Читать книгу Virolution - Frank Ryan - Страница 9

What [The Double Helix] conveys … is how uncertain it can be, when a man is in the black cave of unknowing, groping for the counters of the rock and the slope of the floor, listening for the echo of his steps, brushing away false clues as insistent as cobwebs to recognise that something important is taking shape.

HORACE FREELAND JUDSON¹

A key proposition that has been almost universally misinterpreted among non-scientists as the core of Darwin’s theory is the concept known as the “survival of the fittest”. Nothing could have more alienated religious sensibility, with its potential for misapplication to society, for example its misuse in condoning laissez-faire politics in relation to poverty and hunger, and worst of all its extrapolation to racial and ethnic abuse. It is important, therefore, to clarify the fact that Darwin did not invoke the term. On the contrary, the concept of survival of the fittest was the brainchild of the social philosopher Herbert Spencer, who first proposed it in his book, Principles of Biology, published in 1864.² Spencer had been developing his own thread of thought even before he read Darwin’s Origin of Species, which was published some five years before his own Principles of Biology, but the social philosopher was not educated in biology, and, although his concept was widely seen as synonymous with, or even a clearer exposition of, what Darwin was supposed to have meant by his term “natural selection”, Spencer misunderstood Darwin’s scientifically grounded theory, and he misapplied it as an endorsement of his sociological philosophy. The scientific historians, and philosophers, who have examined Spencer’s ideas have concluded that he saw evolution as a purposeful progression of the physical world, including all biological organisms, the human mind, and human culture and society. Unfortunately it was Spencer’s sociological concept of survival of the fittest, as opposed to Darwin’s scientific concept of natural selection, that led to the inaptly named Social Darwinism of the early nineteenth century, with all of its unfortunate ramifications.

There was never any true scientific foundation to Spencer’s ideas, but since they conveniently fitted with some of the prevailing prejudices of class, and the ethnic and racial bias of the late nineteenth century, extending into the first half of the twentieth century, they became deeply ingrained and influenced political and social belief. It is tragic that Spencer’s ideas still influence a lot of non-scientists today, so that one frequently hears the expression “survival of the fittest” raised in defence or excuse of some prejudicial action. So ingrained did Spencer’s ideas become that, during his lifetime, Darwin himself was put under a lot of pressure, by Spencer and others, to change his basic premise, but, although he briefly flirted with Spencer’s idea, he quickly recovered his senses and returned to his original concept.

Why am I making such a fuss of this when it might be argued that a similar concept of “fitness” is central to Darwinian theory even today? Of course fitness is a core concept to evolutionary biology, but this Darwinian expression is far from the judgemental notion proposed by Spencer. What then did Darwin really imply with his theory of evolution by means of natural selection, and how does the Darwinian concept of “fitness” differ from Spencer’s notion of “the survival of the fittest”?

Admirers of David Attenborough’s Blue Planet series will have observed how, in the warmth of summer, the female Atlantic lobster, a species that can grow up to 20 kilograms in weight, decides that the time has come to lay her eggs. She has already mated – often this happens as soon as she has moulted – but for seven months she has skulked from view in the freezing, deeper waters of the ocean, safe from predators and winter storms and patient in her determination to choose the most opportune moment for her offspring. But now her mind is made up, she is obliged to trudge her month-long marathon to the sandbanks of the warmer, surface waters, where, on her arrival, she must first do battle, claw for claw, with other lobsters to take control of her favoured sheltered pit. Here at last, some eight months after first fertilisation, she deposits her 20,000 or so eggs, which tumble into the pit from grape-like clusters beneath her abdomen, and from which her young emerge within minutes to take advantage of the warmth and limited shelter afforded by their mother’s endurance, discrimination and fortitude in battle. In the case of other marine invertebrate animals, such as sea urchins, and certain species of fish, a single spawning may give rise to millions of eggs. This behaviour, and the very production of vast numbers of potential offspring, is closely linked to what biologists actually mean when they talk about fitness in its true evolutionary meaning.

Fitness, from the Darwinian perspective, is a measure of how successful an individual is in his or her ability to reproduce and thus to contribute to the broad genetic pool of the species. It is a very simple, non-moralistic and non-judge-mental concept, the real emphasis of which is on reproduction. But, as we see with the lobster, this is more complex than merely laying eggs, or, in the case of human beings, bearing young in a womb. The individual has first to survive in the competitive theatre of life and then to compete with others of the same species for reproduction, and further to make possible, even in such limited life histories as that of the lobster, the survival of as many offspring as possible. In fact evolutionary biologists will usually measure comparative fitness of an individual within a species and what they look for is the proportional contribution of an individual’s genes to the species gene pool in a single generation.

Humans do not give birth to millions of eggs at a very early stage of embryological development, but rather to highly developed infants, which demands that they be nurtured for a very long period of time in the womb. For this purpose evolution has designed the human uterus as a single chamber, roughly the shape of an inverted pear, which is optimally designed for bearing a single foetus. The highest recorded number of living offspring born to a human mother in a single pregnancy is the eight babies born to an American mother in January 2009, all of whom lived. They were not conceived in the normal way but through assisted fertility treatment, and it is unlikely that all would have lived without the assistance of modern obstetric care. Indeed, obstetricians rightfully regard any increase above the normal single offspring as carrying an increased risk to both mother and offspring, even for twins.

Fitness, in human terms, is clearly more complex than we see in lobsters, but nevertheless the same basic non-Spencerian considerations apply, in terms of relative fitness.

The modern Darwinian concept of natural selection is brutally simple and depends on a system of probability, amenable to calculus. Where an individual of any species acquires some slight advantage in terms of survival over its fellows, it is more likely to survive long enough to have offspring, and if the advantage is hereditary, the offspring in turn will enjoy the same advantage over their own generation, so the advantage in time becomes part of the evolving species. From the fitness point of view, the hereditary advantage gives the individual, and its offspring at every subsequent stage of reproduction, the chance of making a bigger contribution to the species gene pool than the average member of the species. It’s really that simple. We can see, from the Darwinian standpoint, that relative fitness is a way of measuring advantage from a natural selection point of view. In time, particularly if the affected group within a species is isolated, geographically or otherwise, from the remainder of the species, an accumulation of such hereditary changes – or a rapidly developing major change – will so alter the affected group that they are no longer capable, or likely, to reproduce with members of the original species. This is the perfectly reasonable Darwinian explanation of how new species arise in a linear-with-branching pattern from ancestral species.

The creation of new species from old is termed “speciation”. Spencer, who was influenced by the French evolutionary biologist, Lamarck, believed that evolution was driving all of life, and most particularly the human species, towards a higher, utopian, destiny. But it is clear that Darwin’s theory of evolution by means of natural selection embraces no such ideal. On the contrary, selection works through the biological necessities of survival and comparative success in reproduction, which have nothing to do with morality, and have no in-built drive towards a philosophic, or religious, ideal of individual or societal perfection.

The concept of natural selection, as proposed by Darwin, was both logical and amenable to experimental confirmation, so that, in spite of considerable opposition from both Church and rivals within his own field, it appealed to the majority of scientists, and eventually to the educated society of his day. However, it embodied a weakness of which Darwin himself was well aware. For selection to work, it demanded a source, or sources, of hereditary change, which would give rise to the key advantages in survival, and thus relative fitness, of one individual, or group, over the others of its own species. Today we know that this implies some sort of genetic, or genomic, innovation, but Darwin was hampered by the ignorance of the mechanisms of heredity in his day. The very concept of genetics was unknown and the enlightenment of DNA would be unavailable until almost a century after publication of The Origin of Species. What Darwin achieved, given the science of his day, was, without exaggeration, world-changing. We cannot criticise him if he was obliged to fall back on now-outmoded concepts of parental mixing, or blending, as if the quaint notion of pedigree could somehow supply what we now realise to be the vast genetic and genomic change necessary to give rise to biodiversity. It was an inherent weakness in his theory that was unlikely to go away.

Thus it was not altogether surprising that, at Oxford, in 1894, during his presidential address to the British Association for the Advancement of Science, the Marquis of Salisbury attacked the concept of natural selection. The distinguished Thomas Henry Huxley was in the audience – cast by his critics as Darwin’s bulldog – but in reality one of the most objective, and formidable, biologists of his day. Huxley was faced with the fact that, where many earlier critics had attacked Darwinism from a religious perspective, adopting the Procrustean stance of faith, Salisbury was a highly educated man, an ex-Prime Minister and amateur scientist, and his attack was based in logic. He did not doubt the reality of evolution and he praised Darwin for convincing science, and the more educated levels of society, of this – rather, it was Darwin’s mechanism of evolution, natural selection, on which he focused his criticism. To date no scientist had ever proved in scientific experiment or observation that natural selection could produce a new species from an ancestral one. Moreover, Darwin’s theory assumed a very slow and gradual change in the evolution of life, and biodiversity, implying that the history of the Earth extended, say, to something like a billion years. Meanwhile Lord Kelvin, widely regarded as the foremost physicist in the world, had calculated the presumed age of the Earth from the physics of a cooling body, and pronounced that it could be no more than a million years old – too little time for life’s diversity to have evolved.

Although Huxley defended Darwin as best he could, he was hampered by the prevailing lack of hard evidence, and so inevitably he lost the battle to the scientific methodology of Kelvin. Darwinism had fallen to its lowest point, a nadir that would subsequently be recalled by Huxley’s own grandson, Julian, as “the eclipse of Darwinism”. Indeed, Julian Huxley would go on to describe the pressures on Darwinism that arose about the end of the nineteenth century and extended into the twentieth, when they were compounded by the growing dichotomy of many of the core disciplines of the biological sciences. In a great series of scientific publications, author after author would simply assume that their observations implied evolutionary adaptations, and thus the influence of natural selection, with ‘little contact of [such] evolutionary speculation with the concrete facts of cytology and heredity, or with actual experimentation’. The new generation of selectionists ignored the rising field of genetics, as pioneered by the writings of the Bavarian monk, Gregor Mendel, and they ignored the discovery of mutation by the Dutch botanist, Hugo de Vries. Evolutionary biology fragmented into three different factions – the selectionists, who had an undying conviction in natural selection, Mendelians (what we would now call geneticists), and mutationists, inspired by de Vries – and for several decades the discord continued.

In the opening chapters of his book, Evolution: The Modern Synthesis, Julian Huxley put his finger on the heart of the problem: ‘The really important criticisms have fallen upon Natural Selection as an evolutionary principle and centred round the nature of inheritable variation.’³

Today we know that Lord Kelvin was wrong and the Earth is far older even than Darwin conjectured, at roughly 4.6 billion years old, with life beginning at a very early stage in the planetary evolution and thus giving plenty of time for the evolution of biodiversity. Kelvin was ignorant of the radiation at the core of the Earth, which has kept the planet much warmer than would be predicted for an otherwise cooling body. Moreover, Huxley’s book, in its very title, indicates how the raging conflicts of this early phase of evolutionary biology were resolved. It may seem ironic, if perhaps predictable, that they were resolved through a synthesis of the three rival concepts: natural selection, the growing understanding of Mendelian genetics, and the potential of mutation to give rise to the much-needed genetic variation that, when it affected the germ cells, such as the sperm or the ovum, was inevitably hereditary. The consummation of all three forces gave rise to the synthesis theory of modern Darwinism. But this, as Huxley made clear, also implied important differences from the perspective originally adopted by Darwin himself.

Darwin had set out his stall for a slow and gradual change, based on the geological ideas of his hero, Charles Lyell. His vision was of a progressive, implicitly seamless, “transmutation” in living beings through parental blending and selection by nature. But the new evolutionary biology proposed genetic change arising through a series of accidents – copying errors during cell division, when the germ cells, such as the ovum and sperm, were formed. It also recognised the Mendelian nature of genes. Unlike the Victorian assumption, heredity was not a matter of parental blending but depended on discrete units of inheritance – rather like beads of coded knowledge – that were handed down, in what amounted to complementary pairings, one from each of the two parents, as part of the process of sexual reproduction. Only when one brought all three mechanisms into a single, all-embracing synthesis did evolutionary biology make sense.

If the publication of Darwin’s great book was the visionary moment that set the science of evolutionary biology in motion, the synthesis theory, also known as Modern Darwinism or neo-Darwinism, was a key stage in the development and amplification of that vision. It blossomed at the very heart of biology, ramifying through all of its disciplines. With the new, and equally iconoclastic, discovery of the chemical structure and hereditary role of DNA, by Watson and Crick, in 1953, and the revolution in molecular biology and genetics that followed it, Modern Darwinism gained further momentum. But, while not detracting a whit from the importance of these advances, let me draw attention to an obvious implication of the synthesis theory, yet one that is rarely drawn to public attention. Only one of the three mechanisms is based in theory – and this is natural selection. The other two mechanisms, mutation and Mendelian genetics, are fact that can be proven with all of the certainty of modern genetics. Why, in the defence of evolutionary theory against the creationists, have evolutionary biologists not produced these two trump cards out of their sleeves?

In part this omission derives from the fact that mutation has historically been promoted by Darwinians as random, and thus non-creative, while natural selection, usually abbreviated to “selection”, has historically been extolled as the exclusive creative force. This perspective, perhaps understandable three generations ago, is still presented today as the explanation of evolution in the majority of schools, colleges and universities in spite of the fact that there is overwhelming evidence that the reality of evolution is more complex, and decidedly more interesting, than this naïve oversimplification. For the moment I shall put aside the illogical and ultimately misleading historical contingencies so that I can concentrate on the importance of mutation and Mendelian genetics to medicine, where we shall see that they play a fundamental role in our understanding of the genetic basis of many diseases.

Cystic fibrosis is one of the commonest of genetic diseases, affecting roughly one in 2,500 children born in the UK and one in 4,000 of those born in the USA, with a similar incidence in Australia and Canada. Although less common in Asian and African populations – for example, the incidence in US-born Caucasian children is the same as in the UK, while the incidence in Asian Americans is roughly one in 30,000 – the disease is actually global in its distribution, affecting boys and girls with equal frequency. In 1989 an international team of scientists discovered the genetic cause, which proved to be mutations affecting a single gene, known as the cystic fibrosis transmembrane regulator gene, or CFTR, which is located on human chromosome 7, and which codes for the transport of salt and water across membranes in glands that produce mucus and sweat in several different organs of the body. The worst-affected organs are the lungs, the digestive organ known as the pancreas, the liver, intestines, sinuses and the sex organs. Normally the mucus produced by these organs is thin and oily, so that it flows easily and smoothly, but in people affected by cystic fibrosis the mucus is thick and sticky, causing local build-ups and obstructions within the organs. For example, in the lungs this can block the airways, which in turn allows bacteria to invade the stagnant parts of the lungs. This means that sufferers are very susceptible to chest infections, including pneumonia, which threaten health, and even life. Similar stagnation damages the pancreas, which is a major digestive organ. This shows up as failure to thrive in infancy, or as malnutrition through failure to digest food, and particularly fat, in older children and adults. The same genetic malfunction causes excessive amounts of salt to be lost in sweat – this is the basis of the diagnostic test for the condition, known as the “sweat test”. Cystic fibrosis shows a wide range of severity, from the very severe form that manifests at or soon after birth, to mild forms that may be diagnosed in late adolescence or even adult life.

Although there is currently no cure, sufferers can be helped by a number of measures, such as physiotherapy to help keep the lungs clear, and replacement therapies for the defective digestive enzymes. Cystic fibrosis is also one of the frontline illnesses in modern medical research aimed at curing the condition by correcting the genetic cause of the disease. To understand what this means, we need to know a little more about genes and how a malfunction of their normal operation can help in understanding the underlying causes of many important diseases. In fact the basis of genetics is quite simple, and logical, so that anybody can grasp the essential details.

One way of looking at genes is to regard each gene as a very long word written in a code we call DNA. The code itself is made up from an alphabet of just four letters. These letters are chemicals known as nucleotides, containing the nucleic acids guanine, adenine, cytosine and thymine, which are conveniently referred to using the letters G, A, C and T. It might appear a very limited alphabet but if you imagine the many different permutations of just those four letters that are possible in a word that is anything from hundreds to thousands of letters long, you appreciate how the DNA code offers virtually an unlimited variety of words. The 20,000 human genes are grouped together into 46 chromosomes – following the word analogy, the chromosomes might be seen as 46 chapters, which make up the book of our nuclear genome. In the formation of eggs and sperm inside the human ovaries and testes, the gene CFTR must be copied. Each of these germ cells will then contribute a single copy of CFTR to the offspring, so that every baby will be born with one gene from the father and another from the mother.

If, during the copying process, an error is made, so that the spelling of CFTR is defective, the code will be altered. This is what we mean by a mutation. But if you think it through, a mutation such as this will only affect one of the two copies of CFTR. Thus if the baby gets one defective copy and one normal copy, the normal copy might still be enough to prevent disease.

Here we turn to another strand of the synthesis – Mendelian genetics. In Mendel’s day, naturalists assumed that heredity arose through a process of blending of the parental characters, which was adopted by Darwin as the basis for hereditary change in his evolutionary theory. Mendel, the abbot of an Augustinian monastery in Czechoslovakia, happened to be a farmer’s son, and he studied the effects of cross-fertilising different varieties of peas, which he grew in the monastery’s vegetable garden. When, for example, he took the pollen from yellow peas and used it to fertilise the female parts of the flowers of green peas, the offspring were not a yellowish green, as one might have expected if parental characteristics blended. Instead they were all yellow. Even more intriguingly, when Mendel crossbred this new all-yellow generation, the next generation reverted to a mixture of yellow and green, like the original parents. Even stranger still, the ratio of yellow to green in the new generation was not equal: there were three times as many yellow as green peas. By analysing his results, Mendel realised that the inheritance of pea colour could not be based on blending, but rather some discrete factors must be responsible for the two different colours. He had discovered that the coding of heredity comes in small packages, which we inherit from either parents and which we now call genes. But this was not all that Mendel had discovered. What was the meaning of the curious ratios he had observed in the colour experiments?

In fact what he had discovered was that when the offspring inherited two different variations of a gene, sometimes one of the two variations dominated over the other. In the case of the peas, the gene for yellow was dominant. Thus when he blended green and yellow, the offspring, although some only had a single gene for yellow, all appeared yellow. When he further crossbred generations that had one yellow and one green gene, on the law of averages the offspring had a one-in-four chance of having two yellow genes, a two-in-four chance of having one yellow and one green, and a one-in-four chance of having two green genes. Not only does this explain Mendel’s findings, it also proves helpful when we go back to consider the genetics of cystic fibrosis.

Medical geneticists have indeed confirmed that when a child inherits one normal copy of the gene CFTR from one parent and a mutated version of the gene from the other parent, the coding for the normal copy dominates over that of the mutated gene. From the coding perspective, the mutated gene is essentially passive in the presence of the second normal gene. And this, in turn, implies that only if he or she inherits a mutated gene from both parents will a child suffer from cystic fibrosis. In medical genetics, this is known as a recessive pattern of inheritance. From this level of understanding, we see that there are two aspects of the recessive inheritance of cystic fibrosis that make it particularly amenable to gene therapy. The disease is the result of a malfunction of a single gene, CFTR. Moreover, the two defective copies of the CFTR in the sufferer’s chromosomes are passive and can be ignored. All that the sufferer needs to correct the condition is the introduction of a single copy of the normal CFTR gene.

I have no doubt that, in time, it will become possible to correct the genetic cause of cystic fibrosis through the introduction of a single copy of CFTR into the chromosomes of sufferers, though there will be problems, both ethical and technical, to be overcome before we reach this stage. For the moment, scientists have restricted their efforts to gene therapy directed exclusively at stem cells within the lungs, which, to date, have had a limited success.

Other single gene disorders may be the result of dominantly inherited mutations, for example achondroplasia, which causes a profound shortening of the limbs, leading to a common form of dwarfism, and Huntington’s disease, which causes jerky involuntary movements of the body and limbs and a decline in mental abilities. When a mutation affects a gene on the sex chromosomes, the genetics becomes a little more complex. For example, haemophilia, which causes excessive bleeding through defects in the blood-clotting factor VIII, is a recessive condition arising from mutations of a gene carried on the X chromosome. But since males only have a single X chromosome, inherited from their mothers, the single copy of the recessive gene will still give rise to the disease. This is why females, who have two X chromosomes, one inherited from each of the parents, rarely suffer from haemophilia – they would need both copies of the gene to be mutated before haemophilia could manifest. Thus we see that haemophilia is not only sex-linked, it is also a Mendelian recessive condition. Other mutations affecting genes on the sex chromosomes can be dominant, for example the condition known as Vitamin-D resistant rickets, so that a mutated gene on just a single X chromosome will cause the disease in either sex.

To date, geneticists have found causative mutations for more than 5,000 single-gene disorders. Other mutations can change the number of chromosomes, as in Down’s syndrome, where the individual has an additional copy of chromosome 21, or delete, duplicate, fragment, or otherwise damage the structure of chromosomes, giving rise to a variety of medical conditions. While specific gene therapy is at an early stage in the treatment of such conditions, a number of approaches to family screening, advice and prevention are already established and available to assist families known to have an increased risk of mutation and hereditary disease.

The medical approach includes prevention, through genetic counselling, public education about the risks of increasing maternal age, avoidance of risk factors such as radiation of the germ cells and foetus, caution over drug and chemical exposure, such as thalidomide, and vaccination against the rubella virus, which is known to damage the developing foetus. Newer genetic measures, such as in vitro fertilisation of the sperm and egg, followed by genetic screening of the resultant foetus when it is at the stage of a ball of cells, can be offered to high-risk families. Known as pre-implantation genetic diagnosis, or PGD, this may be helpful in a variety of diseases, including sex-linked disorders, single gene defects and chromosomal disorders. The potentially amenable sex-linked disorders include haemophilia, fragile X syndrome, most of the neuromuscular disorders (currently there are more than 900 recognised neuromuscular dystrophies) and hundreds of other diseases. Indeed, the potentially amenable single gene defects also include cystic fibrosis, Tay-Sachs disease, sickle-cell anaemia and Huntington’s disease.

As a general rule, we can see that a genetic abnormality is more likely to respond to PGD if it is predictable, because the genetic inheritance is known, and if its effects can be demonstrated in isolated embryological cells. Some people will have ethical objections to such manipulations of the human embryo, but for governments and the groups who monitor the ethics of medicine, the advantages to families will usually outweigh the ethical worries. It is also important to grasp that pre-implantation genetic diagnosis, with selection for healthy embryos, not only removes the risk of serious disease in an affected offspring but in some cases also eliminates the risk to future generations of the family.

A key development over the last decade or so has been our increasing understanding of the role of mutation in cancer.

But before we enter this intriguing, and disturbing, domain, we should spend a minute or two addressing some key questions as to the essential nature of what we are dealing with. What is cancer? Where does it come from? And why does it frighten us so much?

Cancer is a term used for diseases in which our own body’s cells divide without control and are able to invade other tissues. To put it another way, cells that have been programmed to work in perfect harmony with all the other cells, tissues and organs of the body, go ape and declare violent independence. What is at stake, for the aberrant cells, is immortality. Indeed, cancer cells are immortal in cell culture – but such ambitions are disastrous for the tissue, organ, and individual in which such ambitions arise, since it means that they invade the local tissue, or organ, and from there invade the local environment, or bloodstream, where they cause havoc, and possibly the death of the individual.

There are more than a hundred different forms of cancer, often named after the organ where they occur, such as the colon or breast, or after the kind of body cells they arise from, such as “carcinoma”, which arises from skin, or the cells lining internal organs, “sarcoma”, which arise from internal tissues, such as bone or muscle, “leukaemias”, which arise from blood-forming cells, and “lymphomas” and “myelomas”, which arise from cells involved in the immune system. In the words of Professor Karol Sikora, former chief of the WHO cancer programme, ‘Cancer is frightening because it is the enemy within.’⁴ It is also frightening because it is common. One in three of us in developed countries will develop cancer at some point in our lives. In 2008, in the USA alone, some 1,437,180 people were newly diagnosed with cancer, and that same year, in the UK, 1.2 million people were living with the disease from day to day. One of the ironies is that with improvements in healthcare as a result of modern treatments, the numbers of people living with the disease are likely to rise, with Sikora estimating a rise to 3 million in the UK by the year 2020. Indeed, it seems that never a day goes by without a cancer story in the news, with sufferers or their loved ones describing their experiences, and tribulations, on television, in newspaper and magazine articles, or on the personal pages on the Internet. Indeed, if we Google for cancer we discover approximately 300 million websites worldwide. Even the medical term for it and the defining words are hardly reassuring: “a malignant neoplasm”, a disease in which the body’s own cells display “uncontrolled growth”, followed by “metastasis”, which means the invasion of other organs of the body.

We all know that cancer is one of the common diseases and a significant cause of death in any country. We also know that cancer tends to get commoner with increasing age. Many of us probably also know that the term “cancer” is derived from the Latin word for a crab, which would appear to imply that it is a creeping thing that, like the splay of the crab’s many legs, spreads and invades our tissues. In fact, let me assure readers that many cancers are eminently treatable, far more so than when I first qualified as a doctor, and some are even completely curable. As with anything that frightens us, it becomes a good deal less frightening when we come to understand it better. And there can be no doubt at all that the logical approach to cancer, and its treatment, comes from exactly that – from understanding.

Our body is composed of organs and tissues, such as the brain, heart, and the glandular tissues that line the breast, or the prostate, and these in turn are made up of many different types of cells. As part of the wear and tear of life, cells die and must be replaced by the division of neighbouring cells. The first step in understanding cancers is to grasp the fact that nearly all cancers are caused by disturbance in the way genes, and other regulatory factors, exert control over this pattern of reproduction of cells.

Two groups of genes appear to be particularly important in controlling the way cells reproduce themselves. One group, known as “oncogenes” (onco here means tumour), are so-called because if they are inappropriately activated they increase the risk of developing a cancer. A second group are known as “tumour suppressor genes”. As the name suggests, these normally suppress the tendency towards uncontrolled cell proliferation that is such a prominent feature of cancers. Mutations that inappropriately switch on oncogenes or inappropriately switch off tumour suppressor genes are thus a potent cause of cancer. The decoding of the human genome has highlighted the genetic alterations that underlie cancers in such unprecedented detail that it has led two American oncologists, Vogelstein and Kinzler, to declare that ‘cancer is, in essence, a genetic disease’.⁵ They have summarised the mutated genes responsible for various cancers, together with the ways in which these mutations have perverted the normal genetic mechanisms to do so. For example, one in five familial breast cancers have been linked to mutations in the genes BRCA1 and BRCA2. Geneticists can further predict that women who carry these mutations have an 80% risk of developing breast cancer during their lifetime, so that pre-emptive surgery offers the potential of prevention. Recently, PGD has also been extended to help such families, and embryological screening has been made increasingly available for BRCA1 and BRCA2, with the first assisted babies, freed from the terrible risk, already born in a number of countries.

In 2006, a multi-centre screening programme in the USA looked at more than 13,000 genes taken from human breast and colon cancer cells, enabling authorities to compare the genes they found in the two cancers with the normal, and revealing that individual tumours accumulate an average of 90 mutant genes.⁶ Meanwhile, they concluded that a much smaller number of mutations are critical to the early stages of the cancer process, in their estimation perhaps 11 mutations for each of breast and colon cancer. Encouraged by these findings, the US National Institutes of Health is drawing up an atlas of cancer genomes – the Cancer Genome Atlas, or TCGA – with the aim of decoding the genomes of every human cancer and, by comparing these to the normal, extrapolating the genetic abnormalities that underlie all cancers.⁷ A pilot study has begun with cancers of the lung, brain and ovary.

It is not unreasonable to anticipate, as our knowledge of mutation grows, that important preventive and therapeutic aspects will come from it. However, though the understanding and medical applications of mutation have proved to be helpful, mutation is neither the exclusive mechanism of hereditary change in evolution nor the exclusive explanation of the genetic underpinning of disease, including cancer.