Nothing is Impossible


Recent work in molecular bioelectricity has demonstrated the ability to radically alter animals’ morphology despite a normal genomic sequence. Cells make decisions and cooperate towards complex anatomical goal states using bioelectric gradients that are only detectable in the living state and invisible to the mainstream protein or mRNA profiling approaches. The study of these non-neural bioelectrical networks have allowed us to create living “impossible objects” in the highly regenerative planarian flatworm system. For example, flatworms can be made permanently two-headed by a transient change of their bioelectrical circuit. A brief shift of their bioelectric network to a new attractor state permanently alters their pattern memory so that in the future, they will regenerate as two-headed forms out of middle fragments cut in plain water, despite their wild-type genomic sequence.  M. C. Escher was an artist with a keen appreciation of “impossible” or “undecidable” objects, drawing many two-dimensional forms (such as ever-descending staircases) that cannot exist in our three-dimensional world.

We drew inspiration for our image on the cover of the May 23 issue of Biophysical Journal from Escher’s visions, as the worms we report in our paper are in a sense “impossible objects,” whose target morphology does not match their current anatomy. They are also “undecidable objects” because each worm stochastically decides to be one or two-headed upon amputation, persisting in an undecided state. The image is specifically based on the M. C. Escher woodcut Another World II, a.k.a. Other World II, which masterfully depicts paradoxical views of an alien landscape, revealing different aspects of reality but not matching our expectations based on the perspective we take looking through each of the windows in the structure.

This image is a perfect complement to our work on the physiological determinants of patterning. These experiments revealed a new perspective on the control of biological anatomy, which exhibit rules and properties quite different from what is seen when the same object is viewed through the portal of genetic networks or biochemical gradients. To adapt the original woodcut for this image, the color was changed to the blue/red pseudocoloring used to image voltage gradients in the planaria, and the bird-like creature Escher used in the original has been changed to one- or two-headed planaria.

Interestingly, Escher was well aware of the remarkable properties of planaria, as shown  in his 1959 lithograph Planaria (Flatworms). However, the study of bioelectric regulation of growth and form applies well beyond planaria.  It is relevant to the detection and repair of birth defects (especially of the face, brain, and left-right axis), the induction of regeneration of limbs, and detection or reprogramming of cancer, as well as synthetic bioengineering. Much like neural networks in the brain, somatic bioelectric networks store pattern memories and process information that guide development, regeneration, and cancer suppression. Beyond biomedical applications in regenerative medicine and bioengineering, the study of bioelectric communication within tissues in vivo is a branch of the emerging field of primitive cognition.

Evolution takes advantage of biophysical processes to drive computation and decision-making in the brain and body; learning to manipulate this process may allow us to achieve currently impossible biological objects, with structure and function far beyond those we can envision today.

The cover image was created by Jeremy Guay, of Peregrine Creative.

– Fallon Durant, Junji Morokuma, Christopher Fields, Katherine Williams, Dany Adams, Michael Levin