Transformer: The Deep Chemistry of Life and Death

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The chemistry in this book is made more accessible by the narrative elements, but it sure as hell (pardon my French) isn't a layperson's level of, let's say high school chemistry. The chemical reactions that he speaks about here are achievable only under very strict laboratory conditions, with the right ingredients, enzymes, and environmental conditions, like pressure and temperature. Or, as it happens, in every one of the cells in our body.

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’ Pores in hydrothermal vents provide a steady supply of H2 and CO2, in just the right conditions needed to promote their reaction to make carboxylic acids. These form through chemical mechanisms that resemble steps of the reverse Krebs cycle, implying that this chemistry really is the primordial basis for metabolism. Transformer is a complex yet accessible, illuminating, and thrilling exploration of the vitality and elemental mysteries of our existence.

Most of us know the Krebs cycle as a cycle of biochemical reactions linked to energy generation in cells. In short, when we burn fuels like glucose in cell respiration, we first break them down into simpler molecules composed of carbon, hydrogen, and oxygen. These are the intermediates that make up the Krebs cycle. Then we strip out the carbon as CO 2, and we burn the hydrogen in oxygen. The energy released is used to power an electrical charge on the membranes deep within our cells. This charge is as intense as a bolt of lightning—if you shrink yourself down to the size of a molecule, you’d feel an electrical charge of 30 million volts per meter! 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. 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. In this compulsive readable book, Lane takes us on a riveting journey, ranging from the flow of energy to new ways of understanding cancer. Lane provides a luminous understanding of how scientists, including Lane himself, are rethinking energy and living organisms’ To grasp the Krebs cycle is to fathom the deep coherence of biology. It connects the first photosynthetic bacteria with our own peculiar cells. It links the emergence of consciousness with the inevitability of death. And it puts the subtle differences between individuals in the same grand story as the rise of the living world itself.

The greatest risk factor for cancer is older age: cancer incidence increases exponentially with age. One might think this is explained by the steady accumulation of mutations with age. But the buildup of mutations with age seems to be too slow to explain either cancer or ageing as a process. Nor can it explain why humans do not have a higher cancer rate than, mice, despite having ten times as many rounds of DNA copying to make an individual. In a footnote, the author confides that “probably only a tenth of what I wanted to write about actually made it into the book.” On behalf of humanities majors everywhere, I can only say thank goodness. From the renowned biochemist and author of The Vital Question , an illuminating inquiry into the Krebs cycle and the origins of life. When you were a medical student, you were told to sit down, shut up, raise your hand when you wanted to go to the bathroom, and memorize a whole bunch of strange names of carboxylic acids that make up the Krebs cycle. I thought this was a gigantic waste of time and had nothing to do with the practice of medicine. Lane notes that "cancer is a disease of the genome is too close to dogma." Different mutations are found in different parts of many tumours, often with little if any overlap, implying that the mutations accumulated during the growth of the tumor, rather than triggering its inception. Moreover, the same oncogene mutations are often found in normal tissues surrounding a tumor,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. The third peculiarity is the genetic code itself. There are clues that hint at direct interactions between the letters in DNA and the amino acids of proteins. This means the code is not random. A random piece of RNA will template a small protein, giving it a sequence that is specified by those non-random interactions. If that speeds up metabolism—the Krebs cycle for example—then the random sequence will be selected. And that means there’s no problem with the origin of information in biology. 3. The first animals evolved through a high-wire metabolic balancing act. Energy from the sun is captured by plants (photosynthesis) and bottled up in molecules (otherwise known as food that is made of carbon, hydrogen, and oxygen, chemically speaking) which we humans then eat. The human Krebs cycle (electron transport chain) then strips out the energy (electrons) from this food and passes it on for cellular respiration. Think of it as taking a food molecule, ripping out the carbon and oxygen to make CO 2 waste, and then ripping out the hydrogen to make H 2O. This is basically taking hydrogen and burning it in oxygen to give us energy to crawl, walk, or run. Dr Lane describes it as “feeding hydrogen to the ravaging beast called oxygen.” One can think of the entirety of medicine as tending to faulty human cellular respiration. Dr Lane coherently shows how this small sliver of reality is embedded in a much more general evolutionary history, starting with alkaline vents at the bottom of the ocean and ending up at human consciousness. In between, the author plainly tells the tale of the development of DNA, the fluke of photosynthesis, oxygen in the atmosphere, the one-in-a-gabillion appearance of the eukaryotic cell, multicellular organisms, and animal predation, all grounded in survival of the fittest and death/extinction of the weakest. I thought the best part of the book was how the author detailed the scientists’ quest to discover those elusive secrets. I also quite enjoyed the appendix and source material that he used. Rather than just a list of articles and books, the author took the time to review most of the research material in detail, giving the reader many starting points should they wish to further investigate the subject on their own. The great immunologist Peter Medawar said we age because we outlive our allotted time as determined by the statistical laws of selection. This textbook view sees ageing and the diseases of old age as little more than the unmasking of late-acting genes, whose effects do us in.

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’

By Rachel Mesch

Even though nonscientists won’t be able to judge whether Lane makes a convincing case, he is periodically quite clear on his goals. Early on, he posits the essential question as “genes first or metabolism first? The thrust of this book is that energy is primal — energy flow shapes genetic information.” Later, he restates the proposition with added whimsy: 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.”