Identically Different

Why We Can Change Our Genes

Tim Spector

• Publisher: ABRAMS Press
• Year: 2014
• ISBN:
  9781468310405
• Topic: Biological Sciences
• Subtopic: Genetics & Genomics
• Index: Biological Sciences

In this book, a geneticist who studies identical twins "treats the view that genes are destiny with skepticism" ( The New York Times ). How much are the things you choose to do every day determined by your genes and how much is your own free will? Drawing on his own cutting-edge research of identical twins, leading geneticist Tim Spector shows us how the same upbringing, the same environment, and even the same exact genes can lead to very different outcomes. Thought-provoking, entertaining, and enlightening, Identically Different helps us understand the science behind what makes each of us unique and so quintessentially human.

1

THE GENE MYTH

Toads, giraffes and fraud

Genes and environment or nature and nurture cannot, as currently portrayed, explain why our genetically identical cells are so different, or the greater-than-expected differences between relatives or twins, or the countless examples of rapidly changing patterns of disease. This brings us to an eighteenth-century scientist called Lamarck and his ideas of ‘soft inheritance’, which we now call epigenetics. Epigenetics could be the missing third element, alongside nature and nurture.

Jean-Baptiste-Pierre-Antoine de Monet, Chevalier de Lamarck, was born in 1744 near Amiens in northern France. Lamarck was a man of many talents. He started first as a soldier in the war against Prussia, then studied medicine, fossils, then finally botany. He worked in difficult conditions at the time of the Great Terror following the French Revolution, when many of his colleagues had been guillotined for saying things that were not politically acceptable. He published his major works during the Napoleonic wars, and 50 years before Darwin he developed an elaborate theory of evolution.¹

Lamarck was the first to properly study invertebrate animals, and he was an early champion of the controversial idea that something other than divine intervention was responsible for generational changes in plants and animals. His main theory, formulated in 1809 (the year Darwin was born),² was that there was a combination of two evolutionary forces. The first was the vague power of complexity, or ‘le pouvoir de la vie’: simple organisms spontaneously emerge and then slowly evolve to become more complex. The second was force of circumstance, ‘l’influence des circonstances’: animal species had adapted rapidly to their surroundings, and formed habits that exercised and improved (or lost) certain characteristics, such as eyes, tails, colours and muscles. But not only did they seem to be able to adapt to their environment, they also passed some of the newly acquired characteristics on to their offspring. This process has since been called the inheritance of acquired characteristics or ‘soft inheritance’.

Like Darwin after him, Lamarck did not use the term gene – the concept was unknown to him and his contemporaries – so he could not explain how these characteristics were passed on. His most quoted example from the many he used is that of giraffes. The tall trees that giraffes ate from, he argued, made them stretch their necks, and the continuous stretching released fluids that made each generation have slightly longer necks. Until recently he and his giraffe neck theory were the butt of many jokes. His observation that plants adapted to different types of soil that they were planted in was more acceptable to his peers – although these possible ‘epigenetic’ effects on plants were seen as too far removed from ‘divinely created’ humans to be taken seriously.

Lamarck’s theory of evolution was heavily criticised in France by his peers and was soon forgotten. Unlike Darwin, who after a long struggle with creationists ended up triumphantly buried in a prestigious plot in Westminster Abbey, Lamarck finished his life blind and penniless, dumped into an unmarked limepit somewhere in northern France.³ Even after his death, his French colleagues continued to demean and ridicule him, notably in the so-called ‘eulogy’ given by his rival George Cuvier in Paris a few years later. History likes winners and losers, and many a schoolchild since then has learned of the foolish Lamarckian theories, trumped by the brilliant and logical Charles Darwin. But the reality was not so simple. Darwin was actually an admirer of Lamarck, and his works contain several references to the notion that inheritance of acquired characteristics might be an alternative or parallel method of evolution, albeit more minor. But at the time most of the scientific world was more interested in our descent from apes and did not listen.

Nazis, communists and Indian ink

The work of the unfortunate Chevalier de Lamarck was not the only precursor of modern epigenetics. Paul Kammerer was a Viennese musician turned biologist who in the 1920s had a fascination with amphibians and with Lamarck’s ideas. He was a busy man who like many men of his day performed experiments in diverse areas. His own – and from today’s perspective rather eccentric – theories of life were often quoted by Freud and others. Kammerer claimed (without formal proof) that he had skilfully manipulated and bred cave-dwelling salamanders (olms) with no eyes to be able to see. He raised salamanders in very different breeding environments and apparently altered their offspring’s breeding patterns.

He was most famous for claiming to have made midwife toads breed in the water as opposed to on land, just by raising water temperatures. The midwife toad gets its name because the male carries the fertilised eggs around on its hind legs. He also reported that his new generation of toads were now exhibiting black nuptial pads on their feet with tiny spines to stop them slipping during mating in water, just like their distant ancestors.

Kammerer drew big audiences for his international speaking tours, which made him good money. The New York Times in 1923 hailed him as the new Darwin, having proven Lamarck’s ideas of inherited acquired characteristics.⁴ He even had a celebrity mistress, Alma Mahler, the newly widowed spouse of the late Gustav Mahler. Alma Mahler was the femme fatale of her time, who while picking her way through famous musicians and artists, also worked as Kammerer’s assistant. She complained about his sloppy record-keeping and over-eagerness for positive results. Kammerer soon became known in Vienna as the ‘Wizard of Lizards’, as much for his wild social life and strong socialist and pacifist views as for his science. He had also irritated some Americans both from his hyped success in the media and because when he visited America during Prohibition he predicted piously that future generations would benefit from the alcohol-free environment of their parents.

But Kammerer’s fame was not to last. Scandal hit when in 1926 the journal Nature published a letter stating that the famous toad experiment had been faked. G. K. Noble, Curator of Reptiles at the American Museum of Natural History, had visited his old lab in Vienna unannounced when Kammerer was still on his money-making world lecture tour and inspected the famous specimen of the preserved but long-dead toad. The black pads, Noble claimed, had a far more mundane explanation: ‘it had simply been injected there with Indian ink’.⁵ Six weeks later Kammerer shot himself in the forest of Schneeberg, leaving a suicide note with a somewhat ambiguous content. ‘Who besides myself had any interest in perpetrating such falsifications can only be very dimly suspected,’ he wrote. This note was also, strangely, published in Science – an unorthodox posthumous way of improving your CV.⁶

Interest in Kammerer’s experiments revived 40 years later in 1971 with the publication of a book on the incident by the Hungarian author Arthur Koestler. In The Case of the Midwife Toad he suggested that the toad experiments might have been doctored by an early Nazi sympathiser (a so-called Hakenkreuzer, swastika-lover) at the University of Vienna where political activism was rife.⁷ Koestler also pointed out that the dodgy toad had been exhibited earlier in 1923 in Cambridge to known sceptics who had examined the specimens and hadn’t spotted the crude ink injections and claimed to have seen the spines. This suggested that the ink could have been added later.

In 2009 a Chilean biologist, Alexander Vargas, reignited the debate by elevating the vilified Kammerer to the status of the real father of epigenetics and Lamarckian biology. He examined Kammerer’s lab books and breeding experiments, and concluded that many of his findings that were ridiculed in the past could now be supported by modern science and our understanding of so-called imprinted genes.⁸ Not everyone agreed. A subsequent editorial and some detective work in an American biology journal in 2010 showed evidence that he had a track record prior to the toad incident.⁹ He had previously tried to artificially touch up an image of a salamander’s spots while submitting an article for the same journal. They damned him a second time as a fraud and a bad example to others. However, they also admitted that even today, up to 25 per cent of scientific images submitted to journals have some degree of ‘enhancement’. So whether the Wizard of Lizards was just a confident fraudster or a genius who was the first to show Lamarckian inheritance, as well as a victim of jealous Americans and Nazi saboteurs, will never be known for sure.

Two years later in 1928 another remarkable, if unpleasant, scientific character emerged from Stalin’s Russia. Trofim Lysenko may have unwittingly cost Russia the Cold War 50 years later. He was a Ukrainian self-taught biologist of peasant stock who embraced neo-Lamarckism. Like Stalin, he disliked the Western- and then Fascist Germany-dominated world of traditional genetics run by elite intellectuals.¹⁰ Their ideas of genetic determinism, eugenics and the power of heredity ran against socialist ideals, which rejected inherited privilege.

Lysenko first came to Stalin’s notice by performing an amazing farm experiment. This happened during the new collectivisation policy of changing small family-run farms into state cooperatives. Local Soviet methods to improve agricultural output were given top priority as part of the new five-year plan. Lysenko took one large farm’s entire seed supply (without their approval), wetted the seeds and buried them in sacks in the frozen ground to ‘prime’ them for the next year’s harvest, so that they and their progeny would be tougher and produce more wheat. The results were spectacular and more experiments were started immediately, slightly altering the conditions of the priming, or vernalisation, as it was known. Stalin loved the simplicity of his approach, and its PR spinoffs, as all peasants could now become barefoot scientists as well as farmers.

With no need to rely on the infrastructure provided by universities, and on complex and expensive lengthy plant-breeding experiments, Lysenko offered immediate solutions to Stalin and rapidly gained power and influence, becoming head of Soviet biology. He entertained visits from prominent US and European scientists eager to understand his vernalisation methods. But there was a dark side. Anyone who challenged his unorthodox methods or results, or openly supported Mendel or Darwin, was viewed as a traitor to the revolution and either shot or sent on permanent sabbatical to the Gulags. In 1948 genetics was officially banned; it was called a ‘bourgeois pseudoscience’ until 1964.

There was, however, one little problem with the Lysenko alternative of Lamarckism. It was all one big lie. None of his experiments ever succeeded. No crop yields increased, no trees grew. Failures were covered up, although the rolling programme continued to obscure the truth. Millions of Russian peasants died of starvation, and because of the long-term lack of scientists and plant-breeding innovations, postwar Soviet Russia embarrassingly ended up dependent on America for its food imports. The USA had meanwhile successfully bred maize hybrids using traditional Mendelian genetics and were now tripling their yields. The collapse of the Soviet empire was not due to its failures in arms or technology, but ultimately to failures in agricultural genetics and biology.

But the man who, in retrospect, can be regarded as the real father of modern epigenetics was Conrad Waddington, an Englishman born in India in 1905, who was way ahead of his time. He too started in science with a strange interest in amphibians and how they developed – though he wisely stayed clear of toads. He moved on to study genes and heredity in fruit flies. He was, just before the Second World War, the first to suggest and use the term epigenetics, derived from the Greek prefix epi-, above or around, and genetics. He was fascinated in early development of the fetus and interested in the mystery of how cells can start so simply and then develop specialised functions, yet all have the same genetic material.

Before the structure of DNA was discovered, Waddington believed that tiny changes (mutations) around our genes could lead to differences in the way that cells and whole animals develop and could in theory be passed down generations. As a Fellow of the Royal Society, he was one of the most eminent pre-molecular developmental biologists of his time and his work suggested that some of what Lamarck had said might just be correct.¹¹ Unfortunately, following the stir caused by the elucidation of DNA structure and the molecular biology of genes, his work was overshadowed and forgotten for many years.

How do plants know when to flower?

Looked at from today’s perspective, how does Waddington’s or indeed Lamarck’s theory hold up?¹²

While Lamarck made some very interesting and relevant observations, he should perhaps have steered clear of talking about both giraffes and lettuce in the same breath. Plants and animals differ in quite a few ways. One difference is that plant cells are pluripotent (multipurpose): they can all change to another form if needed and become specialised. In this way small cuttings can sprout a whole new plant – unlike someone attempting to plant a human finger. This means that they must have ways of modifying the genetic information from the identical DNA contained in each cell to provide the message to make a specialised daughter cell. Epigenetic mechanisms were supposed to play a part in this, but after the cells divide, these new signals were believed to be wiped clean again, so that the cell could remain pluripotent. This would mean that cells had no remnants of interfering messages – for example trying to make cells become leaves or roots. The idea that all memories of how a cell had diversified were completely wiped clean as the pollen (sperm) and the egg (called gametes) were formed to make a new generation has been central to the traditional view of genetics. We now know this isn’t exactly true. The wiping process isn’t perfect.

Over ten years ago a group in Norwich discovered a natural case of epigenetic changes in plants. Remember this means a heritable effect that is not due to changes in DNA structure. A ‘mutant’ version of the common toadflax plant, a pretty yellow wildflower growing in hedgerows, results in flowers with radial petals (five), rather than the normal two.¹³ What was unusual was that although the DNA structure was the same in both plants, the ‘mutation’ could still be passed on. Normally a mutation is a change in the actual DNA – which was not the case here. The researchers found this change was due to something called ‘methylation’, which is a key part of epigenetics in animals as well as plants, and one that we will return to later. In the mutant plant, a key gene (called Lcyc) is extensively methylated and in the normal plant it is not.

What methylation means is that at certain sites (usually cytosine bases) of the gene’s DNA, small chemical methyl groups (Me) floating around the cell attach themselves to it, rather like sticking an olive on a cucumber with a cocktail stick. This has the effect of stopping the gene producing a protein. We call this inactivating it or ‘switching off’, and we know that in most cases methylation stops a gene from working, or ‘being expressed’, while reversing the process (un-methylating) usually switches the gene back on. By being turned on we mean that it is expressed and more protein is produced. While this process, unlike a mutation, is reversible, it can also last a long time.

The two main epigenetic mechanisms

The Norwich team found that most subsequent generations of toadflax plants had the same radial petal pattern, and carried the same deactivated gene due to methylation. This showed that the information couldn’t have been wiped and reset as previously believed. This was the first clear modern evidence that natural epigenetics occurs and can be passed on across generations. Others were soon to follow.

How do plants know when to flower? It seems a simple question, but until recently we had no idea of the answer. The arabidopsis plant (thale cress) alters the timing of its flowering by epigenetics.¹⁴ In response to prolonged cold (as in winter), the Flowering Locus C gene which normally prevents flowering is methylated and deactivated, allowing this variety to flower in the spring. The trait is then passed on to the next generation, even if there is no cold winter. Ironically this experiment showed that the vernalisation mechanism favoured – and faked – by Lysenko was actuall...

Table of contents

• Cover
• Copyright
• Dedication
• Contents
• Preface
• Introduction: Was Darwin wrong?
• 1 The gene myth
• 2 ‘The happiness gene’
• 3 ‘The talent gene’
• 4 ‘The god gene’
• 5 ‘The parenting gene’
• 6 ‘Bad genes’
• 7 ‘The mortality gene’
• 8 ‘The fat gene’
• 9 ‘The cancer gene’
• 10 ‘The gay gene’
• 11 ‘The fidelity gene’
• 12 Bacteria genes
• 13 Identical genes
• Acknowledgements
• Notes
• Index
• About the Author
• About Identically Different