Jablonka thinks that most animal developmental biologists won’t be surprised by the outcome of experiments like this — but will kick themselves for not having looked for it. “They would probably say, ‘Yes, of course! Why did we not do this simple experiment before?’” she said. Solé suspects others might have accidently stumbled on similar observations, but “thought it was a mistake, or simply impossible.”
Or it might have just been overlooked — because most developmental research only aims to reveal how whole organisms or parts of them grow under normal or mildly manipulated conditions, Jablonka said. But Levin’s work has a new goal, she says: “Constructing an autonomous creature that has nothing to do with the specific form of the [original] organism.”
Xenobots normally live for about a week, subsisting on the nutrients passed down from the fertilized egg they came from. But in rare cases, by “feeding” them with the right nutrients, Levin’s team has been able to keep xenobots active for more than 90 days. The longer-lived ones don’t stay the same but begin to change, as though they are on a new developmental path — destination unknown. None of their incarnations look anything like a frog as it grows from an embryo to a tadpole.
Channels of Communication
Media reports of the earlier handmade xenobots both reveled in and worried about the idea of miniature robots made from living matter. Might they breed and develop minds of their own? In truth, neither possibility was remotely likely: The cells could survive in a nutrient medium, but they couldn’t replicate into new xenobots. And they didn’t have any nerve cells that might act like a mind.
But even though xenobots have no nervous system, that doesn’t mean the cells can’t communicate with one another. One cell might release a chemical that sticks to surface proteins on another cell, triggering a biochemical process within the recipient. This type of cell signaling happens constantly during embryonic development, and it’s one way that neighboring cells control one another’s fate — the type of tissue each cell ultimately becomes. Adhesive proteins enable cells to attach to one another and to sense mechanical forces and deformations. In developing embryos, mechanical cues like this may also guide to become the right tissue type.
Levin thinks that cells also commonly communicate electrically — that this isn’t just a property of nerve cells, although they may have specialized to make good use of it. In a xenobot, “there’s a network of calcium signaling,” Levin said — an exchange of calcium ions like that seen between neurons. “These skin cells are using the same electrical properties that you would find in the neural network of a brain.”
For example, if three xenobots are set spaced apart in a row, and one of them is activated by being pinched, it will emit a pulse of calcium that, within seconds, shows up in the other two — “a chemical signal that goes through the water saying that someone just got attacked,” Levin said.
He thinks that intercellular communications create a sort of code that imprints a form, and that cells can sometimes decide how to arrange themselves more or less independently of their genes. In other words, the genes provide the hardware, in the form of enzymes and regulatory circuits for controlling their production. But the genetic input doesn’t in itself specify the collective behavior of cell communities.
Instead, Levin thinks that it programs cells with an ensemble of tendencies that produce a repertoire of behaviors. Under the normal conditions of embryogenesis, those behaviors follow a certain path toward forming the organisms we know. But give the cells a very different set of circumstances, and other behaviors and new emergent shapes will appear.
“What the genome provides for the cells is some mechanism that allows them to undertake goal-directed activities,” Levin said — in effect, a drive to adapt and survive.
Innate Drives to Survive
One such goal that Levin and his colleagues think they have seen is known as infotaxis, a push for cells to maximize the amount of information they get from their neighbors. Cells may also seek to minimize “surprise,” the chance of encountering something unexpected. The best way to do that, Levin says, is to surround yourself with copies of yourself. Some other goals are based on pure mechanics and geometry, such as minimizing the surface area of a cluster.
The genomic programs for the pursuit of these goals, he says, are very ancient. Indeed, a reversion to something like ancestral behavior from before cells figured out how to work together may emerge in cancers — where cells adopt a potentially lethal mode of organizing themselves that sets proliferation ahead of cooperation.
If that’s right, then the variety of body shapes and functions in natural organisms is not so much the result of specific developmental programs written into their genomes, but of tweaks to the strengths and tendencies of these single-cell behaviors, which may come from both the genome and the environment.
Jablonka guesses that the behaviors on display in the xenobots are probably “something like the most basic self-organization of a multicellular animal-cell aggregate.” That is, they are what happens when both the constraints on form and the resources and opportunities provided by the environment are minimal. “It tells you something about the physics of biological, developing multicellular systems,” she said: “how sticky animal cells interact.” For that reason, she thinks the work might hold clues to the emergence of multicellularity in evolutionary history.
Solé agrees with that. “One of our dreams in the study of synthetic complexity is to be able to move beyond the actual repertoire of life forms that we can see around us, and to explore alternatives,” he said. The fossil traces of simple animals that began to evolve before the Cambrian era, more than about 540 million years ago, give only the vaguest hints of how multicellularity arose through the interactions of single-celled organisms.