T'shuvah as Error Recognition and Repair in the Basic Design of Living Systems

6/29/2005

This is a somewhat modified version of a talk/meditation process that I presented during Yom Kippur Shakharit services for the High Holydays 5753.

I offer here a short drash, commentary, on T'shuvah - from the point of view of a cell biologist. Working with cells and molecules, I tend to draw on images of the natural world for models of Jewish spirituality. The model, image, metaphor that comes to me for T'shuvah is that of DNA repair. DNA is the complex macromolecule that encodes the blueprint information for all that manifests at the physical level as you , as a unique individual. All the living cells of your body contain your unique code. Now, if this code gets altered, it can cause problems down the road. The structures created from the incorrectly coded information can be defective, and dysfunctional. Yet, the way nature has designed if, your DNA is constantly subject to situations that can cause coding errors. Every time the DNA in a cell replicates itself, many errors are introduced. This discovery - the common generation of large number of errors during replication - was initially surprising. Also, as a natural consequence of existing in a complex turbulent world, errors frequently occur in cells in response to stress and environmental insults. So..... nature is efficient, evolution tends to favor things designed to function efficiently - how come all these errors?

In designing a coding material, the solution that turns out to be most efficient overall (given the natural constraints present in the building blocks of the physical world) is not to employ material that is always constant, stable, error free. Rather, it is to allow a fair degree of errors (as occurs with the DNA coding material) and design in parallel very efficient error recognition and repair mechanisms. An essential part of a cell's machinery are repair molecules which continuously monitor the DNA and are capable of recognizing when damage has occurred and mistakes have been introduced. Many types of mistakes cause a distortion in the basic double helical form of the DNA. Monitor-repair molecules are able to detect where the structure is distorted, and then alert excision-repair molecules to come to that place and cut out the inappropriate, inaccurate material. Then another set of repair molecules correctly fills in the excised region (1). Or, if the mistake is just a smaller something-in-the-wrong-place, different sets of molecules recognize this little something being out of place and remove it.

Human cells are also designed to have a prioritizing system (2). Unrepaired errors can eventually lead to serious trouble, either for the health of that individual cell, or for the body as a whole (3). Yet some mistakes are more likely than others to manifest quickly into problems. The cell first repairs the errors in the places that could have immediate adverse effects, and then afterwards takes care of the mistakes in the places where the error may not manifest for a while, if ever. What's more, the cell being very efficient, the material that is cut out is not lost, wasted. It can be recycled, transformed, and reused in the building of healthy structure within the cell.

This is my model for T'shuvah - return to our essential being, naming and correcting our mistakes, seeing where we are distorted, off-center, and doing something to bring us closer to where we want to be. I get from this image that invariant maintenance of fidelity, perfection is not required - we're not created that way. What's most important is to have good effective mechanisms for recognizing when the essential material is damaged, distorted, in error, and good effective mechanisms for correcting the identified errors. Barring extremely stressful environments, problems happen not because of imperfection, but as a consequence of some failure in the error recognition and repair processes. To me, this image is not simply some abstract concept, it is part of the fabric of the universe, the basic design of nature, happening at this moment in all the cells of our body. I think that feeling ashamed of or denying our imperfections and mistakes can impede or delay the repair process.

I ask now for all of us to do a short T'shuvah process. First, take a minute and consider for yourself -how do I recognize errors? What mechanisms do I have to detect distortions in my structure? What cues me in to knowing that my system is not functioning as correctly as possible? How can I know when I'm off? Am I open to recognizing my mistakes? What gets in the way of my ability to recognize errors? And then, what do I do to correct errors that have been identified?

Think about these questions, and later share your thoughts with one or two people close to you. Perhaps some of your error recognition and repair mechanisms are generic, perhaps some will be particular to you. We can learn from each other ways to do this T'shuvah work.

Footnotes:

(1) Repair can happen readily because of the double helix. Information is coded as two complementary mirror images so that when errors occur in one half, the continued existence of the accurate reflecting mirror image provides the template for correct repair. This can break down when damage is massive (e.g., heavy radiation) and errors occur in both halves of the double strand, or in the rare times when by probability two mistakes occur in the same region of both strands. People with inherited propensity for specific diseases may be born with DNA containing specific coding errors.

(2) The capacity to repair is also inducible. That is, when there is more damage due to things like increased environmental stresses, the cell senses the existence of greater than usual damage and responds with increased production of those elements needed for repair. So ..... not to feel easily overwhelmed, more resources are made available when more errors need to be addressed

(3) For example cancer originates from one cell that has accumulated a number of critical, unrepaired coding errors. The deranged growth of this one cell can, if unchecked, lead to the death of the whole organism of which it is a part. Some of the most common errors observed in cancers are those in the coding regions of molecules involved in the pathways of error recognition, repair, and cell " suicide". These errors are thought to be common because: (a) Cells thus damaged are less efficient in correcting further errors that occur, allowing for the accumulation of multiple defects, (b) Normally, when a cell senses it has received such massive damage that it can not all be repaired, or when it receives conflicting signals - such as inappropriate growth signals, it can institute a path known as "programmed cell death" and neatly self-destruct. This preserves the well being of the organism. When this mechanism is disabled by coding errors, deranged cells can continue to proliferate.

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