Chapter 12 — The Handedness Problem

Carbon-based chemistry produces two mirror-image forms of most organic molecules—a left-handed form (L) and a right-handed form (D), called enantiomers. They have identical chemical compositions and nearly identical chemical properties. Abiotic chemistry—chemistry without biological guidance—consistently produces equal mixtures of both forms. This is called a racemic mixture.

Life requires absolute homochirality. Every amino acid in every protein in every living organism is the L-form. Every sugar in every DNA and RNA molecule in every living organism is the D-form. A protein built with even one D-amino acid in the chain will fold incorrectly and lose its function. A DNA or RNA strand incorporating even one L-sugar will not form the correct double-helix geometry. There is no partial benefit to 90 percent homochirality. The cellular machinery requires 100 percent.

No prebiotic process that produces racemic amino acids can explain how life began with pure L-amino acids. No known non-biological mechanism selects for one hand over the other with the consistency required. Walter Bonner of Stanford University spent his research career investigating this problem and concluded that it remains unsolved. The homochirality problem must be solved before the protein folding problem, before the information problem, and before the membrane formation problem. It is the first wall in a room full of walls.

Bonner, W.A. "The Origin and Amplification of Biomolecular Chirality." Origins of Life and Evolution of Biospheres 21 (1991): 59–111. Blackmond, D.G. "The origin of biological homochirality." Philosophical Transactions of the Royal Society B 366 (2011): 2878–2884.

Chapter 13 — The Repair Crew

Every human cell sustains between 10,000 and 100,000 DNA damage events per day from metabolic byproducts, ultraviolet radiation, and chemical mutagens. Without repair, these lesions would accumulate to lethal levels within days. To prevent this, cells deploy multiple independent repair pathways specialized for different types of damage: base excision repair for single-base alterations, nucleotide excision repair for bulky lesions, mismatch repair for replication errors, and double-strand break repair for the most severe damage.

Each pathway requires dozens of precisely coordinated proteins. Base excision repair alone involves a glycosylase to recognize and remove the damaged base, AP endonuclease to cleave the backbone, polymerase to fill the gap, and ligase to seal the strand. Mismatch repair in humans requires at least seven distinct proteins working in sequence. Each pathway must be fully operational to perform its function.

The DNA repair system faces a foundational logical problem in any origin-of-life scenario: it requires the DNA it protects to encode the proteins it is made of, and it must exist before the genome can be faithfully copied. The system must be present and operational before any genome can be reliably inherited. No DNA repair system means no fidelity, and no fidelity means no heritable information, and no heritable information means no life.

Hoeijmakers, J.H.J. "Genome maintenance mechanisms for preventing cancer." Nature 411 (2001): 366–374. Friedberg, E.C. et al. DNA Repair and Mutagenesis, 2nd ed. ASM Press, 2006.