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.
這是一場關於糖和癌症的演說。 我在大學時對糖產生了興趣。 不是這種糖。 是生物學教授上課時教的那種糖, 包裹著你的細胞的那種糖。 也許你不知道你的細胞 被糖所包裹著。 我本來也不知道, 到大學時修了這些課程才學到。 但是當時── 那時是……我們姑且 就說是 1980 年代吧── 人們並不知道為什麼 我們的細胞會被糖所包裹。 而當我翻閱我的筆記時, 我發現我記下的是: 細胞上所包裹的糖, 就像是花生 M&M 豆 外面的糖衣。 人們認為,包裹著我們細胞的糖衣 就像是一層保護塗層, 以某種方式讓我們的細胞 更強壯或更堅韌。
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.
但幾十年之後的現在, 我們知道答案並沒有這麼簡單, 包裹我們細胞的糖其實非常複雜。 如果你把自己縮小成一架迷你飛機, 然後沿著你的細胞表面飛行, 你可能會看到這樣的景象── 有著地理特徵。 複雜的糖就像這些樹和灌木── 隨風搖動、隨波移動 的垂柳, 當我開始思考這些複雜的糖, 它們就像是我們細胞上的葉子, 對於我這個生物學家兼化學家來說, 它變成了我遇過最有趣的問題之一。 現在我們傾向將佈滿在 細胞的表面上的糖視為 是一種語言。 有大量的訊息儲存在 它們複雜的結構中。
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.
但它們想要告訴我們什麼呢? 我可以告訴各位,我們確實知道一些 來自這些糖的訊息, 且這些訊息對於醫學界的重要性 也已經被證明。
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,你的糖能告訴 我們的其中一項資訊 是你的血型。 你的血細胞,你的紅血球細胞, 是被糖所包裹住的, 而這些糖的化學結構 決定了你的血型。 比如,我知道我的血型是 O 型。 有多少人也是 O 型? 請舉手。 這種血型很常見, 舉手的人這麼少, 若不是你們沒認真聽, 就是你們不知道自己的血型, 兩種情況都不太好。
(Laughter)
(笑聲)
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.
不過如果你和我一樣是 O 型, 這意味著我們的血細胞表面的 化學結構是這樣的: 三個單醣連在一起, 形成一個更複雜的糖。 這就是 O 型的定義。
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.
有多少人的血型是 A 型? 在這裡。 這意味著你的細胞裡有一種酶, 它會增加一塊積木, 也就是那紅色糖, 來建立更複雜的結構。 有多少人的血型是 B 型? 還不少。 你們的酶和 A 型的人略有不同, 所以建出來的結構也略有不同, 至於 AB 型的人, 則有分別來自母親和父親的酶, 你所建立的這兩種結構, 在比例上是大約各半。 直到上個世紀,這個現象 才被發現, 因為它,才會有世界上 最重要的醫療手術之一, 當然,也就是輸血。 知道了自己的血型, 當你需要輸血時,我們就可以確保 你的捐血者和你有同樣的血型, 這樣你的身體才不會發現 有外來的糖進入, 它不喜歡外來的糖,一定會排斥。
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?
你細胞表面的糖, 還能告訴我們什麼資訊? 那些糖還可能還可以 告訴我們你得了癌症。 幾十年前, 針對腫瘤組織所做的分析, 開始發現了相關性。 最典型的情況是: 當一名患者被檢測出腫瘤, 會進行活組織切片來切除組織, 該組織接著會被送到病理實驗室, 在那裡進行分析,尋找化學變化, 這些變化或許能幫助 腫瘤學家斷定最適合的療程。 這類研究的發現是, 當細胞由健康轉成病態時, 糖也會發生變化。 而這些相關性一而再、 再而三地出現。 但實做上的一個大問題是:為什麼? 為何癌症會有不同的糖? 其重要性何在? 它為何發生? 若它真的和疾病的進程有關, 我們又能做什麼呢?
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.
我們所研究的各項變化之一, 就是一種特定糖的密度增加, 這種糖叫「唾液酸」。 我認為它將是我們這個時代 最重要的糖其中的一種, 所以我建議大家都熟悉一下這個詞。 唾液酸不是我們吃的那種糖。 那些是不同的糖。 實際上,在你體內的所有細胞上, 都可找到一定量的這種糖。 它在你的細胞上其實很常見。 但由於某種原因, 癌細胞……至少在疾病 成功進展的情況下, 癌細胞的唾液酸量通常會多於 正常健康細胞的唾液酸量。 為什麼呢? 這意味著什麼? 我們所知道的是, 這和你的免疫系統有關。
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.
所以,讓我先告訴各位 免疫系統在癌症中的重要性。 我想,這陣子在新聞中 也有不少相關報導。 人們開始越來越熟悉這個詞: 「癌症免疫治療」。 甚至在座可能就有人認識 這些新式癌症療法的受益者。 我們現在知道,你的免疫細胞, 也就是在你血液中 流動的白血球細胞, 每天保護著你,避免壞事發生── 包括癌症。 在這張圖片中, 這些綠色的球體就是你的免疫細胞, 而那個粉紅色大細胞則是個癌細胞。 這些免疫細胞四處巡邏, 品嚐你體內的所有細胞。 那是它們的職責。 大多數情況下,細胞嚐起來沒問題。
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.
但偶爾,某個細胞 可能嚐起來不太對。 但願那就是癌細胞, 當這些免疫細胞嚐到不對的味道, 它們會傾巢而出,殺死這些細胞。 我們知道這些。 我們也知道,如果你能 賦與那種品嚐行為力量, 如果你能鼓勵那些免疫細胞狠狠地咬 癌細胞一大口, 你每天就更能保護自己免於癌症, 甚至還可能治癒癌症。 目前市面上有幾種用來 治療癌症病人的藥, 正是利用這個過程來產生作用。 它們會活化免疫系統, 讓免疫系統更強而有力, 保護我們免於癌症。
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.
事實上,這些藥物的其中一種, 很可能救了總統吉米卡特的命。 記得嗎,卡特總統 得了惡性黑色素瘤, 癌細胞轉移到他的腦部, 那種診斷通常還會帶著一個數字, 「剩幾個月可活」。 但是他接受了一種 免疫系統刺激藥物的治療, 現在他的黑色素瘤顯然已經緩解, 這結果很了不起, 畢竟他幾年前的狀況還是非常糟的。 事實上,這結果了不起到 引發了這段陳述: 「癌症也有了盤尼西林的時刻」, 人們對於這些新的 免疫治療藥物如是說。 用這樣的方式形容一種我們長年對抗 且通常都打不贏的疾病, 是相當大膽的。 所以這很讓人興奮。
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.
那麼,這與糖有什麼關係呢? 讓我告訴各位我們目前所知道的。 當一個免疫細胞靠向一個 癌細胞,去品嚐它的味道時, 它是在尋找疾病的徵兆, 如果它能找到這種徵兆, 這細胞就會被活化, 發動飛彈攻擊,殺死癌細胞。 但若癌細胞上覆蓋了一層由那種糖, 也就是唾液酸,所組成的茂密樹林, 那它嚐起來的味道就會是好的。 在免疫細胞上有個蛋白質 會抓住唾液酸, 如果那蛋白質被卡在免疫細胞 和癌症細胞之間的突觸上, 就會讓免疫細胞進入睡眠。 如果唾液酸告訴免疫細胞說: 「嘿,這個細胞沒問題。 沒什麼好看的,走開。 去看其他地方。」 換言之, 只要我們的細胞覆蓋著 很厚一層的唾液酸, 它們看起來就很好,對嗎? 那很驚人。 如果你能夠剝除包裹的外層, 把糖給去除掉呢? 那麼,你的免疫系統 就有可能看見癌症細胞的真面目: 該被摧毀的目標。
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.
我們在我的實驗室中就在做這個。 我們正在開發新的藥, 基本上可以說是 細胞表面用的除草機, 分子會前往這些癌症細胞的表面, 把那些唾液酸通通除掉, 這麼一來,免疫系統就能發揮全力, 消滅掉我們身體中的癌症細胞。
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."
最後結尾, 讓我再次提醒各位: 你們的細胞都被糖所包裹著。 糖會告訴那細胞附近的其他細胞 那細胞是好的或是壞的。 那很重要, 因為我們的免疫系統 得要放過好的細胞。 不然我們就會有自體免疫疾病了。 但偶爾,癌症有能力可以 展現出這些新的糖。 現在我們知道 那些糖是如何迷惑免疫系統的, 我們就能做出新的藥 來喚醒那些免疫細胞, 告訴它們:「別理會那些糖, 去吃那細胞, 在癌症上面吃頓美味的點心。」
Thank you.
謝謝大家。
(Applause)
(掌聲)