Gene Mutation Quotes

However, there is a way to know for certain that Noah’s Flood and the Creation story never happened: by looking at our mitochondrial DNA (mtDNA).  Mitochondria are the “cellular power plants” found in all of our cells and they have their own DNA which is separate from that found in the nucleus of the cell.  In humans, and most other species that mitochondria are found in, the father’s mtDNA normally does not contribute to the child’s mtDNA; the child normally inherits its mtDNA exclusively from its mother.  This means that if no one’s genes have mutated, then we all have the same mtDNA as our brothers and sisters and the same mtDNA as the children of our mother’s sisters, etc. This pattern of inheritance makes it possible to rule out “population bottlenecks” in our species’ history.  A bottleneck is basically a time when the population of a species dwindled to low numbers.  For humans, this means that every person born after a bottleneck can only have the mtDNA or a mutation of the mtDNA of the women who survived the bottleneck. This doesn’t mean that mtDNA can tell us when a bottleneck happened, but it can tell us when one didn’t happen because we know that mtDNA has a rate of approximately one mutation every 3,500 years (Gibbons 1998; Soares et al 2009). So if the human race were actually less than 6,000 years old and/or “everything on earth that breathed died” (Genesis 7:22) less than 6,000 years ago, which would be the case if the story of Adam and the story of Noah’s flood were true respectively, then every person should have the exact same mtDNA except for one or two mutations.  This, however, is not the case as human mtDNA is much more diverse (Endicott et al 2009), so we can know for a fact that the story of Adam and Eve and the story of Noah are fictional.   There

Random mutations much more easily debilitate genes than improve them, and that this is true even of the helpful mutations. Let me emphasize, our experience with malaria’s effects on humans (arguably our most highly studied genetic system) shows that most helpful mutations degrade genes. What’s more, as a group the mutations are incoherent, meaning that they are not adding up to some new system. They are just small changes - mostly degradative - in pre-existing, unrelated genes. The take-home lesson is that this is certainly not the kind of process we would expect to build the astonishingly elegant machinery of the cell. If random mutation plus selective pressure substantially trashes the human genome, why should we think that it would be a constructive force in the long term? There is no reason to think so.

I'm quickly approaching the moment of discovery: of myself by myself, which was something I knew all along and yet didn't know; and the discovery by poor half-blind Dr. Philobosian of what he'd failed to notice at my birth and continued to miss during every annual physical thereafter; and the discovery by my parents of what kind of child they'd given birth to (answer: the same child, only different); and finally, the discovery of the mutated gene that had lain buried in our bloodline for two hundred and fifty years, biding its time, waiting for Ataturk to attack, for Hajienestis to turn into glass, for a clarinet to play seductively out a back window, until, comint together with its recessive twin, it started the chain of events that led to me, here, writing in Berlin.

Glenn used to say the reason you can't really imagine yourself being dead was that as soon as you say, "I'll be dead," you've said the word I, and so you're still alive inside the sentence. And that's how people got the idea of immortality of the soul - it was a consequence of grammar. And so was God, because as soon as there's a past tense, there has to be a past before the past, and you keep going back in time until you get to I don't know, and that's what God is. It's what you don't know - the dark, the hidden, the underside of the visible, and all because we have grammar, and grammar would be impossible without the FoxP2 gene; so God is a brain mutation, and that gene is the same one birds need for singing. So music is built in, Glenn said: It's knitted into us. It would be very hard to amputate it because it's an essential part of us, like water.

this sudden appearance of Homo sapiens is attributable to the rapid mutation of only seventeen brain-building genes. A scant few, really.

A carcinogen causes cancer because it is mutagenic—that is, it increases the rate of gene mutation. Given that mutations accumulate randomly, more mutations increase the risk of cancer,

We can’t tweak the genes of the food we eat without suspicion,” Erskine added. “We can pick and choose the naturally mutated ones until a blade of grass is a great ear of corn, but we can’t do it with purpose. Vic had dozens of examples like these. He rattled them off in the cafeteria that day.” Erskine ticked his fingers as he counted. “Vaccines versus natural immunities, cloning versus twins, modified foods. Or course he was perfectly right. The bastard always was. It was the manmade part that would have caused the chaos. It would be knowing that people were out to get us, that there was danger in the air we breathed.

if Darwin were alive today, he would likely revise a significant part of his great works, because the basic logic of evolution has shifted away from capital-n Nature toward two new core drivers: Unnatural selection* Nonrandom mutation*

Activating or inactivating any single gene, he postulated, produced only the first steps toward carcinogenesis. Cancer’s march was long and slow and proceeded though many mutations in many genes over many iterations. In genetic terms, our cells were not sitting on the edge of the abyss of cancer. They were dragged toward that abyss in graded, discrete steps.

As Lynn Margulis writes: “All the world’s bacteria essentially have access to a single gene pool and hence to the adaptive mechanisms of the entire bacterial kingdom. The speed of recombination over that of mutation is superior: it could take eukaryotic organisms a million years to adjust to a change on a worldwide scale that bacteria can accommodate in a few years.

The coming genetic mutation from homo sapiens into homo sanctus will bring wave after wave of enlightened children into the world who will seek only that which is built on natural cosmic laws, not the old systems which were rooted in fear and competition.

The Human Genome Project, the full sequence of the normal human genome, was completed in 2003. In its wake comes a far less publicized but vastly more complex project: fully sequencing the genomes of several human cancer cells. Once completed, this effort, called the Cancer Genome Atlas, will dwarf the Human Genome Project in its scope. The sequencing effort involves dozens of teams of researchers across the world. The initial list of cancers to be sequenced includes brain, lung, pancreatic, and ovarian cancer. The Human Genome Project will provide the normal genome, against which cancer’s abnormal genome can be juxtaposed and contrasted. The result, as Francis Collins, the leader of the Human Genome Project describes it, will be a “colossal atlas” of cancer—a compendium of every gene mutated in the most common forms of cancer: “When applied to the 50 most common types of cancer, this effort could ultimately prove to be the equivalent of more than 10,000 Human Genome Projects in terms of the sheer volume of DNA to be sequenced.

Cancer, we have discovered, is stitched into our genome. Oncogenes [cancer causing cells] arise from mutations in essential genes that regulate the growth of cells. Mutations accumulate in these genes when DNA is damaged by carcinogens, but also by seemingly random errors in copying genes when cells divide. The former might be preventable, but the latter is endogenous [originating from within]. Cancer is a flaw in our growth, but this flaw is deeply entrenched in ourselves. We can rid ourselves of cancer, then, only as much as we can rid ourselves of the processes in our physiology that depend on growth — aging, regeneration, healing, reproduction.

Valkyrie stood there and waited for her to start making sense. "There is a vegetable-plant hybrid we've been working on, modifying the genes and receptors, mutating the proteins and acids so that they are, in effect, neurotransmitters. Our work on the synapses alone has been quite illuminating." Valkyrie stood there and waited for her to start making sense.

The very effect of X-rays killing rapidly dividing cells—DNA damage—also created cancer-causing mutations in genes.

The Ethics of Genetic Control. “As we learn to direct mutations medically, we should do so. Not to control when we can is immoral.

Incomplete penetrance” meant that even if a mutation was present in the genome, its capacity to penetrate into a physical or morphological feature was not always complete.

In 2002, Pääbo and his colleagues discovered two mutations in the gene FOXP2 that seemed to be candidates for propelling the great changes that occurred after around fifty thousand years ago.

No matter who you are, who your parents are, you have innate genome flaws, and we do not yet know enough about the vast majority of these potential flaws, and their true risks, to make really intelligent choices.

Evolution can craft perfectly adapted organisms, but not in an intentional manner: it is not just a "blind watchmaker", but also a forgetful one. Its sole driver is survival and selection; its only memory is mutation.

The difference between the Platonic theory and the morphic-resonance hypothesis can be illustrated by analogy with a television set. The pictures on the screen depend on the material components of the set and the energy that powers it, and also on the invisible transmissions it receives through the electromagnetic field. A sceptic who rejected the idea of invisible influences might try to explain everything about the pictures and sounds in terms of the components of the set – the wires, transistors, and so on – and the electrical interactions between them. Through careful research he would find that damaging or removing some of these components affected the pictures or sounds the set produced, and did so in a repeatable, predictable way. This discovery would reinforce his materialist belief. He would be unable to explain exactly how the set produced the pictures and sounds, but he would hope that a more detailed analysis of the components and more complex mathematical models of their interactions would eventually provide the answer. Some mutations in the components – for example, by a defect in some of the transistors – affect the pictures by changing their colours or distorting their shapes; while mutations of components in the tuning circuit cause the set to jump from one channel to another, leading to a completely different set of sounds and pictures. But this does not prove that the evening news report is produced by interactions among the TV set’s components. Likewise, genetic mutations may affect an animal’s form and behaviour, but this does not prove that form and behaviour are programmed in the genes. They are inherited by morphic resonance, an invisible influence on the organism coming from outside it, just as TV sets are resonantly tuned to transmissions that originate elsewhere.

The world has been changing even faster as people, devices and information are increasingly connected to each other. Computational power is growing and quantum computing is quickly being realised. This will revolutionise artificial intelligence with exponentially faster speeds. It will advance encryption. Quantum computers will change everything, even human biology. There is already one technique to edit DNA precisely, called CRISPR. The basis of this genome-editing technology is a bacterial defence system. It can accurately target and edit stretches of genetic code. The best intention of genetic manipulation is that modifying genes would allow scientists to treat genetic causes of disease by correcting gene mutations. There are, however, less noble possibilities for manipulating DNA. How far we can go with genetic engineering will become an increasingly urgent question. We can’t see the possibilities of curing motor neurone diseases—like my ALS—without also glimpsing its dangers. Intelligence is characterised as the ability to adapt to change. Human intelligence is the result of generations of natural selection of those with the ability to adapt to changed circumstances. We must not fear change. We need to make it work to our advantage. We all have a role to play in making sure that we, and the next generation, have not just the opportunity but the determination to engage fully with the study of science at an early level, so that we can go on to fulfil our potential and create a better world for the whole human race. We need to take learning beyond a theoretical discussion of how AI should be and to make sure we plan for how it can be. We all have the potential to push the boundaries of what is accepted, or expected, and to think big. We stand on the threshold of a brave new world. It is an exciting, if precarious, place to be, and we are the pioneers. When we invented fire, we messed up repeatedly, then invented the fire extinguisher. With more powerful technologies such as nuclear weapons, synthetic biology and strong artificial intelligence, we should instead plan ahead and aim to get things right the first time, because it may be the only chance we will get. Our future is a race between the growing power of our technology and the wisdom with which we use it. Let’s make sure that wisdom wins.

The secret to battling cancer, then, is to find means to prevent these mutations from occurring in susceptible cells, or to find means to eliminate the mutated cells without compromising normal growth. The conciseness of that statement belies the enormity of the task. Malignant growth and normal growth are so genetically intertwined that unbraiding the two might be one of the most significant scientific challenges faced by our species. Cancer is built into our genomes: the genes that unmoor normal cell division are not foreign to our bodies, but rather mutated, distorted versions of the very genes that perform vital cellular functions. And cancer is imprinted in our society: as we extend our life span as a species, we inevitably unleash malignant growth (mutations in cancer genes accumulate with aging; cancer is thus intrinsically related to age). If we seek immortality, then so, too, in a rather perverse sense, does the cancer cell.

It is fundamental to the idea of a replicator that when a mistake or ‘mutation’ does occur it is passed on to future copies: the mutation brings into existence a new kind of replicator which ‘breeds true’ until there is a further mutation

Mutations litter the chromosomes. In individual specimens of breast and colon cancer, between fifty to eighty genes are mutated; in pancreatic cancers, about fifty to sixty. Even brain cancers, which often develop at earlier ages and hence may be expected to accumulate fewer mutations, possess about forty to fifty mutated genes. Only a few cancers are notable exceptions to this rule, possessing relatively few mutations across the genome. One of these is an old culprit, acute lymphoblastic leukemia: only five or ten genetic alterations cross its otherwise pristine genomic landscape.* Indeed, the relative paucity of genetic aberrancy in this leukemia may be one reason that this tumor is so easily felled by cytotoxic chemotherapy. Scientists speculate that genetically simple tumors (i.e., those carrying few mutations) might inherently be more susceptible to drugs, and thus intrinsically more curable. If so, the strange discrepancy between the success of high-dose chemotherapy in curing leukemia and its failure to cure most other cancers has a deep biological explanation. The search for a “universal cure” for cancer was predicated on a tumor that, genetically speaking, is far from universal. In

In 1962, Watson, Crick, and Wilkins won the Nobel Prize for their discovery. Franklin was not included in the prize. She had died in 1958, at the age of thirty-seven, from diffusely metastatic ovarian cancer-an illness ultimately linked to mutations in genes.

A mutation is only “abnormal” in a statistical sense: it is the less common variant. The desire to homogenize and “normalize” humans must be counterbalanced against biological imperatives to maintain diversity and abnormalcy. Normalcy is the antithesis of evolution.

...to remind myself that a person can die while they're still alive, simply by not choosing to live." It's taken me a long time to understand what she'd meant by that. Worry can be pernicious. Left unchecked, it slowly bleeds the soul of joy and replaces it with fear.

Felicia Boylan. I run the festivals here in town.” The woman paused. “Interesting that we’re all natural redheads. Only about two percent of the population has red hair. The gene itself is recessive. I believe the color is caused by a mutation of the MC1R. That’s a gene that—

Glenn used to say the reason you can't really imagine yourself being dead was that as soon as you say, "I'll be dead," you've said the word I, and so you're still alive inside the sentence. And that's how people got the idea of immortality of the soul--it was a consequence of grammar. And so was God, because as soon as there's a past tense, there has to be a past before the past, and you keep going back in time until you get to I don't know, and that's what God is. It's what you don't know--the dark, the hidden, the underside of the underside of the visible, and all because we have grammar, and grammar would be impossible without the FoxP2 gene, so God is a brain mutation, and that gene is the same one birds need for singing. So music is built in, Glenn said: it's knitted into us. It would be very hard to amputate it, because it's an essential part of us, like water.

Life managed without males for its first billion years, much of which was passed as single cells in a series of warm ponds. Then, in some ancient and neutral Eden, the fruit of the tree of sexual knowledge - a new mutation - persuaded members of a particular clone to fuse with cells from another, and then to divide. That ingenious idea is good news for the novel gene, as it doubles its rate of spread, but is a lot less so for those who receive it, who are obliged to copy the extra DNA. At once, two factions emerge, one keen to force itself upon the other. Thus sex was invented. Soon one contestant began to cheat. Large cells are expensive, but are better at dividing because they have more food reserves. Small cells are cheaper to make, but cannot afford to split. Their sole chance of success hence lies in fusion with a large cell. The first males had appeared on the scene.

Cancer, we have discovered, is stitched into our genome. Oncogenes arise from mutations in essential genes that regulate the growth of cells. Mutations accumulate in these genes when DNA is damaged by carcinogens, but also by seemingly random errors in copying genes when cells divide. The former might be preventable, but the latter is endogenous. Cancer is a flaw in our growth, but this flaw is deeply entrenched in ourselves. We can rid ourselves of cancer, then, only as much as we can rid ourselves of the processes in our physiology that depend on growth—aging, regeneration, healing, reproduction.

Yet to define genes by the diseases they cause is about as absurd as defining organs of the body by the diseases they get: livers are there to cause cirrhosis, hearts to cause heart attacks and brains to cause strokes. It is a measure, not of our knowledge but of our ignorance that this is the way the genome catalogues read. It is literally true that the only thing we know about some genes is that their malfunction causes a particular disease. This is a pitifully small thing to know about a gene, and a terribly misleading one. It leads to the dangerous shorthand that runs as follows: ‘X has got the Wolf-Hirschhorn gene.’ Wrong. We all have the Wolf-Hirschhorn gene, except, ironically, people who have Wolf-Hirschhorn syndrome. Their sickness is caused by the fact that the gene is missing altogether. In the rest of us, the gene is a positive, not a negative force. The sufferers have the mutation, not the gene.

We do know that humans got hit hard by the Toba Super Volcano. We were on the brink of extinction. That caused what population geneticists call a ‘population bottleneck.’ Some researchers believe that this bottleneck caused a small group of humans to evolve, to survive through mutation. These mutations could have led to humanity’s exponential explosion in intelligence. There’s genetic evidence for it. We know that every human being on the planet is directly descended from one man who lived in Africa around sixty thousand years ago—a person we geneticists call Y-Chromosomal Adam. In fact, everyone outside of Africa is descended from a small band of humans, maybe as few as one hundred, that left Africa about 50,000 years ago. Essentially, we’re all members of a small tribe that walked out of Africa after Toba and took over the planet. That tribe was significantly more intelligent than any other hominids in history.

For evolution to be true, there would have been innumerable transitional forms between different types of creatures. Therefore, for every known fossil species, many more must have existed to connect it to its ancestors and descendents [sic]. This is yet another example of evolutionary conclusions coming before the evidence. Really, the claim is an implicit admission that large numbers of transitional forms are predicted, which heightens the difficulty for evolutionists, given how few there are that even they could begin to claim were candidates. . . . Evolutionists believe that mutation provides new information for selection. But no known mutation has ever increased genetic information, although there should be many examples observable today if mutation/selection were truly adequate to explain the goo-to-you theory. . . . Adaptation and natural selection are biological facts; amoeba-to-man evolution is not. Natural selection can only work on the genetic information present in a population of organisms--it cannot create new information. For example, since no known reptiles have genes for feathers, no amount of selection will produce a feathered reptile. Mutations in genes can only modify or eliminate existing structures, not create new ones. If in a certain environment a lizard survives better with smaller legs, or no legs, then varieties with this trait will be selected for. This might more accurately be called devolution, not evolution. . . . Note that even if such a mutation were ever discovered, evolutionists would still need to find hundreds more to give their theory the observational boost it desperately needs.

EVOLUTION RESTS ON three steps: (a) certain biological traits are inherited by genetic means; (b) mutations and gene recombination produce variation in those traits; (c) some of those variants confer more “fitness” than others. Given those conditions, over time the frequency of more “fit” gene variants increases in a population.

a result, the most efficient way for evolutionary forces to spread beneficial mutations has often been to invent mutations anew rather than to import them from other populations.44 The limited migration rates between some regions of Africa over the last few thousand years has resulted in what Ralph and Coop have described as a “tessellated” pattern of population structure in Africa. Tessellation is a mathematical term for a landscape of tiles—regions of genetic homogeneity demarcated by sharp boundaries—that is expected to form when the process of homogenization due to gene exchanges among neighbors competes with the process of generating new advantageous variations in each region.

Every generation of humans will produce variants and mutants; it is an inextricable part of our biology. A mutation is only “abnormal” in a statistical sense: it is the less common variant. The desire to homogenize and “normalize” humans must be counterbalanced against biological imperatives to maintain diversity and abnormalcy. Normalcy is the antithesis of evolution.

Surprisingly, palindromes appear not just in witty word games but also in the structure of the male-defining Y chromosome. The Y's full genome sequencing was completed only in 2003. This was the crowning achievement of a heroic effort, and it revealed that the powers of preservation of this sex chromosome have been grossly underestimated. Other human chromosome pairs fight damaging mutations by swapping genes. Because the Y lacks a partner, genome biologists had previously estimated that its cargo was about to dwindle away in perhaps as little as five million years. To their amazement, however, the researchers on the sequencing team discovered that the chromosome fights withering with palindromes. About six million of its fifty million DNA letters form palindromic sequences-sequences that read the same forward and backward on the two strands of the double helix. These copies not only provide backups in case of bad mutations, but also allow the chromosome, to some extent, to have sex with itself-arms can swap position and genes are shuffled. As team leader David Page of MIT has put it, "The Y chromosome is a hall of mirrors.

Josie suffers from a very rare disease," he said. "It's caused by a genetic mutation. But the good news is that researchers are working on a gene therapy that could correct the mutation. It's still in the experimental stage, but there's a good chance it'll work. If it does, Josie could be cured." And I wondered, as I often did these days, whether Artificial Friends could help with such work.

In the above examples, a sample of the tumor (e.g., biopsy) is tested to determine the molecular signature. Testing may be by genetic sequence tests (e.g., for BCR-ABL, mutated EGFR, or HER2 gene amplification) or tissue protein stains (e.g., for the presence of ER/PR receptors or HER2 protein overexpression). The results of the testing will guide the choice of treatment—it will be personalized for the individual.

That is why urban evolution can proceed so rapidly: the animals and plants that need to adapt to whatever new feature humans release in their urban environment do not need to wait for the right mutations to come along. Mostly, the necessary gene variants are already there, waiting in the wings of the standing genetic variation. It only takes natural selection to bring them out into the limelight, and give them a chance to shine.

If a program or strategy is successful, this means that copies of it will tend to become more numerous in the population of programs and will ultimately become almost universal. It will therefore come to be surrounded by copies of itself. If it is to remain universal, therefore, it must be successful when competing against copies of itself, successful compared with rare different strategies that might arise by mutation or invasion.

The contamination of drinking water in dense urban settlements did not merely affect the number of V. cholerae circulating through the small intestines of mankind. It also greatly increased the lethality of the bacteria. This is an evolutionary principle that has long been observed in populations of disease-spreading microbes. Bacteria and viruses evolve at much faster rates than humans do, for several reasons. For one, bacterial life cycles are incredibly fast: a single bacterium can produce a million offspring in a matter of hours. Each new generation opens up new possibilities for genetic innovation, either by new combinations of existing genes or by random mutations. Human genetic change is several orders of magnitude slower; we have to go through a whole fifteen-year process of maturation before we can even think about passing our genes to a new generation.

When contemplating humanity’s potential future technologies and their use and effect on our world, we should bear in mind that the coming mutation will directly affect the way we think. Since our primary awareness is shifting to the solar plexus area, all future insights and breakthroughs in science will come from this awareness rather than from our logical mind. This will entirely change scientific approach. Instead of beginning with doubt and then working to resolve that doubt through scientific method, we will begin with certainty and use logic to confirm and deepen that certainty. This will give birth to a new era of science and technology, and the future science will be a science of synthesis. Science will work hand in hand with art, music, mythology, and psychology and, of particular importance, it will be rooted in the physical structure and understanding of the body.

The drive to change the genome of a human embryo has turned into an intercontinental arms race. As of this writing, four other groups in China are reportedly working on introducing permanent mutations in human embryos. By the time this book is published, I would not be surprised if the first successful targeted genome modification of a human embryo had been achieved in a laboratory. The first "post-genomic" human might be on his or her way to being born.

Another way is via genetic engineering. Here the germ is inserted into plasmid that has been manipulated by scientists. This type of plasmid is circular segments of DNA extracted from bacteria to serve as a vector. Scientists can add multiple genes and whatever genes they want into this plasmid. In case of vaccines, this includes a genetic piece of the vaccine germ and normally a gene for antibiotic resistance. This means that when the toxic gene is cultured inside the yeast, it has been designed with a new genetic code that makes it resistant to the antibiotic it’s coded for. The gene-plasmid combo is inserted into a yeast cell to be replicated. When the yeast replicates, the DNA from the plasmid is reproduced as a part of the yeast DNA. Once enough cells have been replicated, the genetic material in the new and improved yeast cell is extracted and put into the vaccine. Examples of this vaccine are the acellular pertussis and hepatitis B vaccines. One thing that doesn’t seem to concern scientists is the fact that the manmade genetic combination becomes the vaccine component. This mixture of intended and unintended genetic information may cause our immune system to overreact. This can be especially complicated for a child with compromised immune system. Another concern is that this new genetic code can become integrated with our own genetic material. Yeast, for instance, is very much like human DNA. It shares about one third of our proteins.

Normal cells could acquire these cancer-causing mutations through four mechanisms. The mutations could be caused by environmental insults, such as tobacco smoke, ultraviolet light, or X-rays—agents that attack DNA and change its chemical structure. Mutations could arise from spontaneous errors during cell division (every time DNA is replicated in a cell, there’s a minor chance that the copying process generates an error—an A switched to a T, G, or C, say). Mutant cancer genes could be inherited from parents, thereby causing hereditary cancer syndromes such as retinoblastoma and breast cancer that coursed through families. Or the genes could be carried into the cells via viruses, the professional gene carriers and gene swappers of the microbial world. In all four cases, the result converged on the same pathological process: the inappropriate activation or inactivation of genetic pathways that controlled growth, causing the malignant, dysregulated cellular division that was characteristic of cancer.

When changes in one genetic trait are the source of selection for changes in a second, the rate of response in the latter depends in parts on the rate of change in the former, which, as a rule, is not fast. In comparison, if a cultural practice modifies selection acting on human genetic variation, then the greater the proportion of individuals in the population that exhibit the cultural trait, the stronger the selection on the gene. As a consequence, the rapid spread of a cultural practice often leads quickly to the maximally strong selection of the advantageous genetic variant, which rapidly increases in frequency. Cultural practices typically spread more quickly than genetic mutations, simply because cultural learning typically operates at faster rates than biological evolution. What does the speed with which a culturla trait spreads depend upon? Answer: the fidelity of cultural transmission. The very factor that is critical to the emergence of complex cumulative culture in humans is also a major determinant of evolutionary responses to that culture.

In 1993, a New York hospital launched an aggressive program to screen Ashkenazi Jews for three genetic diseases, including cystic fibrosis, Gaucher’s disease, and Tay-Sachs disease (mutations in these genes are more prevalent in the Ashkenazi population). Parents could freely choose to be screened, to undergo amniocentesis for prenatal diagnosis, and to terminate a pregnancy if the fetus was found to be affected. Since the launch of the program, not a single baby with any of these genetic diseases has been born at that hospital.

Every human that ever existed came into being as a result of male sperm inseminating a female egg. Think of the first baby to possess a soul. That baby was very similar to her mother and father, except that she had a soul and they didn’t. Our biological knowledge can certainly explain the birth of a baby whose cornea was a bit more curved than her parents’ corneas. A slight mutation in a single gene can account for that. But biology cannot explain the birth of a baby possessing an eternal soul from parents who did not have even a shred of a soul.

The idea that germline editing was “unnatural” began to recede in her thinking. All medical advances attempt to correct something that happened “naturally,” she realized. “Sometimes nature does things that are downright cruel, and there are many mutations that cause enormous suffering, so the idea that germline editing was unnatural began to carry less weight for me,” she says. “I am not sure how to make a sharp distinction in medicine between what is natural and what is unnatural, and I think it’s dangerous to use that dichotomy to block something that could alleviate suffering and disability.

Should we consider allowing parents to fully sequence their children’s genomes and potentially terminate pregnancies with such known devastating genetic mutations? We would certainly eliminate Erika’s mutation from the human gene pool—but we would eliminate Erika as well. I will not minimize the enormity of Erika’s suffering, or that of her family—but there is, indubitably, a deep loss in that. To fail to acknowledge the depth of Erika’s anguish is to reveal a flaw in our empathy. But to refuse to acknowledge the price to be paid in this trade-off is to reveal, conversely, a flaw in our humanity.

It is the impulse of science to try to understand nature, and the impulse of technology to try to manipulate it. Recombinant DNA had pushed genetics from the realm of science into the realm of technology. Genes were not abstractions anymore. They could be liberated from the genomes of organisms where they had been trapped for millennia, shuttled between species, amplified, purified, extended, shortened, altered, remixed, mutated, mixed, matched, cut, pasted, edited; they were infinitely malleable to human intervention. Genes were no longer just the subjects of study, but the instruments of study.

Let the chromosomes be represented by the keyboard of a grand piano-a very grand piano with thousands of keys. Then each key will be a gene. Every cell in the body carries a microscopic but complete keyboard in its nucleus. But each specialised cell is only permitted to sound one chord, according to its specialty-the rest of its genetic keyboard has been inactivated by scotch tape. The fertilised egg, and the first few generations of its daughter cells, had the complete keyboard at their disposal. But succesive generations have, at each 'point of no return', larger and larger areas of it covered by scotch tape. In the end, a muscle cell can only do one thing: contract-strike a single chord. The scotch tape is known in the language of genetics as the 'repressor'. The agent which strikes the key and activates the gene is an 'inducer'. A mutated gene is a key which has gone out of tune. When quite a lot of key have gone quite a lot out of tune, the result, we were asked to believe, was a much improved, wonderful new melody- a reptile transformed into a bird, or a monkey into a man. It seems that at some point the theory must have gone wrong. The point where it went wrong was the atomistic concept of the gene.

of now, the main difference has been found in the HAR1 (human accelerated region 1), a segment of a recently discovered RNA gene. The RNA that is expressed in early development (HAR1F) is specific to the reelin-producing Cajal-Retzius cells in the brain. HAR1F comes to expression together with reelin in the seventeenth to nineteenth weeks of fetal development, a crucial stage in the formation of the six-layered cerebral cortex. The mutations in this human gene are probably over a million years old and could have played a crucial role in the emergence of modern humankind. Throughout our evolution, an enormous

The fact that the genome also encodes genes to repair damage to the genome was discovered by several geneticists, including Evelyn Witkin and Steve Elledge. Witkin and Elledge, working independently, identified an entire cascade of proteins that sensed DNA damage, and activated a cellular response to repair or temporize the damage (if the damage was catastrophic, it would halt cell division). Mutations in these genes can lead to the accumulation of DNA damage-and thus, more mutations-ultimately leading to cancer. The fourth R of gene phyisiology, essential to both the survival and mutability of organisms, might be "repair.

The CF gene codes a molecule that channels salt across cellular membranes. The most common mutation is a deletion of three bases of DNA that results in the removal, or deletion, of just one amino acid from the protein (in the language of genes, three bases of DNA encode a single amino acid). This deletion creates a dysfunctional protein that is unable to move chloride-one component of sodium chloride, i.e., common salt-across membranes. The salt in sweat cannot be absorbed back into the body, resulting in the characteristically salty sweat. Nor can the body secrete salt and water into the intestines, resulting in the abdominal symptoms.

The concept of internal selection, of a hierarchy of controls which eliminate the consequences of harmful gene-mutations and co-ordinates the effects of useful mutations, is the missing link in orthodoxy theory between the 'atoms' of heredity and the living stream of evolution. Without that link, neither of them makes sense. There can be no doubt that random mutations do occur: they can be observed in the laboratory. There can be no doubt that Darwinian selection is a powerful force. But in between these two events, between the chemical changes in a gene and the appearance of the finished product as a newcomer on the evolutionary stage, there is a whole hierarchy of internal processes at work which impose strict limitations on the range of possible mutations and thus considerably reduce the importance of the chance factor. We might say that the monkey works at a typewriter which the manufacturers have programmed to print only syllables which exist in our language, but not nonsense syllables. If a nonsense syllable occurs, the machine will automatically erase it. To pursue the metaphor, we would have to populate the higher levels of the hierarchy with proof-readers and then editors, whose task is no longer elimination, but correction, self-repair and co-ordination-as in the example of the mutated eye.

In 2006, the Vogelstein team revealed the first landmark sequencing effort by analyzing thirteen thousand genes in eleven breast and colon cancers. (Although the human genome contains about twenty thousand genes in total, Vogelstein’s team initially had tools to assess only thirteen thousand.) In 2008, both Vogelstein’s group and the Cancer Genome Atlas consortium extended this effort by sequencing hundreds of genes of several dozen specimens of brain tumors. As of 2009, the genomes of ovarian cancer, pancreatic cancer, melanoma, lung cancer, and several forms of leukemia have been sequenced, revealing the full catalog of mutations in each tumor type. Perhaps

It will be agreed that you can’t divide a cake up into its component crumbs and say ‘This crumb corresponds to the first word in the recipe, this crumb corresponds to the second word in the recipe’, etc. In this sense it will be agreed that the whole recipe maps onto the whole cake. But now suppose we change one word in the recipe; for instance, suppose ‘baking-powder’ is deleted or is changed to ‘yeast’. We bake 100 cakes according to the new version of the recipe, and 100 cakes according to the old version of the recipe. There is a key difference between the two sets of 100 cakes, and this difference is due to a one-word difference in the recipes. Although there is no one-to-one mapping from word to crumb of cake, there is one-to-one mapping from word difference to whole-cake difference. ‘Baking-powder’ does not correspond to any particular part of the cake: its influence affects the rising, and hence the final shape, of the whole cake. If ‘baking-powder’ is deleted, or replaced by ‘flour’, the cake will not rise. If it is replaced by ‘yeast’, the “cake will rise but it will taste more like bread. There will be a reliable, identifiable difference between cakes baked according to the original versoin and the ‘mutated’ versions of the recipe, even though there is no particular ‘bit’ of any cake that corresponds to the words in question. This is a good analogy for what happens when a gene mutates.

It will be agreed that you can’t divide a cake up into its component crumbs and say ‘This crumb corresponds to the first word in the recipe, this crumb corresponds to the second word in the recipe’, etc. In this sense it will be agreed that the whole recipe maps onto the whole cake. But now suppose we change one word in the recipe; for instance, suppose ‘baking-powder’ is deleted or is changed to ‘yeast’. We bake 100 cakes according to the new version of the recipe, and 100 cakes according to the old version of the recipe. There is a key difference between the two sets of 100 cakes, and this difference is due to a one-word difference in the recipes. Although there is no one-to-one mapping from word to crumb of cake, there is one-to-one mapping from word difference to whole-cake difference. ‘Baking-powder’ does not correspond to any particular part of the cake: its influence affects the rising, and hence the final shape, of the whole cake. If ‘baking-powder’ is deleted, or replaced by ‘flour’, the cake will not rise. If it is replaced by ‘yeast’, the “cake will rise but it will taste more like bread. There will be a reliable, identifiable difference between cakes baked according to the original version and the ‘mutated’ versions of the recipe, even though there is no particular ‘bit’ of any cake that corresponds to the words in question. This is a good analogy for what happens when a gene mutates.

But what is “natural”? I wonder. On one hand: variation, mutation, change, inconstancy, divisibility, flux. And on the other: constancy, permanence, indivisibility, fidelity. Bhed Abhed. It should hardly surprise us that DNA, the molecule of contradictions, encodes an organism of contradictions. We seek constancy in heredity—and find its opposite: variation. Mutants are necessary to maintain the essence of our selves. Our genome has negotiated a fragile balance between counterpoised forces, pairing strand with opposing strand, mixing past and future, pitting memory against desire. It is the most human of all things that we possess. Its stewardship may be the ultimate test of knowledge and discernment for our species.

That’s how one complex adaptation can jump-start a new complex adaptation. Complexity can also accrete incrementally, starting from a single mutation. First comes some gene A which is simple, but at least a little useful on its own, so that A increases to universality in the gene pool. Now along comes gene B, which is only useful in the presence of A, but A is reliably present in the gene pool, so there’s a reliable selection pressure in favor of B. Now a modified version of A* arises, which depends on B, but doesn’t break B’s dependency on A∕A*. Then along comes C, which depends on A* and B, and B*, which depends on A* and C. Soon you’ve got “irreducibly complex” machinery that breaks if you take out any single piece.

But what *is* "natural"? I wonder. On one hand: variation, mutation, change, inconstancy, divisibility, flux. And on the other: constancy, permanence, indivisibility, fidelity. Bhed. Abhed. It should hardly surprise us that DNA, the molecule of contradictions, encodes an organism of contradictions. We seek constancy in heredity—and find its opposite: variation. Mutants are necessary to maintain the essence of our selves. Our genome has negotiated a fragile balance between counterpoised forces, pairing strand with opposing strand, mixing past and future, pitting memory against desire. It is the most human of all things that we possess. Its stewardship may be the ultimate test of knowledge and discernment for our species. 

The fundamental units of natural selection, the basic things that survive or fail to survive, that form lineages of identical copies with occasional random mutations, are called replicators. DNA molecules are replicators. They generally, for reasons that we shall come to, gang together into large communal survival machines or ‘vehicles’. The vehicles that we know best are individual bodies like our own. A body, then, is not a replicator; it is a vehicle. I must emphasize this, since the point has been misunderstood. Vehicles don’t replicate themselves; they work to propagate their replicators. Replicators don’t behave, don’t perceive the world, don’t catch prey or run away from predators; they make vehicles that do all those things.

One of the most studied organisms in this context is the tiny polyp Hydra, which possesses only a hundred thousand cells. Its neural network is concentrated in its head and foot: a first evolutionary step toward developing a brain and spinal cord. Hydra’s nervous system contains a chemical messenger—a minuscule protein—that resembles two of our own: vasopressin and oxytocin. A protein of this kind is called a neuropeptide. In vertebrates, the gene for this particular neuropeptide first doubled and then mutated in two places, creating the two closely related but specialized neuropeptides vasopressin and oxytocin, which have recently become the focus of interest, partly because of their important role as messengers in our social brains (see chapter 9).

Vaccinations are the application of evolutionary principles in action. If we can control the contact made between pathogen and lymphocyte populations, we can go a long way toward eliminating disease.108 It doesn’t require total annihilation but rather a control on population dynamics. Vaccines are the way we use selective cloning to keep a pathogenic population in a state of benign coexistence. The process is based on evolution, as pointed out by Nobel laureate Susumu Tonegawa: “Genes can mutate and recombine. These dynamic characteristics of genetic material are essential elements of evolution. Do they also play an important role during the development of a single multicellular organism? Our results strongly suggest that this is the case for the immune system.

Genetic atomism is dead. Hereditary stability and hereditary change are both based, not on a mosaic of genes, but on the action of the gene-complex 'as a whole'. But this face-saving expression-which is now coming into increased use-is empty, like so many other holistic formulations, unless we interpolate between the gene-complex as a whole, and the individual gene, a hierarchy of genetic sub-assemblies-self-regulating holons of heredity, which control the development of organs, and also control their possible evolutionary modifications, by canalising the effects of random mutations. A hierarchy with its built-in, self-regulatory safeguards is a stable affair. It cannot be pulled in here, pulled out there, like Patou belabouring his model. It is capable of variation and change, but only in co-ordinated ways and only in limited directions.

Whereas new genes arise solely by chance through random mutations, humans often generate cultural variations intentionally. Inventions like farming, computers, and Marxism were created through ingenuity and for a purpose. In addition, memes are transmitted not just from parents to offspring, but from multiple sources. Reading this book is just one of your many horizontal exchanges of information today. Finally, although cultural evolution can occur randomly (think of fashions like tie width or skirt length), cultural change often happens through an agent of change, such as a persuasive leader, television, or a community’s collective desire to solve a challenge like hunger, disease, or the threat of Russians on the moon. Together, these differences make cultural evolution a faster and often more potent cause of change than biological evolution.

The travels to discovery my heritage revealed to me that the South might not be a place so much as it is a series of moments, which in proper composition communicate an indelible history that people cling to as horseshoes do to old barns. In cooking, the style of Southern food is more verb that adjective; it is the exercise of specific histories, not just the result. In food it becomes less a matter of location than of process, and it becomes difficult to separate the nature of the process from the heritage by which one acquired it. Southern cuisine is a series of geographic and gastronomic mutations made long ago by people whose fade into the earth provides half of the justification for why their descendants keep the process going at all. Our ancestry is not an afterthought; it is both raison d'etre and our mise en place, it is action and reaction.

Glenn used to say the reason you can’t really imagine yourself being dead was that as soon as you say, “I’ll be dead,” you’ve said the word I, and so you’re still alive inside the sentence. And that’s how people got the idea of the immortality of the soul — it was a consequence of grammar. And so was God, because as soon as there’s a past tense, there has to be a past before the past, and you keep going back in time until you get to I don’t know, and that’s what God is. It’s what you don’t know — the dark, the hidden, the underside of the visible, and all because we have grammar, and grammar would be impossible without the FoxP2 gene; so God is a brain mutation, and that gene is the same one birds need for singing. So music is built in, Glenn said: it’s knitted into us. It would be very hard to amputate it because it’s an essential part of us, like water.

Here’s a simple example. The wooly mammoth inhabited the northern parts of Eurasia and North America, and was adapted to the cold by bearing a thick coat of hair (entire frozen specimens have been found buried in the tundra).3 It probably descended from mammoth ancestors that had little hair—like modern elephants. Mutations in the ancestral species led to some individual mammoths-like some modern humans—being hairier than others. When the climate became cold, or the species spread into more northerly regions, the hirsute individuals were better able to tolerate their frigid surroundings, and left more offspring than their balder counterparts. This enriched the population in genes for hairiness. In the next generation, the average mammoth would be a bit hairier than before. Let this process continue over some thousands of generations, and your smooth mammoth gets replaced by a shaggy one.

gene, the mutation of whose DNA building blocks accelerated after the split between humans and chimpanzees, around 5.5 million years ago. The theory has also been put forward that the human brain is still evolving, on the grounds that a genetic variant of ASPM is thought to have originated only 5,800 years ago and then spread rapidly through the population. A genetic variant of the microcephalin gene (D allele of MCPH1), which regulates brain size, is thought to have only entered the DNA of Homo sapiens during the last ice age, around 37,000 years ago—yet 70 percent of the current world population carries this variant. A rapid increase of this kind is only possible if a variant confers a clear evolutionary advantage. Genes whose mutations are associated with human language have also been found. Mutations of the FOXP2 gene cause language and speech disorders that run in families. And ASPM and microcephalin also appear to have a linguistic connection.

With the rise of molecular genetics, it has become possible to search for possible changes (mutations, polymorphisms) in target genes. Much effort has gone into investigating variations in genes that contribute to serotonin transmission, because serotonin-related drugs have antidepressant and anxiolytic properties. This assumes, however, that the treatment mechanism is the same mechanism that gives rise to the disorder.53 Although this is consistent with the old chemical imbalance hypothesis, it is not a conclusion that should simply be accepted without careful assessment. Nevertheless, studies of the genetic control of serotonin have found interesting results. For example, people with a certain variant (polymorphism) of a gene controlling a protein involved in serotonin transmission are more reactive to threatening stimuli, and this hyperreactivity is associated with increased amygdala activity during the threat.54 Further, it has been reported that this variant of the gene can account for 7 percent to 9 percent of the inheritance of anxiety.55

By the end of this decade, permutations and combinations of genetic variants will be used to predict variations in human phenotype, illness, and destiny. Some diseases might never be amenable to such a genetic test, but perhaps the severest variants of schizophrenia or heart disease, or the most penetrant forms of familial cancer, say, will be predictable by the combined effect of a handful of mutations. And once an understanding of "process" has been built into predictive algorithms, the interactions between various gene variants could be used to compute ultimate effects on a whole host of physical and mental characteristics beyond disease alone. Computational algorithms could determine the probability of the development of heart disease or asthma or sexual orientation and assign a level of relative risk for various fates to each genome. The genome will thus be read not in absolutes, but in likelihoods-like a report card that does not contain grades but probabilities, or a resume that does not list past experiences but future propensities. It will become a manual for previvorship.

Viruses, for instance, perform a really irritating function of intermingling the DNA from every species on Earth with every other. As Richard Lewontin puts it . . . It used to be thought that new functions had to arise by mutations of the genes already possessed by a species and that the only way such mutations could spread was by the normal processes of reproduction. It is now clear that genetic material has moved during evolution from species to species by means of retroviruses and other transposable particles. . . . What is so extraordinary in its implications for evolution is that transposition can occur between forms of life that are quite different, between distantly related vertebrates, for example, or even between plants and bacteria. . . . Thus, the assumption that species are on independent evolutionary pathways, once they have diverged from each other and can no longer interbreed, is incorrect. All life-forms are in potential genetic contact and genetic exchanges between them are going on. . . . The evolutionary “tree of life” seems the wrong metaphor. Perhaps we should think of it as an elaborate bit of macramé.16

Familial schizophrenia (like normal human features such as intelligence and temperament) is thus highly heritable but only moderately inheritable. In other words, genes-hereditary determinants-are crucially important to the future development of the disorder. If you possess a particular combination of genes, the chance of developing the illness is extremely high: hence the striking concordance among identical twins. On the other hand, the inheritance of the disorder across generations is complex. Since genes are mixed and matched in every generation, the chance that you will inherit that exact permutation of variants from your father or mother is dramatically lower. In some families, perhaps, there are fewer gene variants, but with more potent effects-thereby explaining the recurrence of the disorder across generations. In other families, the genes may have weaker effects and require deeper modifiers and triggers-thereby explaining the infrequent inheritance. In yet other families, a single, highly penetrant gene is accidentally mutated in sperm or egg cells before conception, leading to the observed cases of sporadic schizophrenia.

In contrast, ever since the Cognitive Revolution, Sapiens have been able to change their behaviour quickly, transmitting new behaviours to future generations without any need of genetic or environmental change. As a prime example, consider the repeated appearance of childless elites, such as the Catholic priesthood, Buddhist monastic orders and Chinese eunuch bureaucracies. The existence of such elites goes against the most fundamental principles of natural selection, since these dominant members of society willingly give up procreation. Whereas chimpanzee alpha males use their power to have sex with as many females as possible – and consequently sire a large proportion of their troop’s young – the Catholic alpha male abstains completely from sexual intercourse or raising a family. This abstinence does not result from unique environmental conditions such as a severe lack of food or want of potential mates. Nor is it the result of some quirky genetic mutation. The Catholic Church has survived for centuries, not by passing on a ‘celibacy gene’ from one pope to the next, but by passing on the stories of the New Testament and of Catholic canon law.

In network models of the interactome, these truncating mutations can be thought of as the removal of one node along with all its edges - a node removal. Nonconservative missense mutations of amino acids in the protein core that lead to major folding problems, protein aggregation, and premature protein degradation can also be modeled as node removals. At the other end of the mutational spectrum are small in-frame indels or missense mutations. These can preserve protein folding, but may modify the active site of an enzyme or affect the binding to another protein or macromolecule. In network models, these mutations, which specifically perturb a single molecular interaction, have been labeled as edge-specific or "edgetic". While investigation of the precise interaction defects associated with point mutations is of course not new, the term edgetic promotes a subtle yet meaningful archetype shift from conventional gene-centered models, which emphasize consideration of which specific edges are affected by a mutation, complement and extend classic gene-centric models, which ascertain only whether a gene product is present or not present and neglect less overt alterations of a given gene or gene product.

The Case of the Eyeless Fly The fruit fly has a mutant gene which is recessive, i.e., when paired with a normal gene, has no discernible effect (it will be remembered that genes operate in pairs, each gene in the pair being derived from one parent). But if two of these mutant genes are paired in the fertilised egg, the offspring will be an eyeless fly. If now a pure stock of eyeless flies is made to inbreed, then the whole stock will have only the 'eyeless' mutant gene, because no normal gene can enter the stock to bring light into their darkness. Nevertheless, within a few generations, flies appear in the inbred 'eyeless' stock with eyes that are perfectly normal. The traditional explanation of this remarkable phenomenon is that the other members of the gene-complex have been 'reshuffled and re-combined in such a way that they deputise for the missing normal eye-forming gene.' Now re-shuffling, as every poker player knows, is a randomising process. No biologist would be so perverse as to suggest that the new insect-eye evolved by pure chance, thus repeating within a few generations an evolutionary process which took hundreds of millions of years. Nor does the concept of natural selection provide the slightest help in this case. The re-combination of genes to deputise for the missing gene must have been co-ordinated according to some overall plan which includes the rules of genetic self-repair after certain types of damage by deleterious mutations. But such co-ordinative controls can only operate on levels higher than that of individual genes. Once more we are driven to the conclusion that the genetic code is not an architect's blueprint; that the gene-complex and its internal environment form a remarkably stable, closely knit, self-regulating micro-hierarchy; and that mutated genes in any of its holons are liable to cause corresponding reactions in others, co-ordinated by higher levels. This micro-hierarchy controls the pre-natal skills of the embryo, which enable it to reach its goal, regardless of the hazards it may encounter during development. But phylogeny is a sequence of ontogenies, and thus we are confronted with the profound question: is the mechanism of phylogeny also endowed with some kind of evolutionary instruction booklet? Is there a strategy of the evolutionary process comparable to the 'strategy of the genes'-to the 'directiveness' of ontogeny (as E.S. Russell has called it)?

Working independently, Baltimore and Temin discovered an enzyme found in retroviruses that could build DNA from an RNA template. They called the enzyme reverse transcriptase-"reverse" because it inverted the normal direction of information flow: from RNA back to DNA, or from a gene's message backward to a gene, thereby violating Crick's "central dogma" (that genetic information only moved from genes to messages, but never backward). Using reverse transcriptase, ever RNA in a cell could be used as a template to build its corresponding gene. A biologist could thus generate a catalog, or "library" of all "active" genes in a cell-akin to a library of books grouped by subject. There would be a library of genes for T cells and another for red blood cells, a library for neurons in the retina, for insulin-secreting cells of the pancreas, and so forth. By comparing libraries derived from two cells-a T cell and a pancreas cell, say-an immunologist could fish out genes that were active in one cell and not the other (e.g., insulin or the T cell receptor). Once identified, that gene could be amplified a millionfold in bacteria. The gene could be isolated and sequenced, its RNA and protein sequence determined, its regulatory regions identified; it could be mutated an inserted into a different cell to decipher the gene's structure and function. In 1984 this technique was deployed to clone the T cell receptor-a landmark achievement in immunology.

The humanities, in contrast, emphasise the crucial importance of intersubjective entities, which cannot be reduced to hormones and neurons. To think historically means to ascribe real power to the contents of our imaginary stories. Of course, historians don’t ignore objective factors such as climate changes and genetic mutations, but they give much greater importance to the stories people invent and believe. North Korea and South Korea are so different from one another not because people in Pyongyang have different genes to people in Seoul, or because the north is colder and more mountainous. It’s because the north is dominated by very different fictions. Maybe someday breakthroughs in neurobiology will enable us to explain communism and the crusades in strictly biochemical terms. Yet we are very far from that point. During the twenty-first century the border between history and biology is likely to blur not because we will discover biological explanations for historical events, but rather because ideological fictions will rewrite DNA strands; political and economic interests will redesign the climate; and the geography of mountains and rivers will give way to cyberspace. As human fictions are translated into genetic and electronic codes, the intersubjective reality will swallow up the objective reality and biology will merge with history. In the twenty-first century fiction might thereby become the most potent force on earth, surpassing even wayward asteroids and natural selection. Hence if we want to understand our future, cracking genomes and crunching numbers is hardly enough. We must also decipher the fictions that give meaning to the world.

Unlike any other chromosome, the Y is “unpaired”—i.e., it has no sister chromosome and no duplicate copy, leaving every gene on the chromosome to fend for itself. A mutation in any other chromosome can be repaired by copying the intact gene from the other chromosome. But a Y chromosome gene cannot be fixed, repaired, or recopied from another chromosome; it has no backup or guide (there is, however, a unique internal system to repair genes in the Y chromosome). When the Y chromosome is assailed by mutations, it lacks a mechanism to recover information. The Y is thus pockmarked with the potshots and scars of history. It is the most vulnerable spot in the human genome. As a consequence of this constant genetic bombardment, the human Y chromosome began to jettison information millions of years ago. Genes that were truly valuable for survival were likely shuffled to other parts of the genome where they could be stored securely; genes with limited value were made obsolete, retired, or replaced; only the most essential genes were retained (some of these genes were duplicated in the Y chromosome itself—but even this strategy does not solve the problem completely). As information was lost, the Y chromosome itself shrank—whittled down piece by piece by the mirthless cycle of mutation and gene loss. That the Y chromosome is the smallest of all chromosomes is not a coincidence: it is largely a victim of planned obsolescence (in 2014, scientists discovered that a few extremely important genes may be permanently lodged in the Y). In genetic terms, this suggests a peculiar paradox. Sex, one of the most complex of human traits, is unlikely to be encoded by multiple genes. Rather, a single gene, buried rather precariously in the Y chromosome, must be the master regulator of maleness.I Male readers of that last paragraph should take notice: we barely made it.

Until recently, three unspoken principles have guided the arena of genetic diagnosis and intervention. First, diagnostic tests have largely been restricted to gene variants that are singularly powerful determinants of illness—i.e., highly penetrant mutations, where the likelihood of developing the disease is close to 100 percent (Down syndrome, cystic fibrosis, Tay-Sachs disease). Second, the diseases caused by these mutations have generally involved extraordinary suffering or fundamental incompatibilities with “normal” life. Third, justifiable interventions—the decision to abort a child with Down syndrome, say, or intervene surgically on a woman with a BRCA1 mutation—have been defined through social and medical consensus, and all interventions have been governed by complete freedom of choice. The three sides of the triangle can be envisioned as moral lines that most cultures have been unwilling to transgress. The abortion of an embryo carrying a gene with, say, only a ten percent chance of developing cancer in the future violates the injunction against intervening on low-penetrance mutations. Similarly, a state-mandated medical procedure on a genetically ill person without the subject’s consent (or parental consent in the case of a fetus) crosses the boundaries of freedom and noncoercion. Yet it can hardly escape our attention that these parameters are inherently susceptible to the logic of self-reinforcement. We determine the definition of “extraordinary suffering.” We demarcate the boundaries of “normalcy” versus “abnormalcy.” We make the medical choices to intervene. We determine the nature of “justifiable interventions.” Humans endowed with certain genomes are responsible for defining the criteria to define, intervene on, or even eliminate other humans endowed with other genomes. “Choice,” in short, seems like an illusion devised by genes to propagate the selection of similar genes.

Modeling the evolution of modularity became significantly easier after a kind of genetic variation was discovered by quantitative trait locus (QTL) mapping in the lab of James Cheverud at Washington University called 'relationship QTL' or r-QTL for short. An r-QTL is a genetic locus that affects the correlations between two quantitative traits (i.e. their variational relationship, and therefore, 'relationship' loci). Surprisingly, a large fraction of these so-mapped loci are also neutral with respect to the character mean. This means one can select on these 'neutral' r-QTLs without simultaneously changing the character mean in a certain way. It was easy to show that differential directional selection on a character could easily lead a decrease in genetic correlation between characters. Of course, it is not guaranteed that each and every population has the right kind of r-QTL polymorphisms, nor is it yet clear what kind of genetic architecture allows for the existence of an r-QTL. Nevertheless, these findings make it plausible that differential directional selection can enhance the genetic/variational individuality of traits and, thus, may play a role in the origin of evolutionary novelties by selecting for variational individuality. It must be added, though, that there has been relatively little research in this area and that we will need to see more to determine whether we understand what is going on here, if anything. In particular, one difficulty is the mathematical modeling of gene interaction (epistasis), because the details of an epistasis model determine the outcome of the evolution by natural selection. One result shows that natural selection increases or decreases mutational variance, depending on whether the average epistatic effects are positive or negative. This means that the genetic architecture is more determined by the genetic architecture that we start with than by the nature of the selection forces that act upon it. In other words, the evolution of a genetic architecture could be arbitrary with respect to selection.

Neo-Darwinism and Mutations In order to find a solution, Darwinists advanced the "Modern Synthetic Theory," or as it is more commonly known, Neo-Darwinism, at the end of the 1930s. Neo- Darwinism added mutations, which are distortions formed in the genes of living beings due to such external factors as radiation or replication errors, as the "cause of favorable variations" in addition to natural mutation. Today, the model that stands for evolution in the world is Neo-Darwinism. The theory maintains that millions of living beings formed as a result of a process whereby numerous complex organs of these organisms (e.g., ears, eyes, lungs, and wings) underwent "mutations," that is, genetic disorders. Yet, there is an outright scientific fact that totally undermines this theory: Mutations do not cause living beings to develop; on the contrary, they are always harmful. The reason for this is very simple: DNA has a very complex structure, and random effects can only harm it. The American geneticist B. G. Ranganathan explains this as follows: First, genuine mutations are very rare in nature. Secondly, most mutations are harmful since they are random, rather than orderly changes in the structure of genes; any random change in a highly ordered system will be for the worse, not for the better. For example, if an earthquake were to shake a highly ordered structure such as a building, there would be a random change in the framework of the building which, in all probability, would not be an improvement. Not surprisingly, no mutation example, which is useful, that is, which is observed to develop the genetic code, has been observed so far. All mutations have proved to be harmful. It was understood that mutation, which is presented as an "evolutionary mechanism," is actually a genetic occurrence that harms living things, and leaves them disabled. (The most common effect of mutation on human beings is cancer.) Of course, a destructive mechanism cannot be an "evolutionary mechanism." Natural selection, on the other hand, "can do nothing by itself," as Darwin also accepted. This fact shows us that there is no "evolutionary mechanism" in nature. Since no evolutionary mechanism exists, no such any imaginary process called "evolution" could have taken place.

A note of caution: epigenetics is also on the verge of transforming into a dangerous idea. Epigenetic modifications of genes can potentially superpose historical and environmental information on cells and genomes—but this capacity is speculative, limited, idiosyncratic, and unpredictable: a parent with an experience of starvation produces children with obesity and overnourishment, while a father with the experience of tuberculosis, say, does not produce a child with an altered response to tuberculosis. Most epigenetic “memories” are the consequence of ancient evolutionary pathways, and cannot be confused with our longing to affix desirable legacies on our children. As with genetics in the early twentieth century, epigenetics is now being used to justify junk science and enforce stifling definitions of normalcy. Diets, exposures, memories, and therapies that purport to alter heredity are eerily reminiscent of Lysenko’s attempt to “reeducate” wheat using shock therapy. Mothers are being asked to minimize anxiety during their pregnancy—lest they taint all their children, and their children, with traumatized mitochondria. Lamarck is being rehabilitated into the new Mendel. These glib notions about epigenetics should invite skepticism. Environmental information can certainly be etched on the genome. But most of these imprints are recorded as “genetic memories” in the cells and genomes of individual organisms—not carried forward across generations. A man who loses a leg in an accident bears the imprint of that accident in his cells, wounds, and scars—but does not bear children with shortened legs. Nor has the uprooted life of my family seem to have burdened me, or my children, with any wrenching sense of estrangement. Despite Menelaus’s admonitions, the blood of our fathers is lost in us—and so, fortunately, are their foibles and sins. It is an arrangement that we should celebrate more than rue. Genomes and epigenomes exist to record and transmit likeness, legacy, memory, and history across cells and generations. Mutations, the reassortment of genes, and the erasure of memories counterbalance these forces, enabling unlikeness, variation, monstrosity, genius, and reinvention—and the refulgent possibility of new beginnings, generation upon generation.

The key point is that these patterns, while mostly stable, are not permanent: certain environmental experiences can add or subtract methyls and acetyls, changing those patterns. In effect this etches a memory of what the organism was doing or experiencing into its cells—a crucial first step for any Lamarck-like inheritance. Unfortunately, bad experiences can be etched into cells as easily as good experiences. Intense emotional pain can sometimes flood the mammal brain with neurochemicals that tack methyl groups where they shouldn’t be. Mice that are (however contradictory this sounds) bullied by other mice when they’re pups often have these funny methyl patterns in their brains. As do baby mice (both foster and biological) raised by neglectful mothers, mothers who refuse to lick and cuddle and nurse. These neglected mice fall apart in stressful situations as adults, and their meltdowns can’t be the result of poor genes, since biological and foster children end up equally histrionic. Instead the aberrant methyl patterns were imprinted early on, and as neurons kept dividing and the brain kept growing, these patterns perpetuated themselves. The events of September 11, 2001, might have scarred the brains of unborn humans in similar ways. Some pregnant women in Manhattan developed post-traumatic stress disorder, which can epigenetically activate and deactivate at least a dozen genes, including brain genes. These women, especially the ones affected during the third trimester, ended up having children who felt more anxiety and acute distress than other children when confronted with strange stimuli. Notice that these DNA changes aren’t genetic, because the A-C-G-T string remains the same throughout. But epigenetic changes are de facto mutations; genes might as well not function. And just like mutations, epigenetic changes live on in cells and their descendants. Indeed, each of us accumulates more and more unique epigenetic changes as we age. This explains why the personalities and even physiognomies of identical twins, despite identical DNA, grow more distinct each year. It also means that that detective-story trope of one twin committing a murder and both getting away with it—because DNA tests can’t tell them apart—might not hold up forever. Their epigenomes could condemn them. Of course, all this evidence proves only that body cells can record environmental cues and pass them on to other body cells, a limited form of inheritance. Normally when sperm and egg unite, embryos erase this epigenetic information—allowing you to become you, unencumbered by what your parents did. But other evidence suggests that some epigenetic changes, through mistakes or subterfuge, sometimes get smuggled along to new generations of pups, cubs, chicks, or children—close enough to bona fide Lamarckism to make Cuvier and Darwin grind their molars.

In physical terms, we know that every human action can be reduced to a series of impersonal events: Genes are transcribed, neurotransmitters bind to their receptors, muscle fibers contract, and John Doe pulls the trigger on his gun. But for our commonsense notions of human agency and morality to hold, it seems that our actions cannot be merely lawful products of our biology, our conditioning, or anything else that might lead others to predict them. Consequently, some scientists and philosophers hope that chance or quantum uncertainty can make room for free will. For instance, the biologist Martin Heisenberg has observed that certain processes in the brain, such as the opening and closing of ion channels and the release of synaptic vesicles, occur at random, and cannot therefore be determined by environmental stimuli. Thus, much of our behavior can be considered truly “self-generated”—and therein, he imagines, lies a basis for human freedom. But how do events of this kind justify the feeling of free will? “Self-generated” in this sense means only that certain events originate in the brain. If my decision to have a second cup of coffee this morning was due to a random release of neurotransmitters, how could the indeterminacy of the initiating event count as the free exercise of my will? Chance occurrences are by definition ones for which I can claim no responsibility. And if certain of my behaviors are truly the result of chance, they should be surprising even to me. How would neurological ambushes of this kind make me free? Imagine what your life would be like if all your actions, intentions, beliefs, and desires were randomly “self-generated” in this way. You would scarcely seem to have a mind at all. You would live as one blown about by an internal wind. Actions, intentions, beliefs, and desires can exist only in a system that is significantly constrained by patterns of behavior and the laws of stimulus-response. The possibility of reasoning with other human beings—or, indeed, of finding their behaviors and utterances comprehensible at all—depends on the assumption that their thoughts and actions will obediently ride the rails of a shared reality. This is true as well when attempting to understand one’s own behavior. In the limit, Heisenberg’s “self-generated” mental events would preclude the existence of any mind at all. The indeterminacy specific to quantum mechanics offers no foothold: If my brain is a quantum computer, the brain of a fly is likely to be a quantum computer, too. Do flies enjoy free will? Quantum effects are unlikely to be biologically salient in any case. They play a role in evolution because cosmic rays and other high-energy particles cause point mutations in DNA (and the behavior of such particles passing through the nucleus of a cell is governed by the laws of quantum mechanics). Evolution, therefore, seems unpredictable in principle.13 But few neuroscientists view the brain as a quantum computer. And even if it were, quantum indeterminacy does nothing to make the concept of free will scientifically intelligible. In the face of any real independence from prior events, every thought and action would seem to merit the statement “I don’t know what came over me.” If determinism is true, the future is set—and this includes all our future states of mind and our subsequent behavior. And to the extent that the law of cause and effect is subject to indeterminism—quantum or otherwise—we can take no credit for what happens. There is no combination of these truths that seems compatible with the popular notion of free will.

These alterations arise through small mutations in the gene that constitutes the blueprint for that protein. Sometimes a mutation makes little difference in the protein’s stability or activity. Sometimes it damages the protein and reduces the viability of the virus. Other times, though, it enhances survival, such as by reconfiguring a site on hemagglutinin that was formerly recognized by an antibody.

When antigenic shift occurs, strains crop up bearing a totally new hemagglutinin spike, and sometimes also a new neuraminidase molecule, that most people have never encountered. As a result the virus may evade the antibody repertoire carried by all populations around the globe and trigger a pandemic. In today’s jet-linked world, people can spread a dangerous new virus from one part of the earth to another in a day. Such a drastic metamorphosis cannot occur through simple genetic mutation. The best-studied process leading to antigenic shift involves the mixing of two viral strains in one host cell, so that the genes packaged in new viral particles (and their corresponding proteins) come partly from one strain and partly from the other. This reassortment can take place because the genome, or genetic complement, of the influenza virus consists of eight discrete strands of RNA (each of which codes for one or two proteins). These strands are easily mixed and matched when new influenza A particles form in a dually infected cell. For instance, some influenza viruses infect both people and pigs. If a pig were somehow invaded by a human virus and by a strain that typically infected only birds, the pig might end up producing a hybrid strain that was like the human virus in every way except for displaying, say, a hemagglutinin molecule from the bird virus.

The idea of natural selection is not hard to grasp. If individuals within a species differ genetically from one another, and some of those differences affect an individual’s ability to survive and reproduce in its environment, then in the next generation the “good” genes that lead to higher survival and reproduction will have relatively more copies than the “not so good” genes. Over time, the population will gradually become more and more suited to its environment as helpful mutations arise and spread through the population, while deleterious ones are weeded out. Ultimately, this process produces organisms that are well adapted to their habitats and way of life.

feces. If a wild bird infects a chicken on a poultry farm, the virus may get opportunities to interact with a range of additional viruses through close contact with pigs and other animals. This is indeed what has happened in the live animal markets and backyard farms of China and southern Asia. Influenza viruses are notorious for their ability to change, through a combination of mutation and “reassortment”—a borrowing of genes from other viruses. An open farm acts like a virus convention, where different strains swap genetic material like conventioneers swap business cards.

If you think about most genetic diseases, they’re caused by one gene, and in fact one mutation at one amino acid,” said Roger Reeves, a leading researcher in the field and professor at the Institute for Genetic Medicine at Johns Hopkins University School of Medicine. “With Down syndrome, you have an extra copy of all five hundred or so genes on chromosome 21.” For decades, Lejeune’s discovery served to scare off scientists from any serious effort to find a medical treatment for what they were soon calling “trisomy 21.” It just seemed impossibly complex.

The first view, solidly anchored in popular linguistic theory, holds that language is a uniquely human phenomenon, distinct from the adaptations of all other organisms on the planet. Species as diverse as eagles and mosquitoes fly, whales and minnows swim, but we are the only species that communicates like we do. Not only does language differentiate us from all other animal life; it also exists separate from other cognitive abilities like memory, perception, and event he act of speech itself. Researchers in this tradition have searched for a "language organ," a part of the brain devoted solely to linguistic skills. They have sought the roots of language in the fine grain of the human genome, maintaining, in some cases, that certain genes may exist for the sole purpose of encoding grammar. One evolutionary scenario in this view maintains that modern language exploded onto the planet with a big genetic bang, the result of a fortuitous mutation that blessed the Cro-Magnon with the gift of tongues.

The high degree of intertumoral heterogeneity revealed by TCGA shocked everyone. No single mutation could be identified that was required for the disease to start. No combination of mutations that initiated the disease could be found. Other than a few commonly mutated oncogenes, there was a frightening degree of randomness. The studies sequenced the tumors from eleven individuals with breast cancer and eleven individuals with colon cancer. Over eighteen thousand genes were sequenced, almost forty times the number in the initial studies and the most exhaustive sequencing to date. Vogelstein was stunned by the seeming random nature of the cancer genome seen two years into the project. He posed the question on everybody’s mind: “Is it possible to make sense out of this complexity?

Homologous recombination.”               “Homo-what?”               “It’s precision genetic engineering.  Basically, two enzymes fix sections of broken DNA.  They scissor out the broken section and replace it with a new chunk of DNA.  No one knows how it works, but it happens occasionally in Petri dishes.” “Could that cure someone?” “Absolutely.  Defective genes and gene mutations play a primary role in some of the worst diseases that exist today: heart disease, diabetes, immune system disorders, and birth defects.

I grew up believing that drinking cow’s milk was normal, and that those who can’t – because it gives them painful flatulence – are the odd ones. But, it turns out that milk-slurpers are the new kids on the block. Our prehistoric ancestors were hunting animals millions of years ago, but it wasn’t until the Neolithic era that humans actually consumed their milk. Is it simply that it hadn’t occurred to us before? Were we too busy hiding from cave lions? Well, maybe. But in reality it’s biology that determined the success of the switchover, not lack of effort. Until about 7,500 years ago, our adult ancestors simply couldn’t process the sugary lactose in milk, just as 70 per cent of the world’s people can’t today. It was only random mutations in the MCM6 gene that produced an enzyme called lactase that stops the uncomfortable build-up of stomach gas.

It’s abundantly clear that these events do happen, and quite frequently, but often it’s been difficult to identify exactly how a tumour suppressor has mutated. In the last fifteen years, we’ve started to realise that there is another way that a tumour suppressor gene can become inactivated. The gene may be silenced epigenetically. If the DNA at the promoter becomes excessively methylated or the histones are covered in repressive modifications, the tumour suppressor will be switched off. The gene has been inactivated without changing the underlying blueprint.