CRISPR, with Prof Fyodor Urnov
发布时间 2021-09-12 23:00:00 来源
摘要
Prof Fyodor Urnov tells us how CRISPR is already changing the lives of people with genetic disorders, and why it’s essential that gene editing therapies are accessible to all.
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Hello and welcome to Instant Genius, a bite-sized Masterclass in podcast form. I'm Sarah Riggby, online assistant at BBC Science Focus Magazine.
大家好，欢迎来到《Instant Genius即时天才》，这是一个迷你的播客形式的大师课程。我是BBC科学聚焦杂志的线上助理Sarah Riggby。
In 2020, Jennifer Daugner and Emmanuel Chalponte won the Nobel Prize in Chemistry for their development of CRISPR, a revolutionary method of gene editing. In this episode, I talk to Professor Fiora Ernoll. He works with Daugner at the Innovative Genomics Institute at UC Berkeley in California, and he featured in Human Nature, a 2019 documentary about CRISPR. He tells me how CRISPR is already changing the lives of people with genetic disorders, and why it's essential that gene editing therapies are accessible to all.
在2020年，珍妮弗·道格纳和埃曼纽尔·沙尔旁特因其开发的CRISPR（一种革命性的基因编辑方法）获得了诺贝尔化学奖。在这一集中，我和Fiora Ernoll教授谈话。他和道格纳一起在加利福尼亚大学伯克利分校的创新基因组学研究所工作，并出现在2019年的纪录片《Human Nature》中。他告诉我，CRISPR已经开始改变患有遗传疾病的人们的生活，为什么基因编辑疗法能够被所有人接受是至关重要的。
CRISPR is something that probably most of us have heard of, if we're at least vaguely aware of science news, but it might not be something that everyone knows exactly what it is, and it's a very complex topic. So just to start, could you please, in one sentence, just describe what CRISPR is?
CRISPR 是一个我们大部分人听说过的东西，如果我们至少模糊了解科学新闻，但并不是每个人都确切知道它是什么，而且这是一个非常复杂的话题。因此，为了开始，您能否请用一句话简单描述一下什么是 CRISPR？
CRISPR is the equivalent of a word processor for the genetic material of any living organism from cow to human that allows us to change that genetic material in a way we specify.
CRISPR 就像是一台基因材料的文字处理器，可适用于从牛到人的任何生物，使我们能够按照我们指定的方式改变这种基因材料。
So CRISPR is a form of gene editing, but there are other forms out there as well, aren't there? How is it different to other forms of gene editing?
那么CRISPR是一种基因编辑形式，但还有其他形式存在，不是吗？它与其他基因编辑形式有何不同？
I will admit that asking yours truly this question is a bit like asking a koala to speak about the different kinds of eucalyptus leaves that can be found in Australia. Targeted genetic engineering was first practiced in smaller organisms such as yeast in the late 70s, and what then happened is scientists attempted to use it in other systems and it just didn't work.
我要承认，问我这个问题有点像让考拉谈谈在澳大利亚可以找到哪些不同种类的桉树叶子。有针对性的基因工程最初是在20世纪70年代晚期在像酵母这样的小生物中进行的，当时科学家们试图将其运用到其他系统中，但却并不奏效。
So, in the parts of the living world where we would most wanted to work like repair and mutation that causes disease, or change, let's say, a gene that causes a rice plant to become susceptible to drought. So fast forward to 2012 here at Berkeley, Jennifer Daugna discovers that CRISPR Cass can be used for targeted genetic engineering.
嗯，我们最想要从事修复和导致疾病或变化的基因突变等生物世界的部分。比如，我们想改变某个基因，使水稻变得耐旱。那么，快进到2012年，在伯克利，詹妮弗·道格纳发现CRISPR-Cas可以用于精准基因工程。
Now it happens to be the case that genome editing was put together and named before that discovery. But in all practical terms, as far as the real world is concerned, looking out the window, what will that look like 10 years from now in terms of what has been gene edited, the vast majority of those things will have been done using CRISPR.
现在情况是，基因组编辑是在发现CRISPR之前被组合并命名的。但就实际意义而言，就现实世界而言，从窗户外看，10年后进行基因编辑的大部分工作都将使用CRISPR完成。
And the reason for such a long answer to such a simple question is it's one of those situations where I think we need to be mindful of the broader outcome of a technology rather than its specific instantiation. In other words, I have no idea whether people will share music via Spotify or something else. The point is that online music is a thing. CRISPR is today's non-Jouhour for the most efficient gene editing technology we have.
我们为什么要对这样一个简单的问题作出如此长的回答呢？因为这是一个需要我们对技术的广泛影响有所意识的情况，而不仅仅是关注于它的具体实现。换句话说，我不知道人们是否会通过Spotify或其他方式分享音乐。关键是，在线音乐即使是一个实际存在的事务。CRISPR是我们今天最高效的基因编辑技术，是当今的非物质文化遗产。
So you work for the innovative genomics institute. What is it that you do there?
那你在创新基因组学研究所工作，你在那里做什么？
Try to use CRISPR to make for a better world. There is, has been $11 billion with a B put into the overall sector of genetic engineering just in human health. So I'm not mentioning agriculture or discovery of drugs. And that shows that the for-profit sector is very excited about what you can do with gene editing.
尝试使用CRISPR让世界变得更美好。在整个基因工程领域，仅人类健康方面就已经投入了110亿美元。所以我并未提到农业或药物发现。这表明营利性领域对基因编辑所能带来的兴奋程度非常高。
As we have learned through the pandemic of COVID-19, there is no global council for the equitable and just distribution of technologies to the planet in a world where everybody benefits equitably. So Jennifer Daudn has vision for founding the innovative genomics institute is to make sure that this extraordinary tool that we have is also used and applied and made available to settings where I suppose spontaneously emerging market-based processes may or may not lead it to. For example, the engineering of crops for parts of the developing world where climate change and other circumstances are creating major challenges or doing better diagnostics for things like SARS-CoV-2 where it's pretty clear that we're still lagging behind in terms of being able to rapidly and in the real world diagnose whether somebody has the virus or not.
正如我们通过COVID-19的大流行所学到的那样，在一个所有人能够平等获益的世界中，没有全球公平公正分配技术的机构。因此，詹妮弗·道德恩创立创新基因组研究所的愿景就是确保我们拥有的这种非凡工具在各种背景下得到应用和共享，其中可能存在自发涌现的市场进程，也可能不存在。例如，在发展中国家中气候变化和其他情况正在造成重大挑战的地区进行作物工程改良，或者针对SARS-CoV-2等事物做出更好的诊断，明显地，我们在能够快速和现实地诊断某人是否感染该病毒方面仍然落后。
And the part where yours truly spends all of his life, how do we deliver medical treatments based on CRISPR to those who are most in need and who for reasons that will probably require five episodes of instant genius. The current, I guess, for profit space in a health care may not address.
关于我自己度过生命的那部分，我们如何向那些最需要的人提供基于CRISPR的医疗治疗，而这些人可能需要五个即时天才的原因。目前的、为了盈利的医疗保健领域可能无法解决这个问题。
The most obvious sort of use of CRISPR of gene editing is in treating genetic diseases. So what kind of diseases could it be and is it being used to treat?
CRISPR基因编辑最明显的应用是治疗遗传疾病。那么它能够治疗哪些疾病，而且是否正在被使用呢？
You know, if you had asked me this question 10 years ago, I would have gone on a long string of hypotheticals with featuring words like, we are hopeful to end perhaps or someday. Here we are in September 2021 when I can give you specific examples about human beings walking the earth that has been crisper and not only has that happened, they are feeling better. And thus we are sharing our planet with our fellow genetically engineered humans, which is an amazing thing to say.
你知道的，如果你在10年前问我这个问题，我会用一大堆假设的话来回答，比如说“我们希望能够在某个时候结束”之类的。但现在是2021年9月了，我可以给你一些具体的例子，人们在走在地球上，这个世界变得更加清晰，不仅如此，他们也感觉更好了。因此，我们和我们的同样是基因工程人类的同胞们一起分享地球，这真是一件令人惊奇的事情。
Earlier this year, we learned that the most prevalent type of genetic disease on earth, which are disorders of red blood cell production.. One is called sickle cell disease and the other is called beta thalassemia, has been as best as we can tell safely and effectively treated by using CRISPR, where people's blood stem cells were removed.
今年早些时候，我们得知在世界上最普遍的遗传病中，红细胞生成的紊乱是其中最为普遍的一种。其中一种叫镰状细胞病，另一种叫β地中海贫血。据我们所知，使用CRISPR已被证实是安全有效的治疗方法，其中人们的血干细胞被移除。
They got CRISPR put back in and major disease symptoms such as needing blood transfusions or experiencing pain appear to have resolved. Now everyone who works in this field will tell you that nobody who works in this field is doing a victory lap.
他们成功让CRISPR再次发挥作用，重要的疾病症状，如需要输血或感觉疼痛，似乎已经得到缓解。现在，每个从事这个领域的人都会告诉你，没有人会为此沾沾自喜。
It will take years to make sure that these treatments are actually safe. And then of course we have the formidable challenge of how to make them accessible.
我们需要花费数年时间来确保这些治疗方法真的是安全的。然后，我们还需要克服巨大挑战，即如何使它们变得更易接近。
But we learned about sickle cell disease in Western medicine in I think 1910. We have known that sickle cell as genetic since the 1930s. Vernon Ingram told us about the molecular cause of sickle in 1956, I believe. And yet here we are only in 2021.
我认为，我们在西医学中了解到镰状细胞性贫血症大约是在1910年左右。自从20世纪30年代，我们就知道镰状细胞是遗传性疾病。我相信1956年，Vernon Ingram告诉我们关于镰状细胞的分子病因。但是现在我们还只是到2021年。
A long time before we can say to the world, okay, after more than a century of study of this disease, we have actually built a technology that appears to be able to not just treat it, but as best as we can tell, cured it.
很长一段时间过去了，我们才能告诉世界，经过一百多年的研究这种疾病，我们实际上开发出一项技术，似乎不仅能治疗它，而且据我们所知，它已经被治愈了。
The challenge with what I just described and the reason that it's expensive to administer such a therapy has to do with as I mentioned, taking the cells out of the body, then crispering them and putting them back in.
我刚刚描述的问题和进行这种治疗昂贵的原因在于，就像我之前提到的那样，需要从体内取出细胞，然后进行基因剪切，最后再放回去。
And let's just say that it's a laborious and sophisticated operation which involves dozens of people large specialized facilities where people wear the kinds of protective gear you see in science fiction films.
我们来说说这是一个艰苦而复杂的工作，它涉及到数十人和大型专门设施，那些人身上穿戴着你在科幻电影里见到的那种防护装备。
And that's because of I need to make sure that the therapies are made properly. But what if we could just inject crisper? And crisper would somehow go to where it needs to go and fix the gene it needs to fix and then go away.
那是因为我需要确保治疗方法做得正确。但是，如果我们只用CRISPR注射，它会自己找到需要修复的基因，然后离开呢？
You know, quoting Eliza Dulittle, wouldn't that be leverally? That's happened.
你知道的，引用伊丽莎·杜利托的话，那不是很优秀吗？这种情况已经发生了。
So the first clinical trial I just described for sickle cell disease was done by a US biotechnology company and European as well, CRISPR therapeutics.
所以，我刚刚描述的针对镰状细胞贫血的第一次临床试验是由美国生物技术公司和欧洲公司CRISPR Therapeutics进行的。
What I'm about to describe was done by a tech company called Intelia. And they took a number of people, including some of the United Kingdom, who have a disease with a long name, TTR Ameloidosis, which most of you audience has not heard of.
我要描述的是由一家科技公司 Intellia 完成的。他们选了一些来自英国的人，他们患有一个很长的名字，叫做 TTR Ameloidosis，这是大多数观众没有听说过的疾病。
It's one of those things that would used to be called genetic doom or genetic destiny. It's like, you know you have the disease and you kind of know what's going to happen to you and you're like, you're looking with a sense of dread at the bleakness ahead.
这是那种过去被称为遗传厄运或遗传命运的事情之一。就像你知道你有这种病，你有点知道会发生什么，你会感到非常担心未来的黯淡。
Well, so Intelia has engineered a crisper to get rid of the gene that causes the disease.
所以，Intelaiya研制出了一个能消除导致疾病发生基因的脆皮。
That's not enough. They figured out a way how to get it into the human body, literally via an injection. Okay, well, we've been able to do injections for a long time. But the best part is they figured out how to get crisper to the organ, which needs crispering and that's the liver.
这不够好。他们摸索出一种方式，就是通过注射让它真的进入人体。好吧，我们早就能打针了。但最好的部分是，他们找出了如何让CRISPR到达需要CRISPR的器官，那就是肝脏。
Last but not least, if an average person on the street with a disease says, would you like to carry some crisper in you?
最后但并非最不重要的一点是，如果一个患病的普通人问你，你想在你的身体里植入一些转基因植物吗？
You know, most people would say, well, I wasn't planning on it. And the beautiful thing about geneticing and this I think is really what sets us apart from anything else we've ever had in this space is the genetic edit that crisper makes in your DNA is permanent. But the crisper itself is gone.
你知道的，大多数人会说，嗯，我没有计划。而最美好的事情在于基因编辑，我认为这真的是让我们与以往任何其他领域不同的地方，是crisper所做出的遗传编辑在你的DNA中是永久性的。但crisper本身已经消失了。
It's like literally a repair person. Imagine you have something wrong with your house or apartment like you have a leaking roof. The repair person doesn't move into your house to stay there after the repair is done. They just leave.
这就像真正的修理工一样。想象一下，你的房子或公寓有什么问题，比如你的屋顶在漏水。修理工完成修理后不会搬进你的房子住，他们只是离开了。
Similarly, in this clinical trial, crisper got injected, went into the liver of six individuals, got rid of the gene that needed to be gotten rid of and then basically vanished.
同样地，在这个临床试验中，CRISPR 被注射进了六个人的肝脏中，去除掉需要被除去的基因，然后基本上消失了。
Or the technical term has got rapidly degraded. So I will admit to you, if you were asking me five years ago to write a utopia that says, theater, why don't you just fantasize about how great the future could be with the crisper clinical thing?
或者说技术术语已经迅速恶化。所以我要告诉你，如果你五年前让我写一个乌托邦，说戏剧，你为什么不幻想一下，用更清晰、更精确的临床技术，未来会有多么美好呢？
It really couldn't write a better story than reality has brought us. Here we are with more than 35 people who have been crisper for their severe disease of the blood, safely and effectively, early days but still.
现实带给我们的故事真的再好不过了。现在，超过35人已经成功地治愈了他们身患的严重血液疾病，这是早期但仍然安全有效的治疗。
And six people got crisper for a severe disease of their nerves and heart and they appear to be quite well. So no victory laps, nobody is eating scoops of ice cream at two in the afternoon.
有六个人因神经和心脏的严重疾病而变得更健康了，他们似乎状态良好。所以没有在胜利之后狂喜欢庆祝，没有在下午两点吃着一勺勺的冰淇淋。
But the palpability of the excitement is there.
但是兴奋感是可以感觉到的。
I'm amazed that you can just inject crisper and it can work in the body. So I always imagined you would take a sample and then you would do the gene editing in a lab and then put that back in the body as you described with the sickle cell disease.
我很惊讶你可以直接注入CRISPR，它就能在身体里发挥作用。所以我一直想象你会先取样，然后在实验室里进行基因编辑，再像你描述的镰状细胞病一样把它放回体内。
So how is it exactly that crisper actually works that allows you to be able to just inject it into the body and it can cure what it needs to cure? Sorry, I realize this may be a very complex question.
那么，究竟是如何让CRISPR能够被注入到人体并治愈所需的疾病的？对不起，我知道这可能是一个非常复杂的问题。
Not in the slightest, happy to explain. Think about this as a set of directions to a party..
完全没有问题，我很乐意解释。就像给你参加派对的路线一样，请你想象一下。
Counting backwards from when you've walked into the room and you give the host a bag of cookies you baked.
从你走进房间并将你烤的曲奇饼干递给主人开始倒数。
So in order to do that, you need to get through the door. You need to get to the house. And in order to get there, you need directions from where you are to where you're going.
所以为了做到这点，你需要通过门。你需要到达房子。而为了到达那里，你需要从你现在所在的地方到你要去的地方获得方向。
So for crisper, the Nobel Prize winning discovery by Jennifer Daudna and her colleague in Manu and Shobankya has to do with the last step, which is when inside your body, when inside your cell, when inside the nucleus of your cell, where your DNA is, how does crisper get to the destination?
因此，Jennifer Daudna和她的同事Manu和Shobankya所获得的诺贝尔奖，与crisper有关，尤其是最后一步，即在您的身体内，当在您的细胞内，当在您的细胞核内（即您的DNA所在处）时，crisper如何到达目的地。
You know, when there's a person on American TV, her name is Marie Kondo and she talks about this concept of things having to spark joy. This is the part of crisper that sparks joy because you know, your audience of course is familiar with a classic structure of DNA where one strand pairs with another in a way that James Watson and Francis Crick figured out an informable part based on data from Roslyn Franklin and Maurice Wilkins and others.
你知道吗，在美国电视上有一个人，她叫玛丽·康多，谈论的是物品必须激发喜悦的概念。这个激发喜悦的部分是指DNA的经典结构，你的听众当然熟悉DNA的结构，其中一个链与另一个链配对，就像詹姆斯·沃森和弗朗西斯·克里克根据罗斯琳·富兰克林、莫里斯·威尔金斯等人的数据确定的可证明部分。
And your audience will remember from elementary school that there are these very simple rules through which one strand matches with another where there if one strand has an A, the other has a T, if one has a G, the other has a C, it's one of those facts like Pythagoras' theorem that you kind of learn when you're 11 and forget for the rest of your life.
你的听众会记得从小学起就有一些非常简单的规则，可以让一条链与另一条链匹配，其中一个链如果有A，另一个链就有T，如果一个链有G，另一个链就有C，这就像是毕达哥拉斯定理一样的事实，在你11岁的时候学到，却很快忘记了。
Jennifer and Demanuel discovered that if you arm crisper with a tiny snippet of nucleic acid with a string of 20 letters, then crisper will run around the nucleus in a way we still don't completely understand. And then we'll find in this enormous stretch of genetic text which is human DNA and let's remind ourselves that the human DNA is very long.
珍妮弗和德曼纽尔发现，如果你给crisper装上一个只有20个字母的核酸小片段，它就会在细胞核周围跑来跑去，我们目前还没有完全理解这一过程。然后，我们会在这个极长的遗传密码文本中找到人类DNA，需要提醒自己，人类DNA非常长。
If you read a letter of it a second, you know, like a G, C, T, it'll take you a century to read the whole thing, a century. It's a very long text. So now imagine having a molecular machine, you give it a 20 letter string and it runs around the entire human genetic text and finds a match.
如果你每秒钟读一个字母，比如说G、C、T，那么要读完整个基因组的话，需要一百年的时间，一整个世纪。这个文本非常长。现在想象一下，如果有一台分子机器，你输入一个20个字母的字符串，它可以遍历整个人类基因组，并找到匹配的部分。
I mean, you know, I suppose we humans think of this quite naturally, you know, if I tell your audience what is the origin of the phrase, oh, brave new world that has such creatures in it, you know, everybody will say, my goodness, it's the tempest, it's what Miranda says to Prosperer, right? Well, I use that quote on purpose, talk about brave new world that has such creatures in it, crisper.
我是说，你知道，我想我们人类自然会考虑到这点。如果我告诉你的观众这个短语的起源，哦，勇敢新世界拥有这样的生物，你知道，每个人都会说，天哪，那是《暴风雨》里玛丽安达对普罗斯珀罗说的话，对吧？好了，我有意引用了这句话，来谈论这个勇敢新世界，拥有这样的生物，CRISPR。
It's Mother Nature's machine to take a tiny snippet of nucleic acid genetic text and run around any amount of genetic information and find a perfect match.
这是大自然的机制，可以将很小的核酸基因文本快速地匹配相关的遗传信息，找到完美的配对。
Okay, so that's how crisper gets to the gene. Now how does crisper get inside the cell?
好的，这就是CRISPR是如何到达基因的。那么，CRISPR又是如何进入细胞的呢？
So it gets inside the cell because it got packaged in a little droplet of a lipid and the lipid is built to fuse with the cell and release so fat basically and the fat releases the cargo into the cell. How does the, I'm starting to sound a bit like, you know, this is the house that Jack built. How does that lipid droplet with the crisper get to the liver?
所以它能进入细胞，因为它被包裹在一个小的脂质液滴中，而这种脂质是构建成与细胞融合并释放脂肪的，而脂肪则将货物释放到细胞中。但是，这种带有CRISPR的脂质液滴如何到达肝脏呢？我开始听起来有点像“杰克建造的房子”了。
It was engineered to go there. So the way that is technically done is scientists. And I should also say this is one of those amazing examples where people from different disciplines have to converge to get this to work.
它是专门设计去那里的。技术上是由科学家完成的。我也应该说这是一个令人惊奇的例子，在这个过程中需要不同学科的人聚集在一起才能使它工作。
You know, you kind of have to have different skills, different superpowers. And so a separate group, a group of people separate from the crisper engineers have spent a lot of time figuring out how to, you know, package things and then inject them into the body in a way where they go to a specific destination.
你知道的，你需要具备不同的技能和超能力。因此，一个与crisper工程师不同的团队，花费了很多时间来研究如何将东西打包并以一种方式注射到身体中，使它们前往特定的目的地。
And they're the ones who figured out how to get something to the liver. So the long answer to your very short question is crisper gets packaged in a special little droplet, which is technically called the lipid nanoparticle that has been engineered to a, get to the liver, in this case, B, release the crisper cargo into the cell.
他们是那些想出如何将物质输送到肝脏的人。所以，对于你的简短问题的详细回答是：CRISPR 基因编辑技术被装入了一个特殊小滴，技术上被称为脂质纳米粒子，这个脂质纳米粒子经过了改良，以实现 A. 到达肝脏， B. 将 CRISPR 载荷释放到细胞中。
And then Mother Nature takes over armed with Jennifer's and Demanuel's Nobel Prize winning insight to then route that crisper to the gene of interest to do to it what we need to do.
然后自然界便发挥Jennifer和Demanuel获得诺贝尔奖的洞见，把分子剪切器引导到我们需要操作的基因上，以达到我们所需要的效果。
That's example number one. A shorter example is in some settings, it's actually beneficial and logistically better to put crisper inside a virus. Viruses are Mother Nature's way to get into things.
这是第一个例子。另外一个更简短的例子是，在某些情况下，把脆脆放在病毒中实际上是有利的，也更方便。病毒是大自然进入事物的途径。
Now let's be just be clear. This is not the disease causing virus. This is an inert virus that has been gutted of all its viral, viralitude. Instead, its gut has been replaced with crisper. The only thing that is left of its virusness is the ability to get into a particular cell type.
现在让我们明确一点。这不是一种引起疾病的病毒。这是一种已经被去除了所有的病毒因素的无毒病毒。相反，它的内部被更换成了更为清晰。它所保留的唯一病毒特性是能够进入特定细胞类型。
And I'm really excited in about two weeks we should hear from biotechnology company called Editas. And they're about to tell us what happened on their clinical trial when they put crisper and a virus and injected it into the eye of somebody who I hope I'm using the word right had congenital blindness because if our hopes and dreams are fulfilled, they should be able to see.. We don't know yet. Fingers crossed.
我真的很兴奋，在大约两周的时间里，我们应该会收到一家名为Editas的生物科技公司的消息。他们将要告诉我们，在临床试验中，当他们将Crisper和病毒注射到某人的眼睛里时，发生了什么。我希望我用的是正确的词，那个人有先天性失明，因为如果我们的希望和梦想得以实现，他们应该能够看到...但我们还不知道。祈祷好运。
So I can kind of intuitively understand how gene editing could be used to treat genetic disorders. You know, you can just in some way, you can go in and you can change the genes or you can turn off the genes. But are there any diseases it can cure that aren't specifically caused by genetics? That's the big hope.
那么，我有点直觉地理解基因编辑可以用来治疗遗传疾病。你知道，通过某种方式，你可以进去并改变基因或关闭基因。但是它能治愈那些不是由基因特定引起的疾病吗？这是我们的希望。
You know, there are 5,000 different genetic diseases and collectively they affect, you know, 200 million people at least on Earth. You know, it's a it's a it's a raw fact of the living universe that, you know, everyone will at some point succumb to a disease. How do we deal with those? There is clear promise on two fronts.
你知道，有五千种不同的遗传性疾病，它们共同影响了至少两亿人在地球上。你知道，这是生命宇宙中一个残酷的事实，每个人都将在某个时候因疾病而屈服。我们如何处理这些问题？有明显的两个方面的前途。
The first one has to do with cancer. We've made pretty remarkable progress over the past 2 decades in understanding the molecular basis of what causes cancer. And you know, there are some remarkable examples where that understanding has led to very strong medicines. So for example, melanoma, especially when it metastasizes is a horrific cancer and there is a there's a medicine called key truda, which is a protein which which causes the human immune system when injected into a human to attack the tumor.
第一个与癌症有关。在过去20年中，我们在了解是什么导致癌症的分子基础方面取得了相当显著的进展。你知道，有些非常显著的例子，这种理解已经导致了非常强大的药物。例如，黑素瘤，特别是在转移时是一种可怕的癌症，有一种叫做凯特鲁达的药物，它是一种蛋白质，当注入人体时会引起人体免疫系统攻击肿瘤。
Incidentally, I bring this up because that fundamental notion was discovered and reduced to practice by Berkeley's previous Nobel laureate, Jamalisins, I mean previous before, before Jennifer's discovery. But you know, to be honest with you, we don't really have cures with a capital C for most cancers. Using CRISPR to genetically engineer human immune cells to attack the cancer in a specific and potent way. There have been some early stage clinical trials with a bit of promise.
说起来，我之所以提起这个问题，是因为伯克利大学的前一位诺贝尔奖得主Jamalisins发现并将这个基础概念付诸实践，我是说在Jennifer的发现之前先发现的。但说实话，我们并没有真正的“C级治愈法”能够治愈大多数的癌症。使用CRISPR技术对人类免疫细胞进行基因改造，以特定和强效的方式攻击癌症。一些初期临床试验表现出了一些希望。
Now before anyone in your audience starts to, you know, frantically search clinical trials don't go for a CRISPR and I think they're absolutely coming. This field is well very rapidly developing. It needs, I'd say about another two to three to four years to start delivering on the promise of what we think would happen. But in the big picture, the vision is this, the vision is to make cells that have been crisper to attack a cancer and critically resist the cancer's attempts to defend itself.
现在，在你们的听众纷纷开始疯狂搜索临床试验之前，我觉得需要提醒大家，CRISPR技术的开始已经非常接近了。这个领域正在迅速发展，但我们需要大约再过两三到四年来实现我们的承诺。但是从大局来看，我们的愿景是这样的：利用经过CRISPR技术改造的细胞来攻击癌细胞，并对癌细胞的自我保护机制产生抗性。
And a really good example, I keep mentioning Berkeley, well, I wonder if you can tell which, why I'm a professor. But it just so happens, it's a center of innovation. So there's a biotech company in the Bay Area called Caribou. And it came out of work at UC Berkeley. And they are one of the companies along with others, for example, such as Allogene and others who are trying to build these off the shelf T cells to fight cancer. I want to be clear, we need a few years for this to play out. So that's sort of non-simple genetic disease number one.
一个非常好的例子就是伯克利。我不知道你是否能猜出为什么我是一名教授。很巧合的是，伯克利是一个创新中心。在湾区有一家生物技术公司叫做卡里布。它的起源是来自于加州伯克利分校的研究工作。与其他公司一起，例如阿洛基姆等，他们正在试图构建这些即用型T细胞来对抗癌症。我想要明确的是，我们需要几年的时间来了解这个问题。这是一个不简单的遗传疾病问题。
The other, and for this, I will admit, to having a sort of an emotional conflict of interest, heart disease runs in my family. And I'm not excited. So there is a biotech company called Verve. And they're doing what I think is some of the most interesting work and putting crisper to use for a common disease, which as you guessed, it happens to be cardiovascular disease.
另外，我要承认，因为心脏病在我家族中比较普遍，所以我有一种情感上的利益冲突。我并不是很兴奋。所以有一家名叫Verve的生物技术公司，他们正在针对一种普通疾病——心血管疾病，利用CRISPR技术进行一些我认为非常有趣的工作。
So you will say to me, but fiery or cardiovascular disease is not genetic or at least not trivially genetic. Like, it has to do with history and diet and this, that. We don't know, right? Right. Except that there are people who are genetically protected from it. I mean, I don't want to use the word one, the genetic lottery. There is no genetic lottery. But there are rare individuals who lack a normal form of aging. And nothing appears to be wrong with them, except they appear to be really resistant to heart disease, no matter what their lifestyle.
你会跟我说，但是热情或心血管疾病不是遗传的，或者至少不仅仅是遗传的。它涉及历史和饮食等等。我们不知道，对吗？对。除了那些基因上有保护作用的人。我不想用“基因彩票”这个词。其实没有基因彩票这种说法。但是存在一些罕见的人，他们没有一般人会有的衰老问题，而且看起来身体健康，无论他们的生活方式如何，他们似乎都很抵抗心脏病。
And you know, if I were speaking with mother nature, I would definitely ask her for that gene, but it's a bit too late. I'm already here. Well, so the remarkable thing is it's not too late. So what Verve is doing is they are developing a way to put crisper into humans to give people that heart disease protective gene. How do you actually do that in the world of medicine where it's kind of hard to do a sort of a preventative treatment when it's what you're doing is so experimental?
你知道的，如果我和大自然交流的话，我一定会问她要那个基因，但现在太晚了，我已经在这里了。不过，令人惊奇的是，事情并没有太晚。Verve正在研发一种将CRISPR（一种基因编辑工具）应用于人类的方法，从而给予人们具有心脏病保护作用的基因。在医学领域，如何在预防性治疗方面做到这一点，特别是当你所做的是如此实验性的时候，这确实是一件比较困难的事情。
So it turns out that there is a charted path for this. And it's also in the cardiovascular disease space. I strongly suspect that a good fraction of your audience takes statins for cardiovascular disease prevention.
原来有一条明确的路线可以解决这个问题。而且它也在心血管疾病领域。我强烈怀疑你的听众中有很多人正在服用他汀类药物预防心血管疾病。
It so happens that they weren't developed or approved for prevention. They were developed and approved to treat a rare severe form of heart disease. That is genetic. Because they were so novel at the time. This was the late, the early 80s.
恰巧它们并没有被开发或批准用于预防。它们是为治疗罕见的严重心脏病而开发和批准的。那是一种遗传性疾病。因为当时它们非常新颖。这是80年代末到80年代初的时期。
And so scientists developed this thing called statins and they tested it on people who are really succumbing to genetic heart disease and they improved.. Then scientists and medicine physicians turned to the regulatory authority such as the Food and Drug Administration and the US and said, hey, this is working really well in genetic heart disease. Can we try it for sporadic heart disease? They tried it and it worked.
所以科学家们发展了一种叫作他汀的东西，并在那些真正患有基因性心脏病的患者身上进行了测试，然后情况得到了改善。随后，科学家们和医药专家们转向像美国食品药品监督管理局这样的监管机构，并说，嘿，这个在基因性心脏病方面有很好的效果。我们能不能尝试用于散发性心脏病？他们试了试，结果效果很好。
And then the physician said, look, it's working so well. Can we prescribe it for prevention? And that's why, you know, I think there are like 220 million prescriptions, including one from my dad, who's 86, to take a statinous disease prevention rather than treatment.
然后医生说：看，他的效果非常好。我们可以开处方来预防吗？这就是为什么我认为有大约2.2亿个处方，包括我父亲的一份，他已经86岁了，用于预防这种疾病而不是治疗。
So the path that verivestaking with CRISPR is conceptually similar. They have developed a way to use CRISPR again injected into the bloodstream to get rid of the gene that, you know, and we know that getting rid of it should protect against heart disease. They've shown some pretty magnificent data in the most important non-human model that you have to do this experiment in which is non-human primates.
所以，采用CRISPR的verivestaking路径在概念上类似。他们开发了一种方法，可以再次将CRISPR注入血液中，以摆脱某种基因，可以保护心脏疾病不发生，你我都知道。他们在非人灵长类动物这个最关键的非人类模型中展示了一些相当不错的数据。
And they have spoken publicly about the fact that sometime next year they are intending to take folks, you guessed it, with genetic heart disease and try to use CRISPR to give them this protective variant. If that works, I am certain that what they're going to do is try to follow in the footsteps of statins, which is to turn to the Food and Drug Administration and say, hi. This is working really well in genetic disease. Can we try it for sporadic?
他们已经公开表示，明年他们有意带一些有遗传性心脏病的人，试图使用CRISPR技术给他们提供一种保护性基因变种。如果成功的话，我确信他们会试图效仿他那样的做法，也就是转向食品药品监督管理局，说：“嗨，这在遗传性疾病中效果非常好。我们可以尝试用它来治疗零星疾病吗？”
So that's example number one. Also number two has to do with pain, which is, you know, talk about it now for something completely different.
那么这是第一个例子。第二个例子涉及到疼痛，你知道的，现在说它完全是出于不同的原因。
The reason I bring up pain is the theme is similar, you know, like tens and tens and tens and tens of millions of folks in the states and certainly worldwide suffer from chronic pain of that sort or other. And some of it is severe, like trigeminal neuralgia can be terrible or pain when you have cancer which really resists opioids.
我提到疼痛的原因是主题相似，你知道，在美国和全世界有数以千万计的人们患有这种或其他慢性疼痛。其中一些疼痛非常严重，比如三叉神经痛可以很可怕，或者癌症疼痛由于不能用阿片类药物治疗，也非常难熬。
So right now the way this has managed, quote unquote, is using very strong medicine such as fentanyl, which unfortunately is addictive and addiction to it, you know, has killed tens of thousands of my fellow Americans in this past year and continues to.
现在这种管理方式所使用的，引号内的话，是像芬太尼这样非常强烈的药物，不幸的是，它具有成瘾性，它的成瘾已经导致了去年数以万计的美国同胞的死亡，而且这种情况仍在继续。
So is there a way? Is there a CRISPR play here? There is. So it turns out that there are rare individuals who experience no pain. They lead a terrible life. You can't live without pain.
那么，有什么办法吗？有CRISPR的应用方式吗？有的。事实证明，有些人很少会感到疼痛。他们的生活很糟糕。生活中没有疼痛是不可能的。
Having said, when people look at their DNA, it turns out that the reason they experience no pain is they don't have a function in copy of a gene which makes a protein which lives in your spine, which sends the pain signal from wherever you're pained, like a knee or your face to your brain. And so the pain signal is the transmission of the pain signal is broken.
说到这一点，当人们查看他们的DNA时，结果是他们不感觉疼痛的原因是因为他们的一份基因副本中缺少一个功能，该功能是制造一种在脊柱中寄生的蛋白质，它将从你疼痛的任何地方（如膝盖或脸）发出疼痛信号发送到你的大脑。因此，疼痛信号的传输就被中断了。
Now that you've heard me speak about verve trying to create a natural protective variant for heart disease and people who don't have that variant, I'm sure it will not surprise you that a company called Mediga is trying to do the same but for the pain gene.
现在你听了我说关于Verve试图为心脏疾病创造一种自然保护变异体和那些没有这种变异体的人，我相信你不会感到惊讶，也有一家名叫Mediga的公司正试图利用同样的方式处理疼痛基因。
Namely, they are trying to use a different form of CRISPR to inject it into the spine, to tune down in people who experience severe pain for one reason or another, the gene that drives the pain sensation. Not to the point where they don't feel any pain, that's not good, but where the pain is tolerable.
具体而言，他们正在尝试使用CRISPR的另一种形式注入脊髓，以调节那些因为某种原因经历严重疼痛的人体内驱动疼痛感觉的基因。并不是让这些人完全不感受到疼痛，那样是不好的，而是让疼痛能够被容忍。
So taking a step back, I've described two specific examples, one in heart disease and one in pain, with the same underlying theme. We study human genetic variation, we find rare individuals who are either susceptible or protective to a disease.
那么，退一步说，我描述了两个具体的例子，一个是心脏疾病，一个是疼痛，它们都有同样的基本主题。我们研究人类基因变异，找出罕见的人，他们有可能对一种疾病易感或具保护作用。
And in the case of finding variants that protect us, what you then do is you use CRISPR in its various forms and you develop a plan speaking with a food and drug administration or the European Medicines Agency to try to give a person without the variant that gene genetic variant using CRISPR to treat existing disease and if that works, to then expand the scope of that use to less severe forms.
在寻找保护我们的变异体时，您可以使用CRISPR及其各种形式，与食品药品监督管理局或欧洲药品管理局进行沟通，以治疗已经存在的疾病并使用CRISPR给一个没有基因变异体的人。如果这种方法奏效，可以将其应用范围扩大到病情较轻的人身上。
So frankly, I am hopeful, I'm 52, I think. I am hopeful in 10 years to please be CRISPR for my heart disease risk. That would be amazing. I strongly suspect I will develop chronic pain of some sort other than my heart, and I'm just kidding.
坦率地说，我很有希望，我猜我今年52岁了。我希望在未来十年内，我的心脏病风险能够通过CRISPR来治疗，那将会是非常神奇的。我很有信心将来会患上某种慢性疼痛，但我只是开玩笑。
I will experience chronic pain and I'd love to be CRISPR for that as well. And I want to be clear, I'm joking, of course, there's nothing to do with me.
我将经历慢性疼痛，如果可能的话，我也希望能像CRISPR一样治疗它。我想要强调的是，我是在开玩笑的，当然，这与我无关。
The dream, of course, is that folks, that this would be broadly and equitably available. And what I think is really inspiring about the promise of CRISPR is it could be a one and done.. Right? So statins have to be taken daily. Opioids for pain have to be taken frequently.
当然，人们的梦想是广泛且公平地使用它。我认为 CRISPR 的承诺真正让人振奋的是它可以一劳永逸。对吧？因此，他汀类药物必须每天服用。镇痛剂必须经常服用。
The vision for CRISPR as an amazing way to help the world is you get CRISPR at once and then you wish that person a happy, healthy life. And that, of course, going back to telling you about the innovative genomics institutes is really what we're trying to achieve here.
CRISPR被看作是一种帮助世界的惊人方式，因此你现在想立即获得CRISPR并祝愿那个人健康幸福。当然，这就是我们在这里试图实现的创新基因组学研究所的目标。
We want to build ways in which CRISPR can be affordably developed and delivered to make sure that it's not just you know some Berkeley professor daydreaming about being CRISPR, but like the rest of the world. Right, absolutely.
我们希望建立一种能够以可负担的价格开发和提供CRISPR技术的方法，以确保这不仅仅是某个伯克利教授梦想成为CRISPR，而是全世界的机会。没错，绝对如此。
Thank you. And this is a really, really massive topic. So we can talk about this for hours, I'm sure, but I'd just like to wrap up this first episode by asking you what three things do you really think that everyone should know about CRISPR?
谢谢您。这是一个非常非常庞大的话题。我敢肯定我们可以谈论数个小时，但我只想在第一集结束时请问您，您认为每个人都应该了解CRISPR的三件事是什么？
It came out of human curiosity. Jennifer Gaudner was not trying to build a revolutionary gene editing tool. She's just deeply curious about how the world works.
这源于人类的好奇心。詹妮弗·高德纳并不是在试图打造革命性的基因编辑工具，她只是非常好奇世界是如何运作的。
And so I think your audience should take comfort in the fact that the formidable investment that governments around the world make in such fundamental research gave us such an amazing technology to affect human health.
所以我认为您的听众应该感到安慰，因为世界各地政府在这样的基础研究中所做出的巨大投资，给我们带来了如此惊人的技术，以改善人类健康。
Two, the promise of CRISPR to make a better world is much greater than the many worst-case scenarios that you hear out there. When I speak with folks about CRISPR, they, the very first thing that comes out of their mouth is, oh designer babies. And I go, no, no, no, no, no, not designer babies. Nobody's making designer babies.
二、CRISPR技术让世界变得更美好的承诺远比那些恶劣的最坏情况多得多。当我和人们谈论CRISPR技术时，他们第一时间说出的是：哦，设计婴儿。但是我会说：不，不，不，没有人会制造设计婴儿。
This is, and nobody ever should. I tell them about cancer and heart disease and sickle cell disease and blindness. So thing number two to know about CRISPR is the real world uses to treat genetic disease and other disease are the thrilling future of this technology.
这是不应该发生的事情。我告诉他们癌症、心脏病、镰状细胞贫血和失明的相关知识。因此，关于CRISPR的第二件事是，治疗基因病和其他疾病的现实世界应用是这项技术的令人激动的未来。
And three, for all of the astonishing promise of CRISPR in human health, our vision here at the Innovative Genomics Institute and frankly worldwide. And everybody who works with this is that the bigger impact will be in the context of global warming.
还有第三点，尽管CRISPR在改善人类健康方面有着惊人的前景，但在创新基因组研究所以及全球范围内，我们的愿景是利用它来应对全球变暖问题，所有从事这项工作的人都认为其更大的影响将在这方面体现。
We can make CRISPR crops and animals in a way where they have no foreign DNA. So they're not, they don't have, have a different gene. They just have a natural variant which protects them from drought or disease. So we are not, you know, some people say quote, playing God.
我们可以通过CRISPR技术培育作物和动物，而不用引入外来的DNA。因此，它们没有不同的基因。它们只是具有自然变异，可以保护它们免于干旱或疾病的影响。所以，我们不会，你知道的，有些人会说，“在扮演上帝的角色”。
We're collaborating with Mother Nature. We are listening to her language and speaking with her on her own terms and respectfully taking her discoveries and just putting them to good use. So the promise of CRISPR to address global warming with a particular angle on engineering that the crops and animals that we humans need to lead an equitable and sustainable life is very formidable.
我们正在与自然母亲合作。我们在倾听她的语言，以她的方式与她交流，并尊重地利用她的发现。CRISPR对应对全球变暖的承诺是非常强大的，特别注重于工程化人类所需的具有公平和可持续性的农作物和动物。
And I think this is something we work on very hard at the IGI and many people work on and that your audience should be excited. Thank you for listening to this episode of Instant Genius. That was Professor Fjörö Ernolf.
我认为这是我们在IGI非常努力工作的事情之一，许多人都在努力，我认为你的听众应该会很兴奋。谢谢收听这期Instant Genius节目。这就是Fjörö Ernolf教授。
If you want to know more about CRISPR, check out Documentary Human Nature which is available on Netflix or Amazon Prime video or to hear and tell me more about gene editing, head over to the Instant Genius Extra Podcast.
如果您想了解更多关于CRISPR的信息，可以在Netflix或Amazon Prime视频上观看纪录片《人类本质》。如果您想听更多有关基因编辑的信息，可以前往“即刻天才Extra播客”进行了解。
The September issue of BBC Science Focus magazine is out now. Pick up a copy and install or visit sciencefocus.com.
BBC Science Focus杂志的9月号现已发布。赶快去拿一本，安装或访问sciencefocus.com。