Transformer: The Deep Chemistry of Life and Death

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Levinson, Gene (2020). Rethinking evolution: the revolution that's hiding in plain sight. World Scientific. ISBN 978-1786347268. Lane’s focus on energy and the essential dynamism of life has been an important thread running through his research. One of the most creative of today’s biologists, his work ranges from the evolution of sex and the rise of planetary oxygen to the origin of complex cells and the first life on Earth.

Most bacteria and archaea don't use a closed Kreb's cycle; rather they use a forked pathway that allows them to adapt to oxygen availability. Lane suggests that the Ediacaran fauna (500 million years before the Cambrian) had little tissue differentiation and were unable to adapt to changing environmental conditions. In contrast, the bilateral ancestors of the Cambrian fauna had a variety of tissues that could work together to seek metabolic balance. By the dawn of the Cambrian, they were able to deal with oxygen and "Rising oxygen just gave them a turbocharge." October 2006). "Cell biology: Power games". Nature. 443 (7114): 901–903. Bibcode: 2006Natur.443..901L. doi: 10.1038/443901a. PMID 17066004. S2CID 4430396.Over time damage occurs to molecular machinery such as proteins. Repairing or replacing them is one of the most energy-sapping tasks that cells face. Eventually the respiratory machinery itself is damaged, and ROS flux creeps up. Cells do what they must and compensate by suppressing respiration a little. NADH is oxidized less effectively and the Krebs cycle loses forward momentum. Intermediates such as succinate start to accumulate and seep out from the mitochondria. They activate proteins such as HIF1α, which in turn alter the behavior of thousands of genes, pushing cells into a senescent state or to their demise. A warts-and-all portrait of the famed techno-entrepreneur—and the warts are nearly beyond counting. The founder of Microsoft, Bill Gates, reviewed the book under the heading "This Biology Book Blew Me Away". It moved him to read two of Lane's other books, and to bring him to New York to interview him. Gates noted that "As much as I loved The Vital Question, it's not for everyone. Some of the explanations are pretty technical. But this is a technical subject, and I doubt anyone else will make it much easier to understand without sacrificing crucial details." [21] So this chemistry is thermodynamically favored. It’s just these first steps which are recalcitrant, but the electrical charges on the hydrothermal vent seem to lower the barrier to that first step, so the rest can happen. In effect what you have is a continuous flow of hydrothermal fluids going through this electrochemical reaction, converting gases in the environment into more organic molecules, which you can imagine snuggling into the cell-like pores, structuring themselves into cell-like entities and making more of themselves. It’s a very rough form of growth, but it’s lifelike in that sense. But then how did these first proto-cells become independent from the proton gradients they got for free in the hydrothermal vents?

It’s not possible to construct a plausible story by starting with a computer chip. Energy drives everything and life began at an energy gradient. The Krebs cycle is a series of chemical reactions that take place (in part or entirely) in most living organisms. Running in one direction it explains respiration, the process by which organic molecules undergo controlled combustion to produce energy, while in reverse it is one of the ways that complex organic molecules can be constructed. At the same time we see the importance of flows of energy and electrical potentials in understanding life. It's heady stuff. Lane goes on to show how the same processes that support life can produce cancers - and why these processes change over time, resulting in ageing and death. If all this language sounds like Klingon, that is because this book is really far from an easy read, which can be said for all Lane's books I have seen. He is an excellent writer (albeit prone to digressions), but the topic is so disconnected from other popularized science that it requires a lot of new learning and understanding. It does not help that all claimed rules have many exceptions, leaving me with a fuzzy feeling that I got a glimpse of something great, but cannot dare to make my own conclusions (such as, should I give up my metformin while I follow a ketogenic diet and active lifestyle because it seems to follow from the book outlook applied to metformin-related published papers that metformin acts like a handbrake i.e. that it hinders my progress and increases cancer occurrence risk, while it could help sedentary carb-overloaded persons).Until now, biology has tended to study the materials that make up the instruments. The time has come to close our eyes and listen to the music.” Plants make use of rubisco for photosynthesis. Rubisco is inefficient and is as likely to fix CO2 as O2. CO2 levels were high when the molecule evolved, but even today the buildup of CO2 within the leaf causes crops to lose as much as one quarter of their yield. Amazingly, rubisco now turns out to be widespread in ancient bacteria, doing a totally different job: degrading sugars derived from the RNA of other cells, to support growth fueled by eating other cells. A living cell and one that just died have the same DNA. Put differently, both cells have precisely the same information content. Just as the flow of people and goods, rather than the arrangement of the buildings, determines that a city is alive, the fluxes of metabolites and energy characterise a living cell. Modern biology is often solely discussed in terms of information. In "Transformer", Lane argues that metabolism is at least as important. This viewpoint of "follow the goods" is also emphasised on a completely different scale by Vaclav Smil in "How the World Really Works". Hugely ambitious and tremendously exciting ... Transformer shows how a molecular dance from the dawn of time still sculpts our lives today. I read with rapt attention’