A book is made of wood. But it is not a tree. The dead cells have been
repurposed to serve another need.
Now a team of
scientists has repurposed living cells — scraped from frog embryos — and
assembled them into entirely new life-forms. These millimeter-wide “xenobots”
can move toward a target, perhaps pick up a payload (like a medicine that needs
to be carried to a specific place inside a patient) — and heal themselves after
being cut.
“These are novel
living machines,” says Joshua Bongard, a computer scientist and robotics expert
at the University of Vermont who co-led the new research. “They’re neither a traditional
robot nor a known species of animal. It’s a new class of artifact: a living,
programmable organism.”
The new
creatures were designed on a supercomputer at UVM — and then assembled and
tested by biologists at Tufts University. “We can imagine many useful
applications of these living robots that other machines can’t do,” says
co-leader Michael Levin who directs the Center for Regenerative and
Developmental Biology at Tufts, “like searching out nasty compounds or
radioactive contamination, gathering microplastic in the oceans, traveling in
arteries to scrape out plaque.”
The results of the new research were published January 13 in the Proceedings
of the National Academy of Sciences.
Bespoke Living Systems
People have been
manipulating organisms for human benefit since at least the dawn of
agriculture, genetic editing is becoming widespread, and a few artificial
organisms have been manually assembled in the past few years — copying the body
forms of known animals.
But this
research, for the first time ever, “designs completely biological machines from
the ground up,” the team writes in their new study.
With months of
processing time on the Deep Green supercomputer cluster at UVM’s Vermont
Advanced Computing Core, the team — including lead author and doctoral student
Sam Kriegman — used an evolutionary algorithm to create thousands of candidate
designs for the new life-forms. Attempting to achieve a task assigned by the
scientists — like locomotion in one direction — the computer would, over and
over, reassemble a few hundred simulated cells into myriad forms and body
shapes. As the programs ran — driven by basic rules about the biophysics of
what single frog skin and cardiac cells can do — the more successful simulated
organisms were kept and refined, while failed designs were tossed out. After a
hundred independent runs of the algorithm, the most promising designs were
selected for testing.
Then the team at Tufts, led by Levin and with key work by microsurgeon
Douglas Blackiston — transferred the in silico designs into life. First they
gathered stem cells, harvested from the embryos of African frogs, the species Xenopus
laevis. (Hence the name “xenobots.”) These were separated into
single cells and left to incubate. Then, using tiny forceps and an even tinier
electrode, the cells were cut and joined under a microscope into a close
approximation of the designs specified by the computer.
Assembled into
body forms never seen in nature, the cells began to work together. The skin
cells formed a more passive architecture, while the once-random contractions of
heart muscle cells were put to work creating ordered forward motion as guided
by the computer’s design, and aided by spontaneous self-organizing patterns —
allowing the robots to move on their own.
These reconfigurable
organisms were shown to be able move in a coherent fashion — and explore their
watery environment for days or weeks, powered by embryonic energy stores.
Turned over, however, they failed, like beetles flipped on their backs.
Later tests
showed that groups of xenobots would move around in circles, pushing pellets
into a central location — spontaneously and collectively. Others were built
with a hole through the center to reduce drag. In simulated versions of these,
the scientists were able to repurpose this hole as a pouch to successfully
carry an object. “It’s a step toward using computer-designed organisms for
intelligent drug delivery,” says Bongard, a professor in UVM’s Department of
Computer Science and Complex Systems Center.
Living Technologies
Many
technologies are made of steel, concrete or plastic. That can make them strong
or flexible. But they also can create ecological and human health problems,
like the growing scourge of plastic pollution in the oceans and the toxicity of
many synthetic materials and electronics. “The downside of living tissue is
that it’s weak and it degrades,” say Bongard. “That’s why we use steel. But
organisms have 4.5 billion years of practice at regenerating themselves and
going on for decades.” And when they stop working — death — they usually fall
apart harmlessly. “These xenobots are fully biodegradable,” say Bongard, “when
they’re done with their job after seven days, they’re just dead skin cells.”
Your laptop is a
powerful technology. But try cutting it in half. Doesn’t work so well. In the
new experiments, the scientists cut the xenobots and watched what happened. “We
sliced the robot almost in half and it stitches itself back up and keeps
going,” says Bongard. “And this is something you can’t do with typical machines.”
Cracking the Code
Both Levin and
Bongard say the potential of what they’ve been learning about how cells
communicate and connect extends deep into both computational science and our
understanding of life. “The big question in biology is to understand the
algorithms that determine form and function,” says Levin. “The genome encodes
proteins, but transformative applications await our discovery of how that
hardware enables cells to cooperate toward making functional anatomies under
very different conditions.”
To make an
organism develop and function, there is a lot of information sharing and
cooperation — organic computation — going on in and between cells all the time,
not just within neurons. These emergent and geometric properties are shaped by
bioelectric, biochemical, and biomechanical processes, “that run on
DNA-specified hardware,” Levin says, “and these processes are reconfigurable,
enabling novel living forms.”
The scientists see the work presented in their new PNAS study
— “A scalable pipeline for designing reconfigurable organisms,” — as one step
in applying insights about this bioelectric code to both biology and computer
science. “What actually determines the anatomy towards which cells cooperate?”
Levin asks. “You look at the cells we’ve been building our xenobots with, and,
genomically, they’re frogs. It’s 100% frog DNA — but these are not frogs. Then
you ask, well, what else are these cells capable of building?”
“As we’ve shown,
these frog cells can be coaxed to make interesting living forms that are
completely different from what their default anatomy would be,” says Levin. He
and the other scientists in the UVM and Tufts team — with support from DARPA’s
Lifelong Learning Machines program and the National Science Foundation —
believe that building the xenobots is a small step toward cracking what he
calls the “morphogenetic code,” providing a deeper view of the overall way
organisms are organized — and how they compute and store information based on
their histories and environment.
Future Shocks
Many people
worry about the implications of rapid technological change and complex
biological manipulations. “That fear is not unreasonable,” Levin says. “When we
start to mess around with complex systems that we don’t understand, we’re going
to get unintended consequences.” A lot of complex systems, like an ant colony,
begin with a simple unit — an ant — from which it would be impossible to
predict the shape of their colony or how they can build bridges over water with
their interlinked bodies.
“If humanity is
going to survive into the future, we need to better understand how complex
properties, somehow, emerge from simple rules,” says Levin. Much of science is
focused on “controlling the low-level rules. We also need to understand the
high-level rules,” he says. “If you wanted an anthill with two chimneys instead
of one, how do you modify the ants? We’d have no idea.”
“I think it’s an
absolute necessity for society going forward to get a better handle on systems
where the outcome is very complex,” Levin says. “A first step towards doing
that is to explore: how do living systems decide what an overall behavior
should be and how do we manipulate the pieces to get the behaviors we want?”
In other words,
“this study is a direct contribution to getting a handle on what people are
afraid of, which is unintended consequences,” Levin says — whether in the rapid
arrival of self-driving cars, changing gene drives to wipe out whole lineages
of viruses, or the many other complex and autonomous systems that will increasingly
shape the human experience.
“There’s all of
this innate creativity in life,” says UVM’s Josh Bongard. “We want to
understand that more deeply — and how we can direct and push it toward new
forms.”
Journal article: https://www.pnas.org/content/early/2020/01/07/1910837117
Source: https://myfusimotors.com/2020/01/15/living-robots-built-using-frog-cells/
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