Martin Hanczyc: The line between life and not-life

So historically there has

been a huge divide between what people

consider to be non-living systems on one

side, and living systems on the other side.

So we go from, say, this beautiful and

complex crystal as non-life, and this rather

beautiful and complex cat on the other side.

Over the last hundred and fifty years or so,

science has kind of blurred this distinction

between non-living and living systems, and

now we consider that there may be a kind

of continuum that exists between the two.

We'll just take one example here:

a virus is a natural system, right?

But it's very simple. It's very simplistic.

It doesn't really satisfy all the requirements,

it doesn't have all the characteristics

of living systems and is in fact a parasite

on other living systems in order to, say,

reproduce and evolve.

But what we're going to be talking about here

tonight are experiments done on this sort of

non-living end of this spectrum -- so actually

doing chemical experiments in the laboratory,

mixing together nonliving ingredients

to make new structures, and that these

new structures might have some of the

characteristics of living systems.

Really what I'm talking about here is

trying to create a kind of artificial life.

So what are these characteristics that I'm

talking about? These are them.

We consider first that life has a body.

Now this is necessary to distinguish the self

from the environment.

Life also has a metabolism. Now this is a

process by which life can convert resources

from the environment into building blocks

so it can maintain and build itself.

Life also has a kind of inheritable information.

Now we, as humans, we store our information

as DNA in our genomes and we pass this

information on to our offspring.

If we couple the first two -- the body and the metabolism --

we can come up with a system that could

perhaps move and replicate, and if we

coupled these now to inheritable information,

we can come up with a system that would be

more lifelike, and would perhaps evolve.

And so these are the things we will try to do

in the lab, make some experiments that have

one or more of these characteristics of life.

So how do we do this? Well, we use

a model system that we term a protocell.

You might think of this as kind of like a

primitive cell. It is a simple chemical

model of a living cell, and if you consider

for example a cell in your body may have

on the order of millions of different types

of molecules that need to come together,

play together in a complex network

to produce something that we call alive.

In the laboratory what we want to do

is much the same, but with on the order of

tens of different types of molecules --

so a drastic reduction in complexity, but still

trying to produce something that looks lifelike.

And so what we do is, we start simple

and we work our way up to living systems.

Consider for a moment this quote by

Leduc, a hundred years ago, considering a

kind of synthetic biology:

"The synthesis of life, should it ever occur,

will not be the sensational discovery which we

usually associate with the idea."

That's his first statement. So if we actually

create life in the laboratories, it's

probably not going to impact our lives at all.

"If we accept the theory of evolution, then

the first dawn of synthesis of life must consist

in the production of forms intermediate

between the inorganic and the organic

world, or between the non-living

and living world, forms which possess

only some of the rudimentary attributes of life"

-- so, the ones I just discussed --

"to which other attributes will be slowly added

in the course of development by the

evolutionary actions of the environment."

So we start simple, we make some structures

that may have some of these characteristics

of life, and then we try to develop that

to become more lifelike.

This is how we can start to make a protocell.

We use this idea called self-assembly.

What that means is, I can mix some

chemicals together in a test tube in my lab,

and these chemicals will start to self-associate

to form larger and larger structures.

So say on the order of tens of thousands,

hundreds of thousands of molecules will

come together to form a large structure

that didn't exist before.

And in this particular example,

what I took is some membrane molecules,

mixed those together in the right environment,

and within seconds it forms these rather

complex and beautiful structures here.

These membranes are also quite similar,

morphologically and functionally,

to the membranes in your body,

and we can use these, as they say,

to form the body of our protocell.

Likewise,

we can work with oil and water systems.

As you know, when you put oil and water together,

they don't mix, but through self-assembly

we can get a nice oil droplet to form,

and we can actually use this as a body for

our artificial organism or for our protocell,

as you will see later.

So that's just forming some body stuff, right?

Some architectures.

What about the other aspects of living systems?

So we came up with this protocell model here

that I'm showing.

We started with a natural occurring clay

called montmorillonite.

This is natural from the environment, this clay.

It forms a surface that is, say, chemically active.

It could run a metabolism on it.

Certain kind of molecules like to associate

with the clay. For example, in this case, RNA, shown in red

-- this is a relative of DNA,

it's an informational molecule --

it can come along and it starts to associate

with the surface of this clay.

This structure, then, can organize the

formation of a membrane boundary around

itself, so it can make a body of

liquid molecules around itself, and that's

shown in green here on this micrograph.

So just through self-assembly, mixing things

together in the lab, we can come up with, say,

a metabolic surface with some

informational molecules attached

inside of this membrane body, right?

So we're on a road towards living systems.

But if you saw this protocell, you would not

confuse this with something that was actually alive.

It's actually quite lifeless. Once it forms,

it doesn't really do anything.

So, something is missing.

Some things are missing.

So some things that are missing is,

for example, if you had a flow of energy

through a system, what we'd want

is a protocell that can harvest

some of that energy in order to maintain itself,

much like living systems do.

So we came up with a different protocell

model, and this is actually simpler than the previous one.

In this protocell model, it's just an oil droplet,

but a chemical metabolism inside

that allows this protocell to use energy

to do something, to actually become dynamic,

as we'll see here.

You add the droplet to the system.

It's a pool of water, and the protocell

starts moving itself around in the system.

Okay? Oil droplet forms

through self-assembly, has a chemical

metabolism inside so it can use energy,

and it uses that energy to move itself

around in its environment.

As we heard earlier, movement is very

important in these kinds of living systems.

It is moving around, exploring its environment,

and remodeling its environment, as you see,

by these chemical waves that are forming by the protocell.

So it's acting, in a sense, like a living system

trying to preserve itself.

We take this same moving protocell here,

and we put it in another experiment,

get it moving. Then I'm going

to add some food to the system,

and you'll see that in blue here, right?

So I add some food source to the system.

The protocell moves. It encounters the food.

It reconfigures itself and actually then

is able to climb to the highest concentration

of food in that system and stop there.

Alright? So not only do we have this system

that has a body, it has a metabolism,

it can use energy, it moves around.

It can sense its local environment

and actually find resources

in the environment to sustain itself.

Now, this doesn't have a brain, it doesn't have

a neural system. This is just a sack of

chemicals that is able to have this interesting

and complex lifelike behavior.

If we count the number of chemicals

in that system, actually, including the water

that's in the dish, we have five chemicals

that can do this.

So then we put these protocells together in a

single experiment to see what they would do,

and depending on the conditions, we have

some protocells on the left that are

moving around and it likes to touch the other

structures in its environment.

On the other hand we have two moving

protocells that like to circle each other,

and they form a kind of a dance, a complex dance with each other.

Right? So not only do individual protocells

have behavior, what we've interpreted as

behavior in this system, but we also have

basically population-level behavior

similar to what organisms have.

So now that you're all experts on protocells,

we're going to play a game with these protocells.

We're going to make two different kinds.

Protocell A has a certain kind of chemistry

inside that, when activated, the protocell

starts to vibrate around, just dancing.

So remember, these are primitive things,

so dancing protocells, that's very

interesting to us. (Laughter)

The second protocell has a different

chemistry inside, and when activated,

the protocells all come together and they fuse

into one big one. Right?

And we just put these two together

in the same system.

So there's population A,

there's population B, and then

we activate the system,

and protocell Bs, they're the blue ones,

they all come together. They fuse together

to form one big blob, and the other protocell

just dances around. And this just happens

until all of the energy in the system is

basically used up, and then, game over.

So then I repeated this experiment

a bunch of times, and one time

something very interesting happened.

So, I added these protocells together

to the system, and protocell A and protocell B

fused together to form a hybrid protocell AB.

That didn't happen before. There it goes.

There's a protocell AB now in this system.

Protocell AB likes to dance around for a bit,

while protocell B does the fusing, okay?

But then something even more interesting happens.

Watch when these two large protocells,

the hybrid ones, fuse together.

Now we have a dancing protocell

and a self-replication event. Right. (Laughter)

Just with blobs of chemicals, again.

So the way this works is, you have

a simple system of five chemicals here,

a simple system here. When they hybridize,

you then form something that's different than

before, it's more complex than before,

and you get the emergence of another kind of

lifelike behavior which

in this case is replication.

So since we can make some interesting

protocells that we like, interesting colors and

interesting behaviors, and they're very easy

to make, and they have interesting lifelike

properties, perhaps these protocells have

something to tell us about the origin of life

on the Earth. Perhaps these represent an

easily accessible step, one of the first steps

by which life got started on the early Earth.

Certainly, there were molecules present on

the early Earth, but they wouldn't have been

these pure compounds that we worked with

in the lab and I showed in these experiments.

Rather, they'd be a real complex mixture of

all kinds of stuff, because

uncontrolled chemical reactions produce

a diverse mixture of organic compounds.

Think of it like a primordial ooze, okay?

And it's a pool that's too difficult to fully

characterize, even by modern methods, and

the product looks brown, like this tar here

on the left. A pure compound

is shown on the right, for contrast.

So this is similar to what happens when you

take pure sugar crystals in your kitchen,

you put them in a pan, and you apply energy.

You turn up the heat, you start making

or breaking chemical bonds in the sugar,

forming a brownish caramel, right?

If you let that go unregulated, you'll

continue to make and break chemical bonds,

forming an even more diverse mixture of

molecules that then forms this kind of black

tarry stuff in your pan, right, that's

difficult to wash out. So that's what

the origin of life would have looked like.

You needed to get life out of this junk that

is present on the early Earth,

four, 4.5 billion years ago.

So the challenge then is,

throw away all your pure chemicals in the lab,

and try to make some protocells with lifelike

properties from this kind of primordial ooze.

So we're able to then see the self-assembly

of these oil droplet bodies again

that we've seen previously,

and the black spots inside of there

represent this kind of black tar -- this diverse,

very complex, organic black tar.

And we put them into one of these

experiments, as you've seen earlier, and then

we watch lively movement that comes out.

They look really good, very nice movement,

and also they appear to have some kind of

behavior where they kind of circle

around each other and follow each other,

similar to what we've seen before -- but again,

working with just primordial conditions,

no pure chemicals.

These are also, these tar-fueled protocells,

are also able to locate resources

in their environment.

I'm going to add some resource from the left,

here, that defuses into the system,

and you can see, they really like that.

They become very energetic, and able

to find the resource in the environment,

similar to what we saw before.

But again, these are done in these primordial

conditions, really messy conditions,

not sort of sterile laboratory conditions.

These are very dirty little protocells,

as a matter of fact. (Laughter)

But they have lifelike properties, is the point.

So, doing these artificial life experiments

helps us define a potential path between

non-living and living systems.

And not only that, but it helps us

broaden our view of what life is

and what possible life there could be

out there -- life that could be very different

from life that we find here on Earth.

And that leads me to the next

term, which is "weird life."

This is a term by Steve Benner.

This is used in reference to a report

in 2007 by the National Research Council

in the United States, wherein

they tried to understand how we can

look for life elsewhere in the universe, okay,

especially if that life is very different from life

on Earth. If we went to another planet and

we thought there might be life there,

how could we even recognize it as life?

Well, they came up with three very general

criteria. First is -- and they're listed here.

The first is, the system has to be in

non-equilibrium. That means the system

cannot be dead, in a matter of fact.

Basically what that means is, you have

an input of energy into the system that life

can use and exploit to maintain itself.

This is similar to having the Sun shining

on the Earth, driving photosynthesis,

driving the ecosystem.

Without the Sun, there's likely to be

no life on this planet.

Secondly, life needs to be in liquid form,

so that means even if we had some

interesting structures, interesting molecules

together but they were frozen solid,

then this is not a good place for life.

And thirdly, we need to be able to make

and break chemical bonds. And again

this is important because life transforms

resources from the environment into

building blocks so it can maintain itself.

Now today, I told you about very strange

and weird protocells -- some that contain clay,

some that have primordial ooze in them,

some that have basically oil

instead of water inside of them.

Most of these don't contain DNA,

but yet they have lifelike properties.

But these protocells satisfy

these general requirements of living systems.

So by making these chemical, artificial

life experiments, we hope not only

to understand something fundamental

about the origin of life and the existence

of life on this planet, but also

what possible life there could be

out there in the universe. Thank you.

(Applause)