The Gene: An Intimate History

The Gene: An Intimate History elegantly traces the history of genetics. Inside is the story of the gene.

It all started with Mendel’s pea plants. Mendel: monk and scientist. In the 1850s, Mendel began experiments with hybrids. His experiments began to unfurl the keys of heredity: dominant trait and recessive trait, parent to offspring. One might imagine a fleeting thought entering Mendel’s mind: the idea of a courier of heredity—the gene. He published his results, full of groundbreaking discoveries ready to be found … but nobody looked.

But Mendel had planted the seed for genetics, and, slowly but surely, it grew. Others discovered his paper and the field began to grow like Mendel’s hybrid pea plants: gene, mutation, DNA, A-T and C-G, double-helix, replication, RNA, transcription, translation, protein. Scientists had soon found the essential function of the gene.

But how, scientists asked themselves, could an embryo give rise to life. How did gene know when to activate at the right times? The answer to this question lay in the genes itself: Even though every cell contains the same set of genes—an identical genome—the selective activation or repression of particular subsets of genes allows an individual cell to respond to its environments. The genome was an active blueprint—capable of deploying selected parts of its code at different times and in different circumstances. Proteins act as regulatory sensors, or master switches, in this process—turning on and turning off genes, or even combinations of genes, in a coordinate manner … Genes specified proteins that switched on genes that specified proteins that switched on genes—and so forth, all the way to the very first embryological cell. It was genes, all the way.

Genes were Regulated through proteins. We also learned that DNA Replicates to form new cells. It was now time to begin Recombining. A breakthrough was made when scientists figured a way to “cut and paste DNA.” With gene cloning, DNA from different organisms could be mixed and matched to create sequences that had never been found before. This would prove to be a crucial step in the merging of medicine and genetics.

So how could genetics be used in medicine? Imagine a disease. If the disease is linked to a polymorphism (a variant gene), call it VARIANT, individuals with the disease will have VARIANT. Using VARIANT as a marker, we could compare all the genes near the marker from a individuals with and without the disease. Through a technique pioneered Sanger, the individual base pairs could be read. Mutations in the gene of the individual with the disease could thus be found this way. This gene-mapping technique resulted in the finding of the gene responsible for Huntington’s disease.

Through genetics, we have found that human genes are strikingly similar between races. Dr. Mukherjee says of race: You can use genome to predict where X or Y came from. But, knowing where A or B came from, you can predict little about the person’s genome. Or: every genome carries a signature of an individual’s ancestry—but an individual’s racial ancestry predicts little about the person’s genome … The geneticist goes home happy; the racist returns empty-handed … In a society where black men and women experience routine, pervasive, and insidious discrimination, such a propensity could become fully self-reinforcing: black children do worse at tests because they’ve been told that they are worse at tests, which makes them perform badly in tests and furthers the idea that they are less intelligent—ad infinitum. (342–348)

Given that genes have the instructions of life, then what different are we from robots? But, on the contrary, identical twins inherit the same genome, but still wind down different paths in life. Epigenetics reveals the true drivers of our fate: Illnesses. Accidents. Traumas. Triggers. A missed train; a lost key; a suspended thought. Fluctuations in molecules that cause fluctuations in genes, resulting in slight alterations in forms.III Rounding a bend in Venice and falling into a canal. Falling in love. Randomness. Chance. Is that an infuriating answer? After decades of musing, have we reached the conclusion that fate is, well … fate? (389)

But how does our genome “remember” our experiences? In other words, why can experiences shape our fate? Once again, we looked to the genes. With proteins, our experiences are etched into are genome, like footnotes on the instruction of life. These “footnotes” are modified in response to different stimuli. But how these “footnotes” affect our genes has yet to be resolved.

A general question held by scientists was how humans could effectively alter our own genes. Then, the 2000s, scientists working on yogurt discovered that certain bacteria had developed a system to maim their long-time enemies (viruses): The bacterial defense system was soon found to involve at least two critical components. The first piece was the “seeker”—an RNA encoded in the bacterial genome that matched and recognized the DNA of the viruses. The principle for the recognition, yet again, was binding: the RNA “seeker” was able to find and recognize the DNA of an invading virus because it was a mirror image of that DNA—the yin to its yang … Once the viral DNA had been recognized and matched as foreign (by its reverse-image), a bacterial protein named Cas9 was deployed to deliver the lethal gash to the viral gene. (471)

We have now learned to replicate this technique, called CRISPR/Cas9, ourselves. Scientists have since learned to program it for specific purposes.

Since Mendel’s time, we have learned to program our genes. Through the Human Genome Project, we have also read our genome. The problems that now confront us our not physical, but moral. Now that we as humans know our instructions, the gene has become a powerful yet dangerous tool. One step out of line, and we modern civilization topples.

I was entranced by the skill with which Dr. Mukherjee presented scientific concepts. His words convey feelings and ideas with stunning detail. Dr. Mukherjee is truly a brilliant scientist and writer. In this superlative book, Dr. Mukherjee presents the knowledge found in textbooks while articulating a literary masterpiece.