This Book Enhanced How I Think About Life - The Gene

This Book Enhanced How I Think About Life - The Gene

This one of those books where I can feel brain swelling like a sponge against my skull as I turn each page.  It makes me feel smart.  The author, Siddhartha Mukherjee, crafts the narrative of our discovery of genetics through a series of page-turning stories, complete with heroes and villains, in a such a way that I wasn't reading non-fiction, but I was in the pea garden with Gregor Mendel and assembling the structure of DNA alongside Watson and Crick (and Franklin).

The keyword in the book's subtitle, intimate, is the operative word in understanding why I love this book so much.  In addition to making you feel smart and present for major discoveries, Mukherjee discusses the complex social implications that arose as our understanding of genetics grew.  Each time a groundbreaking discovery is made, Mukherjee swings the story to genetics' dark shadow, eugenics.

I was initially attracted to this book in 2018, when the Chinese scientist, He Jiankui, spontaneously announced to the world that he had crossed the line, and used CRISPR gene editing technology on human embryos to remove the CCR5 gene, which would confer resistance to HIV.  I was painfully unaware of just what he had done, and why the scientific community was upset with him.  Seems like getting rid of disease ought to be an overall good thing, right?  Since diving deeper into the story, I've been harboring a notion that the intersection of computer science with genetics will make our world a vastly different place in the next decade.  Gene editing is the next steam engine, the next personal computer, and therefore I ought to know a bit more about it.

The book begins with the stories of Charles Darwin's expedition on the HMS Beagle to the Galapagos islands where his observations led him to the theory of evolution, and Gregor Mendel's meticulous puttering-about in his pea garden to yield a discovery of dominant and recessive genes.  It's the contrast of the macro view of evolution with the micro view of inheritance.  Amazingly, in 1860, while much feather-ruffling was happening due to Darwin's theory, Mendel's discoveries went pretty much unnoticed until 1900 when 3 botanists simultaneously and unknowingly reproduce the results to his famous pea experiments.

We then discover how genes can be thought of like beads on a string as Thomas Hunt Morgan observes linkages in fruit fly phenotypes while studying a mutant white-eyed fly.  He observed that the gene for white eyes was sex-linked in that he only found it in males in subsequent generations.  His work led to validate the chromosomal theory of inheritance.

The story breaks to Darwin's cousin, Francis Galton, considered to be the father of eugenics.  He's the one who asks the question, "If we can breed better cattle and better wheat, why not better humans?"  Upon posing this question, the eugenics movement catches wind in America with Better Babies contests and the first involuntarily sterilization of Carrie Buck who had been diagnosed as feebleminded and an imbecile.  In 1927, the US Supreme Court ruled 8 to 1 that states can forcibly sterilize those who are "unfit to procreate".  Buck v. Bell triggered the event which eventually led to over 30,000 forced sterilizations in the United States.  Meanwhile, in a jail cell for treason on the other side of the world, Adolf Hitler intently reads publications by the American Eugenics Society as he writes Mein Kampf.  We all know where that ends.

And the discoveries keep coming.  James Watson and Francis Crick, aided by an Xray crystallography photograph taken by Rosalind Franklin, build the famous double-helical structure of DNA.  When the Nobel prize is announced, Ms. Franklin's name is not to be heard.

So we reach a point in the story where we now understand the opening chapters of a biology textbook, the basic principles of DNA and how it works, so the discovery shifts from scientific nature to that of engineering.

Synthetic insulin gets manufactured in a lab in Stanford by flailing venture capitalist Bob Swanson and scientist Herb Boyer.  Boyer is the first person to cut and paste a gene.  By splicing the insulin-producing gene into an E. Coli bacteria, he gives birth to genetic engineering and modernizes how insulin is made, no longer requiring thousands of fetal pig pancreases.  The two form a private company to sell it, Genentech.  Should one be able to patent a gene?

The race to sequence the entire human genome in the 1990's further highlights the question of who owns genetic discoveries.  It's a fierce competition between the private and public domain.  The Human Genome Project vs. Celera Inc.  Ultimately, a feeble truce is reached with a joint announcement brokered by Bill Clinton in 2000, but the promise of profit from genetic engineering spurs private industry to own parts of the genome and processes to manufacture drugs.

Mukherjee wraps many of these stories with real life examples of gene therapy, many still pending results.  Cystic Fibrosis, Spinal Muscular Atrophy, Sickle cell, Huntington's Disease, Down Syndrome, and Cancer are all featured.  He even includes an example from his own family, which carries a history of Schizophrenia.  It is in the context of these diseases that he provides very nuanced ways of thinking about the science of genetics.  I particular appreciated his 13 point manifesto at the end of the book where he says

What we read and write into our genome is our fallibilities, desires, and ambitions. It is human nature (p. 479).

In particular, I like how he guides the reader to think of illness not as a mutation from normalcy (in fact, mutation IS normalcy) but as a mismatch between genome and environment.

9. Every genetic “illness” is a mismatch between an organism’s genome and its environment. In some cases, the appropriate medical intervention to mitigate a disease might be to alter the environment to make it “fit” an organismal form (building alternative architectural realms for those with dwarfism; imagining alternative educational landscapes for children with autism). In other cases, conversely, it might mean changing genes to fit environments. In yet other cases, the match may be impossible to achieve: the severest forms of genetic illnesses, such as those caused by nonfunction of essential genes, are incompatible with all environments. It is a peculiar modern fallacy to imagine that the definitive solution to illness is to change nature—i.e., genes—when the environment is often more malleable. (p. 482)

The Gene is well worth the read, and a book that I will keep close by for reference.  The magic of this book is that it reads like a textbook turned upside-down.  Traditionally, if you I was to study genetics, the textbook would start me off with building blocks: nucleic acids, DNA, RNA, proteins.  Each chapter might have, tucked in at the end, a pleasantly skippable paragraph, before the multitude of homework problems, and surrounded with a blue border, that describes the person and the experiment behind a groundbreaking discovery.  Mukherjee flips that formula.  Each chapter is dedicated to the person and his or her wonderful experiment, complete with social and political context of the day as well as implications for the future.  Through this method, the reader is more strongly motivated to understand those building blocks and mechanism.  The Gene is some of the most fun I have had learning.