Cancer reflects the processes of the evolution of life

Origins of cancer in both animals and plants reflect the development of biology over time

PUBLISHED : Sunday, 27 January, 2013, 12:00am
UPDATED : Sunday, 27 January, 2013, 7:25am

Medical science treats cancer as a disease in which rogue cells proliferate uncontrollably, running amok around the body. Therapy focuses on killing the cancer before it kills the host.

In the frantic search for an elusive "cure", few researchers stand back and ask a very basic question: why does cancer exist? What is its place in the grand story of life? Astonishingly, in spite of decades of research, there is no agreed theory of cancer, no explanation for why, inside almost all healthy cells, there lurks a highly efficient cancer subroutine that can be activated by a variety of agents - radiation, chemicals, inflammation and infection. Cancer, it seems, is embedded in the basic machinery of life. That suggests it is not a modern aberration but has deep evolutionary roots, a suspicion confirmed by the fact that it is not confined to humans but is widespread among animals and even plants. Scientists have identified genes implicated in cancer that are thought to be hundreds of millions of years old. Clearly, we will fully understand cancer only in the context of biological history.

Two relevant evolutionary transitions stand out. The first occurred over two billion years ago, when large, complex cells emerged containing mitochondria - tiny factories that supply energy to the cell. Biologists think mitochondria are the remnants of ancient bacteria. Tellingly, they undergo systematic changes as cancer develops, profoundly altering their chemical and physical properties.

For most of Earth's history, life was confined to single-celled organisms. Over time, however, a new possibility arose. Earth's atmosphere became polluted by a highly toxic and reactive chemical - oxygen - created as a waste product of photosynthesis. Cells evolved ingenious strategies to either avoid the accumulating oxygen or to combat oxidative damage in their innards. But some organisms turned a vice into a virtue and found a way to exploit oxygen as a potent new source of energy. With the appearance of energised oxygen-guzzling cells, the way lay open for the second major transition relevant to cancer - the emergence of multicellular organisms. This required a drastic change in the basic logic of life. Single cells have one imperative - to go on replicating. In that sense, they are immortal. But in multicelled organisms, ordinary cells have outsourced their immortality to specialised germ cells - sperm and eggs - whose job is to carry genes into future generations. The price that the ordinary cells pay for this contract is death; most replicate for a while, but all are programmed to commit suicide at their use-by date, a process known as apoptosis.

Biologists are familiar with the fact that organisms may harbour ancient traits that reflect their ancestral past, such as the atavistic tails or supernumerary nipples some people are born with. Evolution necessarily builds on earlier genomes. Sometimes older genetic pathways are not discarded, just silenced. Atavisms result when something disrupts the silencing mechanism.

Charles Lineweaver, of the Australian National University, and I have proposed a theory of cancer based on its ancient evolutionary roots. We think that as cancer progresses in the body it reverses, in a speeded-up manner, the arrow of evolutionary time. Increasing deregulation prompts cancer cells to revert to ever earlier genetic pathways.

Ancient genes remain functional only if they continue to fulfil a biological purpose. In early-stage embryo development, when the basic body plan is laid down (also in low-oxygen conditions, incidentally) ancestral genes help guide developmental processes before being switched off. Every human, for example, possesses tails and gills for a time in the womb. Significantly, researchers have recently identified examples of early-stage embryonic genes being reawakened in cancer.

By unravelling the details of cancer initiation and progression, scientists can open a window on the past through which we can gain tantalising glimpses of life in a bygone age.

Paul Davies is director of the Beyond Centre for Fundamental Concepts in Science at Arizona State University.

The Guardian


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