On March 31, 2013, the death of two men in China raised an international alarm. This was because they had contracted bird flu and a global pandemic was feared because the virus was already spreading rapidly throughout China. Although there were and there are methods to produce a vaccine and stop the spread of the disease, at best it would not be available for at least six months. This was because the process of producing that vaccine was slow and outdated.
The standard process for producing the vaccine against avian influenza consists of separating the virus from infected patients, injecting it into some hen eggs and then allowing the eggs to incubate for several weeks in order to prepare the virus for a production process consisting of several stages over several months.
Fortunately, this was not the only option; an American company called Novartis had just invented a biological printer, which allows instructions for the vaccine to be downloaded from the internet and printed immediately. This drastically accelerated the vaccine production process, potentially saving millions of lives.
The biological printer affects our ability to read and write DNA and begins to focus on what is called "biological teleportation". DNA can be modified and reprogrammed, just as a programmer writes code to create all the functionality of a computer. Even the applications are different; some modify the second generation of a species, some give life to other self-replicating living cells, entities such as vaccines and therapies that operate in ways that even just a few years ago were science fiction. Some researchers like Craig Venter, winner of the National Medal of Science, and Nobel Prize winner Ham Smith shared a similar vision. The vision started from the fact that all the functions and characteristics of all biological entities, including viruses and living cells, are written in DNA code. So if you can write and read that code, then you can rewrite those characteristics in a remote location. This is what is understood as "biological teleportation". To implement this vision, Craig and Ham set the goal of creating, for the first time, a synthetic cell from the genetic code inserted in a computer.
A genome is a complete set of DNA within an organism. Following the "Human Genome Project" in 2003, an international effort to identify the complete genetic model of a human being, a genomic revolution took place. Scientists began to master the techniques to read DNA. In order to determine the order of the nitrogen bases; Adenine, Cytosine, Thymine and Guanine within an organism. The work of a biological printer is very different; it is essential to master the techniques to actually "write" DNA. Researchers have been like authors: they started by writing short sentences, or sequences of the genetic code, which soon became real paragraphs and novels written in genetic code, to create important biological commands for proteins and living cells. Living cells are the most efficient machines in nature. They alone account for 25% of the production of the total pharmaceutical market, which amounts to billions of dollars. Knowing how to write DNA would have given a further boost to this bioeconomy, as soon as cells could be programmed like computers. It went without saying that the ability to write DNA would allow "biological teleportation", the printing of a defined biological material, starting with the genetic code.
The first step was to create, for the first time, a synthetic bacterial cell, starting from a genetic code inserted in a computer. Synthetic DNA is a product. It is possible to order short DNA sequences from a number of companies, which will use five chemicals of which the DNA itself is composed - i.e. Guanine, Adenine, Thymine, Cytosine and Uracil - and build those short DNA sequences for those who require them. Over the past 15 years, pharmaceutical companies have developed the technology to sew those short DNA sequences together into complete bacterial genomes. The largest genome ever made contained over a million letters (more than twice as many as a typical novel), and each letter had to be arranged in the correct order, without even one mistake. They were able to accomplish this thanks to a procedure called the "single-phase isothermal method of recombination in vitro", also known as "Gibson Assembly" after the discoverer Dan Gibson. The "Gibson Assembly" is now the standard method used in laboratories around the world to create short and long DNA sequences.
After chemically synthesizing a complete bacterial genome, the next challenge was to find a way to convert it into a living, self-replicating cell. It was enough to think of the genome as the operating system of the cell, with the cell containing the hardware needed to start the genome (or the self-replicating "program"). Through numerous attempts and errors, it has been possible to develop a procedure where it is possible to reprogram cells and even convert them from one bacterial species to another, replacing the genome of one cell with that of another (i.e. obtain a different cell from the original one). This genome transplantation technology then opened the way for genomes written by scientists and not by Mother Nature. In 2010, all these technologies developed to read and write DNA combined when the creation of the first synthetic cell was announced.
Since the creation of the first bacterial genome in 1995, thousands more bacterial genomes have been created and stored in computer databases. The incredible thing was the demonstration of the feasibility of the reverse process: to take a complete sequence of bacterial genome from the computer and convert that information into a living, self-replicating cell with all the expected characteristics of the created species. This new technology is expected to drive the next industrial revolution and transform industries and economies to meet the challenges of global sustainability. There are truly endless possibilities: just think of clothes made from bio-based and renewable materials, machines that use biofuel designed by microbes, plastics made from biodegradable polymers and tailor-made therapies, printed directly from the patient.
Thanks to the robustness of these technologies, it has been possible to automate processes and move the workflow from scientists to computers. In 2013, the first genetic printer called BioXp was built. It was shortly after BioXp was built that Novartis received an email about the fear of avian flu in China. A team of Chinese scientists had already separated the virus, created it and uploaded the genetic sequence to the internet. At the request of the U.S. government, Novartis downloaded that sequence and, in less than 12 hours, was able to print it using BioXp. Subsequently, they transformed the synthetic DNA into a vaccine. Meanwhile, the Center for Disease Prevention and Control (CDC), using technology dating back to 1940, was still waiting for the virus to arrive from China, so they could begin their egg-based approach. For the first time, a vaccine was developed just in time to counter a new and potentially dangerous form of influenza before the epidemic spread unchecked.
With this in mind, Novartis began to build the first biological teleportation, the DBC, the "digital to biological converter". DBC begins with the digitized genetic code (the "cell novel") and converts it into real biological entities, such as DNA, RNA, proteins and viruses.
Metaphorically, BioXp is like a DVD player that requires a concrete DVD, the genome, to be "projected". While the DBC is like a streaming site where, in order to watch a movie, just click on an icon. To build the DBC, a team of biologists and geneticists worked with software engineers to close multiple workflows into a single machine. This includes software algorithms to predict which DNA to build, chemistry to connect Guanine, Adenine, Thymine and Cytosine by first building the short gene sequences, the Gibson Assembly to sew those short sequences together into long sequences, and finally biology to convert DNA into increasingly complex biological entities such as proteins.
This technology has created and creates therapeutic medicines and vaccines. And workflows that once took weeks or months can now be done in a few days. All this without any human intervention, activated simply by the receipt of an email that could be sent from anywhere in the world. But researchers have not stopped there, they are working to reduce the size of the DBC: more reliable, cheaper, faster and more precise. Accuracy is extremely important when synthesizing DNA, because a single modification to a DNA letter could make the difference between success and failure, or the life or death of the synthetic cell.
DBC will be useful to distribute the production of medicines from DNA. Every hospital in the world could use DBC to print medicines tailored to their inpatients. You can also imagine a day where it will be routine for people to have a DBC and connect it to their computer or smartphone as a means to download prescriptions, such as insulin for diabetics or antibody therapies for immunodepressants. DBC could also be located in strategic areas around the world as a rapid response to epidemics. For example, the CDC in Atlanta could send instructions for the vaccine to a DBC in the other part of the world, where the vaccine is produced on the front line. The vaccine can also be specifically tailored to the influenza strain circulating in that local area. Sending vaccines via a digital file, instead of making a stockpile to physically ship, promises to save millions of lives.
Of course, the jobs go as far as the imagination itself. It's not hard to imagine a DBC on another planet. Scientists on Earth could send digital instructions to that DBC to create new medicines or synthetic organisms that produce oxygen, food, fuel and building materials, as a means to make the target planet more habitable for humans.
With digital information traveling at the speed of light, it would take a few minutes to send that information from Earth to Mars, but it would take months to physically deliver the same samples with a spaceship. For now, we could be happy to send new medicines around the world fully automated and on demand, saving lives from emerging infectious diseases and printing cancer medicines for those who don't have time to wait.