The post-genomic world needs a manifesto (Book Review)

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Book: The Gene — An Intimate History; Author: Siddhartha Mukherjee; Publisher: Penguin Random House Company; Pages: 545; Price not mentioned

Sample this:

“Genetics like any language is built out of basic elements — alphabet, vocabulary, syntax and grammar. The alphabet of genes has only four letters. These are the four bases of DNA — abbreviated as A,C,G and T.

“The vocabulary consists of the ‘triplet code’ — three bases of DNA — which, read together, encodes one amino acid in a protein (there are 20 amino acids in all). A protein is the ‘sentence’ encoded by the gene using alphabets strung together in a chain.

“The ‘regulator’ sequences appended to a gene that turn a gene on or off at certain times and in certain cells can be imagined as the internal grammar of the genome. These sequences might be likened to punctuation marks and annotation — inverted quotes, a coma, a capitalized letter,” and the language is complete.

With such metaphors and puns generously sprinkled across its 545 pages to explain the difficult concepts of genetics, you don’t need a degree in biology to read and appreciate “The Gene — An Intimate History,” by New Delhi-born Dr.Siddhartha Mukherjee, a cancer researcher at New York’s Columbia University and Pulitzer Prize-winning author of “The Emperor of All Maladies: A Biography of Cancer” (2010).

While practically trying to teach a whole course in genetics, the book, as its title says, “is a very personal story.” Mental illness had claimed Mukherjee’s two uncles on his father’s side, and his cousin is confined to a mental asylum in Kolkata. “The history of mental illness in the family and the heredity component that lurked behind it was cutting through my consciousness,” says Mukherjee. To give vent to his feelings he decided to tell the story of the gene.

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And the way the story unfolds in his skilled hands will tempt a reader to finish the book in one go. As Paul Berg, winner of the Nobel Prize in Chemistry, commented on the book, which is packed with all the famous names in genetics: “It is a magnificent synthesis of the science of life.” No doubt the science of biochemistry and cellular biology gets increasingly complex as you turn the pages but Mukherjee, adept with metaphors and writing in a journalistic style, can explain difficult genetic concepts with great clarity and simplicity.

The guided “gene tour” begins with Aristotle (350 BC), who argued that hereditary information is transmitted in the form of messages, and takes you to Darwin (1859) who theorized that humans descended from ape-like ancestors and then on to the Augustine monk, Gregor Johann Mendel. To understand heredity, Mendel (1865) bred mice in his room to produce hybrids and then switched his experiments to pea plants in the flower garden in his monastery. By studying the progeny produced by the crosses, he concluded that heredity could be easily explained by the passage of discreet pieces of information from parents to offspring. “He did not give this unit of heredity a name but he had discovered the essential features of a gene,” says Mukherjee.

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If heredity was transmitted as information, how was that information encoded and translated?

Answers to these and many more questions came from a string of post World War-II discoveries beginning with the identification of DNA, or deoxyribonucleic acid, as the carrier of genetic information, and the finding that DNA is actually made of two intertwined helical chains. “A double helix of DNA was thus envisioned as a code written with four alphabets forever entwined with its mirror image code,” explains Mukherjee. In their Nature paper in 1953 James Watson and Francis Crick wrote that DNA’s capacity to transmit information from cell to cell and organism to organism was buried in that double helix structure.

But how did that code become transcribed and translated into actual form and function of an organism? How did four bases — A, C, G and T — in a molecular string of DNA determine the hair colour and how could a sequence of DNA carry instructions to build a protein?

That was answered by subsequent discoveries that Mukherjee narrates like a detective story which runs like this: Genetic information in DNA first gets copied — transcribed in genetics parlance — into that of RNA (ribonucleic acid) molecules and these copies are used as “messengers” — a professional go-between — to build a protein.

Because none of the four bases (A,C,G and T) can singly carry the message to build any part of a protein, the precise sequence of three bases (triplet) is the code that carries the genetical information. One triplet in the RNA, codes one amino acid, the next triplet another, and so on thereby translating the RNA chain into a chain of amino acids leading to the construction of a protein. With this, the basic alphabet of the genetic code was complete in 1963.

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The explosive growth in genetics research that followed — creation of recombinant DNA and new techniques to clone and amplify genes — was on expected lines. In the 1980s, geneticists began using the techniques to map and identify genes linked to human diseases such as Huntington disease and cystic fibrosis, and genetic mutations were identified in cancer.

The climax came in June 2001 with the publication of the draft sequence of all the three billion base pairs in the entire human DNA — a culmination of the 10-year Human Genome Project, hailed by then US president Bill Clinton as “the most important map ever produced by human kind.” Mukherjee says “the sequence of human genome marked the starting point of the fourth phase of genetics — era of genomics.”

“If genes determine the nature and fate of an organism, and if organisms now begin to determine the nature and fate of their genes, the circle of logic closes on itself,” says Mukherjee. “We need a manifesto, or at least a hitchhiker’s guide, for a post genomic world.”

(17.05.2016 – K.S. Jayaraman is a veteran science journalist. He can be contacted at [email protected])



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