The Theory of Pleomorphic Provolution

Imagine a world where bacteria can radically change their form—shifting from a harmless sphere to an invasive rod to an entirely different organism altogether. This concept, known as pleomorphism, sparked one of the most bitter scientific controversies of the 19th and early 20th centuries, pitting prominent researchers against each other in a battle that would ultimately determine the future course of microbiology and medicine.

For decades, the scientific community was divided into two opposing camps: the monomorphists, who believed microorganisms maintained a fixed, unchanging form, and the pleomorphists, who argued that microbes could undergo dramatic morphological transformations in response to their environment. The monomorphists, led by giants like Louis Pasteur and Robert Koch, eventually prevailed, establishing the paradigm that has dominated medical science ever since. But now, with advances in our understanding of cellular biology and genetics, the heretical ideas of pleomorphism are being reexamined through a new lens—The Theory of Pleomorphic Provolution—suggesting the original debate may have been more nuanced than we thought.

In recent years, biologist Stuart Grace has attempted to resurrect and reformulate pleomorphism through what he terms the "Theory of Pleomorphic Provolution" ^{5 7} . This updated framework acknowledges the validity of monomorphism while also recognizing that microorganisms can exhibit remarkable plasticity in their morphology and function.

The modern understanding of pleomorphism differs significantly from its historical predecessor. Today, pleomorphism is defined as the ability of some microorganisms to alter their morphology, biological functions, or reproductive modes in response to environmental conditions ⁵ . This differs from the original pleomorphist position that saw these changes as heritable transformations.

PGCCs are large, often multinucleated cancer cells with abnormally high genomic content. They were long considered to be senescent, non-dividing cells, but recent research has demonstrated their viability and capability to generate mitotically active daughter cells through amitotic mechanisms ⁹ .

Researchers using long-term time-lapse imaging of patient-derived cancer organoids have observed PGCCs undergoing remarkable transformations, including the formation of transient "fecundity cells" - new cells that develop inside the host PGCC ⁹ . These fecundity cells can be decellularized to facilitate nuclear fusion and synchronized with other nuclei for subsequent nuclear replication, creating complex tissue structures termed "fecundity structures" ⁹ .

UPS tumors exhibit complex karyotypes and frequently harbor mutations in tumor suppressor genes including TP53, RB, and PTEN, along with disruptions in cell cycle regulators ² . Unlike many sarcomas, however, UPS is not associated with a defining genetic mutation, suggesting its development may involve more complex cellular transformations rather than simple genetic determinism ² .

Recent genomic studies of UPS have revealed frequent copy number alterations, with gains often observed at genes including JUN, EGFR, and CDK6 and losses at WNT8B, RB1, and PTEN ³ . These complex genomic patterns contribute to the profound pleomorphism observed in these tumors and represent potential therapeutic targets.

The journey of pleomorphism from scientific orthodoxy to heresy and back to respectful consideration illustrates how scientific understanding evolves through cycles of discovery, rejection, and rediscovery. The Theory of Pleomorphic Provolution represents not a return to the original discredited ideas, but rather a synthesis that acknowledges both the stability of genetic inheritance and the remarkable plasticity that cells can exhibit under certain conditions.

This modern understanding has significant implications for both microbiology and cancer biology. It suggests that cellular identity is more fluid than previously thought, with organisms possessing sophisticated mechanisms for adapting their form and function in response to environmental pressures. In cancer biology, recognizing the role of cellular plasticity in tumor evolution may open new therapeutic approaches targeting the processes that enable this plasticity.

As we continue to develop more sophisticated tools for observing and understanding biological systems, we may find that other scientific heresies contain kernels of truth waiting to be rediscovered and reformed.