It was medical necessity that brought genetics back into the human sphere after the disastrous experience with 1940s eugenics. Encountering patients with obviously inherited illnesses, Victor McKusick, a doctor from Johns Hopkins university, decided to catalog genetic diseases in humans. He founded the Moore Clinic at Johns Hopkins, where he had cataloged 2,239 genes linked with diseases in humans by the mid-1980s.

McKusick’s studies revealed four important ideas. One, mutations in a single gene could cause a disease affecting multiple organs. Two, the reverse was also possible, with many mutations influencing a single physiological function. Third, as geneticists before him had predicted, the presence of a gene did not mean it was expressed fully or at all in the physical organism. His fourth insight was the most critical: A mutation, McKusick described, is not a disease, but a variation. What is termed a “disease” is actually a mutation mismatched with its environment. For instance, a person born with dwarfism is not disabled, but lacking the right environment. This right environment can be provided with counselling and practical aids. McKusick’s approach to disease and disability was unique because it focused not on restoring so-called normalcy, but allowing a person to live their best life.

In 1966, the scientists Mark Steele and Roy Breg developed the technique of amniocentesis, where amniotic fluid could be extracted to test for genetic mutations in the embryo. If an embryo was found to possess a mutation associated with an impaired quality of life, such as Trisomy 18—where an extra copy of chromosome 18 drives multiple severe changes—the parent could choose to terminate the pregnancy.

The flip side of prenatal genetic testing was that it opened the grey area of selecting the “right” kind of babies. Scientists and doctors were quick to distance this new eugenics—termed “newgenics”—from the old bugbear of Nazi experiments. One major difference is that eugenicists like Galton focused on abstract qualities like intelligence, while late 20th-century doctors dealt in actual disease-causing mutations. Despite the reassurances, Mukherjee notes that the concept of newgenics “was riddled with some of the same fundamental flaws that cursed eugenics” (275), namely that it did not take into account the effects of environment, triggers, and variance.

While certain monogenic (arising from one gene or chromosome) conditions, such as Trisomy 18, do not show great variance, others like Trisomy 21, or Down’s Syndrome, do. Most individuals with Trisomy 21 deal with cognitive disabilities, but some go on to lead highly functional and independent lives. How can one determine which individual will show the most severe form of the condition? These questions grow even more complex when dealing with polygenic conditions that depend on the interplay between multiple genes, such as autism. McKusick also believed that applying genetics to human selection would lead to the “genetic-commercial” complex. These pertinent questions still hold true.

To know all the chromosomes and genes leading to genetic conditions, all mutations had to be discovered, gene by gene. The herculean task began with Kerry Kravitz and Mark Skolnick of the University of Utah studying hemochromatosis in a population of Mormons. Hemochromatosis is a rare genetic disease in which the body absorbs too much iron through the intestines, slowly choking with iron deposits. Since genes are coordinate on a chromosome, Kravitz and Skolnick thought of locating the hemochromatosis gene through possible links. Serendipitously, they found an immune response gene with a known location occurring with the hemochromatosis gene, and could thus locate the gene for the disease to the same chromosome.

Meanwhile, geneticists David Bolstein and Ron Davis—who had first discovered DNA polymorphism in 1970—realized minute variations (polymorphisms) in the DNA could act as genetic signposts to help map genes. As Bolstein, Davis, Skolnick, and geneticist Ray White presented their ideas, they caught the eye of psychologist Nancy Wexler.

Wexler had a personal interest in mapping the genome as in 1968, her mother Leonore had been diagnosed with Huntington’s Disease, a devastating condition that does not manifest itself till an individual’s 30s or 40s. Characterized by inadvertent shaking so abrupt it resembles a dance, the neurological illness ultimately leads to cognitive decline and malnourishment. After Leonore died in 1979, Wexler visited Barranquitas and Lagunetas, two Venezuelan villages with a high prevalence of Huntington’s Disease, collected blood samples from the population and sent them to a lab. The lab work found a single piece of variant DNA (the signpost) occurring in several samples, and located it to chromosome four. The gene for Huntington’s had been mapped.

Davis, Bolstein, and Skolnick’s technique for mapping genes was also used to locate the gene for cystic fibrosis, a common mutation in which the body is unable to move chloride (a component of salt) across membranes, leading to excessive sweating, impaired lungs, and other devastating symptoms. Since the CF gene was mapped, the combination of prenatal screening and in utero tests has led to disease incidence falling by 30 to 40% in high-risk populations, highlighting the transformative impact of mapping genes.

Even though the popular press celebrated the gradual mapping of crucial genes, scientists and patients worried about the slow pace of the “gene by gene” process. James Watson, and worm scientist John Suston, were among the most vocal critics of the pace of the current gene-mapping project. Watson wanted the entire genome to be sequenced. This “normal” genome could act as a template to detect mutations, and would also serve as a guide to locate novel genes in the future.

Two other drivers were pushing the sequencing of the entire genome, the first being the need to plan medical therapies for polygenic diseases. Polygenic conditions—like autism, or the NPH which Mukherjee’s father had—cannot be understood through the action of a single gene, but through the interplay of multiple genes. The greatest example of a polygenic disease threatening humans is cancer.

The second driver was the misguided panic around mental illnesses, such as schizophrenia, thought to be linked with crime in the 1980s. As it became clear mental illnesses had a genetic component, the clamor to understand the genes behind mental illnesses rose, on the assumption that this would curb both mental illness and the crime associated with it.

Driven by urgency, the search for the human genome diverged along two lines: Teams of scientists would work, in parallel, on the genomes of simpler organisms, such as the fly, and on the human genome. Each project would be named for the organism, such as the Fruit Fly Genome Project, and the Human Genome Project.

Mukherjee pauses to return to Carrie Buck, the young woman sterilized in Virginia. Buck died at 76 in 1983. Though she had been declared mentally unfit, she returned to work three years after her sterilization. Her daughter, Vivian, who had also been declared an “imbecile,” died in childhood, but not before receiving A’s and B’s in Grade 1.

Right before the Human Genome Project kicked off, Craig Venter, a little-known neurologist at NIH (the National institute of Health, one of the backers of the project), came up with a shortcut to genome sequencing. Venter’s strategy relied on intergenic DNA or filler DNA, as well as introns, which are spacers between genes themselves. Neither intergenic DNA nor introns code proteins. Venter’s epiphany was to focus on sequencing only the protein-coding parts of DNA. In fact, he proposed to shorten the process even more by sequencing only fragments of even the protein-coding parts. The fragments would then be extrapolated to decipher the whole.

Watson was appalled at what he considered a shoddy, incomplete scientific approach. The conflict between Watson and Venter deepened and in 1992, Venter left the NIH to launch his private institute, The Institute for Genomic Research or TIGR. Soon, Venter parted ways with TIGR as well, founding Celera. Venter’s plan to sequence a genome involved shattering the genome of the Hemophilus Influenzae bacteria into a million pieces using a shotgun-like tool, sequencing fragments at random, and feeding them to a computer so it could generate the bacterial genome by connecting the overlapping sequences.

Meanwhile, the Human Genome Project proceeded with a more systematic approach: Assembling genomic fragments, cloning them to confirm identity and overlaps, and locating them as if in a map. As Celera sequenced Hemophilus, the Worm Genome Project successfully used the cloning approach to generate the genomic sequence of the worm C. elegans. The C. elegans genome also threw a surprise discovery: Genes did not just encode proteins, they also encoded micro-RNAs. 

With successes piling up for both Celera and the Human Genome Project, the race for the human genome accelerated. The rivalry became so intense that President Bill Clinton had to direct the Department of Energy to intervene to prevent a public controversy. Venter and Francis Collins—Watson’s successor at the Genome Project—agreed to reveal their advances on the human genome jointly at the White House. In 2001, both Celera and the Human Genome Project separately published the genomic sequence of a human being.

Structured as 23 points, after the 23 pairs of chromosomes in the human genome, this chapter provides vital facts and insights about human genetics and environment. One of these facts is that if the genome were to be published as a book (the book of man) in standard-size font, the book would run to a whopping 1.5 million pages. Another is that the number of genes does not positively corelate to a more advanced life-form. For instance, corn has 12,000 genes more than the 20,687 genes in humans. It is the “sophistication of gene networks” that determined the “difference between ‘human’ and ‘breakfast cereal’” (322).

Mukherjee draws attention to the dynamic nature of the human genome, reshuffling sequences in cells to constantly create novel variants. This is seen especially in the case of antibodies, the missile-like proteins that attach to pathogens. As pathogens evolve, human antibodies too shuffle their sequence to adapt. The genome is also filled with mysteries and puzzles, such as the fact that genes form only 2% of the genomic map, the rest being intergenic DNA and introns. Another mystery is that it has repeated elements that appear frequently for a reason yet unknown, such as a 300-base-pair-sequence called Alu which keeps cropping up at random intervals.

Though humans understand the genetic code, Mukherjee reveals that “we comprehend virtually nothing of the genomic code” (325) which governs how multiple genes coordinate to build and maintain a human being. Finally, the genome is resilient, unique, and “designed to survive” (326).