Summary for "The Gene"

基因传

8.6

[美] 悉达多·穆克吉 / 2018 / 中信出版社

Prologue:

• Two of Mukherjee’s father’s brothers and Mukherjee’s cousin are diagnosed with schizophrenia.
• Twentieth century: Atom, byte, and gene.
• A personal history, an intimate history

Part One: “The Missing Science of Heredity”

1865-1935

• Gregor Johann Mendel, as a monk, was given a chance to go to university at Brno and study science.
• Christian Doppler: Doppler’s effect.
• Pythagoras: Hereditary information was principally carried in male semen （Spermism). Comparisons between triangle to a family and a child’s birth.
• Aristotle: The fetus is formed by mutual contributions of male and female parts.
• The alchemist Paracelsus: “Mini man in sperm theory”, that normal child was merely the transfer of this minuhuman—the homunculus—from the father’s sperm into mother’s womb. Also call Preformation, which was prevalent in seventeenth century.
• Charles Darwin went to expedition and discovered 13 different finches on nearby islands, then started wondering if they have a common ancestor. Then he thought all organisms produce minute particles containing hereditary information—gemmules. Pangenesis—genesis from everything.
• Flemming Jenkins: Blending of genetic traits would finally dilute the hereditary information one carries.
• Mendel’s paper about his findings and date were published in 1865.
• In 1900, Hugo de Vries rediscovered Mendel’s paper with envy and despondency.
• William Bateson made Mendel’s contribution clear to the public and coined the word “Genetics”, meaning to give birth. Wilhelm Johannsen coined the word “Gene”
• Francis Galton, Darwin’s cousin, believing intelligence is heritable, such as in his family, conducted researches on human inheritance. He claimed that human inheritance can be manipulated for human benefit. Race hygiene.
• Carrie Buck, daughter of Emma Buck, was identified as feebleminded and get sterilized. Buck vs. Priddy, Priddy was the person who executed sterilization law.

Part Two: “In the sum of the Parts, There are only the parts.”

1930-1970

• Boveri-Sulton hypothesis proposes that genes reside in chromosomes.
• Thomas Morgan started to study fruit flies. Mutations, traits, and linkage.
• Genotype + environment + triggers + chances= phenotype
• Frederick Griffith used transformation, the horizontal exchange of genes, to prove that hereditary information can be transmitted through a cell.
• Hermann Muller discovered that radiation can cause mutation, realizing the broader implication of positive human eugenics. Sick of the United States, in 1932, he left for Berlin.
• Nazism, racial hygiene. Extermination of 6 million Jews. Two hundred thousand Gypsies. Several million Soviet and Polish citizens.
• The Soviet believed in absolute gene reprogrammability to achieve a radical collective good.
• Avery——predicable and inducible changes.
• Erwin Chargaff discovered paring rules between nucleotide bases.
• Maurice Wilkins, Rosalind Franklin, James Watson, and Francis Crick discovered DNA structure.
• Francis Crick— Central Dogma. (DNA-RAN-Protein)
• Regulation, Replication, Recombination.
• Jacques Monod investigated the diet of E. coli, a short pause while changing from glucose to lactose. Metabolic readjustment. Induce specific lactose-digesting enzyme.
• Pardee, Jacob, ad Monod published a paper(Pajama paper), suggesting that even though every cell contains the same set of genes, the selective activation or repression of particular subsets of genes allows an individual cell to respond to its environment.

Part Three: “The Dreams of Geneticists”

1970-2001

• Berg and David Jackson joined two pieces of DNAs, creating “recombinant DNA” in 1970.
• Swanson and Boyer started a company “Genentech”
• Discovery of AIDS(Acquired Immunodeficiency Syndrome) in 1982.

Part Four: “The Proper Study of Mankind is man”

2001-2015

• Penetrance of diseases. For example, for breast cancer, the penetrance is not 100. However, for Tay-Sachs Disease, the penetrance is largely complete: the inheritance of the gene mutation virtually guaranteed the development of the disease.
• Mutation, in 1960s, became a popular topic in American fantasies. 1961, Fantastic Four. Then it comes to Spider Man, and then X-Men.
• Down, Klinefelter, and Turner Syndrome can be diagnosed in utero, and the pregnancy could voluntarily be terminated if fetal chromosomal abnormalities were detected after 1956.
• Because of that, a new form of eugenics emerged by examining the genetic composition of a fetus.
• Huntington’s disease: one copy of DNA precipitates the disease. Occasional mood swings or subtle signs of social withdraw. Involuntary “Dance”. Deep cognitive decline, and near-complete loss of motor function. Patients die of malnourishment, dementia, and infections. Chance: 1/10000. Cause: an increase in the number of repeats, from less than thirty-five in the normal gene to more than forty in mutants.
• Cystic fibrosis: Affect the lungs, pancreas, bile ducts, and intestines. Cannot be cured. Cause: deletion of three bases of DNA. Dysfunctional protein unable to move chloride, nor can the body secrete salt and water into the intestines. Selective advantage of one copy of mutant CF gene: relatively protected from the most devastation complication of cholera.
• Schizophrenia: a complex, polygenic illness, involving multiple variants, multiple genes, and potential environment or chance triggers.
• January 28, 1983. Launch of the Human Genome Project. On the eve of this day, Carrie Buck died. “Her birth and death had bookended the near century of the gene. Her generation had borne witness to the scientific resurrection of genetics, its forceful entry into public discourse, its perversion into social engineering and eugenics, its postwar emergences as the central theme of the ‘new’ biology, its impact on human physiology and pathology, its powerful explanatory power in our understanding of illness, and its editable intersection with questions of fate, identity, and choice. She had been one of the earliest victims of the misunderstandings of a powerful new science.”
• June 10, 1992. Venter launched his private gene-sequencing institute The Institute for Genomic Research, then changed the name to Celera.
• Venter used Shot-gun sequencing to compete with the government’s project. HGP.
• On February 15 and 16, 2001. Celera and Human Genome Project published their paper in Science, and Nature, respectively. 66000 words in Nature, the the largest study on Nature.
• All other apes, such as gorillas, chimpanzees, and orangutans, have twenty four pairs——We lost a chromosome, but gained a thumb.
• 3,088,286,401 letters of DNA.
• A pesky, mysterious three-hundred base pair sequence called Alu appears and reappears tens of thousands of times. Origin and function unknown.
• “Pseudogenes”——Genes that were once functional but have become nonfunctional.
• “Telomeres” are like the little bits of plastic at the ends of shoelaces.
• “It is posed to evolve.” “It is designed to survive” “It resembles us”

Part Five: “Through the Looking Glass”

(2001-2015)

• Neanderthal, a hominid, coexisted with modern human(then called Cro-Magnons). Neanderthal extinct forty thousand years ago, having overlapped with early modern human about five thousand years. They were our neighbors and rivals. We interbred with them and we also competed with them for food and resources, which contributed to their extinction.
• Human mitochondrial genes resemble material genes more than human ones. (Since sperm do not pass their mitochondria to the embryo, sons cannot pass their mitochondrial genome to their children.)
• Modern humans appear to have emerged exclusively from a rather narrow slice of earth, somewhere in sub-Saharan Africa, about one hundred to two hundred thousand years ago, and then migrated northward and eastward to populate the Middle East, Europe, Asia, and the Americas.
• “So, we’re the same. Just a different color.”
• A Y chromosome gene cannot be fixed, repaired, or recopied.
• Sex was invented for enabling recombination.
• Swyer syndrome: A “woman” who had been born with male chromosomal pattern(XY chromosomes) in all of her parts, but had somehow failed to signal “maleness” to her body.
• SRY gene was mutated in females with Swyer Syndrome, and non mutated in their unaffected siblings.
• Gay men tended to have gay uncles——but only one the maternal side. Reasons unclear.
• Genes encode RNAs to build Proteins to form/regulate Organisms that sense Environment that influence Epigenomes that regulate Genes
• Why double stranded? A backup copy is need—a mirror image to protect the original or to restore the prototype if damaged.

Part Six: “Post-Genome”

2015-……

• Human ES cells do not have the same capabilities as mouse ES cells.
• Gene therapy failures of Ashi DeSilva, Jesse Gelsinger, and Cynthia Cutshall.
• CRISPR-Cas9 System might enables more successful gene therapy in the future.
• Conclusions:

1. A gene is the basic unit of hereditary information.
2. The genetic code is universal.
3. Genes influence form, function, and fate, but these influences typically do not occur in a one-to-one pattern.
4. Variations in genes contribute to variations in features, forms, and behaviors.
5. When we claim to find “gens for” certain human features or functions, it is by virtue of defining that feature narrowly.
6. It is nonsense to speak about “nature” or “nurture” in the absolute or abstracts.
7. Every generations of humans will produce variants and mutants; it is an inextricable part of our biology.
8. Many human diseases—including several illnesses previously thought to be related to diet, exposure, environment, and chance—are more powerfully influenced by genes.
9. Every genetic “illness” is a mismatch between an organism’s genome and its environment.
10. In exceptional case, the genetic incompatibility may be so deep that only extraordinary measures, such as genetic selection, or directed genetic interventions, are justified.
11. There is nothing about genes or genomes that makes them inherently resistant to chemical and biological manipulation.
12. A triangle of considerations—extraordinary suffering, highly penetrant genotypes, and justifiable interventions—has, thus far, constrained our attempt to intervene one human.
13. History repeats itself, in part because the genome repeats itself. And the genome repeats itself, in part because the history does.

Epilogue:

• What is “natural”?

“Variation, mutation, change, inconstancy, divisibility, flux.”

Versus

“Constancy, permanence, indivisibility, fidelity.”

• Contradictions and constancy