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
