之前的每个活细胞,都是用4个基因来制造每一种蛋白质。
These cells are living and growing and making protein with a six-letter alphabet.
这些细胞用6个字母的基因来生活、成长、制造蛋白质。
These are a new form of life. This is a semisynthetic form of life.
这是一种新的生命。这是一种半合成生命。
So what about the future? My lab is already working on expanding the genetic alphabet of other cells, including human cells,
那么未来呢?我的实验室正在努力扩展其他细胞的基因,包括人类细胞,
and we're getting ready to start working on more complex organisms. Think semisynthetic worms.
我们已经准备开始研究更复杂的生物。想想半合成蠕虫。
The last thing I want to say to you, the most important thing that I want to say to you,
最后我想说的是,也是我想说的最重要的一点,
is that the time of semisynthetic life is here. Thank you.
半合成生命就在这里。谢谢。
I mean, Floyd, this is so remarkable. I just wanted to ask you,
弗洛伊德,这是非常了不起的。我想问问你,
what are the implications of your work for how we should think about the possibilities for life, like, in the universe, elsewhere?
你的工作对于我们思考生命的可能性有什么影响,比如在宇宙中,或是其他地方?
It just seems like so much of life, or so much of our assumptions are based on the fact that of course, it's got to be DNA,
它看起来就像我们的生命,或者我们的假设是基于这样的事实,当然它必须是DNA,
but is the possibility space of self-replicating molecules much bigger than DNA, even just DNA with six letters?
但是自我复制分子的可能性比DNA大得多,即使是只有6个基因的DNA?
Absolutely, I think that's right, and I think what our work has shown, as I mentioned,
当然,我认为这是正确的,而且我认为我们的工作表明,就像我提到的,
is that there's been always this prejudice that sort of we're perfect, we're optimal,
我们总是存在这种偏见,认为我们是完美的,我们是最好的,
God created us this way, evolution perfected us this way.
上帝创造了我们,进化完善了我们。
We've made molecules that work right alongside the natural ones,
我们制造的分子与天然分子一起工作,
and I think that suggests that any molecules that obey the fundamental laws of chemistry and physics
我认为这表明任何细胞可以遵循化学和物理学基本定律,
and you can optimize them could do the things that the natural molecules of life do.
并且你可以优化它们,使它们做生命中自然分子所做的事情。
There's nothing magic there. And I think that it suggests that life could evolve many different ways,
这并非是什么魔术。而且我认为这表明生命可以通过许多不同的方式进化,
maybe similar to us with other types of DNA, maybe things without DNA at all.
也许和我们一样,有其他类型的DNA,也许根本就没有DNA。
I mean, in your mind, how big might that possibility space be? Do we even know?
在你看来,这个可能性有多大?我们能知道吗?
Are most things going to look something like a DNA molecule,
是不是大多数东西看起来像DNA分子,
or something radically different that can still self-reproduce and potentially create living organisms?
或者根本不同的东西,仍然可以自我复制并可能创造生物体?
My personal opinion is that if we found new life, we might not even recognize it.
我的个人观点是,如果我们找到新的生命,我们甚至可能都没认识到。
So this obsession with the search for Goldilocks planets in exactly the right place with water and whatever,
所以痴迷寻找一个适居星球,那里正好有水和其他资源,
that's a very parochial assumption, perhaps.
这可能是一个非常狭隘的假设。
Well, if you want to find someone you can talk to, then maybe not,
嗯,如果你想找一个可以跟你说话的人,那么也许不是,
but I think that if you're just looking for any form of life, I think that's right,
但我想如果你只是在寻找任何形式的生命,我认为这是对的,
I think that you're looking for life under the light post.
我认为你在正确地寻找生命。
Thank you for boggling all our minds. Thank so much, Floyd.
谢谢你让我们惊叹不已。非常感谢,弗洛伊德。

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