In 1974 Pilla developed a model of cell signaling and gene expression where the molecular components of cell membranes reflect current expression of chromosomal DNA within the nucleus.³⁷ The function and structure of protein and receptor sites embedded in/on the membranes in particular are controlled by chromosomal DNA via Messenger DNA. Pilla hypothesized the function of a cell at any instant in time is determined by a feedback loop between chromosomal DNA and macromolecules liberated from the membrane by means of an enzyme derived from messenger RNA activity within the cell. The induction activity of these membrane-bound proteins is strongly modulated by changes in the concentration of divalent ions (such as calcium Ca⁺⁺ and magnesium Mg⁺⁺) absorbed on the mem­brane. ^{34 38 39}

BEST may electrically elicit these ionic changes and signal the nucleus to switch chromosomal gene expression “on” through cAMP for neuropeptide production.

In C fibers the process of membrane depolarization carried out by the influx of sodium ions seems to be followed by an increase in intracellular Ca⁺⁺ concen­tration, thereby triggering the cyclic AMP transduction cascade for activating DNA/gene expression and subsequent peptide synthesis in neurons susceptible to the BEST stimulus.

Pilla confirmed the existence of cellular “windows” for signaling that open most effectively when certain frequencies, pulse widths, and pulse amplitudes are present. These findings support BEST technology and its perfected, clearly defined waveforms.