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  • 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.

  • Itll 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 calledthe 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 were 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, theyre 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.

Microbes are microscopic organisms that we use to bake bread, brew beer, and lately,

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