Brian Miller: Thermodynamics and the Origin of Life


(Brian Miller) #76

No worries, I am used to such interactions. Dr. Hunt actually helped me to focus my attention on certain important issues, for which I am immensely grateful.

Chemical reactions in cells are accelerated due to enzymes. Morowitz fell within the metabolism-first camp, so he believed enzymes came later in the game. A nice book on his ideas is The Origin and Nature of Life on Earth (ONLE). Here is a helpful quote to understand his thinking:

Energy Flow and the Organization of Life

The common feature of ionized air in a lightning bolt and wall storms in a hurricane is that both create channels to transport currents of matter and energy between two reservoirs at different potential. For lightning the potential is voltage and the current is charge, and for convective weather the potential is temperature and the current is heat. Without lightning or hurricanes, charge or heat could still move by diffusion, but the resistance to their motion through near-equilibrium states is much greater and the transport much slower than through the channel state. We understand well how voltage or temperature differences can drive these non-equilibrium channels to form and stabilize them under perturbations, and we have ways to predict the main features of the channel states from the properties of the systems in which they arise.

Whereas weather is a diffuse phenomenon primarily involving mass transport and physical state change, life creates transport channels in the chemical domain, employing the more concentrated energy flows associated with molecular re-arrangements.

The basic idea is that life started in a non-equilibrium state where the flow of energy and mass through the system caused certain chemical pathways to self-organize similarly to the formation of a funnel cloud. His model, like all others, faces four major challenges:

  1. Accessing a constant supply of high-energy reactants or other energy source.
  2. Ensuring the right reactions move forward while blocking deleterious ones.
  3. Coupling that source of energy to the energetically unfavorable reactions.
  4. Localizing the essential molecules while blocking out the others.

In relation to the first issue, he proposed several possible sources of energy, but the problem is that raw energy would have driven the system toward greater entropy. Specifically, it would have caused such damage as breaking apart macromolecules. Morowitz comments (ONLE p. 558):

For driven non-equilibrium systems, the situation is far worse. In addition to the constant thermal disruption of microscopic order, the same random reactions by which order is assembled stands ready to degrade it away. Unless a driven system is continually self-amplifying, it cannot even persist. It is as if, in addition to handling the customers, the watchmakers were bedeviled continually by gremlins that disassembled any module not kept in hand.

In relation to the second issue, the metabolism-first model has been severely criticized due to the implausibility of maintaining only life-friendly target reactions without highly specific enzymes. Leslie Orgel provided one of the most comprehensive critiques:

Almost all proposals of hypothetical metabolic cycles have recognized that each of the steps involved must occur rapidly enough for the cycle to be useful in the time available for its operation. It is always assumed that this condition is met, but in no case have persuasive supporting arguments been presented. Why should one believe that an ensemble of minerals that are capable of catalyzing each of the many steps of the reverse citric acid cycle was present anywhere on the primitive Earth, or that the cycle mysteriously organized itself topographically on a metal sulfide surface? The lack of a supporting background in chemistry is even more evident in proposals that metabolic cycles can evolve to “life-like” complexity. The most serious challenge to proponents of metabolic cycle theories—the problems presented by the lack of specificity of most nonenzymatic catalysts—has, in general, not been appreciated. If it has, it has been ignored.

Morowitz also recognized this problem:

James Trefil, Harold J. Morowitz, and Eric Smith, The Origin of Life, American Scientist

Networks of synthetic pathways that are recursive and self-catalyzing are widely known in organic chemistry, but they are notorious for generating a mass of side products, which may disrupt the reaction system or simply dilute the reactants, preventing them from accumulating within a pathway. The important feature necessary for chemical selection in such a network, which remains to be demonstrated, is feedback-driven self-pruning of side reactions, resulting in a limited suite of pathways capable of concentrating reagents as metabolism does.

However, the really serious problem is related to issue 3: directing the energy from some source (e.g. proton gradient) toward driving multiple target reactions which are energetically unfavorable. The solution must involve the continuous production of some energy currency molecule (e.g. ATP) through some sort of molecular/chemical engine, and it must include a host of complex enzymes to couple the reactions. Only enzymes could properly target and couple the right reactions and avoid others.

(S. Joshua Swamidass) #77

I agree.

@art posted his final comment, and @bjmiller just posted his. Thank you both for a substantive engage in which I honestly learned a lot. The goal is to understand and be understood. Progress to this end was certainly made here.

At this time, I am closing the thread. If either of the principles desire to post more on this, they may. Just ask the @moderators to temporarily open the thread for you.

Though disagreement remains, @Art’s question is salient and hopefully answered:

(S. Joshua Swamidass) #78

(S. Joshua Swamidass) #79

(S. Joshua Swamidass) #80

@Art it is possible misunderstood @bjmiller’s claims. He clarified on another thread: Is it Peaceful to Misrepresent?

I’m reopening the thread for it to be resolved here.

(Arthur Hunt) #81

I don’t think I misunderstood anything.

Recall that my original point was that any claims to the effect that the structures we see in living cells in some way violate the second law (in that they are inherently low-entropy in nature) are incorrect. There may be a few loose ends, so to speak (Brian hasn’t addressed the glaring error in Davies’ paper, for example), but Brian’s remarks have evolved in ways that suggests that he is willing to consider the validity of my argument. I don’t think there is any need for further elaboration.

My problems with his references to Morowtiz’ books remain, but are better left to other discussions (that need not be initiated at this time, since the forum has lots of interest in other matters).

(Brian Miller) #82

You have quite a talent for understatement.

My “glaring” error was to say Davies “calculated” the entropy change instead of “cited”. Fair enough, my mistake. Davies references Marin et al. (2009) in their estimate of the entropy reduction due to the compartmentalization of solutes in Saccharomyces cerevisiae. The process of compartmentalization relates to a reduction in entropy since concentrating solutes (at least until cohesive forces are significant) relates to a free energy increase given by DG = RT*ln(Conc_final/Conc_initial). And, the increase relates to a decrease in entropy. Their calculation is actually far too conservative, for the real problem is taking highly dilute building blocks for cells in the environment and concentrating them in a cell membrane. More below.

Fair point. Jackson did not address the current theories.

Let me summarize the challenges to Lane’s model, including Jackson’s legitimate general concerns. These challenges would generally relate to all models.

Creation of Microenvironment
For Lane’s model to work, he needs a membrane which has the right properties to form over a micropore or the equivalent in the alkaline vent. The micropore needs to access high pH fluid from the vent to allow for the proton gradient to continuously operate. Yet, it cannot allow the developing metabolism to escape. The membrane has to allow all of the needed metabolites and building blocks to enter, but it has to then prevent them from leaving. No membrane which even remotely matches these criteria has ever been observed or generated in a laboratory setting. Suffice it to say, such an environment appearing would be very rare.

Energy Conversion
The next challenge is for the energy from the proton flow to drive chemical reactions. Lane in ideal laboratory settings has demonstrated that a “little bit” of formaldehyde could be created from the reduction of carbon. The challenge is then for a miraculous combination of molecules to embed in the membrane to help drive other needed reactions for life. As the metabolism developed, increasing amounts of energy would need to be converted to maintain it. In the smallest cells, dozens of ATP synthases are required. No realistic chance exists for the membrane complex to generate anywhere near so much energy for a fully functional metabolism to emerge which would allow the protocell to be birthed. The distance between experiment and reality is stark.

Directing Needed Reactions
The cell would soon need complex proteins/enzymes to drive active transport across the membrane to maintain homeostasis, drive the correct reactions, and to couple the breakdown of energy currency molecules to driving unfavorable reactions. The perfect set of conditions would have to take place to generate several different types of homochiral amino acids. Then, another set of perfect conditions would be required to combine them into long chains. As mentioned previously, the probability for chains of length N to emerge drops exponentially with N, so the chance of a chain long enough to form into useful enzymes is exceedingly small. A 100 aa length chain corresponds to a probability of around 1 in 10^30 based on the Flory-Schulz distribution in conditions far more optimal than could be imagined on the early earth.

Long chains would have to be produced in the trillions - I am being very conservative - to have any chance of stumbling upon the right sequences to drive reactions, particularly the coupled ones. And, trillions of copies of each correct enzyme would have to form for one to have any possibility to successfully migrate to the developing cell before it broke apart. And, this process would have to repeat itself for hundreds of proteins. The formation of the cell is analogous to an individual winning the lottery many times in a row.

Generating the nucleotides is vastly more difficult than amino acids. Even in the most miraculous set of conditions, they would be in minuscule quantities. They would then need to be concentrated and transported into the protocell. Or, the metabolism would have to develop to manufacture them inside the membrane, which would be equally miraculous. Then, the proteins would have to be encoded into DNA chains, and the translation machinery would have to develop to create more proteins before the initial ones broke apart.

Escape from Vent
For the cell to escape, lipids would have to coalesce around the developing metabolism with the right selective semipermeable properties including active transport. At the same time, the machinery would have to emerge for the cell to create its own proton gradient, allow it to flow through the membrane, and harness the energy. Jackson discussed the challenges for this stage in a recent article. The cell would also need to develop full cellular replication before it perished.

When such theories are examined in detail, they always have to invoke a neverending series of miraculous events. Most OOL researches in each camp see the theories in every other camp as completely implausible. They embrace their own theories by strongly downplaying the challenges. The key issue is that any theory has to justify how large numbers of molecules moved against the thermodynamic drives and arranged themselves into fantastically improbable configurations.

(S. Joshua Swamidass) #83

@bjmiller I apologize for closing this thread too abruptly. Thank yoi for letting me know, so I could reopen it. I want to be sure you are fairly represented here. Peace.

(Arthur Hunt) #84

The loose end I was thinking of was this:

Frankly, the source of this quote is an incoherent, error-strewn mishmash of stream-of-consciousness ramblings. I would never ever allow a student of mine to put such drivel in a thesis (let alone a paper in a journal), and it speaks very poorly of the journal that it was published. The quoted excerpt above is a glaring error that relates to the specific point I was raising, and it calls into question any reference to the article as support for an argument or proposition.

Again, this is the main loose end I was thinking of.


It is safer to say that a bit of hyperbole is what moved this discussion to a convenient stopping point.

(S. Joshua Swamidass) #85

@bjmiller, it would be helpful if you could answer @art’s question here.

(Brian Miller) #86

My mistake. I apologize. I emailed one of the authors for clarification without mentioning the more colorful comments. I will report his response.

Whatever his response, I will repeat my previous comments. The formation of the membrane is thermodynamically favorable if all of the right building blocks are present in sufficient concentrations. However, the fact that this step is favorable will not help other processes move forward. For that and other reasons, the OOL community takes for granted that the formation of a cell from the chemicals present on the early earth represents a serious barrier in terms of the needed increase in free energy/decrease in entropy.

Update: The author I contacted was drawing from another author. I am going to contact an expert I know in lipids who might provide some interesting insights, and I will report back.

(Arthur Hunt) #87


Maybe there is a participant here who has published research on membranes and membrane transport?

(Brian Miller) #88

I found the original source for the claim. It comes from
Introduction to Molecular Biophysics by ­­­Jack A. Tuszynski Michal Kurzynski, p. 413

They may have simply made a mistake, or they may be including all of the other structures in the membrane as part of the “order”.

I heard back from the lipid expert, and he commented that any lipids produced on the early earth which could have been candidates for a viable cell membrane would have been in very small quantities. As a consequence, their concentration and purification would have corresponded to a significant drop in entropy before they reached a concentration where the formation of a membrane would have been thermodynamically favorable.

(Brian Miller) #90

I was asked about my views on common ancestry and whether I believed cells just popped into existence. The questions can be summarized into what would I expect to see if I traveled back in time to watch the appearance of life. The answer is that I do not know. I am open to many possibilities. In terms of origin of life my scientific sensibilities would lean toward the most parsimonious infusion of information into the system as possible. In other words, I would expect that everyday physical processes would be allowed to act as much as possible, and infusions of information would be a strategic points.

In the case of OOL, the formation of a cell would have to be in dramatic jumps since each stage represents increasing the free energy of the system. And, nature would push back toward equilibrium more forcefully as the system moved away from it. Imagine pushing a bolder up a hill. If one stopped pushing, it would immediately roll back down the hill. The same is true in any OOL scenario. At any stage, if the next miraculous set of conditions and chemical modifications did not take place, the entire system would move back toward simple, low-energy molecules.

You have highlighted why I believe an ID perspective is essential for the advancement of biology. Materialist scientists have constantly fallen into the imperfection-of-the-gaps fallacy:
In the case of the importance of proton gradients, Nick Lane explained their advantage of accessing energy from reactions in fractional proportions.

But one glaring problem with aerobic respiration is that it doesn’t balance. Exactly how much ATP is produced per oxygen molecule consumed? The amount varies, but it’s somewhere around 2.5 ATP molecules. That works out to 28–38 ATPs per glucose — again, a variable number, and never an integer (Silverstein 2005). Aerobic respiration is not stoichiometric, so it’s really not chemistry. And that’s why the long search for a high-energy chemical intermediate (a molecule able to transfer the energy from the oxidation of glucose to form ATP) was doomed to failure.

In place of such an intermediate, Mitchell proposed a proton gradient across a membrane: the proton motive force (Mitchell 1961). It works much like a hydroelectric dam. The energy released by the oxidation of food (via a series of steps) is used to pump protons across a membrane — the dam — creating, in effect, a proton reservoir on one side of the membrane. The flow of protons through amazing protein turbines embedded in this membrane powers the synthesis of ATP in much the same way that the flow of water through mechanized turbines generates electricity. This explains why respiration is not stoichiometric: a gradient, by its very nature, is composed of gradations.

Speaking theologically, can the claim that living systems look poorly designed possibly fit within any traditional theistic framework? Does not such a claim imply that a Creator played no meaningful part in Creation, but we are simply an accident of nature?

In addition, the positive evidence for design has constantly increased as biology and technology have advanced. The correspondence of the two keeps increasing, and engineering presupposes direct intelligent agency. Imagine a spaceship crashed on earth. What approach would yield more useful insights, assuming the vessel was purely a product of natural processes or the product of advanced engineering. A minimally complex cell looks more much more like a spaceship than a glob of tar.

Moreover, a self-replicating autonomous system demands exacting constraints. It is combining a machine, its manufacturing facility, and its operator into a single entity. It demonstrates teleology (purpose) at a level beyond human engineering since it possesses closure to efficient causation. If you really wish to learn how deep the rabbit hole goes, study Rosen’s work on life:

(Joseph Akins) #91

Hi Brian,

I appreciate your insights into OoL research and hope that we have many future discussions on it. Besides the difference in your ID vs my hypernaturalistic approach is that 1) you presuppose information, whereas I focus on energy dissipation, 2) you focus on past improbabilities whereas I look at the existing commonalities of archaea, bacteria and eukaryotes to alkaline vent processes and 3) I hold to Big Bang ((BB) cosmology which I suspect you do not.

The BB was a high energy, far from equilibrium and low entropy event. It is the relentless increase in entropy of the universe that defines the arrow of time, so there are deep philosophical, theological and scientific possibilities to explore. My bias, as stated previously, is strongly toward a chain of energy from the BB to stars to mantle convection on Earth to alkaline vents to life to humanity relying on low entropy energy from the sun for our physical lives. It is powerful to me that even as we increase the entropy of the universe we act on a local scale to bring order from disorder for 6 days then spend one day reflecting on the absurdity of it in light of the relentless passage of time which is God’s domain. This ties back to my fascination with the Lane-Russell-Carroll trifecta and my rejection of projecting biology on to OoL.

(Brian Miller) #92

Thank you.

(S. Joshua Swamidass) #93

I agree with you on this.

I also agree that this is in error. We noted this article from you here: Denis Lamoureux on the God-of-the-Gaps Fallacy.

(Joseph Akins) #94

I’m very confused by this. Poorly designed is not the issue; it’s that if any design is less than perfect how does that imply direct divine agency? I guess I part with “any traditional theistic framework” since I find no logical, or scriptural, necessity to expect perfection in any aspect of physical creation. The purpose of this world is not as a stage for demonstration of God’s perfection outside of Christ. This world has been designed not just for the origin of physical life which just needs to be good enough to accomplish God’s plan of redemption, but Eternal Life which is by definition knowing True Perfection. You seem to conflate this creation at any point in time with the New Creation. I find this scripturally indefensible, but may be wrong. Very interesting, especially since our disagreements on the origin of physical life are inconsequential compared to our agreement on the origin of Eternal Life in Christ by nothing we can earn, or even deserve!

(Brian Miller) #95

I actually do hold to a BB cosmology. Although, I am skeptical of inflation and more exotic models such as string landscapes.


This statement is very striking to me. A lot of the discussion have been centered on the entropy of the production of cell membranes. Suppose that production of cell membranes do produce a large amount of entropy. @Art, what about the rest of the cell? Do the same principles apply and their production also generate a large amount of entropy?