Transformer: The Deep Chemistry of Life and Death

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Metabolism is the sum total of reactions occurring in an organism at any one moment. Metabolism keeps us alive—it is what being alive is. In one of our own cells, there are more than a billion metabolic reactions every second. That’s about a hundred billion trillion reactions in the last second, or a billion times the number of stars in the known universe. These reactions don’t all work properly, and damage inevitably accumulates. Oxygenic photosynthesis first arose in cyanobacteria or their predecessors, but exactly when remains uncertain. The first unequivocal evidence is the Great Oxidation Event (familiarly called the ‘GOE’) around 2.3 billion years ago, when the planet turned rusty red and froze. The underlying problem in cancer is an environment that continuously and erroneously shouts ‘grow!’. This toxic environment can be induced by mutations, infections, low oxygen levels … or the decline in metabolism associated with ageing itself.

Lane is among the vanguard of researchers asking why the Krebs cycle, the “perfect circle” at the heart of metabolism, remains so elusive more than eighty years after its discovery. Transformer is Lane’s voyage, as a biochemist, to find the inner meaning of the Krebs cycle—and its reverse—why it is still spinning at the heart of life and death today.

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of Medical Journal Editors (ICMJE) recommends the following citation style, which is the now nearly universally pagination, the shorter form provides sufficient information to locate the reference. The NLM now lists all authors. A thrilling tour of the remarkable stories behind the discoveries of some of life’s key metabolic pathways and mechanisms. [Lane] lays bare the human side of science… The book brings to life the chemistry that brings us to life. From the renowned biochemist and author of The Vital Question , an illuminating inquiry into the Krebs cycle and the origins of life.

Ageing is not driven by mutations in genes accumulating over time, but by changes in gene activity – epigenetics. If that’s as clear to your ears as a morning hello, have I got a book for you! Unfortunately, it’s not to me: The tour of the chem lab during my high-school orientation included an eyewash station to save your sight from an errant spray of acid and a furled blanket with which you could smother yourself in case you caught fire. I’ve given chemistry a wide berth ever since. Lane explains cellular processes for producing energy particularly cellular respiration in animals. He recounts the history of key discoveries that underlie our understanding of cellular respiration and profiles the scientists involved. He compares cellular respiration with photosynthesis in plants and variants of these processes in microbes, pointing out the similarities and differences. He shows how early forms of the same processes could have initiated life detailing a specific scenario in hydrothermal vents. Lane explores how cellular respiration impacts health and aging. He makes the case that increasing dysfunction in cellular respiration is a primary factor in the increased rate of cancer and Alzheimer’s as we age and in aging itself. 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).When I saw this book being offered up on NetGalley, I was particularly interested in the subject, having majored in Biology/Human Anatomy and Physiology in college. Besides, the Kreb’s Cycle (and my favorite organelle, the mighty mitochondria) is one of the most important processes in the human body, one that provides the energy that allows it to hum along. Lane seems firmly established in the scientific establishment — he’s a professor at University College London — but his book carries a whiff of the heretic. He’s glad that “the simplistic notion that genes control metabolism is beginning to unravel” but frustrated that “the idea that mutations cause cancer remains the dominant paradigm”— a paradigm that, to his mind, is “too close to dogma.” He also states plainly: “I want to turn the standard view upside down.”

The Krebs cycle is more of a roundabout than a complete cycle. The traffic flow of metabolism has to be controlled to do particular jobs. The single-celled organisms that came before animals could mostly do one thing at a time, so they needed to adjust their traffic flow. But animals have multiple tissues and can balance traffic flow through the Krebs cycle in one tissue differently than in another tissue. It’s a kind of symbiosis between mutually dependent tissues. An exhilarating account of the biophysics of life, stretching from the first stirrings of living matter to the psychology of consciousness. I felt as if I was there, every step of the way’ Mitochondrial genes tend to evolve much ten to fifty times faster than nuclear genes, as they are copied far more than nuclear genes, and so they accumulate more mutations. A clean-up process in early life sieves out the most detrimental mutations. That’s why mitochondrial diseases directly affect only about 1 in 5,000 of us.

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." The Krebs cycle is a set of nine reactions arranged in a circular fashion, each generating intermediate organic chemicals. In respiration, the primary output is ATP, but some of the intermediates are drawn off as precursors for the synthesis of amino acids, fats, sugars and more.