Past, Present and Future of Electroporation

Words are important. A word describes an object, a situation, a process… but, implicitly or explicitly, words orient our mind towards mechanisms and applications (of a process) or conditions and consequences (of a situation)…

The word “electroporation” was coined by Eberhard Neumann (1982), even though Neumann himself co-authored a paper with Kurt Rosenheck, 10 years before (1972), in which they used the term “permeability change”. However, the application of electric pulses to destabilize the biological membranes started well before, in the food treatment (Flamenbaum 1953), more or less at the same time as H. P. Schwan (1957) elaborated theoretical considerations on the derivation of the fundamental Maxwell’s equations in the case of living cells.

With a small number of justified simplifications, Schwan provided a simple equation to calculate the changes in the transmembrane electric potential difference, revealing that membranes charge during the pulses delivery. Thus, the effect of the electric pulses concentrates at the level of the membranes. This supported the use of the terms “membrane electrical breakdown” for a couple of decades, in particular within the work of Sale and Hamilton (1967a,b) or of Schwister and Deuticke (1985).

Later, technological developments promoted the use of novel types of electric pulses. Indeed, all started with exponentially decaying pulses (the discharge of a capacitor) whose characteristics are dependent on the load. This can result in high variability of the results. Then, pulses with controlled parameters (in terms of duration, amplitude, number of pulses and their repetition frequency) were applied, with increased reproducibility: these were the so-called millisecond and microsecond pulsed electric fields (msPEF and µsPEF). Indeed, the progress in the electronics and sensing devices allowed to maintain the voltage applied through a constant adaptation of the current delivered to the load. This adaptation to the load allowed to find conditions preserving cell viability (Mir et al. 1988) and the translation from in vitro settings to in vivo ones, and even to the clinics (for example in the case of the electrochemotherapy, for which the first treatment of tumors in mice resulted in the first cures of animals (Mir et al. 1991a,b)).

In later developments, delivery of even shorter pulses (the nsPEF of nanoseconds durations) resulted in large advances in the understanding of the effects at the membrane level. However, dependance to the load reappeared, which may somehow restrict clinical applications.

The history of cells manipulation using electric pulses highlights that biology laboratory discoveries are not only a fundamental step in the understanding of the pulses effects, but also a crucial step before their practical applications. Looking forward, the existent applications in medicine (namely in oncology, cardiology, pediatrics, etc.) as well the present applications in the food and environment technologies will not only continue their development, since, with further technological developments and the increase of our knowledge, there will be a surge of the applications of this approach that should be termed electric pulses delivery, or electropulsation, whatever the result of cells electropulsation is: reversible electropermeabilization, irreversible electroporation, mild electroporation, no electroporation, membrane proteins modifications, signals transduction, metabolic changes, etc.

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