Susan Solomon: The promise of research with stem cells

Translator: Joseph Geni Reviewer: Morton Bast

譯者: Yu-Sheng Lin 審譯者: Yuguo Zhang

So, embryonic stem cells

在人的身體裡有一種神奇的細胞

are really incredible cells.

叫做胚胎幹細胞

They are our body's own repair kits,

這就像是身體裡的修補工具

and they're pluripotent, which means they can morph into

而且這些細胞具有多樣的潛能,

all of the cells in our bodies.

可以變成我們身體裡的各種細胞

Soon, we actually will be able to use stem cells

在不久的將來, 我們應該可以利用這些幹細胞

to replace cells that are damaged or diseased.

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,

不過呢, 今天我所要談的不是這個方向

because right now there are some really

今天要談的是關於

extraordinary things that we are doing with stem cells

我們正在進行的關於幹細胞的特殊研究

that are completely changing

這將會完全改變

the way we look and model disease,

我們看待與學習疾病的方式

our ability to understand why we get sick,

以及我們對於為什麼人會生病的研究

and even develop drugs.

甚至於是藥物的開發

I truly believe that stem cell research is going to allow

我深信幹細胞的研究, 可以讓我們的下一代

our children to look at Alzheimer's and diabetes

面對阿茲海默症(老年癡呆)或是糖尿病這些重大疾病時

and other major diseases the way we view polio today,

就如同我們現在面對脊髓灰質炎(小兒麻痺)一般

which is as a preventable disease.

能有預防的方法

So here we have this incredible field, which has

在幹細胞這個奇妙的研究領域

enormous hope for humanity,

有著人類的許多新希望

but much like IVF over 35 years ago,

但是就如同試管嬰兒這個研究領域 一直到了35年前

until the birth of a healthy baby, Louise,

第一個健康的試管嬰兒 露薏絲 的誕生 (1978.07.25)

this field has been under siege politically and financially.

才脫離了政治上與經費上的困境

Critical research is being challenged instead of supported,

重要而具有爭議性的研究 經常被質疑的而不是被支持

and we saw that it was really essential to have

所以我們認為, 一個私立的研究避風港

private safe haven laboratories where this work

讓這些研究不受干擾

could be advanced without interference.

是非常重要的

And so, in 2005,

所以在2005年

we started the New York Stem Cell Foundation Laboratory

我們成立了 紐約幹細胞基金會實驗室

so that we would have a small organization that could

這樣我們就可以有個小型組織

do this work and support it.

來資助並進行相關的研究

What we saw very quickly is the world of both medical

我們很快的就發現到

research, but also developing drugs and treatments,

在醫學研究還有藥物與療程的發展這兩個領域

is dominated by, as you would expect, large organizations,

如大家所預期的, 是由大型的組織所主宰的

but in a new field, sometimes large organizations

但是這些大型組織, 在面對新的領域時

really have trouble getting out of their own way,

常常會受限於既有的模式

and sometimes they can't ask the right questions,

有時候無法發現正確的問題方向

and there is an enormous gap that's just gotten larger

而且在兩者之間鴻溝日益擴大

between academic research on the one hand

一邊是學術研究

and pharmaceutical companies and biotechs

另一邊是研發新藥與療程的

that are responsible for delivering all of our drugs

藥廠與生技公司

and many of our treatments, and so we knew that

我們認為, 若想要

to really accelerate cures and therapies, we were going

加速藥物與治療方式的發展,

to have to address this with two things:

我們必須注重兩件事情

new technologies and also a new research model.

新的技術, 還有新的研究模式

Because if you don't close that gap, you really are

因為如果不弭平兩邊的鴻溝

exactly where we are today.

我們只會停留在目前的困境中

And that's what I want to focus on.

這就是我想要強調的

We've spent the last couple of years pondering this,

我們花了過去幾年的時光在這上頭

making a list of the different things that we had to do,

列出了我們想做的一些研究主題

and so we developed a new technology,

開發了一個新的技術

It's software and hardware,

包括軟體與硬體

that actually can generate thousands and thousands of

可以用來產生數以百萬計的

genetically diverse stem cell lines to create

不同的遺傳多樣性幹細胞系列, 來建構一個

a global array, essentially avatars of ourselves.

全面性的陣列, 本質上就是我們的多重化身

And we did this because we think that it's actually going

我們做這件事的出發點, 是基於

to allow us to realize the potential, the promise,

想要了解人類基因序列的

of all of the sequencing of the human genome,

各種潛在可能性

but it's going to allow us, in doing that,

以這種方式我們將可以在培養皿裡面

to actually do clinical trials in a dish with human cells,

針對真的人體細胞進行各項臨床實驗

not animal cells, to generate drugs and treatments

而不是以動物的細胞, 來進行藥物與療程的開發

that are much more effective, much safer,

這將會是一種更有效, 更安全

much faster, and at a much lower cost.

更快速, 更便宜的做法

So let me put that in perspective for you

接下來讓我先作一些說明

and give you some context.

讓各位了解相關的背景

This is an extremely new field.

這是一個非常新的研究領域

In 1998, human embryonic stem cells

人類的胚胎幹細胞, 在 1998 年

were first identified, and just nine years later,

第一次被分離出來, 而在僅僅九年之後

a group of scientists in Japan were able to take skin cells

一群日本的科學家, 發展出了將表皮細胞

and reprogram them with very powerful viruses

透過非常強力的病毒進行改造

to create a kind of pluripotent stem cell

產出了一種具有多種潛能的幹細胞

called an induced pluripotent stem cell,

叫做 誘導式多能性幹細胞

or what we refer to as an IPS cell.

簡稱 IPS 細胞

This was really an extraordinary advance, because

這是一個非常重要的突破, 因為

although these cells are not human embryonic stem cells,

雖然這種幹細胞並不是 人類胚胎幹細胞

which still remain the gold standard,

不算是 研究上的黃金標準等級的幹細胞

they are terrific to use for modeling disease

但是仍然非常的有用, 可以用來建構疾病的模型

and potentially for drug discovery.

也有機會用來發展新藥

So a few months later, in 2008, one of our scientists

在幾個月之後, 我們的一位科學家, 在 2008年的時候

built on that research. He took skin biopsies,

以前面提到的研究為基礎, 從一個 漸凍人(ALS),

this time from people who had a disease,

在英國也稱為 運動神經元疾病

ALS, or as you call it in the U.K., motor neuron disease.

的患者的表皮組織切片

He turned them into the IPS cells

培養出前面提到的 IPS 細胞

that I've just told you about, and then he turned those

並且將這些 IPS 細胞轉化為

IPS cells into the motor neurons that actually

在這種漸凍人疾病中

were dying in the disease.

實際會逐漸凋亡的運動神經元細胞

So basically what he did was to take a healthy cell

所以基本上我們可以把患者身上的一個健康的細胞

and turn it into a sick cell,

轉化成具有該病症的生病細胞

and he recapitulated the disease over and over again

並且在培養皿裡面一次又一次重覆這樣的程序

in the dish, and this was extraordinary,

這是一個非凡的成果

because it was the first time that we had a model

因為這是我們第一次可以掌握一個疾病的模型

of a disease from a living patient in living human cells.

直接從病人的身上取得的活體細胞來研究

And as he watched the disease unfold, he was able

當他觀察這個疾病的過程時, 發現到

to discover that actually the motor neurons were dying

這些運動神經元細胞的實際致死因素

in the disease in a different way than the field

與先前研究所認知的不同

had previously thought. There was another kind of cell

是由於有另一種細胞

that actually was sending out a toxin

釋放出了某種毒素

and contributing to the death of these motor neurons,

才導致了運動神經元的凋亡

and you simply couldn't see it

而這樣的發現只有透過這種新的人體細胞模式

until you had the human model.

才有辦法被觀察到

So you could really say that

所以基本上可以這樣說

researchers trying to understand the cause of disease

研究者在研究疾病原因的時候

without being able to have human stem cell models

如果沒有辦法透過人體幹細胞這種方式

were much like investigators trying to figure out

就好像墜機事件的調查員

what had gone terribly wrong in a plane crash

想找出飛機到底出了什麼差錯而墜毀

without having a black box, or a flight recorder.

卻沒有找到黑盒子 (飛行記錄器) 一般的困難

They could hypothesize about what had gone wrong,

他們可以假設一些可能出錯的原因

but they really had no way of knowing what led

但是卻無法明白導致悲慘事件的

to the terrible events.

真正成因

And stem cells really have given us the black box

而幹細胞就是我們研究疾病時的黑盒子

for diseases, and it's an unprecedented window.

這種方式開啟了一個嶄新的門戶

It really is extraordinary, because you can recapitulate

這真的是一項非比尋常的突破

many, many diseases in a dish, you can see

因為你可以在培養皿裡面, 一再重複各種疾病的進程

what begins to go wrong in the cellular conversation

觀察到在細胞層次的轉換發生了什麼問題

well before you would ever see

可以早到病人身上

symptoms appear in a patient.

都還沒有出現疾病癥狀之前

And this opens up the ability,

而這樣的研究也開啟了一種可能性

which hopefully will become something that

在不久的將來, 以人體細胞

is routine in the near term,

來進行藥物測試

of using human cells to test for drugs.

可以成為標準的研究流程

Right now, the way we test for drugs is pretty problematic.

在目前, 進行藥物測試的方法有相當多的問題

To bring a successful drug to market, it takes, on average,

要把一種新藥導入到市場

13 years — that's one drug —

平均要花13年的時間

with a sunk cost of 4 billion dollars,

並且花費40億美元的成本, 才能完成

and only one percent of the drugs that start down that road

而且在新藥研發的統計上

are actually going to get there.

只有百分之一的比例能成功進行到市場導入的階段

You can't imagine other businesses

你無法想像在其他的行業中

that you would think of going into

在發展並成功推出一項新產品時

that have these kind of numbers.

會有這麼高的成本與時間

It's a terrible business model.

這樣的模式在商業上來看很糟糕

But it is really a worse social model because of

從社會的角度來看更糟糕

what's involved and the cost to all of us.

這些成本都是我們要去負擔的

So the way we develop drugs now

在目前開發新藥的方式

is by testing promising compounds on --

是將一些可能具有效果的化合物

We didn't have disease modeling with human cells,

在還沒有人體細胞的疾病模式的方式之前

so we'd been testing them on cells of mice

只能利用老鼠或是其他動物的細胞

or other creatures or cells that we engineer,

來進行藥物實驗

but they don't have the characteristics of the diseases

但是這些被拿來做實驗的動物細胞

that we're actually trying to cure.

並不具備我們想治療的疾病的特性

You know, we're not mice, and you can't go into

畢竟人不是老鼠

a living person with an illness

你也不能直接找一個病人

and just pull out a few brain cells or cardiac cells

直接取出他的腦細胞或是心血管細胞

and then start fooling around in a lab to test

拿到實驗室裡來測試

for, you know, a promising drug.

可能具有療效的新藥

But what you can do with human stem cells, now,

而我們發展出這種人體幹細胞的研究方式之後

is actually create avatars, and you can create the cells,

就可以製造出疾病患者的各種細胞分身

whether it's the live motor neurons

例如 運動神經元細胞

or the beating cardiac cells or liver cells

心血管細胞, 肝臟細胞

or other kinds of cells, and you can test for drugs,

來進行藥物測試

promising compounds, on the actual cells

可能有效的化合物, 用在實際的細胞上

that you're trying to affect, and this is now,

來驗證想要發生的效果, 現在有辦法做到了.

and it's absolutely extraordinary,

這絕對是空前的突破

and you're going to know at the beginning,

你將可以在一開始的時候

the very early stages of doing your assay development

從藥物分析開發與測試的最早階段

and your testing, you're not going to have to wait 13 years

而不是等了13年的時間

until you've brought a drug to market, only to find out

直到藥物導入市場的階段, 才發現沒有療效

that actually it doesn't work, or even worse, harms people.

甚至更糟的, 是會傷害到人體的

But it isn't really enough just to look at

更進一步來說,

the cells from a few people or a small group of people,

只從一小群人的細胞 來做這樣的實驗是不夠的

because we have to step back.

如果我們退一步來看

We've got to look at the big picture.

必須從更廣泛的角度來思考

Look around this room. We are all different,

就以這個房間裡的人來說, 大家都不一樣

and a disease that I might have,

一種疾病對我的影響

if I had Alzheimer's disease or Parkinson's disease,

比如說 阿茲海默症 或是 巴金森氏症

it probably would affect me differently than if

很可能會不同於

one of you had that disease,

另外一個得到相同疾病的人

and if we both had Parkinson's disease,

就算兩個人得到相同的 帕金森(Parkinson's)症

and we took the same medication,

採取相同的治療方式與藥物

but we had different genetic makeup,

也可能因為兩個人的基因組成不同

we probably would have a different result,

而產生不同的治療結果

and it could well be that a drug that worked wonderfully

有可能同樣的藥物對其中一人有神奇的療效

for me was actually ineffective for you,

對另一個人卻完全沒有效果

and similarly, it could be that a drug that is harmful for you

同樣的, 一種藥可能對你產生傷害

is safe for me, and, you know, this seems totally obvious,

對我卻是安全的. 這聽起來很明顯的道理

but unfortunately it is not the way

卻不幸地沒有被

that the pharmaceutical industry has been developing drugs

製藥產業在開發藥物時進行實施

because, until now, it hasn't had the tools.

因為在今天之前, 並沒有適當的工具可用.

And so we need to move away

我們必須脫離這種

from this one-size-fits-all model.

"一視同仁" 的模式

The way we've been developing drugs is essentially

過去的藥物發展方式

like going into a shoe store,

就像是進到一家鞋店

no one asks you what size you are, or

沒有人問你腳的尺寸

if you're going dancing or hiking.

也沒人管你是要用來跳舞或健行

They just say, "Well, you have feet, here are your shoes."

店員只告訴你, "嗯, 你有一雙腳, 我們賣你這雙鞋"

It doesn't work with shoes, and our bodies are

這樣賣鞋是行不通的. 而人的身體

many times more complicated than just our feet.

比穿鞋的腳要複雜上許多倍

So we really have to change this.

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.

在過去的十年間, 有一個不幸的例子

There's a wonderful drug, and a class of drugs actually,

有一種藥, 詳細點說來是一種藥系

but the particular drug was Vioxx, and

叫做 Vioxx 的關節炎藥品

for people who were suffering from severe arthritis pain,

對於關節疼痛的患者

the drug was an absolute lifesaver,

簡直就是救命仙丹

but unfortunately, for another subset of those people,

但不幸的對於其中的一些患者

they suffered pretty severe heart side effects,

會產生嚴重的心臟方面的副作用

and for a subset of those people, the side effects were

這些產生副作用的患者中

so severe, the cardiac side effects, that they were fatal.

有些還因此而死亡

But imagine a different scenario,

如果能在未來採用不同的做法

where we could have had an array, a genetically diverse array,

想像我們能有一個在基因上多樣化的陣列的

of cardiac cells, and we could have actually tested

心血管細胞類型, 我們可以測試這種Vioxx 藥物

that drug, Vioxx, in petri dishes, and figured out,

在培養皿裡就能發現到

well, okay, people with this genetic type are going to have

某種基因類型的人, 會產生心血管方面的副作用

cardiac side effects, people with these genetic subgroups

另外一些種類基因類型的人

or genetic shoes sizes, about 25,000 of them,

大約有 25,000 種,

are not going to have any problems.

是不會產生副作用的

The people for whom it was a lifesaver

那麼這些人仍然可以使用這種藥物

could have still taken their medicine.

當作是關節疼痛的救命仙丹

The people for whom it was a disaster, or fatal,

而另外那些會產生致命副作用的人

would never have been given it, and

就不會被開立這種藥的處方

you can imagine a very different outcome for the company,

你可以想像這家藥廠, 將可以有完全不同於

who had to withdraw the drug.

完全回收這種藥物所造成的下場 (股價大跌)

So that is terrific,

這樣不是很棒嗎?

and we thought, all right,

所以呢,

as we're trying to solve this problem,

當我們試著解決這個問題的時候

clearly we have to think about genetics,

很明確的我們必須考慮基因學

we have to think about human testing,

我們必須考慮藥物的人體測試

but there's a fundamental problem,

而且還有個更根本的難題

because right now, stem cell lines,

就是目前這些幹細胞系列

as extraordinary as they are,

雖然如此的非凡與特別

and lines are just groups of cells,

仍然只是一群的細胞

they are made by hand, one at a time,

必須用人工一個一個的培育

and it takes a couple of months.

每次需要花上幾個月的時間

This is not scalable, and also when you do things by hand,

這樣是無法擴大規模的, 而且用手工的方式

even in the best laboratories,

就算是在最好的實驗室

you have variations in techniques,

也會因為操作技巧而造成差異

and you need to know, if you're making a drug,

但是在藥物的生產上必須要能一致化

that the Aspirin you're going to take out of the bottle

你買了一瓶阿斯匹靈打開來,

on Monday is the same as the Aspirin

星期一拿出一顆來吃

that's going to come out of the bottle on Wednesday.

跟你在星期三拿出來吃的那顆是完全相同的

So we looked at this, and we thought, okay,

從這點來看, 我們知道

artisanal is wonderful in, you know, your clothing

手工生產是不錯的, 如果是衣服

and your bread and crafts, but

麵包或是工藝品這些東西

artisanal really isn't going to work in stem cells,

但如果是 幹細胞 的生產, 手工是行不通的

so we have to deal with this.

這個問題必須被解決

But even with that, there still was another big hurdle,

除此之外, 還有另外一個大難題

and that actually brings us back to

就是回歸到

the mapping of the human genome, because

人的基因序列

we're all different.

每個人都不一樣

We know from the sequencing of the human genome

每個人的基因序列

that it's shown us all of the A's, C's, G's and T's

都是由四種核苷酸 A, C, G, T

that make up our genetic code,

組成我們的基因碼

but that code, by itself, our DNA,

但是這些基因碼, 就是我們的 DNA

is like looking at the ones and zeroes of the computer code

就像是電腦裡面的 1 與 0 這些位元碼

without having a computer that can read it.

但是我們並沒有能讀基因碼的電腦

It's like having an app without having a smartphone.

我們現在就像是有了手機APP 但是還沒有智慧型手機

We needed to have a way of bringing the biology

我們需要找出一種方式, 將生物學

to that incredible data,

對應到這些基因碼

and the way to do that was to find

而可行的方式是找到

a stand-in, a biological stand-in,

一種生物學上的 替身

that could contain all of the genetic information,

可以涵蓋所有的基因資訊

but have it be arrayed in such a way

並且能夠進行各種基因排列

as it could be read together

並且能夠被解讀

and actually create this incredible avatar.

而且實際製作出各種特別的分身

We need to have stem cells from all the genetic sub-types

我們需要收集各種基因類型的幹細胞

that represent who we are.

來代表各種類型的人

So this is what we've built.

這裡可以看到我們已經發展的

It's an automated robotic technology.

一套自動化機械化的技術

It has the capacity to produce thousands and thousands

具備產生數以百萬計的幹細胞系列的能力

of stem cell lines. It's genetically arrayed.

能夠產生多樣化的基因陣列

It has massively parallel processing capability,

可以進行大規模的平行作業

and it's going to change the way drugs are discovered,

這將會改變發現新藥的方式

we hope, and I think eventually what's going to happen

我們衷心的希望, 而且相信在未來遲早會成真

is that we're going to want to re-screen drugs,

就是對藥物重新進行檢測

on arrays like this, that already exist,

用已收集到的各種幹細胞基因系列,

all of the drugs that currently exist,

來檢測目前存在的所有藥物

and in the future, you're going to be taking drugs

而在未來, 我們所服用的藥物還有所接受的治療

and treatments that have been tested for side effects

都會事先被測試過, 對身體的各種器官的細胞

on all of the relevant cells,

是否會產生副作用

on brain cells and heart cells and liver cells.

例如 腦細胞 心血管細胞 肝細胞 等等

It really has brought us to the threshold

這將會帶領我們進到一個新的境界

of personalized medicine.

製藥個人化的時代

It's here now, and in our family,

我們所遭遇的, 就以我自己為例

my son has type 1 diabetes,

我的兒子患有第一型的糖尿病

which is still an incurable disease,

這在目前是無法治癒的

and I lost my parents to heart disease and cancer,

我的父母親死於心臟病與癌症

but I think that my story probably sounds familiar to you,

這聽起來可能讓你覺得很熟悉

because probably a version of it is your story.

也許你也有類似的遭遇

At some point in our lives, all of us,

在我們的人生中, 我們自己

or people we care about, become patients,

或是我們在意的人, 都有生病的時候

and that's why I think that stem cell research

這就是為什麼我們認為, 幹細胞研究

is incredibly important for all of us.

對於每個人來說, 都是非常重要的

Thank you. (Applause)

謝謝大家

(Applause)

(掌聲)