The mother of inventions. Review by Steven Rose at The Guardian

From: The mother of inventions: Nick Lane’s Power, Sex, Suicide attempts to show that there is more to life than DNA. Steven Rose follows the trail.

The Guardian, November 2005

Power, sex, suicide; the words evoke blood and thunder, whodunit territory. But then that subtitle. The last bit is clear enough, but mitochondria? If you’ve got biology at GCSE you might just remember that these are the tiny sausage-shaped structures packed into every living cell and generally glibly referred to as the cellular “powerhouse” – the site of its major energy-generating systems. That might link them to power, but how about the rest? Could we be into fashionable forensics?

Perhaps sadly, no. Nick Lane is a biochemist and his book devotedly plots the latest findings and controversies in a field whose protagonists have exasperatedly – if also affectionately – long been known as mitochondriacs by their less committed colleagues. In a world where popular accounts of biology seem exclusively concerned with genetics, Lane’s ambition is to convince the rest of us that there is more to life than DNA – or at least that portion of the cell’s DNA locked up in its nucleus and which, for our species, has been laboriously sequenced in the Human Genome Project.

What atoms are to physicists, cells are to biologists: the units, 100th to a 10th of a millimetre in diameter, of which all living creatures are composed. We owe the term – by analogy to monk’s cells in a monastery – to the 19th-century microscopists who identified them and later found that each contained a small round structure embedded within it: the nucleus. Surrounding the nucleus was what was initially assumed to be a clear gel, which was named protoplasm. It wasn’t until the development of higher powered light and then electron microscopes that the “protoplasm” turned out to be traversed by complex membranes and packed with granules, among them the mitochondria, generally about 300 to 400 per cell, although some can contain 10 times more. By the 1950s, there were techniques for smashing the cells and centrifuging out their separate components to study in isolation, and mitochondriology came of age.

All creatures require energy to survive, and most of us obtain that energy by the slow burning of carbohydrates and fats, oxidising them to carbon dioxide and water. The energy released by this burning is used to synthesise a small molecule, known as ATP, a sort of “energy currency” which can then in turn be traded in for the multitude of cellular needs, from building proteins to contracting muscles or transmitting signals down nerves. Oxidising sugars, and coupling that oxidation to the synthesis of ATP, is what most of us older biochemists were taught that mitochondria are about, although it took many years, ingenious experiments and much quite savage controversy before the extraordinary mechanism for such synthesis won the rich and eccentric biochemist Peter Mitchell his Nobel prize in 1978. Lane tells the story of that discovery in all its excruciating detail.

But although this is where older biochemical stories (including my own Chemistry of Life) would have started and even ended, it is not where Lane begins, and for a fascinating reason. Except in bacteria, which don’t have one, nearly all the cell’s DNA is in the nucleus, packed into chromosomes. But it turns out that there is residual DNA in the mitochondria as well, some 13 genes-worth, coding for some, though far from all, of the mitochondrial proteins. Why? In 1967 Lynn Margulis proposed the initially scandalous but now universally accepted hypothesis that dominates Lane’s early chapters. The consensus among biologists is that in life’s early days, 3.5 billion years ago, many and varied forms of single celled organisms floated in a thin soup of abiotically synthesised chemicals, perhaps in the vicinity of drying seas, thermal vents or volcanoes, deriving their energy from where they could grab it. Margulis argued that mitochondria were originally free-living organisms, which became engulfed by other cells, which, themselves lacking the mitochondrial capacity to oxidise, struck a different bargain. Instead of eating the creatures they swallowed, they used the mitochondria to perform the chemical transformations needed to derive the maximum energy from their other foodstuffs.

The mitochondria sacrificed their own individuality, but the combined – symbiotic – cells were so efficient that they out-reproduced most other life forms and became the basic stock from which all today’s multicellular organisms evolved.

Single celled organisms can reproduce by budding; most multicellular forms use sex, in which two cells merge and shuffle their genes. But for this to occur, the merged cell also requires energy, which comes from the mitochondria. So in sex, one cell, the sperm, is reduced to little more than packaged DNA, while the other, the egg, retains its mitochondria and so provides the essential nurturing environment required for development. Hence the essential biological asymmetry between male and female in reproduction. Unlike our nuclear DNA therefore, our mitochondria are exclusively (Lane says almost) female in descent, a fact that has been used to study human ancestry from some so-called “mitochondrial Eve” living in Africa about 170,000 years ago – a story of which he is a little cautious.

Like one of those elaborate word games in Round Britain Quiz, we now have the power and sex of Lane’s title. As for suicide, this refers to the fact that, during development from the single fertilised egg to the fully formed adult, whether the few thousands of a tiny worm or the hundred trillion in the human body, many times more cells are born than survive; this over-production is, it seems, a necessary part of development and many of the cells that die en route are indeed “programmed” so to do, and it is their mitochondria, he argues, that generate the chemicals which kill them.

Lane goes further; mitochondria, he argues, carry the secret of ageing and even potentially of postponing death. Whether this constitutes the meaning of life remains debatable. His book does not make for an easy read; it is eccentrically organised and packed with more detail than any other than committed mitochondriacs might wish to know. But embedded within it is one of the most interesting stories modern biology has to tell.