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1、Cancer can teach us about our own evolutionMedical 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. Unfortunately, the emphasis on cancer cells as defective loose cannons
2、is at odds with the stubborn way they outwit both the bodys defences and the physicians armoury.Cancer is such a ruthless adversary because it behaves as if it has its own fiendishly cunning agenda. Cancer cells come pre-programmed to execute a well-defined cascade of changes, seemingly designed to
3、facilitate both their enhanced survival and their dissemination through the bloodstream. There is even an air of conspiracy in the way that tumours use chemical signals to create cancer-friendly niches in remote organs.In the frantic search for an elusive cure, few researchers stand back and ask a v
4、ery 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 activate
5、d by a variety of agents radiation, chemicals, inflammation and infection.Cancer, it seems, is embedded in the basic machinery of life, a type of default state that can be triggered by some kind of insult. That suggests it is not a modern aberration but has deep evolutionary roots, a suspicion confi
6、rmed by the fact that it is not confined to humans but is widespread among mammals, fish, reptiles 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 biologic
7、al history.Two relevant evolutionary transitions stand out. The first occurred over 2 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 underg
8、o systematic changes as cancer develops, profoundly altering their chemical and physical properties.For most of Earths history, life was confined to single-celled organisms. Over time, however, a new possibility arose. Earths atmosphere became polluted by a highly toxic and reactive chemical oxygen
9、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. In modern organi
10、sms, it is mitochondria that harness this dangerous substance to power the cell.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 l
11、ife. 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
12、 pay for this contract is death; most replicate for a while, but all are programmed to commit suicide when their use-by date is up, a process known as apoptosis. And apoptosis is also managed by mitochondria.Cancer involves a breakdown of the covenant between germ cells and the rest. Malignant cells
13、 disable apoptosis and make a bid for their own immortality, forming tumours as they start to overpopulate their niches. In this sense, cancer has long been recognised as a throwback to a selfish cell era. But recent advances in research permit us to embellish this picture. For example, cancer cells
14、 thrive in low-oxygen (even zero-oxygen) conditions, reverting to an earlier, albeit less efficient, form of metabolism known as fermentation.Biologists are familiar with the fact that organisms may harbour ancient traits that reflect their ancestral past, such as the atavistic tails or supernumerar
15、y 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 th
16、eory 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 that recapitulate successively earlier ancestral life styles. We predict that the various hallmarks of cancer progression will systematically correlate with the activation of progressively older ancestral g
