- The modern assumption
of regenerative medicine is that it's a clockwork.
So if you have a gene regulatory network
or a pathway,
the only way you're gonna get it
to do something different is through bottom-up rewiring.
But if you're willing to entertain the idea
that there are other competencies,
you might find out that you're much better off
giving stimuli to those tissues
to get them to learn certain associations,
and change their preferences
and change their set points that will then cascade
into complex, highly integrated interactions;
almost like a telescope or a periscope for peering
into another space to which we normally do not have access.
So this is the opportunity before us.
If we were able to communicate to a set of cells
exactly what it is that we want them to build,
we would have the solution
for birth defects,
lost organs of various kinds and limbs.
We could reprogram tumors back to normal.
So all of this would be solved if we could communicate
with the collective intelligence of cells.
And so, the technology
of the future is going to look a lot less like chemistry,
and a lot more like a kind of behavior science
or even a kind of computational psychiatry.
I'm Mike Levin and I'm a professor of biology
at Tufts University.
I'm also at the Wyss Institute at Harvard,
and my group works
on a variety of problems on diverse intelligence
in natural, artificial, and hybrid systems.
We are very used to genetically defined hardware
having a very particular outcome.
Acorns make oak trees,
frog eggs make frogs.
When you ask about
why a certain creature has a shape or a behavior,
the answer is, "Well, the genome,"
then that's what determines it.
But one of the amazing things we're finding is
that around that standard outcome is an option space,
a latent space of possibilities that is huge
and diverse and very hard to guess at.
So for example, oak leaves are typically flat green things
and you might look at those cells and say,
"Okay, so the genome of the oak,
it has the information
that enables them to make this flat green structure."
But if prompted by a parasite,
such as a wasp embryo,
in fact, these same cells can make
a large, round, spiky, red object called a "gall."
And these come in amazing shapes and sizes,
and you you would've never known
that a shape like that is
within the possibility of these plant cells.
It is not a set of pushes
and pulls that forces the chemistry
to go a particular way.
It is a set of signals
that literally change the perception
and the memory of that cellular system
about what to do next.
Almost every aspect of biomedical needs,
all of these things boil down to one fundamental problem:
How do we convince a group
of cells to build a nice, healthy organ?
We may not want to,
in fact, we're not going to be able to micromanage all
of the gene expression, all of the cells,
all the stem cell activity
towards complex states that we're trying to achieve:
For example, regrow somebody's limb,
or provide new eyes or normalize a tumor.
But, if we can take advantage of the native competencies
of cells that are already good at solving certain kinds
of problems, then we have a great ability
to achieve large-scale outcomes that are too complex
for us to micromanage.
So I give a simple example:
The frog, which is an animal that normally
does not regenerate its legs as an adult,
but what we've discovered is that actually
we can give those cells a trigger that take them
down to the path of building an entire leg.
And it's not because we told it how to build a leg
or where the leg goes,
or how many toes the leg is supposed to have,
none of that.
What we did was to communicate
to those cells a simple prompt
that causes them to take on the path
of going in morphous space,
of moving from that injured state to the regenerative state.
And so, all of the tools of neuroscience,
of behavioral science,
they all work in other spaces-
in morphological spaces and physiological spaces.
And so this is now the opportunity for biomedicine.
So some of our recent work
we produce something called a 'Xenobot.'
It's a named after a Xenopus Laevis,
is the name of the frog that we used,
and "bot" because we think it's a biorobotics platform.
At the simplest level,
a Xenobot is what happens when you take some skin
off of an early frog embryo.
You take it away from all the instructive interactions
and all the hacking that normally causes those
cells to have this kind of boring two-dimensional life
on the outer surface of the tadpole.
And you, you ask them,
"Well, what do you wanna do now
that you're not being controlled by these other cells?"
And what they do is self-assemble
into this round little thing which we call a Xenobot
that starts to move around on its own.
It rose against the water and against the bottom
of the Petri dish that they're sitting on.
But it also does things like spontaneously turn around.
Another example, one of the amazing things
that they can do, is they
do something called 'kinematic self-replication.'
So remember that we've made it impossible
for these things to reproduce
on their own because they're just skin.
There's no neurons.
None of the rest of the systems that are needed
for frog-style reproduction are there.
But if you provide them with loose materials,
so basically loose skin cells in their vicinity,
what they do is they run around
and they collect those materials into little piles
and they sort of shape the little piles
and make a little snowball out of them.
That little ball matures
into the next generation of Xenobot.
And guess what it starts to do?
It does exactly the same thing.
It runs around collecting more cells
and makes the next generation of Xenobot.
This is basically Von Neumann's dream
of a robot that goes around and finds materials
in the environment and makes copies of itself.
And none of this was obvious at all
from what we know about frogs and tadpoles,
and their genome.
And so we're just scratching the surface now
of what they're capable of.
We're actively researching their ability to sense,
and remember and what preferences they have,
and can they learn and all of these things.
And so one answer to what is a Xenobot is
it's a biorobotics platform where we can take advantage
of the self-assembling properties
of frog skin cells to make useful biological robots.
It's not just that you could make living machines,
synthetic living machines
that do specific things,
it's actually a sandbox in which
you can learn the rules of morphogenesis;
you can learn to prompt the system
and actually understand what else is it capable of.
And so I think
that the Xenobots are just the first harbingers
of a huge option space of novel bodies,
novel minds that are going to be
with us in the coming decades.
Just that first step into that world
of truly diverse intelligence.
Anytime a technology such as this comes along,
there is a reaction from people
which is basically, "Everything is fine."
And what we need to do is make sure
that these scientists don't screw it up.
And I'm not even a clinician,
but I'm here to tell you that I get phone calls daily
from people with the most unbelievable medical needs.
Things are not fine.
I consider it to be an absolute moral imperative for all
of us in the community to move forward with this work
so that we can provide a better lived experience
for everybody on Earth.
We think very carefully
about the ethics of all of these things,
but that calculus is not just what could go wrong.
The calculus is what is already wrong
if you do nothing.