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Thank you very much. So one word of notice before we begin,
all the technologies that you are going to see here now are real.
And with that said
I'd like to first tell you the story about
this uh... little girl named Dana
she's very special for me because she's my daugther
and Dana was born with a leg condition requiring frequent surgeries like this one
uh... she had when we were in Boston
and um... I remember taking her to that particular surgery
and uh...
I rembember her being admitted and she was excited at first
and then just before they got into her the OR
I looked at her and she was... afraid, she was little worried and
who wouldn't be? Because surgeries today are complicated
and they're often very risky.
Now let's imagine a few years into the future, into the near future hopefully,
Dana will arrive to hospital for her ??? surgery
and instead of being prepped for anesthesia for the OR
the surgeon will just take a syringe and inside the syringe
there are millions of tiny robots, of tiny machines
that will be injected into Dana's bloodstream.
They will autonomously locate the place they need to be in,
they will excite out the injured tissue,
then will remove dead cells,
then they will...
stimulate and guide the regrowth of healthy cells across those tissue gaps,
they will release drugs that relief pain and reduce inflammation
and all the while Dana will be sitting on the chair
eating a sandwich, reading a book, might be the next
twilight saga book which she'll be able to read because she will be 16 by then
And...(giggles)
uh... when these robots
have completed their job they'll simply disintegrate
and disappear from her bloodstream the next day.
So these nanobots have been envisioned in the past 30 years
by people like Eric Drexler, Robert Freitas and Ray Kuzweil.
Today I'm going to show you that these robots exist
here in Israel.
I'll show you this syringe
which I've brought from my lab.
So this syringe has inside it a thousand billion robots.
So these robots are each fifty nanometers
long as you can see in this slide under the microscope.
Fifty nanometers is about 2000 times thinner than the thickness of your hair
OK? And... umm... These robots were born actually 3 years ago
in a research I did with Shawn Douglas, now a UCSF Professor.
But over the past year and a half
in my group at Bar-Ilan University
We've been developing and testing robots for a variety of
medical and therapeutic tasks.
We've invented ways of making them safe for use
and non-inmunogenic
and we learned how to tune their stability in our bloodstream
to fit either short-term or long-term
even days long medical procedures.
So to carry out medical and therapeutic procedures in our body
with the upmost precision,
we need to be able to control molecules
Controlling molecules is a very simple challenge
in modern scientific knowledge.
OK? Let's speak for example about the class of molecules we know as drugs
So despite...
amazing progress made in the past four decades
the way we think about drugs and we the way we use drugs
has been essentially unchanged
and it's similar as two hundred years ago
right? You hear about about big pharmaceutical companies
spending huge amounts of money
searching for better, safer drugs.
Attempts that usually fail.
OK? but,
searching for let's say a safer cancer drug,
half it is a concept that has a flaw in it.
Because searching for a safer cancer drug
is basically like searching for a gun that kills only bad people
We don't search for such guns,
what we do is training soldiers to use that gun properly
Of course in drugs we can't do this because it seems very hard
But there are things we can do with drugs
for example, we can put the drugs
in particles from which they difuse slowly.
We can attach a drug to a carrier
which takes someplace but, this is not real control.
When we were thinking about control we're thinking about
processes is the real world around us
and what happens when we want to control a process
that's beyond our capabilities as humans
we just connect this process to a computer
and let the computer control this process for us.
OK? So that's what we do.
But obviously this cannot be done with drugs because
the drugs are so much smaller than the computers as we know them
The computer is in fact so much bigger
it's about a hundred million times bigger that any drug molecule.
Our nanobots which were in the syringe
solve this problem because they are in fact
computers the size of molecules.
and they can interact with molecules
and they can control molecules directly,
so just think about all those
drugs that have been withdrawn from the market
for excessive toxicity
right?
It doesn't mean that they are not effective,
they were amazingly effective,
they were just guns shooting in all directions
but in the hands of a well-trained soldier
or a well-programed nanobot
using all the existing drugs
we could hypothetically kill almost any disease.
So we might not need even new drugs.
We have amazing drugs already,
we just don't know how to control them, this is the problem
and our nanobots...
hopefully solve this problem and I'll show you how.
So there is an interesting question "how do we build
a robot or a machine the size of a molecule?"
so the simple answer would be: we can use molecules
to build this machine.
So we're using molecules, but we're not using just any molecule.
We're using the perfect, most beautiful molecule on earth, at least in my opinion,
which is DNA.
And in fact every part of the robot,
every part of out nanorobots:
Moving parts, axis, locks, chasis, software,
everything is made from DNA molecules.
And the techonology that enables us to do this
originated thirty years ago when the pioneering works of Nadrian Seeman,
culminating 7 years ago in the works of Paul Rothemund from Caltech,
which was also featured in TED,
and it's called DNA origami.
Now in DNA origami we do not use a piece of paper,
we use a single long strand of DNA
and we fold it into virtually any shape we want.
For example these shapes, so these are actual microscopic images
of shapes the size of molecules that were folded from DNA.
so the smiley you see here in the center of the screen for example
are a hundred nanometers in size
and we make billions of them in few... in a single reaction.
Now since 2006 several researchers, really talented ones,
have been expanding the limits of the technically feasible in DNA origami
and now we have an astonishig array of shapes and objects which we can build
using this technique.
And these researchers also gave us computer-aided design tools
that enable everyone
very very simply to design objects from DNA
So these CAD tools amazingly
enable us to focus o n the shape we want
forgetting the fact that these structures are in fact assemblies of molecules.
so this is for example a shape the computer can actually turn into DNA molecules.
and the output of this CAD software, as you can see,
is a spreadsheet with fragments of DNA
which you can attach to a message and send to a company
one of two dozen companies that make DNA by order and you'll get those DNA's
several days later to your doorstep
and when you get them all you need to do is just mix them in a certain way
and these molecular bricks will self-assemble into
millions of copies of the very structure that you designed using that CAD software
which is free by the way, you can download it for free.
So, let's have a look at our nanorobots.
So, this is how the nanorobots look like, it's built from DNA as you can see
And it resembles a clam shell in which you can put cargo
You can load anything you want starting from small molecules, drugs,
proteines, enzymes, even nano-particles. Virtually any function
that molecules can carry out, can be loaded into the nanobot
and the nanobot can be programmed to turn on and off
these functions at certain places and at certain times
this is how we control those molecules
and so this particular nanorobot is in an off state, it's closed,it's securely
sequestres anything, any payload you put inside
so it's not accessible to the outside of the robot,
for example, it cannot engage target cells or target tissues
But we can program the nanobot to switch to an on state
based on molecular cues it finds from the environment
so programming the robot is virtually like assemblying a combination lock
using disks that recognize digits,
but of course instead of digits we are assemblying disks that recognize molecules.
So these robots can turn from off to on and when they do
any cargo inside is now accessible,
it can attack target cells or target tissues
or other robots which you'll see later on.
And so we have robots that can switch from off to on
and off again, we can control their kinetics of transition.
We can control which payload becomes accessible at which time point
Let's see an example how these robots for example control a cancer drug
So what you can do is you can take nanobots,
you can put the nastiest cancer drug you may find
into the robots, even a cancer drug
that's been withdrawn because of excessive toxicity
Ok? When the robot is locked
and you put them in your mixture of healthy cells and tumor cells
nothing happens, no cell is affected, because the robot
safely sequesters those drugs inside.
When we unlock the robots
all cells die because the cargo inside the [robot] attacks anything on sight.
So all cells eventually die. In this case this is a fluorescent molecule
to help us see better the output.
But when we program the nanobots to search for tumor cells particulary,
so only the tumor cells
uh... only the tumor cells die because
the robot doesn't care about the bystander cells, about the healthy cells.
So it does not harm them at all.
And we have nanorobots in our lab that can target
about ten types of cancer already and other cell targets
and my team keeps expanding this range monthly.
So these are nanorobots and to another topic
organisms in nature, like bacteria and animals
have learned very early in evolution that working in a coordinated group
conveys advantage
and capabilities beyond those of the individual
and since we are interested in
very complex medical procedures, very complex therapeutic settings,
we're wondering what we could do
if we could engineer artificial swarm behaviors
into our nanobots as well so we could have extraordinarily large groups of nanobots
Can we teach them to behave like animals, like insects
and how do you do this? So the question is interesting.
So you could think one way to do it would be
to look at a natural swarm like this one of fish
and simulate the dynamics of the entire swarm and then try to write the codes
in molecules of course
that mimic the same behaviour
this is virtually impossible, it's impractical
what we do is we take the single fish or a single nanobot in our case
and you design a very basic set of interaction rules
and then you take this one, this nanobot, you make a billion copies of it
and you let the behaviours emerge from that group
let me show you some examples of the things we can already do
for example, just as ants
can shake hands and form physical bridges between two trees
or two remote parts of the same tree,
we already have nanorobots that can reach out for each other
touch each other and shake hands in such a way
they form physical bridges.
Then you can imagine these robots
extending, making bridges extending from one-half
to the other half of an injured tissue,
an injured spinal cord for example
or an injured leg in the case of Dana, my daughter
and once they stretched over that tissue gap
they can apply growth factors, as payloads, and those growth factors
stimulate the re-growth and guide re-growth of cells across the gap.
So we already did that and...
we have robots that can cross regulate each other just like animals do in groups
and this is amazing because as you can see here
you can have two types of robots, Type-A and Type-B
they can cross regulate each other, such that "A" is active
while "B" is not and viceversa.
So this is good for combination therapy
with combination therapy we take multiple drugs, right?
and sometimes two or more of these drugs
can collide and generate side effects,
but here you can put one drug here, one drug here
and the robots will time the activities so that
one drug is active, the other is not and then they can switch
and so two or more drugs can operate at the same time without actually colliding.
Another example that we did is the quorum sensing.
Now quorum sensing is great, it's a bacterial inspired behaviour
It means nanorobots can count themselves
and they can switch to "on" only when reaching a certain population size
this is a mechanism invented by bacteria in evolution
and they regulate amazing behaviours based on just their population density
for example, bioluminescence, this one of the well-studied examples
so our robots can count themselves and switch to on
only when reaching a certain population size which we can program.
This is great because this is a mechanism of programming a drug
to become active only when reaching a certain dose
around the target, regardless of its inherent dose-response curve.
One last I'm gonna show to you is computing,
so this nanobots can do computing.
How's so? If you think about your computer at home,
the processor of the computer is in fact a gigantic swarm of transistors
In an i7 core for example you have 800 million transistors approximately
and they're set to interact in certain ways to produce logic gates
and these logic gates are set to interact to produce computations
so we can also produce computation by setting interactions between nanorobots
to emulate logic gates like you see here
and they form chains and they form pairs
and my team in Bar-Ilan University [has] already developed several architectures
of computing based on interacting nanorobots
and to prototype these
we are using animals, very interesting animals
these are cockroaches,
they are very easy to work with, the're very sweet,
they're actually from South America
and I'm a Soutamerican myself so I fell kinda related
[Laughter]
And hum... so what we do is we inject those robots into the cockroach
and to do that we of course had to put the cockroaches to sleep
have you ever tried putting cockroach to sleep?
We put in the freezer for seven minutes
in they fall asleep
and we can inject these nanorobots inside
and after 20 minutes they start running around, they're happy.
And those robots
while they're doing this, the robots read molecules
from the cockroaches' inputs
and they write their outputs in the form of drugs
activated on those cockroaches' cells
so we can do, we can see that and we already have, as you can see,
architectures of interecting nanorobots that can emulate logical operators
and you can use these as modular parts to build any type universal computer you want
[....]
that can control multiple drugs simultaneously
as a result of biocomputing, this is real universal computing in a living animal.
Now we already have systems that have [the] computing capacity
of an 8-bit computer like Commodore 64.
To make sure we don't lose control over the nanobots after they're injected
my team [has] developed nanorobots that carry antennae
these antennae are made from metal nano-particles.
Now, the antennae enable the nanobots
to respond to externally applied electromagnetic fields
so these nanorobots, this version of nanobots
can actually be activated with a press of a button on a joystick
or for example using a controller
such as the Xbox or Wii if you ever had the chance of playing with those
and you can see one of my students in the lab configuring an Xbox app
to control nanobots.
For example you can imagine nanorobots being injected
to Dana, my daughter for example,
and the doctor can guide those robots
into the site, into the leg and just activate them with a hand gesture.
And you can already see an example where we actually took
cancer cells and loaded robots with cancer drugs
and activated the drug by a hand gesture.
and we can actually kill cancer cells just by doing this,
as you can see here.
And the interesting thing is that
because the controller like the Xbox is connected to the internet,
the controller actually links those nanobots to the network
so they have an actual IP address
and they can be accessed from a remote device sitting on the same network,
for example, my doctor's smartphone
So, OK?, just like controlling a controller, this can be done.
The last thing I'm gonna show is, if you look at our body
you'll see that every cell type, every organ, every tissue
has their own unique molecular signature
and this is equivalent to a physical IP address made of molecules
and if you know these molecules
you can use those nanobots to browse the Organism Wide Web, as we call it
and you can program them to look for bits,
this could be for example signally molecules between cells,
and either fetch them for diagnostics
or carry them to different addresses.
And we already have robots that can hijack
signals between cells
and manipulate an entire network of communications between cells
and this is great for controlling very complex diseases in which many cell types
communicate and orchestrate to perpetuate a disease.
So before I finish I'd just like to thank
my amazing team at Bar-Ilan University
and all the colleagues that took part in this extraordinary journey,
starting from the George Chuch's Lab in Harvard
and ending today in Bar-Ilan University in the new Faculty of Life Sciences,
and I really hope that
anywhere between a year and five years from now
we'll be able to use this in humans
and finally with this the emergence of nanobot society.
Thank you very much.