Ishaan Madan

How did increasingly organized living systems emerge if their simplest molecular building blocks were not themselves uniquely favored? All known cellular life uses the same five nucleobases—adenine, cytosine, guanine, uracil, and thymine—despite prebiotic chemistry producing a much broader inventory of plausible heterocycles. We introduce a Ladder of Molecular Complexity to explore where selection of this canonical genetic alphabet may have occurred. Our approach distributes potential constraints across increasing levels of organization: molecular formation and persistence, self-assembly, polymer formation and stability, replication, and biological function. As a test of the lower levels of this ladder, we computationally compare the reaction energetics of canonical and noncanonical heterocycles at the nucleobases, nucleosides, and nucleotides levels. Across four computational treatments, we find no thermodynamic favorability that distinguishes the canonical alphabet as a set. Three of the five canonical bases—adenine, cytosine, and guanine—do rank among the most favorable, falling within the nine most favorable of twenty-one heterocycles in every treatment. Thymine and uracil, however, rank mid-to-low throughout. Notably, the three favorable bases are exactly those shared by RNA and DNA, while the two that are not are the pair that distinguishes them. These results suggest that the properties relevant to life's molecular organization may not reside in isolated components, but emerge through increasingly complex relationships among them. This origins-of-life perspective offers an empirical contribution to broader questions of how chemistry gives rise to organization, information, self-sustainability, and ultimately the conditions from which conscious life can emerge.

Ishaan Madan is a computational astrobiologist and PhD student in Planetary Science and Astrobiology at Purdue University, where he studies how life’s chemistry may have emerged on early Earth and what those origins can teach us about life beyond it. His current computational chemistry project investigates why life converged on the familiar genetic alphabet of A, C, G, U, and T from a much broader prebiotic chemical inventory, helping clarify how molecular selection may have shaped the earliest genetic systems. His work utilizes computational tools (quantum chemistry, molecular dynamics, thermodynamic modeling) to examine chemical possibility across diverse environments. His published research includes prebiotic chemistry relevant to NASA’s Dragonfly mission to Titan, phase behavior of Titan surface molecules, and alternative carbon-free chemistries for life in Venusian clouds. Ishaan earned a B.A. in Biochemistry, summa cum laude, with a minor in Physics from Wheaton College Massachusetts, and completed additional machine-learning training through DeepLearning.AI and Stanford University. He has received the NSF Graduate Research Fellowship, Frederick N. Andrews Fellowship, Barry Goldwater Scholarship, CASSUM Research Fellowship, and many others. Ishaan has delivered invited and highlighted presentations at the Astrobiology Science Conference and Telluride Science Workshop and presented at the American Geophysical Union Fall Meeting, Lunar and Planetary Science Conference, and Midwest Geobiology Conference.

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