Hacking Darwin - Jamie Metzl

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Here is a summary of the fiction and nonfiction works mentioned by Jamie Metzl:

FICTION:

• Eternal Sonata
• Genesis Code
• The Depths of the Sea

NONFICTION:

• Western Responses to Human Rights Abuses in Cambodia, 1975–1980

The introduction provides context about the author’s visit to a cryobank to store his sperm cells for long-term storage, given his views on the future of genetic engineering and human reproduction. It outlines some of the author’s perspectives on humanity taking control of its own evolutionary process through technologies like genetic engineering.

Here is a summary of the key details in the passage:

• The narrator works on national security issues related to emerging technologies and becomes obsessed with genetics/biotechnology as an important issue.

• He testifies before Congress about the national security implications of genetics and this increases his profile on the issue.

• He writes science fiction novels to more effectively communicate the implications of genetics advances in an engaging way.

• On book tours, people are very interested when he discusses real genetics science rather than just the fiction. This inspires him to ask difficult questions about human genetic engineering.

• As a late 40s man without children, he reflects on how his faith in technology may conflict with concerns about genetically enhancing humans.

• The passage argues we have all the tools needed for human genetic alteration, similar to the moon landing in the 1960s, so realization is inevitable, just a matter of when and under what values.

• Advances in genetic technologies like IVF, embryo selection, gene editing tools like CRISPR are accelerating a coming human genetic revolution. This will transform human reproduction and potentially how we alter future children.

• Parents will increasingly use IVF and embryo selection to eliminate genetic diseases, select traits like intelligence, and enhance capabilities. Governments and insurance will encourage this to reduce costs of genetic diseases.

• Gene editing tools like CRISPR will allow precisely altering embryo genetics by inserting new DNA sequences for traits and capabilities from humans, animals or synthetic sources.

• This raises fundamental questions about how we use these technologies - to expand or limit humanity? Will benefits go to all or just a privileged few? Who decides impacts on the human gene pool? We need informed global discussions to guide this revolution.

• While exciting, this transformation also causes unease as it challenges ideas of nature, chance, and spirituality. If not addressed carefully, it could increase divisions in our ideologically diverse world. Our collective responses will shape who we become.

• Understanding the issues is urgent as the revolution arrives sooner than expected. We must see ourselves as contributing to deciding our shared future through open conversations on optimizing benefits and minimizing harms.

• The speaker argues that enhancing humans through genetic modification could help reduce suffering and unlock human potential, but it also risks dividing societies and undermining diversity if not done carefully.

• They acknowledge concerns about a “slippery slope” but say excitement and fear are both warranted responses. Individual choices will shape where genetic technologies lead on both personal and societal levels.

• They provide background on evolution, noting that sexual reproduction first emerged over 1 billion years ago and greatly expanded genetic diversity, allowing species to better adapt through natural selection. This accelerated evolutionary change.

• While genetic enhancement could help humanity, the speaker stresses the importance of deciding collectively how to guide its development to avoid potential downsides like inequality, commodification of life, and international conflict. Both opportunities and risks are enormous.

So in summary, the speaker outlines perspectives on both the promise and perils of human genetic enhancement, emphasizing the responsibility individuals and societies have to collectively determine how to shape emerging technologies for the benefit of humanity. Both individual choices and policy decisions will be crucial according to their argument.

• Some organisms like salmon release thousands of eggs into rivers, increasing the odds of fertilization but eliminating parenting. Parenting confers major evolutionary advantages by allowing offspring to develop skills.

• Our ancestors produced fewer offspring but kept eggs inside females and provided parenting after birth. This allowed offspring’s brains to develop more skills beyond what salmon offspring could achieve.

• In the 1600s, Anton van Leeuwenhoek discovered sperm under a microscope, but its role remained unclear. Various views developed on fertilization.

• In the 1700s, Lazzaro Spallanzani showed through frog experiments that sperm is necessary for fertilization. It took another century to determine both egg and sperm contribute to the fertilized egg.

• For millennia, people intuitively understood heredity through observing trait inheritance. This led to early domestication of plants and animals like dogs from wolves.

• Charles Darwin developed the theory of evolution by natural selection in 1859, but the mechanism of heredity was still unknown.

• In the 1860s, Gregor Mendel performed pea plant experiments and deduced the basic laws of heredity involving genes and traits. But his work was overlooked until the early 1900s.

• Over decades, scientists showed how genetics works across many organisms using Mendelian genetics and Darwinian evolution. This provided the foundation to understand biology.

• All genetic code is made of DNA, which contains instructions for cells to make proteins. DNA is made up of four nucleotide bases: A, T, C, G. Sequences of these bases form genes.

• Humans have about 21,000 genes encoded in 23 pairs of chromosomes. While genes code for proteins, nearly 99% of DNA is non-coding but still important for regulation.

• Epigenetics controls which genes are expressed in different cell types. This allows a single fertilized cell to develop into many specialized cell types.

• The Human Genome Project aimed to sequence the entire human genome. Advances in automation and new technologies like nanopore sequencing have dramatically reduced costs over time.

• While sequencing provides the raw data, understanding what the genetic code means and how genes interact with each other and the environment is still an ongoing challenge. Model organisms and computational analysis help researchers correlate genes to traits.

So in summary, advances in sequencing provided the raw genetic data, but understanding how genetics works to produce traits requires correlating the genetic code with biological functions across many levels of complexity. Both sequencing technology and analytical approaches continue advancing our genetic insights.

• CId (RNA) plays an important role in gene expression and epigenetic marks help determine how genes are expressed. Understanding complex genetic traits was difficult early on but analyzing single gene mutations was more feasible.

• Examples of single-gene mutation diseases (Mendelian diseases) include cystic fibrosis, Huntington’s disease, muscular dystrophy, sickle cell disease, and Tay-Sachs disease. Some are dominant or recessive based on inheritance patterns.

• These Mendelian diseases are rare but cause suffering. Due to their rarity, there is less incentive to invest in cures compared to more common diseases.

• Tay-Sachs disease results from a single genetic mutation. After the mutation was identified, genetic screening reduced transmission among Jewish communities worldwide through community outreach and genetic testing of prospective parents and embryos.

• Techniques like in vitro fertilization and embryo screening, combined with genetic analysis, transformed human reproduction by allowing genetic traits to be assessed before pregnancy. This started with basic experiments in the late 1800s and led to the first “test tube baby” in 1978 through IVF pioneers like Edwards and Steptoe.

• Preimplantation genetic diagnosis (PGD) was developed to screen embryos for genetic abnormalities and diseases before implantation. It has since been expanded to include preimplantation genetic screening (PGS) of embryos without known risks. Both are now referred to as preimplantation genetic testing (PGT).

• PGT was initially used for chromosomal abnormalities causing miscarriage but now screens for over 10,000 single-gene disorders. It allows testing of multiple blastocysts in vitro rather than a single embryo in utero.

• While individual rare diseases have low risks, collectively 1-2% of traditionally conceived children may have a screenable disorder. PGT massively reduces these risks.

• As PGT screening capabilities and embryo selection increase, parents will have to weigh natural conception risks versus benefits of embryo selection. Natural risks will remain constant while perceived health benefits of PGT will likely rise over time.

• Iceland widely uses prenatal Down syndrome screening, with over 90% of women terminating pregnancies after a positive result. This points to increasing acceptance of embryo screening and selection to prevent genetic disorders. However, critics argue this devalues lives of people with disabilities.

• If IVF and embryo selection become common, parents may feel compelled to screen and select embryos without genetic abnormalities or face social condemnation for exposing children to preventable risks, paralleling views on anti-vaxxers. This could fundamentally change norms around baby-making.

• Screening embryos for genetic diseases before implantation through IVF would allow parents to avoid diseases like Down syndrome without resorting to abortion, which many see as less brutal.

• Governments and insurers have financial incentives to encourage IVF screening to avoid lifetime costs of treating genetic diseases. For example, cystic fibrosis treatment costs $600,000 per lifetime on average.

• Rough calculations suggest if preimplantation screening could reduce lifetime treatment costs of genetic diseases born to 80,000 US newborns each year (2% of total) by $600,000 each, it would save $48 billion over 37 years.

• Bringing forward this $48 billion to today’s value would provide $16,500 per woman for IVF/preimplantation genetic testing, covering the costs for many seeking it.

• As technologies advance and costs fall, more will opt for IVF/screening rather than natural conception to select embryos without genetic diseases. Employers are starting to cover these costs, increasing access.

• Exponential genome sequencing progress will further propel this shift away from natural conception towards selecting embryos based on their genetic profiles to avoid diseases.

Here is a summary of the key points about humility from the passage:

• Scientists have become more cautious and humble about our ability to understand genetics and biological systems based on the immense complexity involved. Collecting genetic data through sequencing does not directly translate to understanding.

• Even seemingly simple genetics turn out to be complex when we study a diverse range of people, as the same mutations can have different effects in some individuals.

• Model organisms are being used to systematically study biological systems from the bottom up, starting with simpler organisms. This process is building understanding slowly.

• Approaches like GWAS and next-generation sequencing analyze huge genetic datasets, but making sense of this data at a systemic level requires sophisticated analytical tools beyond human abilities alone.

• Artificial intelligence and machine learning will be critically important to help analyze massive genetic and biological datasets and discover complex patterns that reveal principles of how these systems function. Overall scientists acknowledge the need for humility given the enormity of what remains unknown.

• The passage discusses how AI and big data analytics are helping scientists make more sense of the complexity of human biology and genetics. Advances in machine learning allow analysis of vast amounts of genomic and health data.

• Companies like Deep Genomics are using AI to uncover patterns in disease pathogenesis by analyzing genomic data. Google and other companies have developed AI systems to analyze genomic sequencing data.

• Understanding genetics requires matching vast numbers of sequenced genomes with detailed life records and phenotypes. This requires standardized health records and willingness to share data.

• Iceland’s homogeneous population and records make it well-suited for genetic research. A company called deCODE gained access to health records and blood samples to study disease genetics, though privacy concerns later limited data sharing.

• Governments are also pursuing large genomic studies, like the UK’s 100,000 Genomes Project and the US NIH’s All of Us Research Program aiming to sequence over 1 million Americans to advance genetic research. The intersection of AI, large genomic datasets, and health records holds promise for new biological insights.

• China is making large investments in precision medicine and aims to sequence 50% of newborns by 2020 to build genetic databases. It is also establishing a shared electronic health record system.

• It is estimated that up to 2 billion human genomes may be sequenced in the next decade as costs decline and computing power increases.

• Much genetic and health data will be placed in digital databases, allowing large-scale data analysis to improve understanding of genetic disorders and human biology.

• The shift toward personalized medicine means treatment will be tailored based on an individual’s full genetic and medical profile rather than averages. Genome sequencing will become standard in medical care.

• Initiatives like Geisinger Health System offering free genome sequencing aim to enable earlier identification of health risks and more targeted prevention and treatment.

• As more data is collected, researchers will better understand complex polygenic conditions influenced by many genes using techniques like polygenic risk scoring.

• Unlocking disease genetics will ultimately require understanding broader human traits and characteristics like intelligence, aging and height at the genetic level.

• The US health system creates perverse incentives for everyone involved due to its highly irrational nature.

• Things like assisted reproduction and embryo selection have become more like competitive customer service businesses focused on consumer choice and satisfaction.

• Doctors are now able to provide much more genetic information to prospective parents, including predictive likelihoods for developing complex genetic disorders later in life based on multiple gene patterns.

• The law requires doctors to get consent from parents before providing information about non-disease traits as well, such as longevity, height, and IQ.

• There is an ongoing debate about how far assisted reproduction and genetic selection should go, and whether it risks playing God or reducing a child to just genetics. Parents have to grapple with what feels ethical in optimizing their future child’s traits and life outcomes.

• The passage discusses the complex debate around nature vs nurture - how much our traits and characteristics are determined by genetics vs environment.

• Studies of identical twins separated at birth have provided insights, showing genetics play a significant role in traits like personality and behavior. However, environmental factors are also important as not all identical twins share the same characteristics.

• While genetics influences us substantially, it is impossible to draw an exact line between nature and nurture. Their effects are interactive and complex. Understanding their balance is important for issues like genetic selection and editing.

• The passage acknowledges we must be humble about limitations in knowledge but also recognize humanity’s tendency to push boundaries. Assessing genetic determinism has implications for how to address problems - either genetically or environmentally.

So in summary, the passage explores the ongoing debate on the interplay between genetics and environment in shaping human traits and behavior, and how better understanding this balance could inform issues like genetic selection. Both nature and nurture play important but intertwined roles.

The research analyzed traits from over 14.5 million pairs of twins across 39 countries. It confirmed that all measured human traits have a heritable component, with some traits being more genetic than others. Traits related to neurology, heart, personality, vision, cognition and ears/nose/throat were found to be highly genetic. Overall, 49% of trait differences on average were attributed to genetics, supporting the idea that humans are about half defined by their genes.

Height is known to be strongly influenced by genes. While single gene mutations can cause extreme height variations, hundreds or thousands of genes typically influence normal height differences. Studies have used genetic data to predict people’s heights within 1 inch on average. This approach could also be used to predict traits and disease risks once large enough genetic databases are available.

Intelligence is an extremely important and complex trait but also difficult to define and measure. While IQ tests initially aimed to identify students needing help, they were later misused to argue for genetic differences between racial groups. IQ nevertheless correlates with various life outcomes. The heritability and genetic bases of intelligence remain highly debated topics. Larger genetic datasets will be needed to make meaningful predictions regarding intelligence and other polygenic traits.

• IQ and other cognitive abilities are positively correlated, with high IQ people tending to score well on other tests. However, critics argue IQ is inaccurate, biased, and questionable.

• The 1994 book The Bell Curve renewed debates about genetics influencing IQ differences between groups. While it acknowledged genetics and environment both play roles, it controversially suggested restricting reproduction by poor women could increase average IQ. This sparked intense backlash.

• Twin and sibling studies show 70-80% of IQ is genetic. However, one study found genetics was less predictive of IQ for children from disadvantaged families, possibly due to greater environmental impacts.

• Over 200 gene variants have been linked to higher IQ since 2016, but each accounts for a small percentage and genetics alone can’t predict intelligence. Continued research as more genomes are sequenced may identify thousands more genes influencing IQ.

• Personality is also partly genetic based on twin studies. A 2016 study identified some genetic markers associated with the Big Five personality traits like extraversion and neuroticism. More research may uncover additional genetic underpinnings of personality.

• Advances in genetics and IVF are allowing for more precise and individualized healthcare and reproductive choices. We will gradually move from general population-based care to personalized “precision medicine” based on genetic predispositions.

• Genetic information will also be integrated into reproductive decision-making, like selecting embryos. This raises ethical questions about the implications and safety.

• Initial embryo selection using IVF will have a relatively low safety threshold and result in naturally conceived children. But genetic technologies applied to reproduction will likely not stop there.

• IVF is becoming a more common way for all types of families to have children, including gay couples. For IVF to be more widely used, it needs to be less painful and clinical for women.

• In the future, stem cell technology may allow easier egg retrieval by taking a small blood sample rather than undergoing an invasive medical procedure, making IVF selection more accessible and appealing compared to natural conception. This represents a new frontier in “hacking” human biology and reproduction.

• Early cells growing out of a seed must be able to develop into different types of cells to form an organism and keep it functioning by regenerating cell types.

• Stem cells play this role - they grow into different cell types and continue regenerating cells. They are like the “seeds” that later enable the growth of tissues/organs.

• Researchers struggled for decades to understand, identify, and isolate stem cells. Embryonic stem cells were first extracted from mice in 1981 and from humans in 1998, launching enthusiasm for their medical potential.

• These embryonic stem cells came from leftover embryos from fertility clinics, raising ethical concerns about destroying potential life. This debate polarized views on stem cell research.

• Discoveries in the 2000s by scientists like Shinya Yamanaka showed cells can be “reprogrammed” through certain factors, transforming specialized adult cells back into pluripotent stem cell-like states with regeneration potential. This opened new avenues for research.

Here is a summary of the key events in the passage:

• The narrator’s blood sample is taken and used to generate induced pluripotent stem cells, which are then turned into egg precursor cells and ultimately eggs through a process called reprogramming.

• Over a thousand eggs are fertilized using the sperm, resulting in 100 early stage embryos that are sequenced and their genetic profiles analyzed.

• The genetic analysis is displayed as a grid showing probability estimates for each embryo having various traits or health outcomes. Traits like risk of diseases, physical attributes, cognitive abilities are represented.

• The doctor explains this provides many more reproductive options compared to traditional means. They discuss eliminating embryos with high disease risks and then focusing on traits deemed most important by the prospective parents based on the analysis.

• The passage explores some of the ethical issues around selecting embryos based on genetic traits, while also acknowledging the desire to minimize health risks for the child. The narrator is torn but sees the utility of optimizing based on the new information available.

In summary, it describes a hypothetical future where a person’s cells can be used to generate many eggs and embryos for selection based on comprehensive genetic analysis, enabled by advances in stem cell reprogramming and genome sequencing.

• Selective breeding has significantly altered chickens from their wild ancestors over thousands of years, enabling domesticated chickens to lay around 300 eggs per year compared to 12 for wild chickens. This shows how biology can be “hacked”.

• The process described could theoretically enable accelerating human genetic selection and evolution similar to how chickens have been breed. It involves extracting cells from early-stage embryos to generate gametes (eggs/sperm), then fertilizing those to create new embryos that would be the “children” of the original embryos.

• This could hypothetically reduce the human generation time from around 28 years to just 6 months, equivalent to chickens. This would enable over 50 generations of selection in the same time it now takes for one, dramatically speeding up genetic changes.

• Future generations may consider this to push enhancement traits like IQ if it was deemed safe. While frightening, it could offer parents incentive to endow children with greatest potential if selection was for positive traits. However, others may view it as dehumanizing.

• In summary, the passage explores how accelerated human genetic selection through embryo breeding could in theory mirror what we’ve done with chickens, but raises serious ethical concerns about implications for human evolution and enhancement.

• Charles Shulman and Nick Bostrom attempt to quantify how much IQ could potentially increase through genetic selection of embryos.

• Their calculations suggest mating 5 generations of embryos selected for highest IQ could create a 65 point IQ bump, and mating for 10 generations could create a 130 point IQ bump.

• Stephen Hsu believes that within a decade, it may be possible to select embryos based on genes associated with intelligence, potentially creating a person with an IQ of 1000.

• However, there is uncertainty about what health or psychological impacts significantly increasing IQ through genetic selection could have, as large increases may require physical changes not possible within the constraints of the human body.

• If human intelligence eventually merges with artificial intelligence, mental capacities could potentially expand exponentially without physical constraints. But this process would pose huge social and ethical challenges.

So in summary, the passage discusses estimates for how genetic selection and embryo mating could substantially increase IQ over generations, but also notes major uncertainties and ethical issues with such an approach.

• CRISPR is a bacterial immune system that stores snippets of viral DNA to help it recognize and destroy invaders in the future. Bacteria use the Cas9 enzyme to cut viruses at matching DNA sequences.

• Scientists discovered CRISPR in 1987 but it took years of research to understand its function. By the 2010s, researchers like Doudna, Charpentier, and Zhang had adapted it into a precise gene editing tool.

• The CRISPR-Cas9 system uses a guide RNA to target a specific DNA sequence, where the Cas9 enzyme cuts. This cut can be repaired by adding a new DNA sequence, allowing genes to be edited.

• CRISPR has major advantages over previous tools like being cheaper, easier to design, and able to target multiple sites. However, its cuts also create a risk of unintended effects.

• Research is advancing CRISPR beyond cutting to also edit epigenetics and expression of genes. It is becoming more precise, versatile and widespread through global scientific collaboration.

• Early applications are using CRISPR’s precision to study genes and advance basic research. But it is moving towards increasingly substantial human uses as well.

• CRISPR gene editing is being used to create disease-resistant and more productive crops, livestock and pets. Examples mentioned include browning-resistant Arctic apples, virus-resistant papayas and potatoes, higher fiber wheat, milk-producing “supercows”, and smaller pet pigs.

• Gene editing has potential to boost global food security by developing more resilient crops that need less water and are better suited to warmer climates. It could save billions in crop losses and millions of lives in developing countries.

• Animal gene editing via CRISPR is also being used to develop livestock that are healthier, grow faster, produce more milk/meat, and are resistant to diseases and extreme temperatures. This could save commercial agriculture hundreds of millions per year.

• Acceptance of gene edited foods and animals may increase acceptance of gene therapies and applications to humans as well. Gene therapies are advancing as a way to treat and cure diseases by manipulating genes without inheriting changes.

• Early gene therapy trials had setbacks but techniques improved, and CRISPR now allows more precise in vivo gene editing of cells inside the body to potentially treat many diseases. This is moving gene therapies from research into real-world medical applications.

The passage discusses recent advances in precision gene editing using CRISPR-Cas9 that could potentially cure diseases like cystic fibrosis, hereditary tyrosinemia, sickle cell disease, and more. As these gene therapies become more common and effective at treating diseases, it will make the public more comfortable with the idea of human genetic alteration. Demand for these medical treatments will play an important role in increasing acceptance of gene editing technologies. The success of therapies in safely and precisely editing the genome to cure disease will provide confidence that gene editing could also be used to prevent diseases before they occur.

• The passage discusses mitochondrial transfer/replacement therapy as a potential treatment for mitochondrial disease. It allows transfer of healthy mitochondria from a donor egg or embryo into a patient’s egg or embryo to prevent transmission of mitochondrial disease.

• Mitochondrial transfer is currently allowed in some places like the UK but banned in others. It describes the limited options available to mothers in places where it is banned, such as adopting, IVF/PGT screening (which isn’t fully reliable), or traveling abroad for treatment.

• Advocacy groups for mitochondrial disease are lobbying to legalize mitochondrial transfer in more locations. As evidence shows it is safe and effective in the UK, pressure will increase on other governments to fund research and allow this therapy.

• Once a therapy is proven safe and effective, demand will likely grow from parents of children with other genetic diseases to use gene editing technologies to prevent transmission of those diseases as well. Disease advocacy groups lobby heavily for more research funding which influences policy decisions.

• The passage argues that parental demand for technologies to treat and prevent genetic diseases in their children will continue increasing pressure on governments and policies regarding heritable human genetic modification.

• Researchers studying West African women exposed to Ebola found some had antibodies despite no exposure, suggesting genetic immunity. They identified a gene (NPC) that Ebola targets.

• Having one mutated copy of NPC (recessive) can confer increased resistance to Ebola, similar to how sickle cell carriers have malaria resistance.

• Scientists search for single-gene mutations that confer benefits, like disease resistance. It’s difficult due to identifying absence of disease rather than symptoms.

• Studies have found genes like LRP5, MSTN, SCN9A etc. that impact traits like bone strength, muscle mass, pain sensitivity when mutated.

• CRISPR could potentially edit these kinds of beneficial mutations. However, early CRISPR is still inaccurate and risks unsafe off-target edits. Improving specificity and avoiding off-targets is a focus of ongoing research.

• New versions like base editing allow changes without cutting DNA, reducing uncertainty but still needing more precision for human use. Gene editing holds promise but is not yet safe for humans due to technical limitations.

• CRISPR-SKIP is a new CRISPR approach that can deactivate disease-causing gene mutations with fewer off-target effects than other CRISPR systems. It works by skipping over targeted gene regions instead of editing them.

• Progress is being made in using CRISPR to edit epigenetic marks and RNA guides, making gene editing and expression more precise.

• A challenge is mosaicism, where gene edits are not uniformly applied across cells. Recent studies show CRISPR editing sooner after fertilization or editing sperm/eggs before fertilization can reduce mosaicism.

• There is ongoing debate among genetic researchers about whether we have sufficient ability to precisely edit human embryos intended for implantation. Safety and accuracy need to be fully proven before clinical use.

• Reaching the same error rate as natural conception would help increase confidence, but new technologies often need to be much safer than nature to be adopted.

• Editing single genes for certain conditions may be the only way for some parents to have biologically related children without inherited disorders.

• Editing complex traits is more remote, as they are influenced by many interacting genes in complex ways that are not fully understood. The more genes involved, the harder accurate editing becomes.

Our understanding of biology has grown significantly in recent decades due to more sophisticated tools that have enabled deeper knowledge. Mapping the human cell atlas is providing comprehensive reference maps of all human cells over time.

While the complexity of the human body still towers over our current tools and knowledge, technological progress is accelerating exponentially. Innovations build on each other, driving faster advances. Moore’s law has seen computing power double every two years.

This has given rise to greater connectivity and collaboration through the internet. Networks of thousands working together can be far more innovative than individuals alone. Growing artificial intelligence capabilities may eventually exceed all humans combined.

Emerging technologies are pushing the boundaries of what was once imagined. Ancient myths of human-animal chimeras are becoming reality through techniques like CRISPR. Insulin from cows and animal organs have long helped humans. Gene editing now aims to make pig organs safer for transplantation to address the dire shortage of human donors. The ultimate goal is growing entire human organs inside animals. San Diego scientists have taken a first step by generating chimeric pig embryos with human stem cells.

• Scientists have made progress in growing human cells and organs in other species. A human cell was integrated into pig cells. Mouse pancreatic cells were inserted into rat embryos that grew mouse pancreases inside rats, which were then transplanted to treat diabetes in mice.

• In 2018, researchers at UC Davis developed sheep embryos with a very small fraction (0.001%) of human cells. The goal is to eventually grow human organs in other animals using the person’s own genetics to provide replacement organs for those needing transplants.

• Advances in gene editing like CRISPR could allow integrating genes from other species into humans. While integrating whole genetic systems from other animals is not yet possible, single gene transfers may occur, like cancer-resistant genes from naked mole rats.

• Synthetic biology allows designing and manufacturing new genetic material and lifeforms not found in nature. This field is growing rapidly, with applications in producing fuels, materials, drugs and custom microbes. Genetic parts are widely shared to facilitate designing new synthetic organisms.

• Full synthesis of bacterial genomes has been achieved, demonstrating control over rewriting biological code. The goal is to ultimately synthesize and manipulate the entire human genome. Initiatives like Genome Project-write aim to raise funds for synthesizing more complex genomes towards this goal.

• These advances will transform what it means to be human by engineering biology at its most basic level through reading, writing and hacking the genetic code. They could enable enhancing human traits and extending healthy lifespan far beyond what is possible today.

• The ancient Mesopotamian epic of Gilgamesh tells of Gilgamesh’s quest for immortality after being told by gods that humans cannot live forever.

• Gilgamesh finds Utnapishtim, a man who survived a great flood and was granted immortality. Utnapishtim tells Gilgamesh how to find a magical plant that restores youth.

• Gilgamesh finds the plant but loses it when a snake steals it and becomes young again. Gilgamesh returns home accepting his mortality.

• For millennia, cultures have sought ways to extend life and overcome death, like magic plants, elixirs, or retaining youthful testicles. Average lifespans were short until modern advances in health, sanitation, safety gradually increased lifespans over the 20th century.

• As lifespans increase, expectations of a “full life” also increase. Understanding aging and its underlying biological processes may one day allow scientists to further push lifespan limits through genetics and biotechnology. However, defining and fully understanding the complex, multi-factorial process of aging remains challenging.

• Curing individual diseases of aging only extends lifespan a little, as other diseases will soon take their place. To significantly extend healthy lifespan, the focus needs to shift to slowing aging itself.

• Aging affects the entire body in a systemic way, so targeting central mechanisms of aging may be more effective than treating individual aging systems separately. Measuring systemic biological aging could help assess anti-aging interventions.

• Biological age gauges genetic and environmental factors driving how fast individuals age, unlike chronological age. Developing reliable biomarkers of biological age would allow evaluating anti-aging treatments. Progress is being made using metrics like epigenetics, telomeres, mobility, facial aging.

• Evolution hasn’t strongly selected for longevity since grandparents mattered less for species survival than babies and parents. This leaves potential to extend lifespan. However, humans have been selected for surviving hardship, leaving a built-in ability to live longer through calorie restriction/reduced metabolism.

• Studies on calorie-restricted monkeys and humans suggest lowered metabolism may decrease aging effects and enable longer, healthier lives. The longest lived human, Jeanne Calment at 122, provides a glimpse at our lifespan potential.

• Jean Calment lived to 122 years old, beyond the biblical limit of 120 years from Genesis but after 120, genetics plays a bigger role than lifestyle.

• Nir Barzilai studies long-living Ashkenazi Jewish centenarians in New York to understand their genetics and find factors like certain genes that protect against diseases and inflammation.

• Lifestyle can help people live somewhat longer but the best way to live past 100 today is through genetics. Identifying longevity genes may allow introducing them via gene therapy or mimicking their effects.

• Places like Sardinia and Okinawa have “blue zones” where people live longer on average due to lifestyles like moderate exercise, purpose, community, plant-based diets, and moderate alcohol. However, genetics are still key to reaching ages like 122.

• Naked mole rats live over 30 years on average, much longer than expected for their size, due to genetics that give them cancer resistance, pain insensitivity, and efficient DNA repair. Research aims to learn from their genes and biology to expand human healthspans.

• The hard clam (Mercenaria mercenaria) lives around 40 years on average. Its closely related cousin the Icelandic quahog clam (Arctica islandica) has been found to live over 500 years.

• A major study compared these two clams and found the quahogs have remarkable resistance to oxidative stress, the damage cells incur from free radicals over time. This likely contributes to their extreme longevity.

• Understanding longevity in other species like naked mole rats, quahog clams and the immortal jellyfish Turritopsis dohrnii is providing clues about aging processes and potential ways to manipulate aging in humans.

• T. dohrnii is unique in its ability to reverse aging and revert from an adult jellyfish back into a polyp stage when faced with adversity. Studying its regeneration could help unlock secrets of cellular rejuvenation.

• Lifestyle factors like calorie restriction and exercise are effective first steps to “hack” epigenetic signals and longevity pathways in the body. Moderate exercise and intermittent fasting show benefits akin to continuous calorie restriction with less burden. Comparative studies of long-lived species continue to provide insights into aging biology applicable to humans.

• NAD+ levels decrease as animals age, weakening DNA repair. Drugs like NMN and NR can boost NAD+ levels by converting to it inside cells. Studies giving these drugs or increasing sirtuin/NAD+ levels in mice found benefits like improved organ function and longevity.

• Metformin is a diabetes drug that also shifts cells from growth to repair mode. Studies found metformin users lived longer than expected and had reduced risks of certain diseases and cognitive impairment. This suggests metformin targets multiple aging processes.

• Rapamycin also shifts cells to repair mode by regulating mTOR. It consistently extends lifespan in studies of various species by about 25%. It treats certain diseases but also has side effects when given long-term, so research aims to develop safer derivatives.

• Potential anti-aging drugs aim to mimic benefits of calorie restriction or target hallmarks of aging. NAD+ boosters, metformin, and rapamycin may be among the first, but more compounds are being investigated. Trials in humans are ongoing to maximize benefits and minimize risks.

• Research suggests pruning senescent cells in aging mice through genetic or drug-based approaches can lead to benefits like longer lifespan, regrowth of hair, stronger muscles and organs, and reduced diseases. This has sparked a race to develop drugs called senolytics that can selectively target and remove senescent cells.

• Autophagy, the process cells use to recycle biomass and remove harmful proteins, also declines with age. New treatments aim to manipulate autophagy at a cellular level to help older cells behave in a more youthful manner.

• Clinical trials are now exploring potential impacts of senolytic and autophagy-boosting drugs on age-related diseases as a first step toward treating aging itself directly. However, more work is needed to ensure safety and avoid unintended negative effects.

• Cellular reprogramming research shows it may be possible to partially reverse the epigenetic aging process in cells and whole organisms through controlled application of factors like Yamanaka factors, offering another potential avenue to tackle aging.

• Parabiosis research linking the bloodstreams of old and young animals demonstrates youthful factors in young blood can rejuvenate aging in recipient older animals, driving efforts to identify and isolate these factors for anti-aging therapies.

• Wealthy older people may soon pay younger people to transfuse their blood to stay healthy, as shown in the TV show Silicon Valley. In the future, people may store their own blood for later self-transfusions or transfuse plasma from others.

• As genes for longevity are identified, parents may use IVF and embryo selection to choose embryos most likely to live long healthy lives. They may also genetically alter embryos to further increase longevity chances.

• As we live longer, our body parts will break down more. But technologies like nanobots, 3D biological printers, and genetic tools may help fix and replace parts to upgrade our bodies over time.

• More investment in aging research could yield huge cost savings and quality of life gains compared to focusing just on aging-related diseases. It could pay for infrastructure repairs, education, and global clean water initiatives.

• Immortality may not be possible biologically, but digital transfer of brain function or disembodied semi-consciousness could in theory provide limited immortality. The ethics of enhancing and extending humanity will be a challenge as our understanding and ability to modify biology increases.

Genetic tools are powerful and how we understand and apply them will shape our future as a species. There are complex ethical issues around responsibility, diversity, and equity.

Our genetics are highly complex and interconnected - eliminating one disease risk could increase another. The sickle cell mutation both causes disease but also protects against malaria. Interventions often solve one problem while creating new unknowns, like with gene drives against mosquitos potentially damaging ecosystems.

We should be cautious about “playing God” given our limited understanding, but nature is also hostile and we’ve always fought diseases and challenges. If we accept humans as part of nature, then our technologies are also natural. We must balance progress with responsibility by thoughtfully considering risks of each step.

Debates will continue around heritable genetic changes, but perfect knowledge is impossible and progress inevitable given human nature. The focus should be wise decisions that consider future impacts on children. While some argue this removes childrens’ agency, others believe parents have an obligation to give children the best chances possible. Complex issues with reasonable perspectives on both sides.

The concept of human genetic engineering raises the specter of eugenics from the past. The term “eugenics” was coined in the 19th century but the concept of selective breeding and culling humans has ancient origins. Francis Galton popularized applying Darwin’s idea of natural selection to human societies in the late 1800s, arguing societies should promote reproduction among the “fit” and discourage it among the “unfit.”

Eugenics gained prominence in the early 20th century, embraced by scientists and progressives who saw it as a way to guide evolution and improve society. However, it also became intertwined with racist ideas, especially in the U.S. Many states passed compulsory sterilization laws for those deemed “unfit” like criminals or people with disabilities. Over 60,000 Americans were forcibly sterilized.

German scientists widely adopted Galton’s theories before WW2. The Nazis drew directly from the U.S. eugenics movement in formulating their own racist policies. They forcibly sterilized hundreds of thousands and later systematically murdered those deemed to have “lives unworthy of life,” like people with disabilities. Their deadly pseudoscientific program grew out of eugenics ideas that had been considered legitimate science in the early 20th century. This dark history hangs over any modern attempts to engineer human genetics and raises concerns about reopening the door to eugenics.

Here is a summary of the key points about hereditary biology and racial hygiene:

• In the early 20th century, eugenics aimed to improve human heredity by promoting reproduction by people with desired traits and reducing reproduction by people with less desired traits. This was based on the now discredited idea that human traits are solely determined by genes.

• The eugenics movement gained traction in the US and Europe in the early 1900s. By the 1930s-40s, it was widely discredited due to its association with Nazi human experimentation and atrocities.

• Some argue modern genetic technologies like prenatal testing or embryo selection could inadvertently lead to a “new eugenics” if not carefully regulated. Others counter that today’s practices are voluntary rather than coercive.

• The prospect of genetic engineering raises debates around parental choice, state control, and balancing individual freedoms with societal impacts. Views differ on where to draw the line between medical interventions and genetic enhancement.

• While historical eugenics focused on race and class, modern debates center more on individual choice and medical ethics. However, the long-term societal effects of widespread genetic selection are still uncertain.

So in summary, it outlines the history of discredited racial hygiene programs under early 20th century eugenics and ongoing debates around balancing individual choice, medical ethics and societal impacts with new genetic technologies.

• Genetic diversity has allowed human ancestors to evolve and adapt over time in response to environmental changes. Diversity ensures some members of a species will have traits that help them survive new conditions.

• However, if too many individuals make choices that reduce diversity, like selecting for specific traits in embryos or gene editing, it could make the whole species less able to withstand future challenges. This is like how domesticating corn for higher yields made it less genetically diverse and more vulnerable to disease.

• While some diversity is beneficial, it would be a mistake to fetishize every aspect of it. Some genes cause diseases and disabilities, so genetic engineering could in theory both enhance and reduce diversity.

• Any new technologies are likely to be adopted unequally at first. If only some groups can access genetic enhancements, it could worsen inequities and allow those groups to dominate societies over time due to perceived advantages. Equitable access will be important to avoid these negative outcomes.

• Absolute equality should not necessarily be the goal, as some genetic advantages could have practical benefits (e.g. enhanced traits for space travel). However, inequality left unchecked could also become problematic.

• New technologies are often initially adopted only by elites before becoming more widely available over time at lower costs (e.g. smartphones). Trying to mandate equal initial access could inhibit development and later widespread access.

• Governments and insurers may incentivize genetic screening and editing to avoid costly lifelong care for genetic diseases. However, not all parents will rely on these incentives and some may aggressively select and enhance their children regardless.

• Genetic identification of potential and predispositions could help disadvantaged individuals realize their talents but must not be used to rigidly determine individuals’ roles or limit opportunities. Providing enhanced opportunities to the genetically gifted may benefit society.

• Genetic inequality is already present due to differences in environments and life circumstances. Addressing current inequalities should be a priority over hypothetical future issues with genetic engineering. Some level of genetic diversity is also important for humanity.

So in summary, the key debate is around balancing genetic equality and opportunity versus allowing enhancement and realizing genetic potential, within a framework that promotes overall equality and opportunity today. Absolute equality should not be the goal if it comes at the cost of benefits to society or fulfilling human potential.

This passage discusses the tensions between humanity’s drive to control nature and the need for ethical limits and regulation. While genetic engineering could help overcome human limitations, it also faces many of the same issues that debates around environmentalism, reproduction, and other topics address.

The history of human societies shows an initial respect for nature gradually replaced by domination as populations grew and technologies advanced. Though views have evolved over time, differences remain between cultures and ideologies. This diversity will shape debates over using genetic technologies for human enhancement or modification.

Regulation is important to balance scientific progress with ethics, but finding agreement will be challenging given competing interests within and between nations. As the science advances exponentially while public understanding grows linearly, establishing effective oversight structures risks lagging behind developments. The intellectual link between eugenics and transhumanism also serves as a warning about potential overreaches if limits are not respected. Overall, embracing yet carefully guiding the future of genetic engineering will be key to enabling humanity’s potential while avoiding past mistakes.

Here is a summary of the key views and debates around genetically modified crops discussed in the passage:

• Scientists have understood genetics for over a century and have long selectively bred crops to enhance traits. Genetic engineering allows direct modification by transferring genes between organisms.

• When this technology emerged in the 1970s, some scientists raised safety concerns and advocated for standards, which led to the 1975 Asilomar conference to discuss responsible use.

• The U.S. and China have widely adopted GM crops due to perceived benefits of increased yields and profits for farmers. Public opinion in these countries is generally accepting based on science showing GM safety.

• However, some groups oppose GM technology due to distrust of corporations, fears over food safety and contamination, or preference for traditional farming. They have spread disinformation countering the scientific consensus on safety.

• While GM crops are judged safe to eat by scientific consensus, legitimate issues like over-reliance or super-weeds require thoughtful regulation to balance the technology’s benefits and risks.

• Different societies have strongly disagreed over this issue, with the U.S. and China more open to GM and parts of Europe more skeptical based on non-scientific safety concerns. It remains a contentious debate around human relationships with nature and new technologies.

• Many Europeans are resistant to genetically modified foods due to beliefs that GM foods are “unnatural”. This activism particularly took hold in Europe, where polls showed majorities believing GM foods were unsafe and their development should be discouraged.

• In response to public opinion, European regulators took a precautionary approach and required GM food labeling. However, full GM labeling would be misleading since many common foods contain genetically modified ingredients.

• Anti-GMO groups like Greenpeace have disrupted GM research and destroyed GM crop trials. This put pressure on European politicians, who allowed countries to individually restrict GM crops against scientific evidence. By 2015, 17 European countries had banned GM crop cultivation.

• Regulators acknowledged restricting GMOs went against science, but public opinion had forced their hand. It was alleged Greenpeace lobbied against labeling GM enzymes to avoid undermining anti-GMO support. The EU also ruled gene-edited crops would face the same regulations as GM crops.

• Europe’s bans have economic costs but do not directly risk lives. However, they have negatively impacted developing nations by limiting crop exports and adoption of GM crops that could boost nutrition, yields and resilience to drought. Anti-GMO campaigns are seen as doing more harm than good by Nobel laureates and experts.

• After the Roe v. Wade decision legalized abortion in the US, anti-abortion pressure increased, especially in conservative states. Nearly 300 attacks were carried out on abortion clinics over 40 years.

• In China, abortion was initially banned under Mao but legalized in 1988 to support the one-child policy. The policy, in place until 2015, led to forced abortions and over 400 million fewer people than projected.

• Abortion views differ across religions and cultures. Liberal Christian denominations generally support abortion rights while Catholic, Mormon, Baptist views oppose it. Chinese culture sees abortion as ensuring healthy families.

• Global abortion laws vary widely. Over a quarter of countries only allow abortion to save a mother’s life, while 42% place major restrictions. Restrictive laws are more common in religious-dominated societies.

• US public opinion on abortion is divided (58-40% in 2017) while European countries generally support it more. Views correlate with religious affiliation.

• The genetics debate mirrors abortion politics. Some fear “GM babies” from gene editing embryos, like “pro-life” opposition to abortion, while others support medical benefits like earlier acceptance of IVF. Public views on genetic selection depend on purpose and intervention level.

• Polls show that Americans are more comfortable with genetic interventions for clear medical purposes than other uses, and that acceptance levels are growing over time. Religious Americans are less comfortable than non-religious Americans.

• Acceptance of genetic technologies has increased significantly in the UK since 2001 due to extensive public education campaigns. Over 3/4 support altering embryos that would affect future generations to treat genetic disorders.

• China has seen the biggest swing toward widespread acceptance of assisted reproduction technologies due to cultural emphasis on healthy birth and stigma around disability. Genetic screening and abortion is seen as less of a religious issue.

• Attitudes differ between religious groups, with Catholicism strongly opposing embryo selection and genetic alteration, while Judaism is more supportive as a way to repair the world and ensure healthy offspring. Views within religions are also diverse.

• Laws governing genetic technologies differ globally, with the US having the most permissive system and some European countries like Germany and Italy being more restrictive.

• Countries have diverse and varying regulations regarding genetic technologies like germline genetic modification, reproductive cloning, gene therapy, preimplantation genetic diagnosis, embryonic stem cell research, and human cloning for research.

• The US, Australia, Belgium, Brazil, Canada, France, Germany, and the Netherlands prohibit inheritable gene editing. Some countries like France and the Netherlands ban initiating pregnancies from genetically modified embryos. The UK allows some exceptions on a case-by-case basis.

• Genetic privacy laws also vary widely. The EU has the strongest protections under the GDPR, while countries like the US and Canada mainly ban genetic discrimination but offer less comprehensive data protections. China recently passed a privacy law but it is aimed at government control over data rather than individual privacy.

• This diversity creates a “laboratory of nations” where different approaches can be tested, but it also risks a race to the lowest regulatory standards as countries feel pressure to remain competitive. The impact of different national restrictions is muted due to international travel for procedures and differing oversight cultures.

• Genetic nondiscrimination laws apply to things like health insurance and military service, to prevent discrimination based on genetic information.

• As universal genetic sequencing becomes more common, it will show that everyone has some preexisting condition or increased risk for disorders. This will make genetic nondiscrimination even more important.

• Competitive pressures may lead to a “genetic arms race” as gene editing technologies advance. People will seek enhancements to gain advantages over others in areas like sports, and the line between therapy and enhancement will blur.

• Sports provide an example where genetic advantages already play a large role in elite athletic performance. Certain genetic mutations have been linked to endurance, speed, and muscle growth.

• Groups like the Kenyan Kalenjin tribe dominate long distance running partly due to genetic traits like body type that aid performance. Identifying genetic potentials could lead countries to filter citizens for athletic development.

So in summary, genetic discrimination laws will become more crucial as sequencing reveals universal genetic risks and variations, while competitive pressures may fuel a genetic arms race and identification of genetic traits for enhancing performance in various areas like sports.

• The passage describes noticing differences between American and Chinese women’s volleyball teams at the 2008 Olympics - Americans were more varied physically while Chinese athletes seemed more uniformly selected and trained.

• It argues this reflects different societal models - the individualistic US system vs China’s statist system that identifies potential athletes young based on physical attributes and trains them intensely.

• As genetic testing identifies more predispositions for athletic success, it will be less fair for those without them to compete. But penalizing genetic differences would be problematic too.

• One response could be categorizing athletes by genetic profiles, but this has many issues and diversity is important in sports.

• Parents are already using consumer genetic tests and intense training from young ages, hoping to realize kids’ athletic dreams.

• Countries like China and Uzbekistan have begun integrating genetic testing into national sports programs to identify future prospects.

• As testing improves, more countries may feel pressure to adopt this approach to remain competitive, potentially clearing the way for more direct genetic enhancements over time.

This passage discusses the immense pressure and competition in education systems in places like South Korea and China. Parents in these countries go to great lengths to give their children advantages, like paying for expensive cram schools or plastic surgery as graduation gifts. Some Chinese parents pay large bribes to get kids into good middle schools.

Similar pressures exist in the US through the SAT prep industry. Some argue this level of pressure can harm children’s well-being. However, parents see advantages in education as important for future success.

Direct-to-consumer genetic tests are now being marketed to parents to provide insights into children’s traits and talents. Chinese companies claim to predict talents in areas like sports, arts, etc. based on genetics. While the tests have limitations now, pressure on parents to access this technology exists due to desires to give children competitive advantages.

Some governments have banned certain direct-to-consumer tests due to accuracy concerns. But as tests improve and people become more educated about genetics, wider access may become more acceptable. The passage suggests some highly competitive parents may eventually pursue embryo selection or genetic alteration to optimize children for success, if given the option.

• Parents are already putting a lot of effort into giving their children advantages after birth through things like activities, education, etc. Genetic enhancement would be just a bigger step of giving pre-birth advantages.

• Competition will drive the process forward. Those who opt-in for genetic optimization may ensure their kids don’t get diseases, are healthier, and excel in certain tasks. This could create an accelerating advantage over generations.

• Those who opt-out risk their kids being at a disadvantage compared to genetically optimized peers. The gap between opt-ins and opt-outs could grow over time, creating two classes.

• States also have competitive incentives to adopt genetic enhancement to optimize their populations and gain national advantages over other countries. China in particular sees technologies like AI and genetic engineering as keys to overtaking the US as the global leader.

So in summary, both at the individual parent and country level, competition is likely to be a driving force propelling the adoption of genetic enhancement as a way to give children pre-birth advantages over others.

• The document called for increased cooperation between China’s military and civilian sectors to promote the development of AI technologies. This aims to integrate AI across different fields for efficiency gains.

• By contrast, the Trump administration was slow to prioritize AI and science. Key science leadership positions remained vacant and budgets were cut for agencies involved in AI research. Immigration restrictions may have hampered talent acquisition.

• With less support from the US, China is aggressively pursuing leadership in advanced genetics and precision medicine. Its initiatives far exceed past US plans. China is building large genetic datasets and increasing scientific publications/patents. R&D spending growth outpaces the US and EU.

• The competition between the US and China in AI and advanced technologies will help define their relationship in the future. It is increasingly a two-horse race as both ecosystems innovate. This competition will drive faster progress but also zero-sum outcomes as advantages shift between countries.

• National champions will likely emerge from this rivalry in the life sciences, analogously to tech companies like BAT and FAAMG. Companies like iCarbonX in China are positioning themselves in this role by combining genetic/health data with AI.

• While competition drives progress, it also risks fueling conflicts within and between societies over issues like access to genetic technologies and population-level impacts. Managing these tensions will be challenging.

• Countries have three main options regarding human genetic enhancement: 1) Opt out and accept potential consequences like losing competitiveness, or 2) Hold the line but allow a referendum to opt in, or 3) Opt out but push for global limits on enhancement.

• Option 3 recognizes that opting out alone may not work given genetic changes could spread across borders. The main approaches proposed are persuasion, building an alliance to pressure others, and using sanctions or potentially military force against countries that will not comply.

• Military force is suggested as a potential “last resort” option, particularly if a powerful enhancing country like China resisted limits. However, using force over genetic changes could spark the same level of conflict as current geopolitical tensions.

• Avoiding worst-case scenarios will require global cooperation to optimize benefits and minimize dangers, but succeeding will be challenging given historical failures to fully cooperate on existential issues like nuclear weapons and climate change. Competitive pressures make genetic engineering hard to contain without collective guidance on values and limits.

Here is a summary of the key points about standards for nuclear nonproliferation under the NPT:

• The NPT created standards for the five original nuclear weapon states (Britain, China, France, US, USSR) to possess nuclear weapons.

• It established incentives for other states to refrain from developing or acquiring nuclear weapons by promising help for peaceful nuclear energy development.

• Since adoption, the NPT’s impact has been mixed. It prevented an arms free-for-all but nuclear stockpiles grew enormously in US and Russia. Ukraine and Libya gave up programs but were later invaded. Others like Israel, India, Pakistan acquired outside the NPT. Risk of breakout remains.

• The system is imperfect but still better than no system at all in containing proliferation. When thinking about preventing genetic risks, the author looked to the nuclear example as genetics also risks benefits but could harm humanity if uncontrolled.

In summary, the NPT set standards for the five original nuclear states while creating incentives for others to refrain from pursuing weapons in exchange for civilian nuclear assistance, but proliferation challenges remained and show the difficulty of such international nonproliferation efforts.

• Early human ancestors gathered around a fire discussing rules for their tribe. One suggested not killing others within their own tribe, which the others agreed was a good rule.

• A more visionary ancestor proposed preventing conflict with other tribes by bringing them together to agree only using spears for hunting, not harming each other. The others were silent in response.

• A scrawny man then suggested using spears to hunt animals and steal from other tribes for more food and stuff. The others nodded in agreement, thinking this was a good idea.

• Through technological revolutions like the industrial age, well-meaning warnings about potential dangers were often ignored. International cooperation and regulations have helped manage threats like nuclear weapons and environmental destruction, though not perfectly.

• For human genetic engineering, some level of global harmonization of approaches will likely be needed to balance progress and risks, as an unrestricted approach could lead to conflicts within and between societies. Past successes point to smart international regulation as a key part of any effective approach.

• However, reaching consensus on principles and regulations has been challenging given different perspectives on issues like human rights and responsibilities. Several past efforts by UN bodies have not established legally binding or truly global agreements.

• International efforts so far to establish consensus and restrictions on human genetic engineering have failed due to disagreement between cautious and aggressive stakeholders.

• Restricting “any modification” in descendants’ genomes was too simplistic in the past and progress in therapies like mitochondrial transfer shows restrictions need flexibility.

• As genetic tools advance to eliminate disease risks, avoiding all modifications looks less humanitarian and more dangerous. Regulations must balance enabling beneficial science and restricting harm.

• Drawing regulations too permissively or restrictively will fail; an agreement needs vague flexibility to accommodate scientific progress without offending stakeholders or impeding innovation.

• The only feasible initial restrictions may be a shared definition of “redlines” like dangerous human experimentation or enhancing traits beyond dignity.

• Any standard requires renegotiation as science and social acceptance change. Advanced nations could incentivize participation by helping others develop capabilities.

• Extreme violations by “rogue” actors may require escalating pressures like sanctions, though military intervention risks are concerning given poor intervention track records.

• The top priority is developing national public education, ethics frameworks, and tailored regulations to build understanding and shared practices before international coordination is feasible. Individual responsibility and grassroots movements are also important to guide norm development.

Norm-building around issues like human genetic engineering takes time through conversations, research, debates and sometimes conflict. Key ideas and processes outlined include:

• Small groups of committed people can create change over time through dialog and coalition building.

• Past global issues like industrialization and nuclear power lacked today’s connectivity, but more people are now online, enabling broader discussion.

• A global, species-wide conversation is needed on genetic engineering as the science advances quickly.

• An international commission could frame essential questions to help structure local and online dialogues worldwide.

• partner organizations would facilitate discussions in many venues to involve diverse perspectives.

• Ongoing feedback loops would inform expert recommendations and help societies define acceptable limits.

• While a long process, public engagement is crucial to develop norms that guide genetic technologies in a way that respects humanity. The alternative risks negative public backlash without input.

• Values like humanism, diversity and equality must underpin how we enhance biology while respecting our shared humanity.

• Starting the global conversation now is urgent, as difficult as it may be, to positively influence humanity’s coming genetic transformation.

Here is a summary of key points:

• Human-caused greenhouse gas emissions are contributing to global climate change and rising temperatures. The Paris Agreement aimed to reduce emissions but the US withdrew under President Trump.

• Ratification of climate treaties takes time - as of 2018, only 29 of 47 Council of Europe members had ratified the Paris Agreement and passed domestic laws implementing it.

• Harvard biologist E.O. Wilson said humanity has “created a Star Wars civilization, with Stone Age emotions, medieval institutions, and godlike technology.” This points to a disconnect between our advanced capabilities and social/political structures.

• Futurist Stewart Brand also commented that as our technologies become more powerful, we must work to use them responsibly and for the benefit of humanity. The quotes suggest our social and technological progress are out of balance.

Here is a summary of the provided citations:

• Citation 1 discusses differences in human psychological traits and how much of that is due to genetic versus environmental factors, based on a famous twin study from 1990.

• Citation 2 examines evidence from genome-wide association studies and polygenic scores on traits like height, BMI, and disease risk, finding genetics can help predict individual outcomes.

• Citation 3 discusses a medical algorithm developed by Genomic Prediction that analyzes whole genomes to predict disease risks and healthier lifestyle choices.

• Citation 4 describes Geisinger Health’s initiative to implement whole genome sequencing in primary care as preventative medicine, finding it ready for clinical use.

• Citation 5 presents findings from the All of Us Research Program, a large national effort to gather genetic and health data on over 1 million US participants.

• Citation 6 discusses China’s large-scale national genomic initiatives, with goals of sequencing millions of citizen genomes to advance precision medicine capabilities.

• Citation 7 examines the substantial data generated each minute worldwide and challenges of analyzing high-throughput omics data.

• Citation 8 provides context on precision medicine initiatives in countries like Iceland, the UK, and Estonia, as well as private sector collaborations.

Here is a summary of the key points from the article “Aits Based on Fifty Years of Twin Studies,” Nature Genetics 47 (2015): 702–709:

• The article examines over 50 years of twin studies that have contributed to our understanding of the genetic and environmental factors influencing complex human traits and diseases.

• Early twin studies in the 1960s and 1970s provided evidence that genetics plays a role in many psychiatric and behavioral traits. For example, genetics accounts for around 60-70% of the variance in schizophrenia risk.

• Larger sample sizes in more recent twin studies have allowed researchers to tease apart the effects of shared versus non-shared environmental factors. Non-shared factors, like differing life experiences between twins, often have as much influence on traits as genetic factors.

• Genome-wide association studies and molecular genetic techniques combined with twin data have identified hundreds of genetic variants associated with traits like BMI, height and disease risks. This confirms that complex traits are influenced by many genes of small effect.

• Future directions include studying epigenetic factors, gene-environment interactions, using DNA sequencing to find rare variants, and combining multiple “omics” datasets to better understand the interplay between nature and nurture.

• Overall, twin studies have proven invaluable for quantifying hereditability and disentangling genetic and environmental sources of variation for human traits and diseases over the last 50+ years. They continue providing key insights as genomic research evolves.

Here is a summary of the article “Inside the Efforts to Finally Identify the Size of the Nation’s LGBT Population,” Time, May 18, 2016:

• Until recently, there has been no consensus on the size of the LGBT population in the US due to limited and flawed data collection. Most estimates have ranged from 3-10% of the population.

• Researchers and government officials have made efforts to better measure the LGBT population through sound surveys and data collection methods. In 2014, the CDC included questions about sexual orientation on a national health survey for the first time.

• Some key findings from recent rigorous surveys suggest 3.5% of American adults identify as lesbian, gay or bisexual, and about 1% as transgender. Younger generations are more likely to identify as LGBT.

• Better data can help direct funding and policies to support the health and well-being of LGBT communities. However, challenges remain as some are still uncomfortable disclosing sexual orientation or gender identity. Ongoing research continues to refine estimates of the LGBT population size.

• Source 30 describes a limited study that tracked children born from ooplasmic transplantation, a technique that transfers mitochondria from a donor egg to the recipient egg.

• Source 31 discusses the regulatory landscapes around mitochondrial replacement therapy (MRT) in the UK and US. The UK began administering MRT treatments in 2018 to prevent transmission of mitochondrial diseases.

• Source 32 notes that information about the UK mitochondrial transfer babies is being withheld until birth, but logically the first birth would be in 2019 based on treatment timelines.

• Sources 33-34 describe controversies around biomedical companies like Darwin Life using unapproved techniques like egg cytoplasm transfer, as well as a Ukrainian clinic claiming success with three-parent babies to treat infertility.

• Sources 35-37 provide context on preimplantation genetic diagnosis and its limitations for treating mitochondrial diseases, as well as calls for more funding and research on such conditions.

• Sources 38-41 describe advances in CRISPR-Cas9 gene editing, including its first use in human embryos by Chinese scientists to modify diseases, though off-target mutations remain a risk.

Here is a summary of the key points from the sources provided:

• Source 1 discusses how artificial intelligence could lead to superintelligence if it achieves human-level intelligence and then surpasses it due to recursive self-improvement. It recommends an article with an insightful explanation of this issue.

• Sources 2-3 are translations of ancient works, the Iliad and Divine Comedy respectively.

• Source 4 looks at perspectives from different religions (Judaism, Islam, Hinduism) on using pig and cow surgical products.

• Source 5 argues against an opt-out system for organ donation. Monty Python parodies live organ transplants.

• Source 6 suggests policy changes like shifting to an opt-in system or allowing compensation could address organ donation shortfalls.

• Source 7 provides an overview of immunosuppression.

• Source 8 discusses inactivating porcine endogenous retroviruses in pigs using CRISPR-Cas9 to make pig organs safer for human transplantation.

• Source 9 reports on a breakthrough growing sheep embryos containing human cells.

• Sources 10-11 describe open-source biological parts and gene databases for synthetic biology.

• Sources 12-13 provide statistics and forecasts on the growth of the synthetic biology market.

• Sources 14-15 discuss investor interest in synthetic biology and the creation of a synthetic microbe with fewer than 500 genes.

• Source 16 interviews a synthetic biologist about the possibility of synthetic humans. Ethical considerations are important.

• Source 17 stresses ethical review of initiatives like writing a synthetic yeast genome.

• Source 18 speculates about using synthetic biology to modify the human genome and achieve radical life extension.

• Sources 19-21 provide context on early attempts at rejuvenation and ideas from ancient texts.

Here is a summary of the key points from the article:

• Naked mole-rats are extremely long-lived for their size, living over 30 years which is unusually long for a rodent.

• They exhibit few signs of aging throughout their lifetimes and have a very low occurrence of cancer.

• Studies have found they are highly resistant to oxidative stress and damage from reactive oxygen species due to efficient antioxidant defenses and natural repair mechanisms.

• Their metabolism runs very cold and slow compared to other mammals, which may help protect against damage accumulation over time.

• They are also tolerant of low oxygen environments which may protect cells from oxidative stress.

• More research is looking at naked mole-rat genes, proteins and cells to better understand their biology and identify potential longevity secrets that could benefit human health. Understanding how they defy typical aging processes could provide insights into extending healthy lifespans.

So in summary, the article discusses how naked mole-rats are exceptionally long-lived for rodents and resistant to aging effects, looking at potential biological reasons for this tied to protection against oxidative stress and damage.

• Indigenous populations in places like North America contributed to extinctions of large mammals through overhunting (Krech). Whether humans were solely responsible is debated.

• Mao’s Great Leap Forward in China in the late 1950s caused a massive famine that killed tens of millions due to misguided agricultural and environmental policies (Dikötter).

• Economic development in China has come at tremendous environmental costs, including widespread pollution of waterways (Economy).

• In 1980, the Supreme Court ruled in Diamond v. Chakrabarty that genetically engineered organisms could be patented, opening the door to commercial biotechnology.

• In 1974, scientists at Asilomar conference warned of potential biohazards of recombinant DNA research and called for cautious experimentation and oversight (Berg et al.).

• Guidelines were established in 1975 for recombinant DNA research based on the Asilomar discussions (Berg et al.).

• Public opinion on genetically modified foods in the US is mixed, with concerns about safety but also a sizable minority who believe benefits outweigh risks (Blizzard, Funk & Kennedy).

• Trust in scientists working on GM foods is moderate but has declined somewhat in recent years (Funk & Kennedy).

This article discusses genetically modified foods and trust in scientists associated with them. Some key points:

• The global market for genetically modified seeds is growing at around 9.83% annually and was valued at $27 billion in 2016.

• Regulations of GM crops differ between countries like China and the US. China remains cautious but is also a major consumer of GM crops.

• Public attitudes toward GM foods differ - a 2015 study found Chinese were neutral to positive, while Europeans tended to be more wary according to other surveys cited.

• Trust in scientific consensus on GM safety is an important factor. Several major scientific organizations are cited affirming GM safety based on studies conducted over 20 years. However, some anti-GM groups continue to raise concerns.

• Issues around labeling of GM foods and new gene-editing technologies like CRISPR are also discussed in relation to regulations and public perceptions. Overall the article explores the debate around GM foods with a focus on scientific evidence and differences in trust and policy internationally.

• A 2014 Pew poll found that residents of the largely Catholic Philippines oppose abortion the most, while residents of mostly secular France oppose it the least. Views on abortion vary significantly around the world based on cultural and religious factors.

• Countries regulate abortion differently - some ban it entirely, some allow it only in limited circumstances like rape or health risks, and others have broad access. Around the world, views on stem cell research, IVF, and genetic technologies also vary based on cultural and ethical perspectives.

• Public opinion polls in Western countries generally find increasing acceptance of technologies like IVF and preimplantation genetic diagnosis over time, though views on human germline modification and gene editing of embryos remain more mixed. Some religious groups oppose technologies that involve modifying human embryos.

• China has embraced technologies like embryo selection but questions have been raised about the level of informed consent and regulation. Public attitudes in China toward genetic technologies have also become more accepting in recent years. However, concerns have emerged about privacy and use of genetic data by the Chinese government.

• International differences in laws and attitudes have contributed to the rise of medical tourism or “reproductive tourism” as patients travel across borders to access procedures not allowed in their home countries. This raises ethical issues around accountability and informed consent.

The article discusses two reports on the situation of Uighurs in Xinjiang, China. The first is a New York Times report that cited “credible reports” of China holding over 1 million Uighurs in secret camps. Beijing denied this claim. The second article discusses a state-run Chinese newspaper refuting the detention claims and saying China has “prevented a great tragedy” in Xinjiang.

The summary also mentions that in 2018, the UK Home Office was exploring creating a centralized database of biometric data collected from UK citizens. However, this detail is not as relevant to the main discussion and comparison of the two reports on the situation of Uighurs in China. The summary focuses on synthesizing the key details from the two news articles on the situation in Xinjiang rather than including unrelated tangential details.

Here is a summary of the article:

• The White House announced the creation of a new Select Committee on Artificial Intelligence within the National Science and Technology Council.

• The committee will help coordinate artificial intelligence research and development across federal agencies and ensure cooperation between the government and private sector.

• It will be chaired by Michael Kratsios, the White House’s chief technology officer. Other members will include officials from the departments of Defense, Commerce, Energy, Health and Human Services, and Transportation.

• The committee’s goals are to advance AI research, promote safety standards, shape AI policies, and prepare the workforce for new AI-related jobs. It aims to develop strategies and recommendations for the administration on AI technology and applications.

• Experts say the committee is needed to address concerns around AI’s effects on the economy and national security. It shows that American leadership in AI is a priority under the Trump administration. However, some question if more specific policy proposals or funding commitments are needed.

In summary, the White House announced a new committee focused on coordinating AI policy and development across the US government to maintain American leadership in AI and address related issues. The committee will be chaired by the CTO and include other government officials.

The author thanks his agent Jill Marsal for helping him find the perfect editor and publisher for his book. He had some initial nerves about sitting down to write but his agent helped guide him.

He expresses gratitude for his phenomenal editor Grace Menary-Winefield at Sourcebooks publishing. She and the rest of the team, including Liz Kelsch, Lizzie Lewandowski, and Cassie Gutman, did incredible work bringing the book to life.

He also thanks the thousands of people who attended his talks on the book topics over the years, as their questions and comments helped expand his thinking.

The book is dedicated to the memory of Scott Newman and Irwin Blitt, as well as to the author’s parents and two nieces.

A brief bio of the author Jamie Metzl is then provided, noting his background working in national security and foreign relations. He currently works as a technolgy futurist and commentator.