So, embryonic stem cells are really incredible cells. They are our body's own repair kits, and they're pluripotent, which means they can morph into all of the cells in our bodies. Soon, we actually will be able to use stem cells to replace cells that are damaged or diseased.
在人的身體裡有一種神奇的細胞 叫做胚胎幹細胞 這就像是身體裡的修補工具 而且這些細胞具有多樣的潛能, 可以變成我們身體裡的各種細胞 在不久的將來, 我們應該可以利用這些幹細胞 來替換身體裡損壞了的或是生病了的細胞
But that's not what I want to talk to you about, because right now there are some really extraordinary things that we are doing with stem cells that are completely changing the way we look and model disease, our ability to understand why we get sick, and even develop drugs. I truly believe that stem cell research is going to allow our children to look at Alzheimer's and diabetes and other major diseases the way we view polio today, which is as a preventable disease.
不過呢, 今天我所要談的不是這個方向 今天要談的是關於 我們正在進行的關於幹細胞的特殊研究 這將會完全改變 我們看待與學習疾病的方式 以及我們對於為什麼人會生病的研究 甚至於是藥物的開發 我深信幹細胞的研究, 可以讓我們的下一代 面對阿茲海默症(老年癡呆)或是糖尿病這些重大疾病時 就如同我們現在面對脊髓灰質炎(小兒麻痺)一般 能有預防的方法
So here we have this incredible field, which has enormous hope for humanity, but much like IVF over 35 years ago, until the birth of a healthy baby, Louise, this field has been under siege politically and financially. Critical research is being challenged instead of supported, and we saw that it was really essential to have private safe haven laboratories where this work could be advanced without interference. And so, in 2005, we started the New York Stem Cell Foundation Laboratory so that we would have a small organization that could do this work and support it.
在幹細胞這個奇妙的研究領域 有著人類的許多新希望 但是就如同試管嬰兒這個研究領域 一直到了35年前 第一個健康的試管嬰兒 露薏絲 的誕生 (1978.07.25) 才脫離了政治上與經費上的困境 重要而具有爭議性的研究 經常被質疑的而不是被支持 所以我們認為, 一個私立的研究避風港 讓這些研究不受干擾 是非常重要的 所以在2005年 我們成立了 紐約幹細胞基金會實驗室 這樣我們就可以有個小型組織 來資助並進行相關的研究
What we saw very quickly is the world of both medical research, but also developing drugs and treatments, is dominated by, as you would expect, large organizations, but in a new field, sometimes large organizations really have trouble getting out of their own way, and sometimes they can't ask the right questions, and there is an enormous gap that's just gotten larger between academic research on the one hand and pharmaceutical companies and biotechs that are responsible for delivering all of our drugs and many of our treatments, and so we knew that to really accelerate cures and therapies, we were going to have to address this with two things: new technologies and also a new research model. Because if you don't close that gap, you really are exactly where we are today. And that's what I want to focus on. We've spent the last couple of years pondering this, making a list of the different things that we had to do, and so we developed a new technology, It's software and hardware, that actually can generate thousands and thousands of genetically diverse stem cell lines to create a global array, essentially avatars of ourselves. And we did this because we think that it's actually going to allow us to realize the potential, the promise, of all of the sequencing of the human genome, but it's going to allow us, in doing that, to actually do clinical trials in a dish with human cells, not animal cells, to generate drugs and treatments that are much more effective, much safer, much faster, and at a much lower cost.
我們很快的就發現到 在醫學研究還有藥物與療程的發展這兩個領域 如大家所預期的, 是由大型的組織所主宰的 但是這些大型組織, 在面對新的領域時 常常會受限於既有的模式 有時候無法發現正確的問題方向 而且在兩者之間鴻溝日益擴大 一邊是學術研究 另一邊是研發新藥與療程的 藥廠與生技公司 我們認為, 若想要 加速藥物與治療方式的發展, 我們必須注重兩件事情 新的技術, 還有新的研究模式 因為如果不弭平兩邊的鴻溝 我們只會停留在目前的困境中 這就是我想要強調的 我們花了過去幾年的時光在這上頭 列出了我們想做的一些研究主題 開發了一個新的技術 包括軟體與硬體 可以用來產生數以百萬計的 不同的遺傳多樣性幹細胞系列, 來建構一個 全面性的陣列, 本質上就是我們的多重化身 我們做這件事的出發點, 是基於 想要了解人類基因序列的 各種潛在可能性 以這種方式我們將可以在培養皿裡面 針對真的人體細胞進行各項臨床實驗 而不是以動物的細胞, 來進行藥物與療程的開發 這將會是一種更有效, 更安全 更快速, 更便宜的做法
So let me put that in perspective for you and give you some context. This is an extremely new field. In 1998, human embryonic stem cells were first identified, and just nine years later, a group of scientists in Japan were able to take skin cells and reprogram them with very powerful viruses to create a kind of pluripotent stem cell called an induced pluripotent stem cell, or what we refer to as an IPS cell. This was really an extraordinary advance, because although these cells are not human embryonic stem cells, which still remain the gold standard, they are terrific to use for modeling disease and potentially for drug discovery.
接下來讓我先作一些說明 讓各位了解相關的背景 這是一個非常新的研究領域 人類的胚胎幹細胞, 在 1998 年 第一次被分離出來, 而在僅僅九年之後 一群日本的科學家, 發展出了將表皮細胞 透過非常強力的病毒進行改造 產出了一種具有多種潛能的幹細胞 叫做 誘導式多能性幹細胞 簡稱 IPS 細胞 這是一個非常重要的突破, 因為 雖然這種幹細胞並不是 人類胚胎幹細胞 不算是 研究上的黃金標準等級的幹細胞 但是仍然非常的有用, 可以用來建構疾病的模型 也有機會用來發展新藥
So a few months later, in 2008, one of our scientists built on that research. He took skin biopsies, this time from people who had a disease, ALS, or as you call it in the U.K., motor neuron disease. He turned them into the IPS cells that I've just told you about, and then he turned those IPS cells into the motor neurons that actually were dying in the disease. So basically what he did was to take a healthy cell and turn it into a sick cell, and he recapitulated the disease over and over again in the dish, and this was extraordinary, because it was the first time that we had a model of a disease from a living patient in living human cells. And as he watched the disease unfold, he was able to discover that actually the motor neurons were dying in the disease in a different way than the field had previously thought. There was another kind of cell that actually was sending out a toxin and contributing to the death of these motor neurons, and you simply couldn't see it until you had the human model.
在幾個月之後, 我們的一位科學家, 在 2008年的時候 以前面提到的研究為基礎, 從一個 漸凍人(ALS), 在英國也稱為 運動神經元疾病 的患者的表皮組織切片 培養出前面提到的 IPS 細胞 並且將這些 IPS 細胞轉化為 在這種漸凍人疾病中 實際會逐漸凋亡的運動神經元細胞 所以基本上我們可以把患者身上的一個健康的細胞 轉化成具有該病症的生病細胞 並且在培養皿裡面一次又一次重覆這樣的程序 這是一個非凡的成果 因為這是我們第一次可以掌握一個疾病的模型 直接從病人的身上取得的活體細胞來研究 當他觀察這個疾病的過程時, 發現到 這些運動神經元細胞的實際致死因素 與先前研究所認知的不同 是由於有另一種細胞 釋放出了某種毒素 才導致了運動神經元的凋亡 而這樣的發現只有透過這種新的人體細胞模式 才有辦法被觀察到
So you could really say that researchers trying to understand the cause of disease without being able to have human stem cell models were much like investigators trying to figure out what had gone terribly wrong in a plane crash without having a black box, or a flight recorder. They could hypothesize about what had gone wrong, but they really had no way of knowing what led to the terrible events. And stem cells really have given us the black box for diseases, and it's an unprecedented window. It really is extraordinary, because you can recapitulate many, many diseases in a dish, you can see what begins to go wrong in the cellular conversation well before you would ever see symptoms appear in a patient. And this opens up the ability, which hopefully will become something that is routine in the near term, of using human cells to test for drugs.
所以基本上可以這樣說 研究者在研究疾病原因的時候 如果沒有辦法透過人體幹細胞這種方式 就好像墜機事件的調查員 想找出飛機到底出了什麼差錯而墜毀 卻沒有找到黑盒子 (飛行記錄器) 一般的困難 他們可以假設一些可能出錯的原因 但是卻無法明白導致悲慘事件的 真正成因 而幹細胞就是我們研究疾病時的黑盒子 這種方式開啟了一個嶄新的門戶 這真的是一項非比尋常的突破 因為你可以在培養皿裡面, 一再重複各種疾病的進程 觀察到在細胞層次的轉換發生了什麼問題 可以早到病人身上 都還沒有出現疾病癥狀之前 而這樣的研究也開啟了一種可能性 在不久的將來, 以人體細胞 來進行藥物測試 可以成為標準的研究流程
Right now, the way we test for drugs is pretty problematic. To bring a successful drug to market, it takes, on average, 13 years — that's one drug — with a sunk cost of 4 billion dollars, and only one percent of the drugs that start down that road are actually going to get there. You can't imagine other businesses that you would think of going into that have these kind of numbers. It's a terrible business model. But it is really a worse social model because of what's involved and the cost to all of us. So the way we develop drugs now is by testing promising compounds on -- We didn't have disease modeling with human cells, so we'd been testing them on cells of mice or other creatures or cells that we engineer, but they don't have the characteristics of the diseases that we're actually trying to cure. You know, we're not mice, and you can't go into a living person with an illness and just pull out a few brain cells or cardiac cells and then start fooling around in a lab to test for, you know, a promising drug. But what you can do with human stem cells, now, is actually create avatars, and you can create the cells, whether it's the live motor neurons or the beating cardiac cells or liver cells or other kinds of cells, and you can test for drugs, promising compounds, on the actual cells that you're trying to affect, and this is now, and it's absolutely extraordinary, and you're going to know at the beginning, the very early stages of doing your assay development and your testing, you're not going to have to wait 13 years until you've brought a drug to market, only to find out that actually it doesn't work, or even worse, harms people.
在目前, 進行藥物測試的方法有相當多的問題 要把一種新藥導入到市場 平均要花13年的時間 並且花費40億美元的成本, 才能完成 而且在新藥研發的統計上 只有百分之一的比例能成功進行到市場導入的階段 你無法想像在其他的行業中 在發展並成功推出一項新產品時 會有這麼高的成本與時間 這樣的模式在商業上來看很糟糕 從社會的角度來看更糟糕 這些成本都是我們要去負擔的 在目前開發新藥的方式 是將一些可能具有效果的化合物 在還沒有人體細胞的疾病模式的方式之前 只能利用老鼠或是其他動物的細胞 來進行藥物實驗 但是這些被拿來做實驗的動物細胞 並不具備我們想治療的疾病的特性 畢竟人不是老鼠 你也不能直接找一個病人 直接取出他的腦細胞或是心血管細胞 拿到實驗室裡來測試 可能具有療效的新藥 而我們發展出這種人體幹細胞的研究方式之後 就可以製造出疾病患者的各種細胞分身 例如 運動神經元細胞 心血管細胞, 肝臟細胞 來進行藥物測試 可能有效的化合物, 用在實際的細胞上 來驗證想要發生的效果, 現在有辦法做到了. 這絕對是空前的突破 你將可以在一開始的時候 從藥物分析開發與測試的最早階段 而不是等了13年的時間 直到藥物導入市場的階段, 才發現沒有療效 甚至更糟的, 是會傷害到人體的
But it isn't really enough just to look at the cells from a few people or a small group of people, because we have to step back. We've got to look at the big picture. Look around this room. We are all different, and a disease that I might have, if I had Alzheimer's disease or Parkinson's disease, it probably would affect me differently than if one of you had that disease, and if we both had Parkinson's disease, and we took the same medication, but we had different genetic makeup, we probably would have a different result, and it could well be that a drug that worked wonderfully for me was actually ineffective for you, and similarly, it could be that a drug that is harmful for you is safe for me, and, you know, this seems totally obvious, but unfortunately it is not the way that the pharmaceutical industry has been developing drugs because, until now, it hasn't had the tools.
更進一步來說, 只從一小群人的細胞 來做這樣的實驗是不夠的 如果我們退一步來看 必須從更廣泛的角度來思考 就以這個房間裡的人來說, 大家都不一樣 一種疾病對我的影響 比如說 阿茲海默症 或是 巴金森氏症 很可能會不同於 另外一個得到相同疾病的人 就算兩個人得到相同的 帕金森(Parkinson's)症 採取相同的治療方式與藥物 也可能因為兩個人的基因組成不同 而產生不同的治療結果 有可能同樣的藥物對其中一人有神奇的療效 對另一個人卻完全沒有效果 同樣的, 一種藥可能對你產生傷害 對我卻是安全的. 這聽起來很明顯的道理 卻不幸地沒有被 製藥產業在開發藥物時進行實施 因為在今天之前, 並沒有適當的工具可用.
And so we need to move away from this one-size-fits-all model. The way we've been developing drugs is essentially like going into a shoe store, no one asks you what size you are, or if you're going dancing or hiking. They just say, "Well, you have feet, here are your shoes." It doesn't work with shoes, and our bodies are many times more complicated than just our feet. So we really have to change this.
我們必須脫離這種 "一視同仁" 的模式 過去的藥物發展方式 就像是進到一家鞋店 沒有人問你腳的尺寸 也沒人管你是要用來跳舞或健行 店員只告訴你, "嗯, 你有一雙腳, 我們賣你這雙鞋" 這樣賣鞋是行不通的. 而人的身體 比穿鞋的腳要複雜上許多倍 所以這樣的方式真的需要改變.
There was a very sad example of this in the last decade. There's a wonderful drug, and a class of drugs actually, but the particular drug was Vioxx, and for people who were suffering from severe arthritis pain, the drug was an absolute lifesaver, but unfortunately, for another subset of those people, they suffered pretty severe heart side effects, and for a subset of those people, the side effects were so severe, the cardiac side effects, that they were fatal. But imagine a different scenario, where we could have had an array, a genetically diverse array, of cardiac cells, and we could have actually tested that drug, Vioxx, in petri dishes, and figured out, well, okay, people with this genetic type are going to have cardiac side effects, people with these genetic subgroups or genetic shoes sizes, about 25,000 of them, are not going to have any problems. The people for whom it was a lifesaver could have still taken their medicine. The people for whom it was a disaster, or fatal, would never have been given it, and you can imagine a very different outcome for the company, who had to withdraw the drug.
在過去的十年間, 有一個不幸的例子 有一種藥, 詳細點說來是一種藥系 叫做 Vioxx 的關節炎藥品 對於關節疼痛的患者 簡直就是救命仙丹 但不幸的對於其中的一些患者 會產生嚴重的心臟方面的副作用 這些產生副作用的患者中 有些還因此而死亡 如果能在未來採用不同的做法 想像我們能有一個在基因上多樣化的陣列的 心血管細胞類型, 我們可以測試這種Vioxx 藥物 在培養皿裡就能發現到 某種基因類型的人, 會產生心血管方面的副作用 另外一些種類基因類型的人 大約有 25,000 種, 是不會產生副作用的 那麼這些人仍然可以使用這種藥物 當作是關節疼痛的救命仙丹 而另外那些會產生致命副作用的人 就不會被開立這種藥的處方 你可以想像這家藥廠, 將可以有完全不同於 完全回收這種藥物所造成的下場 (股價大跌)
So that is terrific, and we thought, all right, as we're trying to solve this problem, clearly we have to think about genetics, we have to think about human testing, but there's a fundamental problem, because right now, stem cell lines, as extraordinary as they are, and lines are just groups of cells, they are made by hand, one at a time, and it takes a couple of months. This is not scalable, and also when you do things by hand, even in the best laboratories, you have variations in techniques, and you need to know, if you're making a drug, that the Aspirin you're going to take out of the bottle on Monday is the same as the Aspirin that's going to come out of the bottle on Wednesday. So we looked at this, and we thought, okay, artisanal is wonderful in, you know, your clothing and your bread and crafts, but artisanal really isn't going to work in stem cells, so we have to deal with this.
這樣不是很棒嗎? 所以呢, 當我們試著解決這個問題的時候 很明確的我們必須考慮基因學 我們必須考慮藥物的人體測試 而且還有個更根本的難題 就是目前這些幹細胞系列 雖然如此的非凡與特別 仍然只是一群的細胞 必須用人工一個一個的培育 每次需要花上幾個月的時間 這樣是無法擴大規模的, 而且用手工的方式 就算是在最好的實驗室 也會因為操作技巧而造成差異 但是在藥物的生產上必須要能一致化 你買了一瓶阿斯匹靈打開來, 星期一拿出一顆來吃 跟你在星期三拿出來吃的那顆是完全相同的 從這點來看, 我們知道 手工生產是不錯的, 如果是衣服 麵包或是工藝品這些東西 但如果是 幹細胞 的生產, 手工是行不通的 這個問題必須被解決
But even with that, there still was another big hurdle, and that actually brings us back to the mapping of the human genome, because we're all different. We know from the sequencing of the human genome that it's shown us all of the A's, C's, G's and T's that make up our genetic code, but that code, by itself, our DNA, is like looking at the ones and zeroes of the computer code without having a computer that can read it. It's like having an app without having a smartphone. We needed to have a way of bringing the biology to that incredible data, and the way to do that was to find a stand-in, a biological stand-in, that could contain all of the genetic information, but have it be arrayed in such a way as it could be read together and actually create this incredible avatar. We need to have stem cells from all the genetic sub-types that represent who we are.
除此之外, 還有另外一個大難題 就是回歸到 人的基因序列 每個人都不一樣 每個人的基因序列 都是由四種核苷酸 A, C, G, T 組成我們的基因碼 但是這些基因碼, 就是我們的 DNA 就像是電腦裡面的 1 與 0 這些位元碼 但是我們並沒有能讀基因碼的電腦 我們現在就像是有了手機APP 但是還沒有智慧型手機 我們需要找出一種方式, 將生物學 對應到這些基因碼 而可行的方式是找到 一種生物學上的 替身 可以涵蓋所有的基因資訊 並且能夠進行各種基因排列 並且能夠被解讀 而且實際製作出各種特別的分身 我們需要收集各種基因類型的幹細胞 來代表各種類型的人
So this is what we've built. It's an automated robotic technology. It has the capacity to produce thousands and thousands of stem cell lines. It's genetically arrayed. It has massively parallel processing capability, and it's going to change the way drugs are discovered, we hope, and I think eventually what's going to happen is that we're going to want to re-screen drugs, on arrays like this, that already exist, all of the drugs that currently exist, and in the future, you're going to be taking drugs and treatments that have been tested for side effects on all of the relevant cells, on brain cells and heart cells and liver cells.
這裡可以看到我們已經發展的 一套自動化機械化的技術 具備產生數以百萬計的幹細胞系列的能力 能夠產生多樣化的基因陣列 可以進行大規模的平行作業 這將會改變發現新藥的方式 我們衷心的希望, 而且相信在未來遲早會成真 就是對藥物重新進行檢測 用已收集到的各種幹細胞基因系列, 來檢測目前存在的所有藥物 而在未來, 我們所服用的藥物還有所接受的治療 都會事先被測試過, 對身體的各種器官的細胞 是否會產生副作用 例如 腦細胞 心血管細胞 肝細胞 等等
It really has brought us to the threshold of personalized medicine. It's here now, and in our family, my son has type 1 diabetes, which is still an incurable disease, and I lost my parents to heart disease and cancer, but I think that my story probably sounds familiar to you, because probably a version of it is your story. At some point in our lives, all of us, or people we care about, become patients, and that's why I think that stem cell research is incredibly important for all of us. Thank you. (Applause) (Applause)
這將會帶領我們進到一個新的境界 製藥個人化的時代 我們所遭遇的, 就以我自己為例 我的兒子患有第一型的糖尿病 這在目前是無法治癒的 我的父母親死於心臟病與癌症 這聽起來可能讓你覺得很熟悉 也許你也有類似的遭遇 在我們的人生中, 我們自己 或是我們在意的人, 都有生病的時候 這就是為什麼我們認為, 幹細胞研究 對於每個人來說, 都是非常重要的 謝謝大家 (掌聲)