Power, Sex, Suicide: Mitochondria and the Meaning of Life (2 page)

A number of friends and family members have also read chapters and given me a good indication of what the general reader is prepared to tolerate. I want to thank in particular Allyson Jones, whose unfeigned enthusiasm and helpful comments have periodically sent my spirits soaring; Mike Carter, who has been friend enough to tell me frankly that some early drafts were too difficult (and that later ones were much better); Paul Asbury, who is full of thoughts and absorbing conversation, especially in wild corners of the country where talk is unconstrained; Ian Ambrose, always willing to listen and advise, especially over a pint; Dr John Emsley, full of guidance and inspiration; Professor Barry Fuller, best of colleagues, always ready to talk over ideas in the lab, the pub, or even the squash court; and my father, Tom Lane, who has read most of the book and been generous in his praise and gentle in pointing out my stylistic infelicities, while working to tight deadlines on his own books. My mother Jean and brother Max have been unstinting in their support, as indeed have my Spanish family, and I thank them all.

The frontispiece illustrations are by Dr Ina Schuppe Koistenen, a researcher in biomedical sciences in Stockholm and noted watercolorist, who is making a name in scientific art. The series was specially commissioned for this book, and inspired by the themes of the chapters. I’m very grateful to her, as I think they bring to life the mystery of our microscopic universe, and give the book a unique flavour.

Special thanks to Ana, my wife, who has lived this book with me, through
times best described as testing. She has been my constant sparring companion, bouncing ideas back and forth, contributing more than a few, and reading every word, well, more than once. She has been the ultimate arbiter of style, ideas, and meaning. My debt to her is beyond words.

Finally, a note to Eneko: he is antithetical to writing books, preferring to eat them, but is a bundle of joy, and an education in himself.

Clandestine Rulers of the World

Mitochondria are tiny organelles inside cells that generate almost all our energy in the form of ATP. On average there are 300–400 in every cell, giving ten million billion in the human body. Essentially all complex cells contain mitochondria. They look like bacteria, and appearances are not deceptive: they were once free-living bacteria, which adapted to life inside larger cells some two billion years ago. They retain a fragment of a genome as a badge of former independence. Their tortuous relations with their host cells have shaped the whole fabric of life, from energy, sex, and fertility, to cell suicide, ageing, and death.

A mitochondrion—one of many tiny power-houses within cells that control our lives in surprising ways

Mitochondria are a badly kept secret. Many people have heard of them for one reason or another. In newspapers and some textbooks, they are summarily described as the ‘powerhouses’ of life—tiny power generators inside living cells that produce virtually all the energy we need to live. There are usually hundreds or thousands of them in a single cell, where they use oxygen to burn up food. They are so small that one billion of them would fit comfortably in a grain of sand. The evolution of mitochondria fitted life with a turbo-charged engine, revved up and ready for use at any time. All animals, the most slothful included, contain at least some mitochondria. Even sessile plants and algae use them to augment the quiet hum of solar energy in photosynthesis.

Some people are more familiar with the expression ‘Mitochondrial Eve’—she was supposedly the most recent ancestor common to all the peoples living today, if we trace our genetic inheritance back up the maternal line, from child to mother, to maternal grandmother, and so on, back into the deep mists of time. Mitochondrial Eve, the mother of all mothers, is thought to have lived in Africa, perhaps 170 000 years ago, and is also known as ‘African Eve’. We can trace our genetic ancestry in this way because all mitochondria have retained a small quota of their own genes, which are usually passed on to the next generation only in the egg cell, not in the sperm. This means that mitochondrial genes act like a female surname, which enables us to trace our ancestry down the female line in the same way that some families try to trace their descent down the male line from William the Conqueror, or Noah, or Mohammed. Recently, some of these tenets have been challenged, but by and large the theory stands. Of course, the technique not only gives an idea of our ancestry, but it also helps clarify who were
not
our ancestors. According to mitochondrial gene analysis, Neanderthal man
didn’t
interbreed with modern
Homo sapiens
, but was driven to extinction at the margins of Europe.

Mitochondria have also made the headlines for their use in forensics, to establish the true identity of people or corpses, including several celebrated cases. Again, the technique draws on their small quota of genes. The identity of the last Russian Tzar, Nicholas II, was verified by comparing his mitochondrial genes with those of relatives. A 17-year-old girl rescued from a river in Berlin at the end of the First World War claimed to be the Tzar’s lost daughter Anastasia, and was committed to a mental institution. After 70 years of dispute, her claim was finally disproved by mitochondrial analysis following her death in 1984.
More recently, the unrecognizable remains of many victims of the World Trade Center carnage were identified by means of their mitochondrial genes. Distinguishing the ‘real’ Saddam Hussein from one of his many doubles was achieved by the same technique. The reason that the mitochondrial genes are so useful relates partly to their abundance. Every mitochondrion contains 5 to 10 copies of its genes. Because there are usually hundreds of mitochondria in every cell, there are many thousands of copies of the same genes in each cell, whereas there are only two copies of the genes in the nucleus (the control centre of the cell). Accordingly, it is rare not to be able to extract any mitochondrial genes at all. Once extracted, the fact that all of us share the same mitochondrial genes with our mothers and maternal relatives means that it is usually possible to confirm or disprove postulated relationships.

Then there is the ‘mitochondrial theory of ageing’, which contends that ageing and many of the diseases that go with it are caused by reactive molecules called free radicals leaking from mitochondria during normal cellular respiration. The mitochondria are not completely ‘spark-proof’. As they burn up food using oxygen, the free-radical sparks escape to damage adjacent structures, including the mitochondrial genes themselves, and more distant genes in the cell nucleus. The genes in our cells are attacked by free radicals as often as 10 000 to 100000 times a day, practically an abuse every second. Much of the damage is put right without more ado, but occasional attacks cause irreversible mutations—enduring alterations in gene sequence—and these can build up over a lifetime. The more seriously compromised cells die, and the steady wastage underpins both ageing and degenerative diseases. Many cruel inherited conditions, too, are linked with mutations caused by free radicals attacking mitochondrial genes. These diseases often have bizarre inheritance patterns, and fluctuate in severity from generation to generation, but in general they all progress inexorably with age. Mitochondrial diseases typically affect metabolically active tissues such as the muscle and brain, producing seizures, some movement disorders, blindness, deafness, and muscular degeneration.

Mitochondria are familiar to others as a controversial fertility treatment, in which the mitochondria are taken from an egg cell (oocyte) of a healthy female donor, and transferred into the egg cell of an infertile woman—a technique known as ‘ooplasmic transfer’. When it first hit the news, one British newspaper ran the story under the colourful heading ‘Babies born with two mothers and one father’. This characteristically vivid product of the press is not totally wrong—while all the genes in the nucleus came from the ‘real’ mother, some of the mitochondrial genes came from the ‘donor’ mother, so the babies did indeed receive
some
genes from two different mothers. Despite the birth of more than 30 apparently healthy babies by this technique, both ethical and practical concerns later had it outlawed in Britain and the US.

Mitochondria even made it into a Star Wars movie, to the anger of some aficionados, as a spuriously scientific explanation of the famous force that may be with you. This was conceived as spiritual, if not religious, in the first films, but was explained as a product of ‘midichlorians’ in a later film. Midichlorians, said a helpful Jedi Knight, are ‘microscopic life forms that reside in all living cells. We are symbionts with them, living together for mutual advantage. Without midichlorians, life could not exist and we would have no knowledge of the force.’ The resemblance to mitochondria in both name and deed was unmistakeable, and intentional. Mitochondria, too, have a bacterial ancestry and live within our cells as symbionts (organisms that share a mutually beneficial association with other organisms). Like midichlorians, mitochondria have many mysterious properties, and can even form into branching networks, communicating among themselves. Lynn Margulis made this once-controversial thesis famous in the 1970s, and the bacterial ancestry of mitochondria is today accepted as fact by biologists.

All these aspects of mitochondria are familiar to many people through newspapers and popular culture. Other sides of mitochondria have become well known among scientists over the last decade or two, but are perhaps more esoteric for the wider public. One of the most important is apoptosis, or programmed cell death, in which individual cells commit suicide for the greater good—the body as a whole. From around the mid 1990s, researchers discovered that apoptosis is not governed by the genes in the nucleus, as had previously been assumed, but by the mitochondria. The implications are important in medical research, for the failure to commit apoptosis when called upon to do so is a root cause of cancer. Rather than targeting the genes in the nucleus, many researchers are now attempting to manipulate the mitochondria in some way. But the implications run deeper. In cancer, individual cells bid for freedom, casting off the shackles of responsibility to the organism as a whole. In terms of their early evolution, such shackles must have been hard to impose: why would potentially free-living cells accept a death penalty for the privilege of living in a larger community of cells, when they still retained the alternative of going off and living alone? Without programmed cell death, the bonds that bind cells in complex multicellular organisms might never have evolved. And because programmed cell death depends on mitochondria, it may be that multicellular organisms could not exist without mitochondria. Lest this sound fanciful, it is certainly true that all multicellular plants and animals
do
contain mitochondria.

Another field in which mitochondria figure very prominently today is the origin of the
eukaryotic
cell—those complex cells that have a nucleus, from which all plants, animals, algae, and fungi are constructed. The word
eukaryotic
derives from the Greek for ‘true nucleus’, which refers to the seat of the genes in the cell. But the name is frankly deficient. In fact, eukaryotic cells contain many
other bits and pieces besides the nucleus, including, notably, the mitochondria. How these first complex cells evolved is a hot topic. Received wisdom says that they evolved step by step until one day a primitive eukaryotic cell engulfed a bacterium, which, after generations of being enslaved, finally became totally dependent and evolved into the mitochondria. The theory predicted that some of the obscure single-celled eukaryotes that
don’t
possess mitochondria would turn out to be the ancestors of us all—they are relics from the days before the mitochondria had been ‘captured’ and put to use. But now, after a decade of careful genetic analysis, it looks as if all known eukaryotic cells either
have
or once
had
(and then lost) mitochondria. The implication is that the origin of complex cells is inseparable from the origin of the mitochondria: the two events were one and the same. If this is true, then not only did the evolution of multicellular organisms require mitochondria, but so too did the origin of their component eukaryotic cells. And if that’s true, then life on earth would not have evolved beyond bacteria had it not been for the mitochondria.