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.
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.
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.
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.
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.
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.
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."
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.
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.
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.
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.
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.
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.
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.
This was when I began to appreciate, more than ever, the power of biological teleportation.
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.
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.
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.
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.
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.
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.
Thank you.
