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The Gene: An Intimate History

Siddhartha Mukherjee

In the early 1870s, Charles Darwin read an obscure paper on plant hybridisation. We know this because he made extensive notes on pages 50, 51, 53 and 54, but not on page 52. Darwin died in 1882, his great theory of natural selection intact, but crucially incomplete. He had not found the mechanism by which genetic information was passed down the generations.

Or he had ignored it. In 1866, a Czech monk named Gregor Mendel had already published the solution to this problem. His experiments on pea plants had established the fundamental mechanism of heredity. Nobody paid any attention, but Mendel's findings were reported in that paper Darwin read - on page 52. Mendel died in 1884 entirely unnoticed by the world.

Such details, dramatic and precise, litter this thrilling and comprehensive account of what seems certain to be the most radical, controversial and, to borrow from the subtitle, intimate science of our time. Genetics, says Siddhartha Mukherjee, alters our conception of what it means to be 'human'. Mukherjee is an academic, cancer doctor and stem-cell biologist. His previous book, The Emperor of All Maladies: A Biography of Cancer, won the 2011 Pulitzer prize. No wonder, he is a natural storyteller. Although this book has some longueurs, overall it is a page-turner.

For Mukherjee this is plainly personal. He starts with a harrowing history of schizophrenia in his family in India. Schizophrenia is one of the many conditions now known to have a large genetic component. His father developed a form of dementia that runs down the generations and this familial connection was one of Mukherjee's first glimpses of the potency of the gene.

Mendel's discovery (it was recognised and resurrected in the late 19th and early 20th centuries), when combined with Darwin's theory, became the modern synthesis, an understanding of life and evolution that now dominates the intellectual and imaginative world of our time.

But it took a while. After Mendel and Darwin's post-mortem handshake, the first thing that happened was that the modern synthesis was catastrophically simplified - this happened three times.

First, there was the mania for eugenics, born of the idea that, knowing how heredity worked, we could improve society by preventing the poor, criminal and disabled from breeding. This was initially most brutally applied in America. Mukherjee's storytelling is at its best when he recounts the tale of Carrie Buck, the first case of legalised sterilisation in America. She was classed as a 'middle-grade moron' without any supporting evidence whatsoever and, though the case went to the Supreme Court, the sterilisation order was still upheld. The great judge Oliver Wendell Holmes Jr stained his career with the remark: 'Three generations of imbeciles are enough.' In the wake of the case, 62,000 people, mainly women, were sterilised in America.

Next came Nazism, a quasi-scientific attempt ('perverted science', Winston Churchill called it) to purify European humanity. This was, like compulsory sterilisation, a weaponisation of genetics. The logic was groundless, but the effects were horrific and need no further recounting here.

Finally, with the unravelling of the structure of DNA, the carrier of genes, by Francis Crick and James Watson in 1953, there was a widespread belief that the code of life had been cracked and that it was all terribly simple. The four-letter DNA cipher looked a lot like computer code; the assumption was that we were rather like the machines we had just started building.

In fact, as Mukherjee shows with clarity and energy, there is nothing simple about the working of our genes. They cascade, interact, dance and generally refuse to behave anything like your laptops. The recognition of the complexities of gene behaviour accelerated in the 1990s. By the time of the first announcement in 2000 by Tony Blair and Bill Clinton of the mapping of the human genome, it was already clear that this map was only the beginning. It was not simply the existence and location of the genes that mattered, it was their myriad interactions and control systems.

These findings destroyed old eugenical superstitions. For example, kinship studies around the world have repeatedly come up with percentages indicating the 'heritability' of certain human traits, notably intelligence. Identical twins reared together have a much more than 50% likelihood of having similar IQs. But with non-identical siblings, the correlation plummets. And with families living apart the number drops even further. The point is that heritability (a genetic cause) isn't the same as inheritability, the transfer of traits down the generations. Intelligence is clearly based on a vast complex of genes and their interactions that are highly unlikely to be passed on intact from parents to children.

Along with now proven flaws in the whole idea of IQ, these new discoveries utterly discredit all attempts to make crude connections between race and intelligence. With the development of the theory of epigenetics, which argues that genes can be responsive to environmental factors, we now know that events in life can change the genetic destiny of future generations.

Epigenetics and gene interactions were unanticipated complexities, confounding the initial computer-like image of DNA. Complexities have also held back a fourth simplification: gene therapy. This was assumed, from the 1980s onwards, to be just around the corner. In 1999, this premature optimism crashed into the case of Jesse Gelsinger, an 18-year-old who suffered from a rare single-gene defect called OTC that sentences victims to a lifetime of living with a precisely calibrated diet. Ambitious doctors thought they could fix this with a viral infusion that would import a healthy gene. It failed horribly and Jesse died, as, for a decade, did the hopes of gene therapy.

Now, Mukherjee makes clear, we are on the verge of mastering the complexity that has emerged from the human genome. A new eugenics is on the way based not on government fiat but on individual choice, as ever more exact ways are found of testing and then aborting or altering babies in the womb.

Large-scale prenatal removal of unwanted foetuses would plainly alter the human population. We could go even further with genetic changes (enhancements) of children or adults. At some point, it is thought, this would lead to a 'post-human future' in which we would, in effect, become a new species. The problem is we have no idea whether this future is desirable, because we have no common view of what constitutes an enhancement. Definitions by the West, the Pope, the Chinese, Putin or Isis would be likely to vary wildly. Meanwhile, western ethical concerns will crumble. The Chinese are conducting experiments on embryos that we would not, for the moment, countenance. The pressure to compete will be overwhelming.

Mukherjee raises all these questions without resolving them. This is understandable. The answers depend on factors that lie far beyond any one person's competence; we can only wonder. 'Can we,' he asks, 'make our genomes a 'little better' without risking the possibility of making ourselves substantially worse?' The answer is obviously no, but we will risk it, nonetheless.

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