Some interesting observations: the Cambrian explosion was when the Krebs cycle was first used primarily to generate energy not biosynthesis, taking advantage of the increased oxygen available. Rubisco in plants is considered inefficient as it does not adequately distinguish oxygen from carbon dioxide, but this may be necessary to prevent oxidative damage. People with type II diabetes have double the risk of Alzheimer’s, which is increasingly looking like a metabolic disease to Lane and others. Although I love this book, it does inevitably suffer part way through from the problems of a biology book being read by non-biologists. To start with I was carried along with enthusiasm engendered by those stories and Lane's novel presentation, but there are a couple of chapters midway through where the sheer volume of molecules named becomes somewhat overwhelming and I had to fight myself not to skip to a more interesting bit. It's hard to see how this could be avoided - but it does remain an issue. I reluctantly rate this book 3.5/5. It’s really well-written and enjoyable in spots, but I found myself slogging through the rest. I wouldn’t say that this is a book in search of an audience, but the audience has to be carefully found. 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. 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.

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. 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. 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. ageing, related diseases and cancer newly explained as consequences of slowing and reversing the Krebs cycle

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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. One of the most creative of today's biologists ... this is a book filled with big ideas, many of which are bold instances of lateral thinking.

A warts-and-all portrait of the famed techno-entrepreneur—and the warts are nearly beyond counting. The green sulfur bacterium Chlorobium thiosulfatophilum lives by photosynthesis in stinking, sulfurous waters such as hot springs. It reverses the Krebs cycle by using ferredoxin which has a biologically unparalleled ability to press electrons onto even the most unreactive molecules. However, ferredoxin reacts spontaneously with oxygen, becoming readily oxidized by even low levels of the gas. So in the presence of oxygen the reverse Krebs cycle usually grinds to a halt. Bacteria that use it today are normally restricted to environments with very low oxygen levels.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. 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. 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. Life started out using the Krebs cycle to convert gases into living cells—the engine of biosynthesis. But modern animals use it for biosynthesis and to generate energy. They can’t spin the cycle in both directions at the same time, so how did they manage?

Another impressive aspect of this book is the way it brings the real scientific method into the spotlight. This is something that science writing tend to over-simplify and treat with almost religious awe. Yet it is undertaken by flawed human beings. In showing how explanations of the Krebs cycle, the workings of mitochondria and more were gradually developed, Lane gives us plenty of stories of human endeavour and how the development of good science is not a straight line to success, but involves detours, misunderstandings and, yes, sometimes human pettiness. Transformer is a monstrous tome. And it's even more of a chimera in audiobook form. Having read the author's previous book, The Vital Question, I knew a bit of what to expect, a high-level explanation of an important biochemical process, with all the history, false starts, important scientists and, most crucially, the chemistry behind it. This is probably the best book on biology (and more specifically biochemistry) that I've ever read. 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’

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’ pagination, the shorter form provides sufficient information to locate the reference. The NLM now lists all authors. Ageing is not driven by mutations in genes accumulating over time, but by changes in gene activity – epigenetics. In glycosis, pyruvate is converted to lactate, allowing the cell to produce small amounts of ATP in the absence of oxygen. Warburg noted the propensity of cancers to ferment glucose in the presence of oxygen. However, many cancers don’t depend on aerobic glycolysis at all, normal tissues are also capable of aerobic glycolysis, and stem cells typically depend on ATP from aerobic glycolysis for their energy needs.

Ageing itself raises our risk, by switching metabolism towards aerobic glycolysis, promoting cellular growth. The combination of a cancer spawning event "set in a permissive metabolic context" allows proliferation and active cancer. Above is the information needed to cite this article in your paper or presentation. The International Committee Here’s my analogy. You discover oil and design a crude diesel engine. Then you use that engine to help you mine more minerals and oil to make more diesel engines. Then you use those engines to makes things that growth your wealth. Then you use that growth to enable abundant credit. Then you use that credit to invest in complex factories to make computer chips. Then you use those computer chips to make your diesel engine more fuel efficient with less emissions. From the renowned biochemist and author of The Vital Question , an illuminating inquiry into the Krebs cycle and the origins of life.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. 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".