Stairway to Life by Change L. Tan and Rob Stadler

Molecular Biologist Change L. Tan and bio medical engineer Rob Stadler offer a critique of origin of life, particularly what was learned in light of Craig Ventner synthetic life experiments.


I interviewed Dr. Tan on her book.


Salvador Cordova and friends talk with Professor Change L. Tan about her recently published book, Stairway to Life, that re-examines the improbability of life emerging spontaneously. She also talks briefly about how her study of Eukaryotic cells motivated her to question the prevailing view about the ease with which Eukaryotic cells can naturally evolve. Her analysis of Eukaryotic evolution motivated her to also re-examine the origin of life from her perspective as a biologist and physical organic chemist. Dr. Tan got her PhD at University of Pennsylvania and her post-doctoral work at Harvard. She is currently a professor of molecular biology at University of Missouri.

Rob Stadler posted a video anticipating what they would publish in their book. It had some minor corrections, but I haven’t found much to take issue with at all, and further shows the collapse of naturalistic explanations ( as in explanations by ordinary mechanisms) as explanations for the origin of life.

Rob Stadler received a BS in biomedical engineering from Case Western Reserve University, an MS in electrical engineering from MIT, and a PhD in medical engineering from the Harvard/MIT Division of Health Sciences and Technology. As a scientist in the medical device industry for over twenty years, he has obtained more than 140 US patents, has been elected fellow of the American Institute of Medical and Biomedical Engineers, and has contributed to medical devices that are implanted in millions of patients worldwide.

I actually read the first draft written by Dr. Tan only, and it was also very good, but very technical. I had to crawl through some of the organic chemistry concepts which were emphasized in the first draft of the book.

A lot of the book could be summarized by Steve Benner’s review paper:

The Asphalt Paradox (Neveu et al. 2013). An enormous amount of empirical data have established, as a rule, that organic systems, given energy and left to themselves, devolve to give uselessly complex mixtures, “asphalts”. Theory that enumerates small molecule space, as well as Structure Theory in chemistry, can be construed to regard this devolution a necessary consequence of theory…

Thus, even if we solve the asphalt paradox, the water paradox, the
information need paradox, and the single biopolymer paradox, we still must mitigate or set aside chemical theory that makes destruction, not biology, the natural outcome of are[sic, should be “our”] already magical chemical system.

  • Steve Benner

Orig Life Evol Biosph (2014) 44:339–343 DOI 10.1007/s11084-014-9379-0

I haven’t watched it yet, but Jon Perry just had a conversation/debate with Stadler about whether or not OoL research should continue to be funded. Might be interesting.

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I watched about half of the Jon Perry debate with Rob Stadler, and both were very civil.

Life can arise naturally in the sense that a pre-existing cell can naturally create another cell. The issue is if a cell like a bacteria can emerge from random environments and environmental changes. The asphalt paradox will hold in a large spectrum of environments. If one is looking for that one environmental scenario where the asphalts paradox is violated, then how probable is that?

If life is the result of a miracle, what kind of research would be needed for someone to arrive at that inference. I guess everyone has their own threshold for how bad a research program must fail before they might even consider the supernatural.

BUT, the point of the Stairway of Life book is to point out the research has regressed, whereas Jon Perry insists its progressing with many breakthroughs!

Yes, how probable is that? How do you compute the probability that such an environment exists? And how probable is it that life was magically wished into existence? If we’re going to pick the more probable option, we need actual numbers. But you have question marks on both sides of the scale here.

Yes I have to agree, how could you scientifically explore that question? Rob Stadler claimed multiple times there had been no supernatural creationist research done because all the money was going to tackling a natural origin life. But what experiment would he be doing to determine how life was magically wished to exist?

Well to begin with how about if it actually fails?

Which is of course completely ridiculous and wrong, since in point of fact new discoveries are constantly made about what is possible. Just to pick two example, recent work by Nick Lane on the possibility of forming stable fatty acid vesicles in seawater. Or that mere iron catalyzes the reverse Krebs’s cycle and acetyl-CoA pathways. They used to think that was impossible.


I’ve only seen the first half of the debate, and I have to say I’m not at all impressed with Stadler. He repeats a lot of the same canards we’ve been hearing for years, and doesn’t demonstrate the slightest appreciation for what is actually being achieved by OoL research.

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I don’t think Rob was out to debate, he was out to get information as that’s how this got started according to Jon Perry.

The video of Rob at TCCSA (twin cities creation ) actually making his case was a stronger presentation, and even moreso the book which included the asphalt paradox which I wasn’t aware of till recently.

The press hypes up only one side of the OOL story, the “progress”, they don’t highlight the known regresses, and they are serious. Koonin would not be thinking of invoking multiple universes if the problems weren’t getting serious.

In anycase, I was commissioned to write a follow on book, tentatively titled Stairway to Understanding. I saw the Stairway to Life project developing and was a non-technical reviewer of the book. I was listed in the acknowledgements.

One of the major problems as Dr. Tan pointed out, though she doesn’t use the words, is the law of large numbers, which makes difficult the origin and uniformity of large numbers of isomers (nucleotides and amino acids) forming homo linked biopolymers. These are known problems too which were really borne out in Craig Ventners work, specifically the use of technology like the Blue Herron process.

Perhaps she knows what the law of large numbers actually is.

What are these regresses you speak about?

Really? How so, be very specific.

Right now the enterprise is built on faith in the face of contrary facts like the asphalt paradox and the water paradox (which were covered briefly in Rob’s TCCSA video), and in more detail in the book. The problem is abiogenesis research hasn’t succeeded though it is advertised as succeeding when it is actually failing. They’ve actually redefined the problem that needs to be solved, which is really equivocation, not a real solution. The problem isn’t building pre-cursors or replicators that evolve – That’s not the real problem!

Regarding vesicles, without transmembrane proteins to enable selective transport of food-in and waste-out, it’s a nice way to build a tomb for the would-be percursors of life, so Lane’s work is moot, but it sure isn’t advertised as such. For each “success” we discover several more failures and obstacles. That is not promising for the OOL enterprise.

But regarding the question of using science to infer (guess is perhaps a better word) the supernatural – suppose someone is blind and healed after a prayer in the name of Jesus. It could be a coincidence, but maybe not. I asked ex-Christian turned atheistic evangelist Tracie Harris about a blind girl healed after astronaut Charles Duke prayed for her. I said if I had been blind and someone prayed for me in the name of Jesus and then I got healed, I would follow the Jesus the rest of my life. In contrast, Tracie Harris, on the TV show where I called in to ask, she didn’t say she would follow Jesus but rather try to find a naturalistic answer or find a mechanism that cured the girl of blindness and try to get everyone healed.

The issue then is how we decide what is true in the face less facts available to us than we might like, and at what point does someone decide an event is a miracle of God. Jon Perry didn’t seem to see the problem being posed to him by Rob, and maybe Rob could have been more forthright in stating the problem.

As far as iron catalysis of the citric acid cycle, the problem of life is NOT achieving reactions the simplest way, but the extravagant ways it does it – reproduction in peafowls involves the peacock’s tail. It’s extravagant. And such extravagant Rube Goldberg machines are a problem for naturalism because, even as Darwin suspected, natural selection should not favor extravagance.

Smart lady. Christians should adopt that approach in that situation as well.

Citation needed

Sexual selection can

But you’re not explaining why it’s failing or regressing. You’re just declaring that it’s faith, and then saying the problem is that it hasn’t already succeeded. If not having already succeed means regression and failure, then no person can succeed at running a marathon, and will be in a continuous state of failure and “regression” up until the very moment they cross the finish line. Such a long run, and all for nothing.

Your argument is bunk right out of the gate, as I suspected there is nothing here. It’s just smoke and mirrors, a piece of not-even-cleverly constructed rhetoric in a historically long line of “Imminent collapse of Darwinism”-type propagandist talking points.

They’ve actually redefined the problem that needs to be solved

[citation needed]

And this is where you reveal that you actually have no understanding of the actual progress in research into primitive cell membranes. Fatty acid vesicles actually have an intrinsic capacity to allow small molecules(such as single amino acids, mononucleotides, and water) to diffuse across the membrane, a process which is inherently self-regulating in a manner similar to osmosis. As food is located outside the membrane but not inside, the difference in concentration will attempt to equilibrate, so food will diffuse into the vesicle. The waste products produced inside will not exist outside, thus there will be a greater concentration of waste inside than outside, and so the tendency will be for waste to keep diffusing out, while food keeps diffusing in. These are experimentally confirmed facts. The whole point is that actually using prebiotically plausible molecules like simple fatty acid mixtures, as opposed to modern phospholipid membranes which really are almost totally impermeable without active transport machinery, really does alleviate this problem. And here you are, showing zero signs of even being aware that this problem was solved long ago.

I could go on and on, but it’s obvious you’re just making stuff up as you go along. You and Stadler actually have nothing at all but rhetoric and manifest ignorance.

So your suggestion for a creationist research program into the origin of life is to pray for Jesus to make life spontaneously appear in the test tubes? How long must this continue before we declare it a failure?

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I don’t think that was a smart policy on her part, and it does relate to the topic at hand – how much failure of naturalistic OOL must happen before an individual decides something is a miracle? If somone will be healed of blindness after prayer in the name of Jesus, given such conditions are not known to spontaneously change, much less even supposing they did, should it happen after a prayer, how much evdience is enough evidence – everyone has their threshhold of when they would decide a supernatural event happened.

If it’s not to personal to ask, do you believe Jesus rose from the dead through a miraculous act of God? I thought you said you were a Christian. Perhaps I was mistaken. Apologies in advance if I misread your statements in the past.

I thought I was. But I learned I was lying to myself and being intellectually dishonest because I really wanted Christianity to be true and I still do. I’m firmly in the agnostic camp as of now

Really? Not try to investigate and find an explanation to help others? So just screw everyone else? You seem like a swell guy. Making yourself look like a jerk just to hold onto your lousy argument.

And I have to ask. How does one go about measuring extravagance? How much extravagance can known evolutionary processes accomplish? Where’s that edge?

Good question, and it’s worth it to go over as it relates to the law of large numbers, I’ll have to reply in pieces since this is a technical issue.

The is the sort of adenine nucleotide (deoxy Adenosine Monophosphate) found in life.

It consistes of 3 functional groups: adeneine base, deoxy ribose, and monophosphate group. [corrections welcome as I’m not schooled in organic chemistry, yet, though I was allowed to take several biochemistry with instrctor permision]

From a pre-biotic standpoint, the are numerous ways to configure the 3 functional groups, not just the way in the diagram, and random soups with the 3 functional groups will not uniformly result in this configuration. Agree or disagree? Corrections welcome. Thanks in advance for comments.

While on the subject of primitive cell membranes, I consider the work done by the Szostak lab on fatty acid vesicles to be more relevant, illuminating, and important to understanding the origin of life, than any of the work they have done on the RNA world hypthesis.

Important selected publications that can help someone understand why I say this:
Semipermeable lipid bilayers exhibit diastereoselectivity favoring ribose. Sacerdote MG, Szostak JW. Proc Natl Acad Sci U S A. 2005 Apr. PDF


Nutrient uptake by a primitive cell would have been limited by the permeability characteristics of its membrane. We measured the permeabilities of model protocellular membranes to water, five of the six pentoses, and selected aldohexoses, ketohexoses, and three to six carbon alditols by following volume changes of vesicles after the addition of solute to the external medium. Solute hydrophobicities correlated poorly with permeability coefficients within one structural class of compounds. The permeability coefficients of diastereomeric sugars differed by as much as a factor of 10, with ribose being the most permeable aldopentose. Flexible alditols and sugars, sugars biased toward or restricted to furanose forms, and sugars having anomers with hydrophobic faces permeated more quickly than compounds lacking these features. Among the aldopentoses, only ribose possesses all of these properties. Ribose permeated both fatty acid and phospholipid membranes more rapidly than the other aldopentoses or hexoses. The enhanced permeability conferred by the unique conformational preferences of ribose would have allowed faster assimilation of ribose by primitive cells as they passively absorbed materials from the environment. The kinetic advantage of ribose over the other aldopentoses in crossing membranes may therefore have been one factor that facilitated the emergence of the RNA world.

Fatty Acid/Phospholipid Blended Membranes: A Potential Intermediate State in Protocellular Evolution. Jin L, Kamat NP, Jena S, Szostak JW . Small. 2018 Feb PDF.


Prior to the evolution of membrane proteins, intrinsic membrane stability and permeability to polar solutes are essential features of a primitive cell membrane. These features are difficult to achieve simultaneously in model protocells made of either pure fatty acid or phospholipid membranes, raising the intriguing question of how the transition from fatty acid to phospholipid membranes might have occurred while continuously supporting encapsulated reactions required for genomic replication. Here, the properties of a blended membrane system composed of both oleic acid (OA), a monoacyl fatty acid, and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), a diacyl phospholipid are described. This hybrid vesicle system exhibits high stability to divalent cations (Mg2+ ), while simultaneously maintaining its permeability to small charged molecules such as nucleotides and divalent ions such as Mg2+ . This combination of features facilitates key reactions expected to occur during a transition from primitive to modern cells, including nonenzymatic RNA replication, and is also compatible with highly evolved functions such as the ribosomal translation of a protein. The observations support the hypothesis that the early transition from fatty acid to phospholipid membranes could be accomplished through intermediate states in which membranes are composed of amphiphile mixtures, and do not require protein transporters.

Physical effects underlying the transition from primitive to modern cell membranes. Budin I, Szostak JW. Proc Natl Acad Sci USA. 2011 Mar. PDF


To understand the emergence of Darwinian evolution, it is necessary to identify physical mechanisms that enabled primitive cells to compete with one another. Whereas all modern cell membranes are composed primarily of diacyl or dialkyl glycerol phospholipids, the first cell membranes are thought to have self-assembled from simple, single-chain lipids synthesized in the environment. We asked what selective advantage could have driven the transition from primitive to modern membranes, especially during early stages characterized by low levels of membrane phospholipid. Here we demonstrate that surprisingly low levels of phospholipids can drive protocell membrane growth during competition for single-chain lipids. Growth results from the decreasing fatty acid efflux from membranes with increasing phospholipid content. The ability to synthesize phospholipids from single-chain substrates would have therefore been highly advantageous for early cells competing for a limited supply of lipids. We show that the resulting increase in membrane phospholipid content would have led to a cascade of new selective pressures for the evolution of metabolic and transport machinery to overcome the reduced membrane permeability of diacyl lipid membranes. The evolution of phospholipid membranes could thus have been a deterministic outcome of intrinsic physical processes and a key driving force for early cellular evolution.

A simple physical mechanism enables homeostasis in primitive cells. Engelhart AE, Adamala KP, Szostak JW. Nat Chem. 2016 May. PDF.

### Abstract

The emergence of homeostatic mechanisms that enable maintenance of an intracellular steady state during growth was critical to the advent of cellular life. Here, we show that concentration-dependent reversible binding of short oligonucleotides, of both specific and random sequence, can modulate ribozyme activity. In both cases, catalysis is inhibited at high concentrations, and dilution activates the ribozyme via inhibitor dissociation, thus maintaining near-constant ribozyme specific activity throughout protocell growth. To mimic the result of RNA synthesis within non-growing protocells, we co-encapsulated high concentrations of ribozyme and oligonucleotides within fatty acid vesicles, and ribozyme activity was inhibited. Following vesicle growth, the resulting internal dilution produced ribozyme activation. This simple physical system enables a primitive homeostatic behaviour: the maintenance of constant ribozyme activity per unit volume during protocell volume changes. We suggest that such systems, wherein short oligonucleotides reversibly inhibit functional RNAs, could have preceded sophisticated modern RNA regulatory mechanisms, such as those involving miRNAs.

Work by other groups have corroborated similar phenomena:

Black RA, Blosser MC. A Self-Assembled Aggregate Composed of a Fatty Acid Membrane and the Building Blocks of Biological Polymers Provides a First Step in the Emergence of Protocells. Life (Basel). 2016 Aug 11;6(3). pii: E33. doi: 10.3390/life6030033


We propose that the first step in the origin of cellular life on Earth was the self-assembly of fatty acids with the building blocks of RNA and protein, resulting in a stable aggregate. This scheme provides explanations for the selection and concentration of the prebiotic components of cells; the stabilization and growth of early membranes; the catalysis of biopolymer synthesis; and the co-localization of membranes, RNA and protein. In this article, we review the evidence and rationale for the formation of the proposed aggregate: (i) the well-established phenomenon of self-assembly of fatty acids to form vesicles; (ii) our published evidence that nucleobases and sugars bind to and stabilize such vesicles; and (iii) the reasons why amino acids likely do so as well. We then explain how the conformational constraints and altered chemical environment due to binding of the components to the membrane could facilitate the formation of nucleosides, oligonucleotides and peptides. We conclude by discussing how the resulting oligomers, even if short and random, could have increased vesicle stability and growth more than their building blocks did, and how competition among these vesicles could have led to longer polymers with complex functions.

These articles are all well worth reading if you’re interested in understanding how primitive cells could have functioned without modern phospholipid membranes and complicated transport proteins, and they really do document experiments showing that these physical mechanisms work. And it’s based on actual experiments that documents these very real physical effects.

People who say there’s no progress in origin of life research are simply talking nonsense.