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Trying to understand life without clearly watching it in action
想要了解生命，却没有清楚观察生命怎么运作，
is like an alien species trying to understand the rules of a football game from just a few snapshots.
就像是外星人只看几张照片，就想要了解美式足球的规则。
We can learn a lot from these images. For example, there's players on and off the field.
我们从这些影像中能了解很多。比如，有球员在场上，也有球员在场外。
There's a band. There's even cheerleaders having a great time watching the game.
有乐团，甚至还有很享受看比赛的拉拉队。
And of course, despite learning all of this information from watching these pictures, we still cannot piece together the rules of the game.
当然，尽管看这些照片就能得到上述这些信息，我们仍然无法拼凑出比赛的规则。
In order to be able to do that, we need to actually watch the game in action.
想了解规则，我们就得要真正看比赛的进行。
Much of what we know about how life works comes from watching these snapshots.
我们对于生命如何运作的了解，绝大部分来自于看这些照片。
Scientists have been able to figure out a lot by looking at similar snapshots,
科学家透过研究类似的照片，已经得到了许多信息，
but ultimately, for them to understand how life works, they need to actually watch it in action.
但最终，若想要了解生命的原理，还是得去看生命的实际运作。
And this is essentially where life happens, is trying to understand how the fundamental unit of life works.
基本上，这就是生命产生的地方，试图了解生命的基础单位如何运作。
And to be able to watch this, we need to be able to understand how life is.
若要观察这种基础单位，我们就得要了解生命是怎样的。
Compared to this ant, a human cell is about a hundred million times smaller in volume.
和这只蚂蚁相比，人类细胞的体积大约是牠的一亿分之一。
Do you see the cell that's right next to this ant? It's right there.
有看到蚂蚁旁边的细胞吗？就在那里。
To be able to watch this cell, we need to make the invisible visible, and we do this by building microscopes.
若要观察这个细胞，我们就得看见看不见的东西，做法就是建造显微镜。
Not these microscopes; the ones that we build look something like this.
不是这种显微镜；我们建造的显微镜是像这种的。
It helps that I'm part of a paparazzi -- well, of sorts.
它对我很有帮助，我算是某种狗仔队。
Instead of taking pictures of people, I'm more interested in taking pictures of famous cells.
只是我不拍人的照片，我更感兴趣的是去拍著名的细胞。
Well, my own career path up until this moment in time has been pretty windy,
在这个时间点之前，我的职业生涯一路都很蜿蜒，
starting with my first childhood obsession and continued passion in computer science,
一开始是我童年时迷恋计算机科学，这份热情一直持续下去，
which took a sharp transition to looking at engineering, and more recently, a very sharp transition to trying to understand cell biology.
后来急转弯，变成去研究工程学，最近，又是一个急转弯，去试图了解细胞生物。
Now, it's this combination of disciplines that has led me to where I am today.
这种结合多学科的背景，让我走到今天这一步。
I'm able to carry out interdisciplinary research with one clear goal.
我可以针对一个清楚的目标，进行跨学科的研究。
And the idea is to be able to advance innovation and discovery by bringing together experts from these different disciplines
想法是将不同学科的专家集结起来，让创新与发现再向前推进，
to be able to work together and solve problems that each of us can't.
同心协力解决个人无法解决的问题。
Now, we're interested in understanding the cell.
而我们很想要了解细胞。
The cell... what is it? Well, it's the fundamental unit of life. Simply put, it's just a bag.
细胞...它是什么呢？它是生命的基础单位。简单来说，它只是个袋子。
It's a bag that has trillions of inanimate molecules, whether it's proteins, carbohydrates, lipids or fat.
袋子里有数兆个无生命的分子，可能是蛋白质、碳水化合物、脂质或脂肪。
And it turns out, over the past half a century, molecular biologists and biochemists have figured out ways to make these proteins glow.
结果发现，在过去半个世纪，分子生物学家和生物化学家已经找出方法让这些蛋白质发光。
They light up just like fireflies.
它们会像萤火虫一样亮起来。
Now, microscope developers have been able to make better and better instruments
显微镜开发者也做出更好的仪器，
to be able to capture this light emitted from these molecules,
能够捕捉到这些分子释放出来的光，
and computer scientists and mathematicians have been able to understand the signals that are being recorded from the cameras.
而计算机科学家和数学家能够了解这些摄影机记录到的信号代表什么。
And by bringing these tools together, we're actually being able to understand the organization of these molecules inside of these cells,
将这些工具集合起来，我们就能了解这些分子在细胞内的如何组织，
understand how that changes over time, and that's essentially what we're interested in, trying to understand life at its essence.
了解它如何随时间变化，基本上，这就是我们想要做的，试图从根本上了解生命。
So we want to go from imaging life, which has traditionally been confined to two dimensions, to being able to image life in three dimensions.
传统呈现生命的方式，是用二维成像，我们想要做到用三维成像。
So how do you make a two-dimensional image into a three-dimensional image?
所以，要如何把二维影像变成三维影像？
Well, turns out it's pretty straightforward.
结果发现答案十分直接。
We just collect a series of two-dimensional images as we're moving the sample up and down,
只要一边把样本上下移动，一边收集一系列的二维影像，
and then we stack the images on top of each other and create a three-dimensional volume.
接着把这些影像堆栈起来，就能创造出三维的体积。
The problem with this approach is that traditional microscopes, they dump way too much energy into the system.
这个方法的问题在于，传统的显微镜会把太多能量送入到系统中。
That means that this cell that you see over here, it's experiencing a lot of light toxicity, and that's a problem.
那就表示，各位在这里看到的细胞受到了相当大量的光所毒害，那是个问题。
Let me explain that a little bit better.
让我进一步解释一下。
For example, let's say that on this planet, life evolved under just one sun, yes?
举例来说，比如，在地球上，生命是在一个太阳下演化吧？
Now, let's say I wanted to watch the shoppers on this street to understand their shopping habits:
假设我想要观察这条街上的购物者以了解他们的购物习惯：
how long they linger in front of stores window shopping, how many stores they go into and how long they spend inside of each of the stores.
会在商店橱窗前逗留多久、会进入多少间商店、在每一间商店花多少时间。
And if I was sitting down at a coffee shop just people-watching, many wouldn't even notice that I'm watching them.
如果我坐在咖啡厅里观察这些人，许多人不会注意到我在观察他们。
Now, what if all of a sudden I was shining the equivalent of what is,
如果，突然间，我开始发光，
say, the light or the sunlight from about five or, say, 10 different suns?
发出的光等同于五个或十个太阳的光，会如何？
Would they still behave as they normally did? Would they still linger outside for just as long?
他们仍然会继续正常的行为吗？他们还是会在橱窗边逗留那么久吗？
Can I really believe that their behavior hasn't been altered as a consequence of being exposed to this much sunlight?
我能相信他们的行为没有因为暴露在超强太阳光下而被改变吗？
No. Most microscopes these days, and conventional microscopes,
不能。现今大部分的显微镜以及常见的显微镜，
have been able to dump between 10 to 10,000 times the sunlight that we're exposed to on this planet, where life actually evolved.
倾御的光都比生命在地球上演化所接受的太阳光强十倍到一万倍。
And because of this, well, turns out I'm part of the cell paparazzi,
因为这个理由，嗯，结果发现我是细胞狗仔队的一员，
so we need to be very careful in terms of how much light we actually put into the cell.
所以我们得非常注意我们会投射多少光到细胞里。
Otherwise, we might end up with a deep-fried cell.
要不然，我们可能会得到油炸细胞。
And, turns out, there's really nothing natural about trying to watch a damaged cell whose behavior has been significantly altered.
结果发现，去观察行为已经大大改变的受损细胞，实在是看不到什么自然的行为。
Well, let's take this cell for example. It's sitting on a piece of glass. You see the spots everywhere?
咱们用这个细胞为例。它位在一片玻璃上。有看到到处都是亮点吗？
Those spots represent molecular machines that are assembling on the surface of the cell
这些点代表分子机器，它们在细胞表面上集结，
in order to be able to shuttle food from outside the cell into the cell.
目的是要将食物从细胞外搬运到细胞内。
Our lab uses something called the lattice light sheet microscopy,
我们的实验室使用所谓的晶格层光显微术，
which generates a very, very thin sheet of light, paying attention not to damage the cells or not to put too much light into the system.
这种显微术会产生非常薄的层光，能注意不要损伤到细胞，或不要将大量的光带入到系统中。
And when we do this, we're able to watch the dynamics of that process for much longer without really stressing out these cells.
当我们这么做的时候，我们就能更长时间观察这个过程动态，同时不会让这些细胞感到焦虑。
We've used this microscopy technique and tools to be able to understand how viruses infect cells.
我们已经用这种显微术和工具来了解病毒如何感染细胞。
In this example, we've exposed the cell to rotavirus.
在这个例子中，我们让细胞接触轮状病毒。
It's an extremely contagious pathogen that kills over 200,000 people every year.
这是一种感染力超强的病原体，每年会造成二十万人死亡。
And by watching these molecules, these virus particles, how they diffuse on the surface of the cells,
透过观察这些分子、这些病毒粒子、它们如何在细胞表面扩散，
we can actually understand the rules that they're playing by.
我们就能了解它们的游戏规则。
And when we understand these rules, we can start to outsmart them, whether through intelligent drug therapies,
若我们能了解这些规则，我们就能以机智胜过它们，也许是用智能药物治疗，
to be able to mitigate, manage or even prevent the virus from binding into the cell in the first place.
来减轻、管理，甚至预防病毒，打从一开始就不要让病毒与细胞结合。
Now, we've made the invisible visible, but the question remains: When can we believe what we actually see?
我们已经看见看不见的东西了，但问题还在：我们何时才能相信我们所看见的？
Everything I've shown you up until this point has been a cell that's been held prisoner on a piece of glass or in a petri dish.
目前我给大家看的一切都来自被困在玻璃上或培养皿中的一个细胞。
Well, it turns out that cells didn't really evolve on a piece of glass. Right?
结果，细胞在一片玻璃上并不会演化吧？
They didn't evolve in isolation, and they didn't evolve outside their physiological context.
细胞在孤立状态下或生理环境以外的地方，都不会演化。
To truly understand cells' natural behavior, we need to able to watch them in action where actually is their home turf.
要真正了解细胞的自然行为，我们必须要观察它们在自家地盘上怎么活动。
So, let's take a look at this complex system. This is a developing zebra fish embryo,
所以，咱们来看看这个复杂的系统。这是处于发育中的斑马鱼胚胎，
where you're looking at cells that are organizing themselves in order to form tissues, in order to form organ systems.
可以看到这些细胞在自我组合，目的是要形成组织，再形成器官系统。
And when we watch the movie again, you'll see that at about 20 hours, you start to form the eye and the tail of the zebra fish.
再看一次，在大约第二十小时处，可以看到斑马鱼的眼睛和尾巴成形。
Now, we can watch this, not in this low resolution, we can watch this in exquisite detail,
我们可以观察这个过程，不是在低分辨率的情况下，而是看到精致的细节，
and we want to be able to watch this in three dimensions over the course of minutes, seconds, hours or even days.
并且我们希望能用三维的影片观看数分钟、数秒、数小时，或甚至数天的过程。
So the problem with these complex systems is that we scramble the light,
这些复杂系统的问题在于我们扰乱了光，
or they scramble the light that we actually shine onto them, which causes us to record very blurry images.
或者它们扰乱了我们用来照射它们的光，导致我们记录到非常模糊的影像。
And it turns out that astronomers have had a similar problem,
结果发现，天文学家也有类似的问题，
but for them, the problem comes when they're trying to record the light from distant stars on telescopes that are ground-based.
但对他们来说，问题是发生在他们要用地球上的望远镜来记录遥远星体发出的光。
The problem is, when the light travels thousands of light years
他们的问题是，光行进了数千光年，
and it hits our turbulent atmosphere all of a sudden, the light gets scrambled.
突然撞到我们扰动的大气，光就被扰乱了。
They've also, luckily, figured out a solution to this for over half a century.
他们也很幸运在半个世纪前找到了解决方案。
What they do is they generate an artificial star at about 90 kilometers above the Earth's surface,
他们的做法是制造一个人工星体，放在地球表面上方九十公里处，
and they use that light, which passes through the same turbulent atmosphere as the distant star's light,
人工星体的光也会和远方星体的光一样，穿过同样的扰动大气，
and they're able to understand how the light is getting scrambled,
他们就能了解光会如何被扰乱，
and they take a mirror that can change its shape in order to compensate or undo that scrambling.
然后他们使用一面能改变形状的镜子，来补偿或还原大气造成的扰乱。
So what we've done is we've taken those ideas and we've implemented that with our microscope system.
我们的做法是，我们把那些想法用在我们的显微镜系统中。
And when you do that, you can more or less unscramble the complexity of the scrambling
这么做或多或少可以将扰乱的复杂度减低，
and the fuzziness that's happening as a consequence of complex systems.
也能减少复杂系统造成的模糊。
And we do this in zebra fish. We like zebra fish because, like us, they're vertebrates.
我们用斑马鱼来实验。我们喜欢斑马鱼，是因为它们跟我们一样是脊椎动物。
Unlike us, they're mostly transparent.
而它们是透明的，这点和我们不同。
That means that when we shine light on them, we can watch the cellular and the subcellular dynamics with exquisite detail.
那就表示，当我们用光照射它们时，我们可以看到细胞和亚细胞的动态细节。
Let me show you an example. In this video, you're watching the spine and the muscle of a zebra fish.
让我举个例子。这支影片呈现的是斑马鱼的脊椎和肌肉。
We can look at the organization of the cells -- hundreds of cells in this particular volume
我们可以看到细胞怎么结合--有数百个细胞在这个体积中，
in the presence and absence of adaptive optics.
包括有调适光学和没有调适光学的情况。
Now, with these tools, we can watch more clearly than we've ever been able to before.
有了这些工具，我们就能观察得比以前更清楚。
And in a very specific example, looking at how the eye develops in the zebra fish,
非常明确的例子就是能够看到斑马鱼的眼睛如何发育，
you can really see the commotion inside of this developing zebra fish embryo.
真的可以看到这个发育中的斑马鱼胚胎中发生什么骚动。
So you can see the cells that are dancing around. In one example, you see how the cell is dividing.
可以看到细胞跳来跳去。在其中一个例子中，可以看到细胞分裂。
In another example, you see cells trying to get places and squeezing past another cell.
另一个例子，可以看到细胞为了移动到某处而挤过其他细胞。
And in the last example, you see a cell being completely rowdy to its neighbors by just punching its neighbors. Right?
在最后一个例子中，可以看到细胞对它的邻居非常粗暴，直接揍它的邻居。对吧？
This technology really enables us to watch deeper and more clearly,
这种科技让我们能够看得更深、更清楚，
almost as if we're watching single cells on a piece of glass where they've been held prisoner.
几乎就像是在观察被困在一片玻璃上的单一细胞。
And to demonstrate the promise that this technology holds, we've partnered with some of the best scientists from around the world.
为了展示这种科技的前景，我们和全世界顶尖的科学家合作。
And we've started to ask a range of fundamental questions that we're starting to work on right now together.
我们开始问许多基本的问题，现在我们开始连手要解决。
For example, how does cancer spread through the body?
比如，癌症如何在体内扩散？
In this example, you're looking at human breast cancer cells that are basically kind of migrating,
在这个例子中的是人类的乳癌细胞，它们大概是正在转移，
where they're using the blood vessels that are shown in magenta.
它们会使用图上洋红色的血管。
They're basically using these blood vessels as highways to move about the cabin.
它们用血管来当高速公路，在舱中四处移动。
You can basically see them squeezing through the blood vessels.
你大体上可以看见它们挤过血管。
You can see them rolling where there's enough space.
若空间足够，可以看到它们滚动。
And in one example, well, you see what looks like Ridley Scott's trailer for the next "Alien" movie.
有一个例子看起来很像雷德利·斯科特下一部《异形》电影的预告片。
This cancer cell is literally trying to claw its way out of the blood vessel in order to invade another part of the body.
癌症细胞是真的想要破血管而出，去入侵身体的其他部分。
In the last example I'm going to show you, we're trying to understand how the ear develops.
最后一个例子是我们想了解耳朵是怎么发育的。
In this case, we were completely upstaged by crawling neutrophils.
在这个例子中，缓缓移动的嗜中性白血球抢尽了镜头。
These immune cells are basically on patrol all the time. Basically, they don't get any time off.
这些免疫细胞时时刻刻都在巡逻。基本上，它们不休假。
They're working constantly to understand whether there's stranger danger, trying to understand whether there's an infection.
它们不停地工作，以了解是否有陌生人危险存在，试图了解是否有感染发生。
They're sensing the environment, constantly moving around.
它们在感测环境，不停地四处移动。
Now, we can watch these images and these movies in greater detail than has ever been possible before in our time up until now.
我们看到的这些图像和影片，细节细致度都是以前不可能达成的，直到现在才实现。
Now, as with all new technologies, new capabilities come with new challenges, and for us, the big one is how we handle the data.
有了这些新科技，新能力会带来新的挑战，对我们来说，其中一大挑战就是要如何处理数据。
These microscopes generate a ton of data. We generate anywhere from one to three terabytes of data per hour.
这些显微镜会产生出极大量的数据。产生的数据量在每小时1TB-3TB之间。
To put that into context: we're filling up two million floppy disks every hour, for our more experienced audience members.
用更清楚的方式来说：每小时可以装满两百万张软盘片，这是说给资深观众听的比喻。
Roughly equal, then, to about 500 DVDs,
大约等同于五百张DVD，
or to put things into better context for the Gen Z, that's about a dozen iPhone 11s that I'm filling up every hour.
或者，用Z世代能懂的方式来说，大约每小时能装满十多台iPhone 11s。
We have a ton of data. We need to find new ways to be able to visualize this.
我们有一大堆数据。我们得找新方法来呈现它们。
We need to be able to find new ways to be able to extract biologically meaningful information from these data sets.
我们得找新方法来从这些数据集中粹取出有生物意义的信息。
And more importantly, we want to make sure that we can put these advanced microscopes into the hands of scientists from all around the world.
更重要的是，我们希望能将这些先进的显微镜送到世界各地科学家的手中。
And we're giving the designs of these microscopes for free.
我们免费提供这些显微镜的设计。
But the key important part is, we need to collaborate even more to make an impact.
但关键点在于，我们必须要更团结，来产生影响力。
We're bringing together scientists who can develop new biological and chemical tools.
我们将能够开发生物化学新工具的科学家集结在一起。
We're working together with data scientists and instrumentation scientists to be able to build and manage the data.
我们和数据科学家及仪器科学家合作，来建造和管理这些数据。
And because we're giving these instruments out for free for all academic and nonprofits,
因为我们免费提供这些仪器给所有学术圈和非营利组织，
we're also building advanced imaging centers to house them,
因此我们也在建造先进的成像中心供他们使用，
to be able to bring together the group of people that are microscopists, that are the biologists and the computational people,
能组成一个团体，包括显微学家、生物学家及做计算的人，
and to build a team that's able to solve the types of problems that each of us individually cannot.
并成立一个团队，来解决我们个人无法解决的问题。
And thanks to these microscopes, the frontier of science is open again.
因为有这些显微镜，科学的前沿再次开放了。
So let's take a look together. Thank you.
咱们一起去看看吧。谢谢。
