A Guided Tour

Siddhartha Mukherjee won the Pulitzer Prize for his New York Times bestseller The Emperor of All Maladies – the source material for the eponymous Ken Burns documentary. Mukherjee writes about medical science with greater clarity. He weaves a fascinating history of hereditary science and genetic discovery while explicating three broad themes: the interplay of genes and the environment on each person’s phenotype; the marvels that genetics delivers to the medical field; and the real and potential dangers of genetic engineering. Mukherjee writes with brilliance and verve to bring this seemingly arcane world alive.

Genome

Genes recombine and can mutate when the chromosomes of parents mix. A person’s genome doesn’t determine his or her phenotype. You are who you are based on a broad and complex mix of genes plus environmental factors, certain triggers and dumb luck.

Genotype plus environment plus triggers plus chance equals phenotype. Siddhartha Mukherjee

A subdiscipline of genetics, epigenetics, arose in the 1950s to address the effects of environment on genes. Studies of identical twins with identical genomes but raised apart, show that genes account for only about half of a person’s development.

Sexual Identity

Sexual determination boils down to one gene on a shrunken chromosome that makes a person male or, in its absence, female. Maleness and femaleness exist on a continuum in everyone. The decades-long search for a gay gene in the 1980s proved fruitless. A person’s sexual identity doesn’t change with counseling, with training or by physically altering sexual organs or injecting hormones.

When environments are constraining, they exert a disproportionate influence. When the constraints are removed, genes become ascendant. Siddhartha Mukherjee

Genes predispose a person to many things; overt or subtle combinations of environment and life experiences determine which genes manifest themselves; that is, nature plus nurture.

Gene Mapping

In 1989, the US National Institutes of Health and the US Department of Energy put James Watson at the head of a multibillion-dollar project to map the human genome. Begun in 1989, the endeavor turned into a race between two teams. Watson led the favored team, which had government financing. Renegade scientist Craig Venter led the underdog team, which enjoyed private funding and embraced methods that left conservative scientists aghast. For more than a decade, the teams raced neck and neck, crossing the finish line in a dead heat in 2001, both sharing in the momentous achievement of mapping the entire human genome.

Race and the Genome

This mapping shows that everyone on Earth likely evolved from Mitochondrial Eve, a woman who lived in Southern Africa about 200,000 years ago.

The genetic diversity within any racial group dominates the diversity between racial groups – not marginally, but by an enormous amount. Siddhartha Mukherjee

The differences within races so greatly exceed those between races that classification of people by race proves a useless differentiator.

Recombinant DNA

Genetic manipulation is the editing or introduction of a certain gene or genes to fundamentally alter a human being.

Darwin’s cousin Francis Galton recognized the possibilities for engineering improved people, a process he called “eugenics.” Galton’s work inspired a chilling movement, particularly in the United States, where, in the first decades of the 20th century, eugenics became official policy. Eight states legalized or required sterilization of people considered mentally or physically inferior. In 1927, Justice Oliver Wendell Holmes wrote for the majority in a US Supreme Court decision in favor of sterilizing “imbeciles.” Eugenics spread to Europe and led to twisted Nazi genetic experiments.

The genetic code is simple: DNA is used to build RNA, and RNA is used to…build a protein. Siddhartha Mukherjee

The discovery of DNA added fuel to dreams of genetic engineering. In the early 1970s, Paul Berg of Stanford University inserted a gene into a virus and then into other cells. He used viruses to combine DNA from different sources – recombinant DNA. His process mimicked reproduction – the mixing of paternal and maternal chromosomes. In 1973, Herb Boyer and Stanley Cohen spliced bacteria to combine two foreign DNA sequences into an entirely new life form – the first created by humans.

Empathy, altruism, sense of equity, love, trust, music, economic behavior and even politics are partially hardwired.psychologist Thomas Bouchard

These breakthroughs in gene manipulation and sequencing changed biology and genetics. Researchers could recombine and clone genes in endless experimentation. A pivotal conference brought together many of the world’s top biologists and geneticists in 1975 to discuss what restrictions, if any, should be placed on the science. After realizing the dire legal liabilities and the existential threat to labs and universities should any incident occur, the group agreed to strict self-regulation.

Boyer’s company, Genentech, patented processes in recombinant DNA and genetic cloning that made him and his partners wealthy. Boyer developed synthetic production of insulin and later the blood-clotting factor VIII. Boyer and his team cracked the code for producing proteins synthetically by cloning genes – one of the greatest breakthroughs in medical history that enabled the production of limitless new medicines.

Parents can use gene therapy and screening to decide whether to abort a fetus carrying genes likely to produce debilitating conditions.

A combination of stem cell technologies, nuclear transfer and epigenetic modulation, and gene-editing methods has made it conceivable that the human genome can be broadly manipulated and that transgenic humans can be created. Siddhartha Mukherjee

Genetic engineering based on embryonic stem cells stands on the verge of enabling eugenics. Gene-editing enables efficient, precise and scalable alteration of the human genome. Only ethics and laws stand between science and a “post-human” world.

Passionate Detail

Mukherjee balances scientific arcana – at times perhaps a bit too much of it for the layperson – and the human drama behind scientific breakthroughs and their impacts on humans, medicine and culture. He dissects culture and politics with the intense gaze and enthusiasm he applies to medicine and science. This is an immersing work that you may prefer, given that intensity, to read in segments. However, Mukherjee’s original voice, meticulous research and rare ability to turn hard science into a compelling story make this an accessible, illuminating genetics manual for everyone. 

Siddhartha Mukherjee also wrote The Emperor of All Maladies; The Laws of Medicine; and The Song of the Cell. Other worthy works on genetics include Walter Isaacson’s The Code Breaker; and Jennifer A. Doudna and Samuel H. Sternberg’s A Crack in Creation.