Transformer: The Deep Chemistry of Life and Death

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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. 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. An] indefatigable exploration of the genesis of biology . . . [Lane] beautifully lays out the sheer improbability of our biosphere, explains why life may be exceedingly rare in our universe, and considers death as a process, not simply as an instantaneous end.

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. On average, we have one SNP every thousand letters, meaning that there are four or five million letters that differ across the human genome. Only a modest proportion of these are likely to influence the risk of a particular disease The chances of life starting on an oxygenated planet are arguably close to zero: hydrogen must react with CO2 to form organic molecules, but does so very reluctantly if at all in the presence of oxygen We are so aware of the vast amounts of information stored in our genes, that we sometimes overlook the obvious. There’s no difference in the information content between a living organism and one that died a moment ago. What stopped was metabolism. ageing, related diseases and cancer newly explained as consequences of slowing and reversing the Krebs cycleTo 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. This is a dense book. I read two others by Lane that discuss cellular respiration and its variants. Both cover many of the same points and were challenging but far more accessible. In particular, reading The Vital Question before reading this one was very helpful to me. I recommend it highly for those of us who prefer following fewer chains of chemical reactions and more text aimed at the non-biochemist. My review of The Vital Question covers much of what is in this book, so I will just write some brief notes here. Also interesting was that many of our diseases, like cancer, are caused more by respiration problems than genetic problems.

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: 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. Yet Transformer is being marketed to laypeople, so it’s appropriate to get a non-chemist’s take. Well, here it is. Because of the author’s obvious enthusiasm, the writing is never dry, despite all the long words and formulas. For me, reading it was like listening to a friend excitedly unspool a story you can’t really follow. You endure it because the emotion is gripping and you can tell she really needs to share. In fact, at one point, Lane breathlessly announces a certain experiment “was so beautiful I have to tell you about it.” This is probably the best book on biology (and more specifically biochemistry) that I've ever read.The reverse Krebs cycle requires an input of energy (ATP) to work, which in modern bacteria is normally obtained from photosynthesis. H2 will react with CO2, using iron–sulfide catalysts, but works best at pressures of around 100 bar, equivalent to an ocean depth of about 1 kilometre. I read several of previous Lane's books, namely Vital Question, Life Ascending and Oxygen. My thinking about origins of life was since dominantly shaped by his work, which filled a major gap for me in my worldview about abiogenesis. Cancer cells need NADPH for biosynthesis and growth, and it is as important to them as ATP. Cells must wire their metabolism to get the balance between ATP, NADPH and carbon skeletons right. Aerobic respiration produces too much ATP, which actually switches off the glycolytic breakdown of glucose. Cancer cells must not make too much ATP, as it slows down their growth. Cancer cells switch over to aerobic glycolysis precisely because it makes less ATP, favoring faster growth.