Metabolism First! And the origin of life

Two and a half weeks until classes resume, so I’m shifting brain gears to get excited about cell biology again. One of the tools I use to get into the right mindset is reading more biochemistry, and lately that means reading more Nick Lane, who is one of those biochemists who is obsessed with evolution and does a marvelous job of integrating the finicky little details electrons and protons and small molecules and chemistry with the big picture of where all this comes from and how it has shaped life.

I’ve read and reread Lane’s latest book, Transformer: The Deep Chemistry of Life and Death, and recommend it highly. I’ve been struggling with how to explain it’s contents, and it’s not easy — in my class, I spend weeks just gradually building up the background needed to understand the chemistry of the cell, which makes it hard to dump on a blog or a single video as anything but a huge indigestible bolus. And of course it took Lane 400 pages in a densely packed book to cover it all.

I should have known I could just let Nick Lane do all the hard work.

“KREBS CYCLE” is not a phrase that usually gets students excited — I know from experience — but this is juicy stuff. The talk itself covers a huge amount of ground, giving the basics of metabolic cycles and going into the origins of life and the great leap forward provided by mitochondria in endosymbiosis, and the diverse ways various organisms have taken the basic toolkit of the Krebs cycle and used it in novel ways. That’s all good solid science, and I don’t understand how anyone can have any doubts about the general chemistry that leads to life (well, I sorta do — they don’t know any biochemistry. All the YouTube debates about the origin of life are a waste of time, given that creationists are disgracefully ignorant of even the most rudimentary understanding of biochemistry).

Near the end, he gets farther out into weeds with speculation about aging, cancer, and consciousness. It’s interesting and he could very well be right — he’s a smarter man than I am — but the ideas range from very likely (metabolic shifts as agents of senescence and cancer), to potentially revolutionary but still on the fringe (the role of calcium and membrane potentials in Alzheimers), to some that, well, sound like how a biochemist would view neuroscience, for instance claiming that consciousness is a product of the electrical potential across the membrane of a cell, which is rather too reductionist for me.

Watch the video, though. If there are bits that you find heavy slogging, or just too out there to grasp, let me know in the comments. That’s information I can use to present these ideas to a class of second year students. And if you find it really deeply enlightening, go out and read Transformer. It contains a lot of the ideas about cellular metabolism I’d like to get across to my students.

It would make my life a whole lot easier if I could just show a one hour video that explains everything, then say, “Well, that’s all done then. We spend the rest of the semester reading poetry and dancing and playing video games! Yay!” I suspect I should probably fill in a lot more background and talk about the details, but maybe the video would be a nice dessert for the end of the semester. I’ll have done my job if all the students can watch it and say they already knew all that, but that Lane did a fine job of tying it all together.


  1. Ted Lawry says

    I too, love Nick Lane’s books. It is funny how ID, which claims to be all about the science, never gets into stuff like this.

  2. Ted Lawry says

    I too, love Nick Lane’s books. It is funny how ID, which claims to be all about the science, never gets into stuff like this.

  3. Jazzlet says

    Our teacher took her whole biology A Level class to meet Kreb, he was very kind, but I think he was as bemused by a group of seventeen year old girls as we were by such an eminent, if elderly (at least to our eyes), man. I mean what do you say to someone like that?

  4. azpaul3 says

    Nick Lane is right. All life, all consciousness, all thought is electrical potential across a membrane. Fine, next step: back out a couple orders magnitude and see how that change in potential effects the other membranes in the area, and out further and further and so on. I know, easier said than done.

    Can we control the membrane potential of single neurons? lf so, like proton collisions at LHC, can we chart the cascade of charge propagating from that neuron through the surrounding matrix? I have no idea what the smart guys would see in this data, but the Higgs was buried deep, too.

  5. Tethys says

    Life and consciousness are both phenomena that emerge from electrical potential across a membrane, but I think it’s misleading to use the term consciousness to describe basic cell metabolism.

    Proton gradients and magnetic charges aren’t consciously doing anything. Electrical potential across a membrane is not limited to living things, so conflating consciousness with something because it reacts to electrochemical stimulus seems very anthropomorphic.

    Most of the simplest life forms lack brains altogether, so although they clearly can sense and respond to their environments, it does not follow that a bacteria or individual cell has consciousness or motivations.

  6. Matt G says

    I was in the physiology department in grad school, and many of our labs did patch-clamping. I loved the idea that we’ve been able to study the behavior of single ion channels (i.e., individual proteins (or multimers)) for many decades.

  7. jacksprocket says

    There’s far too much reductionism in science. Let’s hear it for oxidisationism!

  8. birgerjohansson says

    If you want to know how some deepwater vertebrates manage 2-century life spans (bowhead whale/right whale and rockfish) keep an eye on future DNA research about those species.

  9. chrislawson says

    Given what we know of neuroscience, “consciousness is a product of the electrical potential across the membrane of a cell” is a reasonable statement and only excessively reductionist if it’s intended as a complete explanation or used to deny the possibility of other forms of consciousness (e.g. possible future AI, which may not have cells or membranes at all).

    It’s no different really than saying “chemistry is a product of stellar nucleosynthesis,” which is true without being able to explain chemistry.

  10. Matt G says

    An hour well spent!

    I learned in grad school that 90% of the energy used by the nervous system powers the sodium pump, which maintains the sodium and potassium gradients across the plasma membrane. Yes, electrical gradients are important! I hope that number – and my memory – is still accurate. Looking for confirmation now.

  11. PaulBC says

    While electrical potential is important in our consciousness, it strikes me as a red herring in defining consciousness itself. You can build a computer out of toilet flush values or for that matter, you can reduce computation to rigid tile constraints. It is not only reductionist but a case of magical thinking to equation consciousness with one particular physical implementation of it. At least, assuming consciousness is an emergent property of the computation (and I do assume so, though I can’t really justify this), then all this talk about electrical potential is as silly as it was when Kenneth Strickfaden was doing the effects for Frankenstein (1931) and it stood in for a “life force.”

    Not knocking Nick Lane. It sounds like he was straying outside his expertise or maybe just being poetic. He’s definitely on my to-read list now (or more likely audiobook list).

  12. John Morales says


    Not knocking Nick Lane. It sounds like he was straying outside his expertise or maybe just being poetic.

    The latter more than the former.
    Nick Lane is basically a science writer and communicator, and that’s the approach he takes.

    There’s a YEC (banned here) wanking on about him on Mano’s blog.
    (Doing the usual quote-mining, needless to say)

  13. KG says

    John Morales@15,

    Lane is very much a working scientist as well as a science writer: Professor of Evolutionary Biochemistry at University College London (one of the UK’s top research universities) – take a look at his publications list.

  14. John Morales says

    KG, true. Misapplied emphasis on my part.

    Point being, he’s hardly a loonie.

  15. says

    txpiper should keep his stupid mouth shut, rather than misrepresenting actual scientific work.

    Lane has a very specific point of view that he spells out carefully in his work: its all about flux, the flow of work and energy, and he sees consciousness as an example of how energy is transformed. He’s certainly right, but there are so many other details that need to be worked out. Like, I could look at an internal combustion engine and say, “Aha! I understand how it works! It’s all about coupling the release of energy stored in hydrocarbons into the mechanical rotation of these metal doohickeys here!” and I’d be correct, but it wouldn’t help me fix a broken-down car in the slightest.

  16. moarscienceplz says

    “Watch the video, though. If there are bits that you find heavy slogging, or just too out there to grasp, let me know in the comments.”
    Well, for starters I’m a bit confused about his idea that a mitochodrian can just reverse its Krebs cycle willy-nilly. Can enzymatic reactions be reversed so easily?

  17. PaulBC says

    John Morales@15 Maybe you were thinking of Nicholas Wade. I had forgotten Wade’s name, just that he had written an article promoting the lab leak hypothesis for COVID that he prefaced dishonestly as a balanced presentation of the facts. (Reasonable people can agree with his conclusion, but my characterization of the article still holds.)

    I had to look them up to make sure they weren’t the same. I am looking for some non-fiction right now and needed to make sure they weren’t the same person (but I didn’t think so).

    Lane sounds well worth reading and I plan to (or TBH probably listen to an audiobook). I still have trouble letting it pass when people assuming electricity has anything to do with computation, let alone human consciousness. While electric potential plays an important role in pretty much any physical process I can think of, it’s the wrong level of abstraction when discussing computation in the abstract. That I equate consciousness with computation shows my own bias and maybe there is something else to it, but it strikes me as very unlikely that its particular embedding in the laws of our universe are a requirement.

  18. Matt G says

    moarscienceplz@18- Absolutely they can! The vast majority of enzymatic reactions are in equilibrium, so can go forwards or backwards depending on the availability of reactants/products. While researching my claim that 90% of the energy used by the nervous system powers Na+/K+-ATPase I came across the report that neither this pump nor the Ca2+ pump are near their thermodynamic equilibria, which I gather to mean that they are operating non-stop to maintain their gradients (I welcome correction on this).

  19. chrislawson says


    Echoing Matt G. As a general rule, enzymes increase the reaction rate in both directions. They seem to work in one direction because there is a probability gradient. Having said that, there are enzymes that are unidirectional such as RNA polymerase. Glycolysis/gluconeogenesis is an interesting example because most of the enzymes in the chain are bidirectional and are used for both processes. But several of the enzymes only work one direction.

  20. says

    The reverse Krebs cycle is not identical to the familiar Krebs cycle. There are several enzyme substitutions that enable it.

  21. Rob Grigjanis says

    Just watched the video. Apart from learning that my speculation in #23 was wrong, the main take away for me was that the talk should have been a few hours longer. Too much stuff crammed in without explanation for a lay person (well, for this one anyway).

  22. Tethys says

    PZ @Mano’s Dino thread

    The metabolism first model proposes that protocells had no genes, that they carried out biochemistry with simple metabolites.

    If I understand it correctly, there was abiotic RNA and DNA, which became incorporated into protocells, where those chemically active amino acids were enclosed in a membrane. It is more difficult to understand how that is not equivalent to genes?

    He didn’t spend much time on LUCA. I’m not sure of the timespan involved between the first protocells and LUCA, but there must have been speciation if they are reconstructing it as a symbiont between a RNA based cell and a DNA based cell. This implies that both cells had a biocompatible basic structural framework, that incorporates both types. Or were they both symbionts who evolved in isolation to use either RNA or DNA, which eventually fused into a far more vigorous symbiont that had both, and gave rise to multicellular dipoblasts and tripoblasts?

    Chemosynthetic ecosystems like black smokers and alkaline seeps are rife with examples of endosymbiosis, and are used as a proxy for Earth’s anoxic and chemical rich early oceans.

    Biofilms are the earliest forms of life, and are crucial to many of the strange life forms that have evolved to exist in the dark depths of our oceans.

  23. Tethys says

    I also wondered how viruses fit into abiogenesis, as they are examples of free floating, infectious zombie DNA which embed themselves into living cells as a mode of reproduction.

    I found this article very enlightening at laying out the basic framework of abiogenesis and the various domains of life, including the empire of viral life.

    Comparative genomics and metagenomics have transformed our understanding of the genetic universe. New discoveries have revealed the previously unrealized prominence of the viral world. This second biological empire seems to be even more vast and diverse than the empire of cellular life-forms. A second key transformation in our understanding is that a complex network of treelike and netlike routes better explains evolution than does a single TOL. Even under this new network perspective, the three domains of cellular life — Bacteria, Archaea, and Eukarya — remain objectively distinct. Although these domains are distinct, the eukaryotes are archaebacterial chimeras, which evolved as a result of, or at least under the strong influence of, an endosymbiotic event that gave rise to the mitochondria.

    Archaebacterial chimeras is probably the best term for the results of two symbionts merging into one genome. Viral gene transfer is well documented, so perhaps viral infection was the selective force that underlies the endosymbiotic event?

  24. Matt G says

    I don’t remember if Lane made it clear, but LUCA is the last universal common ancestor, not necessarily the first living cell. For comparison, Mitochondrial Eve was the most recent matrilineal grandmother of all humans alive today, but (obviously) not the only woman alive at the time.

  25. Tethys says

    LUCA had both RNA and DNA as a result of endosymbiosis.

    Archeabacterial chimeras cannot occur without multiple species of cellular life, but viruses have managed to evolve in an entirely different strategy by infecting cells and embedding themselves into the DNA.

    I can theorize that oxygen fueled cell respiration and multiple cellular membranes evolved as a response to viral infection, but I lack the science eduction to know if that is a valid deduction.