TED2019
David Baker: 5 challenges we could solve by designing new proteins
大衛 · 貝克: 透由設計新的蛋白質，我們能夠解決五大挑戰
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蛋白質是非凡的分子機器：能消化食物、激發神經元、為免疫系統提供動力等等。 如果能設計出具有前所未有功能的新蛋白質會如何？ 大衛 · 貝克在這對未來的非凡展望中，分享他的蛋白質設計團隊如何從零開始創造全新的蛋白質，以及如何有助於解決人類所面臨的五大挑戰。 （這雄心勃勃的計劃是 TED 激勵和資助全球變革的大膽計劃〔Audacious Project〕的一部分。）
David Baker - Computational biologist
David Baker designs new biomolecules (proteins) from first principles to address 21st-century challenges in health and technology. Full bio
David Baker designs new biomolecules (proteins) from first principles to address 21st-century challenges in health and technology. Full bio
Double-click the English transcript below to play the video.
00:12
I'm going to tell you about the most
amazing machines in the world
amazing machines in the world
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我將講述世界上最神奇的機器
00:17
and what we can now do with them.
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以及我們現在能用它來做什麼。
00:19
Proteins,
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你在細胞中看到的一些蛋白質，
00:20
some of which you see inside a cell here,
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00:22
carry out essentially all the important
functions in our bodies.
functions in our bodies.
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基本上在我們體內
執行所有重要的功能。
執行所有重要的功能。
00:26
Proteins digest your food,
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蛋白質可消化食物、
00:28
contract your muscles,
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收縮肌肉、
00:30
fire your neurons
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激發神經元，
00:32
and power your immune system.
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為免疫系統提供動力。
00:34
Everything that happens in biology --
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生物學中發生的一切，
00:36
almost --
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幾乎全都因蛋白質而發生。
00:37
happens because of proteins.
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00:39
Proteins are linear chains
of building blocks called amino acids.
of building blocks called amino acids.
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蛋白質是由稱為「氨基酸」的
積木構成的線性鏈。
積木構成的線性鏈。
00:44
Nature uses an alphabet of 20 amino acids,
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大自然用了 20 種氨基酸字母，
00:47
some of which have names
you may have heard of.
you may have heard of.
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你們可能聽過其中若干名稱。
00:50
In this picture, for scale,
each bump is an atom.
each bump is an atom.
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這圖中比例相對的
每個凹凸都是個原子。
每個凹凸都是個原子。
00:55
Chemical forces between the amino acids
cause these long stringy molecules
cause these long stringy molecules
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氨基酸間的化學力
使這些長而細的分子
使這些長而細的分子
01:00
to fold up into unique,
three-dimensional structures.
three-dimensional structures.
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折疊成獨特的立體結構。
01:03
The folding process,
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雖然折疊的過程看似隨機，
01:05
while it looks random,
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01:06
is in fact very precise.
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實際上非常的精確。
01:08
Each protein folds
to its characteristic shape each time,
to its characteristic shape each time,
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蛋白質總是折疊成其特徵的形狀，
01:13
and the folding process
takes just a fraction of a second.
takes just a fraction of a second.
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而折疊的過程只需幾分之一秒。
01:18
And it's the shapes of proteins
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蛋白質的形狀
01:19
which enable them to carry out
their remarkable biological functions.
their remarkable biological functions.
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使其能夠發揮卓越的生物功能。
01:24
For example,
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例如，
01:25
hemoglobin has a shape
in the lungs perfectly suited
in the lungs perfectly suited
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肺裡的血紅蛋白
具有完全適合結合氧分子的形狀。
01:29
for binding a molecule of oxygen.
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01:31
When hemoglobin moves to your muscle,
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當血紅蛋白移到肌肉時，
01:33
the shape changes slightly
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形狀會稍微改變，
01:35
and the oxygen comes out.
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釋出氧氣。
01:39
The shapes of proteins,
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蛋白質的形狀及其奇妙的功能
01:40
and hence their remarkable functions,
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01:43
are completely specified by the sequence
of amino acids in the protein chain.
of amino acids in the protein chain.
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完全由蛋白質鏈的氨基酸序列所定。
01:49
In this picture, each letter
on top is an amino acid.
on top is an amino acid.
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這張圖片頂部的每個字母都是氨基酸。
01:54
Where do these sequences come from?
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這些序列來自哪裡？
01:57
The genes in your genome
specify the amino acid sequences
specify the amino acid sequences
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基因組中的基因
訂定蛋白質的氨基酸序列。
02:02
of your proteins.
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每個基因
02:03
Each gene encodes the amino acid
sequence of a single protein.
sequence of a single protein.
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為單個蛋白質的氨基酸序列編碼。
02:09
The translation between
these amino acid sequences
these amino acid sequences
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這些氨基酸序列
與蛋白質的結構和功能之間的翻譯
02:13
and the structures
and functions of proteins
and functions of proteins
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02:15
is known as the protein folding problem.
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被稱為蛋白質的折疊問題。
02:18
It's a very hard problem
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這是個非常困難的問題，
02:20
because there's so many different
shapes a protein can adopt.
shapes a protein can adopt.
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因為蛋白質能有許多不同的形狀。
02:24
Because of this complexity,
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由於它這麼複雜，
02:25
humans have only been able
to harness the power of proteins
to harness the power of proteins
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人類只能透由稍微更動
02:28
by making very small changes
to the amino acid sequences
to the amino acid sequences
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自然界蛋白質的氨基酸序列
02:32
of the proteins we've found in nature.
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來利用蛋白質的能量。
02:34
This is similar to the process
that our Stone Age ancestors used
that our Stone Age ancestors used
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這相當於石器時代祖先用來製作
我們在周遭世界發現的
02:38
to make tools and other implements
from the sticks and stones
from the sticks and stones
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木棒、石製工具和其他工具的過程。
02:42
that we found in the world around us.
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02:45
But humans did not learn to fly
by modifying birds.
by modifying birds.
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但是人類並非透由
修改鳥類來學習飛行。
修改鳥類來學習飛行。
02:50
(Laughter)
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（笑聲）
02:52
Instead, scientists, inspired by birds,
uncovered the principles of aerodynamics.
uncovered the principles of aerodynamics.
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相反地，受鳥類啟發的科學家
發現氣體動力學的原理，
發現氣體動力學的原理，
02:59
Engineers then used those principles
to design custom flying machines.
to design custom flying machines.
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接著工程師用這些原理
來設計和製作飛行機器。
來設計和製作飛行機器。
03:04
In a similar way,
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多年來，我們已經用類似的方式
03:05
we've been working for a number of years
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03:07
to uncover the fundamental
principles of protein folding
principles of protein folding
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揭示蛋白質折疊的基本原理，
03:10
and encoding those principles
in the computer program called Rosetta.
in the computer program called Rosetta.
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並用名為 Rosetta 的
電腦軟體將這些原理編碼。
電腦軟體將這些原理編碼。
03:15
We made a breakthrough in recent years.
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我們近年來有了突破，
03:19
We can now design completely new proteins
from scratch on the computer.
from scratch on the computer.
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能夠在電腦上從頭開始
設計全新的蛋白質。
設計全新的蛋白質。
03:24
Once we've designed the new protein,
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一旦設計出新的蛋白質，
03:27
we encode its amino acid sequence
in a synthetic gene.
in a synthetic gene.
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我們就會在合成基因中
將其氨基酸序列編碼。
將其氨基酸序列編碼。
03:31
We have to make a synthetic gene
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我們必須合成基因
03:33
because since the protein
is completely new,
is completely new,
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是因為蛋白質是全新的，
03:35
there's no gene in any organism on earth
which currently exists that encodes it.
which currently exists that encodes it.
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目前地球上沒有任何生物體
有它的基因編碼。
有它的基因編碼。
03:41
Our advances in understanding
protein folding
protein folding
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我們在理解蛋白質的折疊
和如何設計蛋白質方面取得的進展，
03:45
and how to design proteins,
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03:47
coupled with the decreasing cost
of gene synthesis
of gene synthesis
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加上基因合成費用的降低，
03:51
and the Moore's law increase
in computing power,
in computing power,
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以及符合摩爾定律提高的運算能力，
03:54
now enable us to design
tens of thousands of new proteins,
tens of thousands of new proteins,
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使我們現在能夠設計出成千上萬種
具有新形狀和新功能的新蛋白質，
03:59
with new shapes and new functions,
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04:01
on the computer,
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在電腦上設計，
04:03
and encode each one of those
in a synthetic gene.
in a synthetic gene.
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並編碼合成每個基因。
04:08
Once we have those synthetic genes,
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一旦擁有這些合成的基因，
04:09
we put them into bacteria
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我們將其置入細菌，
04:11
to program them to make
these brand-new proteins.
these brand-new proteins.
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讓它們製造這些全新的蛋白質。
04:15
We then extract the proteins
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然後我們提取蛋白質，
04:17
and determine whether they function
as we designed them to
as we designed them to
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看它們的功能是否符合我們的設計，
04:20
and whether they're safe.
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以及它們是否安全。
04:23
It's exciting to be able
to make new proteins,
to make new proteins,
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能製造新的蛋白質令人振奮，
04:26
because despite the diversity in nature,
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因為儘管自然界多姿多樣，
04:28
evolution has only sampled a tiny fraction
of the total number of proteins possible.
of the total number of proteins possible.
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卻只演化出
所有可能的蛋白質
總數中的一小部分。
總數中的一小部分。
04:35
I told you that nature uses
an alphabet of 20 amino acids,
an alphabet of 20 amino acids,
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我說過大自然用了
20 個氨基酸字母，
20 個氨基酸字母，
04:39
and a typical protein is a chain
of about 100 amino acids,
of about 100 amino acids,
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典型的蛋白質是
大約 100 個氨基酸的長鏈，
大約 100 個氨基酸的長鏈，
04:43
so the total number of possibilities
is 20 times 20 times 20, 100 times,
is 20 times 20 times 20, 100 times,
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所以可能性的總數
是 20 乘以 20 乘以 20，
乘 100 次，
04:49
which is a number on the order
of 10 to the 130th power,
of 10 to the 130th power,
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是 10 的 130 次方，
04:52
which is enormously more
than the total number of proteins
than the total number of proteins
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遠遠超過自地球出現生命以來
04:56
which have existed
since life on earth began.
since life on earth began.
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曾經存在過的蛋白質總數。
04:59
And it's this unimaginably large space
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而這正是我們現在能用運算能力
來設計和探索蛋白質的
來設計和探索蛋白質的
05:02
we can now explore
using computational protein design.
using computational protein design.
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難以想像的廣大空間。
05:07
Now the proteins that exist on earth
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現存地球的蛋白質以進化
05:10
evolved to solve the problems
faced by natural evolution.
faced by natural evolution.
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來解決自然演化所面臨的問題。
05:14
For example, replicating the genome.
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例如，複製基因組。
05:18
But we face new challenges today.
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但我們今天面臨新的挑戰。
05:20
We live longer, so new
diseases are important.
diseases are important.
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我們活得更長，
因此新疾病極其重要。
因此新疾病極其重要。
05:23
We're heating up and polluting the planet,
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我們正污染地球和令其升溫，
05:25
so we face a whole host
of ecological challenges.
of ecological challenges.
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因此面臨著一系列的生態挑戰。
05:29
If we had a million years to wait,
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如果我們能等百萬年，
05:31
new proteins might evolve
to solve those challenges.
to solve those challenges.
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新的蛋白質演化
或許能解決這些挑戰。
或許能解決這些挑戰。
05:35
But we don't have
millions of years to wait.
millions of years to wait.
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但我們無法等上百萬年。
05:38
Instead, with computational
protein design,
protein design,
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取而代之，透由運算來設計蛋白質，
05:41
we can design new proteins
to address these challenges today.
to address these challenges today.
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我們能設計新的蛋白質
來對付當前的挑戰。
來對付當前的挑戰。
05:47
Our audacious idea is to bring
biology out of the Stone Age
biology out of the Stone Age
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我們的大膽想法
是透由蛋白質設計的技術革命
05:52
through technological revolution
in protein design.
in protein design.
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帶生物學跳脫石器時代。
05:56
We've already shown
that we can design new proteins
that we can design new proteins
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我們已經證明能夠設計出
具有新形狀、新功能的新蛋白質。
05:59
with new shapes and functions.
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06:01
For example, vaccines work
by stimulating your immune system
by stimulating your immune system
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例如，疫苗透由刺激免疫系統
06:05
to make a strong response
against a pathogen.
against a pathogen.
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對病原體產生強烈的反應作用。
06:09
To make better vaccines,
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為了製造更好的疫苗，
06:11
we've designed protein particles
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我們設計蛋白質顆粒
06:13
to which we can fuse
proteins from pathogens,
proteins from pathogens,
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來融合病原體中的蛋白質——
06:17
like this blue protein here,
from the respiratory virus RSV.
from the respiratory virus RSV.
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就像此處藍色的蛋白質，
取自呼吸道融合病毒 RSV。
（Respiratory Syncytial Virus）
（Respiratory Syncytial Virus）
06:22
To make vaccine candidates
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為確認候選的疫苗
真的含有病毒蛋白，
真的含有病毒蛋白，
06:23
that are literally bristling
with the viral protein,
with the viral protein,
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06:27
we find that such vaccine candidates
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我們發現這候選疫苗
對病毒的免疫反應
對病毒的免疫反應
06:30
produce a much stronger
immune response to the virus
immune response to the virus
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勝過先前已經測試過的任何疫苗。
06:33
than any previous vaccines
that have been tested.
that have been tested.
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06:36
This is important because RSV
is currently one of the leading causes
is currently one of the leading causes
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這很重要，因為
呼吸道融合病毒 RSV
呼吸道融合病毒 RSV
目前是全球嬰兒夭折的主要原因之一。
06:40
of infant mortality worldwide.
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06:44
We've also designed new proteins
to break down gluten in your stomach
to break down gluten in your stomach
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我們還設計新的蛋白質
來分解胃中的麩質，
來分解胃中的麩質，
06:48
for celiac disease
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對付腹腔疾病；
06:50
and other proteins to stimulate
your immune system to fight cancer.
your immune system to fight cancer.
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也設計其他的蛋白質
來刺激免疫系統對抗癌症。
來刺激免疫系統對抗癌症。
06:55
These advances are the beginning
of the protein design revolution.
of the protein design revolution.
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這些進步是蛋白質設計革命的開始。
07:00
We've been inspired by a previous
technological revolution:
technological revolution:
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我們受先前技術革命的啟發。
07:04
the digital revolution,
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數位革命大大歸功於
07:05
which took place in large part
due to advances in one place,
due to advances in one place,
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貝爾實驗室所取得的進步。
07:10
Bell Laboratories.
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07:12
Bell Labs was a place with an open,
collaborative environment,
collaborative environment,
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貝爾實驗室是個開放、協作的環境，
07:15
and was able to attract top talent
from around the world.
from around the world.
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吸引世界各地的頂尖人才。
07:19
And this led to a remarkable
string of innovations --
string of innovations --
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這引領一系列的創新：
07:22
the transistor, the laser,
satellite communication
satellite communication
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電晶體、雷射、衛星通信
07:27
and the foundations of the internet.
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和網際網路的基礎。
07:29
Our goal is to build
the Bell Laboratories of protein design.
the Bell Laboratories of protein design.
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我們的目標是建立
蛋白質設計的貝爾實驗室。
蛋白質設計的貝爾實驗室。
07:34
We are seeking to attract
talented scientists from around the world
talented scientists from around the world
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我們正尋求吸引
世界各地的優秀科學家
世界各地的優秀科學家
07:37
to accelerate the protein
design revolution,
design revolution,
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來一起加速蛋白質設計的革命，
07:40
and we'll be focusing
on five grand challenges.
on five grand challenges.
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我們將專注於五大挑戰。
07:46
First, by taking proteins from flu strains
from around the world
from around the world
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首先經由從世界各地的流感病毒株中
提取蛋白質，
並將它們放在我之前展示的
蛋白質設計顆粒的頂部，
蛋白質設計顆粒的頂部，
07:51
and putting them on top
of the designed protein particles
of the designed protein particles
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07:55
I showed you earlier,
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07:57
we aim to make a universal flu vaccine,
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我們著眼於製造
一種通用的流感疫苗，
一種通用的流感疫苗，
08:00
one shot of which gives a lifetime
of protection against the flu.
of protection against the flu.
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打一針就能保護終生免於流感。
08:05
The ability to design --
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設計能力——
08:06
(Applause)
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（掌聲）
08:12
The ability to design
new vaccines on the computer
new vaccines on the computer
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在電腦上設計新疫苗的能力
08:15
is important both to protect
against natural flu epidemics
against natural flu epidemics
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對於防止自然的流感疫情
08:20
and, in addition, intentional
acts of bioterrorism.
acts of bioterrorism.
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和防範刻意的生物恐攻都很重要。
08:25
Second, we're going far beyond
nature's limited alphabet
nature's limited alphabet
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其次，我們用遠遠超出大自然
有限的 20 個氨基酸字母
08:28
of just 20 amino acids
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08:30
to design new therapeutic candidates
for conditions such as chronic pain,
for conditions such as chronic pain,
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來設計新的治療候選藥物，
來對付像是慢性疼痛，
08:35
using an alphabet
of thousands of amino acids.
of thousands of amino acids.
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用的是數千種氨基酸字母。
08:38
Third, we're building
advanced delivery vehicles
advanced delivery vehicles
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第三，我們正在建立先進的載運工具，
08:42
to target existing medications
exactly where they need to go in the body.
exactly where they need to go in the body.
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以便將現有的藥物準確定位在
它們應該進入的體內位置。
它們應該進入的體內位置。
08:47
For example, chemotherapy to a tumor
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例如，腫瘤的化療，
08:49
or gene therapies to the tissue
where gene repair needs to take place.
where gene repair needs to take place.
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或修復組織的基因治療。
08:55
Fourth, we're designing smart therapeutics
that can do calculations within the body
that can do calculations within the body
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第四，我們正在設計
能在體內運算的智慧療法，
能在體內運算的智慧療法，
09:01
and go far beyond current medicines,
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遠遠超出目前的藥物，
09:03
which are really blunt instruments.
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那些是非常遲鈍的藥物。
09:06
For example, to target a small
subset of immune cells
subset of immune cells
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例如，目標對準
造成自身免疫疾病的
一小部分免疫細胞，
一小部分免疫細胞，
09:10
responsible for an autoimmune disorder,
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09:12
and distinguish them from the vast
majority of healthy immune cells.
majority of healthy immune cells.
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將其與絕大多數
健康的免疫細胞區隔開來。
健康的免疫細胞區隔開來。
09:16
Finally, inspired by remarkable
biological materials
biological materials
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最後，靈感來自
絲綢、鮑魚殼、牙齒等
非凡的生物材料，
非凡的生物材料，
09:20
such as silk, abalone shell,
tooth and others,
tooth and others,
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以及其他材料，
09:25
we're designing new
protein-based materials
protein-based materials
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我們正在設計新的蛋白質基底材料，
09:28
to address challenges in energy
and ecological issues.
and ecological issues.
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以對付能源和生態問題的挑戰。
09:33
To do all this,
we're growing our institute.
we're growing our institute.
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為要做到這一切，
我們正在擴展我們機構。
我們正在擴展我們機構。
09:36
We seek to attract energetic,
talented and diverse scientists
talented and diverse scientists
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我們尋求吸引世界各地
精力充沛、才華橫溢、
多元的科學家——
多元的科學家——
09:42
from around the world,
at all career stages,
at all career stages,
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涵蓋所有的職涯階段——
09:45
to join us.
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來加入我們。
09:47
You can also participate
in the protein design revolution
in the protein design revolution
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你還可以透由我們線上的
折疊和設計遊戲「Foldit」
折疊和設計遊戲「Foldit」
09:50
through our online
folding and design game, "Foldit."
folding and design game, "Foldit."
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參與蛋白質設計革命。
09:55
And through our distributed
computing project, Rosetta@home,
computing project, Rosetta@home,
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透由我們的分散式運算專案
Rosetta@home，
Rosetta@home，
09:59
which you can join from your laptop
or your Android smartphone.
or your Android smartphone.
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可以在筆記型電腦
或安卓智慧手機上操作。
或安卓智慧手機上操作。
10:04
Making the world a better place
through protein design is my life's work.
through protein design is my life's work.
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透由設計蛋白質使世界變得更好
是我的終生職志。
是我的終生職志。
10:08
I'm so excited about
what we can do together.
what we can do together.
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我們能一起做點什麼的想法
深深鼓舞著我。
深深鼓舞著我。
10:11
I hope you'll join us,
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希望你能加入我們。
10:13
and thank you.
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謝謝。
10:14
(Applause and cheers)
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（掌聲）
ABOUT THE SPEAKER
David Baker - Computational biologistDavid Baker designs new biomolecules (proteins) from first principles to address 21st-century challenges in health and technology.
Why you should listen
David Baker is fascinated by biological self-organization. For example: How does the information stored in DNA translate into the intricate world of proteins and cells? The DNA code was solved more than 50 years ago, but the protein folding code has remained one of biology's greatest challenges. Starting 20 years ago, Baker's research team began using computers to model the structures of proteins. His work has advanced to the point where he can now not only predict the shape of natural proteins but also design completely new ones. In recent years, he's designed new experimental cancer therapies, vaccines, nanomaterials and more. He believes that the emerging field of protein design will fundamentally change how people make medicines, materials and more around the world. Now that the protein folding code is solved, the sky's the limit.
Baker is a Professor of Biochemistry and the Director of the Institute for Protein Design at the University of Washington in Seattle. He's also an Investigator at the Howard Hughes Medical Institute and Adjunct Professor of Genome Sciences, Bioengineering, Chemical Engineering, Computer Science, and Physics at the UW. With his colleagues, he developed the Rosetta Commons, the Rosetta@Home project and Foldit, a science video game. He has also launched more than ten companies that are seeking to bring designed proteins into the real world.
David Baker | Speaker | TED.com