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Mel Greaves


The evolutionary legacy

Book review by Anthony Campbell. The review is licensed under a Creative Commons License.

The subtitle of this book tells you the approach the author takes, which is a profoundly evolutionary one. Darwinism relates to cancer in two main ways—the why and the how. It explains why cancer exists as a consequence of evolution and how it arises and develops within the body as an evolutionary process.

Greaves is concerned to counter simplistic views about cancer. There are many different kinds of the disease and many things determine whether it will occur. "The risk of getting cancer is a complicated mosaic of inherited genetics, exposure patterns, other modifying activities (diet, for example), and, inevitably, chance." There is therefore no single "cause" and no prospect of a single cure.

We are often told that cancer is a consequence of the "unnatural" way we live, and certainly cultural factors such as smoking and diet example are important in its production. Some industries have been responsible for inducing cancer in those who work in them. But, as Greaves emphasizes, cancer is not a new disease; it is even detectable in fossils. And it is best understood as the inevitable consequence of the fact that we are multicellular organisms with a complex structure and lengthy developmental history.

The starting point of cancer is mutation. Cell reproduction is not, and cannot be, error-free. If cells reproduced themselves with perfect fidelity there would be no evolution. But because DNA copying is not error-free it can lead to cancer. This is why tissues containing cells which reproduce particularly rapidly, such as those in the bone marrow, the skin, and the intestines often give rise to cancer. But slowly growing cancers are often more lethal than those that develop more rapidly.

Cancer usually begins with a single cell that goes off the rails and gives rise to a clone. There is nothing abnormal about cloning, however. It goes on all the time; all the cells in our body are members of a single clone that derived from just one cell (the fertilised egg). Numerous subclones develop as the embryo matures, leading to the various tissues that are found in the mature individual.

In fact, our immune system would not work were it not for cloning coupled with natural selection, because lymphocytes are generated continuously in the bone marrow using a process of random gene shuffling to generate millions of antibodies, ready to match the antigens of almost any bacterial invader. Natural selection then allows the appropriate lymphocytes to multiply and produce more antibodies. So cloning is absolutely essential for our survival, even though it is also potentially lethal. Cancer is a clone that becomes autonomous and wild. A cancer clone can give rise to subclones just like any other clone in the body.

Cancer can occur at any time in our lives, but it tends to do so mainly in either childhood or old age. The two manifestations have different roots. Childhood cancer is due to a developmental error and is therefore similar to other kinds of developmental abnormality. Cancers in old age are often due to insults that were received many years earlier; cancer typically takes a long time to develop although once it does it can accelerate rapidly.

As others have done, Greaves sees a similarity between cancer cells and exogenous parasites such as bacteria and viruses. This is more than an analogy—it is an exact description. In fact, cancer could be thought of a form of endogenous parasitism. And just as we have evolved mechanisms to resist exogenous parasites, so also we have mechanisms to prevent multiplication of rogue clones in our bodies. Usually these work—most cancers do not survive or never progress very far.

To succeed, a cancer clone has to pass through several evolutionary bottlenecks. There are intrinsic restraints that normally prevent the uncontrolled proliferation of cells. If it bypasses these successfully the tumour needs to acquire a blood supply in order to grow; there are constraints on this too, and interfering with the generation of new vessels may be potentially one of the best weapons we have for treating cancer. Even if the tumour becomes established it may be restricted by the size of its environment, so it has to find a way of disseminating itself more widely; tumours do this by spreading via the blood stream or the lymphatics, for example. Finally, cells generally have a finite life span, so cancer cells need to make themselves immortal by ignoring or turning off the internal "clock" which normally limits the number of times a cell can reproduce. Some cancer cell lines in the laboratory are potentially immortal.

Our cancer treatments are still fairly crude, although this is beginning to change. There is a close parallel between the ways that bacteria evolve resistance to antibiotics and cancer cells evolve resistance to anti-cancer drugs. In both cases the usual mechanism is that a subclone appears that, by chance, is resistant, and this then survives by means of natural selection. This is evolution in miniature, so to speak, but there is also a parallel between cancer evolution and species evolution. Cancer progression nearly always proceeds in a jerky manner, with starts and stops, offering "a clear evolutionary parallel to both species diversification and parasite adaptation".

Although Greaves does discuss some of the historical and social aspects of his subject, his main message is that cancer can only be understood in the evolutionary context. Because it is so deeply rooted in our nature we cannot expect to be free from it, though we may certainly hope to control it better. "There is a sense in which all our ailments and particularly our 'modern' chronic disorders are reflections of design limitations, delayed trade-offs, and nature–nurture mismatches. They are part of the natural scheme of things even if we would like to believe that we have been sculpted to perfection."

Although this book is about cancer it has implications for our understanding of disease as a whole. It deals with what has been called Darwinian medicine, something which many doctors, even today, are unfamiliar with. Reading it deepens one's understanding of disease and indeed of evolution.

1 May 2008

%T Cancer
%S The evolutionary legacy
%A Mel Greaves
%I Oxford University Press
%C Oxford
%D 2000
%G ISBN 0-19-262835-6
%P vi + 276pp
%K medicine, evolution
%O illustrated

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