Alright, let me tell you about building synthetic cells and printing life. But first, let me tell you a quick story. On March 31, 2013, my team and I received an email from an international health organization, alerting us that two men died in China shortly after contracting the H7N9 bird flu. There were fears of a global pandemic as the virus started rapidly moving across China. Although methods existed to produce a flu vaccine and stop the disease from spreading, at best, it would not be available for at least six months. This is because a slow, antiquated flu vaccine manufacturing process developed over 70 years ago was the only option.
Ben, déixenme falarlles da fabricación de células artificiais e de como imprimir vida. Pero primeiro, voulles contar unha rápida historia. O 31 de marzo de 2013, o meu equipo e mais eu recibimos un correo dunha organización de saúde internacional que nos alertaba da morte de dous homes en China pouco despois de contraer a gripe aviaria H7N9. Temíase unha pandemia global, xa que o virus comezou a propagarse rapidamente na China. Era posible producir unha vacina contra a gripe e deter a súa propagación, pero isto levaría polo menos seis meses. O único método de produción que se tiña naquel momento era un proceso lento e anticuado, desenvolvido había xa 70 anos.
The virus would need to be isolated from infected patients, packaged up and then sent to a facility where scientists would inject the virus into chicken eggs, and incubate those chicken eggs for several weeks in order to prepare the virus for the start of a multistep, multimonth flu vaccine manufacturing process. My team and I received this email because we had just invented a biological printer, which would allow for the flu vaccine instructions to be instantly downloaded from the internet and printed. Drastically speeding up the way in which flu vaccines are made, and potentially saving thousands of lives.
Había que illar o virus de pacientes infectados, envasalo e envialo a un laboratorio, onde os científicos inxectarían o virus en ovos de galiña e incubaríanos durante varias semanas para preparar o virus e poder dar inicio a un proceso de numerosas etapas de elaboración da vacina que levaría varios meses. Eu e o meu equipo recibimos ese correo porque acabábamos de inventar unha impresora biolóxica que permitiría que as instrucións da vacina se descargasen e imprimisen desde Internet de forma inmediata, acelerando drasticamente a produción da vacina e potencialmente salvando milleiros de vidas.
The biological printer leverages our ability to read and write DNA and starts to bring into focus what we like to call biological teleportation. I am a biologist and an engineer who builds stuff out of DNA. Believe it or not, one of my favorite things to do is to take DNA apart and put it back together so that I can understand better how it works. I can edit and program DNA to do things, just like coders programing a computer. But my apps are different. They create life. Self-replicating living cells and things like vaccines and therapeutics that work in ways that were previously impossible.
A impresora biolóxica fai uso da nosa habilidade para ler e escribir ADN e achéganos ao que nos gusta chamar "teletransporte biolóxico". Eu son biólogo e enxeñeiro, e constrúo cousas con ADN. Créano ou non, unha das cousas das que máis gozo é desarmar ADN e xuntalo outra vez entendendo mellor o seu funcionamento. Podo editar e programar ADN como se programara unha computadora. Pero as miñas apps son diferentes. Crean vida. Células vivas autorreplicantes e cousas como vacinas e terapias que funcionan de formas antes consideradas imposibles.
Here's National Medal of Science recipient Craig Venter and Nobel laureate Ham Smith. These two guys shared a similar vision. That vision was, because all of the functions and characteristics of all biological entities, including viruses and living cells, are written into the code of DNA, if one can read and write that code of DNA, then they can be reconstructed in a distant location. This is what we mean by biological teleportation. To prove out this vision, Craig and Ham set a goal of creating, for the first time, a synthetic cell, starting from DNA code in the computer. I mean, come on, as a scientist looking for a job, doing cutting-edge research, it doesn't get any better than this.
Aquí temos a Craig Venter, gañador da Medalla Nacional de Ciencia, e ao premio Nobel Ham Smith. Estes dous homes compartían a mesma idea: se todas a funcións e características de todas as entidades biolóxicas, incluíndo os virus e as células vivas, están escritas no código de ADN, se se pode ler e escribir ese código de ADN pódese reconstruír nunha localización remota. Isto mesmo é ao que nos referimos con teletransporte biolóxico. Para demostrar esta visión, Craig e Ham propuxéronse crear a primeira célula artificial usando código de ADN na computadora. Como científico que busca traballo en investigacións de vangarda, é o mellor que podía pasar!
(Laughter)
(Risas)
OK, a genome is a complete set of DNA within an organism. Following the Human Genome Project in 2003, which was an international effort to identify the complete genetic blueprint of a human being, a genomics revolution happened. Scientists started mastering the techniques for reading DNA. In order to determine the order of the As, Cs, Ts and Gs within an organism. But my job was far different. I needed to master the techniques for writing DNA. Like an author of a book, this started out as writing short sentences, or sequences of DNA code, but this soon turned into writing paragraphs and then full-on novels of DNA code, to make important biological instructions for proteins and living cells. Living cells are nature's most efficient machines at making new products, accounting for the production of 25 percent of the total pharmaceutical market, which is billions of dollars.
O xenoma é a totalidade do material xenético que ten un organismo. Despois do Proxecto Xenoma Humano de 2003, unha iniciativa internacional para identificar e cartografar o xenoma completo do ser humano, desatouse unha revolución no campo da xenómica. Os científicos comezaron a dominar as técnicas para descodificar ADN e así poder determinar a orde das bases A, C, T e G dentro dun organismo. O meu traballo foi diferente. Tiña que entender as técnicas para escribir ADN. Como o escritor dun libro, comecei a escribir oracións curtas, ou secuencias de ADN, que axiña se converteron en parágrafos e logo en novelas enteiras de ADN con instrucións biolóxicas importantes para proteínas e células vivas. As células vivas, son a mellor máquina natural para crear novos produtos, e son responsables da produción do 25% do mercado farmacéutico, que vale miles de millóns de dólares.
We knew that writing DNA would drive this bioeconomy even more, once cells could be programmed just like computers. We also knew that writing DNA would enable biological teleportation ... the printing of defined, biological material, starting from DNA code. As a step toward bringing these promises to fruition, our team set out to create, for the first time, a synthetic bacterial cell, starting from DNA code in the computer. Synthetic DNA is a commodity. You can order very short pieces of DNA from a number of companies, and they will start from these four bottles of chemicals that make up DNA, G, A, T and C, and they will build those very short pieces of DNA for you.
Sabíamos que a escritura de ADN impulsaría aínda máis esta bioeconomía, cando puidéramos programar células igual que unha computadora. Tamén sabíamos que esta escritura, posibilitaría o teletransporte biolóxico, a impresión específica de material biolóxico a partir de un código de ADN. O paso inicial para cumprir este obxectivo, foi a pioneira creación dunha célula bacteriana sintética, a partir do código xenético almacenado na computadora. O ADN sintético é unha materia prima. Existen compañías onde se pode encargar segmentos moi curtos de ADN, elaborados a partir de catro ingredientes básicos: G, A, T e C. Fabrican os segmentos de ADN a pedido.
Over the past 15 years or so, my teams have been developing the technology for stitching together those short pieces of DNA into complete bacterial genomes. The largest genome that we constructed contained over one million letters. Which is more than twice the size of your average novel, and we had to put every single one of those letters in the correct order, without a single typo. We were able to accomplish this by developing a procedure that I tried to call the "one-step isothermal in vitro recombination method."
Durante os últimos 15 anos, os meus equipos desenvolveron a tecnoloxía para xuntar estes segmentos de ADN e formar xenomas bacterianos completos. O xenoma máis grande que construímos tiña máis dun millón de letras. É máis do dobre do tamaño dunha novela media e tivemos que poñer cada letra na orde correcta, sen unha soa gralla. Lográmolo desenvolvendo un procedemento que intentei bautizar "método de recombinación isotérmica in vitro dun solo paso"
(Laughter)
(Risas)
But, surprisingly, the science community didn't like this technically accurate name and decided to call it Gibson Assembly. Gibson Assembly is now the gold standard tool, used in laboratories around the world for building short and long pieces of DNA.
Sorprendentemente, á comunidade científica non lle gustou un nome tan preciso e decidiron chamarlle "ensamblaxe de Gibson". A ensamblaxe de Gibson é a ferramenta modelo que se usa hoxe nos laboratorios de todo o mundo para construír segmentos de ADN, sexan curtos ou longos.
(Applause)
(Aplausos)
Once we chemically synthesized the complete bacterial genome, our next challenge was to find a way to convert it into a free-living, self-replicating cell. Our approach was to think of the genome as the operating system of the cell, with the cell containing the hardware necessary to boot up the genome. Through a lot of trial and error, we developed a procedure where we could reprogram cells and even convert one bacterial species into another, by replacing the genome of one cell with that of another. This genome transplantation technology then paved the way for the booting-up of genomes written by scientists and not by Mother Nature. In 2010, all of the technologies that we had been developing for reading and writing DNA all came together when we announced the creation of the first synthetic cell, which of course, we called Synthia.
Unha vez sintetizado quimicamente o xenoma bacteriano completo, o seguinte era encontrar a maneira de convertelo nunha célula viva independente e autorreplicante. Para nós, o xenoma era como o sistema operativo da célula e a célula contiña o hardware necesario para iniciar o xenoma. Logo de ensaios de proba e erro, desenvolvemos un procedemento para reprogramar células, e incluso converter unha especie bacteriana noutra distinta substituíndo o xenoma dunha célula polo xenoma doutra. Esta tecnoloxía de transplante dos xenomas abriu o camiño para iniciar xenomas creados por científicos e non pola nai natureza. En 2010, todas as tecnoloxías que fomos creando para ler e escribir ADN deron por fin os seus froitos cando anunciamos a creación da primeira célula sintética, á que loxicamente lle chamamos Synthia.
(Laughter)
(Risas)
Ever since the first bacterial genome was sequenced, back in 1995, thousands more whole bacterial genomes have been sequenced and stored in computer databases. Our synthetic cell work was the proof of concept that we could reverse this process: pull a complete bacterial genome sequence out of the computer and convert that information into a free-living, self-replicating cell, with all of the expected characteristics of the species that we constructed.
Dende que se secuenciou o primeiro xenoma bacteriano en 1995, milleiros de xenomas bacterianos foron secuenciados na súa totalidade e arquivados en bases. O noso traballo con células artificiais demostrou que o proceso se podía reverter: podíase coller dunha computadora un xenoma bacteriano completo e converter a información nunha célula independente e autorreplicante con todas as características esperables, para a especie que creamos.
Now I can understand why there may be concerns about the safety of this level of genetic manipulation. While the technology has the potential for great societal benefit, it also has the potential for doing harm. With this in mind, even before carrying out the very first experiment, our team started to work with the public and the government to find solutions together to responsibly develop and regulate this new technology. One of the outcomes from those discussions was to screen every customer and every customer's DNA synthesis orders, to make sure that pathogens or toxins are not being made by bad guys, or accidentally by scientists. All suspicious orders are reported to the FBI and other relevant law-enforcement agencies.
Podo entender que haxa preocupación en canto á seguridade desta manipulación xenética. Temos claro que a tecnoloxía ten potencial para beneficiar moito a nosa sociedade, pero tamén ten potencial para facer dano. Tendo esto en conta, antes de desenvolver o primeiro experimento, o noso equipo traballou coa cidadanía e co Goberno para achar solucións xuntos que axudaran a desenvolver e regular esta tecnoloxía Unha das solucións consistiu en analizar cada cliente e cada pedido de ADN sintético para asegurarse de non crear patóxenos e toxinas por encargo de delincuentes, ou para evitar erros dos científicos. Todos os pedidos sospeitosos son denunciados ao FBI e a outros organismos de seguridade.
Synthetic cell technologies will power the next industrial revolution and transform industries and economies in ways that address global sustainability challenges. The possibilities are endless. I mean, you can think of clothes constructed form renewable biobased sources, cars running on biofuel from engineered microbes, plastics made from biodegradable polymers and customized therapies, printed at a patient's bedside. The massive efforts to create synthetic cells have made us world leaders at writing DNA. Throughout the process, we found ways to write DNA faster, more accurately and more reliably.
A tecnoloxía das células artificiais levaranos á próxima Revolución Industrial, e os cambios que se xerarán nas industrias e nas economías permitirannos enfrontar o desafío global da sustentabilidade. As posibilidades son infinitas. Poderíamos elaborar prendas con materiais renovables de base biolóxica, biocombustible para vehículos a partir de microbios modificados, plásticos a partir de polímeros biodegradables e terapias personalizadas, impresas no cuarto do paciente. O xigantesco traballo que fixemos con estas células converteunos en líderes mundiais na xeración de ADN. No noso camiño, atopamos modos de xerar ADN moito máis rápido, con maior exactitude e máis confianza.
Because of the robustness of these technologies, we found that we could readily automate the processes and move the laboratory workflows out of the scientist's hands and onto a machine. In 2013, we built the first DNA printer. We call it the BioXp. And it has been absolutely essential in writing DNA across a number of applications my team and researchers around the world are working on.
A solidez destas tecnoloxías permitiunos automatizar os procesos facilmente e transferir os protocolos de laboratorio a unha máquina. En 2013 construímos a primeira impresora de ADN. Chamámoslle "BioXp". A máquina foi crucial no proceso de escribir ADN nunha cantidade de aplicacións en que o meu equipo está colaborando con investigadores de todo o mundo.
It was shortly after we built the BioXp that we received that email about the H7N9 bird flu scare in China. A team of Chinese scientists had already isolated the virus, sequenced its DNA and uploaded the DNA sequence to the internet. At the request of the US government, we downloaded the DNA sequence and in less than 12 hours, we printed it on the BioXp. Our collaborators at Novartis then quickly started turning that synthetic DNA into a flu vaccine. Meanwhile, the CDC, using technology dating back to the 1940s, was still waiting for the virus to arrive from China so that they could begin their egg-based approach. For the first time, we had a flu vaccine developed ahead of time for a new and potentially dangerous strain, and the US government ordered a stockpile.
Ao pouco tempo de construir a BioXp foi cando recibimos o correo sobre a gripe aviaria H7N9 en China. Un equipo de científicos chineses xa conseguira illar o virus, secuenciar o seu ADN e subilo a Internet. A pedimento do goberno de EE.UU., descargamos a secuencia de ADN e en menos de 12 horas, imprimímola na BioXp. Os nosos colaboradores de Novartis comezaron axiña a converter ese ADN sintético nunha vacina antigripal. En tanto, o Centro de Control de Enfermidades, con tecnoloxía do anos 40, aínda estaba esperando que o virus chegara de China para poder comezar co método dos ovos. Por primeira vez, tiñamos unha vacina antigripal, en tempo récord, contra unha cepa nova e potencialmente perigosa, e o Goberno dos EE.UU. fixo un pedido.
(Applause)
(Aplausos)
This was when I began to appreciate, more than ever, the power of biological teleportation.
Nese momento, comencei a apreciar máis que nunca o poder do teletransporte biolóxico.
(Laughter)
(Risas)
Naturally, with this in mind, we started to build a biological teleporter. We call it the DBC. That's short for digital-to-biological converter. Unlike the BioXp, which starts from pre-manufactured short pieces of DNA, the DBC starts from digitized DNA code and converts that DNA code into biological entities, such as DNA, RNA, proteins or even viruses. You can think of the BioXp as a DVD player, requiring a physical DVD to be inserted, whereas the DBC is Netflix. To build the DBC, my team of scientists worked with software and instrumentation engineers to collapse multiple laboratory workflows, all in a single box. This included software algorithms to predict what DNA to build, chemistry to link the G, A, T and C building blocks of DNA into short pieces, Gibson Assembly to stitch together those short pieces into much longer ones, and biology to convert the DNA into other biological entities, such as proteins.
Como é evidente, con esto en mente, construímos un teletransportador biolóxico. Chamámoslle DBC, abreviatura de "convertedor dixital-biolóxico" A diferenza da BioXp, que traballa con segmentos curtos de ADN prefabricados o DBC toma código de ADN dixitalizado e convérteo en entidades biolóxicas, como ADN, ARN, proteínas e incluso virus. Poderíase dicir que a BioXp é como un reprodutor de DVD, que precisa que se lle insira un disco físico, mentres que o DBC é como Netflix. Para crear o DBC, o meu equipo colaborou con enxeñeiros en software e instrumentación para integrar unha multitude de protocolos de laboratorio nunha única máquina. Esto incluíu algoritmos para determinar o ADN que se vai fabricar, química para unir as bases de ADN G, A, T e C e formar segmentos curtos, a ensamblaxe de Gibson para unilos e formar outros máis longos e bioloxía para converter o ADN noutras entidades biolóxicas, como as proteínas.
This is the prototype. Although it wasn't pretty, it was effective. It made therapeutic drugs and vaccines. And laboratory workflows that once took weeks or months could now be carried out in just one to two days. And that's all without any human intervention and simply activated by the receipt of an email which could be sent from anywhere in the world. We like to compare the DBC to fax machines. But whereas fax machines received images and documents, the DBC receives biological materials. Now, consider how fax machines have evolved. The prototype of the 1840s is unrecognizable, compared with the fax machines of today. In the 1980s, most people still didn't know what a fax machine was, and if they did, it was difficult for them to grasp the concept of instantly reproducing an image on the other side of the world. But nowadays, everything that a fax machine does is integrated on our smart phones, and of course, we take this rapid exchange of digital information for granted.
Este é o prototipo. Non era bonito, pero era efectivo. Fabricaba medicamentos e vacinas, e protocolos de laboratorio, que antes levaban semanas ou meses, ahora podían executarse tan só nun día ou dous. Todo sen intervención humana e activado de forma sinxela por un correo electrónico que podía ser enviado dende calquera parte do mundo. Gústanos comparar o DBC coas máquinas de fax. A diferenza é que as máquinas de fax recibían imaxes e documentos, e o DBC recibe materiais biolóxicos. Pensen agora na evolución das máquinas de fax. O prototipo da década de 1840 é irrecoñecible comparado cos fax que hai hoxe. Nos anos 80, a maioría da xente aínda non sabía o que era o fax, e se o sabían, resultaba difícil de entender o concepto de que unha imaxe se reproducía instantaneamente noutra parte do mundo. Hoxe, todas as tarefas dun fax están integradas nos nosos teléfonos intelixentes, e por suposto, damos por feito este veloz intercambio de información dixital.
Here's what our DBC looks like today. We imagine the DBC evolving in similar ways as fax machines have. We're working to reduce the size of the instrument, and we're working to make the underlying technology more reliable, cheaper, faster and more accurate. Accuracy is extremely important when synthesizing DNA, because a single change to a DNA letter could mean the difference between a medicine working or not or synthetic cell being alive or dead.
O noso DBC hoxe en día vese así. Prevemos que o DBC evolucionará de maneira similar á maquina de fax. Traballamos para reducir o seu tamaño, e para facer que a tecnoloxía de base sexa máis fiable, económica, veloz e exacta. A exactitude é o máis importante na síntese de ADN, xa que cambiar tan só unha letra do ADN pode determinar se un medicamento funciona ou non, ou se unha célula sintética está viva ou morta.
The DBC will be useful for the distributed manufacturing of medicine starting from DNA. Every hospital in the world could use a DBC for printing personalized medicines for a patient at their bedside. I can even imagine a day when it's routine for people to have a DBC to connect to their home computer or smart phone as a means to download their prescriptions, such as insulin or antibody therapies. The DBC will also be valuable when placed in strategic areas around the world, for rapid response to disease outbreaks. For example, the CDC in Atlanta, Georgia could send flu vaccine instructions to a DBC on the other side of the world, where the flu vaccine is manufactured right on the front lines. That flu vaccine could even be specifically tailored to the flu strain that's circulating in that local area. Sending vaccines around in a digital file, rather than stockpiling those same vaccines and shipping them out, promises to save thousands of lives.
O DBC será útil na fabricación distribuída de medicamentos a partir de ADN. Todos os hospitais do mundo poderían usar un DBC para imprimir medicamentos personalizados para cada paciente no seu cuarto. Ata podo imaxinar que chegará o día no que será normal ter un DBC na casa conectado á computadora ou ao móbil para descargar receitas médicas, como insulina ou terapias de anticorpos. O DBC tamén será útil en sitios estratéxicos de todo o mundo para responder rapidamente a brotes de enfermidades. Por exemplo, o CDC en Atlanta, Georgia, podería enviar instrucións a un DBC ao outro lado do mundo para fabricar unha vacina antigripal directamente onde se precisa. Podería incluso ser unha vacina específica para a cepa da gripe que está circulando nesa zona. Enviar vacinas nun arquivo dixital, en lugar de almacenalas e envialas fisicamente. promete salvar milleiros de vidas.
Of course, the applications go as far as the imagination goes. It's not hard to imagine placing a DBC on another planet. Scientists on Earth could then send the digital instructions to that DBC to make new medicines or to make synthetic organisms that produce oxygen, food, fuel or building materials, as a means for making the planet more habitable for humans.
Por suposto, podemos imaxinar todo tipo de aplicacións. Non é difícil imaxinar un DBC instalado noutro planeta. Os científicos poderían mandar a ese DBC instrucións dixitais dende a Terra para fabricar novos medicamentos ou para crear organismos sintéticos que produzan osíxeno, alimento, combustible ou materiais de construción co obxectivo de facer ese planeta máis apto para a vida humana.
(Applause)
(Aplausos)
With digital information traveling at the speed of light, it would only take minutes to send those digital instructions from Earth to Mars, but it would take months to physically deliver those same samples on a spacecraft. But for now, I would be satisfied beaming new medicines across the globe, fully automated and on demand, saving lives from emerging infectious diseases and printing personalized cancer medicines for those who don't have time to wait.
Xa que a información dixital viaxa á velocidade da luz, sería cuestión de minutos enviar esas instrucións da Terra a Marte, pero levaríanos meses enviar as mesmas mostras fisicamente nunha nave espacial. Por agora, conformaríame con enviar novos medicamentos por todo o mundo de forma automática e baixo pedido, salvar vidas de novas enfermidades infecciosas e imprimir menciñas contra o cancro, para os pacientes que non poden esperar.
Thank you.
Grazas.
(Applause)
(Aplausos)