What is it about?

The utilization of biological logic circuit(s) involving hard ON/OFF switches in the integration and regulation of DNA repair is discussed. This mode of regulation likely also applies to many other areas of cell biology. Sequential logic processes always require a clock to orchestrate the orderly processing of events. In the proposed hypothesis, the pulses in the expression of p53 (the guardian of the genome) serve this function. Given the advantages of logic type control, one would expect that in the course of ~ 3 billion years of evolution, where single cell life forms were likely the only forms of life, a biological logic type control system would have evolved to control at least some biological processes, or have even arise in the abiotic phase of evolution. Several other required components have been identified, such as; a method to temporarily inactivate repair processes when they are not required.

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Why is it important?

I believe this type of control/regulation/decision making likely applies to many areas of cell biology. The very first computers were mechanical devices and these are better in my point of view for visualizing digital bio-computation than modern electronic computers, because their computing is based on mechanical switches/gates which are very analogous conformational changes. Computers in fact can be made of almost anything that has two defined orientations/conformations that can interact with similarly structured components. I first described this idea in 1998 to a group of my lab colleagues, and explained how decision making circuits could be constructed using know biological components. Many digital/logic circuits are sequential circuits, and these all require a clock/square wave to orchestrate the processing of data, and biological logic would be no different. In 2006 the square wave in [H2O2] was discovered, and in 2009 the square wave in p53 expression was discovered. These two (predicted by my hypothesis) findings convinced me that this was indeed a very tenable theory, so I attempted to publish the idea in a manuscript restricted to DNA repair. However, even a quarter century later it was still difficult to get this idea published, as the manuscript garnered eight outright rejections from eight different journals, and a no response from another, before finally being accepted with enthusiasm in early 2021, and published 01/01/2022. I wanted to include much more in this paper, but page limitations and article focus prevented me from including more. However, I was able to include this additional material in various presentations (see links below) Penketh PG. (2023). Is The Cell A Digitally Controlled System? Nano Intellects meeting, 14th September, 2023. Berlin, Germany. DOI: 10.13140/RG.2.2.21483.31527 This above presentation can be download from the above doi link, or the link below. https://www.researchgate.net/publication/373924257_Is_the_cell_a_digitally_controlled_system I hope this potential area of research is the focus of many future investigations. Furthermore, I hope that within my lifetime, I will learn if this hypothesis has gained widespread credence, or been discounted.


Personally I feel biology will have used a fusion of analog and digital control mechanisms depending upon the required balance of accuracy, complexity, and energy costs. Thus, I think the biological control will be a fusion of digital and analog mechanisms. This will be somewhat analogous to the 1960s battle between the two ideas for ATP synthesis. The more standard substrate level phosphorylation model, and the newer chemiosmotic hypothesis. Most people would say the chemiosmotic hypothesis won, however they are both correct in mammals, 10% of our ATP is from substrate level phosphorylation, 90% from chemiosmotic. In erythrocytes and other cell types that lack mitochondria, and some other cell forms it is 100% substrate level phosphorylation. Thus, both hypotheses are true. I believe that nature will likely have exploited both digital and analog approaches but time will reveal their relative importance. It may be possible at some point in the future to create an interface between bio-logic with electronic logic, which will enable some types of cellular reprogramming.

Dr Philip Gerard Penketh
Yale University

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This page is a summary of: Is DNA repair controlled by a biological logic circuit?, Theory in Biosciences, January 2022, Springer Science + Business Media,
DOI: 10.1007/s12064-021-00360-8.
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