Theoretical origin of life: made in a lab, impossible (Introduction)

by David Turell , Tuesday, November 16, 2021, 14:56 (1103 days ago) @ David Turell

A strong opinion:

https://www.grisda.org/synthesizing-life-in-the-lab?mc_cid=5a79992abf

"Quoting a prominent scientist on this subject: “…life itself can be seen as an emergent property: the molecules that constitute a living cell (DNA, proteins, polysaccharides, lipids, etc.) are not living. The quality “life” arises from the assembly of these non-living elements, duly arranged in space and time.”

"Underlying all efforts in synthetic biology is the fundamentally crucial assumption that it is possible to assemble living matter stepwise from a set of biomolecules. A corollary of this supposition is that, at least in principle, living matter may be disassembled reversibly and reassembled. While such is the nearly universal consensus within the scientific community, as of now, these assumptions have not been verified experimentally.

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"However, a more cautious reviewer of the subject states: “…it is important to note that minimal life has not yet been achieved in the laboratory. Does this mean that it is in principle not possible? I do not believe so, although as a scientist it is always good to have a bit of doubt (perhaps we missed something important in our theoretical analysis)”

"This communication points to just such an oversight, the underestimation of the essential nature of the “out-of equilibrium” state of living matter.

"All life processes, metabolism, growth, stimulus response and replication are driven by on-going chemical reactions. Every chemical reaction exists in one of two states, non-equilibrium and equilibrium. On-going chemical processes are always in states of non-equilibrium.

"When a chemical reaction, aA + bB ⇌ cC + dD runs its course, equilibrium ensues, where the mass action ratio Γ=[C]cx[D]d/[A]axb becomes the equilibrium constant, Keq. At equilibrium, the change in free energy ∆F=0 and in this state the reaction cannot generate or absorb any energy.

"During chemical reactions there is a net flux of matter from reactants to products or the reverse. However, at equilibrium the flux stops.

"Moreover, the state of equilibrium resists change. As the Le Chatelier’s principle[20] states, if a chemical system at equilibrium experiences a change in concentration, temperature, volume, or partial pressure, then the equilibrium shifts to counteract the imposed change and a new equilibrium is established. Thus, according to this principle, any change from a state of non-equilibrium to equilibrium is irreversible.

"Even though in living cells each reaction is pushed toward equilibrium by an enzyme (so as to forestall the possibility of slower, random non-biological chemical events), if any of the hundreds to thousands of chemical processes could actually reach equilibrium, an irreversible metabolic block would result. Multiple such equilibriums would kill the cell. However, in live cells there are no isolated reactions and the problem of equilibrium is avoided. Rather, chemical events are linked into pathways, so that the products of reactions do not accumulate, but immediately react with another substance.

"The end products of metabolic pathways are either utilized immediately or they are secreted from the cell. Moreover, regulatory systems such as “feedback inhibition” help maintain homeostasis.

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"Current practitioners of synthetic biology, while recognizing the compulsory “out-of-equilibrium homeostatic state” of living matter, do not appear to appreciate the irreversibility <non-spontaneity?> of the state of equilibrium. Building artificial cells in a modular fashion will inevitably result in the onset of chemical equilibrium within each module. Once equilibrium is reached, the artificial cell, figuratively speaking, “runs into a brick wall”. It is no longer capable of growth or accomplish any net chemical process.

"No technology is known to achieve modular assembly of artificial cells while preserving the non-equilibrium status of each component reaction. While these considerations do not apply to polymerizations, such as RNA or DNA synthesis, as each incremental extension of the polymer is accompanied by the hydrolysis of a high-energy bond rendering these steps essentially irreversible, any other metabolic event is very much subject to termination due to reaching equilibrium. Until the construction of cell-like structures harboring metabolisms in homeostatic non-equilibrium states become reality, the most sophisticated efforts of synthetic biology will come to naught.

"Therefore, more than a century later, our response to Jacques Loeb’s call for the synthesis of living matter is that we are not there yet. We need to find ways to generate steady state non-equilibrium conditions within the artificial cells. These technologies await inventions in the future."

Comment: in our reality only life begets life. This exposition of the complexity of cells should show dhw how the automaticity of life is necedssary.