TED：病毒如何幫助我們解決抗生素危機 ？
雙語演講稿
Take a moment and think about a virus. What comes to your mind? An illness? A fear? Probably something really unpleasant. And yet, viruses are not all the same. It's true, some of them cause devastating disease. But others can do the exact opposite -- they can cure disease. These viruses are called "phages."
花一點時間， 去想想病毒。你腦海中浮現的是什麼？一種疾病？一種恐懼？可能是很不愉悅的東西。但是，病毒並不是全都一樣。的確，有些病毒會造成 很有破壞性的疾病。但有些其他病毒的作用 完全相反——它們能治癒疾病。這些病毒叫做「噬菌體」。
Now, the first time I heard about phages was back in 2013. My father-in-law, who's a surgeon, was telling me about a woman he was treating. The woman had a knee injury, required multiple surgeries, and over the course of these, developed a chronic bacterial infection in her leg. Unfortunately for her, the bacteria causing the infection also did not respond to any antibiotic that was available. So at this point, typically, the only option left is to amputate the leg to stop the infection from spreading further. Now, my father-in-law was desperate for a different kind of solution, and he applied for an experimental, last-resort treatment using phages. And guess what? It worked. Within three weeks of applying the phages, the chronic infection had healed up, where before, no antibiotic was working. I was fascinated by this weird conception: viruses curing an infection. To this day, I am fascinated by the medical potential of phages. And I actually quit my job last year to build a company in this space.
我第一次聽到噬菌體， 是在 2013 年。我的岳父是外科醫生， 他告訴我，他在治療一位女士。這位女士有膝傷， 需要進行多個手術， 在這些手術的過程中， 她的腳發生了 一種慢性的細菌性感染。對她來說，很不幸， 造成感染的細菌對於可取得的 抗生素藥物都沒有反應。所以，在這個時點，通常， 唯一的選擇就是將那條腿截肢， 來阻止感染進一步散播。我的岳父非常希望能找到 一種不同的解決方案， 他申請用噬菌體的實驗性治療， 這是他能用的最後手段。猜猜如何？治療見效了。在採用了噬菌體之後的三週內， 慢性感染就治癒了， 之前，任何抗生素都沒有用。這個怪異的概念讓我很著迷， 用病毒來治癒感染。至今，噬菌體的醫療潛力 仍然讓我著迷。去年，我真的辭掉了我的工作， 為此成立了一間公司。
Now, what is a phage? The image that you see here was taken by an electron microscope. And that means what we see on the screen is in reality extremely tiny. The grainy thing in the middle with the head, the long body and a number of feet -- this is the image of a prototypical phage. It's kind of cute.
噬菌體是什麼？各位看到的影像是用 電子顯微鏡拍攝的。意思就是，我們在螢幕上 看到的東西，實際上非常小。中間的粒狀物有個頭， 有很長的身體， 有好幾隻腳—— 典型的噬菌體就長這個樣子。還蠻可愛的。
Now, take a look at your hand. In our team, we've estimated that you have more than 10 billion phages on each of your hands. What are they doing there?
看看你們的手。我們的團隊估計， 在每一隻手上， 都有超過一百億個噬菌。它們在那裡做什麼？
Well, viruses are good at infecting cells. And phages are great at infecting bacteria. And your hand, just like so much of our body, is a hotbed of bacterial activity, making it an ideal hunting ground for phages. Because after all, phages hunt bacteria. It's also important to know that phages are extremely selective hunters. Typically, a phage will only infect a single bacterial species. So in this rendering here, the phage that you see hunts for a bacterium called Staphylococcus aureus, which is known as MRSA in its drug-resistant form. It causes skin or wound infections.
嗯，病毒很擅長感染細胞。而噬菌體則很擅長感染細菌。而你們的手， 就像我們大部分的身體， 是細菌活動的溫床， 對噬菌體來說， 就是打獵最理想的地方。畢竟，細菌是噬菌體的獵物。還要知道一件重要的事， 噬菌體是非常挑的獵人。一般來說，一種噬菌體只會 感染一種細菌物種。所以在這張圖上，你們看到的噬菌體 獵取的目標是一種叫做 金黃色葡萄球菌的細菌， 它的抗藥型縮寫為 MRSA。它會造成皮膚或傷口的感染。
The way the phage hunts is with its feet. The feet are actually extremely sensitive receptors, on the lookout for the right surface on a bacterial cell. Once it finds it, the phage will latch on to the bacterial cell wall and then inject its DNA. DNA sits in the head of the phage and travels into the bacteria through the long body. At this point, the phage reprograms the bacteria into producing lots of new phages. The bacteria, in effect, becomes a phage factory. Once around 50-100 phages have accumulated within the bacteria cell, the phages are then able to release a protein that disrupts the bacteria cell wall. As the bacteria bursts, the phages move out and go on the hunt again for a new bacteria to infect.
噬菌體獵取的方式是用它的腳。這些腳其實是非常敏感的接受器， 負責留心細菌細胞上 有沒有對的表面。一旦找到對的表面， 噬菌體就會插上細菌的細胞壁， 接著注入它的 DNA。DNA 存在於噬菌體的頭部， 透過長長的身體，傳輸到細菌中。此時，噬菌體就會改變 細菌的 DNA 編碼， 來產生出很多新噬菌體。實際上，細菌就變成了 噬菌體生產工廠。等到細菌細胞中累積有 大約 50~100 個噬菌體時， 噬菌體就能夠釋放出一種蛋白質， 導致細菌的細胞壁裂開。當細菌爆裂開，噬菌體就會跑出來， 繼續去打獵，尋找並感染新的細菌。
Now, I'm sorry, this probably sounded like a scary virus again. But it's exactly this ability of phages -- to multiply within the bacteria and then kill them -- that make them so interesting from a medical point of view. The other part that I find extremely interesting is the scale at which this is going on. Now, just five years ago, I really had no clue about phages. And yet, today I would tell you they are part of a natural principle. Phages and bacteria go back to the earliest days of evolution. They have always existed in tandem, keeping each other in check. So this is really the story of yin and yang, of the hunter and the prey, at a microscopic level. Some scientists have even estimated that phages are the most abundant organism on our planet. So even before we continue talking about their medical potential, I think everybody should know about phages and their role on earth: they hunt, infect and kill bacteria.
對不起，這可能聽起來 又像是駭人的病毒。但正是噬菌體的這種能力—— 在細菌裡面繁殖並殺死細菌—— 讓噬菌體從醫學的觀點 來看十分有趣。還有另一部分， 我也覺得非常有趣， 就是這個現象發生的規模。五年前，我對噬菌體一無所知。但，現今，我會告訴各位， 它們是自然法則的一部分。噬菌體和細菌可以 追溯回演化的最早期。它們一直一前一後地存在， 彼此相互制衡。所以，這其實是一個陰和陽、 獵人和獵物的顯微級故事。有些科學家甚至估計， 噬菌體是地球上最大量的有機體。所以，在我們繼續談 它們的醫療潛力之前， 我想大家應該要了解一下噬菌體 及它們在地球上的角色：它們會獵取、感染，並殺死細菌。
Now, how come we have something that works so well in nature, every day, everywhere around us, and yet, in most parts of the world, we do not have a single drug on the market that uses this principle to combat bacterial infections? The simple answer is: no one has developed this kind of a drug yet, at least not one that conforms to the Western regulatory standards that set the norm for so much of the world. To understand why, we need to move back in time.
為什麼在大自然中 我們每天身邊都有著 運作得這麼好的法則， 但在世界上大部分的地方， 市場上都沒有任何藥物 使用這項法則來對抗細菌感染？答案很簡單：還沒有人開發出這種藥物， 至少沒有發明出符合 西方法規標準的藥物， 畢竟西方標準是世界主要的基準。若要了解為什麼， 我們得要回到過去。
This is a picture of Félix d'Herelle. He is one of the two scientists credited with discovering phages. Except, when he discovered them back in 1917, he had no clue what he had discovered. He was interested in a disease called bacillary dysentery, which is a bacterial infection that causes severe diarrhea, and back then, was actually killing a lot of people, because after all, no cure for bacterial infections had been invented. He was looking at samples from patients who had survived this illness. And he found that something weird was going on. Something in the sample was killing the bacteria that were supposed to cause the disease.
這位是費里斯·代列爾。他是發現噬菌體的兩位科學家之一。不過，當他在 1917 年 發現噬菌體時， 他完全不知道他發現了什麼。他對一種疾病很感興趣， 叫做細菌性痢疾， 它是一種細菌感染， 會造成嚴重腹瀉， 那時造成了很多死亡。因為，畢竟還沒有發明出 能治癒細菌感染的解藥。他檢視的樣本來自得過這種疾病 但存活下來的病人。他發現有很奇怪的現象發生。在樣本中有某樣東西在殺死 造成疾病的那些細菌。
To find out what was going on, he did an ingenious experiment. He took the sample, filtered it until he was sure that only something very small could have remained, and then took a tiny drop and added it to freshly cultivated bacteria. And he observed that within a number of hours, the bacteria had been killed. He then repeated this, again filtering, taking a tiny drop, adding it to the next batch of fresh bacteria. He did this in sequence 50 times, always observing the same effect. And at this point, he made two conclusions. First of all, the obvious one: yes, something was killing the bacteria, and it was in that liquid. The other one: it had to be biologic in nature, because a tiny drop was sufficient to have a huge impact. He called the agent he had found an "invisible microbe" and gave it the name "bacteriophage," which, literally translated, means "bacteria eater." And by the way, this is one of the most fundamental discoveries of modern microbiology. So many modern techniques go back to our understanding of how phages work -- in genomic editing, but also in other fields. And just today, the Nobel Prize in chemistry was announced for two scientists who work with phages and develop drugs based on that.
為了瞭解發生了什麼事， 他做了一項很聰明的實驗。他把樣本拿來過濾， 直到他能確保留下來的東西 都是非常小的東西， 接著取一小滴的樣本， 加入新鮮培養出來的細菌中。據他觀察，在幾小時之內， 細菌都被殺死了。他接著重覆這個實驗， 同樣地，過濾，再取一小滴， 加到下一批新鮮細菌上。他依序做了五十次， 總是觀察到同樣的效果。此時，他做出兩項結論。首先，很明顯的是：是的， 有某樣東西會殺死細菌， 且就存在於那液體中。另一項結論：它一定是 大自然中的生物， 因為只要一小滴， 就足以產生很大的影響。他把他發現的這種媒介稱為 「看不見的微生物」， 取名為「bacteriophage」， 字面上直譯的意思 就是「噬菌體」。順便一提，這是現代生物學中 最重要的基礎發現之一。好多現代技術都是建立在我們對於 噬菌體運作方式的瞭解之上—— 基因編輯以及其他領域。今天，諾貝爾化學獎公佈了， 得獎的兩位科學家做的是 噬菌體的研究並應用來開發藥品。
Now, back in the 1920s and 1930s, people also immediately saw the medical potential of phages. After all, albeit invisible, you had something that reliably was killing bacteria. Companies that still exist today, such as Abbott, Squibb or Lilly, sold phage preparations. But the reality is, if you're starting with an invisible microbe, it's very difficult to get to a reliable drug. Just imagine going to the FDA today and telling them all about that invisible virus you want to give to patients. So when chemical antibiotics emerged in the 1940s, they completely changed the game. And this guy played a major role.
在 1920 和 1930 年代時， 大家也馬上就看出了 噬菌體在醫療上的潛力。畢竟，儘管看不見， 總是可以依靠它來殺死細菌。現今仍然存在的公司， 如亞培、施貴寶、禮來， 都販售噬菌體製劑。但，現實是，如果你從 看不見的微生物開始著手， 要做出可靠的藥品是很困難的。想像一下就知道了， 現今如果要去食品及藥物管理局， 告訴他們你想要給病人 用一種看不見的病毒。所以，在 1940 年代， 當化學抗生素出現時， 它們完全改變了這個遊戲。這個傢伙扮演了重要的角色。
This is Alexander Fleming. He won the Nobel Prize in medicine for his work contributing to the development of the first antibiotic, penicillin. And antibiotics really work very differently than phages. For the most part, they inhibit the growth of the bacteria, and they don't care so much which kind of bacteria are present. The ones that we call broad-spectrum will even work against a whole bunch of bacteria out there. Compare that to phages, which work extremely narrowly against one bacterial species, and you can see the obvious advantage.
他是亞歷山大弗萊明， 得過諾貝爾醫學獎， 他因為開發出最早的抗生素 盤尼西林而得獎。抗生素的運作方式和噬菌體差很多。大多數的情況下， 抗生素是抑制細菌的成長， 它們並不太在乎 出現的細菌是哪一種細菌。有一種抗生素叫做廣效抗生素， 它甚至會對抗一大堆細菌。相較之下，噬菌體只會針對 一種細菌物種，作用範圍很狹窄， 它的優勢十分明顯。
Now, back then, this must have felt like a dream come true. You had a patient with a suspected bacterial infection, you gave him the antibiotic, and without really needing to know anything else about the bacteria causing the disease, many of the patients recovered. And so as we developed more and more antibiotics, they, rightly so, became the first-line therapy for bacterial infections. And by the way, they have contributed tremendously to our life expectancy. We are only able to do complex medical interventions and medical surgeries today because we have antibiotics, and we don't risk the patient dying the very next day from the bacterial infection that he might contract during the operation.
在當時，感覺大概 就像是夢想成真一樣。你的病人有疑似細菌感染， 你給他服用抗生素， 對於造成疾病的那種細菌， 你並不需要知道任何資訊， 許多病人復元了。隨著我們開發出越來越多的抗生素， 它們很理所當然地成為了 對抗細菌感染的第一線治療。順便一提，對於我們的壽命延長， 它們也有極大的貢獻。我們現今能夠做到複雜的 醫療干預以及醫療手術， 都是因為我們有抗生素， 不用再擔心病人 在手術過程中受到 細菌感染，導致隔天死亡。
So we started to forget about phages, especially in Western medicine. And to a certain extent, even when I was growing up, the notion was: we have solved bacterial infections; we have antibiotics. Of course, today, we know that this is wrong. Today, most of you will have heard about superbugs. Those are bacteria that have become resistant to many, if not all, of the antibiotics that we have developed to treat this infection.
所以，我們開始忘卻了噬菌體， 特別是在西藥的領域中。而且忘卻程度已經到了， 我成長過程中聽到的觀念是：我們已經解決了細菌感染， 我們有抗生素。當然，現今我們知道這是錯的。現今，大部分人都聽過超級細菌。這些細菌變成已經能夠抵抗 所有或大部分我們為了治療感染 所開發出來的抗生素。
How did we get here? Well, we weren't as smart as we thought we were. As we started using antibiotics everywhere -- in hospitals, to treat and prevent; at home, for simple colds; on farms, to keep animals healthy -- the bacteria evolved. In the onslaught of antibiotics that were all around them, those bacteria survived that were best able to adapt. Today, we call these "multidrug-resistant bacteria." And let me put a scary number out there. In a recent study commissioned by the UK government, it was estimated that by 2050, ten million people could die every year from multidrug-resistant infections. Compare that to eight million deaths from cancer per year today, and you can see that this is a scary number.
我們是怎麼走到這一步的？我們沒有自己想像的那麼聰明。當我們開始到處使用抗生素—— 在醫院用來做治療和預防；在家中用來治感冒；在農場用來維持動物的健康—— 細菌演化了。細菌到處受到抗生素的猛攻， 存活下來的細菌是適應力最強的。現今，我們稱這些細菌為 「多重抗藥性細菌」。讓我給各位看一個可怕的數字。英國政府近期委任進行的一項研究 估計到了 2050 年， 每年會有一千萬人因為 多重抗藥性感染而死。現今每年死於癌症的人數 是八百萬，相比之下， 就看得出那個數字有多可怕。
But the good news is, phages have stuck around. And let me tell you, they are not impressed by multidrug resistance.
但好消息是，我們還有噬菌體。讓我告訴各位，它們不覺得 多重抗藥性有什麼了不起的。
(Laughter)
（笑聲）
They are just as happily killing and hunting bacteria all around us. And they've also stayed selective, which today is really a good thing. Today, we are able to reliably identify a bacterial pathogen that's causing an infection in many settings. And their selectivity will help us avoid some of the side effects that are commonly associated with broad-spectrum antibiotics. But maybe the best news of all is: they are no longer an invisible microbe. We can look at them. And we did so together before. We can sequence their DNA. We understand how they replicate. And we understand the limitations. We are in a great place to now develop strong and reliable phage-based pharmaceuticals.
它們就是很樂意獵殺掉 我們周圍的細菌。且它們也保有選擇性， 在現今這是一件好事。現今，在許多情況下， 我們可以很可靠地 辨視出造成感染的病原體。而它們的選擇性能夠協助我們避開 廣效抗生素常見的一些副作用。但，也許最好的消息是：它們不再是看不見的微生物。我們能夠看見它們。我們剛剛也一起看過了。我們能夠將它們的 DNA 定序。我們瞭解它們如何複製。我們瞭解限制。現在我們擁有好的技術和資源來開發 強效且可靠的噬菌體藥品。
And that's what's happening around the globe. More than 10 biotech companies, including our own company, are developing human-phage applications to treat bacterial infections. A number of clinical trials are getting underway in Europe and the US. So I'm convinced that we're standing on the verge of a renaissance of phage therapy. And to me, the correct way to depict the phage is something like this.
那也是現在全球正在做的事。超過十間生物科技公司， 包括我們自己的公司， 都在開發人類噬菌體的應用， 來治療細菌感染。在歐洲以及美國已經有許多 臨床試驗在進行中。所以，我深信我們已經 很接近噬菌體治療的復興。對我來說，描述噬菌體的 正確方式是這樣。
To me, phages are the superheroes that we have been waiting for in our fight against multidrug-resistant infections.
對我來說，噬菌體是我們 一直在等待的超級英雄， 來協助我們對抗多重抗藥性感染。
So the next time you think about a virus, keep this image in mind. After all, a phage might one day save your life.
所以，下次當你想到病毒時， 別忘了這張圖。畢竟，也許有一天， 噬菌體會救你一命。
Thank you.
謝謝。
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