Books

Siddhartha Mukherjee Prepares Us for a Crucial Moment in the History of the Genome

With his new book, the author takes a step back from the urgency and desperate clamour attendant to a chronicle of cancer and into the more sterilised, yet even more transformative, world of genes.

Siddhartha Mukherjee
The Gene: An Intimate History
Penguin, 2016.

Like most of the great eras shaped by human thought and action, there was a designated time of genetics, and it couldn’t have come any sooner. There had been two millennia of little positive progress since a rudimentary ‘debate’ between Aristotle and Plato about how parents transmitted biological information to their children – with the former providing a convincing argument that they were transmitted as some sort of messages. But in the same period of silence, what genetics ought to be became more clearly defined, as exchanges between experimenters, philosophers and theologians dismissed many hypotheses that could not withstand scrutiny.

Uncovering the fundamental ingredients of genetics was not a straightforward process, where one discovery immediately followed from the last. Yes, there was an underpinning logic, distinct notes that when strung together would make the melody, but the long history of how each note was found has one repetitive attribute: Our genes were full of surprises.

These are the surprises sprinkled through American oncologist and writer Siddhartha Mukherjee’s new book, The Gene: An Intimate History. Mukherjee offers it as a prequel to his Pulitzer-Prize-winning The Emperor of All Maladies (2010). And in doing so he takes a step back from the urgency and desperate clamour attendant to a chronicle of cancer and into the more sterilised, yet even more transformative, world of genes and the proteins they encode. As the author writes in the prologue: “… to study cancer, I realized, is to also study its obverse. What is the code of normalcy before it becomes corrupted by cancer’s coda?” The Gene aspires to being a documentation of that normalcy, and how it came to be, and it mostly succeeds.

The importance of causality

The principal thing that stands to drive such a text into the ground is detail. The Gene is more science than sociology or economics, and the technical parts are unpacked over a few thousand words every time. However, there is no tedium in consuming them because, second, Mukherjee is a master-writer, but first, the exposition of modern genetics recapitulates the evolution of modern genetics itself. What made its perfect understanding take 2,000 years to arrive at is also what requires a history of the gene to be so exhaustive: causality.

In the early nineteenth century, Gregor Mendel and Charles Darwin, working separately, arrived at two distinct insights into a theory of heredity. In a span of seven years, Mendel had found that any trait of a living thing was defined by its dominant and recessive ‘forms’ (later called alleles). Darwin had realised that there was a natural selection at work that slowly killed off unfavourable variations and preserved favourable variations as new species. Their contemporaneity is instructive because we miss it in our biology textbooks – building our knowledge of genes in serial and not in parallel, as it is often developed.

To recreate the sequence of events, which continue in similar fashion beyond Mendel and Darwin, Mukherjee has organised his book into thematic mini-eras. There are six all together, discussing advances made from 1865 to post-2015. Each era stands on the shoulders of the previous one – becoming smaller in duration because scientists were encouraged to make bigger leaps of thinking – while possessing a unique zeitgeist. The first era is of Mendel and Darwin, who went from ‘zero to one’ and planted the seeds of what would come. Their struggles are a template for the rest of the book – defined by patiently making out sense from seeming nonsense.

Next comes the defence of the duo’s ideas and their subsequent representation in biochemistry. In this phase, the notion of a gene as the building block of hereditary information became quantified, and with quantification came reproduction – in literature, in laboratories. Even if the genes were still surrounded by mysteries, its existence made them susceptible to possession or – as Nazi Germany would have it – dispossession. As Mukherjee writes, “That “Jewishness” or “Gypsyness” was carried on chromosomes, transmitted through heredity, and thereby subject to genetic cleansing required a rather extraordinary contortion of belief – but the suspension of skepticism was the defining credo of the culture.’ The Nazis would further Francis Galton’s hypothesis of ‘genetic superiority” in gruesome ways, but they would also do some good: by placing “the ultimate stamp of shame on eugenics.”

Preparing for a flip in intent

Siddhartha Mukherjee. Source: YouTube

Siddhartha Mukherjee. Source: YouTube

While Nazism was on the decline, there was a flurry of activity in the labs of North America and Europe. Scientists – biochemists, biophysicists, physiologists – had gradually learnt that proteins were not the carriers of genetic information but that a giant molecule called DNA (deoxyribonucleic acid) was. Just as Albert Einstein had found, half a century earlier, that function followed form, scientists had also realised that DNA’s structure was the key to understanding how the molecule acquired, carried and transmitted hereditary information. It was soon found to be a spiralling ladder made of two strands of nucleotides with covalent bonds for rungs. The gene became a fragment of DNA and the recipe for making specific proteins; humans had 21,000 of them.

Much as the biochemical refinement of the gene signalled a cognitive shift from a thing of mystery to a well-defined container of rational information, so did the identification of its true form anticipate a cognitive shift from its being a thing to be understood to an instrument of control. This control defines the era we currently live in: In the history of science, our attitudes toward the gene are completing a slow turn of intent from pandering to its biological whims to making it serve us. It is another ‘zero to one’ moment.

The Gene prepares us well for it by plunging us into the depths of its many origins, and dredging up over 489 pages the book’s greatest achievement: exposing the uncertainties still prevalent in our investigation of our genome. For every problem we solved by deciphering the information contained in our genetic material, every disease surmounted, the uncertainties multiplied in significance for what they told us about the problems we could not solve. The perfect example from biology is familial schizophrenia; others examples are our cultural, sexual and political identities, our knowledge of genetics tempting us to reduce them to chemical signatures by way of some convoluted epigenetic pathway.

Toward the close, the book discusses CRISPR/Cas9, a genome-editing tool that gives some skilled humans the ability to edit our DNA like it was a text file: changing spellings, rearranging paragraphs, even adding new words. It is a strange ability to grapple with – to consider that we can remake ourselves. But by this point, into the last pages, the hubris is implicit; Mukherjee mentions that CRISPR’s makers were seeking a moratorium on gene-editing technologies even as he was finishing up the book.

Perhaps we are not yet comfortable with the idea that we can reconfigure ourselves. But if we have come this far, then we will surely attempt to distill the ultimate biochemistry of humanness out of a single molecule in the future. After all, as the last postulate of Mukherjee’s ‘gene manifesto’ says: “History repeats itself, in part because the genome repeats itself. And the genome repeats itself, in part because history does.”