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.
