Book Review: The Gene, an intimate history by Siddhartha Mukherjee

This is a fantastic book. If you’re interested in biology, you’ll learn a lot. If you’re not interested, you will become interested and learn a lot!

Siddhartha Mukherjee takes the reader on a riveting journey – starting from Mendel and Darwin to Dobzhanky’s ideas, the discovery of the DNA and the race to find its structure to chromosomes, linkage and recombination, the central dogma to epigenetics, sequencing DNA to the human genome project, gene editing to CRISPR/Cas9 and sexuality to free-will.

What makes this book especially interesting is that these concepts are not only beautifully explained, but are linked to world events such as the horrors of eugenics, the excitement and anticipation of the announcement of the human genome, and the first cases of gene therapy. It describes the stories behind the achievements, connecting them to the lives of the scientists involved – their successes and failures, their hopes and beliefs, their ups and downs, proving that science is a very human endeavor. We readers, can’t help but get involved in the narration and follow it with palpable excitement.

I’d like to highlight two examples from the book that, to me, beautifully depict the excitement and frustrations of discoveries and the scientists who made them, making the reading so gripping.

Mutant flies

Thomas Morgan was studying fruit flies at Colombia University. Hoping to find mutants, he painstakingly screened thousands of flies, eventually finding a handful over 30 years. Hermann Muller, his least favorite student, went on to set up a lab in Texas to use mutants to understand heredity. Being very understandably fed up with the excruciatingly slow hunt for mutants, he decided to try to speed it up. After a few years’ work, he found that irradiating the flies with low level radiation, and crossing the irradiated males with females produced hundreds of mutants. “Each time Muller found a new mutant, he shouted down the window (to the only other scientist working so late in the night), “I got another!” It had taken nearly three decades for Morgan and his students to collect about fifty fly mutants in New York. … Muller had discovered nearly half that number in a single night.” The description of this discovery, the late-night setting, the lone scientist trying outlandish ideas, and his excitement at the discovery, is not only memorable, but also very relatable, especially as a fellow scientist. This discovery made him internationally famous, having shown that genes are made of matter, and that they are changeable. However, there was no happy ending for Muller. We learn that Muller was an advocate for the rights of women, African Americans and workers. This whiff of socialist ideas made him a pariah among his colleagues. The FBI investigated him, and the newspapers called him a freak. After a failed suicide attempt, he left, in 1932, for what he thought would be a more liberal country – Germany.

Parasitic frog eggs

In the 1950s, scientists emptied the contents of unfertilized frog eggs and injected genomes of young embryos into it. A small fraction of the eggs grew into healthy tadpoles, showing that the cell without the genome still had everything necessary to make an embryo with a new genome. However, because the success rate was so low, the project was abandoned. John Gurdon, someone who “had never been a particularly promising student – he once scored 250th in a class of 250 in a science exam”, modified the experiment in a way that could be straight out of science fiction. He injected the emptied egg with the genome of a cell from an adult frog intestine, overcoming immense technical challenges. His approach resulted in embryos that were the exact copies of the adult frog from which the cells were taken. This was the first cloning procedure, which inspired scientists all over the world to try it – resulting in Dolly, and for which Gurdon received the Nobel Prize in 2012. However, what I found more intriguing was the other branch of biology this discovery opened. Gurdon’s technique had a very low yield. Why should this be? Do cells lose information of some kind as they grow older, preventing them from producing embryos? These questions opened the door to cellular memory. One aspect of this episode inspires me – a single painstaking experiment opened two huge fields of research – and another makes me ponder – if someone who went on to win the Nobel Prize scored lowest in an exam, what does it say about our education system?

Mukherjee keeps the readers on their toes by interspersing scientific narration with its impact on real people. Rather than broad examples, he offers concrete instances. For instance, we follow the shocking story of the forced sterilization of Carrie Buck, simply for being “feeble-minded” and “troublesome” – an example of misinterpretation and misuse of genetics. Throughout the book the author’s own family members’ struggles with mental health is described in relation to genetics and mutations. We learn how neurologist Nancy Wexler’s mother and brothers succumbed to Huntington’s disease, making her determined to understand it. Her journey to a remote village in Venezuela that has a very high prevalence of the disease and eventual discovery of the gene that causes it, makes for fascinating reading. His description of Jesse Gelsinger’s failed gene therapy reads like a thriller. It is moving, poignant and a cautionary tale against rushing into treatments without proper checks. In all such descriptions, we can relate to the people involved, understand their motivations, be excited at their successes and disappointed at their failures.

The book is a striking blend of historical narration, science, and dramatic story-telling involving real and relatable people. I learnt facts that blew my mind; all humans can trace their mitochondria (which is inherited from the mother) to a single woman in Africa about two hundred thousand years ago! I learnt how worried scientists were with recombinant DNA technology; the Who’s Who of genetics met at a tense conference in Alisomar, California to discuss its ethics and come up with rules for safety. A special mention to the numerous footnotes – they are full of interesting tidbits for those looking for a bit more.

To sum up – an excellent read for those even vaguely interested in biology.