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Committees for the National Academies of Science have observed that chemists have held skeptical views of abiogenesis because of extensive laboratory experience indicating that there are numerous chemical problems that inhibit nature, which has no direction or goal, from synthesizing any complex biochemical molecules that are needed for cellular life to even emerge.<ref name="NAS">Committee on the Limits of Organic Life in Planetary Systems; Committee on the Origins and Evolution of Life (2007). The Limits of Organic Life in Planetary Systems. National Academies Press. pp. 58–60. ISBN 978-0309104845. "Chemists’ objection to the notion that life is a natural consequence of organic reactivity is simple and comes from broadly based empirical experience in organic-chemistry laboratories. Addition of energy to mixtures of organic species makes the mixtures more complex and less likely to support life. Shapiro has provided a thoughtful and detailed discussion of the difficulties. Briefly summarized, it suggests that existing prebiotic chemistry experiments do not offer plausible hypotheses for routes to complex biomolecules. In the complex chemical mixtures generated under prebiotic conditions, one may be able to find trace amounts of amino acids and perhaps nucleobases. Some might indeed catalyze reactions that have some utility. But other compounds may well inhibit catalysis or catalyze undesired reactions. For example, Joyce and Orgel pointed out that the clay-catalyzed condensation of nucleotides to yield small chains performed best, under the conditions that they considered, if only one enantiomer of the starting material was present. If both were present, the desired reaction with the desired enantiomer might be inhibited by the other enantiomer. Furthermore, the combination of any bifunctional molecule into an information-bearing polymer would be expected to be terminated at an early stage by the presence of an excess of molecules that bear only one functionality. Even crystallization, a well-documented method of obtaining order through self-organization, is not a particularly powerful way to separate mixtures of organic chemicals into their constituents. Normally, an organic compound must be relatively pure before crystallization occurs. That salts crystallize better may explain why crystals are more common in the mineral world than in the organic world. Even organic salts can have problems in crystallizing from an impure mixture. Those facts generate the central problem in prebiotic chemistry. Spontaneous self-organization is not known to be an intrinsic property of most organic matter, at least as observed in the laboratory. It can be driven only by an external source of free energy that is coupled to the organic system."</ref> Among the most common problems in prebiotic chemistry is the fact that origin of life research and experimentation relies on so much human intervention and fails to provide evidence for abiogenesis as a result of reliance on such frequent intervention.<ref name="Tour">James Tour, Charles B Thaxton, Walter L Bradley. 2020. The Mystery of Life's Origin. Discovery Press. ISBN 1936599740. 13. We're Still Clueless About the Origin of Life</ref><ref name="Richert">Richert, C. Prebiotic chemistry and human intervention. Nature Communications 9, 5177 (2018). https://doi.org/10.1038/s41467-018-07219-5</ref>

Another major problem in prebiotic chemistry is '''the water paradox''', the fact that water is essential for all living cells and yet it is very destructive to cellular machinery and components, a balance that is incredibly chemically delicate.<ref name="water paradox">Marshall, Michael (10 December 2020). "How the first life on Earth survived its biggest threat — water". Nature. 588 (7837): 210–213. doi:10.1038/d41586-020-03461-4. "This suggested to many researchers that life arose near the surface of the ocean. But many scientists today say there’s a fundamental problem with that idea: life’s cornerstone molecules break down in water. This is because proteins, and nucleic acids such as DNA and RNA, are vulnerable at their joints. Proteins are made of chains of amino acids, and nucleic acids are chains of nucleotides. If the chains are placed in water, it attacks the links and eventually breaks them. In carbon chemistry, “water is an enemy to be excluded as rigorously as possible”, wrote the late biochemist Robert Shapiro in his totemic 1986 book Origins, which critiqued the primordial ocean hypothesis. This is the water paradox. Today, cells solve it by limiting the free movement of water in their interiors, says synthetic biologist Kate Adamala at the University of Minnesota in Minneapolis. For this reason, popular images of the cytoplasm — the substance inside the cell — are often wrong. “We are taught that cytoplasm is just a bag that holds everything, and everything is swimming around,” she adds. “That’s not true, everything is incredibly scaffolded in cells, and it’s scaffolded in a gel, not a water bag.” If living things keep water controlled, then the implication, say many researchers, is obvious. Life probably formed on land, where water was only intermittently present.</ref> The prominent origin of life researcher [[Stanley Miller]] said the origin of life problem was more difficult than he or anyone else had imagined.<ref name="Why Abiogenesis is impossible">[https://web.archive.org/web/20170717223959/https://www.creationresearch.org/crsq/articles/36/36_4/abiogenesis.html Why Abiogenesis is impossible]</ref>