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The Gene: An Intimate History
By Siddhartha Mukherjee, Scribner, 608 pages, $32
Image Credit: Supplied
Even before the beginning of human history, people recognised that parents transmit something — call it “likeness” — to their children, and the children to their children, and so on down the generations. But how?
In the sixth century BC, Pythagoras theorised that male semen conveyed the information into female bodies, which provided nourishment. Two hundred years later, Aristotle, observing that some Greeks resembled their mothers and grandmothers, proposed that women as well as men carry their likeness, in the blood. (We still speak of bloodlines and blood relatives.) Aristotle said, rightly, that creatures must pass along not just material, such as wood for a carpenter, but a message: “the shape and the form”.
During the next two millenniums, little more was learnt. When Charles Darwin published “On the Origin of Species by Means of Natural Selection” in 1859, he was uncomfortably aware that his entire theory rested atop a foundation that could not be seen. A theory of heredity was yet to come.
In 1883, the German biologist August Weismann cut off the tails of seven female and five male white mice. Would their offspring have tails or not? To us it seems obvious, but no one knew for sure. Before he was done, Weismann had severed 901 tails through five generations of mice. No tail-less mice were born. Thus science marches on.
Heredity was the “missing science”, the ever prescient H.G. Wells remarked at the turn of the century: “This unworked mine of knowledge on the borderland of biology and anthropology, which for all practical purposes is as unworked now as it was in the days of Plato, is, in simple truth, 10 times more important to humanity than all the chemistry and physics, all the technical and industrial science that ever has been or ever will be discovered.”
This missing science we now know as genetics. Its elusive fundamental particle, the essential unit of biological information, we call the gene. First the idea of the gene had to be invented. Then the physical entity, present in each cell of our bodies, in every living thing, had to be discovered. The story of this invention and this discovery has been told, piecemeal, in different ways, but never before with the scope and grandeur that Siddhartha Mukherjee brings to his new history, “The Gene”. He fully justifies the claim that it is “one of the most powerful and dangerous ideas in the history of science”.
As he did in his Pulitzer Prize-winning history of cancer, “The Emperor of All Maladies” (2010), Mukherjee views his subject panoptically, from a great and clarifying height, yet also intimately. Framing his story are pieces of his own family history: his cousin and two of his uncles “suffered from various unravellings of the mind”, and the spectre of mental illness, presumably inherited or inheritable, haunts his family and his imagination. The books form a magnificent pair. “The Emperor of All Maladies” is, as Mukherjee notes, the story of the genetic code corrupted, tipping into malignancy. The new book, then, serves as its prequel.
“Nothing about the natural world, at first glance, suggests the existence of a gene,” he writes. “Indeed, you have to perform rather bizarre experimental contortions to uncover the idea of discrete particles of inheritance.” The man who performed those bizarre contortions was the monk Gregor Mendel, living in an abbey in Brno, Austria-Hungary (now in the Czech Republic). The abbey had five acres of garden. Forbidden by the abbot to experiment on field mice, Mendel began growing peas. And he did not just plant them; he made hybrids, crossing tall plants with short plants, white flowers with purple flowers, smooth pods with crumpled pods.
“He began to discern patterns in the data — unanticipated constancies, conserved ratios, numerical rhythms,” Mukherjee writes. “He had tapped, at last, into heredity’s inner logic.” After almost eight plodding years he wrote a paper, which he read in 1865 to a room of farmers and botanists in Brno and published in the yearly “Proceedings of the Brno Natural Science Society”. And then — nothing. The history of science is a tangled web, not a logical arc, and for four decades Mendel’s pioneering work — “the study that founded modern biology”, as Mukherjee describes with only a touch of hyperbole — effectively disappeared.
The founding of modern biology had to wait until the turn of the century. Mendel’s forgotten paper was discovered by biologists in Amsterdam, Cambridge and elsewhere. Mendel had discovered the basic unit of heredity, had proved there must be such a unit, and finally a Danish botanist, Wilhelm Johannsen, gave it a name: “gene”, he suggested — “a very applicable little word”.
What is the gene? First it was an abstraction, an enigma, “a ghost lurking in the biological machine”, Mukherjee writes. By definition the gene was the carrier of any trait that is heritable or partly heritable. One would say there are genes for eye colour, height or even intelligence. But some traits are better defined than others. People have long bred dogs, for example, to be “short-haired, longhaired, pied, piebald, bowlegged, hairless, crop-tailed, vicious, mild-mannered, diffident, guarded, belligerent”.
In the 20th century, new technologies and new disciplines brought this abstract and hypothetical idea into sharper and sharper focus. The epiphany came in the discovery by James Watson, Francis Crick and Rosalind Franklin of a vivid physical form, the famous double helix, the winding base pairs of DNA. Genes are strung along chromosomes like beads on strings (the common metaphor). Scientists isolated them and counted them: 21,000 to 23,000 to make a human being.
The gene is a message. It is an instruction for building a protein. It can be a blueprint encoding the design for a structure, or more accurately, as Richard Dawkins has suggested, a recipe encoding a process. The genome is an algorithm, and at the same time, it is a code, which had to be laboriously and ingeniously deciphered. It is the beginning and ending of an endless circle of life: a gene is a message, which builds a protein, which creates form and function, which regulates the gene.
Mukherjee arranges his history not just chronologically but thematically. This is necessary. Science seldom progresses in a neat logical order anyway, but genetics, especially, encompasses and influences many subjects at once: biology, information science, even psychiatry. Genetics has also played its part in the darkest currents of 20th-century history. One need only remember that Nazi genetics is a subject of its own, aimed at the improvement of Ubermenschen by the elimination of the feebleminded and “degenerate”. But the social impulse for eugenics started earlier, in England and in the United States. More recently, we have lived through debates tinged with poorly understood notions of race. In the 1980s, James Q. Wilson and Richard Herrnstein linked criminal violence to “bad genes” in “Crime and Human Nature”. Herrnstein returned in the 1990s with the incendiary “The Bell Curve”, written with Charles Murray, which claimed that whites and Asians had a genetic advantage over people of African descent in “intellectual capacity”.
Mukherjee’s analysis of these episodes is clarifying and, in my view, definitive. He notes the narrow and shifting definitions of “intelligence” and its measure by flawed and culturally bound tests. To understand the debate properly, though, we need to recognise how artificial our racial categories are to begin with. The explosion of knowledge that has come from the Human Genome Project and its successors allows statistical measures of genetic diversity in groups we classify as “races”. Between the races, diversity is slight; within them, diversity is enormous.
The gene is, and is not, the determiner of our identity. It behooves us to accept this paradox and understand it. As we learn how our genome defines us, we also learn how we transcend our genome. The gene, in the era of recombinant DNA, has become an instrument of its own manipulation. We have gene therapies and gene editing. In what Mukherjee calls the “post-genomic” world, we will wield a power as exhilarating as it is treacherous. Simply put, “We will learn to read and write our selves, ourselves.”
–New York Times News Service
James Gleick’s books include “The Information: A History, a Theory, a Flood” and “Time Travel”, which will be published in autumn.