Subtitles section Play video Print subtitles Microbes are microscopic organisms that we use to bake bread, brew beer, and lately, engineer with synthetic DNA to create new biological systems. In this world of synthetic biology, a microbe is seen as a chassis - or a structural frame to add genes & DNA. It’ll get tested and have its performance improved, so it can hopefully do something useful for the world. Yet this potential to modify living organisms and steer them towards global problems is often met with a dark side. It’s a swing between promise and total peril, and sometimes called “the halfpipe of doom”. To understand why this framing exists, we have to go back to the early 2000s The Human Genome project was nearing the finish line. And scientists had new molecular tools to dream up promising applications. And, a major terrorist attack hit New York City. “There it is the plane went right through the other tower of the World Trade Center. In just a weeks time, we have had four confirmed cases with anthrax all with media connections and a number of anthrax scares as well.” At that point, synthetic biology became a potential tool for a whole new kind of weapon. When most people think about a bio weapon they think about some kind of organism, you might think about anthrax bacteria or the smallpox virus, and that is your weapon. But turning an organism into a lethal pathogen that can do predictable harm requires more sophistication. Not only do you have to have a pathogen, but then you have to actually know how to reliably hold it, grow it, and then determine ways that you can effectively disseminate it so that the bacteria or toxin wouldn't be destroyed. After World War I, multiple state governments launched their own biological weapons programs, as a research endeavor and stockpiling counter-measure. That's probably one of the most sort of top secret pieces of our former bioweapons program is that formulation of how you keep these things stable to survive as a weapon. These things are living organisms, so they are very finicky. In the Soviet biological weapons program, they tried to create a plague bacteria that was resistant to several different antibiotics. They created this super, duper plague weapon, but actually it was a horrible weapon because it would just die. They couldn't have it survive in the environment. With this focused experimentation, scientists ended up creating enough bioweapons to kill every person on the planet. But luckily, national governments signed a treaty to ban biological weapons. Decades later, huge investments in genetics made the tools and techniques cheaper and more accessible. Enough for it to be possible to create an engineered synthetic pathogen. And that’s why synthbio, and its quest to make biology easier to engineer set off alarm bells. In 2002, a group of scientists from the State University of New York at Stony Brook created the first artificial polio virus, synthetically, not using any natural viral components, so that was a real radical innovation. At that time, a congressman picked up the New York Times that day, read about this artificial synthesis of the polio virus, and really got freaked out. Then, a lot of other federal entities got concerned about what happened here. Did we slip up? Should we have done more to have oversight over this? This polio virus study was actually funded by DARPA, an agency within the U.S. government. All this controversy came out: is this experiment a blueprint for bio terrorism? I became very interested in sort of really wondering is that the case? Is it now that easy to create the pathogen from scratch? And, I was, I wasn't sure. There was a lot of focus on the materials that the scientists basically could buy commercially to do their experiments, the fact that they could download information off of the internet, so it wasn't really anything that required highly sophisticated material or equipment. But there’s more to this particular story. I thought it would be interesting to go and interview the scientists involved. And what was really fascinating is once I started kind of probing a little bit about the experiment, they suddenly came to describe this later part, which actually required a significant amount of expertise. Basically if you couldn't do that part of the experiment, the experiment would fail. You couldn't actually create the artificial polio virus. But you wouldn't know that by reading any of the newspaper reports. You wouldn't know that even by reading the scientific paper itself. And that widely unreported part involved a famous cell line...and cow serum. To make this artificial virus, it actually requires, a very rigorous level of purity of these HeLa cell extracts. These HeLa cells are grown in this cow serum. When they've tried to do this experiment using cow serum bought at different times of the year, that can actually cause a failure in experiments. They're hypothesizing because they're not really sure, but maybe in these different times of the year, these cows are eating different kinds of things, and that at a very micro level in the cell actually makes a huge difference. From my perspective, I would just like to see more robust kinds of assessments on these technologies instead of the quick jump to go, "Oh my god, materials, equipment. A garage lab, oh my god, something bad is going to happen." And instead sort of really trying to parse out, "Okay, what is becoming more easy? What is becoming more difficult? Because that is the issue. For example with the polio virus experiment that part of the experiment that was difficult is still difficult today. Nothing, over 18 years, nothing has changed to make that easier. So expertise is really key here. But even the experts understand that there are legitimate security vulnerabilities with a rapidly advancing field like synthetic biology. The National Academies of Science released a major report on it, with a ranked list of threat concerns. High on the list is recreating known pathogenic viruses and making existing bacteria more dangerous, lowest is modifying the human genome with gene drives. Some suggestions in the report involve developing detection tools & computational approaches that can better screen for any rogue engineered organisms. And this is exactly what Ginkgo Bioworks, a synthetic organism factory, is working on. The goal of the Felix program is to determine whether a piece of DNA, a sequence of DNA on a computer, is genetically engineered, or not. IARPA has funded many different performers across the US to take a crack at this problem. And we’re all taking very, very different approaches. You can slice these kind of signatures of engineering in a number of different ways. So some organisms are 80% AT. Some are 80% GC. What this means is that if you take the DNA from different organisms, and glue them together, and you're counting the A's, C's, T's, and G's. Eventually, if you're looking at DNA that's been glued together from disparate sources, you'll see some major swing in those statistics. To investigate these signatures, they’re pooling together data from their own experiments into this massive database for algorithms to then do what they do best. We've developed AI's that can manipulate all of these different styles of genetic engineering, and generate the data for us. So far, they've simulated five million synthetic genomes as a training ground for these machine learning algorithms. The main goal here is to build up a bio-security sector, along with the advance of genetic engineering. So that, unlike in the case of cyber-security, that we're ready when threats actually emerge. It’s a smart way to get out front on the issue, by leveraging the field’s advanced tools and techniques as part of the security solution. We're quizzed, and tested, regularly with blind samples. There are a number of testing and evaluation teams, which come out of the national labs. They are genetically engineering organisms in their laboratories, sequencing them, and sending us blinded samples of all kinds of weird natural organisms, as well as genetically engineered organisms. This happens about every seven or eight months. And we have to report back to them which data sets have been engineered, and which ones haven't. Initiatives like this will continue to take shape as an industry forms around synthetic biology. Because the technology needed to recreate and remix DNA sequences is here, and resurrecting extinct viruses in synthetic form for new medical therapies is part of the field’s evolution. The 2002 poliovirus might have been the first, but it won’t be the last. There are so many laboratories worldwide that use materials and equipment for basic academic research for positive beneficial industry related research, for clinical applications. There's not an easy point in the life sciences where you can say, "Well, this is weapons and it's bad. And this is research and applications and it's good." This duality goes straight to the heart of the field, to the microbes themselves. There are millions of them in our world with dual use, some can make us dangerously sick, and some can fight disease. It’s a wide continuum presented to us by nature itself, and ultimately up to us to navigate through.