For Genome by Matt Ridley
Chromosome 1: Life
Ridley begins the chapter with a parody of the beginning of the Biblical book of Genesis, with “In the beginning was the word...” and later reveals that the “word” is RNA, not DNA. He says that DNA is analogous to written languages: it is written linearly, read from left to right (or right to left), and there is an alphabet (although it is 22 letters shorter than the English version). Ridley then begins talking about the history of life, beginning with RNA, which came before DNA. RNA is much more chemically active and automatic than DNA, but it is also unstable, therefore prehistoric “ribo-organisms” came up with DNA through an evolutionary trial and error process because it was faster, more accurate, and more reliable. LUCA, the Last Universal Common Ancestor, is then introduced. LUCA has been believed to be a bacterium living in a hot marine environment. However, since bacteria do not conform to the laws of genetic inheritance because they “steal genes” from one another (which used to cause evolutionary competition to be between genes rather than species, but now it is more of a team sport), Luca is now believed to be more of a protozoan, because bacteria would have dropped the extra RNA in order to reproduce more quickly, playing to possibly their greatest evolutionary strength. In conclusion, Ridley says that “life has a physical history, not a genealogical one” and that the history of life is written in the genome.
Chromosome 2: Species
In the middle part of the twentieth century, there were thought to be 24 chromosomes in the human genome. Coincidentally, apes such as gorillas and chimpanzees have 24 chromosomes to our 23, because the human Chromosome #2 is a slightly modified fusion of two ape chromosomes. Therefore some religious figures believe that the human soul is somewhere near the centromere of Chromosome 2. “Humans are an ecological success,” because our 300 million tons of biomass is only rivaled by domestic animals and we have colonized virtually every habitat. However, evolution is based on the principle of optimizing one’s adaptations to one’s environment and has no pinnacle. This being said, humans and chimps genetically are 98% the same. The point in time that the split occurred is unclear, but it is clear that after some barrier, whether geological or otherwise, a chimpanzee population split. One population developed a genetic mutation (the fusing of two chromosomes) that prevented the two populations from breeding and thereby forming a new species that eventually became the human species. The human population developed different methods of sexual selection from the other two species, such as a more monogamous system and attraction to more youthful mates. Monogamy also shaped our hunting/gathering habits and a “sexual division of labor” began to emerge. Ridley asserts that the differences between species are in the genes, and while genes do not totally control behavior, they do play a part.
Chromosome 3: History
Ridley introduces a historical figure named Dr. Archibald Garrod who, through working with the disease alkaptonuria, published a shockingly accurate hypothesis in 1902 called “the inborn errors of metabolism.” He assumed that each gene produced one chemical catalyst, and that the inborn errors of metabolism were caused by genetic mutations, which he described as “loss or malfunction of an enzyme,” and that proteins manage virtually every function in the body. His book was well received, but readers missed the point; his virtually perfect theory did not resurface until thirty-five years later. Mendel had no immediate critical reception; he was unheard of until much later. Darwin himself was confused about the principle of inheritance and produced a theory that conflicted with his theory of natural selection but unfortunately never read Mendel. Mendel had proved “the atomic theory of biology.” Darwin’s theory and Mendel’s theory were finally combined in 1918. Later discoveries about mutations revealed that genes were recipes for proteins, and mutations were “altered proteins made by altered genes.” The structure of DNA was discovered by Watson and Crick in England in 1953. Crick also discovered, although solely theoretically, the twenty three-letter “words” that the genome uses. To come full circle, in 1995 scientists returned to alkaptonuria, isolated the gene and found that it is caused by a single base substitution.
Chromosome 4: Fate
Ridley compares identifying genes by the diseases they can cause to identifying organs by the disorders they can suffer in order to show the difference between a gene and a mutation. He uses the example of the Wolf-Hirschhorn gene, where individuals with the gene are healthy, those without the gene have Wolf-Hirschhorn syndrome, and those with a mutated version have Huntington’s chorea. In 1970, a woman named Nancy Wexler and her father, a doctor, knowing that she may carry the mutation for Huntington’s chorea, decided to search for the gene. The gene was finally found in 1993, and it solely a repetition of the codon CAG; the number of repetitions signifies at what age the carrier acquires symptoms—if there is an excess number, there is an excess lump of glutamines in the protein. Excess CAG repeats have been found to induce at least five other neurological disorders and at least twelve known human diseases (polyglutamine diseases). The number of repetitions can increase over time, except in the cerebellum, but especially in sperm production. Ridley then goes on to discuss how people handle the fate of testing positive for a genetic test for Huntington’s, and how it is not always wise to diagnose a disease that cannot be cured before its onset.
Chromosome 5: Environment
The tone of the writing changes in this chapter to almost cynical; the author explains that the world of genetics is not as black & white and Mendelian as he has led the reader to believe. Genetic inheritance is based on the principles of pleiotropy, pluralism, and the environment of the individual. Chromosome 5 houses one of the “asthma genes,” but the disorder cannot be simplified to a genetic level. “Asthma...is much more like real life” (67). The disorder also has a direct relationship with allergies. There are countless supportable theories as to why asthma has been increasing, such as pollution from modern synthetic chemicals such as isocyanates, excessive hygiene (“sterilized” children lack mycobacteria from dirt which balance the Th1 and Th2 parts of the immune system) and others. The hunt for the “asthma gene” was a tedious process, but the closest genes to an asthma-causing gene are the two genes which produce immunoglobulin-E. This protein comes in different forms and is involved with the release of histamine into the body. Additionally, although asthma has been linked to genes, the genes isolated are trivial and inconclusive (a different gene for each ethnicity) and the cause of the disease is usually attributed most to the environment of the individual.
Chromosome 6: Intelligence
Ridley introduces the search for the “intelligence gene,” supported by a study done on the genes of a group of high-IQ children, which found a difference on the gene IGF2R, located on chromosome 6. Through mentioning racist “scientists” and their intelligence testing, he comes to the conclusion that “intelligence genes” do not work in a vacuum—environmental stimulation is necessary for them to function. Studies done on separated twins have shown that there is, in fact, heritability to intelligence and personality, and that there was zero correlation between IQ scores of adopted children living in the same family. Ridley also introduces the concept that the intelligence genes are indeed more expressive later in life rather than less expressive because people begin to choose their own environments and comfort zones, giving more liberty to the genes to express themselves. This is proven by the fact that elementary school children in Head Start programs are no longer ahead of their peers by the end of elementary school. A counterargument to the study can show that genes are even more expressive in egalitarian environments. My favorite sentence was in the concluding paragraph, where Ridley says, “The genes may create an appetite, but not an aptitude” (89).
Chromosome 7: Instinct
Many determinist views about human behavior that have all been revoked are listed, such as Freudianism, Marxism and others, and Ridley implies that genetic determinism of human instinct is much more probable. Human grammar is one of the best examples of this¾ vocabulary is certainly not innate, but grammar might be, because young children can speak with perfect grammar even before learning it. There is a gene on Chromosome 7 that has been linked to a disorder called SLI (Specific Language Impairment), for which the heritability has been shown to approach one hundred percent. Through a study of an English family with history of the disorder, Canadian Myrna Gopnik proposed that SLI does not have its roots in the physical act of speaking, but rather in the ability to learn grammar rules. Individuals with SLI can communicate but must have a much larger vocabulary (past tense verbs would feel like separate, unrelated words) because of the lack of internalized grammar, similar to adults trying to learn a foreign language. It has been found, however, that a mutation to this gene causes a lesion in the brain affecting not only the grammar part, but also the Broca and Wernicke areas which control face movement and hearing respectively. Ridley also ties grammar instincts to natural selection as a means of survival.
Chromosomes X and Y: Conflict
Ridley introduces the genetic “conflict” between the X and Y chromosomes, and states that each respective chromosome attracts genes that are beneficial to that sex. For example, the Y attracts masculine genes for large muscles, while the X attracts genes to benefit reproduction; these genes are often in competition with each other for expression. Because of the intense competition between the two, the relatively outnumbered Y chromosome has effectively minimized itself in order to preserve itself from attacks by the three times more frequent X chromosome. SRY, the “masculinizing” gene on the Y chromosome, has little to no variation in humans, although it varies greatly between species. Therefore it is one of the fastest-evolving genes. However, the conflict between genes for seduction and genes for resistance keeps the molecular biology of sex in balance. This conflict and resulting balance may also be the explanation for the human development of intelligence in that individuals compete with each other through continually advancing forms of seduction and resistance. The conflict has almost been shown to be the attributor for a heritability of homosexuality. Although the gene Xq28 has been discovered to be connected to sexual orientation but has not been definitively proven to be connected, the correlation between birth order and probability of homosexuality has been linked to the immune system reaction of the mother to the Y chromosome of the fetus and the assertion of the mother’s attraction-to-males gene.
Chromosome 8: Self-Interest
Ridley begins by introducing the concept that genes are much more complicated than they need to be, with genetic information in sections called exons with intermittent random sections called introns. Reverse transcriptase, a protein that comes from the most common gene in the genome, is one that is not helpful at all to the human body, and aside from being the fuel for the AIDS virus, the gene exists because several genes (including itself) use it to replicate themselves. Such genes exist solely because they are good at replicating themselves, but they can cause mutations in “proper” genes if they jump into the middle of them. Fortunately, humans possess a capacity to suppress and freeze these junk genes by a process called methylation. The reverse of this process is the first step in the development of cancer. Forensic scientists have found and proliferated a practical use for these junk genes called minisatellites, however, in genetic fingerprinting. Because the length of these minisatellites varies from individual to individual, they can be used like unique fingerprints to match samples between convicts and evidence.
Chromosome 9: Disease
The chapter begins with a discussion of variation in blood type and the previous theory that the variation, like some others, was an effect of random genetic mutations rather than natural selection. However, it has been shown to be linked to immunity vs. susceptibility to cholera (A and AB) and malaria (O). The example of sickle-cell disease vs. malaria is also used; many African populations (and some African-Americans) carry either one or both genes for sickle-cell anemia because of the link to the allele’s resistance to malaria. Ridley explains that many alleles, even some disease-causing ones, are still frequent because of their contribution to the resistance to a more deadly infectious disease. The concluding theme of the chapter is that the genome, like ecology, is always changing. There is no equilibrium or stability, it is based on the principle of change.
Chromosome 10: Stress
Ridley explains that the genome is not the only contributor to an individual’s health. The brain, the body, and the genome are locked in a constant “dance,” as Ridley puts it. A gene on Chromosome 10, CYP17, is responsible for the synthesis of an enzyme that enables the body to convert cholesterol into cortisol, testosterone and oestradiol. The first of these steroids, cortisol, is released when the brain signals stress and sets off a long chain of genetic “triggers,” that is, switching genes on and off and thereby causing other genes to be switched on or off, including suppressing the immune system. “The main purpose of most genes in the human genome is regulating the expression of other genes in the genome” (150). Ridley also asserts that the world, not just the human body, is full of intricate interconnected systems with no control center, like the economy, for example. Heart disease has shown to be linked very highly to the amount of daily cortisol in the bloodstream, which correlates to daily stress level and a feeling of control. For example, in a study, employees in lower-paying and lower-ranking jobs ran a higher risk of heart disease, even when they were not fat, hypertensive, or smokers, than those in higher-ranking positions of authority. The chapter ends with the conclusion that there has been no logical explanation for the correlation between steroids and immune system suppression.
Chromosome 11: Personality
On the short arm of chromosome 11, the gene D4DR is a recipe for a dopamine receptor, and the gene is switched on in certain parts of the brain but not in others. Dopamine is basically a motivational chemical, meaning that lack of it will make an individual lethargic or immobile, while excess can cause schizophrenia, for example. Dean Hamer shows in a study that D4DR correlates with “novelty-seeking” behavior, but only accounts for four percent of such behavior. An additional 36 percent is heritable, and the rest is environmental. This means that there could be over 500 heritable genes to control behavior, as opposed to one, ousting eugenics entirely when it comes to personality because of the sheer number of genes that control it. Additionally, therapists found that depathologizing people’s personalities and reassuring them that their personality is innate rather than some learned flaw helped them to improve their self-esteem. Personality and behavior can also be influenced by diet, specifically cholesterol intake. Antisocial and depressed people have been shown to have lower cholesterol levels, because there is a correlation between cholesterol and serotonin, a chemical similar to dopamine. Lower cholesterol levels mean lower serotonin levels which usually indicate depression or violent desires. At the same time, “biology determines behavior yet is determined by society.”
Chromosome 12: Self-Assembly
Ridley introduces embryonic development as a grand genetic scheme without a control center, because every cell carries the full genome with all the instructions. In a study done with fruit flies, there were eight genes found that controlled anatomical development, called homeotic genes, and they were lined up in order correlating with the body parts that they controlled during development, always beginning with the head and ending with the most posterior part of the body. This is strange because of the normally random placement of genes throughout the genome. It has also been shown that mice and flies and even humans have the same homeotic gene clusters with mostly the same genes. The process works very simply: genes turn each other on in order to give the embryo a head and a rear and everything else in between.
Chromosome 13: Pre-History
Ridley begins the chapter by talking about the development of language, and asserts that there most definitely was once a single people speaking a single language in a single place, and that the people diverged and separate languages evolved. Genetic variation has been mapped to show the expansion of peoples across Eurasia over time. The expansion and/or migration of colonizing people into a territory has contributed to evolution as well. Northern Finnish males have a distinct Y-chromosome because of interbreeding (always foreign males and native females, in this case). BRCA2 is the focus gene of this chapter, which is a “breast cancer gene;” the frequency of the breast-cancer-causing allele is very frequent among inbreeding populations such as that of Iceland.
Chromosome 14: Immortality
James Watson in 1972 discovered that polymerases do not start copying DNA at the tip of the chromosome, they start coding part-way into the DNA, so every time DNA is replicated, a little bit of the telomere (the tip of the chromosome made up of the “word” TTAGGG) is left off. Telomerase, a protein made by the gene TEP1, is most likely responsible for increasing the continuous division of cells. Malignant cancer cells switch the gene on after it has been switched off by most cells in development. This also may explain why brain cells do not divide: so that they do not lose any vital genes. Ridley discusses why aging may be caused by evolution, and asserts that “Natural selection has designed all parts of our bodies to last just long enough to see our children into independence, no more.” Therefore, cancer is most definitely linked to age. Age is its highest risk factor, and it is no coincidence that the most common cancer sites are tissues that often divide their cells.
Chromosome 15: Sex
Ridley begins with two different “genetic diseases,” Prader-Willi syndrome and Angelman’s syndrome, both of which are caused by the lack of the same chunk of chromosome 15, and it has been shown that whether a child inherits one syndrome or the other depends on the parent from whom the mutation is inherited: Prader-Willi from the father, Angelman’s from the mother. This relates to sexual antagonism and the fact that the placenta is controlled by paternal genes in order to be “invasive enough” into the mother’s body and resources. Genetic cloning, like the case of Dolly, seems to erase all genetic “imprints” so the organism still survives. Imprinting has an effect on the brain too, in that the mother’s genes control the development of the cerebral cortex while the father’s control the development of the hypothalamus, so essentially we inherit our mother’s way of thinking and our father’s innate moods. Accordingly, gender roles in behavior have also been shown to be controlled by the genome rather than by environmental situations around an individual.
Chromosome 16: Memory
Ridley introduces the problem of knowledge versus instinct, and learning versus heritability, but then asserts that natural selection will make universal common knowledge like grammar instinct but will leave things like vocabulary to be learned so that it can change with time. Eric Kandel isolated a chemical called cyclic AMP, a chemical found in neurons, that is involved in the process of learning by changing itself when something is learned. It has also been shown without a doubt that humans are not the only creatures capable of learning. Bees, mice, and even sea slugs can learn, as proven by Kandel’s study and many others. However, while the human brain is capable of immense amounts of learning, the brain is created and ultimately controlled by genes and related proteins and chemicals.
Chromosome 17: Death
The chapter focuses on cancer, and introduces it with the principle that cells occasionally reproduce themselves when they are not supposed to. Cancer is when they are not stopped from doing so. A gene called TP53, on the short arm of chromosome 17, is responsible for suppressing rogue cancer cells, and is classified as a tumor-suppressor gene. These genes are the opposite of oncogenes, which are genes that encourage cell growth. Therefore, oncogenes can cause cancer when they are kept switched on, but tumor-suppressor genes can also cause cancer when they are kept switched off. Ridley explains that the reason detecting cancer early is so important is that the more it progresses and the more the cells divide, the more mutations accumulate, which means the progression of the disease actually accelerates with time. Some cancer victims also carry mutations in “mutator genes” such as BRCA1 and BRCA2, in the case of breast cancer. The protein that TP53 produces called p53, which is in clinical trial as a cancer drug, acts as a police officer in cells that begin to duplicate themselves excessively by either halting cell division or by instructing the cell to commit suicide by a process called apoptosis. Ridley explains that in various types of cancers TP53 is mutated very early, which explains why chemotherapy and radiation therapy does not always work effectively in later stages of the disease (chemo and radiation help the body to help itself by damaging DNA which thereby “alerts” p53, but if the gene is mutated this cannot happen). I have attached a quote from page 240 that I found particularly inspiring about “reductionist” cancer research.
Chromosome 18: Cures
The chapter is about genetic manipulation, and the first example Ridley gives is in 1972 Paul Berg made the first man-made “recombinant” DNA by using restriction enzymes and ligase. Since then, there have been several experiments using recombinant DNA where a retrovirus would be stripped of its infectious genes and replaced with a desired gene and then injected into the body either directly or through cultured cell, trying to cure various diseases through gene therapy such as SCID, hemophilia, cystic fibrosis, and cancer. Genetic engineering has very unnecessarily polarized its proponents and radical environmentalists, stemming from the issue of agricultural genetic engineering. Ridley reviews the possibilities of human cloning with genetic improvement through the use of embryonic stem cells and recombinant DNA.
Chromosome 19: Prevention
Ridley introduces the chapter with a discussion of diseases that previously had no cure but now do, and that it is our moral obligation to treat and prevent those diseases when the knowledge to do so becomes available, specifically Alzheimer’s disease and coronary heart disease. He explains the process by which coronary heart disease develops and integrates the APO genes, specifically APOE, which help control the metabolism of fats and cholesterol, and explains that genetic testing could help doctors to suggest healthy eating and exercise habits depending on an individual’s APO genes. Alzheimer’s disease also has a strong connection with APOE, specifically the E4 allele, in that it somehow contributes to the characteristic plaque buildup in the brain cells. Ridley again discusses the issue of genetic testing of patients for an incurable disease such as Alzheimer’s and the associated but unfounded fatalism conveyed to the patient, although unlike Huntington’s disease it is not exactly fatalism because of other environmental factors and that even E4/E4 individuals can live long lives with no symptoms other than neuronal plaque buildup. He suggests that doctors will begin to use genetic tests in everyday diagnoses and prescriptions, but also discusses the negative effects of releasing genetic information to insurance companies and/or the government. “[Your genetic code] is yours, not the government’s, and you should always remember that.”
Chromosome 20: Politics
The chapter’s theme is mystery, and it begins with the story of “scrapie,” a degenerative brain disease found in genetically engineered sheep that seemed to be infectious, but no “microbe” could be found. A similar disease was found among people in Papua New Guinea called kuru that had connections to a cannibalistic ritual. Another similar disease called CJD became an epidemic called iatrogenic CJD, meaning CJD caused by doctors, due to the presence of the disease on surgical materials even after sterilization. In 1982 Stanley Prusiner eventually isolated the gene, PRP, which produces a protein called a prion, which can suddenly change itself into an indestructible sticky lump that sticks together with other prions; they can also recruit other normal prions to the aggregate lumps. Therefore the scrapie disease could be both genetic and transmitted. Ridley discusses governments’ ridiculous methods of dealing with scrapie scares such as restricting consumption of beef and other animals.
Chromosome 21: Eugenics
Ridley begins discussing eugenics with its definition and how it came about as more of a science-ized political creed rather than a politicized science. He begins with a political discussion of American eugenic beliefs stemming from anti-immigration and the fear of diluting the Anglo-Saxon American race. Even the Supreme Court began to allow sterilization, or the prevention of individuals from breeding, in 1927. Ridley also recounts the history of how Britain never passed laws allowing sterilization (not to say that doctors and hospitals never practiced it independently). In today’s world, although sterilization is considered inhumane and a direct violation of civil liberties, eugenics still happens every day in hospitals, especially to those individuals with trisomy 21, the genetic condition leading to Down syndrome. Genetic counseling is also partly based on the principle of eugenics. China is one of the few countries that still encourages eugenics and sterilization, and Ridley says that this is because the culture demands that the good of the society is placed before the good of the individual.
Chromosome 22: Free Will
Ridley blends the two factions of genetic determinism and freedom, saying that the notion that behavior is controlled by one’s environment is just as deterministic as that of genetic determinism. To say that a child abuser acts the way they do because they were abused as a child is just as deterministic and even more prejudicial. Ridley asserts that children actually have more nurture effect on their parents than parents do on their children, because children tend to shape themselves in accordance with their genes and their peers and tend to keep home life separate from the outside world. “Human behavior is therefore unpredictable in the short term, but broadly predictable in the long term” (312). One may choose not to eat lunch one day, but over time one will eat regularly. In the beginning of the chapter Ridley talked about a made-up gene called HFW in order to illustrate the difference between something being controlled by a gene and something innate to each of us, controlled by infinitely many factors including free will, which stems from oneself.
This webpage was produced as an assignment for an AP Biology class at Montgomery High School.