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Alright, let me tell you about building synthetic cells
譯者: Lilian Chiu 審譯者: 易帆 余
and printing life.
好,讓我來跟各位談談建造合成細胞
But first, let me tell you a quick story.
以及列印生命。
On March 31, 2013,
但首先,讓我很快說個故事。
my team and I received an email from an international health organization,
2013 年 3 月 31 日,
alerting us that two men died in China
我的團隊和我收到一封電子郵件, 寄件者是一間國際健康組織,
shortly after contracting the H7N9 bird flu.
內容是警告我們, 在中國有兩個人死亡,
There were fears of a global pandemic
那是他們染上 H7N9 禽流感之後沒多久的事。
as the virus started rapidly moving across China.
大家很怕發生全球性的流行,
Although methods existed to produce a flu vaccine
因為病毒開始在中國快速散播。
and stop the disease from spreading,
雖然的確有方法可以製造流感疫苗
at best, it would not be available for at least six months.
並阻止該疾病散播,
This is because a slow, antiquated flu vaccine manufacturing process
但最好的情況是要等至少 六個月才有疫苗可用。
developed over 70 years ago was the only option.
這是因為流感疫苗的 製造流程很緩慢、很過時,
The virus would need to be isolated from infected patients,
是至少 70 年前發明的, 但它卻是唯一的選擇。
packaged up and then sent to a facility
必須要把病毒和受感染的病人分離,
where scientists would inject the virus into chicken eggs,
包裝起來,接著送到機構去,
and incubate those chicken eggs for several weeks
在機構中,科學家會 把病毒注射到雞蛋中,
in order to prepare the virus for the start of a multistep,
花數週的時間孵那些雞蛋,
multimonth flu vaccine manufacturing process.
這樣才能將病毒準備好, 開始進行這個有很多步驟、
My team and I received this email
要花數個月時間的疫苗製造流程。
because we had just invented a biological printer,
我的團隊和我收到這封電子郵件,
which would allow for the flu vaccine instructions
是因為我們剛發明了 一台生物列印機,
to be instantly downloaded from the internet and printed.
有了它,就能夠馬上從網路上
Drastically speeding up the way in which flu vaccines are made,
下載流感疫苗的說明書, 並將疫苗列印出來。
and potentially saving thousands of lives.
如此製造流感疫苗就能夠加快許多,
The biological printer leverages our ability to read and write DNA
很可能可以拯救數千條性命。
and starts to bring into focus
生物列印機能讓我們 發揮讀寫 DNA 的能力,
what we like to call biological teleportation.
並讓我們所謂的
I am a biologist and an engineer who builds stuff out of DNA.
生物電子傳送開始被重視。
Believe it or not, one of my favorite things to do
我是生物學家及工程師, 我用 DNA 來建造東西。
is to take DNA apart and put it back together
信不信由你, 我最喜歡做的事情之一,
so that I can understand better how it works.
就是把 DNA 拆解, 再把它組裝回去,
I can edit and program DNA to do things, just like coders programing a computer.
這樣我才能更了解它是怎麼運作的。
But my apps are different.
我可以編輯 DNA、為它寫程式, 就像程式人員為電腦寫程式。
They create life.
但我的應用程式不同。
Self-replicating living cells and things like vaccines and therapeutics
它們能創造生命。
that work in ways that were previously impossible.
自我複製的活細胞, 以及像疫苗及治療法等等,
Here's National Medal of Science recipient Craig Venter
都能以過去不可能做到的方式運作。
and Nobel laureate Ham Smith.
這是美國國家科學獎章 得主克萊格凡特,
These two guys shared a similar vision.
及諾貝爾得主漢彌爾頓史密斯。
That vision was, because all of the functions and characteristics
他們兩個人有很相似的遠景。
of all biological entities, including viruses and living cells,
這個遠景就是,
are written into the code of DNA,
因為所有生物實體的功能和特徵,
if one can read and write that code of DNA,
包括病毒和活細胞的,
then they can be reconstructed in a distant location.
全都被寫在 DNA 碼當中,
This is what we mean by biological teleportation.
如果你能夠讀寫 DNA 碼,
To prove out this vision,
就可以從遠端重新建造它們。
Craig and Ham set a goal of creating, for the first time,
我們所謂的生物傳送就是這個意思。
a synthetic cell, starting from DNA code in the computer.
為了證明這個遠景,
I mean, come on, as a scientist looking for a job,
克萊格和漢彌爾頓設定了 一個目標,這是第一次
doing cutting-edge research, it doesn't get any better than this.
合成細胞是從電腦中的 DNA 碼開始創造出來的。
(Laughter)
我的意思是,拜託, 對一個正在找工作的科學家,
OK, a genome is a complete set of DNA within an organism.
做最尖端的研究, 沒有什麼比這更好的了。
Following the Human Genome Project in 2003,
(笑聲)
which was an international effort to identify
好,基因組是在有機體當中 完整的一組 DNA。
the complete genetic blueprint of a human being,
2003 年有一個人類基因組計劃, 它是一項國際合作,
a genomics revolution happened.
要找出人類的完整基因藍圖, 而在這計畫之後,
Scientists started mastering the techniques for reading DNA.
發生了一次基因組學的革命。
In order to determine the order of the As, Cs, Ts and Gs
科學家開始精通讀 DNA 的技巧,
within an organism.
目的是要判斷一個有機體 當中 A、C、T,
But my job was far different.
和 G 的順序。
I needed to master the techniques for writing DNA.
但我的工作非常不同。
Like an author of a book,
我得要精通寫 DNA 的技巧。
this started out as writing short sentences,
就像一本書的作者,
or sequences of DNA code,
一開始是寫簡短的句子,
but this soon turned into writing paragraphs
或是 DNA 碼的序列,
and then full-on novels of DNA code,
但很快就會變成要寫段落,
to make important biological instructions for proteins and living cells.
再來就是要寫 DNA 碼的整本書了,
Living cells are nature's most efficient machines at making new products,
也就是要針對蛋白質和活細胞, 編寫出重要的生物說明書。
accounting for the production
就製造新產品來說,活細胞 是大自然中最有效率的機器,
of 25 percent of the total pharmaceutical market,
產量就佔了
which is billions of dollars.
整個藥品市場的 25%,
We knew that writing DNA would drive this bioeconomy even more,
也就是數十億美元。
once cells could be programmed just like computers.
我們知道一旦寫細胞 DNA 程式 能夠像寫電腦程式一樣,
We also knew that writing DNA would enable biological teleportation ...
就能再進一步推動這種生物經濟。
the printing of defined, biological material,
我們也知道,能寫 DNA 就能讓生物傳送成真……
starting from DNA code.
將定義好的生物材料列印出來,
As a step toward bringing these promises to fruition,
從 DNA 碼開始。
our team set out to create, for the first time,
為了朝實現這個夢想踏出一步,
a synthetic bacterial cell,
我們的團隊打算 做一件史無前例的事:
starting from DNA code in the computer.
從電腦中的 DNA 碼開始,
Synthetic DNA is a commodity.
創造出合成細菌細胞。
You can order very short pieces of DNA from a number of companies,
合成 DNA 是一種商品。
and they will start from these four bottles of chemicals that make up DNA,
你可以向好幾間公司 訂購非常短的 DNA,
G, A, T and C,
它們會從製造 DNA 的 這四瓶化學物質開始:
and they will build those very short pieces of DNA for you.
G、A、T,和 C,
Over the past 15 years or so,
它們會為你建造出 那些非常短的 DNA。
my teams have been developing the technology
在過去 15 年左右,
for stitching together those short pieces of DNA
我的團隊一直在開發一項技術,
into complete bacterial genomes.
將那些非常短的 DNA 組合在一起,
The largest genome that we constructed contained over one million letters.
成為完整的細菌基因組。
Which is more than twice the size of your average novel,
我們建造出來最大的基因組 內容超過一百萬個字母。
and we had to put every single one of those letters in the correct order,
這是一般小說長度的兩倍,
without a single typo.
且我們把所有那些字母 通通都排成正確的順序,
We were able to accomplish this by developing a procedure
沒有任何打字錯誤。
that I tried to call the "one-step isothermal in vitro recombination method."
我們之所以能完成它, 是因為開發出了一種程序,
(Laughter)
我想稱它為「一步驟 等溫室管內重新組合法」。
But, surprisingly, the science community didn't like this technically accurate name
(笑聲)
and decided to call it Gibson Assembly.
但意外的是,科學界並不喜歡 這種在技術面上很精確的命名,
Gibson Assembly is now the gold standard tool,
決定要叫它「吉布森組合」。
used in laboratories around the world
吉布森組合現在是黃金標準工具,
for building short and long pieces of DNA.
全世界的實驗室都在使用它,
(Applause)
用來建造短的及長的 DNA。
Once we chemically synthesized the complete bacterial genome,
(掌聲)
our next challenge was to find a way
一旦我們以化學方式合成了 完整的細菌基因組,
to convert it into a free-living, self-replicating cell.
我們的下一個挑戰是要想辦法
Our approach was to think of the genome as the operating system of the cell,
將它轉換為能獨立生存、 自我複製的細胞。
with the cell containing the hardware necessary to boot up the genome.
我們的方法是把基因組 當作細胞的作業系統,
Through a lot of trial and error,
細胞內含有必要的硬體, 可以啟動基因組。
we developed a procedure where we could reprogram cells
經過許多次的反複試驗,
and even convert one bacterial species into another,
我們發展出了一種程序, 讓我們能為細胞重新寫程式,
by replacing the genome of one cell with that of another.
甚至將一種細菌轉換成另一種,
This genome transplantation technology then paved the way
做法就是將一個細胞的基因組 置換成另一個細胞的基因組。
for the booting-up of genomes written by scientists
這種基因組移植技術奠定了基礎,
and not by Mother Nature.
讓科學家,而非大自然,
In 2010, all of the technologies
所寫的基因組能夠啟動。
that we had been developing for reading and writing DNA
2010 年,我們為了
all came together when we announced the creation
讀寫 DNA 所發展的所有技術
of the first synthetic cell,
通通整合在一起, 那時我們宣佈創造出了
which of course, we called Synthia.
第一個合成細胞,
(Laughter)
當然,我們稱它為辛西雅。 (註:發音近似「合成」。)
Ever since the first bacterial genome was sequenced, back in 1995,
(笑聲)
thousands more whole bacterial genomes have been sequenced and stored
從 1995 年成功完成 第一次基因組定序之後,
in computer databases.
有數千組細菌基因組被定序 並儲存在電腦資料庫中。
Our synthetic cell work was the proof of concept
我們的合成細胞成果 證明了一個概念,
that we could reverse this process:
那就是我們能反轉這個過程:
pull a complete bacterial genome sequence out of the computer
從電腦中拉出一組 完整的細菌基因組列,
and convert that information into a free-living, self-replicating cell,
將那資訊轉換成為獨立生存、 自我複製的細胞,
with all of the expected characteristics of the species that we constructed.
且具有我們所建立之物種 應該要有的所有特徵。
Now I can understand why there may be concerns
我可以了解為什麼有人會擔心
about the safety of this level of genetic manipulation.
這種程度的基因操控是否安全。
While the technology has the potential for great societal benefit,
雖然這項技術可能可以 為社會帶來很大的益處,
it also has the potential for doing harm.
它也有可能會造成傷害。
With this in mind, even before carrying out the very first experiment,
我們的團隊牢記著這一點, 在開始進行最初一次實驗時,
our team started to work with the public and the government
我們就開始和大眾以及政府合作,
to find solutions together
一起想辦法以負責的方式
to responsibly develop and regulate this new technology.
來發展和規範這項新技術。
One of the outcomes from those discussions was to screen every customer
其中一項得出的討論結果 是要審查每一位客戶
and every customer's DNA synthesis orders,
和每一位客戶的 DNA 合成順序,
to make sure that pathogens or toxins are not being made by bad guys,
以確保不會有病原體 或毒物被壞人製造出來,
or accidentally by scientists.
或不小心被科學家製造出來。
All suspicious orders are reported to the FBI
所有可疑的順序都要 回報給聯邦調查局
and other relevant law-enforcement agencies.
和其他相關的執法機關。
Synthetic cell technologies will power the next industrial revolution
合成細胞技術能夠 驅動下一波的工業革命,
and transform industries and economies
並讓產業和經濟體轉型,
in ways that address global sustainability challenges.
進而解決全球永續性問題的挑戰。
The possibilities are endless.
可能性是無盡的。
I mean, you can think of clothes
各位可以想想衣服,
constructed form renewable biobased sources,
從可再生的生物來源建造出來,
cars running on biofuel from engineered microbes,
工程微生物所產生的生物燃料 可以供應給汽車使用,
plastics made from biodegradable polymers
用可生物降解的聚合物來製造塑膠,
and customized therapies, printed at a patient's bedside.
還有客製化的治療, 直接在病人的病床邊列印出來。
The massive efforts to create synthetic cells
我們投入大量心力在創造合成細胞,
have made us world leaders at writing DNA.
也因此我們在寫 DNA 這方面領先全世界。
Throughout the process, we found ways to write DNA faster,
在這個過程中,我們發現了 可以更快速寫 DNA 的方式,
more accurately and more reliably.
這個方式也更正確、可靠。
Because of the robustness of these technologies,
因為這些技術很健全,
we found that we could readily automate the processes
我們發現,我們已經 可以將過程給自動化,
and move the laboratory workflows out of the scientist's hands
科學家不用再處理 實驗室的工作流程,
and onto a machine.
交給機器即可。
In 2013, we built the first DNA printer.
2013 年,我們打造了 第一台 DNA 列印機。
We call it the BioXp.
我們把它取名叫 BioXp。
And it has been absolutely essential in writing DNA
它對於寫 DNA 來說非常重要,
across a number of applications
我的團隊和世界各地的研究者
my team and researchers around the world are working on.
在研究的數種應用都很需要它。
It was shortly after we built the BioXp
在我們打造出 BioXp 之後沒多久,
that we received that email about the H7N9 bird flu scare in China.
我們就收到了那封關於 中國 H7N9 禽流感的電子郵件。
A team of Chinese scientists had already isolated the virus,
中國的一個科學家團隊 已經將病毒分離出來,
sequenced its DNA and uploaded the DNA sequence to the internet.
將它的 DNA 定序, 並把該 DNA 序列上傳到網路上。
At the request of the US government, we downloaded the DNA sequence
在美國政府的請求下, 我們下載了該 DNA 序列,
and in less than 12 hours, we printed it on the BioXp.
不到 12 小時,我們 就用 BioXp 列印了它。
Our collaborators at Novartis
我們在諾華的共同研究者
then quickly started turning that synthetic DNA into a flu vaccine.
很快就開始將那合成 DNA 轉為流感疫苗。
Meanwhile, the CDC, using technology dating back to the 1940s,
同時,疾病防治中心用的是 40 年代發展的技術,
was still waiting for the virus to arrive from China
他們還在等待 從中國送過來的病毒,
so that they could begin their egg-based approach.
收到之後他們才能開始 採用雞蛋培育的那種方式。
For the first time, we had a flu vaccine developed ahead of time
這是第一次,我們針對 一種可能很危險的新菌株
for a new and potentially dangerous strain,
提前開發出了流感疫苗,
and the US government ordered a stockpile.
且美國政府訂購了一堆來儲備。
(Applause)
(掌聲)
This was when I began to appreciate, more than ever,
從這個時候開始,我比以前更加欣賞
the power of biological teleportation.
生物電子傳送的力量。
(Laughter)
(笑聲)
Naturally, with this in mind,
很自然地,因為這一點,
we started to build a biological teleporter.
我們便開始建造生物電子傳送機。
We call it the DBC.
我們稱它為 DBC,
That's short for digital-to-biological converter.
是「數位轉為生物之轉換器」的縮寫。
Unlike the BioXp,
它和 BioXp 不同,
which starts from pre-manufactured short pieces of DNA,
BioXp 是從預先製造的 短 DNA 開始,
the DBC starts from digitized DNA code
而 DBC 是從數位化的 DNA 碼開始,
and converts that DNA code into biological entities,
並將該 DNA 碼轉換為生物實體,
such as DNA, RNA, proteins or even viruses.
比如 DNA、RNA、 蛋白質,或甚至病毒。
You can think of the BioXp as a DVD player,
可以把 BioXp 想成是 一台 DVD 播放機,
requiring a physical DVD to be inserted,
需要放入實體的 DVD,
whereas the DBC is Netflix.
而 DBC 就是網飛。
To build the DBC,
為了打造 DBC,
my team of scientists worked with software and instrumentation engineers
我的科學家團隊和 軟體及儀表工程師合作,
to collapse multiple laboratory workflows,
將多種實驗室工作流程整合起來,
all in a single box.
通通放在單一個盒子中。
This included software algorithms to predict what DNA to build,
這內容包括了用來預測要建造 哪種 DNA 的軟體演算法、
chemistry to link the G, A, T and C building blocks of DNA into short pieces,
將 DNA 的 G、A、T 及 C 積木 連結起來變成短 DNA 的化學、
Gibson Assembly to stitch together those short pieces into much longer ones,
將這些短 DNA 組合成 更長的 DNA 的吉布森組合,
and biology to convert the DNA into other biological entities,
及將 DNA 轉換成其他生物實體 (如蛋白質)的生物學。
such as proteins.
這是它的原型。
This is the prototype.
雖然它長得不好看,但很有效。
Although it wasn't pretty, it was effective.
它能製造出治療用的藥物和疫苗。
It made therapeutic drugs and vaccines.
以前要花數個星期 甚至數個月的實驗室工作流程,
And laboratory workflows that once took weeks or months
現在只要一到兩天就可以完成。
could now be carried out in just one to two days.
且過程是完全不需要人類動手的,
And that's all without any human intervention
只要接收到電子郵件就可以啟動,
and simply activated by the receipt of an email
從世界上任何地方發信都可以。
which could be sent from anywhere in the world.
我們會把 DBC 比喻成傳真機。
We like to compare the DBC to fax machines.
不過傳真機接收的是影像和文件,
But whereas fax machines received images and documents,
而 DBC 接收的是生物材料。
the DBC receives biological materials.
想想看傳真機是如何演化的。
Now, consider how fax machines have evolved.
和現今的傳真機相比,
The prototype of the 1840s is unrecognizable,
1840 年代的原型機大家都不認得了。
compared with the fax machines of today.
八○年代,大部分的人 仍然不知道傳真機是什麼,
In the 1980s, most people still didn't know what a fax machine was,
就算知道,
and if they did,
他們也很難理解那個概念,
it was difficult for them to grasp the concept
無法想像如何能從世界的另一端 立即重新製造出一張影像。
of instantly reproducing an image on the other side of the world.
但現今,傳真機所有的功能 都被整合到我們的智慧手機中,
But nowadays, everything that a fax machine does
我們還視快速交換 數位資訊為理所當然。
is integrated on our smart phones,
現在我們的 DBC 是這樣的。
and of course, we take this rapid exchange of digital information for granted.
我們想像 DBC 和傳真機 用類似的方式演化。
Here's what our DBC looks like today.
我們正在努力 把這台儀器的尺寸縮減,
We imagine the DBC evolving in similar ways as fax machines have.
我們也在努力讓背後要用到的技術
We're working to reduce the size of the instrument,
更可靠、更便宜、更快速且更精確。
and we're working to make the underlying technology
在合成 DNA 時, 精確性是極度重要的,
more reliable, cheaper, faster and more accurate.
因為只要有一個 DNA 字母不一樣,
Accuracy is extremely important when synthesizing DNA,
可能就是藥品是否有效的差別,
because a single change to a DNA letter
或合成細胞是生是死的差別。
could mean the difference between a medicine working or not
若要針對從 DNA 開始的藥品 進行分散製造,
or synthetic cell being alive or dead.
DBC 是很有用的。
The DBC will be useful for the distributed manufacturing
世界上的每一間醫院 都能用一台 DBC
of medicine starting from DNA.
直接在病人的病床邊為他們 列印出個人化的藥品。
Every hospital in the world could use a DBC
我甚至可以想像有一天, 人類的日常會變成是
for printing personalized medicines for a patient at their bedside.
每個人的家中電腦或智慧手機 都和一台 DBC 連結在一起,
I can even imagine a day when it's routine for people to have a DBC
可以直接下載他們的處方,
to connect to their home computer or smart phone
比如胰島素或抗生素治療。
as a means to download their prescriptions,
DBC 還有一個很大的價值, 就是放在世界各地的戰略地區,
such as insulin or antibody therapies.
對疾病的爆發能做出快速應變。
The DBC will also be valuable when placed in strategic areas around the world,
比如,喬治亞州 亞特蘭大的疾病防治中心
for rapid response to disease outbreaks.
就可以把流感疫苗指示 發送給世界另一端的 DBC,
For example, the CDC in Atlanta, Georgia
在另一端,就可以直接在最前線 把流感疫苗製造出來。
could send flu vaccine instructions to a DBC on the other side of the world,
甚至可以針對當地流行的流感菌株
where the flu vaccine is manufactured right on the front lines.
來量身打造流感疫苗。
That flu vaccine could even be specifically tailored to the flu strain
以數位檔案的形式把疫苗送到各地,
that's circulating in that local area.
而不是貯存一堆同樣的疫苗 再將它們運送出去,
Sending vaccines around in a digital file,
這種新方式有望拯救許多條人命。
rather than stockpiling those same vaccines and shipping them out,
當然,想像有多廣,應用就有多廣。
promises to save thousands of lives.
不難想像將 DBC 放到另一個星球上。
Of course, the applications go as far as the imagination goes.
地球上的科學家可以將 數位指示發送到那台 DBC,
It's not hard to imagine placing a DBC on another planet.
製造新的藥物 或製造合成有機物體,
Scientists on Earth could then send the digital instructions to that DBC
來產生氧氣、食物、 燃料,或建造出材料,
to make new medicines or to make synthetic organisms
用這種方式,讓該星球 更適合人類居住。
that produce oxygen, food, fuel or building materials,
(掌聲)
as a means for making the planet more habitable for humans.
如果用光速來傳送數位資訊,
(Applause)
只要花幾分鐘, 就能把數位指示從地球
With digital information traveling at the speed of light,
發送到火星,
it would only take minutes to send those digital instructions
但如果要用太空船 來實際遞送同樣的樣本,
from Earth to Mars,
會花數個月。
but it would take months to physically deliver those same samples
但目前,我已經很滿足,我們 可以向全球各地發送新的藥品,
on a spacecraft.
過程完全自動化,有求必應,
But for now, I would be satisfied beaming new medicines across the globe,
拯救人命,對抗新興的感染性疾病,
fully automated and on demand,
並為沒有時間等待的人, 列印出個人化的癌症藥物。
saving lives from emerging infectious diseases
謝謝。
and printing personalized cancer medicines for those who don't have time to wait.
(掌聲)
Thank you.
(Applause)