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As humans, it's in our nature
譯者: NAN-KUN WU 審譯者: Ying Wang
to want to improve our health and minimize our suffering.
身為人,想要增進健康以及
Whatever life throws at us,
減少痛苦是我們的天性。
whether it's cancer, diabetes, heart disease,
不論我們在生命中得到了什麼,
or even broken bones, we want to try and get better.
不管是癌症、糖尿病、心臟病,
Now I'm head of a biomaterials lab,
或甚至是骨折,我們都想要試著好起來。
and I'm really fascinated by the way that humans
我現在是一間 生物材料實驗室的主持人,
have used materials in really creative ways
我對於人類自古以來,
in the body over time.
在體內所使用的材料方面的創意
Take, for example, this beautiful blue nacre shell.
感到相當驚訝。
This was actually used by the Mayans
例如這個珍珠貝漂亮的殼,
as an artificial tooth replacement.
它曾經被馬雅人
We're not quite sure why they did it.
用來當做人工的牙齒替代品。
It's hard. It's durable.
我們並不清楚他們為什麼這麼做,
But it also had other very nice properties.
它很硬,也很耐用,
In fact, when they put it into the jawbone,
但是它也有其它很棒的特性。
it could integrate into the jaw,
事實上,當它們被放到頜骨裡面,
and we know now with very sophisticated
可能會和骨頭合而為一。
imaging technologies
先進的影像技術顯示,
that part of that integration comes from the fact
兩者相融的一部分原因
that this material is designed
來自於這種材料的
in a very specific way, has a beautiful chemistry,
特殊之處。
has a beautiful architecture.
不論在結構上
And I think in many ways we can sort of think
或是化學上都是如此。
of the use of the blue nacre shell and the Mayans
我認為在某些程度上,
as the first real application
用了藍珍珠貝的馬雅人
of the bluetooth technology.
是藍牙技術的
(Laughter)
先驅。
But if we move on and think throughout history
(笑聲)
how people have used different materials in the body,
如果我們觀察歷史上
very often it's been physicians
人類是如何將不同的材料運用在身體上,
that have been quite creative.
就會發現這些傑作常常
They've taken things off the shelf.
來自富有創意的醫師。
One of my favorite examples
他們時常創新。
is that of Sir Harold Ridley,
我最喜歡的一個例子
who was a famous ophthalmologist,
是關於 Harold Ridley 爵士。
or at least became a famous ophthalmologist.
他是一位有名的眼科醫師,
And during World War II, what he would see
或至少成為了一位有名的眼科醫師。
would be pilots coming back from their missions,
二次大戰期間,
and he noticed that within their eyes
他見到從任務結束后歸來的飛行員。
they had shards of small bits of material
他注意到這些飛行員的眼睛裡
lodged within the eye,
卡了碎片,或是
but the very interesting thing about it
其它的小東西。
was that material, actually, wasn't causing
但是有趣的是
any inflammatory response.
這些東西並沒有
So he looked into this, and he figured out
引起任何的發炎反應。
that actually that material was little shards of plastic
因此他仔細的調查了這件事,
that were coming from the canopy of the Spitfires.
他發現這些塑膠碎片
And this led him to propose that material
其實是來自噴火式戰機的座艙蓋。
as a new material for intraocular lenses.
這讓他提出使用這種物質
It's called PMMA, and it's now used
來製作新型人工水晶體。
in millions of people every year
這種物質叫做 PMMA,它現在每年
and helps in preventing cataracts.
幫助數百萬人
And that example, I think, is a really nice one,
免於罹患白內障。
because it helps remind us that in the early days,
我認為這個例子非常非常棒,
people often chose materials
因為它提醒了我們,
because they were bioinert.
從前的人們總是根據生物惰性
Their very purpose was to perform a mechanical function.
來選擇材料,
You'd put them in the body
它們的唯一目的 就是進行機械的功能;
and you wouldn't get an adverse response.
你會把它們放進身體裡,
And what I want to show you is that
而且不希望身體產生不良反應。
in regenerative medicine,
我想要展示給你們看的是
we've really shifted away from that idea
在再生醫學中,
of taking a bioinert material.
我們並非一如往常地
We're actually actively looking for materials
選擇生物惰性材料。
that will be bioactive, that will interact with the body,
事實上我們積極地尋找
and that furthermore we can put in the body,
會和身體產生反應的生物活性材料,
they'll have their function,
而且當我們把它們放到身體裡。
and then they'll dissolve away over time.
它們會執行功能,
If we look at this schematic,
然後會隨著時間被分解掉,
this is showing you what we think of
當我們仔細思考這個概念,
as the typical tissue-engineering approach.
這是在告訴你們,
We have cells there, typically from the patient.
我們心目中典型的生物工程技術。
We can put those onto a material,
我們有些細胞基本上是來自病人,
and we can make that material very complex if we want to,
我們能夠把這些細胞放到材料上,
and we can then grow that up in the lab
如果想要的話,我們也 可以把這些材料做得很複雜,
or we can put it straight back into the patient.
然後我們在實驗室裡培養這些細胞,
And this is an approach that's used all over the world,
或者直接放回病患體內。
including in our lab.
這項技術在全世界被使用,
But one of the things that's really important
包括我們的實驗室。
when we're thinking about stem cells
但是最重要的一件事情是:
is that obviously stem cells can be many different things,
當我們講到幹細胞時,
and they want to be many different things,
顯然它們能夠做到很多事,
and so we want to make sure that the environment
它們也想做很多事,
we put them into has enough information
所以要確保我們讓它們生長的環境
so that they can become the right sort
擁有足夠的訊息。
of specialist tissue.
使幹細胞特化成為
And if we think about the different types of tissues
正確的組織。
that people are looking at regenerating
人們在世界各地的實驗室裡尋找
all over the world, in all the different labs in the world,
各式各樣
there's pretty much every tissue you can think of.
擁有再生能力的組織,
And actually, the structure of those tissues
你所能想的到的各種組織都有,
is quite different, and it's going to really depend
而且事實上這些組織之間
on whether your patient has any underlying disease,
有很大的差異,
other conditions, in terms of how
也基於病人是否擁有相關疾病,
you're going to regenerate your tissue,
或是其它的條件來決定。
and you're going to need to think about the materials
要如何讓組織再生,
you're going to use really carefully,
也要謹慎選擇材料
their biochemistry, their mechanics,
和使用材料;
and many other properties as well.
要考慮到這些材料的生化、機械
Our tissues all have very different abilities to regenerate,
以及其它的特性。
and here we see poor Prometheus,
我們所有的組織再生的能力迥異,
who made a rather tricky career choice
就像是可憐的普羅米修斯,
and was punished by the Greek gods.
因為他一個狡猾的生涯決定
He was tied to a rock, and an eagle would come
而被希臘諸神所懲罰。
every day to eat his liver.
他被綁在一塊石頭上,每天都會有一隻老鷹
But of course his liver would regenerate every day,
來啄食他的肝臟。
and so day after day he was punished
當然他的肝臟每天都會長回來,
for eternity by the gods.
所以諸神的懲罰日復一日
And liver will regenerate in this very nice way,
直到永遠。
but actually if we think of other tissues,
肝臟有很強的再生能力,
like cartilage, for example,
但是其它的組織就不一樣了,
even the simplest nick and you're going to find it
以軟骨來說,
really difficult to regenerate your cartilage.
即使是一個小缺損
So it's going to be very different from tissue to tissue.
也很難長回來。
Now, bone is somewhere in between,
所以組織之間有很大的差異。
and this is one of the tissues that we work on a lot in our lab.
好,骨骼介於兩者之間,
And bone is actually quite good at repairing.
也是我們實驗室努力研究的對象。
It has to be. We've probably all had fractures
其實骨骼也很善於修補。
at some point or other.
它必須如此。我們可能
And one of the ways that you can think
都曾經經歷過骨折,
about repairing your fracture
有一種你可能想像得到的
is this procedure here, called an iliac crest harvest.
修補骨折的方法,
And what the surgeon might do
叫做髂嵴修補法。
is take some bone from your iliac crest,
外科醫師會做的
which is just here,
是取出髂嵴的部分骨骼,
and then transplant that somewhere else in the body.
就像這樣,
And it actually works really well,
然後移植到身體的其它部位。
because it's your own bone,
這真的相當有效,
and it's well vascularized,
因為它是你自己的骨頭,
which means it's got a really good blood supply.
同時也具有完整的血管系統,
But the problem is, there's only so much you can take,
也就是說它能得到充足的血液供應。
and also when you do that operation,
但是問題在於 你能取出的骨骼很有限,
your patients might actually have significant pain
而且在你進行手術之後兩年內,
in that defect site even two years after the operation.
手術部位可能
So what we were thinking is,
會讓病人感到相當痛苦。
there's a tremendous need for bone repair, of course,
所以我們在思考的是,
but this iliac crest-type approach
當然,骨骼的修復是很重要的,
really has a lot of limitations to it,
但是這種髂嵴修補法
and could we perhaps recreate
有很多限制,
the generation of bone within the body
我們能夠想出一種方法
on demand and then be able to transplant it
讓骨頭在身體裡面再生
without these very, very painful aftereffects
並且能夠移植它
that you would have with the iliac crest harvest?
同時避免像是髂嵴修補法產生的
And so this is what we did, and the way we did it
劇烈疼痛等後遺症嗎?
was by coming back to this typical tissue-engineering approach
我們做到了,我們用的方法又回到 典型的組織工程法
but actually thinking about it rather differently.
我們做到了,我們用的方法 又回到典型的組織工程法,
And we simplified it a lot,
但是卻有不同的思路。
so we got rid of a lot of these steps.
我們也把它簡化了很多,
We got rid of the need to harvest cells from the patient,
所以可以省略很多步驟。
we got rid of the need to put in really fancy chemistries,
我們省略了從病人體內取出細胞的步驟,
and we got rid of the need
省略了把細胞放進 令人眼花繚亂的化學物質
to culture these scaffolds in the lab.
也省略了
And what we really focused on
在實驗室裡培養這些組織的架構。
was our material system and making it quite simple,
我們著重在於
but because we used it in a really clever way,
簡化材料系統,
we were able to generate enormous amounts of bone
這樣的巧思,
using this approach.
讓我們能夠通過這種方法
So we were using the body
作出大量的骨骼。
as really the catalyst to help us
我們把身體
to make lots of new bone.
當做催化劑,
And it's an approach that we call
幫我們做出很多的新骨骼。
the in vivo bioreactor, and we were able to make
我們把這樣的方法
enormous amounts of bone using this approach.
叫做體內生物反應器,利用這樣的方法
And I'll talk you through this.
我們能作出大量的骨骼。
So what we do is,
我現在詳細說明給你們聽。
in humans, we all have a layer of stem cells
我們是這樣做的,
on the outside of our long bones.
在人類的長骨外面
That layer is called the periosteum.
有一層幹細胞。
And that layer is actually normally
叫做骨膜。
very, very tightly bound to the underlying bone,
這層細胞通常會 非常非常緊密的和
and it's got stem cells in it.
下面的骨頭結合,
Those stem cells are really important
幹細胞就位在其中
in the embryo when it develops,
這些幹細胞
and they also sort of wake up if you have a fracture
對胚胎發育很重要,
to help you with repairing the bone.
而它們在你骨折的時候就像被喚醒了一樣
So we take that periosteum layer
幫助你修補骨頭。
and we developed a way to inject underneath it
我們發展出了一種注射法,
a liquid that then, within 30 seconds,
在鼓膜底下
would turn into quite a rigid gel
注射一種液體,
and can actually lift the periosteum away from the bone.
30 秒之內液體就會硬化成膠狀
So it creates, in essence, an artificial cavity
會把骨膜剝離骨骼
that is right next to both the bone
實際上,它在骨頭 跟帶有很多幹細胞的這層膜之間
but also this really rich layer of stem cells.
製造了一個人工腔室,
And we go in through a pinhole incision
但同時含有豐富的幹細胞。
so that no other cells from the body can get in,
然後我們會從一個 針孔般的切口進入,
and what happens is that that artificial in vivo bioreactor cavity
所以身體的其它細胞不會跑進去,
can then lead to the proliferation of these stem cells,
這個人工體內生物反應器
and they can form lots of new tissue,
能夠讓這些幹細胞增殖,
and then over time, you can harvest that tissue
然後它們就可以變成很多新組織,
and use it elsewhere in the body.
一段時間過後你就能收集這些細胞
This is a histology slide
並用在身體的其他部位。
of what we see when we do that,
這是我們做這件事當時的
and essentially what we see
組織切片,
is very large amounts of bone.
我們所看到的基本上
So in this picture, you can see the middle of the leg,
就是很多的骨骼。
so the bone marrow,
在這張圖片裡面,你能看到腿的中段,
then you can see the original bone,
這是骨髓,
and you can see where that original bone finishes,
然後你可以看到原來的骨頭,
and just to the left of that is the new bone
原本的骨頭到這裡為止,
that's grown within that bioreactor cavity,
左邊的是在這個
and you can actually make it even larger.
是在生物反應器裡面長出的新骨頭
And that demarcation that you can see
你也可以讓它長得更大
between the original bone and the new bone
在原來的和新的骨頭之間
acts as a very slight point of weakness,
的界線
so actually now the surgeon can come along,
有著非常微小的脆弱點,
can harvest away that new bone,
外科醫師現在就可以過來
and the periosteum can grow back,
將新的骨骼取走,
so you're left with the leg
然後骨膜會長回去,
in the same sort of state
你的腿
as if you hadn't operated on it in the first place.
在這樣的情況下
So it's very, very low in terms of after-pain
就像沒做過任何事一樣。
compared to an iliac crest harvest.
所以和髂嵴修補法相比之下,
And you can grow different amounts of bone
術後幾乎可以說是完全沒有疼痛感。
depending on how much gel you put in there,
你可以借由調整注射膠的量來
so it really is an on demand sort of procedure.
製造出不同量的骨頭,
Now, at the time that we did this,
所以這個技術確實可以量身訂做。
this received a lot of attention in the press,
好,我們做這個計劃時
because it was a really nice way
這項技術受到了媒體的大量關注,
of generating new bone,
因為這是
and we got many, many contacts
製造新骨骼很棒的方法,
from different people that were interested in using this.
也有很多人跟我們聯絡,
And I'm just going to tell you,
他們對這種方法非常有興趣。
sometimes those contacts are very strange,
我要讓你們知道的是,
slightly unexpected,
有時候這些和我們聯絡的人很奇怪,
and the very most interesting,
甚至有點出乎意料,
let me put it that way, contact that I had,
我所遇過的
was actually from a team of American footballers
最有趣的的聯絡人
that all wanted to have double-thickness skulls
是美式足球隊員。
made on their head.
他們想要有
And so you do get these kinds of contacts,
兩倍厚的頭骨。
and of course, being British
就是這樣的一些人
and also growing up in France,
當然囉,身為一個英國人
I tend to be very blunt,
並且在法國長大,
and so I had to explain to them very nicely
我必須試著很客氣
that in their particular case,
向他們解釋
there probably wasn't that much in there
這裡實在是沒有太多東西需要被保護,
to protect in the first place.
因為
(Laughter)
首先沒有足夠的材料去保護他們。
(Applause)
(笑聲)
So this was our approach,
(掌聲)
and it was simple materials,
這就是我們所用的方法,
but we thought about it carefully.
材料非常簡單,
And actually we know that those cells
但是我們深思熟慮。
in the body, in the embryo, as they develop
我們也確實知道這些 在身體裡、在胚胎裡的細胞
can form a different kind of tissue, cartilage,
當它們發育之後
and so we developed a gel that was slightly different
能變成不同的組織,像是軟骨,
in nature and slightly different chemistry,
因此我們法展出了一種膠,
put it in there, and we were able to get
這種膠和自然存在的不太一樣, 化學性質也不甚相同,
100 percent cartilage instead.
注射進去之後,
And this approach works really well, I think,
我們反而會得到百分之百的軟骨。
for pre-planned procedures,
我認為這項技術
but it's something you do have to pre-plan.
對於有事先規劃的療程非常實用,
So for other kinds of operations,
但是你必須要事先規劃好。
there's definitely a need for other
因此,對於其他手術來說
scaffold-based approaches.
有架構的方法
And when you think about designing
是絕對必須的。
those other scaffolds, actually,
當你想要設計
you need a really multi-disciplinary team.
其他的架構時,實際上,
And so our team has chemists,
你需要有一個全方位的團隊。
it has cell biologists, surgeons, physicists even,
所以我們的團隊有化學家
and those people all come together
細胞生物學家、外科醫師,甚至是物理學家
and we think really hard about designing the materials.
這些人聚在一起,
But we want to make them have enough information
絞盡腦汁才設計出這些材料。
that we can get the cells to do what we want,
我們希望讓他們獲得充足的資訊,
but not be so complex as to make it difficult
讓細胞做到我們期望的,
to get to clinic.
但是不能過於複雜而難以
And so one of the things we think about a lot
應用在臨床上。
is really trying to understand
因此我們想到了
the structure of the tissues in the body.
要了解人
And so if we think of bone,
人體內組織的結構,
obviously my own favorite tissue,
當我們想到骨骼
we zoom in, we can see,
顯然是我最喜歡的組織,
even if you don't know anything about bone structure,
放大來看,
it's beautifully organized, really beautifully organized.
既使你對它一無所知,
We've lots of blood vessels in there.
也會看到它是有組織的,非常有組織。
And if we zoom in again, we see that the cells
裡面有非常多的血管,
are actually surrounded by a 3D matrix
如果再放大來看,會看到細胞是被
of nano-scale fibers, and they give a lot
奈米等級的纖維形成的 3D 結構包圍,
of information to the cells.
這些纖維會
And if we zoom in again,
提供細胞很多訊息。
actually in the case of bone, the matrix
再放大,在骨頭的例子中
around the cells is beautifully organized
包圍細胞的胞外物質,
at the nano scale, and it's a hybrid material
形成了非常有組織
that's part organic, part inorganic.
的奈米結構,
And that's led to a whole field, really,
同時也是兼具有機與無機的結構。
that has looked at developing materials
那是這個領域的根本,
that have this hybrid kind of structure.
也讓我們想到要發展
And so I'm showing here just two examples
兼具有機與無機的材料。
where we've made some materials that have that sort of structure,
我現在要講的兩個例子
and you can really tailor it.
是我們所製造出並具有相似結構的材料
You can see here a very squishy one
而且可以客製化。
and now a material that's also this hybrid sort of material
這個材料質地像糊
but actually has remarkable toughness,
但是與這種材料混合的另一種材料
and it's no longer brittle.
卻具有非同尋常的堅硬度,
And an inorganic material would normally be really brittle,
也不易碎。
and you wouldn't be able to have
一般無機材料是易碎的,
that sort of strength and toughness in it.
也無法擁有
One other thing I want to quickly mention is that
如此的力量與韌性。
many of the scaffolds we make are porous, and they have to be,
我想快速帶過另外一件事情,
because you want blood vessels to grow in there.
很多我們做出的架構是有孔的, 它們也必須如此,
But the pores are actually oftentimes
因為我們希望血管能在其中生長,
much bigger than the cells,
但是這些孔洞常常
and so even though it's 3D,
比細胞大上許多,
the cell might see it more as a slightly curved surface,
所以即使它是 3D 的,
and that's a little bit unnatural.
在細胞看來也是個曲面,
And so one of the things you can think about doing
這件事情不太自然。
is actually making scaffolds with slightly different dimensions
其中一個解決辦法就是,
that might be able to surround your cells in 3D
讓架構在度量上有點不同,
and give them a little bit more information.
讓它能夠以 3D 的形式包住細胞
And there's a lot of work going on in both of these areas.
然後給它們更多的訊息。
Now finally, I just want to talk a little bit about
在這些領域,許多研究正在進行
applying this sort of thing to cardiovascular disease,
最後,我想說說把這些東西在
because this is a really big clinical problem.
心血管疾病上的應用,
And one of the things that we know is that,
因為這些疾病在臨床上相當重要。
unfortunately, if you have a heart attack,
我們知道的一件事情是,很不幸的
then that tissue can start to die,
如果你有了心肌梗塞,
and your outcome may not be very good over time.
那裡的組織就會開始壞死,
And it would be really great, actually,
長期下來的後果不會太好。
if we could stop that dead tissue
如果我們能
either from dying or help it to regenerate.
阻止組織壞死那就太棒了
And there's lots and lots of stem cell trials going on worldwide,
不論是從阻止壞死或是幫助它再生。
and they use many different types of cells,
現在全世界進行著 非常多的幹細胞試驗,
but one common theme that seems to be coming out
他們用了很多種不同的細胞,
is that actually, very often, those cells will die
但是有一件事情常常發生,
once you've implanted them.
那就是這些細胞在被植入
And you can either put them into the heart
之後就會死亡。
or into the blood system,
你可以把它們放進心臟
but either way, we don't seem to be able
或是血液系統裡頭,
to get quite the right number of cells
但無論是哪種方法,我們似乎都不能
getting to the location we want them to
讓細胞
and being able to deliver the sort of beautiful
到達我們希望它們去的部位,
cell regeneration that we would like to have
然後進行美妙的
to get good clinical outcomes.
細胞再生,
And so some of the things that we're thinking of,
得到良好的療效。
and many other people in the field are thinking of,
因此,我們以及在這個領域的很多人
are actually developing materials for that.
在思考的事情是,
But there's a difference here.
發展出能夠做到這些事情的材料。
We still need chemistry, we still need mechanics,
但是不同的是,
we still need really interesting topography,
我們仍然需要化學、力學,
and we still need really interesting ways to surround the cells.
需要很有趣的拓樸學,
But now, the cells also
也需要能夠研究 這些細胞的有趣方法。
would probably quite like a material
目前,這些細胞
that's going to be able to be conductive,
比較像是
because the cells themselves will respond very well
能夠傳導的材料,
and will actually conduct signals between themselves.
因為這些細胞 會對訊號做出很好的回應,
You can see them now
並在彼此之間傳遞這些訊號。
beating synchronously on these materials,
你可以看到這些細胞在材料上
and that's a very, very exciting development
同步跳動,
that's going on.
這真的是
So just to wrap up, I'd like to actually say that
令人相當興奮的進展。
being able to work in this sort of field,
總而言之,我想說的是
all of us that work in this field
能在這個領域工作,
that's not only super-exciting science,
對在這個領域的所有人來說,
but also has the potential
這不只是令人超級興奮的科學,
to impact on patients,
也對病人
however big or small they are,
有潛在影響力,
is really a great privilege.
不論這些影響是大是小,
And so for that, I'd like to thank all of you as well.
都是很好的恩典。
Thank you.
在此我也想要感謝你們所有人。
(Applause)
謝謝。