Multi-scale Chimerism: An experimental window on the algorithms of anatomical control

Despite the immense progress in genetics and cell biology, major knowledge gaps remain with respect to prediction and control of the global morphologies that will result from the cooperation of cells with known genomes. The understanding of cooperativity, competition, and synergy across diverse biological scales has been obscured by a focus on standard model systems that exhibit invariant species-specific anatomies. Morphogenesis of chimeric biological material is an especially instructive window on the control of biological growth and form because it emphasizes the need for prediction without reliance on familiar, standard outcomes. Here, we review an important and fascinating body of data from experiments utilizing DNA transfer, cell transplantation, organ grafting, and parabiosis. We suggest that these are all instances (at different levels of organization) of one general phenomenon: chimerism. Multi-scale chimeras are a powerful conceptual and experimental tool with which to probe the mapping between properties of components and large-scale anatomy: the laws of morphogenesis. The existing data and future advances in this field will impact not only the understanding of cooperation and the evolution of body forms, but also the design of strategies for system-level outcomes in regenerative medicine and swarm robotics. •Biological systems can be recombined at many levels, from molecules to swarms.•Biological modules are highly inter-operable – such constructs are usually viable•Transgenics, grafts, cancer, etc. are examples of a general phenomenon: chimerism•It is very challenging to predict the anatomical and functional outcome of chimeras•Multi-scale chimerism facilitates developing predictive control of emergent complexity