Scientists say they've witnessed a never-before-seen type of replication in organic robots created in the lab using frog cells. Among other things, the findings could have implications for regenerative medicine.
The discovery involves a xenobot – a simple, "programmable" organism that is created by assembling stem cells in a Petri dish — and is described by a team of researchers from Tufts University, Harvard University and the University of Vermont in a paper published this week in the Proceedings of the National Academy of Sciences.
"You can think about this like using the different cells [as] building blocks like you would build with LEGO or with Minecraft," Douglas Blackiston, a co-author of the study, tells NPR.
The researchers hope that one day these xenobots — described by the same team in a paper published nearly two years ago — could be programmed to perform useful functions such as finding cancer cells in the human body or trapping harmful microplastics in the ocean.
The xenobots are made of cells taken from the African clawed frog, or Xenopus laevis. The cells aren't genetically modified at all, but simply combined in different arrangements to produce the xenobots, says Blackiston, a senior scientist at the Allen Discovery Center at Tufts University and the Wyss Institute for Biologically Inspired Engineering at Harvard University.
The xenobots propel themselves by using tiny hair-like structures known as cilia. They have a tendency to spin in a corkscrew fashion, which "turns out to be pretty good for collecting piles of things," such as other cells, Blackiston says.
So the team used an artificial intelligence-driven computer simulation to see how they might manipulate the xenobots into shapes that would be even better at piling things up.
For that purpose, the xenobots' initial spheroid shape is "not the best design," explains Blackiston. Instead, the computer suggested a C-shape similar to a snow plow or, as some have observed, Pac-Man. That shape, he says, is highly efficient at corralling and collecting loose stem cells, which then naturally form into large piles.
But when the xenobots swept up loose frog stem cells in the dish, the researchers observed something remarkable: the piles of cells formed copies of the original xenobots.
Various forms of both sexual and asexual reproduction are, of course, well known in biology.
But what the xenobots did — dubbed kinematic self-replication — is new in living organisms, says Michael Levin, a professor of biology at Tufts and associate faculty member at the Wyss Institute. It does happen at the molecular level, but "we are not aware of any organism that reproduces or replicates in this way," he says.
It takes about five days to produce a copy under optimal conditions, the researchers say. The "offspring" don't take on the C-shaped body type of the parent generation, but revert to the less efficient, original spheroid shape.
Xenobots are collections of living cells and have no brain or digestive system. But in a real sense they can be programmed — to corral other cells, as in this study, or eventually to do other things. That's why the researchers think of them as tiny organic robots.
"The distinction between a robot and an organism is not nearly as sharp as ... we used to think it was," Levin tells NPR. "These creatures, they have properties of both."
In fact, the idea of kinematic self-replication is not entirely new — it was first suggested in the late 1940s by mathematician John von Neumann. He envisioned machines that could choose from basic robot parts to produce copies of themselves, explains Sam Kriegman, a postdoctoral fellow at the Wyss Institute and the lead author of the paper.
"We've had a lot of people try to make von Neumann machines out of robot parts for a long time, and there's been limited success," Kriegman says.
"We found that if you just relax the assumption that the robot has to be made out of metal and circuit boards and electronics, and instead you use living cells, then von Neumann machines are actually kind of easy to make," he tells NPR.
But that concerns some scientists. Nita Farahany, a Duke University professor of law and philosophy, studies the ethics involved in new technologies and was not part of the xenobot research. "Any time we try to harness life ... [we should] recognize its potential to go really poorly," she told Smithsonian Magazine.
However, the researchers note that like a hypothetical von Neumann machine, a xenobot can't copy itself without raw materials. As a result, there's virtually no chance they could escape the lab and begin reproducing on their own. All the researchers have to do is remove the inventory of loose stem cells and there's nothing left from which to make new xenobots.
And since there's no genetic material coming from the parent xenobot, they can't mutate or evolve on their own either, Blackiston says.
"It would be like finding loose parts of a human just floating around and sticking them together to make a copy," he says. "So, it's hard to figure out how [evolutionary] selection would act on that, because there's nothing transferred between each generation — each one's independent."
What the researchers hope is that one day these xenobots and their ability to self-replicate could be harnessed for the good of humanity.
"This is really a first step, but you could think down the line," Blackiston says. "If we could program these better, maybe they can selectively pick up and move specific cell types that we want or help us shape something that we're building in a dish for regenerative medicine."
For Kriegman, what's interesting is that "this form of replication happens spontaneously." Of course, it requires very specific conditions, he says, but "it didn't need to be evolved over billions of years,"
"We think about how long it took for life to evolve on Earth," Kriegman says. "It's a very long story, but here in a dish under the right conditions, we found a completely new form of replication in organisms."
And discovering a new form of self-replication, he says, shows that "maybe life is more expected than unexpected."