1. What we mean by "immortality"

Lima-de-Faria opens not with biology but with a definition. The Encyclopaedia Britannica (Duignan, 2020) defines immortality as "the indefinite continuation of the mental, spiritual, or physical existence of individual human beings." He dissects this definition into four components and finds each of them problematic.

First, "indefinite continuation" rests on the concept of infinity, which entered Western thought through Babylonian astronomy and dominated physics and biology through the 1800s and early 1900s — the universe was assumed infinite, and the number of living organisms assumed enormous. Both assumptions have since narrowed. Second, "physical existence" is treated as a palpable event in individuals, but every phenomenon is dynamic, and this dynamism may be in tension with perpetuity. Third, the definition is restricted to human beings — a Victorian prejudice, in Lima-de-Faria's reading, that treats humans as a species apart with properties solely their own. Fourth, and most damaging, "continuation" is altered drastically by the physical transfer of genetic information from generation to generation. Immortality, in the genetic sense, "is more restricted than it could be imagined."

He closes the definitional section by noting that immortality, like infinity, is an abstraction of the mind — "like our demand for perfect dice and parallel lines." Yet it resurfaces in every era, because it remains a deep desire of the human mind. And, critically, immortality, consciousness, and death turn out to be interlocked: you cannot honestly discuss one without the other two.

2. Bacteria already refuse to accept death

The first surprise is where death refusal shows up: not in vertebrates, not even in eukaryotes, but in bacteria. When penicillin and other antibiotics arrived in the mid-twentieth century, the medical profession assumed bacterial infections would disappear. They did not. Antibiotic resistance became, and remains, one of the central preoccupations of clinical medicine.

The mechanism is genetic and well-characterised. In addition to its main chromosome, a bacterial cell produces R plasmids — small circular DNA segments that carry resistance genes. These plasmids transfer between bacteria by two routes: conjugation (direct DNA transfer between two cells in physical contact, often via a pilus) and transformation (the uptake of naked DNA from the environment). Once acquired, resistance genes are not easily lost and spread rapidly through the population. Multidrug resistance has now been documented in Escherichia coli, Salmonella enterica, Staphylococcus aureus, Mycobacterium tuberculosis, and many others (Dzidic et al., 2008).

Lima-de-Faria's framing is precise: bacteria do not passively accept chemical attack. They share genetic countermeasures across lineages, in effect running a distributed immune system that operates at the level of the population rather than the individual cell. This is death refusal at its most elementary — and, ironically, at its most effective.

For a complementary angle not developed in the original article but well-supported in the literature: Bacillus subtilis and related sporulators also escape death by forming endospores — desiccated, mineral-armoured capsules that can persist for what may be millions of years. Cortesão et al. (2019) showed B. subtilis spores surviving simulated Martian surface conditions. Bacteria thus carry at least two independent death-refusal programmes — horizontal gene transfer for chemical threats, and sporulation for physical ones.

3. Protozoa refuse to die by rewriting themselves

If bacteria refuse death collectively, protozoa — the simplest organisms with a nucleus — refuse it individually, by rewriting their own surface chemistry. Lima-de-Faria's chosen example is Trypanosoma brucei, the agent of African sleeping sickness. The parasite counters the chemicals used against it by editing the messenger RNAs produced from its mitochondrial genes, allowing it to change its protein coat rapidly. By continuously producing new surface proteins, it escapes immune recognition and avoids death (van der Ploeg, 1990).

This is a strikingly different strategy from bacterial plasmid exchange. The trypanosome does not borrow genes from neighbours; it re-edits the RNAs its own genome produces. The information for survival is already present; what changes is which version of that information gets expressed. The mechanism — RNA editing — will return later in the article as one of the central disruptors of immortality.

4. Invertebrates that turn into armoured spheres

Death refusal becomes anatomical in the invertebrates. Millipedes (Class Diplopoda) — more than 7,500 described species (Barnes, 1980) — carry calcium-hardened trunk segments and, when attacked by predators, roll the trunk into a sphere that protects both the vulnerable ventral surface and the head. The result is an animal that, in shape and approximate size, resembles a golf ball. Sheldrake (2020) describes it succinctly: "A millipede coiled up, playing dead."

Spiders, in Preston-Mafham's (1996) detailed survey, "play to perfection" an array of death-avoidance behaviours: faking death by becoming immobile; retreating rapidly into a corner to hide; falling from the web without leaving a thread; even disguising themselves as ants. As Crompton (1950) noted, "almost any animal will show fight when cornered" — but the invertebrates show, beyond fight, a repertoire of deliberate deceptive manoeuvres.

5. Vertebrates that close the door behind them

Among vertebrates, the same logic appears in armour. Turtles and tortoises carry rigid plates protecting internal organs, but a number of species — American box turtles and Egyptian tortoises among them — have evolved a hinge on the carapace. The hinge allows the animal to close the shell with vulnerable parts safely within, transforming the turtle into what is effectively a sealed box. Halliday and Adler (2004) describe this as one of the most efficient predator-avoidance mechanisms in the reptile world.

The hedgehog, one of the oldest mammalian lineages — molecular analysis places the radiation of spiny hedgehogs at the end of the Miocene — takes the same approach with soft tissue. An adult hedgehog carries roughly 7,000 spines. Wilson and Mittermeier (2018) describe the behaviour in detail: when startled, the animal lowers its head and body to the ground, covering tail and feet, and erects the spines. If the threat escalates to physical contact, muscles draw the spiny dorsal skin down to envelope the whole body, with spines set at opposing angles to form a dense barrier. A rolled hedgehog presents a predator with "nothing but a puzzling spiky surface," and can remain rolled for hours.

The pattern across these cases — millipede, spider, turtle, hedgehog — is that death refusal is not a single behaviour but a convergent engineering solution: convert the soft body into something a predator cannot profitably attack.

6. Plants are not passive — they anticipate

Plants cannot run, so their defence is anticipatory. They respond to a wide array of volatile compounds released by microbes, other plants, and insects. Crucially, they respond before being attacked themselves. A plant under herbivore attack releases volatile organic compounds; neighbouring unwounded plants detect these signals and begin producing defensive chemistry hours or days before any herbivore reaches them.

The most striking demonstration Lima-de-Faria cites is from Scots pine (Pinus sylvestris). Bittner et al. (2019) exposed pine trees to the sex pheromones of the sawfly Diprion pini — that is, to a signal of forthcoming egg deposition, not to actual herbivory. The pines responded with the differential expression of several defence-related genes. The plant was not reacting to damage; it was reacting to the chemical announcement of damage-to-come.

This finding is corroborated by a substantial modern literature. A 2022 review in the Journal of Experimental Botany documents the dual function of insect-induced volatiles: direct defence (repelling attackers) and indirect signalling (recruiting parasitoid wasps, priming neighbours). Kinoshita et al. (2026) used real-time calcium bioimaging to watch VOC signalling propagate between plants, confirming that the receiver is not passively accumulating chemistry but actively responding. Anthony Trewavas's foundational case for plant intelligence, published in Interface Focus in 2017, remains the canonical statement of the broader interpretation; Mallatt et al. (2020) remain the most rigorous critics.

7. Humans concretize the refusal in stone

Humans did not begin refusing death in any organised form when the great apes split from the hominid line six million years ago. Even after Homo sapiens populated the planet, there is no early archaeological sign of organised death refusal. The first burials — found below houses — appear between 7,000 and 6,000 BCE. These mark, in Lima-de-Faria's reading, the first concern with immortality: the dead are no longer abandoned but interred, equipped with objects and furnishings to assist life in the afterworld.

The concretization escalates rapidly. Statuary and representational art tied to political power follow. The pyramids of Sudan and Egypt are explicit tombs. The terracotta army excavated at the tomb of the Emperor of China (221 BCE) is an extreme form: an entire military force, replicated in clay, deployed to accompany one man into eternity (Scarre, 2013). Modern cemeteries, with elaborate tombs and statues, are the contemporary continuation of the same refusal.

8. Consciousness as the obligatory prerequisite

If death refusal is this widespread, what is its common denominator? Lima-de-Faria's answer is consciousness — defined not narrowly (the Britannica definition, "perception of what passes in a man's own mind," refers only to humans) but broadly, in the sense proposed by Irwin (2020), who emphasises both the "deep roots" and the "broad distribution" of consciousness across animal species.

The argument rests on a chain of evidence:

1. Memory is the obligatory first component. When a Paramecium bumps into an obstacle, it swims backward; a stimulus to the posterior end speeds it up. Intracellular microelectrodes revealed that electrical charges and calcium concentration are involved. Another protozoan, Stentor, contracts its body using internal microfilaments when mechanically disturbed. Eckert and Randall (1978) concluded that these organisms possess an elementary form of memory. Without an initial memory of an attack, no active defence can begin.
2. Animals behave as if they expect outcomes. Griffin (1984) pointed out that animals behave as though they expect a certain outcome at given times — expectation, not just reaction.
3. Plants anticipate. The volatile-compound priming described above is, in this framing, a form of plant consciousness directly connected with the expectation of danger. Baulcombe and Dean (2014) describe a "molecular memory" of plant cells.
4. Decision is not a human monopoly. Decision, "which before was regarded solely as a human mental process, now emerges as a quality of the simplest cells, and it extends to complex organisms including humans."

The chain is: repeated injury → memory → awareness → response via modification of genetic make-up → active defence against death. The sequence is obligatory. Without prior consciousness of an attack, no active defence appears possible — whether the organism is a bacterium, a plant, or a human.

9. Sleep, melatonin, and consciousness without neurons

If consciousness does not require a large brain, does it even require neurons? The article argues it does not. Sleep, a particular stage of consciousness, "exists in animals without cephalised nervous systems and can be influenced by non-neuronal signals, including those associated with metabolic rhythms" (Anafi et al., 2019).

Plants have no neurons but move, respond to environment, and show strong circadian rhythms. Many synthesize melatonin — the hormone secreted by the human pineal gland, involved in lower vertebrates in pigment-cell aggregation and in humans in circadian rhythms. Even animals that lack neurons altogether, such as sponges and Trichoplax adhaerens (a placozoan), have cells that secrete neuropeptides with direct synaptic effects and indirect modulatory action on nervous systems. Consciousness, in the broad sense, does not need a brain or even neurons. It needs only a cell that can store a trace of yesterday and act on it tomorrow.

Modern single-cell cognition research has begun to characterise this trace at the molecular level. Rajan et al. (2026) traced Stentor habituation to calcium and kinase signalling — the same cascades animal neurons use to encode memory. Kukushkin (2026) calls this "cellular memory: learning without building." The 120-year-old debate that the Marine Biological Laboratory has tracked since Jennings's 1906 work on Stentor is now resolving toward yes: single-celled organisms can learn.

10. Brain size is the wrong metric

The intuition that consciousness scales with brain size was supported by an early finding: the human brain has billions of neurons, and there is broad agreement that neuron number increases with evolutionary complexity. But an extensive study of 28 avian species and several mammals, including apes, overturns the simple version of this claim (Olkowicz et al., 2016).

Corvids (raven, rook) and parrots (macaw, cockatoo) rival great apes across many psychological domains. They manufacture and use tools, solve problems insightfully, recognise themselves in mirrors, plan for future needs, and anticipate the future behaviour of humans and other species. The avian brain lacks a layered neocortex, but large areas of the avian forebrain are homologous to mammalian cortex, conform to the same organisational principles, and play similar roles in higher cognition.

The mechanism is neuron density, not brain volume. Songbird and parrot brains contain very large numbers of neurons at densities far exceeding those of mammals. Parrots and corvids have forebrain neuron counts equal to or greater than those of monkeys with much larger brains. "Avian brains thus have the potential to provide much higher cognitive power per unit mass than do mammalian brains" (Olkowicz et al., 2016). Polilov (2012) had earlier shown that the smallest insects evolve anucleate neurons — a different but equally striking solution to the packing problem.

Lima-de-Faria's point: if a bird with a walnut-sized brain solves the same cognitive problems as a chimpanzee, then "more neurons" is the wrong frame; "better-organised neurons" is the right one. By extension, if plants and single cells solve analogous problems with different substrates, the substrate is not the issue. The information processing is.

11. Cloning is older than humans

If consciousness is the prerequisite for death refusal, cloning is the most ancient implementation of it. The term, coined by Herbert J. Webber, derives from the Greek klon, "twig" — referring to the process whereby a new plant is created from a twig. In nature, many organisms produce clones through asexual reproduction; in biotechnology, cloning refers to creating genetically identical organisms, cells, or DNA fragments.

This is not a laboratory curiosity. It is the reproduction method used by plants, fungi, and bacteria, and has been for hundreds of millions of years. Many horticultural cultivars are clones derived from a single individual. Grapes represent clones propagated for over two millennia. Potatoes, bananas, and tulips are clonally propagated crops. Trees and shrubs form clonal colonies naturally when parts of an individual plant detach and grow separately.

Among animals, asexual reproduction occurs mainly in early-evolution lineages. Hydras (Cnidarians) reproduce by budding: a simple evagination of the body wall forms tentacles and detaches to become an independent hydra. The pattern is consistent: long before humans appeared, plants and animals had ensured their genetic continuity by cloning.

12. Regeneration: a second route to immortality

Regeneration — the capacity to regrow lost body parts — is a phenomenon difficult to distinguish from asexual reproduction, and Lima-de-Faria treats it as a parallel route to immortality. It begins, strikingly, in crystals, which have no genes at all; it expands in simple animals and plants, and slows down in higher vertebrates, where only certain organs retain the capacity (Lima-de-Faria, 2017, 2020).

Regeneration depends on cellular memory: the original pattern is reproduced without external intervention. In crystals, this is a pure atomic process. In unicellular algae, it is the release of chemicals that determines the pattern (Brachet, 1974). In animals, the molecular machinery is now being mapped. Flatworms (Planaria) have been the animal of choice: any piece about one-tenth the size of an adult worm regenerates into a complete worm. The genes involved have been isolated — Wnt3 induces a wave of proliferation, with low expression triggering head regeneration and high levels producing tail regeneration (Li et al., 2015). In starfish and related echinoderms, 694 genes decide the ordered regrowth of organs (Purushothaman et al., 2015).

Plant regeneration is more general still. The pluripotency and totipotency of plant cells was demonstrated as early as 1902, when Haberlandt showed that a single somatic cell could give rise to a whole plant. This remains one of the most striking demonstrations of biological immortality available: any cell, given the right signals, can rebuild the whole.

13. Human cloning in the 1930s: Müller, Haldane, and the Einstein question

Human cloning was considered already in the 1930s. The story Lima-de-Faria tells is one of the more uncomfortable chapters in the history of genetics. Drosophila's giant banded chromosomes had revealed that band changes produce natural mutations. P.H. Müller looked for a way to induce mutations artificially using X-rays, demonstrating that new mutations could be produced at will by physical intervention.

At that time, in Sweden as in the USA, the UK, and Germany, eugenics was not only generally accepted but imposed on people of lower social status. Müller — who received the Nobel Prize in 1946 (the article states 1948, a date that appears to be an internal error) — was a supporter of eugenics. According to Rose and Rose (1999), he speculated on cloning Lenin and Einstein. Another geneticist, J.B.S. Haldane in England, thought of cloning women as well. American novels and films of the 1990s and later have kept the theme alive.

The ethical implications, Lima-de-Faria argues, are extremely serious and at the same time irrelevant. The reason is not abstract ethics but a concrete observation: a human being is born into a social, intellectual, and historical environment that cannot be repeated, and that environment is as important as the genetic constitution in determining intellectual behaviour.

Einstein was born in 1879 in Ulm, Bavaria, and moved to Munich, where he was forced to stand the intolerant and militaristic policy of Chancellor Bismarck; the family emigrated to a tolerant Switzerland (Cahn, 1960). As a child he was slow to talk and slower to read. He refused the dogmatic German school atmosphere imposed with "blood and iron." An elderly uncle introduced him to mathematics. In Switzerland he renounced his German citizenship. Throughout his life, a violin and a sailing boat were among his sources of pleasure. Critically, he lived in a period of revolutionary ferment — the era of Bakunin, Kropotkin, Marx, Lenin — when all previous concepts in science and society were being put in question.

A cloned Einstein would lack this entire familial and intellectual environment. He would have no loving parents, no dedicated uncle, no comparable society. He would be declared a genius at birth — a condition he could not satisfy. Lima-de-Faria's blunt conclusion: "Suicide was most probably the only solution in sight." The cautionary parallel he cites is the Picasso family: one of Picasso's children committed suicide, as did Jacqueline, Picasso's wife, unable to stand the pressures of the mass media. The point is not that cloning is technically impossible. It is that the genome is not the whole person, and a copy of the genome without the environment that produced it is not a copy of the person.

14. The lost history of epigenetics

With Part 3, the article's central claim arrives. Epigenetic effects, Lima-de-Faria argues, disrupt and diminish the perpetuation of immortality by changing the genome. And the first thing to understand about epigenetics is that it is not new.

The embryologist C.H. Waddington coined the term in 1940 (Rieger et al., 1968). By the 1960s, he had created the Department of Epigenetics adjacent to the Institute of Animal Genetics at the University of Edinburgh, and developed the concept in a series of books (Organizers and Genes, 1940; The Strategy of the Gene, 1957; New Patterns of Genetics and Development, 1962). Geneticists of the era, however, refused the approach and even blocked publication of results.

Epigenetics was eventually accepted not because the geneticists relented but because the search for cures for cancer and diabetes — pressing social issues — demanded molecular-level studies that classical genetics alone could not provide. Yet, as late as 2014, American cytologists called epigenetics "a new kind of inheritance" (Skinner, 2014), in effect transforming a European discovery into an American one. Lima-de-Faria treats this as a recurring pattern in the sociology of science, "discarding ethical principles" in the process.

This section is one of the article's most pointed contributions. It is not just a history lesson; it is an argument that the social interests of a given era determine which biological mechanisms are visible, when, and to whom. The implication for immortality is that the leak in the reservoir was visible to some researchers for half a century before the mainstream noticed it.

15. What epigenetics actually does

The article defines epigenetics originally as "the branch of biology which deals with the causal analysis of development" (Rieger et al., 1968) and later as the study of chemical modification of specific genes or gene-associated proteins. These modifications can define how the information in genes is expressed and used by cells. They can determine when — or even if — a given gene is expressed.

The molecular evidence is now overwhelming:

1. DNA sequences change during development — not only through spontaneous mutations and chromosomal rearrangements but mainly through exon-intron shuffling, a widespread event in the genome (Herbert and Rich, 1999). DNA methylation (the addition of a methyl group to a nucleotide) can be transient or permanent, the latter set early in development. This is the principal type of gene modification.
2. Histone modifications — acetylation and phosphorylation — are another permanent modification. Specific modifications of this protein lead to expression or repression of genes in different cell types.
3. DNA is less central than once thought. The rigid order that directs embryonic formation is not directed by DNA but by microRNAs, previously considered irrelevant. These small sequences, 21–22 nucleotides long, carry the road map and charter the events leading to the production of a specific organism. They are transcribed from non-coding genes (Carrington and Ambros, 2003).
4. Some modifications are erased, others inherited. Some genetic modifications are spontaneously erased when cells reproduce, precluding inheritance. Other epigenetic modifications are heritable, passed from parents to offspring — epigenetic inheritance (Fridovich-Keil, 2017).

16. RNA editing: the same trick the trypanosome used

The RNA pool produced by the genome is not a passive read-out. It can be incorporated back into the genome over time by reverse transcription, creating what Lima-de-Faria calls "novel gene constellations" (Herbert and Rich, 1999). As Ponting et al. (2009) put it, "eukaryotic genomes are not the simple, well-ordered substrates of gene transcription that was once believed."

Most nucleotides in the genome are transcribed during development, producing a huge array of RNA molecules differing in size, abundance, and protein-coding capability. Long non-coding RNAs (over 200 nucleotides) regulate transcription. Eukaryotes use relatively little of their genome to code for proteins, and messenger RNA transcripts are extensively processed by alternative splicing and RNA editing — generating many different messages from the same gene.

RNA editing is particularly striking in plants. In chloroplasts and mitochondria of flowering plants, RNA editing changes C (cytidine) nucleotides to U (uridine); in ferns and mosses, it changes U to C. There are approximately 500 editing sites in mitochondria and 40 in plastids of flowering plants (Takenaka et al., 2013). The result: the protein specified by the messenger RNA differs from what the genomic DNA would predict. This is the same trick Trypanosoma brucei used to escape the immune system — and it is a trick available, in different forms, to every eukaryote.

17. MicroRNAs: DICER in animals, DICER-LIKE 1 in plants

Several hundred small RNAs and microRNAs have been identified in animals and plants. They arise from larger precursors transcribed from non-protein-coding genes. The precursors are processed by DICER (in animals) and DICER-LIKE 1 (in plants).

Plant microRNAs generally interact with their targets through near-perfect complementarity, directing messenger RNA degradation. Short interfering RNAs (siRNAs) may also guide nuclear events including histone and DNA methylation, resulting in transcriptional silencing — a typical epigenetic event (Carrington and Ambros, 2003). The same machinery that defends plants against viruses (RNA silencing) is the machinery that shapes their development.

18. Yeast: epigenetics begins early

One of the article's most important observations is that epigenetic events are not a late evolutionary invention. Saccharomyces cerevisiae (baker's yeast) — one of the simplest eukaryotes — already displays them (Allshire and Ekwall, 2014). The five most genetically investigated species — E. coli, S. cerevisiae, C. elegans, Drosophila melanogaster, and Arabidopsis thaliana — span the range from bacterium to flowering plant, and epigenetic phenomena are documented across the entire span.

The implication is direct: if epigenetic disruption of immortality occurs in yeast, it has been present for at least a billion years of eukaryotic evolution. It is not a feature of complex organisms; it is a feature of eukaryotes as such.

19. Plants show epigenetics most vividly

The article's most extensive empirical case studies come from plants, because plants display epigenetic phenomena with unusual clarity. Aquatic plants with partly submerged and partly aerial shoots generally have submerged leaves that are highly dissected and thin, in contrast to thicker, entire or moderately lobed aerial leaves. These different forms were originally attributed to environmental factors — temperature, light, humidity — but Greulach (1973) noted that environmental factors are "of secondary importance."

Ranunculus peltatus displays three different leaf types in one individual: submerged leaves with many linear segments, transitional forms with few segments, and floating palmate leaves. Hedera (ivy) shows two leaf types — juvenile lobed and mature entire — and the difference is a clear epigenetic phenomenon connected with gene imprinting. Cuttings from a flowering branch produce only the entire pattern; the lobed form reappears only when the plant is propagated by seed, i.e., through sexual reproduction (Denffer et al., 1976). Cellular memory and its erasure are now well documented at the cellular level (Gehring, 1985).

Carnivorous plants carry this further: epigenetic changes affect not only structure but function. Within a single Genlisea plant, non-carnivorous flat green leaves appear above ground while subterranean carnivorous leaves form corkscrew traps. Triphyophyllum produces three distinct leaf types during development — juvenile non-carnivorous, carnivorous, and mature flowering with no carnivory. At least eight genera of carnivorous plants produce different leaf types within one individual (McPherson, 2010). This is mainly due to RNA-directed DNA methylation (Herbert, 2004; Matzke et al., 2015).

20. The Agouti mouse: diet rewrites the offspring

Mice carrying the "Agouti" variant of a gene are genetically identical. Yet, depending on what their mother ate during pregnancy, the offspring can differ dramatically: brown and skinny (mutation switched off) or fat, yellow, and prone to obesity and diabetes (mutation switched on). The switch is set by the mother's environment acting on her genome and changing the fate of the offspring.

In the classical experiment, a pregnant yellow mother was fed a diet rich in folic acid and vitamin B12. The Agouti gene was switched off in the pups, which were consequently brown and thin rather than fat and yellow (Chong et al., 2007; Wolff et al., 2007). This is the canonical demonstration of mammalian epigenetic inheritance: the same genome, different epigenomes, different phenotypes — and the difference is set by diet.

Subsequent work has shown that DNA methylation and histone acetylation are the molecular cause of this process (Blewitt and Whitelaw, 2013). The Mouse Genome Database (Eppig et al., 2015) has since facilitated the comparison of mouse results with human biology and disease. The two species are closely related: the mouse has 24,613 protein-coding genes, of which 17,055 have human orthologs; 1,323 human diseases have one or more mouse models.

21. Epigenetics in humans: from choline to psychiatric disorders

In humans, metastable epialleles — genes whose expression varies among genetically identical individuals because of epigenetic establishment rather than DNA sequence — have been identified. These are good candidates for transgenerational inheritance. In mice, the equivalent phenomenon is responsible for color variegation (agouti viable yellow, axin-fused), caused by insertion of a transposon silencing the promoter. DNA methylation at this promoter correlates with silencing; methyl donors including betaine, methionine, and folic acid shift offspring color away from yellow and toward agouti.

Several human diseases result from disruption of the epigenetic state and can be inherited across generations. These include decreased mental capacity, obesity, and colorectal cancer, in which aberrant DNA methylation is implicated. Choline — an essential nutrient involved in epigenetic modulation of gene expression — has a role in carcinogenesis, leading the US FDA and European authorities to recommend adequate intake levels (Zeisel, 2017). Psychiatric disorders, including drug and alcohol dependence, also conform to patterns of epigenetic change (Wong et al., 2011).

22. The Swedish twins: symmetry is epigenetic

Lima-de-Faria closes the empirical section with a striking case study. Müntzing (1961) published a photograph of two Swedish twins, Monica and Gerd. Monica was left-handed with her forelock to the right; Gerd was right-handed with her forelock to the left. They were mirror images of each other. Within the framework of classical genetics — the constancy of gene action — this change in symmetry within an identical genetic constitution was a foreign problem.

It is no longer foreign. Symmetries are now known to be inherent to matter, occurring in elementary particles (the neutrino), in galaxies, in carbon atoms, in quartz crystals, in amino acids, in DNA configurations, in flowers, in snails, and in humans (Lima-de-Faria, 1995). Reversal of left-right forms in mice has been related to mutations in a gene controlling embryonic polarity (Yokoyama et al., 1993). Homeotic genes are involved in bilateral symmetry in chicken, mouse, and humans (Yokouchi et al., 1991). The transcription factor Pitx2 — which has a human homologue — participates in left-right symmetry (Ryan et al., 1998).

The patterns of Monica and Gerd thus indicate an epigenetic effect resulting from mutations in genes directing embryonic development. Identical genomes, mirror-image outcomes — the most literal possible demonstration that the genome alone does not determine the organism.

23. The conclusion: four things we still do not know

Lima-de-Faria's conclusion is not triumphant. The evidence on epigenetic effects, extending from simple organisms to plants and higher vertebrates including humans, is overwhelming. But, he insists, "we are far from knowing the main events participating in this process."

He lists four specific limitations:

1. The evolution of DNA itself is unknown. We do not know the type of mutations that result from this event.
2. The evolution of RNA is not elucidated. RNA editing makes this a major factor.
3. The molecular cascades following DNA and RNA alterations are not known. We can see the inputs and the outputs; the middle of the network is unmapped.
4. The atoms responsible for deciding the final pattern are unknown. The decision is being made at a level below the molecule.

These limitations, he argues, are being addressed by research at the atomic level using large electron and neutron accelerators — specifically, the Max IV synchrotron and the European Spallation Source, both at Lund University (Lima-de-Faria, 2017, 2020). The instruments that will resolve the open questions are, fittingly, the same kind of instruments — particle accelerators — that gave us the concept of infinity Lima-de-Faria began by questioning.

Why immortality is getting harder

The article's final argument ties these threads together. Bacteria achieve functional immortality through plasmid exchange. Protozoa achieve it through RNA editing. Plants achieve it through apomixis, volatile communication, and totipotent cells. Animals achieve it, badly, through regeneration that diminishes with evolutionary complexity. Humans attempt it with burials, statues, pyramids, terracotta armies, and cloning — and discover that the genome they are trying to preserve is, in fact, a moving target.

The reason immortality is becoming more difficult is that the genome is no longer the only thing being inherited. The epigenome is inherited. Small RNAs are inherited across generations in C. elegans, in plants, and increasingly in mammals. The microbiome is inherited behaviourally. Each of these inheritance channels introduces a source of drift.

Lima-de-Faria's conclusion is therefore not a paradox but a quantitative observation. Immortality is not impossible — bacteria have been doing it for four billion years. It is simply that the number of things which must be kept identical in order to achieve it has risen by several orders of magnitude since the origin of eukaryotes, risen again with multicellularity, risen again with nervous systems, and risen again with culture. Each step up in complexity buys new capabilities. Each step up also buys new ways to die.

Bottom line: if you wanted to act on this today, what can we do

If the science in Lima-de-Faria's synthesis is even partly right, then the practical question is not "how do I become immortal." It is "how do I slow the leak in the reservoir." Four actions follow directly from the article's own logic, and each is supported by recent peer-reviewed work.

1. Treat the maternal and early-life environment as an epigenetic intervention, not a background. The Agouti mouse experiment is the clearest demonstration: the same genome produces a sick yellow obese mouse or a healthy brown thin one depending on maternal folic acid and vitamin B12. The implications for human pregnancy are direct and underused — adequate methyl-donor nutrition (folate, B12, choline, betaine, methionine) during pregnancy is not optional; it is epigenetic engineering of the next generation. The FDA and EFSA already recommend adequate choline intake on this basis (Zeisel, 2017).
2. Treat epigenetic drift as a measurable variable. DNA methylation clocks — Horvath's, GrimAge, PhenoAge — quantify the gap between chronological and biological age. Sinclair's group showed in 2023 that loss of epigenetic information, not mutation of the DNA sequence, can drive aging in mice, and that restoring it can reverse aspects of aging. If you are not measuring your epigenetic age, you are flying blind on the one variable most directly tied to the leak. Wang et al. (2022) reviewed the broader evidence: overexpression of histones H3 and H4 in yeast extends lifespan because an increased pool of free histones protects against transcriptional noise.
3. Stop thinking of immortality as a single-cell problem. Bacteria are effectively immortal because they have one cell, one chromosome, and one inheritance channel to preserve. Humans are not. Any serious programme for radically extending human lifespan has to preserve not just the genome but the epigenome, the proteostasis network, the immune repertoire, and the microbial ecosystem — all simultaneously. Work in C. elegans shows that germline immortality depends on faithful inheritance of histone marks and small-RNA populations; when the inheritance machinery mutates, the germline becomes mortal within a handful of generations. Be deeply sceptical of any intervention that promises to extend life by fixing only one of these layers.
4. Do not pursue human cloning as a route to immortality. The article's argument on this point is structural, not ethical. A cloned Einstein would lack the social, intellectual, and historical environment that produced the original — Bismarck's Germany, Swiss refuge, the mathematician uncle, the violin, the sailing boat, the revolutionary ferment of Bakunin and Kropotkin and Marx and Lenin. The Picasso-family suicides are the cautionary parallel. The genome is not the person. Investing in cloning as a personal-immortality strategy is investing in a copy of the hard drive without the operating system that ran on it.

The deepest action, however, is intellectual. The article's value is not as a recipe for immortality. It is as a corrective to the assumption that immortality is a technology waiting to be invented. The bacteria, the plants, the birds, the single-celled ciliates, the trypanosomes were running immortality programmes long before we arrived. Our job is not to invent it. It is to understand why, in a lineage as complex as ours, it has become so hard to keep.

Read the original article (open access, CC-BY).

Title: Genetics and Epigenetics of Immortality from Bacteria to Humans

Author: Antonio Lima-de-Faria (Emeritus Professor of Molecular Cytogenetics, Lund University, Sweden)

Journal: Organisms: Journal of Biological Sciences

Citation: Organisms: Journal of Biological Sciences, Vol. 5, No. 1, pp. 17–31 (2021)

DOI: 10.13133/2532-5876/17508