How to build synthetic DNA and send it across the internet Dan Gibson
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.
(Laughter)
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.”
(Laughter)
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.
(Applause)
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.
(Laughter)
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.
(Applause)
This was when I began
to appreciate, more than ever,
the power of biological teleportation.
(Laughter)
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.
(Applause)
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.
(Applause)