How a long-forgotten virus could help us solve the antibiotics crisis | Alexander Belcredi
327,684 views ・ 2018-12-07
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譯者: Lilian Chiu
審譯者: Keying Chen
00:12
Take a moment
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花一點時間,
00:14
and think about a virus.
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去想想病毒。
00:16
What comes to your mind?
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你腦海中浮現的是什麼?
00:18
An illness?
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一種疾病?
00:20
A fear?
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一種恐懼?
00:21
Probably something really unpleasant.
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可能是很不愉悅的東西。
00:23
And yet, viruses are not all the same.
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但是,病毒並不是全都一樣。
00:25
It's true, some of them cause
devastating disease.
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的確,有些病毒會造成
很有破壞性的疾病。
00:29
But others can do the exact opposite --
they can cure disease.
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但有些其他病毒的作用
完全相反——它們能治癒疾病。
00:33
These viruses are called "phages."
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這些病毒叫做「噬菌體」。
00:36
Now, the first time I heard
about phages was back in 2013.
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我第一次聽到噬菌體,
是在 2013 年。
00:39
My father-in-law, who's a surgeon,
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我的岳父是外科醫生,
00:41
was telling me about a woman
he was treating.
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他告訴我,他在治療一位女士。
00:44
The woman had a knee injury,
required multiple surgeries,
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這位女士有膝傷,
需要進行多個手術,
00:47
and over the course of these,
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在這些手術的過程中,
00:48
developed a chronic
bacterial infection in her leg.
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她的腳發生了
一種慢性的細菌性感染。
00:51
Unfortunately for her,
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對她來說,很不幸,
00:52
the bacteria causing the infection
also did not respond
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造成感染的細菌對於可取得的
抗生素藥物都沒有反應。
00:55
to any antibiotic that was available.
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00:58
So at this point, typically, the only
option left is to amputate the leg
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所以,在這個時點,通常,
唯一的選擇就是將那條腿截肢,
01:02
to stop the infection
from spreading further.
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來阻止感染進一步散播。
01:05
Now, my father-in-law was desperate
for a different kind of solution,
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我的岳父非常希望能找到
一種不同的解決方案,
01:08
and he applied for an experimental,
last-resort treatment using phages.
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他申請用噬菌體的實驗性治療,
這是他能用的最後手段。
01:13
And guess what? It worked.
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猜猜如何?治療見效了。
01:15
Within three weeks of applying the phages,
the chronic infection had healed up,
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在採用了噬菌體之後的三週內,
慢性感染就治癒了,
01:19
where before, no antibiotic was working.
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之前,任何抗生素都沒有用。
01:22
I was fascinated by this weird conception:
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這個怪異的概念讓我很著迷,
01:27
viruses curing an infection.
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用病毒來治癒感染。
01:30
To this day, I am fascinated
by the medical potential of phages.
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至今,噬菌體的醫療潛力
仍然讓我著迷。
01:34
And I actually quit my job last year
to build a company in this space.
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去年,我真的辭掉了我的工作,
為此成立了一間公司。
01:38
Now, what is a phage?
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噬菌體是什麼?
01:41
The image that you see here was taken
by an electron microscope.
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各位看到的影像是用
電子顯微鏡拍攝的。
01:45
And that means what we see on the screen
is in reality extremely tiny.
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意思就是,我們在螢幕上
看到的東西,實際上非常小。
01:49
The grainy thing in the middle
with the head, the long body
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中間的粒狀物有個頭,
有很長的身體,
01:53
and a number of feet --
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有好幾隻腳——
01:54
this is the image of a prototypical phage.
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典型的噬菌體就長這個樣子。
01:57
It's kind of cute.
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還蠻可愛的。
01:58
(Laughter)
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(笑聲)
02:00
Now, take a look at your hand.
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看看你們的手。
02:03
In our team, we've estimated
that you have more than 10 billion phages
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我們的團隊估計,
在每一隻手上,
都有超過一百億個噬菌。
02:08
on each of your hands.
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02:09
What are they doing there?
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它們在那裡做什麼?
02:11
(Laughter)
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(笑聲)
02:12
Well, viruses are good at infecting cells.
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嗯,病毒很擅長感染細胞。
02:15
And phages are great
at infecting bacteria.
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而噬菌體則很擅長感染細菌。
02:18
And your hand, just like
so much of our body,
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而你們的手,
就像我們大部分的身體,
02:20
is a hotbed of bacterial activity,
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是細菌活動的溫床,
02:22
making it an ideal
hunting ground for phages.
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對噬菌體來說,
就是打獵最理想的地方。
02:26
Because after all, phages hunt bacteria.
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畢竟,細菌是噬菌體的獵物。
02:29
It's also important to know that phages
are extremely selective hunters.
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還要知道一件重要的事,
噬菌體是非常挑的獵人。
02:34
Typically, a phage will only infect
a single bacterial species.
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一般來說,一種噬菌體只會
感染一種細菌物種。
02:38
So in this rendering here,
the phage that you see
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所以在這張圖上,你們看到的噬菌體
02:41
hunts for a bacterium
called Staphylococcus aureus,
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獵取的目標是一種叫做
金黃色葡萄球菌的細菌,
02:44
which is known as MRSA
in its drug-resistant form.
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它的抗藥型縮寫為 MRSA。
02:48
It causes skin or wound infections.
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它會造成皮膚或傷口的感染。
02:51
The way the phage hunts is with its feet.
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噬菌體獵取的方式是用它的腳。
02:54
The feet are actually extremely
sensitive receptors,
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這些腳其實是非常敏感的接受器,
02:56
on the lookout for the right surface
on a bacterial cell.
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負責留心細菌細胞上
有沒有對的表面。
03:00
Once it finds it,
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一旦找到對的表面,
噬菌體就會插上細菌的細胞壁,
03:01
the phage will latch on
to the bacterial cell wall
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03:04
and then inject its DNA.
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接著注入它的 DNA。
03:06
DNA sits in the head of the phage
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DNA 存在於噬菌體的頭部,
03:08
and travels into the bacteria
through the long body.
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透過長長的身體,傳輸到細菌中。
03:11
At this point, the phage
reprograms the bacteria
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此時,噬菌體就會改變
細菌的 DNA 編碼,
03:14
into producing lots of new phages.
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來產生出很多新噬菌體。
03:16
The bacteria, in effect,
becomes a phage factory.
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實際上,細菌就變成了
噬菌體生產工廠。
03:19
Once around 50-100 phages have accumulated
within the bacteria cell,
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等到細菌細胞中累積有
大約 50~100 個噬菌體時,
03:23
the phages are then able
to release a protein
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噬菌體就能夠釋放出一種蛋白質,
03:26
that disrupts the bacteria cell wall.
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導致細菌的細胞壁裂開。
03:28
As the bacteria bursts,
the phages move out
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當細菌爆裂開,噬菌體就會跑出來,
03:31
and go on the hunt again
for a new bacteria to infect.
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繼續去打獵,尋找並感染新的細菌。
03:35
Now, I'm sorry, this probably
sounded like a scary virus again.
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對不起,這可能聽起來
又像是駭人的病毒。
03:39
But it's exactly this ability of phages --
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但正是噬菌體的這種能力——
03:41
to multiply within the bacteria
and then kill them --
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在細菌裡面繁殖並殺死細菌——
03:44
that make them so interesting
from a medical point of view.
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讓噬菌體從醫學的觀點
來看十分有趣。
03:47
The other part that I find
extremely interesting
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還有另一部分,
我也覺得非常有趣,
03:50
is the scale at which this is going on.
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就是這個現象發生的規模。
03:52
Now, just five years ago,
I really had no clue about phages.
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五年前,我對噬菌體一無所知。
03:55
And yet, today I would tell you
they are part of a natural principle.
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但,現今,我會告訴各位,
它們是自然法則的一部分。
03:59
Phages and bacteria go back
to the earliest days of evolution.
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噬菌體和細菌可以
追溯回演化的最早期。
04:03
They have always existed in tandem,
keeping each other in check.
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它們一直一前一後地存在,
彼此相互制衡。
04:07
So this is really the story of yin
and yang, of the hunter and the prey,
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所以,這其實是一個陰和陽、
獵人和獵物的顯微級故事。
04:11
at a microscopic level.
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04:14
Some scientists have even estimated
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有些科學家甚至估計,
04:16
that phages are the most
abundant organism on our planet.
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噬菌體是地球上最大量的有機體。
04:20
So even before we continue
talking about their medical potential,
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所以,在我們繼續談
它們的醫療潛力之前,
04:23
I think everybody should know
about phages and their role on earth:
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我想大家應該要了解一下噬菌體
及它們在地球上的角色:
04:27
they hunt, infect and kill bacteria.
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它們會獵取、感染,並殺死細菌。
04:30
Now, how come we have something
that works so well in nature,
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為什麼在大自然中
我們每天身邊都有著
04:33
every day, everywhere around us,
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運作得這麼好的法則,
04:35
and yet, in most parts of the world,
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但在世界上大部分的地方,
04:37
we do not have a single drug on the market
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市場上都沒有任何藥物
04:39
that uses this principle
to combat bacterial infections?
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使用這項法則來對抗細菌感染?
04:43
The simple answer is: no one
has developed this kind of a drug yet,
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答案很簡單:
還沒有人開發出這種藥物,
04:47
at least not one that conforms
to the Western regulatory standards
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至少沒有發明出符合
西方法規標準的藥物,
04:50
that set the norm
for so much of the world.
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畢竟西方標準是世界主要的基準。
04:53
To understand why,
we need to move back in time.
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若要了解為什麼,
我們得要回到過去。
04:57
This is a picture of Félix d'Herelle.
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這位是費里斯·代列爾。
04:59
He is one of the two scientists
credited with discovering phages.
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他是發現噬菌體的兩位科學家之一。
05:02
Except, when he discovered them
back in 1917, he had no clue
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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。
05:06
what he had discovered.
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05:08
He was interested in a disease
called bacillary dysentery,
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他對一種疾病很感興趣,
叫做細菌性痢疾,
05:12
which is a bacterial infection
that causes severe diarrhea,
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它是一種細菌感染,
會造成嚴重腹瀉,
05:14
and back then, was actually
killing a lot of people,
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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。
05:17
because after all, no cure for bacterial
infections had been invented.
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05:21
He was looking at samples from patients
who had survived this illness.
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他檢視的樣本來自得過這種疾病
但存活下來的病人。
05:25
And he found that something
weird was going on.
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他發現有很奇怪的現象發生。
05:27
Something in the sample
was killing the bacteria
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在樣本中有某樣東西在殺死
05:29
that were supposed to cause the disease.
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造成疾病的那些細菌。
05:31
To find out what was going on,
he did an ingenious experiment.
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為了了解發生了什麼事,
他做了一項很聰明的實驗。
05:35
He took the sample, filtered it
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他把樣本拿來過濾,
05:37
until he was sure that only something
very small could have remained,
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直到他能確保留下來的東西
都是非常小的東西,
05:40
and then took a tiny drop and added it
to freshly cultivated bacteria.
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接著取一小滴的樣本,
加入新鮮培養出來的細菌中。
05:45
And he observed
that within a number of hours,
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據他觀察,在幾小時之內,
05:47
the bacteria had been killed.
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細菌都被殺死了。
05:49
He then repeated this,
again filtering, taking a tiny drop,
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他接著重覆這個實驗,
同樣地,過濾,再取一小滴,
05:53
adding it to the next batch
of fresh bacteria.
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加到下一批新鮮細菌上。
05:55
He did this in sequence 50 times,
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他依序做了五十次,
05:58
always observing the same effect.
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總是觀察到同樣的效果。
06:00
And at this point,
he made two conclusions.
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此時,他做出兩項結論。
06:02
First of all, the obvious one:
yes, something was killing the bacteria,
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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。
06:06
and it was in that liquid.
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06:07
The other one: it had to be
biologic in nature,
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另一項結論:它一定是
大自然中的生物,
06:10
because a tiny drop was sufficient
to have a huge impact.
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因為只要一小滴,
就足以產生很大的影響。
06:14
He called the agent he had found
an "invisible microbe"
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他把他發現的這種媒介稱為
「看不見的微生物」,
06:18
and gave it the name "bacteriophage,"
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取名為「bacteriophage」,
06:19
which, literally translated,
means "bacteria eater."
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字面上直譯的意思
就是「噬菌體」。
06:22
And by the way, this is one
of the most fundamental discoveries
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順便一提,這是現代生物學中
06:25
of modern microbiology.
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最重要的基礎發現之一。
06:27
So many modern techniques go back
to our understanding of how phages work --
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好多現代技術都是建立在我們對於
噬菌體運作方式的了解之上——
06:31
in genomic editing,
but also in other fields.
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基因編輯以及其他領域。
06:33
And just today, the Nobel Prize
in chemistry was announced
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今天,諾貝爾化學獎公佈了,
06:36
for two scientists who work with phages
and develop drugs based on that.
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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。
06:41
Now, back in the 1920s and 1930s,
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在 1920 和 1930 年代時,
06:43
people also immediately saw
the medical potential of phages.
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大家也馬上就看出了
噬菌體在醫療上的潛力。
06:46
After all, albeit invisible,
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畢竟,儘管看不見,
06:48
you had something
that reliably was killing bacteria.
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總是可以依靠它來殺死細菌。
06:51
Companies that still exist today,
such as Abbott, Squibb or Lilly,
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現今仍然存在的公司,
如亞培、施貴寶、禮來,
06:54
sold phage preparations.
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都販售噬菌體製劑。
06:57
But the reality is, if you're starting
with an invisible microbe,
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但,現實是,如果你從
看不見的微生物開始著手,
07:00
it's very difficult to get
to a reliable drug.
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要做出可靠的藥品是很困難的。
07:03
Just imagine going to the FDA today
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想像一下就知道了,
現今如果要去食品及藥物管理局,
07:05
and telling them all about
that invisible virus
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告訴他們你想要給病人
用一種看不見的病毒。
07:07
you want to give to patients.
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07:09
So when chemical antibiotics
emerged in the 1940s,
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所以,在 1940 年代,
當化學抗生素出現時,
07:12
they completely changed the game.
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它們完全改變了這個遊戲。
07:14
And this guy played a major role.
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這個傢伙扮演了重要的角色。
07:16
This is Alexander Fleming.
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他是亞歷山大弗萊明,
得過諾貝爾醫學獎,
07:18
He won the Nobel Prize in medicine
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07:19
for his work contributing
to the development
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他因為開發出最早的抗生素
盤尼西林而得獎。
07:22
of the first antibiotic, penicillin.
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1967
07:24
And antibiotics really work
very differently than phages.
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抗生素的運作方式和噬菌體差很多。
07:29
For the most part, they inhibit
the growth of the bacteria,
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大多數的情況下,
抗生素是抑制細菌的成長,
07:31
and they don't care so much
which kind of bacteria are present.
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它們並不太在乎
出現的細菌是哪一種細菌。
07:35
The ones that we call broad-spectrum
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1930
有一種抗生素叫做廣效抗生素,
07:37
will even work against
a whole bunch of bacteria out there.
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它甚至會對抗一大堆細菌。
07:40
Compare that to phages,
which work extremely narrowly
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相較之下,噬菌體只會針對
一種細菌物種,作用範圍很狹窄,
07:43
against one bacterial species,
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1443
07:44
and you can see the obvious advantage.
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它的優勢十分明顯。
07:47
Now, back then, this must have felt
like a dream come true.
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在當時,感覺大概
就像是夢想成真一樣。
07:50
You had a patient
with a suspected bacterial infection,
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你的病人有疑似細菌感染,
07:53
you gave him the antibiotic,
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你給他服用抗生素,
07:55
and without really needing to know
anything else about the bacteria
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對於造成疾病的那種細菌,
你並不需要知道任何資訊,
07:58
causing the disease,
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07:59
many of the patients recovered.
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許多病人復元了。
08:01
And so as we developed
more and more antibiotics,
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隨著我們開發出越來越多的抗生素,
08:03
they, rightly so, became the first-line
therapy for bacterial infections.
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它們很理所當然地成為了
對抗細菌感染的第一線治療。
08:07
And by the way, they have contributed
tremendously to our life expectancy.
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順便一提,對於我們的壽命延長,
它們也有極大的貢獻。
08:12
We are only able to do
complex medical interventions
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我們現今能夠做到複雜的
醫療干預以及醫療手術,
08:14
and medical surgeries today
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08:16
because we have antibiotics,
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都是因為我們有抗生素,
不用再擔心病人
08:17
and we don't risk the patient
dying the very next day
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在手術過程中受到
細菌感染,導致隔天死亡。
08:20
from the bacterial infection that he might
contract during the operation.
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3847
08:24
So we started to forget about phages,
especially in Western medicine.
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3890
所以,我們開始忘卻了噬菌體,
特別是在西藥的領域中。
08:28
And to a certain extent, even when
I was growing up, the notion was:
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而且忘卻程度已經到了,
我成長過程中聽到的觀念是:
08:32
we have solved bacterial infections;
we have antibiotics.
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3832
我們已經解決了細菌感染,
我們有抗生素。
08:37
Of course, today,
we know that this is wrong.
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2723
當然,現今我們知道這是錯的。
08:40
Today, most of you
will have heard about superbugs.
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2397
現今,大部分人都聽過超級細菌。
08:42
Those are bacteria
that have become resistant
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這些細菌變成已經能夠抵抗
08:45
to many, if not all, of the antibiotics
that we have developed
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4514
所有或大部分我們為了治療感染
所開發出來的抗生素。
08:49
to treat this infection.
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1600
08:51
How did we get here?
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我們是怎麼走到這一步的?
我們沒有自己想像的那麼聰明。
08:53
Well, we weren't as smart
as we thought we were.
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2974
08:56
As we started using
antibiotics everywhere --
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2943
當我們開始到處使用抗生素——
08:59
in hospitals, to treat and prevent;
at home, for simple colds;
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3389
在醫院用來做治療和預防;
在家中用來治感冒;
09:02
on farms, to keep animals healthy --
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2262
在農場用來維持動物的健康——
09:05
the bacteria evolved.
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細菌演化了。
09:07
In the onslaught of antibiotics
that were all around them,
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3849
細菌到處受到抗生素的猛攻,
09:11
those bacteria survived
that were best able to adapt.
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3019
存活下來的細菌是適應力最強的。
09:15
Today, we call these
"multidrug-resistant bacteria."
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現今,我們稱這些細菌為
「多重抗藥性細菌」。
09:18
And let me put a scary number out there.
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讓我給各位看一個可怕的數字。
09:20
In a recent study commissioned
by the UK government,
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英國政府近期委任進行的一項研究
09:22
it was estimated that by 2050,
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2396
估計到了 2050 年,
09:25
ten million people could die every year
from multidrug-resistant infections.
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4118
每年會有一千萬人因為
多重抗藥性感染而死。
09:29
Compare that to eight million deaths
from cancer per year today,
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現今每年死於癌症的人數
是八百萬,相比之下,
09:33
and you can see
that this is a scary number.
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2154
就看得出那個數字有多可怕。
09:35
But the good news is,
phages have stuck around.
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2795
但好消息是,我們還有噬菌體。
09:39
And let me tell you, they are not
impressed by multidrug resistance.
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3206
讓我告訴各位,它們不覺得
多重抗藥性有什麼了不起的。
09:42
(Laughter)
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1151
(笑聲)
09:43
They are just as happily killing
and hunting bacteria all around us.
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5753
它們就是很樂意獵殺掉
我們周圍的細菌。
09:50
And they've also stayed selective,
which today is really a good thing.
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3301
且它們也保有選擇性,
在現今這是一件好事。
09:53
Today, we are able to reliably identify
a bacterial pathogen
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3484
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。
09:56
that's causing an infection
in many settings.
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2494
09:59
And their selectivity will help us
avoid some of the side effects
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3098
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。
10:02
that are commonly associated
with broad-spectrum antibiotics.
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3544
10:06
But maybe the best news of all is:
they are no longer an invisible microbe.
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3833
但,也許最好的消息是:
它們不再是看不見的微生物。
10:10
We can look at them.
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1325
我們能夠看見它們。
我們剛剛也一起看過了。
10:11
And we did so together before.
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1445
10:13
We can sequence their DNA.
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1848
我們能夠將它們的 DNA 定序。
我們了解它們如何複製。
10:15
We understand how they replicate.
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1596
10:16
And we understand the limitations.
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1888
我們了解限制。
10:18
We are in a great place
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1367
現在我們擁有好的技術和資源來開發
10:20
to now develop strong and reliable
phage-based pharmaceuticals.
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強效且可靠的噬菌體藥品。
10:24
And that's what's happening
around the globe.
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那也是現在全球正在做的事。
10:26
More than 10 biotech companies,
including our own company,
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2755
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。
10:29
are developing human-phage applications
to treat bacterial infections.
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3585
10:32
A number of clinical trials
are getting underway in Europe and the US.
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4207
在歐洲以及美國已經有許多
臨床試驗在進行中。
10:37
So I'm convinced
that we're standing on the verge
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2310
所以,我深信我們已經
很接近噬菌體治療的復興。
10:40
of a renaissance of phage therapy.
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1960
10:42
And to me, the correct way to depict
the phage is something like this.
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4228
對我來說,描述噬菌體的
正確方式是這樣。
10:46
(Laughter)
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2492
(笑聲)
10:49
To me, phages are the superheroes
that we have been waiting for
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對我來說,噬菌體是我們
一直在等待的超級英雄,
10:52
in our fight against
multidrug-resistant infections.
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來協助我們對抗多重抗藥性感染。
10:56
So the next time you think about a virus,
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所以,下次當你想到病毒時,
10:59
keep this image in mind.
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別忘了這張圖。
11:01
After all, a phage might
one day save your life.
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2984
畢竟,也許有一天,
噬菌體會救你一命。
11:04
Thank you.
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謝謝。
11:06
(Applause)
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5968
(掌聲)
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