Transformer review: Could Krebs cycle play a part in consciousness?

By Michael Marshall

IF WE want to understand the nature of life, we have to think about the flow of energy and matter. So argues biochemist and writer Nick Lane in his new book Transformer. Quoting the poem Like Most Revelations by Richard Howard, he writes that “it is the movement that creates the form”.

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.

In his last book, The Vital Question, he argued that many of these seemingly disparate mysteries could be explained by life’s reliance on electrically charged particles to power itself.

Transformer is no less ambitious. Its focus is a biochemical process called the Krebs cycle: a whirlwind of chemistry that spins around in all our cells many times a second. It is named for biochemist Hans Krebs, who described many details of how it works.

Lane’s thesis is that biochemists have misunderstood the cycle and therefore underestimated it. Textbooks, he says, essentially treat it as a mechanism for obtaining energy from food. But Krebs is also a chemical factory, manufacturing key components of cells. And cells can run it in various ways, so there is no one Krebs cycle. Lane compares it to a furiously busy roundabout, with different vehicles constantly whizzing in from different junctions and hurtling out on others.

The many functions of the Krebs cycle mean it can explain much about life, Lane argues. For one thing, the cycle can run backwards, and this reverse Krebs seems to be much older than the “forwards” one. Lane makes the case that it dates back to the very earliest life, which he believes arose in hydrothermal vents on the seabed. He draws on recent experiments suggesting that parts of the reverse Krebs (and at least some of the forwards Krebs) can happen without complex biochemicals to shepherd them along, and may therefore be primordial.

Moving through the history of life, Lane illustrates the deep links between the reverse Krebs and photosynthesis, which, in turn, led to Earth’s air becoming rich in oxygen for the first time – paving the way for the modern Krebs, which requires oxygen. He also argues that alterations in the cycle may have been key to the blossoming of animal diversity during the Cambrian explosion some 540 million years ago.

Lane brings the story up to date by delving into the role of Krebs in cancer. Our understanding of the disease, like our understanding of life, has been skewed by an undue emphasis on genes, says Lane. For him, the key to cancer (as to so much else) is metabolism: it is shifts in cellular metabolism, not genetic mutations, that explain why our risk of cancer increases so drastically as we age.

If that weren’t enough, Lane even suggests that the electromagnetic fields generated by metabolic processes like Krebs may be the underpinning of consciousness.

Clearly, this is a book filled with big ideas, many of which are bold instances of lateral thinking. Lane says he doesn’t expect to be right about all of it, but that is fine – even the bits that are wrong will advance our knowledge in the disproving.

It is a shame, then, that his book can be dry at times. There is a lot of nitty-gritty biochemistry – some of it essential, but described in exhausting detail. Get ready to hear an awful lot about succinate, pyruvate and alpha-ketoglutarate.Lane tries hard to imbue these chemicals with personality, but his efforts only go so far. Those who persevere will get a lot out of Transformer, but it is hard work.