Jeff Hirsh Read: May 2021
Inspiration: How did CRISPR gene editing technology begin and evolve to its current state?
Summary
Written with the help of ChatGPT, below is a brief summary to understand what is covered in the book.
“A Crack in Creation”, published in 2017 by author, biochemist, and pioneer of CRISPR-Cas9 gene editing technology, discusses the potential and potential dangers of using CRISPR-Cas9 to edit the human genome. She explores the ethical and moral implications of using this technology to cure diseases, enhance human traits, and potentially even bring extinct species back to life. Doudna also delves into the history of CRISPR-Cas9 and the scientific discoveries that led to its development. Throughout the book, she advocates for responsible and cautious use of this powerful tool, and calls for a global conversation about its proper use.
Unedited Notes
Direct from my original book log, below are my unedited notes (abbreviations and misspellings included) to show how I take notes as I read.
DNA is deoxyribonucleic acid, dna carries instructions which transformed to proteins via rna (ribonucleic acid), dna AGCT vs rna AGCU (dna to rna to protein is the flow of genetic information), dna to rna transcription, rna to protein translation, genome size not predict complexity (salamander genome 10x human size), single change in dna letter change protein production and cause disease (substitution), insertion/deletion/inversion also cause disease, recombinant DNA is genetic code made in a lab not nature, homologous recombination = genes cluster together in a region and overlap not all over randomly, no longer need to use viruses to ram new DNA into genome–trick cell to think recombinant DNA is extra chromosome that needs pairing (leverage homologous recomb), needed to build endonuclease to cut DNA in specific place to then insert lab DNA as cell repair–original endonuclease was super specific in 1994 not broadly useful (protein enzyme), 1996 John Hop scientist use zinc finger nuclease to work and be redesigned as need but not good enough, truly useful technique first found 2009 called transcription activator-like effectors (TALEs)–kinda like ZFNs but each segment of TALE recongize 1 letter of DNA vs each ZFN finger was 3 letters–become TALEN (nuclease), TALENs upstaged by CRISPR, CRISPR = Clustered Regularly Interspaced Short Palindromic Repeats–in a specific region of a chromsome, regularly repeating sequences of dna interrupted after 30 letters then repeat and read same forward and back (very uniform repetition is unqiue in genome, CRISPR present is nearly all species so evolutionarily important–fights off viruses, in bacteria immune system, cas genes are separate but appear with CRISPR, crispr provides adaptive immunity—steals snippets of dna from phage dna during infection and splice bw crispr repeats to fight future virus, find RNA required for crispr, crispr RNA can work with RNA and DNA, crispr-cas9 system–use genetic instructions to produce cas9 protein, use crispir-derived rna guide molecule, and use synthetic dna replacement (target right part of genome, cut it, and replace sequence, RNA is guide and cas9 is weapon to destroy specific virus dna, guide RNA has 20-letter code to match 20-letter DNA code and need cas9 alongside, crispr facilitate gene knockouts/corrections/insertion/deletion, crispr can also act as dimmer for gene expression, can use to make healthier food (better storage, fewer toxins), crispr not insert foreign dna (simply alter protein production), can make disease resistant pigs, cows with no horns to save millions from trauma of dehorning (just switch a few dna letters), use cripsr for xenotransplantation (humanize pig organs so can use for transplants and avoid human immune response), editing somatic cells cannot be passed down (less controversy), editing germ cells more controversial but somatic editing harder to do, gene editing repairs mutated genes directly in genome vs therapy splices new healthy genes into genome, crispr easiest ex vivo (outside the living) with blood disease bc can remove and tranfuse back (tissue diseases harder to treat bc need in vivo and avoid immune response, using AAV virus as vector for in vivo crispr, cancer caused by mutations but cancer also causes more mutations so hard to pinpoint tumor cause, immunotherapy (use patients own immune system to fight cancer via T cells), manufacture T cells unique to patient’s cancer aka “adoptive cell transfer” ACT—T cells recognize cancer markers and fight, Dr. Huang in China 2015 test crispr on nonviable human embryos (3 sets of chromsomes)—not very effective and big ethical rejection despite experiment following rules and would be legal in US, genome editing added to 6 weapons of mass destruction, need to regulate germline edits (enhancement vs prevent disease), crispr is eugenic practice just as is prenatal vitamins, ultrasounds, anything to make “healthier child”, about choice, pdg test tell you outlook for IVF child before implanted
