How to Grow a Human - Philip Ball

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

• The book and its contents are copyrighted and protected work. Philip Ball asserts his moral right to be identified as the author.

• Under international copyright conventions, no part of the text can be reproduced, transmitted, downloaded, decompiled or stored without express written permission from the publisher, HarperCollins.

• The publisher holds the exclusive right to publish and distribute the work.

• Copyright is asserted over both the content of the text itself as well as any images included. Individual image copyright holders are acknowledged.

• Information is provided on the book’s ISBN numbers, publication date, publisher imprint and contact details for the publisher.

• The passage establishes the legal framework of copyright over the intellectual property contained in the book. It asserts the author and publisher’s exclusive rights over reproduction and distribution of the copyrighted work.

• The author had a small piece of skin tissue removed from his shoulder by a neuroscientist. This tissue was cultured in a lab to grow neurons and form a miniature “mini-brain” structure over 8 months.

• The mini-brain resembled a lentil-sized cluster of neurons that could signal to each other, though it was not capable of conscious thought. Such organoids are grown to help study brain development and diseases like Alzheimer’s.

• The author’s mini-brain was part of a research project to alter perceptions of dementia and test arts-based interventions. Researchers hope organoids from people with genetic mutations linked to diseases can provide insight into causes and potential cures.

• Remarkably, the mini-brain was grown from the author’s skin cells, showing that any part of the body can potentially be transformed into any other part, including a complete self. This realization challenges views of what it means to be human.

• Advances in cell transformation raise philosophical implications beyond what popular references like Frankenstein and Brave New World address. Possibilities like growing a human brain in an animal body or assembling organs in vitro lead to debates about consciousness, identity and the nature of reality.

So in summary, the author discusses how growing an organoid “mini-brain” from his own cells demonstrates the profound plasticity of the human body and challenges conceptions of selfhood. It also opens speculative possibilities that push the boundaries of what sci-fi has contemplated.

• The chapter discusses the early history of the cell theory and discovery of cells. William Harvey proposed in the 1600s that all living things come from an “egg”, though he was vague on what he meant by egg.

• Robert Hooke made early microscopic observations of cells in cork in the 1660s, though he did not realize cells were a general feature of living things. Antonie van Leeuwenhoek discovered single-celled microorganisms in the 1670s.

• Scientists in the late 1600s-early 1700s observed sperm under microscopes and imagined they saw tiny embryos or “homunculi” inside, supporting the theory of preformation that embryos were preformed rather than developing. This was eventually disproven.

• The early microscopists did not establish that cells are the fundamental units of living things. That idea was proposed in the early 1800s by Theodor Schwann, who said all tissues are made up of cells. Embryology studies in the 1800s also helped disprove preformation theories and support embryonic development from unstructured eggs.

So in summary, the passage outlines the key early discoveries and debates that contributed to the eventual establishment of the modern cell theory in the 1800s, after initial microscopic observations failed to realize cells’ broader significance for life. Early theories about sperm and embryology are also discussed.

• Schwann developed the cell theory while working under Johannes Müller in Berlin. He collaborated with Matthias Schleiden, who focused on plant cells.

• Schleiden initially believed cells were spontaneously generated, but Remak showed cells divide to proliferate. Virchow popularized this discovery and concluded all cells arise from preexisting cells (omnis cellula e cellula).

• Virchow viewed cells and organisms as collections of autonomous units, influenced by Enlightenment philosophy. This paralleled views of society as individuals working together.

• The discovery of microbial pathogens by Pasteur and Koch established the germ theory of disease. Germs came to be seen as foreign invaders, fueling political/racial frameworks for disease.

• Early views of cells incorporated political and philosophical ides of individualism, society, and responsibility. Cell theory reflected beliefs about the natural and social world.

• In the late 19th/early 20th century, advancements in microscopy revealed key internal structures of cells like the endoplasmic reticulum and Golgi apparatus. There was debate around whether the cell’s internal material (protoplasm) was granular, reticular, or filamentous in structure.

• Images by Edmund Beecher Wilson in 1900 showed various internal structures could be seen depending on the cell and time observed. This led Wilson to doubt the usefulness of calling cells “chambers”. Others questioned if the cell was really the fundamental unit of life.

• It became clear cells contain enzymes that enable metabolic reactions. Experiments showed these reactions could still occur outside intact cells.

• Cells were understood to have organized, compartmentalized structures like organelles to carry out specific functions like energy production (mitochondria) and protein processing/transport (Golgi apparatus).

• Key differences emerged between prokaryotic and eukaryotic cells, with the latter having a nucleus. Life’s activity and dynamic, out-of-equilibrium nature distinguish it from inanimate matter.

• The ability of cells to divide and propagate was established but not fully explained. Reproduction allows Darwinian evolution but there is no intrinsic goal or striving in life’s processes. The cell remains the fundamental unit of life.

• In the late 19th century, scientists began to fully recognize cells as the fundamental unit of life. They understood that cells reproduce through cell division (mitosis), not spontaneous formation of new cells.

• Walther Flemming studied cell division in detail in the 1870s-1880s. He observed that the nucleus breaks down into thread-like chromosomes during mitosis. The chromosomes then separate into two groups connected by a mitotic spindle.

• Theodor Boveri discovered the centrosome, which guides chromosome movement via spindle fibers during cell division. This showed cell division is a carefully organized process of passing genetic material (chromosomes) to daughter cells.

• Around 1900, scientists realized chromosomes carry the “genes” (discovered by Mendel), the basic units of inheritance that allow traits to be passed down. Genes are expressed in an organism’s phenotype but are determined by its genotype (Johannsen).

• Walter Sutton and Theodor Boveri independently proposed chromosomes are the carriers of genes. Thomas Hunt Morgan’sexperiments with fruit flies in the 1910s-15s established genetics and chromosome theory, showing gene mapping and position influences inheritance.

• This established our modern understanding of cells dividing to faithfully pass genes (contained in chromosomes) between generations, driving inheritance, evolution, and the replication of life.

• In the 1940s, evidence emerged that genes reside on DNA, though this wasn’t universally accepted until 1953.

• In 1953, Watson, Crick, Wilkins and Franklin revealed the double helix structure of DNA. This showed how genetic information could be encoded and replicated in the DNA molecule through the pairing of nucleotide bases.

• The double helix structure provided a mechanism for inheritance and copying genetic information during cell division. It also explained how random mutations in DNA could drive evolution through natural selection.

• Genes encode the amino acid sequences of proteins. The genetic code specifies which nucleotide triplets correspond to each amino acid.

• Transcription and translation are the two-step process by which genes are used to produce proteins. Transcription copies DNA into messenger RNA, and translation uses this RNA template to assemble proteins from amino acids.

• However, DNA alone does not provide a full set of instructions to produce an organism. Development and the role of most genes is complex. The genome sequence does specify an organism’s identity, but not its form and traits in detail like a blueprint would.

So in summary, the discovery of DNA’s structure resolved key questions but the relationship between genes and phenotypes is more complex than early metaphors like genetic “blueprints” implied.

• Proteins carry out biochemical functions that can be involved in many different traits. They don’t have a one-to-one relationship with a specific trait.

• A genome provides the basic “recipe” or set of instructions for building an organism, but it does not dictate the exact way those instructions will be carried out or the specific traits/structures that will emerge. Development and gene expression are complex, dynamic processes.

• Franklin Harold likens the genome to a “Glass Bead Game” where it functions like a master player engaged in an intricate system of cues and responses, shaped both by internal rules and the player’s will.

• Genes influence traits and behaviors but do not determine them fully. Their effects are filtered through development and dependent on environmental/experiential factors.

• Genetics concepts like “blueprint,” “selfish gene” and “gene for X” are overly simplistic metaphors that can distort our understanding. The relationships are complex and multifaceted.

• Genes only take on meaning and function in the context of living cells/organisms. A lone gene is biologically inert. Developmental/environmental context shapes how genes are expressed and what functions they serve.

• The gene-centric view is just one way to understand life - breaking things down is useful but we must recognize the whole is more than the sum of parts. Development is a dynamic interplay between genetic and non-genetic factors.

• Some physicists claimed they were close to finding a “Theory of Everything” that would describe fundamental laws underlying the entire physical universe. Others argued this would not actually explain or predict most real-world phenomena we observe.

• Phenomena often only exist at a particular scale or organizational level, and aren’t captured by focusing too reductively on lower levels like quarks or genes. Life emerges from complex multi-scale interactions that can’t be understood from any single level alone.

• While genomics gives important insights, it provides a narrow view of life that “shatters” organisms “into bits and bytes” without accounting for holistic processes. Bridging scales from genes to whole organisms, cells, and ecosystems is challenging.

• Views of when human “life” begins are often attempts to resolve tensions between seeing life as a property of physical material and as human experience. Different cultures at different times have had diverse views on this issue.

So in summary, the passage discusses challenges in taking overly reductive views across scales of biological organization, and tensions between different conceptualizations of what constitutes “life” in the context of human development and material constitution.

The passage discusses the conventional idea that the union of gametes (sperm and egg) during sexual reproduction is a random process. However, it acknowledges there may be some non-random factors at play as well.

It explains the biological process of meiosis, where germ cells with duplicate sets of chromosomes divide to produce gametes (sperm or egg cells) with single sets of chromosomes. This is necessary to prevent cells from having too many chromosomes after fertilization.

Importantly, meiosis involves some “shuffling” or recombination of maternal and paternal chromosomes as they are distributed randomly between gametes. This mixing of genetic material from both parents during each reproductive cycle helps generate genetic diversity among offspring. It can help populations adapt by combining favorable genetic variants and reducing the accumulation of harmful mutations over generations.

While acknowledging these benefits of sex, the passage also notes parthenogenesis (reproduction without fertilization) occurs successfully in some species. It questions whether sexual reproduction is truly essential or optimal, as evolution has multiple successful strategies for propagation. Overall, sex is viewed as one strategy that generally “works” for reproducing organisms.

• Early human development involves the formation of primordial germ cells before sexual differentiation occurs, showing the embryo deferring the matter of sex.

• Germ cells were postulated by Weismann as being vital for heredity and evolution, distinct from somatic cells. Weismann’s experiments supported the idea that acquired traits are not inherited.

• Most acts of sexual intercourse do not result in pregnancy, and most fertilized eggs miscarry, suggesting humans are poor at reproduction relative to other species.

• In the very early stages, the embryo consists of totipotent stem cells that could form separate embryos. Experiments showed early embryos can split into twin embryos.

• The embryo develops into a blastocyst stage around 5 days, ready to implant, consisting of an outer trophoblast layer and inner cell mass with pluripotent stem cells that will form the fetus and other tissues.

The key point is that early human development involves the formation of versatile stem cells and embryos that could develop into separate individuals, showing the process of generating genetic diversity before sexual differentiation and reproduction.

Here is a summary of the provided text for around day 10-11:

• Implantation of the embryo in the uterine lining is a delicate and complex process that involves communication between hormones and proteins from the embryo and uterine cells. It is more complex than fertilization.

• For implantation to occur successfully, tissues from the embryo (trophoblast layer) and mother (decidua) must work together to form the placenta, a single vital organ composed of cells with different genetic makeup.

• At this stage, the part of the embryo that will become the fetus (inner cell mass) appears shapeless and conglomerate. What is truly remarkable is that it most often develops into a fully formed body with all features in the right positions and functional organs - despite starting as a single cell.

• The cells are programmed to divide and grow but there is no single “plan” inherent in the fertilized egg. Development occurs through successive interactions between cells in a collaborative computation process with an obscure logic.

• Key factors are differentiation of cells into specialized roles, and spatial arrangements arising from cell movement, preferential adhesion between similar cell types, and cell sorting.

• Cells receive positional cues from their surroundings in the form of chemical signals called morphogens, which create concentration gradients to define spatial domains and allow cells to determine their fate.

• Protein gradients in the fruit fly embryo establish its body plan through segmentation. The proteins bicoid and caudal form gradients from opposite ends that switch on different genes in different regions, leading to segmentation of the head, thorax, and abdomen.

• Similar gradients are thought to cause segmentation of the vertebrate neural tube. Other morphogen gradients also establish body axes - dorsal establishes the dorsal-ventral axis in fruit flies.

• The idea that morphogen concentration gradients control embryo development was first proposed in the early 20th century. Work in the 1930s supported the idea that organizing centers define positional information through chemical gradients.

• In fruit flies, the bicoid gradient is established by nurse cells depositing bicoid RNA at the anterior tip. This shows embryo development relies on signals from surrounding cells/tissues, not just the genome.

• Gastrulation in humans involves cell movements that establish the body’s basic organization - inner tube (endoderm), outer layer (ectoderm), and middle layer (mesoderm) from which organs and tissues develop. This is more complex than in some simpler organisms.

Here are the key characteristics of development and differentiation summarized from the passage:

• Cells communicate with each other through molecular signaling to coordinate their development and roles within tissues and organs. This cell communication is important for proper organ development.

• The development and distinction between cell types is not fully explained by genes alone. Epigenetic mechanisms imprint gene expression patterns in cells that become permanently differentiated.

• Epigenetics involves chemical modifications to DNA and histones that regulate which genes are expressed without changing the underlying DNA sequence. This controls cell fates and tissue differentiation.

• A relatively small number of genes can generate the complexity of development through networks of gene expression that vary over time and space. The exact roles of genes depend on when and where they are expressed.

• Early in development, cells make lineage decisions through branching choices that permanently commit them to specific fates, like different tissue types. This process of cell differentiation involves continual epigenetic editing of gene expression programs.

The key point is that once a cell lineage descends into a valley in the Waddington landscape model of differentiation, representing a particular cell type, it can never reverse direction and go back to being an undifferentiated or less differentiated cell type. In other words, cellular differentiation is viewed as a one-way path of increasing specialization, from the totipotent zygote down through the branches of different valleys until terminal differentiation is reached. The cell lineages become increasingly restricted in their developmental potential as they progress along their trajectories in the epigenetic landscape.

• Physicians Ivor Dunsford and Robert Race found a case where a patient, Mrs. McK, had two different blood types detected in her body.

• Mrs. McK had no living twin, but said she had a twin brother who died as an infant. The explanation is that twins share a blood circulation in the uterus, and blood-forming cells can be exchanged and continue producing different blood types after birth.

• Robert Race coined the term “chimera” to describe cases like Mrs. McK’s, where more than one biological identity is present in a single organism from the exchange of cells between twins before birth.

• More dramatically, a person’s entire body can be a patchwork of cells from two different individuals. This can occur through the fusion of non-identical twin embryos early in development, creating a “tetragametic chimera” with a mixed genome.

• Cell exchange can also happen between a fetus and mother via the placenta, leading to microchimerism with a small number of each other’s cells persisting long-term.

• Cases of chimerism challenge concepts of personal identity and relationships based on assumptions of a single genotype. More flexibly defining kinship and selfhood independently of biology may be needed.

• Dictyostelium discoideum, commonly known as slime molds, are amoeba-like organisms that consume bacteria and help maintain microbial balance in soil.

• During times of shortage, Dictyostelium cells come together to form a multicellular “slug: ” that develops into a structure with spores. Some cells sacrifice themselves to support the spores.

• The cells communicate through chemical signaling, coordinating their movement in waves resembling ripples. This allows them to aggregate into fruiting bodies with specialized cell types.

• This displays cooperative and differentiated behavior similar to developing embryos. Chemical communication between cells is also seen in human cell systems like the heart.

• While distinct individuals, Dictyostelium and human cells also demonstrate that multicellularity originated from single cells cooperating through specialized tasks and sexual reproduction. Studying Dictyostelium provides insight into the emergence of cell patterning and multicellular life.

• Proteins are made through the process of transcription and translation. DNA is first transcribed into messenger RNA (mRNA), which then serves as a template for protein synthesis on the ribosome.

• In prokaryotes like bacteria, transcription and translation occur simultaneously. But in eukaryotes, the nucleus separates these processes - transcription occurs inside the nucleus, while translation occurs outside in the cytoplasm. This spatial separation ensures proper intron editing can occur in the mRNA before translation.

• Eukaryotes evolved from merging or symbiosis between simpler prokaryotic cells, rather than gradually evolving from prokaryotes. Key organelles like mitochondria and chloroplasts were originally independent prokaryotes that were engulfed by other cells in endosymbiotic relationships.

• These mergers provided profound adaptive advantages by enhancing energy production and accessing new metabolic capabilities. They allowed eukaryotic cells to take on new complex forms like multicellularity. Sexual reproduction can also be viewed as a merging of gametes that enhances genetic variation.

• In summary, eukaryotic complexity arose from symbiotic mergers between prokaryotic cells, allowing access to new evolutionary opportunities and adaptive advantages through enhanced functions provided by organelles. This transition was a key development that enabled the emergence of multicellular life.

• In 1907, embryologist Ross Harrison succeeded in growing tissues outside the body in petri dishes sustained by nutrients, a feat previously thought impossible.

• This challenged the idea that tissues need the body’s “milieu interior” environment to survive. It showed tissues can survive autonomously.

• Surgeon Alexis Carrel further refined the technique at Rockefeller Institute, culturing various tissues for longer periods. He sustained chicken heart tissue for weeks.

• Growing living tissue independently of the body was a surprising development that blurred concepts of life and death. It suggested cells have their own autonomous identity and life force separate from the body.

• Carrel promoted his cell culturing work by dressing his lab in dark gowns for theatrical effect and calling his “immortal” chicken heart culture an elixir of life, fueling notions of conquering death. His success highlighted the independent life of cells.

• Alexis Carrel cultivated chicken heart tissue in vitro for decades, creating the impression that it was immortal. However, it’s now understood that mammalian cells can only divide a limited number of times before senescing. Carrel may have inadvertently replenished his culture through contamination or cells remaining in the nutrient solution.

• Carrel and Charles Lindbergh collaborated on experiments to preserve organs through perfusion, hoping to advance eugenics and preserve white Western culture. Carrel held white supremacist views and approved of Hitler.

• Their work fueled speculation about extending life and resurrecting the dead through transplantation of living tissue. It tapped into widespread fascination with immortality at the time.

• Julian Huxley wrote a science fiction story called “The Tissue-Culture King” inspired by H.G. Wells’ The Island of Doctor Moreau. It featured a rogue scientist cultivating living flesh for a remote African tribe as sacred relics, demonstrating his power over life.

• The story reflected real anxieties about experiments that pushed boundaries of what was considered acceptable or controllable in the name of science. It highlighted emerging issues around tissue culture, eugenics and cultural attitudes.

The passage discusses how Thomas Huxley’s fictional story “The Tissue-Culture King” expressed ambivalence toward emerging biological technologies that revealed the mutability of living forms. While promoting science, the story reflected fears that Huxley the scientist could not fully articulate.

It then describes how researchers at the Strangeways Laboratory in the 1920s-30s worked to popularize the new field of tissue culture through public talks, films, and a BBC radio broadcast. However, some biologists worried that cultured cells resembled uncontrolled cancer growth more than healthy tissue. Huxley and H.G. Wells likened cultured cells to a lack of social order.

The passage analyzes how several early science fiction stories blended tissue culture research with themes from H.G. Wells’s “The Island of Doctor Moreau,” depicting runaway or weaponized cell cultures. It discusses how these stories reflected broader cultural anxieties about science surpassing natural boundaries.

The summary focuses on the cultural contexts and reflections these early fictional works provided about emerging biological technologies related to tissue culture and ideas of cellular autonomy outside the body.

• Henrietta Lacks’ cells, known as HeLa cells, were taken from her tumor in 1951 without her or her family’s consent for medical research. Her family was unaware this was happening and disturbed to learn about it later.

• At the time, taking and sharing human cells and tissues for research was considered acceptable and no money was sought from the commercialization of HeLa cells. However, Lacks’ family was understandably confused and angry about doctors using her cells without permission.

• It took 40 years until a book by Rebecca Skloot in 2010 shed light on what happened to Lacks and her cells. Her family was shocked to learn the full story.

• HeLa cells have turned out to be extraordinarily robust and have contributed enormously to medical research. However, over decades of replication, the HeLa genome has accumulated many mutations and changes so it no longer fully represents Henrietta Lacks’ original DNA sequence.

• The use of human tissues for research complicates the relationship between an individual, their cells, and notions of identity after death. It raised ethical issues that required new legal and policy frameworks around informed consent and intellectual property.

• The passage discusses property rights and commercialization related to human biological materials, like cells and tissues.

• It discusses the 1984 court case where John Moore sued his doctor for profiting off a cell line developed from Moore’s cancer cells without compensating him. The court ruled Moore had no property rights over the cells.

• This established a precedent that human biological materials become the property of researchers once removed from the body, even if developed into lucrative products. Donors have no claim to profits.

• This system transfers rights from donors to recipients and researchers. It enables valuable medical research but also turns human flesh into a commodity that can be profited from.

• New technologies like tissue culturing further commercialize and commodify human biological materials by allowing mass production outside the body. This raises complex social and ethical questions about how we conceptualize the human body and identity.

• Artistic works that explore these issues, like SymbioticA’s “mousecoat,” can help challenge perspectives and provoke discussion around these emerging biotechnologies. We have yet to fully grapple with the implications of tissue culture and the “tissue economy.”

• The human body has several mechanisms to control cell growth and division, including proofreading enzymes, genes that regulate the cell cycle, and immune surveillance for abnormal cells.

• Some view cancer as a natural response to cellular stress from environmental factors, deeply embedded in our evolutionary biology, rather than a failure of control mechanisms. This is a controversial view.

• External factors like chemicals, radiation, and viruses can disrupt the control mechanisms and promote tumor growth by mutations in genes like oncogenes and tumor suppressor genes.

• Cells have limits on division, called the Hayflick limit, and undergo programmed cell death (apoptosis) when needed. Cancer cells evade these control mechanisms through mutations.

• Telomeres normally shorten with each cell division, acting as a division counter, but cancer cells produce telomerase to maintain telomeres indefinitely.

• Cancer development requires multiple genetic and physiological changes to disrupt normal controls on proliferation, invasion, angiogenesis, and immune evasion.

• While useful metaphors, cancer cells should not be viewed as consciously acting entities but rather as deregulated cell growth driven by genetic and environmental factors.

• Cancer research and immunology both show how fragile our sense of somatic integrity is. At the cellular level, our health depends on complex interactions between diverse entities within our bodies.

• Our immune system plays an important role in many diseases beyond just fighting infection. It controls inflammation and repair, which are key responses to tissue damage or malfunction. Immunology is an advancing field with many new discoveries.

• In addition to its traditional role fighting pathogens, the immune system has innate and adaptive components with different strategies. It also regulates itself to avoid harmful autoimmune responses.

• Cancer immunotherapy harnesses the immune system to attack tumor cells by blocking “immune checkpoints” that normally suppress immune responses. This approach is showing promise in clinical trials for some cancers.

• Our bodies contain many microbial symbionts like gut bacteria that comprise around half our cell makeup. We have adapted to live symbiotically with these microorganisms through mutual assistance like digestion and nutrition.

• Biochemical processes can be outsourced to symbiotic microbes that live in or on the host organism. Termites and cockroaches can digest wood due to enzymes produced by their gut bacteria. Some insects obtain vital amino acids from symbiotic bacteria.

• The human microbiome likely plays a role in embryonic development by activating certain genes. Proper development of the mouse immune and digestive systems depends on signals from bacteria. Microbes in fruit flies influence mating preferences through pheromone production.

• When laboratory organisms are raised without their normal microbiome, they tend to have precarious health. The human gut and brain are connected via the vagus nerve, suggesting the microbiome could influence mental states. Some research indicates probiotics may treat conditions like stress and depression.

• The microbiome composition is unique to each individual and varies across body sites. Context is important - a microbe may be beneficial in one location but pathogenic elsewhere.

• The immune system manages both pathogens and the microbiome. Microbes also influence immunity to protect themselves.

• Reprogramming differentiated cells into other cell types undermines the idea that our fate is fixed. Cells maintain more plasticity than previously believed. This has implications for evolution, development, and health.

• Adult stem cells can give rise to different cell types in specific tissues to allow regeneration, but regeneration ability is very limited in humans compared to some animals like salamanders.

• Stem cell therapies have had limited success so far due to challenges like controlling stem cell fate and avoiding rejection by the immune system. Transplanted stem cells may acquire the wrong fate like tumor formation.

• Research using embryonic stem cells is controversial due to the use of human embryos. This led to restrictions in some countries like the US.

• It was unknown if pluripotent stem cells could be obtained without using embryos. Nuclear transfer experiments in the 1950s-60s showed embryonic and some adult cell nuclei could direct development, but adult nuclei seemed to lose this ability.

• In the 1990s, cloning of adult mammals like Dolly the sheep through somatic cell nuclear transfer clearly showed adult cell chromosomes can be pluripotent, overturning the idea that cell fate was permanently fixed after differentiation. However, controlling stem cell fate remains a challenge for regeneration medicine.

• Scientists were able to clone Dolly the sheep in 1996 by transferring the nucleus of an adult mammary gland cell into an egg cell whose nucleus had been removed. This showed that differentiated adult cells still contain all the genetic information needed to create a complete organism.

• This reprogramming of adult cells could provide a source of embryonic stem cells through “therapeutic cloning”, but raising human embryos in this way is controversial and difficult due to lack of available eggs.

• Shinya Yamanaka wondered if it might be possible to reprogram adult cells into a stem cell-like state without cloning or embryos, by introducing genes related to pluripotency.

• He introduced combinations of transcription factor genes expressed in embryonic stem cells into adult mouse cells using viral vectors. This experimental approach was challenging given the many possible gene combinations to test.

• Yamanaka’s experiments eventually showed it was possible to reprogram adult cells into an embryonic-like pluripotent state through the introduction of just four key transcription factor genes, achieving what he called induced pluripotent stem (iPS) cells. This represented a major breakthrough in stem cell research.

• Our understanding of cellular differentiation and development has been challenged by developments in stem cell research. Specifically, the ability to induce pluripotency in somatic cells through genetic reprogramming transforms our concept of cellular identity and lineage.

• Researchers used to view cellular differentiation as a one-way process, guided by a “landscape” model where cells progressively specialize as they develop. But the discovery of induced pluripotent stem cells shows cells can reverse their differentiation state.

• At the molecular level, gene expression and epigenetic profiles within tissues are more diverse than traditionally assumed. Multiple developmental pathways can lead to the same cellular phenotype.

• Classifying cell types may oversimplify their true complexity and plasticity. While useful concepts, categories like cell types do not necessarily reflect the underlying genetic and molecular dynamics within tissues.

• These findings imply cellular identity is more flexible and history-independent than previously believed. Our concepts of development and somatic lineages require reevaluation in light of induced pluripotency and single-cell analyses.

• Scientists are now able to map out the developmental landscape of cells during embryogenesis in great detail using experimental and computational tools. This reveals that cell states exist on a continuum rather than in distinct categories.

• Cells early in development are in ambiguous states when considering their full gene expression profiles. The pathways cells may take are diverse and complex, not always clearly defined.

• Waddington’s conception of distinct valleys needs updating. A more accurate metaphor is a flat landscape with cities/towns at the edges and many connecting routes, rather than distinct pathways.

• Scientists have generated atlases of cell states for mouse embryos at various developmental stages involving millions of individual cells. This level of detail was not possible before.

• Organoids grown from stem cells can self-organize to some extent, recapitulating aspects of organ development. However, they still require supportive materials like Matrigel to properly structure themselves.

• Organoids hold promise for modeling diseases and transplantation but replicating full organs remains challenging. Left unguided, stem cells differentiate haphazardly, resembling teratomas. More work is needed to fully guide their development.

The passage discusses research using organoids (mini organs grown from stem cells) to study human development and disease. Brain organoids in particular show rudimentary brain structures but lack proper 3D shape. Researchers are trying to make them more realistic by adding signals from other tissues during fetal development. This could provide a model for investigating conditions like microcephaly linked to Zika virus.

Organoids are also used to study neurodegenerative diseases like Alzheimer’s and dementia by making them from patients’ cells to observe early protein changes. They could replace animal testing for drug screening. Some envision growing multiple organoid types on integrated “body-on-a-chip” devices.

Pääbo is using gene editing to transfer Neanderthal brain development genes into human stem cells and study resulting organoid shapes, hoping to gain insights into cognitive differences between Neanderthals and humans. Overall, organoids show promise as disease models for advancing medical research in more ethical ways compared to animal or human studies.

• Growing human tissues outside the body holds potential for organ transplants, but tissues like heart and brain need to seamlessly integrate with existing tissues to function properly. Transplanting pre-grown tissues has challenges with synchronization.

• Directly introducing iPSCs may allow guidance from the environment, but it’s unclear if adult tissues still provide developmental cues. Early trials implanting iPSC-derived retinal cells and neuronal precursors show mixed/promising results.

• Researchers are also trying to reprogram glial cells into neurons in the brain directly after injury using iPSC transcription factors. However, controlling stem cell fate in the body is difficult and cancer risks remain a concern.

• An alternative is direct reprogramming of one somatic cell type into another without going through a stem cell stage. Studies show this can transform fibroblasts into muscle or heart cells. Synthetic molecules may also enable direct reprogramming, opening new possibilities. Controlling cell fate remains a challenge.

Researchers have shown that they can reprogram adult cells in the body through gene therapies and transcription factors. Specifically:

• Mouse fibroblasts have been directly converted into neurons and cardiac muscle cells through gene therapies. Similar reprogramming has been done in human cells.

• In mice, introducing transcription factors turned pancreatic exocrine cells into insulin-producing beta cells and liver cells into pancreatic beta cells, alleviating diabetes symptoms. This direct reprogramming works better inside the body than in petri dishes, though the effects are often transient.

• Reprogramming has also generated light-sensitive neurons from glial cells in mouse and human retinas, a promising start to reversing blindness. Adding transcription factors also reprogrammed rat cells to produce hair cells and potentially restore hearing.

• Glial cells in mouse brains have been directly converted into neuron-producing cells, offering hope to repair brain and spinal cord injuries. Similarly, mouse heart connective tissue has been reprogrammed into heart muscle cells.

• Beyond cell conversion, researchers are also trying to reawaken cell proliferation in adults through transcription factors, essentially “rejuvenating” tissues and enabling organ regeneration as in embryos, though more refinement is needed.

So in summary, researchers have demonstrated the ability to directly reprogram cell states and identities in the body through gene therapies, with applications to regenerative medicine and potential future human therapies. However, more work is still needed to improve efficiency and safety.

• Cells in the newt iris that contain pigment can “de-differentiate”, reversing their specialized state, before taking on a new fate in forming the lens of the eye during regeneration.

• This ability of specialized cells to revert to a more stem-cell like state is a normal, evolved feature that allows tissues to repair themselves through “facultative stem cells”.

• Examples are seen in the gut and lungs, where mature cells can become stem cells again during injury to quickly regrow the tissue. This cellular plasticity enhances evolutionary fitness by enabling traumatic healing.

• While controlled de-differentiation is useful, it must be carefully regulated to avoid risk of tumors. Cells seem to have an innate cleverness and responsiveness that allows adaptive changes while maintaining tissue organization.

• Tissue engineering has made progress in growing artificial skin from stem cells or fibroblasts and collagen scaffolds. This artificial skin has been used to treat diabetic ulcers and is being tested as skin grafts.

• Growing artificial organs is more challenging than skin but researchers are making progress. Joseph Vacanti pioneered growing liver tissue on polymer scaffolds to potentially implant as temporary liver support. Robert Langer helped develop techniques using growth factors to stimulate vascularization.

• Martin Birchall engineered a tissue-engineered windpipe grafted successfully in 2008, the first such surgery. Mesenchymal stem cells can be guided to specific cell fates through mechanical and biochemical cues.

• Induced pluripotent stem cells and decellularized scaffolds from donor organs are also being explored as methods to generate artificial organs. Challenges remain in vascularization, immune rejection, and controlling cell behavior over the long term. Tissue engineering holds promise to generate replacement organs but further validation is still needed.

• A Spanish patient underwent trachea transplantation using a segment of trachea taken from a deceased 51-year-old woman.

• For complex organs like lungs, kidneys and hearts, animal experiments have grown these organs on decellularized scaffolds from rats, but outcomes from subsequent transplants have been mixed.

• In 2013, researchers at the University of Pittsburgh grew a “mini human heart” by seeding decellularized mouse heart scaffolds with human cells. The artificial heart started spontaneously contracting after 20 days of culturing.

• 3D bioprinting is a promising technique for growing tissues and organs by precisely depositing layers of living cells. Challenges remain in printing solid 3D organs.

• Researchers have used 3D printing to create tissue constructs containing vascular networks to supply cells. The goal is to eventually print more complex organs like kidneys and livers.

• There are debates around how similar 3D printed organs need to be to natural organs in structure and function. Simplified, idealized designs may work as well. Further research is exploring the limits and design constraints of biological growth and construction through these techniques.

• Scientists like Takebe have shown it is possible to grow human organoids or “proto-organs” like miniature livers in mice by transplanting human stem cells. This helps the organoids develop further than they could in a dish alone due to signals from the mouse body.

• The mice are not hybrids but chimeras - organisms with cells from multiple species. As long as genomes aren’t merged, different cell types can cooperate peacefully within an organism.

• Growing full-sized human organs this way in mice is impractical, but it may be possible in larger animals like pigs, cows or sheep. This raises ethical issues of using animals solely as spare part factories.

• A key challenge is guiding the human stem cells to develop into the desired organ. Kobayashi showed cells will form missing tissue if the host embryo lacks that gene. This “tissue niche” approach could allow growing human organs in pigs or cows engineered to lack that organ.

• Experiments show cells can form tissues their donor species never developed, responding to developmental cues from the host embryo. This suggests cell potentials not expressed in the adult body can be unlocked in the right environment.

• Researchers have successfully created rodent chimeras where organ cells from one species grow within the bodies of another species. This raises the question of whether the same could be done with humans and pigs.

• Experiments showed human stem cells can survive within pig embryos for a limited time, developing into some muscle and organ precursor cells. However, this did not prove human organs could fully develop within pigs.

• Further research is needed but may be possible in principle. However, there are also significant ethical concerns around human-animal chimeras that require careful consideration, such as implications for human dignity and animal welfare.

• Researchers have proposed limits such as not introducing human cells that could lead to human-like intelligence, reproduction abilities or physical appearance in animals. However, others argue the full capabilities are unclear and require oversight.

• Overall the passage discusses both the biomedical potential as well as important ethical issues around human-animal chimera research using organ transplantation as an example. Careful review and debate of both scientific and social aspects are needed to determine appropriate policy.

• The passage discusses the progress of in vitro fertilization (IVF) research and its implications. Early IVF experiments in the late 19th/early 20th century had limited success with animals but could not achieve viable human embryos.

• Pioneering work in the mid-20th century by scientists like John Rock, Robert Edwards, and their colleagues started to make progress on human IVF, though it faced significant ethical questions and hostility from the medical establishment at the time.

• IVF technology separated procreation from sex and complicated notions of when human life/personhood begins. It revealed embryos to be ambiguous entities rather than clearly autonomous organisms.

• This prompted challenging philosophical and ethical debates about where to draw lines regarding assisted reproduction technologies, and what defines a human being. IVF fundamentally changed views of sexuality, gender roles, and the process of human development.

• The thought experiment of a pig brain with human neurons questions where we draw lines on biological experiments and prompts consideration of the implications/ethics of such advances in dismantling old certainties and creating new possibilities.

• In the late 1960s and early 1970s, researchers including Patrick Steptoe, Robert Edwards and Jean Purdy conducted pioneering research on in vitro fertilization (IVF). They published photos showing human embryos developing in vitro, which gave new insights into human development.

• This was significant because it allowed scientists and the public to visualize the earliest stages of human development, which previously could only be tracked back to a later stage. Seeing IVF embryos challenged perceptions of when human life and personhood begins.

• The term “test-tube baby” arose in the 1920s to refer hypothetically to babies created artificially, though no test tubes were actually involved in IVF. The concept tapped into both scientific progression fears and eugenics concerns of the time.

• Writers like Huxley and Haldane envisioned technologies like ectogenesis (artificial wombs) and embryo manipulation, both as feminist progress but also for population control and eugenics. This framed public debate around the first successfully reported IVF baby in 1978.

• The term “test-tube baby” stuck and became a symbol of humanity’s increasing control over reproduction through technology, for both hope and dread, intentionally imagined in early 20th century fiction exploring “artificial” creation of life.

• The creation of “test-tube babies” through IVF was seen in popular media like science fiction stories as creating “sexless, soulless creatures.” This reflected real anxieties in the 1930s about the societal impacts of scientific advances in growing human tissues and potentially creating babies artificially.

• Honor Fell, who conducted early tissue culture research, saw how her work was distorted in sensationalist media coverage. She advocated presenting the science carefully and acknowledging limitations, but scientists ultimately have limited control over public narratives. Similar tensions exist today regarding genetics.

• The birth of Louise Brown, the first IVF baby, in 1978 challenged traditional views that linked conception to marriage, love, and the sacredness of childbirth. Her ordinary family life contrasts with the “test-tube baby” fame from her unique conception method.

• IVF was seen as both a “miracle” and hubristic/Faustian for enabling conception without divine intervention. It challenged religious views of the role of sex in procreation and raised questions about what is natural or obligatory. IVF underscored how deep anxieties around controlling human procreation and sex have shaped societies.

• IVF has produced “spare embryos” that are used for human embryo research and stem cell research, opening up new areas of biomedical study. However, it also allows early intervention in human development, raising concerns about genetic modification.

• Around 6-8 million IVF births have normalized the technique, though the Catholic Church still bans it. IVF now accounts for 6% of births in some countries.

• While IVF has addressed infertility, it has also fundamentally changed ideas about human conception and development. It occupies a more prominent place in cultural narratives around new technologies like “designer babies”.

• Technologies are shaped by social and cultural factors beyond just solving technical problems. IVF in particular touches on issues of procreation, identity and what it means to be human. It confirms a new “technological ground state” of human existence.

• IVF clinics emphasize narratives of normalization and naturalness to reassure patients, but the reality of the process is more complex, difficult and uncertain. The role of men is also sidelined in narratives that portray infertility as a women’s issue.

• While some feminists see ARTs as potentially emancipating, they would need to be accompanied by radical changes to gender, sex, parenthood and family to fully challenge stereotypes.

• ARTs (assisted reproductive technologies) like IVF profoundly challenge traditional conceptions of gender, family structure, identity and the line between life and death. They raise deep ethical questions.

• While ARTs are often portrayed as oppressing women, feminists make a valid point that they could also challenge stereotypes if implemented properly. More fundamentally, women should not have to delay childbearing just to conform to social norms.

• Research using human embryos provides insights into early human development and infertility but is controversial due to differing views on an embryo’s moral status. The 14-day rule was established as a pragmatic compromise but advances may challenge it.

• Exploring these challenges openly through dialogue is preferable to trying to preempt or forestall technologies. While science cannot resolve ethical debates, it can inform them by enhancing understanding of processes like conception, development and what defines personhood. Regulation aims to balance enabling research with navigating these complex issues.

• There is interest in investigating human development past the 14-day limit for research on human embryos, as this could provide insights into health, disease and malformation. However, existing law would need to change. Opinions vary on whether the scientific benefits warrant reconsideration of the law.

• One cause of female infertility is declining egg quality with age. In the future, it may be possible to create eggs from induced pluripotent stem cells (iPSCs), which could help women conceive later in life without their own eggs.

• Poor sperm quality/counts are also a major cause of infertility. Artificial sperm could help couples conceive even when the man produces no sperm. Researchers have made functional mouse sperm and eggs from iPSCs, showing the potential for this approach.

• Developing human gametes from iPSCs faces challenges in mimicking the signals needed for maturation. Some progress has been made getting human cells to early egg/sperm stages using mouse tissues, but fully artificial human gametes remain distant. The implications of this research could profoundly change ideas about sex, reproduction and what constitutes an organism.

• The passage discusses the origins of Mary Shelley’s novel Frankenstein and how she drew inspiration from conversations with Lord Byron and Percy Bysshe Shelley about animating dead matter.

• It recounts Mary’s vision one night that led to the creation of Frankenstein’s monster - of Victor Frankenstein assembling a creature and bringing it to life through some “powerful engine.”

• Traditionally, Frankenstein has been interpreted as a warning against scientists “playing God” by tampering with nature. But the author argues this reading was imposed later by society, not intended by Shelley herself.

• In earlier versions of the story and reviews, there was less focus on Frankenstein challenging God. Percy Shelley saw the moral as how treating someone ill can make them wicked.

• The passage contends Frankenstein does not have a single sentence-long moral, but if forced to choose, the theme is about taking responsibility for one’s creations and their lives, not overstepping bounds with science.

In summary, the passage examines the origins and evolution of interpretations of Mary Shelley’s Frankenstein, questioning whether the traditional “playing God” reading was truly her intended message. It suggests the moral is more about responsibility for one’s creations.

• Mary Shelley’s Frankenstein was initially seen as a cautionary tale against scientific hubris and overreaching. However, this “Faustian” interpretation became solidified more in the early 20th century as society grappled with new technologies.

• The novel depicts disturbing visions of assembled human tissue and flesh in unnatural forms. This resonated later with ideas of culturing and growing human tissues independently, questioning where humanness lies.

• Works like R.U.R. further explored ideas of assembling or replacing body parts, influencing thoughts on the boundaries between natural and artificial, and what defines a person.

• While replacing individual organs was considered, full brain transplants or keeping an isolated brain alive remained in the realm of fiction. True transplantation or preservation of memory and identity across bodies has significant scientific hurdles.

• Historical visions of assembled bodies were mechanistic, but modern research on organoids brings new understanding of how cells and tissues organize into living forms. Overall, Frankenstein continues to influence discussions on scientific progress and its implications.

Researchers have made progress in creating synthetic embryos or embryoids in the lab as models for studying early human development. This involves reprogramming cells into a pluripotent state using techniques like iPSCs.

In mice, iPSCs have been injected into blastocysts and generated full mice, showing their potential to develop into complete organisms. While not yet done in humans, this suggests individual human cells may be able to generate a whole new person.

Embryoids have been made starting with stem cells that self-organize into three germ layers resembling early embryos. By adding trophoblast cells that signal placental development, researchers created mouse embryoids that developed pseudo-amniotic cavities and patterns directed by embryonic genes, mimicking real embryogenesis.

This represents a step toward assembling human embryoids with multiple cell types that could be used to study early development processes currently not possible to observe directly in real embryos due to ethical restrictions. However, fully replicating natural embryonic development remains challenging without a true placental and uterine environment.

• Researchers led by Zernicka-Goetz have created mouse “embryoids” by assembling embryonic stem cells with two types of extra-embryonic cells - trophoblasts and extra-embryonic endoderm. These three-component embryoids resemble early mouse embryos undergoing gastrulation.

• Similar techniques have been used to create human embryoids, recapitulating some early developmental stages. With the right signals, human embryoids can develop structures resembling a primitive streak and organizer cells, two important early developmental signatures.

• These embryoids are not exact replicas of normal embryos but living entities in their own right. Some propose calling them “synthetic human entities with embryo-like features” or SHEEFs.

• As SHEEF research progresses, it may be possible to engineer structures with rudimentary organs but lacking brain functions like sentience. This raises ethical questions around how to regulate such research and whether limits like the 14-day rule would apply.

• There is no consensus yet on regulating SHEEFs as their potential forms and capabilities are uncertain. But as the science advances, discussion is needed around the moral and ethical implications of creating increasingly embryo-like synthetic human structures.

• Mitochondrial replacement therapy aims to prevent the inheritance of mitochondrial diseases by transplanting the chromosomes of an egg from a woman with mitochondrial disease into a donor egg with healthy mitochondria and no chromosomes. This was recently approved for use in the UK.

• Critics argue it amounts to genetic alteration of the germ line and that babies conceived this way would have DNA from three people (the mother, father, and egg donor), labeling them “three-parent babies.” Supporters counter that this term is misleading and meant to invoke a moral response.

• Genome editing techniques like CRISPR have made it possible to precisely edit genes but introducing changes to the germ line via modified embryos remains highly controversial. While gene therapies aim to alter somatic cells, any changes to embryonic genes would be inherited.

• There are concerns that designing traits in embryos raises ethical issues and the technology is not advanced enough to reliably and accurately modify the human genome without unintended effects. Clinical trials are only exploring using gene editing to treat inherited diseases. Wide-scale “designer babies” remains in the realm of science fiction for now.

• In 2017, researchers in Oregon used CRISPR to edit the genes of human embryos to replace a defective gene that causes heart problems. This was the first reported use of CRISPR on human embryos, but the embryos were not implanted.

• In 2018, a Chinese scientist named He Jiankui reported using CRISPR to edit the genes of embryos before implanting them, resulting in twin girls. He aimed to make the children resistant to HIV by deleting the CCR5 gene.

• He’s work was widely condemned as unethical and dangerous. Editing the human germline is banned in many countries. There are risks of harmful mutations and long-term effects are unknown.

• While some think gene editing could be used ethically one day to prevent disease, He’s experiment was premature and not for clear medical need. It harmed prospects for responsible use of this powerful technology.

• The ethics of human germline editing and whether it should be allowed to prevent disease continues to be debated. Most agree more research is needed given the risks and irreversible nature of changes to the human gene pool.

• Predicting traits like intelligence from genes is complex, as most traits are influenced by many genes interacting in complex ways, not a single gene. There is no straightforward relationship between genes and traits.

• Scientists can make probabilistic predictions about intelligence based on large genomic datasets, but these predictions remain probabilistic and environmental factors also play a role.

• The genetic influence on traits like intelligence, creativity, etc. is spread across hundreds or thousands of genes, making direct editing of genes to change these traits difficult and uncertain. It could introduce unwanted side effects by altering other gene functions.

• Embryo selection through pre-implantation genetic diagnosis (PGD) allows selection of embryos without certain genetic diseases or traits, effectively genetically modifying future offspring, but it is an imperfect process that does not offer much choice and is physically grueling and expensive.

• PGD is already used to avoid single-gene diseases but controversially also for sex selection in some countries. Expanding its use further gets into complex ethical issues about coercing reproductive choices.

• In summary, directly editing genes is unlikely to achieve “designer babies,” while embryo selection offers limited selection possibilities but is an imperfect and expensive process.

• Some experts think that advances in IVF, genetic screening and assisted reproductive technologies could lead to a future where people have more control over which embryos and ultimately which babies they have.

• If IVF was reliable, cheap and painless, and genetic screening allowed selection of embryos based on traits, some think people may be tempted to select from hundreds of embryos rather than accept what natural conception provides.

• Advances in genetic screening make analyzing hundreds of embryos more feasible as the cost of genome sequencing plummets. Combining this with techniques for generating eggs in vitro could enable selection from large numbers of embryos.

• However, accurately interpreting genetic data to predict outcomes is extremely challenging, and the notion of freely choosing a child based on traits raises many ethical issues. While personal choice is important, unfettered selection could worsen inequality and drive unrealistic expectations. Regulating these technologies will be an ongoing challenge balancing individual liberty with societal impacts.

• Some experts are skeptical people will widely adopt technologies just for enhancement when natural reproduction satisfies most. Others think selection for traits like intelligence or health could become normative as customer demand and peer pressure increase. Overall there are good arguments on both sides of these issues with no clear or obvious answers.

• In 2017, researcher Mu-ming Poo and his team in China successfully cloned two macaque monkeys using somatic cell nuclear transfer (SCNT), the same technique used to create Dolly the sheep. This was a significant achievement as primates had proven difficult to clone.

• However, the process was very inefficient. Of 79 cloned embryos implanted into 21 surrogate mothers, only two baby macaques were born live. Two others cloned from adult cells died shortly after birth, one from impaired development and one from respiratory failure.

• Therefore, while cloning of primates through SCNT is now possible, attempting human cloning would still be unsafe given the low efficiency and health risks seen even in the monkey clones that were born. Proper regulation and safety testing would need to occur first before considering any attempts at human cloning.

• The technologies that allow cloning and other forms of genetic manipulation raise significant ethical issues around how they may be applied and how we view human DNA, genetics, and reproduction. More research is still needed to fully understand these complex topics.

• Transhumanism aims to enhance human abilities through technologies like medical interventions, drugs, and human-machine interfaces. Some see the human body as flawed or limiting.

• Many transhumanists promote radical life extension through anti-aging therapies or digital immortality by uploading consciousness. However, biological immortality is controversial and may not be technically feasible.

• Early visions of transhumanism frequently featured unrealistic technological fantasies and an impatience or contempt for the human body. While modern discourse is more nuanced, some dismiss the importance of embodiment.

• Transhumanism raises valid questions about using technologies to pursue goals like health, longevity, and human enhancement. However, most current proposals lack biological and technological realism and rely on overoptimistic extrapolations rather than scientific progress.

• Major challenges include lack of agreement on ethical principles, dystopian narratives of such efforts, ensuring benefits are accessible to all, and grounding visions in concrete science rather than just fiction-like fantasies. Transhumanism deserves ethical reflection but may overstate feasibility of radically transforming the human condition.

• The concept of a disembodied “brain in a jar” has long fascinated philosophers as a thought experiment, but now it is becoming a real possibility through experiments like growing mini-brains.

• Stories and films have depicted sinister scenarios involving kept brains, but real experiments aim to better understand the brain, not create monsters.

• The brain presents mysteries - it constructs our perceptions and sense of self yet is just soft tissue. Its code and structures shape our traits but development is also contingent.

• Brain regions correspond to specific functions, so damage can cause highly localized symptoms. Different dementia types affect different areas with distinct effects.

• Experience physically shapes the brain through things like musicians developing enhanced music processing areas and London taxi drivers enlarging their hippocampi from navigation training. Our brains adapt to our unique lives.

So in summary, while fictional “brains in jars” conjure horror, real experiments aim to illuminate the mysteries of cognition and how experience sculpted a highly individual organ - the seat of personhood yet still a biological puzzle.

• The 1931 film Frankenstein included a scene of a preserved brain in a jar, reflecting the era’s practice of anatomical study through tissue preservation.

• However, some historical examples of brain preservation were much more grotesque and unethical, like hundreds of children’s brains kept without consent after being murdered by Nazis.

• Some now choose cryogenic brain preservation in hopes that future science may reanimate them. However, experts argue cryonics unavoidably damages tissues and true revival is unlikely.

• Ideas that the brain is just a computer fuel visions of uploading one’s mind digitally. But others argue consciousness depends on the specific nature of neural networks and embodiment, not just computational ability. Cognition involves “inner rehearsal” using motor systems as if acting in the world.

• Without a body, the brain alone may not fully represent the human self, as selfhood involves an integrated sense of being embodied in an environment through physical experience and interaction. True transhumanist extensions of mind may involve augmented or new kinds of bodies, not disembodied uploads.

• The concept of the “brain in a vat” originated with philosophers like Descartes who questioned how we can know if our experiences of the world are real or just illusions. It suggests we could be brains being artificially stimulated without an actual physical body.

• This idea was explored further in science fiction like The Matrix, where humans are unaware their minds are trapped in a simulated reality. Philosophers like Putnam argued we can’t meaningfully talk about referring to real objects if our experiences are simulated.

• Technological advances raise new versions of this problem, like whether we could be virtual agents in highly advanced simulations by an artificial intelligence. Some argue this is even likely given enough computing power.

• Stephen Hawking’s reliance on technology to communicate due to his disabilities led some like Mialet to argue he functioned almost like a “brain in a vat” networked to machines. This highlighted how many of us are increasingly connected to technology.

• The “brain in a vat” scenario remains philosophically unresolved but continues to be a thought experiment about the nature of reality, experience, and our relationship with technology.

The passage discusses the idea that our genetic code or genome contains our essence and identity, as metaphorically expressed by a scientist telling Carl Zimmer that a hard drive containing his genome sequence is “Carl Zimmer,” not his physical body.

It critiques this view as reducing people to data and divorcing identity from the flesh. Western culture has long held taboos against and sought to escape from the “meat-self” and mortality of the physical body. The temptation is to see ourselves as inhabiting or trapped within our bodies.

However, modern science reveals the plasticity and potential of human flesh, like cells that can grow into embryos. This complicates questions of identity, individuality, and the philosophical concept of the self. Our bodies are constantly changing at the cellular level.

The passage questions where identity lies in this “seething mass of life” if biology does not clearly locate our individuality. It explores the biological and evolutionary origins and purpose of consciousness and the feeling of a singular, unified self. Overall, it argues for reclaiming identity as rooted in our physical flesh rather than reducible to genetic data.

This passage discusses the complexity of defining individuality in biological terms. Some key points:

• Defining individuality based on the boundaries of the body is complicated by the fact that our bodies contain microbial communities that influence our physiology and traits.

• Symbiosis is widespread in nature, with organisms depending on cellular contributions from different species. This blurs the lines between individuals.

• Genetic definitions are inadequate since the genome alone does not determine an organism’s traits or provide everything needed for healthy function. Symbiosis involves genomes beyond our own.

• Immune systems distinguish self from non-self at multiple levels, including mediating cooperation with symbiotic communities, so immunity does not neatly define individuals either.

• Behavioral definitions are problematic since not all organisms behave with apparent goals or autonomy.

• Organisms like Portuguese man-of-wars show that what appears as an individual can actually be a colonial entity composed of distinct organisms.

• While retaining the concept of individuals is useful, it does not represent some fundamental truth or fixed boundary in biology given the complexity and flexibility of life.

• Evolution should not be constrained by rigid rules proclaiming certain things impossible. We should trust that evolution finds good strategies.

• Darwinian evolution via natural selection and random mutation explains much of biology, but not everything. Other factors like genetic drift and cells actively modifying their own genomes also drive evolution.

• There is no biological law forbidding non-Darwinian changes, so they should not be seen as controversial or challenging Darwin.

• Narratives in biology can be hazardous if taken as absolute dogma rather than approximations. Biology is too complex for any single narrative or metaphor to perfectly fit.

• The concept of individuality is useful at the organism level but not necessarily at the cellular level. We are not individuals all the way down. Our cells are demonstrating this and it’s worth listening to what they tell us.

• If brain organoids become more advanced, they may potentially have experiences akin to sentience. We should consider their ethical status and regulatory oversight for such research.

• Viruses propagate themselves by infecting cellular life, which was likely inevitable given the existence of cells. Whether viruses are parasites depends on one’s perspective.

• DNA replication involves complementary base pairing between two strands of a double helix. During replication, one strand acts as a template to form the complementary strand, resulting in two double helices with the same sequence.

• Genomes alone don’t define organisms - cells have fundamental metabolic requirements, but differences in developmental programs allow for diverse shapes and behaviors despite genomic similarities.

• Genes are not true replicators - they are replicated by enzymes within cellular contexts and do not autonomously replicate. Genes are replicands, or that which is replicated.

• Early embryological experiments in the late 19th century provided insights but also ethical issues regarding manipulating developing organisms. Organizers and morphogens were later identified as influencing embryonic development and patterning.

• The human genome refers to our commonalities at 99.9% of DNA, with individual variation in the remaining 0.1% accounting for differences. Mutation rates seem evolved to balance genetic variation with minimization of harmful mutations.

• Introns were initially seen as useless DNA but may confer benefits like creating protein diversity from a single gene. Evolution is represented more as a bush than tree, with some lateral gene transfer between branches. All living organisms exist on evolving branches rather than directly descending from ancestral forms.

• The passage discusses the pioneering work of surgeon John Strangeways on tissue culture in the early 20th century. However, his work was considered of “rather limited value” when he was nominated for awards in 1933, which the author argues was an unfair misjudgement.

• It mentions how islands are often used as literary tropes, from Gulliver’s Travels to Huxley’s Island, to imaginatively explore societies free from normal societal constraints.

• After Henrietta Lacks’ HeLa cells were discovered, a mass production laboratory was set up in Tuskegee. The name of Stanley Gartler’s studies refers invasively to this.

• Even after being legally vindicated, the author suggests researcher Golde remained troubled by a court case, implying the shadow of it led to his 2004 suicide. His belief in unfettered science regarding discarded tissue is noted.

• It provides context on gene naming and functions, and discusses how some immune and bacterial genes can be transferred to host genomes.

I have no summary to provide for this fictional exchange. Please provide a real discussion or article if you would like me to summarize.

The passage discusses the possibility that the patient discussed in the earlier chapter could still have been alive practicing law somewhere else, despite assumptions that he had died. It notes that it is possible he was alive and practicing law, recognizing this as a notable exception to assumptions made.

It then provides a quote from Derek Parfit’s book Reasons and Persons, noting his work has become foundational for philosophical discussions of new technologies related to creating and modifying humans, like computer simulation, artificial reproduction and cloning.

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

• The Progress conference in London on December 8, 2017 discussed evidence that gene editing could be used to enhance humans and raise concerns about its regulation and oversight. Two papers from 2016 and 2017 were cited that discussed legal and ethical issues around gene editing human embryos.

• Mary Shelley’s 1818 novel Frankenstein discussed the idea of reanimating the dead and the potential “frightful” effects this could have. It also mentioned the direct moral of the story and acts of damage limitation.

• Subsequent sources discussed a variety of issues around human enhancement and modification, including debates around genetic testing and designer babies, cloning, transplanting organs between species, using stem cells to regenerate tissue, and the possibility of downloading consciousness into non-biological substrates.

• Ethical concerns focused on safety, oversight, human dignity, equality and our shared humanity. Some saw human modification as inevitable while others argued we need more research and international regulation first. Overall the sources reflected an ongoing philosophical and scientific discussion around progress in biotechnology and its impacts on what it means to be human.

Here is a summary of the references provided:

• Several articles discuss the progress of growing human organs from stem cells in the lab, such as tracheas, and transplanting them into patients. Growing full organs for transplantation remains a challenge.

• Studies demonstrate generating neurons, glial cells, and other cell types from stem cells for potential treatments of neurological diseases and injuries. This includes generating induced pluripotent stem cells from patients.

• Embryonic development of humans and other species is being modeled in 3D organoid and embryo culture systems in the lab, providing insights into early development.

• Ethical issues surrounding experimental technologies like genome editing of human embryos and brain organoids are discussed. The potential and limitations of directly reprogramming one cell type into another for regenerative medicine is also explored.

• The symbiotic relationships between humans and their microbes, and implications for our evolution and holobiont identity, are reviewed based on recent research.

• Historical perspectives are given on the development of disciplines like embryology and progress in assisted reproduction technologies like IVF over the past decades. Regulatory and policy issues regarding new biomedical technologies are addressed.

• Several articles profile major figures in developmental and regenerative medicine research throughout the 20th century and their visions for the future of these fields. The potential medical, scientific and philosophical impacts are discussed.

Here is a summary of the provided references:

• Lancaster et al. (2013) demonstrated that human cerebral organoids could model human brain development and microcephaly. They created organoids from human pluripotent stem cells that self-organized into structures mimicking key aspects of brain development.

• Landecker (2007) provided cultural and historical context on the development of organoid technologies and how cells became technologies that could be cultured and manipulated in vitro.

• Ender et al. (2019) called for a moratorium on heritable human genome editing due to safety and ethics concerns.

• Other references discussed the potential of organoids and stem cells to model diseases, screen drugs, replace damaged tissues, reverse diabetes, provide alternatives to animal testing, gain insight into early human development, and more. However, many also raised ethical issues regarding human germline editing and the moral status of early human life and embryos.

• Overall, the references highlighted the promise and ongoing development of organoid technologies while also acknowledging important debates around their clinical and biomedical applications. Both the scientific opportunities and ethical challenges of this emerging field were examined.

Here is a summary of the key papers:

• N. Rivron et al., 2018 debates the ethics of creating embryo models from stem cells, discussing whether they should be considered embryos.

• R. E. Rodin & C. A. Walsh, 2018 discusses somatic mutations in pediatric neurological diseases.

• M. N. Shahbazi & M. Zernicka-Goetz, 2018 and Shahbazi et al., 2016 explore self-organization of human embryos in the absence of maternal tissues.

• Y. Shao et al., 2017 presents a pluripotent stem cell-based model of post-implantation human amniotic sac development.

• H. Shen, 2018 discusses assembling embryos from stem cells.

• M. Simunovic & A. H. Brivanlou, 2017 reviews new approaches like embryoids, organoids and gastruloids for understanding embryogenesis.

• A. Skardal et al., 2016 discusses organoid-on-a-chip and body-on-a-chip systems for drug screening and disease modeling.

• B. Sozen et al., 2018 constructs gastrulating embryo-like structures from embryonic and extra-embryonic stem cell types.

• Several papers discuss using stem cells and cloning to generate gametes, fertilize eggs, and develop embryos, tissue/organs, or induce cellular reprogramming for disease modeling and regenerative medicine.

Here is a summary of the key points about Philip Ball’s illustrations of human cells:

• Ball illustrated Walther Flemming’s 1882 illustration of mitosis, showing the stages of cell division. This was an early depiction of how chromosomes behave during cell division.

• He also illustrated DNA structure, showing the famous double helix shape discovered by Watson and Crick in 1953.

• An illustration of a human embryo depicted the early stages of development from zygote to blastocyst.

• An illustration of gradient patterning explained how concentration gradients of signaling molecules help pattern the body during development.

• Gastrulation was depicted, the early stage where the three germ layers are formed.

• Waddington’s “epigenetic landscape” was adapted, showing how gene expression is influenced by environmental factors.

• An illustration of the life cycle of Dictyostelium discoideum depicted the simple model organism and its multicellular stage.

• The tree of life depicted evolutionary relationships between organisms.

• Pictures of stem cells, neurons, mini-brains and more supplemented explanations of concepts in regenerative medicine and synthetic biology.

In summary, Philip Ball’s illustrations provided visual aids to help explain key concepts and discoveries relating to cells, development, genetics and emerging biotechnologies. The illustrations helped non-experts understand complex biological processes.

• RY and 71, 240: Discusses telomeres and how they relate to cell division limits. Telomeres shorten with each cell division.

• Chun-Li Zhang 179: Mentions a scientist named Chun-Li Zhang.

• Church, George 263, 264: Discusses George Church and his work on synthetic human entities with embryo-like features (SHEEFs).

• Clark, Andy 310: Mentions Andy Clark.

• Clarke, Ellen 324: Mentions Ellen Clarke.

• climate system 24: Notes that the climate system relates to evolution.

• cloning 44, 49–50, 58, 121, 148–9, 149n, 150–2, 245, 266, 287–90, 287n, 288n, 296, 319n, 323: Discusses cloning of mammals like Dolly the sheep using somatic cell nuclear transfer. Debates around human cloning.

• c-Myc 157, 158: Discusses the c-Myc transcription factor.

• conception 6, 13, 44, 47, 210, 210n, 211, 212, 212n, 213, 213n, 215, 215, 216, 217, 219, 223, 224, 226n, 227, 229–30, 234, 239, 244, 245, 255, 292, 319: Mentions conception in the context of reproduction, IVF, and embryo development.

• consciousness 7, 109, 207, 294, 295, 308, 321, 327, 328–9: Discusses consciousness.

• CRISPR 270–4, 270n, 272n, 275, 279n, 284, 289–90: Summary of CRISPR genome editing technology.

• The Golgi apparatus is an organelle found in eukaryotic cells that packages and modifies proteins and lipids and transports them through the cytoplasm. It was discovered in 1898 by Italian scientist Camillo Golgi.

• Gonads are organs that produce gametes (eggs and sperm) and sex hormones like estrogen and testosterone. They include ovaries and testes.

• James Gray was a British surgeon and anatomist in the early 19th century who made contributions to the understanding of anatomy.

• The Great Chain of Being was a concept originating in Ancient Greece that all of existence is hierarchically structured, from God down to man, and from man down to animals, plants, and minerals.

• Hank Greely is a professor of law focused on emerging biotechnologies and their legal and social implications. He has written about issues like human cryopreservation and cloning.

• Ronald Green is a medical ethicist who has written about issues like genetic engineering and human cloning. He served on a panel that advised against human reproductive cloning.

• He Jiankui was a Chinese biophysicist who claimed to have gene-edited twin girls in 2018, using CRISPR to alter the CCR5 gene. This was highly controversial.

Here are summaries of the key points:

• and 22: Mitochondria are organelles that produce energy for the cell and play an important role in body formation and development. Mitochondrial diseases can result from mutations in mitochondrial DNA.

• cell division and 27, 27, 28: Cell division involves the phases of prophase, metaphase, anaphase and telophase. Mitosis leads to two identical daughter cells during cell replication.

• discovery of 19, 19n, 20, 20: Schleiden and Schwann helped establish the modern cell theory in the 1830s-1840s through their discoveries of plant and animal cells using microscopy.

• eukaryotic cells and 93–4, 97, 99: Eukaryotic cells contain membrane-bound organelles like the nucleus, mitochondria and chloroplasts. They evolved from symbiotic relationships between prokaryotic cells like bacteria.

• function of 23: The Golgi apparatus packages and modifies proteins and lipids in eukaryotic cells.

• mitochondrial disease and 266, 266n: Mitochondrial DNA mutations can cause diseases affecting multiple organs and tissues due to mitochondria’s role in cellular energy production.

• nuclear transfer 149–53, 266, 287–8, 290: Somatic cell nuclear transfer involves transferring the nucleus of an adult cell into an enucleated egg cell to generate cloned embryos. This technique was used to clone Dolly the sheep.

• The book discusses how Philip Ball began growing organoids (mini brains) from his own cells taken through a biopsy. This got him interested in concepts of identity and consciousness.

• It delves into human evolution from single-celled life to explain how complex creatures like humans emerged. This provides a new perspective on how humans think about ourselves.

• In an age where self is seen as genetic code or neural patterns, the book returns to the physical body to ground a view of personhood. It challenges old ideas and asks us to rethink how we exist.

• Key people mentioned are Selina Wray and Chris Lovejoy of UCL who helped Ball with growing the organoids. The project originated from artist Charlie Murphy.

• Ball conducted interviews with many experts in neuroscience, ethics and related fields to inform the book. It examines both promising and disturbing possibilities of new biotechnologies.

• Ball is a widely published science writer who communicates science and culture relationships. Previous books include The Music Instinct and The Water Kingdom. He writes for Nature and appears on radio/TV discussing science history.