Brian Miller: Thermodynamics and the Origin of Life

One of the forefronts in biology is the robust conversations taking place between biologists and engineers. The similarities between human design and biological systems are becoming more clear as both fields advance. They are typically at levels in the biological hierarchy where functional relationships are identified. This effort is advancing most in the fields of systems biology, synthetic biology, and biomimetics.

Here is a small sampling of resources:

Survey of Engineering Models for Systems Biology

As a discipline, systems biology shares many characteristics with engineering. However, before the benefits of engineering-based modeling formalisms and analysis tools can be applied to systems biology, the engineering discipline(s) most related to systems biology must be identified. In this paper, we identify the cell as an embedded computing system and, as such, demonstrate that systems biology shares many aspects in common with computer systems engineering, electrical engineering, and chemical engineering.

Control Theory and Systems Biology Laboratory

The logic of the heat shock response is implemented through a hierarchy of feedback and feedforward control architectures that regulate both the amount of sigma-32 and its functionality. We have developed a dynamic model that captures known aspects of the heat shock system and are using it to exploring the logic of the heat shock response from a control theory perspective, drawing comparisons to control systems in engineering.

Systems Biology and the Quest for Design Principles

Some approaches compare living systems to well-functioning engineered systems to identify so-called optimality principles. Examples are the discovery of the general ‘optimal’ branching angle in vascular systems inspired by the designs of pipe systems that minimize the flow of resistance (Rashevsky 1961, Rosen 1967), and Savageau’s demand theory for optimal gene regulation (Savageau 1989). Engineering approaches have recently had a renaissance with the application of graph theoretical tools to biological datasets. In systems biology such principles are typically referred to as design principles. These need not focus on optimal performance but are organizational rules “that underlie what networks can achieve particular biological functions” (Ma et al. 2009, 260).

Engineering and control of biological systems: A new way to tackle complex diseases

It is worth briefly considering the relationship between systems biology and synthetic biology: systems biology can be thought of as the other side of the coin, in that it aims at developing a formal understanding of biological systems through the application of engineering and physics principles. …The drive in merging engineering and biology has begun and shows no sign of slowing down.

An Introduction to Feedback Control in Systems Biology

Although many of these researchers have recently become interested in control-theoretic ideas such as feedback, stability, noise and disturbance attenuation, and robustness, it is still unfortunately the case that only researchers with an engineering background will usually have received any formal training in control theory. Indeed, our initial motivation to write this book arose from the difficulty we found in recommending an introductory text on feedback control to colleagues who were not from an engineering background, but who needed to understand control engineering methods to analyse complex biological systems.

Biomimetics: forecasting the future of science, engineering, and medicine

Leonardo da Vinci’s (1452–1519) work is a fundamental example of biomimicry. He designed a “flying machine” inspired by a bird. In the Far East, General Yi Sun-sin built the turtleship, a warship modeled after a turtle, to fight Japanese raiders during invasions. The Wright brothers (1867–1948) took note of the wings of eagles and made a powered airplane that succeeded in human flight for the first time in 1903. Over the next century, the airplane became faster, more stable, and more aerodynamic. Schmitt was the first to coin the term biomimetics in 1957, and he announced a turning point for biology and technology.

Lecture on Applying Engineering to Life:

Obviously, many differences exist between human engineering and biological systems, but the nature of those differences demonstrates that biological systems are the product of a much higher intelligence. The latter demonstrate greater levels of efficiency (e.g. ATP synthase) and greater levels of ingenuity (e.g. capacities of birds to navigate and control their flight).

I understand you have to think this way, but this is a very selective reading. There is an exchange between engineering and biology, but a large amount of the complexity in biology is best explained by incremental addition of parts, more like a goldberg machine than a fresh de novo design. This is an immensely difficult way to design things for human designers, which is why we have such difficulty engineering biological systems. This complexity, however, actually improves the odds of biological evolution. What biology shows us is that life is not designed at all how a human designer would design it, and it cannot be understood with out engaging its deep history.

I know you are not talking about common descent here, but it is worth asking. Do you affirm common descent? If not, why did not God make it more clear that common descent is false?

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Sorry to jump back a few days, but there are some errors that need to be pointed out. As before, these pertain to Brian’s claims about the entropy status of cells.

Davie’s article makes no such calculation. Moreover, as I have shown here, the paper by Davies et al. is, to be kind, a very unreliable source when it comes to this subject.

This is also mistaken.

And I have never, until our discussion, encountered a serious scientist who would deny the roles that hydrophobic interactions play in the assembly of macromolecular structures, or that hydrophobic interactions are entropy-driven.

The fact remains - cells, today or at the inception of life, are high-entropy entities.

The OOL requires no such thing, and Morowitz’ calculation had nothing to do with such a preposterous claim.

This is a misrepresentation of Morowitz. He “hoped” for no such thing, but rather presented a coherent and entirely reasonable explanation for why life is not (in physical chemical terms) an equilibrium proposition. Moreover, the “order” mentioned here is quite akin to that seen in cells.

To understand the scope of what we are speaking about - recalling that chemical reactions are accelerated by 1000-1,000,000 fold or more in cells, if we equate a 1 mph breeze with uncatalyzed reactions, then we can see that cells are veritable maelstroms, comparable to storms with windspeed of tens of thousands of mph or more. This is quite far in excess of the pitiable storms Brian’s graduate group studied, and it is quite reasonable to suppose that this much-accelerated state of chemistry is going to be quite amenable to the sorts of spontaneous self-assembly and order we see in living cells.

Since cells are high-entropy entities, I believe Morowitz’ book is spot on.

I have to wonder - Brian continues to cling to thermodynamic considerations that completely ignore the fact that water interacts with solutes and macromolecules and makes very significant contributions to the entropy of living cells. It is almost as if Brian (and, by extension, the Discovery Institute) is proposing a new and different status for water - maybe that it is inert aether of sorts. While I haven’t read it, maybe Denton’s recent book about water had some similar ideas. Perhaps Brian can elaborate on this, or at least explain why he continues to completely ignore the principal chemical constituent of all living things.

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Seriously?

If one is going to use this sort of logic, then I believe the reasoning is more like:

Human engineering (intelligent design) cannot come close to accomplishing what we see in living systems. It thus stands to reason that life is beyond the capabilities of intelligent design.

(If one is going to use the logic that Brian is deploying here …)

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What would be the best examples and related research articles which demonstrate your point? You might desire to add some additional commentary to emphasize the salient points.

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No it doesn’t. It merely shows humans in a few hundred years of engineering design haven’t achieved the results natural processes working over 3.5 billion years have achieved.

Why ID-Creationists still think arguments from personal incredulity count as scientific evidence is a real mystery.

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OOL researchers have known for almost a century that cells represent low entropy configurations of matter. Here are a few representative descriptions:

On the Free Energy That Drove Primordial Anabolism

In 1944 Schrödinger published his famous book “ What is Life ”, in which he points out that life is avoiding the rapid decay into the inert state of equilibrium and that it is continually drawing negative entropy from its environment. Although the term negative entropy or negentropy created some confusion and his description is far from being a definition of life, Schrödinger already recognizes a very important basic principle that, with only a few exceptions, is unique to all things that are alive. Life is capable to create order and complexity, the opposite of entropy, by feeding on a suitable kind of free energy. In terms of biochemistry, the continuous supply of free energy is essential for anabolism, which is defined as the processes in metabolism that result in the synthesis of cellular components from precursors of low molecular weight. Reactions that build up complex molecules from smaller building blocks are fundamental to every living being. As a consequence, the utilization of free energy, vitally important for every anabolic reaction, is essential for the origin of life as well.

The Origin of Life

On the theoretical side, we have to start with the realization that if we apply standard equilibrium thermodynamics to living systems, we arrive at something of a paradox. Living systems possess low entropy, which makes them very improbable from the equilibrium thermodynamic viewpoint.

Very few have actually attempted to calculate the precise drop in entropy since doing so is likely very difficult. However, Morowitz in Energy Flow in Biology (EFB) estimates the entropy drop due to the formation of macromolecules (p. 97). A few others have also made attempts.

Dr. Hunt’s confusion is due to his apparently assuming the entropy increase due to the formation of a cell membrane could help compensate for the entropy reduction for the rest of the cell, which is not accurate. The rest of the cellular structures have just as much difficulty going to a lower entropy state. A good book to better understand entropy at a more intuitive level is Entropy and the Second Law by Arieh Ben-Naim. He may also be confusing the entropy change due to the folding of a protein and the creation of a protein.

Morowitz in EFB (p. 66) calculates the probability for a cell forming at roughly 1 in 10 to the power of 100 billion. Later he calculates the probability for monomers in the ocean forming into a cell (p. 99) at roughly 1 in 10 to the power of 10 billion. He was clearly taking into consideration the effect of water.

He also states (p. 68)

Again, we stress in a very firm quantitative way, the impossibility of considering life organizing as a fluctuation in an equilibrium ensemble.

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I think this discussion has run its course. What I have learned from this exchange is that:

  1. Brian doesn’t believe hydrophobic interactions are important for protein folding and assembly, or in other macromolecular associations. (There is bit of irony here since he cites an author who disagrees quite completely with this view. But I do not know the behind the scenes here, so…)

  2. Brian apparently doesn’t believe that water interacts with macromolecules. (Again, this is something that Ben-Naim has published on.)

  3. Since Brian repeatedly cites a calculation by Mrorowitz (“Morowitz in EFB (p. 66) calculates the probability for a cell forming at roughly 1 in 10 to the power of 100 billion” etc.) as support for his position, he obviously believes that living cells are in chemical and thermodynamic equilibrium. (This is the context for Morowitz’ calculations.)

Brian has dug in his heels and doubled down on this erroneous ideas, and it is clear that more discussion will not accomplish anything. While not likely, I would be interested in knowing if the DI brain trust (Behe, Axe, and Gauger, to name three biologists) holds to these views of the chemistry of living things.

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A post was split to a new topic: Does Peaceful Science Misrepresent ID?

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.

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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:

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@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.

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).

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.

RNA/DNA
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.

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@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.

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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.

Also:

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

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

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.

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