Rice University chemist James Tour, along with co-authors M. C. Parker and C. Jeynes, recently published an article in BioCosmos titled “Thermodynamic Limitations on the Natural Emergence of Long Chain Molecules: Implications for Origin of Life.” The study demonstrates that proteins and RNA degrade at rates that render their spontaneous formation under natural, undirected conditions highly implausible. To date, no origin-of-life researcher has provided a substantive response to the thermodynamic challenges outlined in the paper.
Estimating Half-Lives
The authors employed statistical decay theory and quantitative geometrical thermodynamics to calculate the decay time constants of proteins and RNA, which are directly related to their half-lives — the time required for half of the original molecules to degrade. The study found that the decay time constant approximates the decay time constant of a dimer (a pair of amino acids or nucleotides joined by a single bond) divided by the length of the chain. In other words, longer chains degrade more quickly, with the time constant decreasing in direct proportion to chain length. They summarize their results as follows:
For a polymer of N-monomer-units long, or N-mer, which has a dimer decay time constant of t, the polymer decay time constant is proved to be closely approximated by t/N (under rather general assumptions). The implications of this for abiogenesis are profound, namely that there would be small amounts of time available (order of days) for a prebiotic sequence of a condensation polymer to serve as the primary information-bearing code for the last universal common ancestor.
More specifically, the half-life of a dipeptide — two amino acids linked by a peptide bond, as found in proteins — is approximately 7 years. Therefore, a polypeptide chain of 200 amino acids, which is typical for many functional proteins, has a half-life of only 13 days. The situation is even more severe for RNA. A chain of two nucleotides has a half-life of about 100 days, meaning that an RNA strand of 200 nucleotides would degrade in roughly 12 hours. Both classes of molecules decay far more rapidly than they could plausibly form under natural conditions, making their spontaneous emergence highly unlikely in any undirected origin-of-life scenario.
Comparing Rates
In comparison to a protein’s half-life, the rate of polypeptide chain elongation under prebiotic conditions is very long. Yang et al. (2025) identify numerous barriers to sustained polypeptide growth, including the formation of non-peptide linkages and cyclic structures, stringent environmental requirements, and unfavorable thermodynamics. Their analysis establishes that the rate of growth must be far smaller than one added amino acid per chain per day.
Even assuming one addition each day, synthesizing a protein of 200 amino acids would require over six months. However, the growing chain would almost certainly degrade in a much shorter time span. The challenge is even greater for RNA, which has a significantly shorter half-life and encounters additional chemical and structural hurdles during formation.
The localization challenge is even more daunting. Even if a life-essential protein appeared in a confined region containing a developing cell, the time required for it to discover the cell through diffusion vastly exceeds the protein’s half-life. The discovery time can be estimated using the Smoluchowski diffusion-limited reaction rate constant, k = 4πrD, where r is the radius of the cell and D is the protein’s diffusion coefficient. The average time for the protein to contact the cell is the volume of the region that confines them divided by k.
For a typical protein, the discovery time in one liter of water would be on the order of 10,000 years (here, here), which is over 100,000 times longer than most protein half-lives. The situation is even worse for RNA since it has a much shorter half-life. Yet origin scenarios require far larger volumes than a liter. The synthesis of the building blocks of life requires at least eight different environments, so the volume of water that a protein would need to explore to find a nascent cell would be enormous (here, here). The protein could never find its way into a staging ground for life’s origin before degrading.
The Future of Origins Research
The short half-lives of proteins and RNA and the timescales required for their formation and localization pose an insurmountable hurdle for all theories on life’s origin. The calculations presented above represent implausibly favorable situations. More realistic analyses would only heighten the problem. The timescale challenge is based on the fundamental physics underlying biomolecules and diffusion, so no solution appears possible.
Researchers studying the origin of life face a choice: they can either disregard key scientific challenges or broaden their philosophical assumptions to include the possibility that life arose through the action of an intelligent agent. Those who adopt the latter approach can engage more honestly with the evidence pointing to design in even the simplest viable cells. This shift could open new avenues for research and foster meaningful progress in unlocking the mysteries of life.