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The more we understand how cells produce shape and form, Philip Ball explains, the more inadequate the idea of a genomic blueprint looks…

Where in the embryo does the person reside? Morphogenesis – the formation of the body from an embryo – once seemed so mystifying that scholars presumed the body must somehow already exist in tiny form at conception. In the 17th century, the Dutch microscopist Nicolaas Hartsoeker illustrated this ‘preformationist’ theory by drawing a foetal homunculus tucked into the head of a sperm.

This idea finds modern expression in the notion that the body plan is encoded in our DNA. But the more we come to understand how cells produce shape and form, the more inadequate the idea of a genomic blueprint looks, too. What cells follow is not a blueprint; if they can be considered programmed at all, it’s not with a plan of what to make, but with a set of rules to guide construction. One implication is that humans and other complex organisms are not the unique result of cells’ behaviour, but only one of many possible outcomes.

This view of the cell as a contingent, constructional entity challenges our traditional idea of what a body is, and what it can be. It also opens up some remarkable and even disconcerting possibilities about the prospects of redirecting biology into new shapes and structures. Life suddenly seems more plastic and amenable to being reconfigured by design. Understanding the contingency and malleability of multicellular form also connects us to our deep evolutionary past, when single-celled organisms first discovered the potential benefits of becoming multicellular. ‘The cell may be the focus of evolution, more than genes or even than the organism,’ says Iñaki Ruiz-Trillo of the Institute of Evolutionary Biology in Barcelona. Far from the pinnacle of the tree of life, humans become just one of the many things our cells are capable of doing.

In one of the most dramatic demonstrations to date that cells are capable of more than we had imagined, the biologist Michael Levin of Tufts University in Medford, Massachusetts and his colleagues have shown that frog cells liberated from their normal developmental path can organise themselves in distinctly un-froglike ways. The researchers separated cells from frog embryos that were developing into skin cells, and simply watched what the free cells did.

Culturing cells – growing them in a dish where they are fed the nutrients they need – is a mature technology. In general, such cells will form an expanding colony as they divide. But the frog skin cells had other plans. They clustered into roughly spherical clumps of up to several thousand cells each, and the surface cells developed little hairlike protrusions called cilia (also present on normal frog skin). The cilia waved in coordinated fashion to propel the clusters through the solution, much like rowing oars. These cell clumps behaved like tiny organisms in their own right, surviving for a week or more – sometimes several months – if supplied with food. The researchers called them xenobots, derived from Xenopus laevis, the Latin name of the African clawed frog from which the cells were taken.

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Levin and colleagues have recently found a new type of behaviour that xenobots can exhibit. They discovered that these pseudo-organisms can even replicate, after a fashion. Xenobots placed in a dish of cells will move to marshal those loose cells into piles that, over the course of a few days, cluster into new xenobots that then take off through the liquid themselves. Left to their own devices, the xenobots typically manage to produce only a single generation of offspring. But the researchers wondered if they could do better. They made computer simulations to search for xenobot shapes that were better at making new xenobots, using an AI program devised by their team member Josh Bongard of the University of Vermont. The simulations suggested that structures like C-shaped half-doughnuts could sweep up cells more efficiently than the spheroidal xenobots could, making larger (spherical) clusters of ‘offspring’.

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The work shows that, by combining biological xenobots with the exploratory power of AI, it’s possible to make a kind of ‘living machine’ devised for a purpose. ‘AI can be brought in to exaggerate an innate capability,’ says Bongard. ‘The AI can “program” new behaviours into organisms by rearranging their morphology rather than their genes.’ The researchers wonder if the simulations might identify other shapes that can assemble different structures, or perhaps perform other tasks entirely. ‘One of my primary interests in this project is exactly how ‘far’ from the wild type [the natural, spontaneously arising form of xenobots] an AI can push things,’ says Bongard. ‘We’re now working on incorporating several new behaviours into xenobots via AI-driven design.’

This perspective entails a new way of thinking about cells: not as building blocks assembled according to a blueprint, but as autonomous entities with skills that can be leveraged to make all manner of organisms and living structures. You might conceive of them as smart, reprogrammable, shapeshifting robots that can move, stick together, and signal to one another – and, by those means, build themselves into elaborate artifacts.

This might also be a better way to conceptualise how our own bodies are built during embryogenesis…

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The generative potential of cells equipped for multicellular construction was evident almost as soon as this became a lifestyle option, in evolutionary terms. In the Cambrian explosion around 540 million years ago, all manner of strange body shapes appeared, many of which are no longer exhibited by any creatures on Earth. Perhaps we should regard those forgotten ‘endless forms most beautiful’, to borrow Charles Darwin’s resonant phrase, as an illustration of the constructive potential of the metazoan cell – an exuberant expression of the palette of solutions to the problem of cell assembly, which natural selection then stringently pruned.

Acknowledging that the human form is a contingent outcome of the way our cells are programmed for construction raises some mind-bending questions. Are there, for example, human xenobots (perhaps we might call them anthrobots)? If so, are they truly ‘human’? Might there be a kind of organ or tissue that our cells could make but don’t normally get the chance to? Might our still cells ‘remember’ older evolutionary body shapes?…

How our understanding of genetics is changing– a fascinating dispatch from the frontiers of experimental biology: “What on earth is a xenobot?,” from @philipcball in @aeonmag. Eminently worth reading in full.

* Groucho Marx

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As we ponder possibility, we might spare a thought for Hans Spemann; he died on this date in 1941. An embryologist, he was awarded the Nobel Prize for Physiology and Medicine in 1935 for his discovery of embryonic induction, an effect involving several parts of the embryo in directing the development of the early group of cells into specific tissues and organs.

In a way that can be said to have foreshadowed the work described above, Spemann showed that the in the earliest stage, tissue may be transplanted to different areas of the embryo, where it then develops based on the new location and not from where it came. (For example, early tissue cut from an area of nervous tissue might be moved to an area of skin tissue where it then grows into the same form as the surrounding skin.)

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