The Gene读后感第一篇
mark一下，读到了希特勒的部分，残酷地快要读不下去了。第一次知道纳粹种族清洗竟然还有所谓的理论基础: Eugenics. 可笑，可叹，可耻，可悲！ 自然科学因此蒙羞。一切的最开始是无辜的被诊断有先天性缺陷的孩子们被送进毒气办公室处死啊！我想知道这一切的疯狂如何平息，这一切非理性的applied biology怎样回归理性。更加坚信所谓的理性不能独立存在，必须要有人跳出来，从人性的角度质疑现有的理性，才能不断趋近真实的理性吧。
The Gene读后感第二篇
第5本。
相对于物理和数学，到目前为止人类对生物科学的了解太少了。
与物理、化学、数学等其他领域不同，这些领域往往就是数十个大牛人就搞定了一切；然而生物科学领域的科学家太多，各自的贡献太杂，作者能写道这个程度，也算尽力了.....................
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The Gene读后感第三篇
早上9点，公司打卡。接着是每天例行15分钟的早会，每天不同主题，周一所谓“正能量”分享（公司企业文化？），周二同事分享一篇cell上的论文，周三我来分享一种遗传病...... 开完会，我坐到我的办公桌前，打开电脑开始我的工作——阅读疑似罕见遗传病患者的基因测序数据，找出致病变异，然后撰写一份检测解读报告。
换句话说，我的工作就是阅读和评论，只不过不是读别人写的书，而是读每个人的生命之书。当然，其实也没有听上去那么“高大上”。我们能读到的也只是基因测序能发现的部分变异位点以及根据现有科学进展（也就是文献和数据库）给它们加上的注解。所有的科学研究才是真正的读者（Reader），或者说翻译，把基因组这“天书”翻译成我们能理解的意思。而我们所做的也只是去评论（Review）原文和注解（原文若是AGCTCTCC...的序列，注解便是科学家告诉你“BRCA1基因上的功能缺失变异可以导致乳腺癌”）。
这份工作，多数时候是繁杂无趣。全基因组或全外显子组的测序产生了太多的数据和注解，文献和资料。多数都——至少罕见病临床诊断的角度来说——还未能有实际意义。可虽然单调，但当真遇见了可以解释患者疾病——表型异常——的致病突变的时候，仍免不了惊喜激动。
Siddhartha Mukherjee的《基因传——一段亲密史》讲述了人类从古希腊的理论到达尔文、孟德尔再到人类基因组计划等，如何一步步发现并”阅读“基因，同时又有如何一步步尝试去修改或”书写“基因的故事。虽然作者引人入胜地讲述了一个又一个伟大科学发现，但是这本书的主角不是那些我们熟悉或不熟悉的科学家，而是基因，这个早已存在的主角。若有一个关于地球生命的故事，那也许基因才是唯一的主角。正如Richard Dawkins在《自私的基因》中所言：“ There is really only one entity whose point of view matters in evolution, and that entity is the selfish gene."
相比于基因本身的古老，若从达尔文以及孟德尔的19世纪中叶开始算的话，人类认知“基因”的历史实在短得可怜，但这并不妨碍我们认为我们可以揭示并掌控他。从20世纪上半叶的德国纳粹的种族清洗和各种国家层面的优生学，到如今遍地开花的23andme（个人消费者基因检测）和基因编辑技术研究，也许我们从来都不会满足现状，学不会“知天命”（若基因真是我们的“天命”，我们不也正是在不断”知天命“吗？谁又能说这些人类行为的动机，不是早已写在我们的基因里了呢？），当然，现在的个人基因检测和产前筛查不能也不应该和当年的纳粹暴行进行比较。可藏在我们内心的欲望也许是一样的：我们渴望健康和正常（Normalcy）；厌恶疾病和异常（Abnormalcy）。只不过在希特勒那里，所谓的“雅利安”是正常，犹太人是异常。而今天，我们认为我们是正常，而自闭症儿童是异常。其实，无论哪一种认知都是是短浅的。因为正如作者引用Victor McKusick（我的“OMIM老爹”）的理解：“一个突变，只不过是一个统计学实体，而非病理性的或道德层面的。一个变异突变并不意味着疾病，也不特指一个功能的获得或丧失。一个突变只是偏离了正态——也就是所谓的’野生型‘而已。“ 而疾病也只不过是由于个人基因变异和他生存环境之间的不协调导致的特定障碍，换句话说，变异并不导致疾病，这种基因-环境（先天-后天）的错配导致了疾病（p264）。
工作了快一年，同事也是来来去去，有的工作了不到半年，就已去另谋他处。看他朋友圈，已经在转发另一家测序公司的宝宝天赋基因的检测业务。现在这种所谓天赋基因的检测有不少，但真让人怀疑这到底有什么意义。诚然，对于单基因遗传病的诊断来说，现阶段的基因检测是有一定意义的，那是因为对于那些疾病表型，我们可以取很狭窄的定义。而对于所谓的聪慧、美丽这些过于宽泛定义的表型，我想基因检测不能说是无能为力的，但只是它是不全面的，如今的这些业务，也只能说是一种浮夸的科学坑蒙拐骗。正如作者所言：“如果我们定义‘美丽’是有且仅有蓝眼睛，那我们确实能够找到‘美丽基因，如果我们定义‘聪慧’ 是仅通过一种测试方法，那我们也许确实能发现’聪慧基因‘。基因组成了人类想象力宽窄的镜子，这只不过是人类的自恋。（p481）“
工作中另一项非常重要任务，便是通过遵循内部SOP变异评级指南或所谓学业界认可的ACMG guideline （American College of Medical Genetics and Genomics美国医学遗传学&基因组学学会）对发现的变异进行致病性评级，分为5级，也就是良性、疑似良性、临床意义不明、疑似致病和致病变异。而评级所基于的证据包括变异类型、文献案例报道，等位基因人群频率（看是否偏离了正态。）还有计算机预测等。这个工作，英文被叫做variant curation，变异管理（我知道图书馆馆长叫curator，又是一个书的类比。）。这个工作让我想起了作者多处关于镜子的比喻，也许我的工作也只是通过一面镜子来阅读基因，这面镜子便是所有科学研究加在基因和变异上的注释，我们通过阅读其他人有或没有这个变异，来理解眼下患者的变异致病性。我想，可能有一些真实是我们错过了的。
本书时间线止于2015年，接着便是开放式省略号了（历史还在持续），2016年我毕业开始工作，这是奇妙的一年，是我自己与基因持续邂逅的一年，一方面，工作上我开始读很多人的基因（变异），仿佛有一种窥探他人”天命“的感觉（至少是遗传疾病方面），另一方面自己又能有幸遇见这本书，从而可以对基因以及人类认知基因的历史，有一个更线性的了解和梳理。这是一部关于基因的历史，它看似宏伟。但的确，基因史就是一部亲密史，因为每一个人自己的历史，正是从每一个人基因之书开始书写的，我们接着润色台词，给自己加戏，但是这些，导演都看在眼里。
下午5点半，我关上电脑准备下班，这个患者的检测报告还没写完，患者是一名精神发育迟缓的儿童，伴多发畸形。我始终找不到能够解释患者表型的致病变异，临床意义不明的也没有几个，我很沮丧，但也感到无能为力。
The Gene读后感第四篇
对于一个外行人，真是大开眼界。以下是有关知识类的摘录，主要是知道了基因科学发展史里的who's who。以后可以经常复习。
Part One: The “Missing Science of Heredity” 1865–1935
Note - “A Certain Mendel” > Page 59 · Location 1130
De Vries, Independently discovered Mendel's findings 30 years later, but deliberately neglected any mention of Mendel
Part Two: “In the Sum of the Parts, There Are Only the Parts” 1930–1970
Note - “Abhed” > Page 92 · Location 1684
Thomas Hunt Morgan, study mutations in fruit flies and discovered that genes are physically linked to each other, thus also linking the field of cell biology with genetics. "beads on a string". Up until that time, the gene was only considered a 'purely theortical unit'.
Note - “Abhed” > Page 94 · Location 1725
Herman Muller, student of morgan, created first man-made mutations by exposing flies to x-rays. Later move to Nazi Germany and Soviet Union. Proving yet again that genes are of material form (Griffith's discovery). He also thought about the implications of his discovery for eugnenics.
Note - “Abhed” > Page 98 · Location 1803
Hemophilia, 血友病, the "love for blood", a disease caused by a single gene mutation that prevents clotting of blood, so a small wound can accelerate into lethal bleeding crisis. It was run through the family line of Queen Victoria, and the the Russian czarevitch Alexei. Hemophillia later played a role in genetic synthesis and the history of AIDS. Many of the hemophilia patients were treated with HIV-contaminated Factor VIII. Genentech later developed synthetic Factor VIII.
Note - Truths and Reconciliations > Page 103 · Location 1868
Ronald Fisher, the mathematician, explains the "smoothness" of the living world is caused by a combination of genes, and argues against that genes are discrete particles of information. If you mixed the effects of three to five variant genes on any trait, you could generate nearly perfect continuity in phenotype.
Note - Truths and Reconciliations > Page 105 · Location 1912
Theodosius Dobzhansky, combines evolution with genetics, combines Mendel with Darwin (the "Grand Synthesis"), argues that natural selection works through genetic mutations, and that genotype + environment + triggers + chance = phenotype.
Note - Transformation > Page 112 · Location 2046
Frederick Griffith, proves that genes are material, chemical units that carried information. Even Morgan had no idea what his description of genes as "beads on a string" mean in material form
Note - “That Stupid Molecule” > Page 133 · Location 2408
Oswald Avery, discovered gene's molecular chemical nature: DNA
Note - “Important Biological Objects Come in Pairs” > Page 143 · Location 2582
Linus Pauling (1954 nobel chemistry) and Robert Corey, found the technique to take X-rays of proteins through crystallization. Linus Pauling also made the first linking between proteins and a disease, by linking sickle-cell amnesia with loss of hemoglobin B.
Note - “Important Biological Objects Come in Pairs” > Page 159 · Location 2878
DNA double helix structure was discovered by a joint effort involving James Watson, Francis Crick, Maurice Wilkins (1962 nobel) and Rosalind Franklin (who died before Nobel)
Note - “That Damned, Elusive Pimpernel” > Page 161 · Location 2920
Beadle and Tatum, 1958 nobel laureates. students of Thomas Morgan, proposes that genes find their expression through encoding of proteins. Using a "missing ingredient" experiment by cultivating mutant bacteria in minimal medium, they found that every mutant bacteria that couldn't grow was missing a single metabolic function, corresponding to the activity of a single protein enzyme, and genetic crosses revealed that every mutant was defective in only one gene.
Note - “That Damned, Elusive Pimpernel” > Page 164 · Location 2975
Jacque Monod and Fracois Jacob, 1965 nobel, discovered the role of RNA on regulation of genes, and that every gene had specific regulatory DNA sequences appended to it that acted like recognition tags.
Note - “That Damned, Elusive Pimpernel” > Page 168 · Location 3031
Marshall Nirenberg, Heinrich Matthaei and Philip Leder mapped each amino acid to each DNA triplet (three pairs of bases), deciphering the code of DNA alphabet.
Note - “That Damned, Elusive Pimpernel” > Page 169 · Location 3043
Central Dogma: DNA -> RNA -> genes
Note - “That Damned, Elusive Pimpernel” > Page 170 · Location 3050
Sickle cell amnesia, a one-gene, one-amino acid disease, where blood cells morphed into shriveld, scythe-shaped cresents
Note - Regulation, Replication, Recombination > Page 177 · Location 3184
Pa-Ja-Mo paper, the classic paper written by Pardee, Francois Jacob and Jacques Monod, discovered the regulatory mechanism for genes, pointing out that it's proteins that interacts with regulatory tags on genes to turn genes on and off. "To a geneticist, the development of an organism could be described as the sequential induction (or repression) of genes and genetic circuits. 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. "
Note - Regulation, Replication, Recombination > Page 180 · Location 3221
Arthur Kornberg, found the DNA polymerase, the DNA-copying enzyme
Note - Regulation, Replication, Recombination > Page 183 · Location 3289
anatomists, study "what", include Mendel, Morgan, Muller, Avery, Griffith, Watson and Crick. physiologists study how, include Fisher, Dobzhansky, Beadle, Tatum, Monod and Jacob.
Note - From Genes to Genesis > Page 186 · Location 3350
Ed Lewis, found "build a thorax", "build an arm", master-regulatory gene in embryos, that regulates genes that build each body parts and segments
Note - From Genes to Genesis > Page 188 · Location 3380
Christiane Nusslein-Volhard and Eric Wieschaus, found the mechanism thats determines basic orientation and master-structures of in an embryo, activates the "mapmaker" genes
Note - From Genes to Genesis > Page 191 · Location 3432
Sydney Brenner, 2002 nobel, studied a 1-millimeter worm C.elegans, and help solve the puzzle of cell-fate determination. He also discovered necessity of RNA for proteins with Francois Jacob.
Part Three: “The Dreams of Geneticists” 1970–2001
Note - “Crossing Over” > Page 203 · Location 3627
Paul Berg, 1980 nobel, creates first recombinant genes using SV40 virus.
Note - “Crossing Over” > Page 208 · Location 3719
Janet Mertz, inverted Paul Berg's recombinant gene operation by introducing SV40 virus into E.coli gene, enabling mass production of recombinant gene. She also made the process vastly more efficient.
Note - “Crossing Over” > Page 211 · Location 3768
Herb Boyer, supplied DNA-cuttng enzyme to Janet Mertz. Co-founder of Genentech. Along with Stanley N. Cohen, he discovered a method to coax bacteria into producing foreign proteins, thereby jump starting the field of genetic engineering. Filed the US Patent 4,237,224, Process for Producing Biologically Functional Molecular Chimeras”,
Note - The New Music > Page 216 · Location 3858
Frederick Sanger, solved the sequence of insulin in earlin 1950s using conventional disintegration method, and won 1958 chemistry nobel prize. Later became the first person to sequence a DNA and won another nobel prize in 1980.
Note - The New Music > Page 219 · Location 3904
Richard Roberts and Phillip Sharp, independently discovered introns, the stuff space within genes, and RNA splicing (since the RNA message of the gene was "spliced" to remove the intron fragments) Both were awarded 1993 nobel
Note - The New Music > Page 223 · Location 3992
David Baltimore and Howard Temin, discovered an enzyme that could allow building of DNA from RNA, thereby enabling cataloging of all active genes in a cell, similar to creating a library of books grouped by subject. There would be a library of genes for T cells, and another for neurons in the retina, etc.
Note - “Clone or Die” > Page 238 · Location 4239
Robert Swanson, co-founder and CEO of Genentech
Note - “Clone or Die” > Page 241 · Location 4295
Keiichi Itakura, successfully synthesized (built from scratch) the gene for somatostatin, a hormone produced in the human brain, which was not expected to be commercially significant. However, the work was considered a possible first step towards the creation of a synthetic insulin. Itakura developed a technique that reduced the time involved in successful synthesis from years to weeks. He then inserted the gene for somatostatin into E. Coli. This was the first demonstration of a foreign gene inserted into E. Coli.
Part Four: “The Proper Study of Mankind Is Man” 1970–2005
Note - The Birth of a Clinic > Page 260 · Location 4594
Victor McKusick, "father of medical genetics", first person to systemically catalogued genetic mutations in humans.
Note - The Birth of a Clinic > Page 262 · Location 4633
Down syndrome, the extra-chromosome disease. Linked with mental deficits but sweet temperaments.
Note - The Birth of a Clinic > Page 268 · Location 4750
Roe v Wade, centered around the right of a woman to abort a child diagnosed in utero with Down Syndrome
Note - A Village of Dancers, an Atlas of Moles > Page 278 · Location 4905
David Rotstein, Ronald Davis, Mark Skolnick proposed a way to map genes by 1) pinpointing a particularly gene to a nearby genetic marker 2) use polymorphism, tiny and innocuous variations of genes (hitherto thought as useless) as the such markers
Note - A Village of Dancers, an Atlas of Moles > Page 281 · Location 4966
Nancy Wexler, daughter of Huntington disease mother, led the effort to pinpoint huntington disease gene (huntingtin) by using Botstein's method
Note - A Village of Dancers, an Atlas of Moles > Page 289 · Location 5111
Lap-Chee Tsui, with Francis Collins, found the CF gene, cause of cystic fibrosis, by using genetic jumping, a greatly more efficient method compared with Botstein's original method. Francis Collins later succeed James Watson as head of Human Genome Project.
Note - “To Get the Genome” > Page 302 · Location 5338
Karry Mullis, 1993 laureate in chemistry, invented Polymerase Chain Reaction (PCR) that grow human genes exponentially in test tubes, became crucial for the Human Genome Project
Note - The Geographers > Page 306 · Location 5404
Craig Venter, proposed "shotgun strategy", efficient but "fragmented" approach towards gene sequencing, by shredding genes into pieces, ignoring introns and spacers, and later even ignoring genes itself, sequencing at random, and reassemble. Later he left Human Genome Project and started his own firm, TIGR.
Part Five: Through the Looking Glass 2001–2015
Note - “So, We’s the Same” > Page 333 · Location 5847
Allan Wilson, found answer to the question, "How old are humans, where did we come from" by looking at the mini-genome stored in mitochonria. He also proposed the idea of a Mitochonrial Eve.
Note - The First Derivative of Identity > Page 361 · Location 6337
Swyer syndrome: anatomically and physiolgically female, with XY chromosomes.
Note - The First Derivative of Identity > Page 365 · Location 6410
David Reimer, a Canadian man born male but reassigned as a girl and raised female following medical advice and intervention after his penis was accidentally destroyed during a botched circumcision in infancy. The psychologist John Money oversaw the case and reported the reassignment as successful and as evidence that gender identity is primarily learned. The academic sexologist Milton Diamond later reported that Reimer's realization he was not a girl crystallized between the ages of 9 and 11 years[3] and he transitioned to living as a male at age 15. Well known in medical circles for years anonymously as the "John/Joan" case, Reimer later went public with his story to help discourage similar medical practices. He committed suicide after suffering years of severe depression, financial instability, and a troubled marriage.[4]
Note - The Last Mile > Page 371 · Location 6550
Dean Hamer, found the "gay gene"
Note - The Last Mile > Page 373 · Location 6582
J. Michael Baily, found that homosexuality was caused by genes. Bailey’s methodology was classical: if sexual orientation was partly inherited, then a higher proportion of identical twins should both be gay compared to fraternal twins.
Note - The Last Mile > Page 381 · Location 6720
Thomas Bouchard, created "the Minnesota Study of Twins Reared Apart (or “MISTRA”). "
Note - The Last Mile > Page 384 · Location 6785
Richard Ebstein, found D4DR gene, the gene for novalty-seeker
Note - The Last Mile > Page 388 · Location 6861
"the last mile problem" of genetics: genetics. Genes can describe the form or fate of a complex organism in likelihoods and probabilities—but they cannot accurately describe the form or fate itself.
Note - The Hunger Winter > Page 392 · Location 6937
Conrad Waddington, first propose the idea of epigenetics.
Note - The Hunger Winter > Page 396 · Location 7006
John Gurdon, 2012 nobel, known for pioneering work in cloning and gene transfer in frogs
Note - The Hunger Winter > Page 399 · Location 7046
Mary Lyon, best known for discovery of X chromosome inactivation, a visible example of an epigenetic change in an animal cell
Note - The Hunger Winter > Page 404 · Location 7136
Shinya Yamanaka, revert normal cells back to stem cells by using only 4 genes to erase epigenetic marks.
Note - The Hunger Winter > Page 411 · Location 7249
Jack Szostack, tried to create a self-replicating genetic system in a test tube, thereby reconstructing origin of genes. He believe genes emerged out of Stanley Miller's Primordial Soup by chance meeting between two partners: 1) lipids that form micelles, resembling cell membranes. 2) self-replicating RNA strands.
Note - The Hunger Winter > Page 411 · Location 7250
Stanley Miller, attempted to brew a "primordial soup" by mixing basic chemicals known to have existed in ancient atmosphere. He didn't find life, but found traces of amino acids, and trace amounts of the simplest sugars.
Note - The Hunger Winter > Page 414 · Location 7320
Three-parent children: fertilized nucleus from parents + donor egg from third parent.
Part Six: Post-Genome 2015– . . .
Note - The Future of the Future > Page 423 · Location 7466
David Vetter, The Bubble Boy, spent all twelve years in his life in a plastic chamber because of ADA deciency, in which T cells were intoxicated to death.
Note - The Future of the Future > Page 423 · Location 7475
Richard mulligan, operated first genetic transfusion treating ADA deficiency.
Note - The Future of the Future > Page 429 · Location 7565
Jesse Gelsinger, first genetic transfusion death.
Note - Genetic Diagnosis: “Previvors” > Page 438 · Location 7728
Mary-Claire King, discovered BRCA1 gene, that is closely related to breast cancer.
Note - Genetic Diagnosis: “Previvors” > Page 443 · Location 7825
NGS, massively parallel DNA sequencing, or next-generation sequencing
Note - Genetic Diagnosis: “Previvors” > Page 456 · Location 8055
PGD, preimplantation genetic diagnosis: A human embryo can thus be biopsied at this early stage, the few cells extracted used for genetic tests. Once the tests have been completed, cherry-picked embryos possessing the correct genes can be implanted. With some modifications, even oocytes—a woman’s eggs—can be genetically tested before fertilization.
Note - Genetic Therapies: Post-Human > Page 467 · Location 8287
James Thomson, best known for deriving the first human embryonic stem cell line in 1998[1] and for deriving human induced pluripotent stem cells (iPS) in 2007.
Note - Genetic Therapies: Post-Human > Page 471 · Location 8355
Jennifer Doudna and Emmenuel Carpentier, creater of CRISPR/Cas9 technology, deriving from bacterial defense system, which plays a major role in gene editting. CRISPR (/ˈkrɪspər/) (clustered regularly interspaced short palindromic repeats) is a family of DNA sequences found within the genomes of prokaryotic organisms such as bacteria and archaea.[1] These sequences are derived from DNA fragments from viruses that have previously infected the prokaryote and are used to detect and destroy DNA from similar viruses during subsequent infections. Hence these sequences play a key role in the antiviral defense system of prokaryotes Cas9 (or "CRISPR-associated 9") is an enzyme that uses CRISPR sequences as a guide to recognize and cleave specific strands of DNA that are complementary to the CRISPR sequence. Cas9 enzymes together with CRISPR sequences form the basis of a technology known as CRISPR/Cas9 that can be used to edit genes within organisms. This type of gene editing process has a wide variety of applications including use as a basic biology research tool, development of biotechnology products, and potentially to treat diseases.
Note - Genetic Therapies: Post-Human > Page 478 · Location 8470
Huang Junjiu, of Sun Yat Sen University, conducted first gene-editing experiment on human embryos in 2015.
