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Books by Lee Tang
Part One - The Tool
1. The Quest for a Cure
2. A New Defense
3. Cracking the Code
4. Command and Control
Part Two - The Task
5. The CRISPR Menagerie
6. To Heal the Sick
7. The Reckoning
8. What Lies Ahead
About the Author
Summary &Study Guide
Gene Editing and the Unthinkable Power to Control Evolution
Title: Summary & Study Guide - A Crack in Creation
Subtitle: Gene Editing and the Unthinkable Power to Control Evolution
Author: Lee Tang
Publisher: LMT Press (lmtpress.wordpress.com)
Copyright © 2017 by Lee Tang
All rights reserved. Aside from brief quotations for media coverage and reviews, no part of this book may be reproduced or distributed in any form without the author’s permission. Thank you for supporting authors and a diverse, creative culture by purchasing this book and complying with copyright laws.
First Edition: August 2017
Issued in print and electronic formats.
ISBN 9780995943162 (ebook)
ISBN-13: 9781974123100 (paperback)
ISBN-10: 1974123103 (paperback)
Limit of Liability/Disclaimer of Warranty: The publisher and author make no representations or warranties regarding the accuracy or completeness of these contents and disclaim all warranties such as warranties of fitness for a particular purpose. The website addresses in the book were correct at the time going to print. However, the publisher and author are not responsible for the content of third-party websites, which are subject to change.
To my wife, Lillian, who is the source of energy and love for everything I do, and to Andrew and Amanda: watching you grow up has been a privilege.
For a complete list of books by Lee Tang and information about the author, visit https://lmtpress.wordpress.com.
“A Crack in Creation” by Jennifer A. Doudna and Samuel H. Sternberg
The book tells the story of CRISPR and “gene-editing.” CRISPR is a cutting-edge gene-editing technology that mimics what happens naturally in bacteria. It enables scientists to “play god” with plant or animal DNA, with unlimited power and peril.
The technology of gene editing is the most important advance in our era. The possibility of forever altering the genetic composition of humankind is frightening. Yet we can’t overlook the opportunities that may lead to inventions for cures of HIV, debilitating genetic diseases, and cancers, and end food shortages.
The book will demystify this exciting area of science and inspire you to seek answers to tough moral and ethical questions on the use of this technology.
Jennifer A. Doudna is a Professor of Chemistry and of Molecular and Cell Biology at the University of California, Berkeley. She is a leading figure in the "CRISPR Revolution" for her early fundamental work and ongoing leadership in developing the CRISPR gene-editing technology.
Samuel H. Sternberg is a CRISP expert and a Scientist and Group Leader of Technology Development at Caribou Biosciences, Inc.
Important Note About This Study Guide
This guide is a summary and not a critique or a review of the book. It does not offer judgment or opinion on the content of the book. This summary may not be organized chapter-wise but is an overview of the main ideas, viewpoints, and arguments from the book. It is NOT meant to be read as a replacement of the book which it summarizes but, instead, a supplement for review of the book's main premises and to provide commentary and additional resources.
For billions of years, life on earth progressed according to Darwin's theory of evolution. Up to now, human has had limited success to transform nature through the selective breeding of plants and animals because the DNA mutations making up the genetic variations were still generated spontaneously and randomly.
Today, scientists have brought this process of evolution under human control. With a powerful gene-editing tool like CRISPR, scientists can change the genetic code in the genome of any living organism. With CRISPR, changing a genetic code in the genome is as simple as editing a text document.
CRISPR has been used by geneticists to create genetically enhanced versions of animals and plants. It has transformed every genetic disease into a potentially treatable target. In laboratories, researchers have used CRISPR to correct the DNA mistakes that cause Duchenne muscular dystrophy. They have also rearranged over half a million letters of DNA inverted in the genomes of patients with hemophilia anemia. Although we still have a long way to go before CRISPR-based therapies will be widely available to treat human diseases, their potential is clear.
But the CRISPR technology has other profound implications. Scientists could use it to change the genome of the human species in ways that are heritable, forever altering the genetic composition of humankind. This forces us to grapple with where to draw the line when manipulating human genetics. Some call for an outright ban on editing the genomes of unborn humans, but others ask scientists to forge ahead without restraint.
In Part One of this book, the authors share the story of the CRISP technology, including how it began with the study of a bacterial immune system. In Part Two, the authors explore a large number of CRISP applications and discuss the opportunities and challenges that lie ahead.
THE QUEST FOR A CURE
Since the 1960s, researchers at the National Institution of Health (NIH) have been studying a rare hereditary disease known as WHIM syndrome, a painful immunodeficiency disease caused by a single letter mutation in the DNA. Kim, known as WHIM-09 to the NIH researchers, had been diagnosed with the disease since birth and hospitalized multiple times with serious infections caused by the disease. In 2013, Kim presented with her two daughters to the staff at NIH for her follow up study. The two daughters, both in their early twenties, had classic signs of the disease, but Kim herself seemed fine.
After running a battery of tests, the NIH scientists slowly put together an explanation for Kim's cure. They concluded that a single cell in her body must have experienced an uncommon phenomenon known as chromothripsis. Chromothripsis is a phenomenon in which a chromosome suddenly shatters and is then repaired, resulting in a massive rearrangement of the genes. This rearrangement of DNA letters within the chromosome can cause both cancer and congenital diseases. But in Kim's case, the rearranged chromosome had rid of the diseased copy of CXCR4, the gene causing WHIM syndrome. That fortunate cell was a hematopoietic stem cell, which had passed along its rearranged chromosome to all its daughter cells, repopulating Kim's entire immune system with healthy new white cells free of the CXCR4 mutation. This chain of events had wiped out the disease that Kim had since birth.
The odds of being spontaneously cured of a genetic disease by natural gene editing are small, like winning the genetic lottery. Kim's case is the only reported case of a patient being cured by spontaneous chromosome shattering and repairing. But cases exist where a genetic disease was partially or completely cured because the patients' cells had corrected the disease-causing mutation in the genome. These cases show the power and promise of natural gene editing. They also shed lights on a potential avenue of medical intervention: to cure genetic disease by rationally and deliberately correcting the misspellings in the genome. To make this possible, researchers must understand the genome itself; what it is, and how it could be modified and manipulated.
The genome is the entire set of genetic instructions found inside a cell. It comprises molecules called deoxyribonucleic acid, or DNA, constructed of just four nucleotides, A, G, C, and T, shorthand for the chemical groups of adenine, guanine, cytosine, and thymine. The letters of these molecules are connected in long single strands. Two of these strands come together to form the famous double-helix structure of the DNA.
The most important role of the double helix structure is to pass the genetic information along to the two daughter cells upon cell division. Shortly before cell division, the two strands of the double helix are separated by an enzyme. Then each of the two strands acts as a template for its matching pair, resulting in two exact copies of the original double helix.
Each specific sequence of letters in the DNA provides instructions to manufacture a particular protein that carries out specific functions in the body. To transform the instructions in the DNA into protein, cells use an intermediary molecule called ribonucleic acid, or RNA, produced from the DNA template via a process called transcription. RNA has three of the same letters as DNA, but in RNA, the letter T (for thymine) is replaced by the letter U (for uracil). RNA is the messenger, sending the DNA instructions from the nucleus where the DNA lives to the outer regions of the cell where proteins are manufactured by a process called translation. The translation process translates every three letters of RNA into one amino acid, so the sequence of letters in the RNA is translated to a chain of amino acids making up the specific protein.
The size of a genome and the number of genes it contains differ across different species. Viruses have just a few thousand letters of DNA and a few genes. The human genome comprises 3.2 billion letters of DNA, with around 21,000 genes, the same size as a mouse genome, but ten times smaller than the salamander genome.
Different species package their genomes in different ways. Most bacterial genomes exist inside the cell as a single continuous piece of DNA. The human genome comprises twenty-three distinct pieces, called chromosomes. Human cells contain two copies of each chromosome, one from the father, and the other from the mother. Each parent contributes twenty-three chromosomes, which gives the offspring forty-six chromosomes. (Exception to this rule: individuals with Down syndrome