This is a talk about sugar and cancer. I became interested in sugar when I was in college. Not this kind of sugar. It was the sugar that our biology professors taught us about in the context of the coating of your cells. Maybe you didn't know that your cells are coated with sugar. And I didn't know that, either, until I took these courses in college, but back then -- and this was in, let's just call it the 1980s -- people didn't know much about why our cells are coated with sugar. And when I dug through my notes, what I noticed I had written down is that the sugar coating on our cells is like the sugar coating on a peanut M and M. And people thought the sugar coating on our cells was like a protective coating that somehow made our cells stronger or tougher.
这是一个关于糖和癌症的演讲, 我是在上大学的时候 开始对糖感兴趣的。 我说的不是这种糖, 我说的是生物学教授教我们的 包裹在你细胞上的那种糖。 可能你不知道你的细胞 被糖蛋白包裹着。 我之前也不知道, 直到上大学的时候上了这些课, 但在当时—— 那是在,我们就说 1980年代吧—— 人们对于为什么细胞被 糖蛋白包裹所知甚少。 当我翻遍笔记本时, 注意到我曾经写下 我们细胞上的糖蛋白就像是 花生巧克力上的糖衣。 而人们曾以为 我们细胞上的糖蛋白 就像是一个保护层, 在某种程度上使细胞 更强大或者坚韧。
But we now know, many decades later, that it's much more complicated than that, and that the sugars on our cells are actually very complex. And if you could shrink yourself down to a little miniature airplane and fly right along the surface of your cells, it might look something like this -- with geographical features. And now, the complex sugars are these trees and bushes -- weeping willows that are swaying in the wind and moving with the waves. And when I started thinking about all these complex sugars that are like this foliage on our cells, it became one of the most interesting problems that I encountered as a biologist and also as a chemist. And so now we tend to think about the sugars that are populating the surface of our cells as a language. They have a lot of information stored in their complex structures.
但是几十年后的今天,我们知道 实际情况要复杂得多, 我们细胞上的糖蛋白 实际上非常复杂。 如果你能将自己缩小 塞进一个微型飞机, 然后沿着你的细胞表层飞行 就可能看到类似这样的景像—— 有着地理特征。 复杂的糖蛋白就是 里面的树林和树灌木—— 垂柳在风中摇摆, 随波而动。 当我开始思考 这些复杂的糖蛋白 就像是我们细胞上的植物时, 它成为了作为一个 生物学家和化学家的我 所遇到的最有趣的问题之一。 现在我们都倾向于将这些 占据我们细胞表层的糖蛋白 看成一种语言。 有许多的信息都存储在 它们复杂的结构中
But what are they trying to tell us? I can tell you that we do know some information that comes from these sugars, and it's turned out already to be incredibly important in the world of medicine.
但是它们想要告诉我们什么呢? 我可以告诉你我们的确知道 一些来自这些糖蛋白中的信息, 结果发现这些信息 对医学领域非常重要。
For example, one thing your sugars are telling us is your blood type. So your blood cells, your red blood cells, are coated with sugars, and the chemical structures of those sugars determine your blood type. So for example, I know that I am blood type O. How many people are also blood type O? Put your hands up. It's a pretty common one, so when so few hands go up, either you're not paying attention or you don't know your blood type, and both of those are bad.
例如,你细胞上的糖蛋白可以揭示 你们的血型。 你的血细胞,红血细胞 都被糖蛋白包裹着, 而这些糖蛋白的化学结构 决定了你的血型。 例如,我知道我的血型是O型, 在座的有多少人是O型血的? 请举起你们的手。 这是一个很常见的血型。 今天举手的不多, 要么你们没有注意听我说, 要么你们有些人不知道 自己的血型,这都不太好。
(Laughter)
(观众笑声)
But for those of you who share the blood type O with me, what this means is that we have this chemical structure on the surface of our blood cells: three simple sugars linked together to make a more complex sugar. And that, by definition, is blood type O.
但是对于这些跟我一样 是O型血的人来说, 就意味着在我们血细胞的表层 都有着这样的化学结构: 三个单糖连在一起 组成一个更复杂的糖。 按照定义,这就是O型血。
Now, how many people are blood type A? Right here. That means you have an enzyme in your cells that adds one more building block, that red sugar, to build a more complex structure. And how many people are blood type B? Quite a few. You have a slightly different enzyme than the A people, so you build a slightly different structure, and those of you that are AB have the enzyme from your mother, the other enzyme from your father, and now you make both of these structures in roughly equal proportions. And when this was figured out, which is now back in the previous century, this enabled one of the most important medical procedures in the world, which, of course, is the blood transfusion. And by knowing what your blood type is, we can make sure, if you ever need a transfusion, that your donor has the same blood type, so that your body doesn't see foreign sugars, which it wouldn't like and would certainly reject.
有多少人是A型血的? 这里有。 那意味着在你的细胞上有一种酶, 又增加了一个成分, 就是那个红色的单糖, 形成了一个更加复杂的结构。 那么B型血的又有多少人呢? 还不少。 你有一种与A型血的人略有不同的酶, 所以在细胞表面会 形成一种稍有不同的结构。 而那些AB型血的人, 从父母双方那里 同时获得了这两种酶, 形成两种结构,它们大约各占一半。 当这一点被发现以后—— 也就是上个世纪的事—— 这开启了世界上最重要的医疗手段之一, 那当然就是输血。 通过知道你的血型, 我们可以在你需要输血的时候 确保献血者跟你是同样的血型。 这样你的身体里就不会 出现不同的糖蛋白, 也就不会产生排斥。
What else are the sugars on the surface of your cells trying to tell us? Well, those sugars might be telling us that you have cancer. So a few decades ago, correlations began to emerge from the analysis of tumor tissue. And the typical scenario is a patient would have a tumor detected, and the tissue would be removed in a biopsy procedure and then sent down to a pathology lab where that tissue would be analyzed to look for chemical changes that might inform the oncologist about the best course of treatment. And what was discovered from studies like that is that the sugars have changed when the cell transforms from being healthy to being sick. And those correlations have come up again and again and again. But a big question in the field has been: Why? Why do cancers have different sugars? What's the importance of that? Why does it happen, and what can we do about it if it does turn out to be related to the disease process?
你细胞表层上的糖蛋白 还能告诉我们什么呢? 这些糖蛋白还可能告诉我们 你是否得了癌症。 数十年前, 对肿瘤组织进行分析的关系性 统计数据开始出现。 典型的情况是这样的: 一个病人身上被检测出肿瘤, 然后从有肿瘤的组织上取得切片, 送到病理实验室, 在那里对这个组织上的 化学变化进行分析, 以便告知肿瘤医师最好的治疗方案。 而人们从那样的研究中所发现的是, 当细胞由健康转向病态时, 它表层上的糖蛋白发生了变化。 这些分析关系性 一次又一次的被提出来。 但是在这个领域有一个 大的问题,那就是:为什么? 为什么癌变的细胞有不同的糖蛋白? 它的重要性是什么? 为什么它会发生, 如果结果证明它跟病变过程 有关联,那么我们又能做些什么?
So, one of the changes that we study is an increase in the density of a particular sugar that's called sialic acid. And I think this is going to be one of the most important sugars of our times, so I would encourage everybody to get familiar with this word. Sialic acid is not the kind of sugar that we eat. Those are different sugars. This is a kind of sugar that is actually found at certain levels on all of the cells in your body. It's actually quite common on your cells. But for some reason, cancer cells, at least in a successful, progressive disease, tend to have more sialic acid than a normal, healthy cell would have. And why? What does that mean? Well, what we've learned is that it has to do with your immune system.
我们研究的这些变化之一 是某种特定糖蛋白 密度的增加, 这种糖蛋白叫做唾液酸。 我觉得它将成为我们这个时代 最重要的糖蛋白之一, 所以我会鼓励大家去熟悉这个词语。 唾液酸不是那种 我们用来吃的糖, 它们是不同的糖。 这是一种在可以在你身体的 每一个细胞上都能找到的糖蛋白。 实际上它在你的细胞上中很常见。 但出于某种原因, 癌细胞,至少在一场成功的 进行性的病变中 常常比正常、健康的细胞 含有更多的唾液酸。 为什么? 这意味着什么? 我们所了解到, 这与你的免疫系统有关。
So let me tell you a little bit about the importance of your immune system in cancer. And this is something that's, I think, in the news a lot these days. You know, people are starting to become familiar with the term "cancer immune therapy." And some of you might even know people who are benefiting from these very new ways of treating cancer. What we now know is that your immune cells, which are the white blood cells coursing through your bloodstream, protect you on a daily basis from things gone bad -- including cancer. And so in this picture, those little green balls are your immune cells, and that big pink cell is a cancer cell. And these immune cells go around and taste all the cells in your body. That's their job. And most of the time, the cells taste OK.
让我给你们再讲一点关于 免疫系统在对抗癌症中的 重要性。 我想,这也是目前 在新闻中经常出现的内容。 人们正在开始熟悉 “癌症免疫疗法”这个术语。 你们当中有人可能甚至认识 一些从这些非常新的癌症治疗 手段中受益的人。 我们现在知道是你的免疫细胞, 也就是在血流中穿梭的白血细胞 在保护我们在日常中免受伤害—— 包括癌症。 在这张图中, 这些绿色的小球 是你的免疫细胞, 粉红色的大球 是一个癌症细胞。 这些免疫细胞会四处活动, 尝遍你身上的所有细胞, 那是它们的工作。 而大多数时间, 这些细胞尝起来都没有问题,
But once in a while, a cell might taste bad. Hopefully, that's the cancer cell, and when those immune cells get the bad taste, they launch an all-out strike and kill those cells. So we know that. We also know that if you can potentiate that tasting, if you can encourage those immune cells to actually take a big old bite out of a cancer cell, you get a better job protecting yourself from cancer every day and maybe even curing a cancer. And there are now a couple of drugs out there in the market that are used to treat cancer patients that act exactly by this process. They activate the immune system so that the immune system can be more vigorous in protecting us from cancer.
但偶尔会有一个细胞 尝起来不正常。 希望那就是癌症细胞, 当这些免疫细胞 尝到不正常的细胞时, 它们会全力攻击消灭这些细胞。 我们知道这一点。 我们还知道如果 你能强化这种品尝, 如果你能鼓励这些免疫细胞 去大力吞噬一个癌细胞, 你就可以更好的保护自己 免受癌症的侵扰, 甚至还有可能治愈癌症。 现在市场上有一些 治疗癌症的药, 正是通过这个过程起作用的。 它们能够激活免疫系统, 使免疫系统在保护我们不受癌症侵扰时 更加的有活力。
In fact, one of those drugs may well have spared President Jimmy Carter's life. Do you remember, President Carter had malignant melanoma that had metastasized to his brain, and that diagnosis is one that is usually accompanied by numbers like "months to live." But he was treated with one of these new immune-stimulating drugs, and now his melanoma appears to be in remission, which is remarkable, considering the situation only a few years ago. In fact, it's so remarkable that provocative statements like this one: "Cancer is having a penicillin moment," people are saying, with these new immune therapy drugs. I mean, that's an incredibly bold thing to say about a disease which we've been fighting for a long time and mostly losing the battle with. So this is very exciting.
事实上,这些药物中的一种 可能已经延长了前总统 吉米·卡特的生命。 你们记得吗,卡特总统 患有恶性黑色素瘤, 并且癌细胞转移到了脑部 而那种诊断通常还伴有 “只剩下几个月了”这样的描述。 但是他使用了一种 免疫刺激类的药物, 现在他的癌症出现了好转, 跟几年前情况相比 这是非常了不起的。 正因为这样非凡的进步, 所以出现了一些豪言壮志: “有了这些新的免疫疗法药物, 癌症正在被消灭。” 我的意思是,对于一个我们已经与之 斗争了很长时间, 并以失败居多的疾病而言 说出这样的话是一件很有勇气的事。 这是非常令人激动的。
Now what does this have to do with sugars? Well, I'll tell you what we've learned. When an immune cell snuggles up against a cancer cell to take a taste, it's looking for signs of disease, and if it finds those signs, the cell gets activated and it launches a missile strike and kills the cell. But if that cancer cell has a dense forest of that sugar, sialic acid, well, it starts to taste pretty good. And there's a protein on immune cells that grabs the sialic acid, and if that protein gets held at that synapse between the immune cell and the cancer cell, it puts that immune cell to sleep. The sialic acids are telling the immune cell, "Hey, this cell's all right. Nothing to see here, move along. Look somewhere else." So in other words, as long as our cells are wearing a thick coat of sialic acid, they look fabulous, right? It's amazing. And what if you could strip off that coat and take that sugar away? Well, your immune system might be able to see that cancer cell for what it really is: something that needs to be destroyed.
那么这又跟糖蛋白有什么关系呢? 下面我就会告诉你们我们的发现。 当一个免疫细胞裹住 一个癌细胞去尝它时, 它是在寻找疾病的信号, 如果它发现了这些信号, 那么它就会被激活, 并发起猛烈的攻击去消灭癌细胞。 但是如果癌细胞拥有丰富的 那种糖蛋白,唾液酸, 那么它会尝起来很好。 免疫细胞中有一种蛋白质 可以抓取唾液酸, 如果这种蛋白质被困在 免疫细胞和癌细胞之间的突触中, 就会使得免疫细胞进入休眠状态。 唾液酸在告诉免疫细胞, “这个细胞没问题, 这里没有什么,继续往前走, 去其它地方看看吧。” 换句话说, 只要我们的细胞被一层 厚厚的唾液酸包裹着, 它们看起来就是极好的,对吧? 真的很神奇。 如果你能剥开这层外衣, 除去那些糖蛋白会怎么样? 那么你的免疫系统 也许会看到癌细胞的真面目: 这是一些需要被消灭的家伙。
And so this is what we're doing in my lab. We're developing new medicines that are basically cell-surface lawnmowers -- molecules that go down to the surface of these cancer cells and just cut off those sialic acids, so that the immune system can reach its full potential in eliminating those cancer cells from our body.
而这也是我们正在实验室里 所进行的研究。 我们正在研发新药, 相当于是细胞表层的割草机—— 让药物微粒进入癌细胞表层, 除去这些唾液酸, 这样就能让免疫系统 发挥全部潜能, 消灭我们体内的癌细胞。
So in closing, let me just remind you again: your cells are coated with sugars. The sugars are telling cells around that cell whether the cell is good or bad. And that's important, because our immune system needs to leave the good cells alone. Otherwise, we'd have autoimmune diseases. But once in a while, cancers get the ability to express these new sugars. And now that we understand how those sugars mesmerize the immune system, we can come up with new medicines to wake up those immune cells, tell them, "Ignore the sugars, eat the cell and have a delicious snack, on cancer."
最后, 让我再提醒你们一次: 你的细胞被糖蛋白包裹着。 这些糖蛋白可以告诉 这个细胞周围的其它细胞 这个细胞是好还是坏。 而这是非常重要的, 因为我们需要免疫系统 不要去打扰正常的细胞, 否则我们就会患上 自身免疫系统疾病。 但是有时癌症会获得 表达这些新糖蛋白的能力, 我们现在知道 这些糖蛋白是如何记住免疫系统的, 可以由此研发出新药 去唤醒这些免疫细胞, 告诉它们,“别管这些糖蛋白, 吞掉这些癌细胞, 享受这些可口的小吃。”
Thank you.
谢谢。
(Applause)
(观众掌声)