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Drug-Provoked Psoriasis: Is It Drug Induced or Drug Aggravated?

Posted: November 23, 2022 at 4:06 am

J Clin Aesthet Dermatol. 2010 Jan; 3(1): 3238.

Understanding Pathophysiology and Clinical Relevance

aDermatology Research Fellow, Mohave Skin & Cancer Clinics, Las Vegas, Nevada

bDermatology Residency Director, Valley Hospital Medical Center, Las Vegas, Nevada, and Director of Dermatology Research, Mohave Skin & Cancer Clinics, Las Vegas, Nevada

aDermatology Research Fellow, Mohave Skin & Cancer Clinics, Las Vegas, Nevada

bDermatology Residency Director, Valley Hospital Medical Center, Las Vegas, Nevada, and Director of Dermatology Research, Mohave Skin & Cancer Clinics, Las Vegas, Nevada

DISCLOSURE: The authors report no relevant conflicts of interest.

Psoriasis is a commonly encountered dermatosis with a variety of internal and external paradoxical factors contributing to the clinical course of the disease. There are several drugs described in the literature that have been associated with the initiation, exacerbation, and aggravation of psoriasis. Understanding the pathophysiology can provide clues to treatment and management of drug-induced and drug-aggravated psoriasis, which may be indistinguishable from idiopathic psoriasis. The clinical manifestations of drug-associated psoriasis can range from plaque-type psoriasis to severe erythroderma, thus warranting astute and sustained clinical observation.

Psoriasis is a chronic, immune-mediated, inflammatory condition seen frequently in the clinical practice with a reported prevalence of 0.6 to 4.8 percent in the general population.1,2 Some factors known to trigger psoriasis include smoking, alcohol consumption, body mass index (BMI), trauma, infection, endocrine disorders, drugs, and acute withdrawal of systemic or potent topical corticosteroids.1 Analysis of comedication in a study of 1,203 psoriasis patients revealed 23.2 percent of patients were taking more than three systemic medications, and of these patients, 11.1 percent were taking more than 10 medications.3 Further analysis demonstrated that comorbid cardiac and metabolic disorders are common in these individuals with a high prevalence of hypertension (28.2%), diabetes (10.5%), and dyslipidemia (12.5%).3 With this in mind, many psoriasis patients can be on multi-drug regimens; therefore, careful analysis of medications that can exacerbate the disease is prudent. Drugs reported to be associated with exacerbation/induction of psoriasis are based mostly on case reports, with no definitive cause-and-effect links between these drugs and onset of psoriasis.

Drugs have several ways in which they can affect the diathesis of psoriasis including 1) precipitation of psoriasis de novo in predisposed and nonpredisposed individuals; 2) exacerbation of pre-existing psoriatic lesions; 3) induction of lesions in clinically normal skin in patients with psoriasis; and 4) development of treatment-resistant psoriasis.4 The clinical presentation of drug-provoked psoriasis spans the spectrum of generalized plaque psoriasis, palmoplantar pustulosis, and erythroderma.4 The nails and scalp can also be involved, thus making the distinction of drug-associated psoriasis a clinically difficult diagnosis.4 In addition, the mechanism of action can also involve both immunological and nonimmunological pathways.5 Therapeutic agents can also be categorized as having a causal relationship to psoriasis, with considerable but insufficient data supporting induction of psoriasis, or occasionally an association with psoriasis.4 Drugs that appear to have a strong causal relationship to psoriasis are beta-blockers, lithium, synthetic antimalarials, nonsteroidal anti-inflammatory drugs (NSAIDs), and tetracyclines, which will be discussed in this review.4

Psoriasiform drug eruption is a broad term referring to a heterogeneous group of disorders that clinically and/or histologically simulate psoriasis at some point during the course of the disease.6 A psoriasiform eruption is used also to describe a histological reaction pattern, which exhibits presence of cellular infiltration, papillomatosis, and epidermal hyperplasia with elongation of rete ridges.6 Hypergranulosis and parakeratosis may also be observed in selected cases.710 This type of eruption can also be seen with seborrheic dermatitis, pityriasis rubra pilaris, secondary syphilis, pityriasis rosea, mycosis fungoides, drugs, and some malignancies.6 These psoriasiform reactions are elicited by inflammatory events that cause dysregulation of cytokines, growth factors, and abnormal keratinocyte proliferation.6 Depending on the disorder, the lesions may vary in size, shape, extent and type of scaling, and anatomic distribution.6

Drug-provoked psoriasis can be divided into two categories (). The first category, drug-induced psoriasis, is where discontinuation of the causative drug stops the further progression of the disease. The second category, drug-aggravated psoriasis, is where the disease progresses even after the discontinuation of the offending drug.4 True drug-induced psoriasis tends to occur in a de-novo fashion in patients with no family or previous history of psoriasis.5 The clinical presentation of these lesions may often mimic the pustular variant of psoriasis, often with no nail involvement or associated arthritis.5 Furthermore, there is an absence of Munro microabscesses, few macrophages, and sparse vascular changes noted histologically.5 Drug-aggravated psoriasis exhibits a propensity to occur in patients with a history of psoriasis or with a genetic predisposition for the disease. Patients can have exacerbation of pre-existing psoriatic lesions or develop new lesions in previously uninvolved skin. Histological examination reveals features that are more characteristic of psoriasis vulgaris.11

Drug-provoked psoriasis: Subtypes4

Beta blockers are a very popular class of drugs used to treat both cardiovascular and noncardiovascular diseases, including hypertension, ischemic heart disease, arrhythmias, heart failure, hyperthyroidism, glaucoma, and anxiety disorders.11 They exert their action by blockade of either 1 receptors (cardioselective) or 2 receptors (noncardioselective), hence their classification. 2-adrenergic receptors are found predominantly on epidermal keratinocytes and on the surface of macrophages.11 Several theories have been proposed regarding the pathogenesis of beta blocker-induced psoriasis. These include a delayed-type hypersensitivity reaction, immunological mechanisms including impaired lymphocyte transformation, or alterations in the cyclic adenosine monophosphate (cAMP) pathway.1214 Cyclic adenosine monophosphate is an intracellular messenger that is responsible for the stimulation of proteins for cellular differentiation and inhibition of proliferation.11 The most reliable proposition is that blockade of epidermal 2 receptors leads to a decrease in intraepidermal cAMP causing keratinocyte hyperproliferation.4 Biopsy specimens from eruptions caused by 1 blockers (metoprolol and atenolol) are characterized by excessive degranulation of neutrophils in the dermis.15 Nonselective beta blockers (propranolol, nadolol, and sotalol) were marked by excessive release of proteolytic enzymes from macrophages.15 Both groups of beta blockers exhibit excessive release of enzymes by lymphocytes, neutrophils, and macrophages, and it is believed that this event is responsible for the presence of hyperproliferation and psoriasiform change. It has also been reported that beta blockers increase phosphorylation in T cells in psoriasis, which may be relevant to intracellular levels of calcium.16 The blockade of these receptors has been implicated in the pathogenesis of drug-provoked psoriasis in both groups of beta blockers.11

Clinical manifestations of beta-blocker-provoked psoriasis. In the past, beta blockers have been known to cause drug-induced/exacerbation of psoriasis, psoriasiform dermatitis, eczematous eruptions, and lichenoid changes.8 Psoriasiform eruptions are the most common cutaneous consequence of beta-blocker therapy, seen more frequently in patients with no past or family history of psoriasis.4,17 Clinical improvement after withdrawal of the implicated drug is the distinguishing feature in many cases suggesting drug-induced psoriasis.4 In a case-controlled and case-crossover study of 110 patients who were hospitalized for extensive psoriasis vulgaris, beta blockers were considered a major factor in triggering or aggravating psoriasis.1820 Practolol is the prototype cardioselective beta blocker, which is no longer available due to the high incidence of cutaneous side effects reported, including psoriasiform eruptions and exacerbations of pre-existing psoriasis.12 Transformation of plaque-type psoriasis into pustular psoriasis with pindolol has also been observed.21 In addition, atenolol has been reported to precipitate psoriasiform pustulosis.22 Topical application of timolol in the treatment of open-angle glaucoma has been reported to induce psoriasis and to transform psoriasis vulgaris into psoriatic erythroderma through the passage into the systemic circulation via the conjunctiva.23,24

Both psoriasiform eruption and drug-induced/aggravated psoriasis from beta-blocker therapy usually appear at 1 to 18 months after initiation of therapy.15 In psoriasiform eruptions, lesions clear after several weeks of discontinuing the medication.15 In addition, re-exposure with oral challenge results in recurrence within a few days.15 Many believe that psoriasiform eruptions from beta blockers are not true representations of psoriasis, partly due to histological features and partly due to clinical presentations exhibiting lesions that are less red, thick, or scaly than classic lesions of psoriasis, and usually with absence of knee and elbow involvement.15 In contrast, beta-blocker-provoked psoriasis improves upon discontinuation of medication, but usually does not completely resolve.11 In regard to beta-blocker-induced, de-novo pustular psoriasis, the duration is much shorter.4 Reasons for these variations remain a mystery and may be due to genetic, environmental, or racial backgrounds.

Management of beta-blocker-provoked psoriasis. Cross reactivity between both groups of beta blockers have led many researchers to believe that the mechanism of action is directly via the skin.5 This has been demonstrated with the observation that switching from one beta blocker to another results in re-introduction of psoriasiform skin lesions.5 However, researchers have found that the cumulative drug exposure to beta blockers is not a substantial risk factor for development of psoriasiform lesions.25 In psoriasiform eruptions, discontinuation alone can cause rapid regression of the disease.4 If psoriasis is present only in localized areas, emollients alone can be helpful.4 Exacerbation of psoriasis by beta blockers can be persistent and resistant to therapy unless they are discontinued.4 Management of drug-provoked psoriasis necessitates the use of conventional therapeutic agents that include topical and systemic agents used in the treatment of psoriasis vulgaris.4 Treatment of erythroderma resulting from beta-blocker therapy should be targeted at decreasing transepidermal fluid loss.26 Hospitalization is required to monitor hypovolemia and hemodynamic instability that requires aggressive fluid resuscitation.26 These cases should be treated aggressively with systemic and topical agents in concordance with discontinuation of the offending drug.26

Lithium is a metal ion that has been used extensively in the treatment of manic-depressive disorder since the 1970s.11 Although utilization of lithium is not as widespread as in the past, it is commonly prescribed. The first association of lithium with psoriasis was reported in 1972, and since then there have been several reports of lithium-induced psoriasis described in individuals with no personal or family history.11 Toxic effects of lithium on organs other than the skin are dose related, with adverse events involving the thyroid, kidneys, central nervous system, and gastrointestinal tract.11 Psoriasiform eruptions are the most common cutaneous side effects, reported to occur in 3.4 to 45 percent of patients treated with lithium.27

Pathogenesis of lithium-provoked psoriasis. There are several theories purported to explain the pathogenesis of lithium-provoked psoriasis. Induction and aggravation of psoriasis through cAMP are now being refuted by some investigators.16 In the past, researchers theorized that the decrease in cAMP from lithium treatment caused low intracellular levels of calcium, leading to a lack of differentiation, increased proliferation of keratinocytes, and enhanced chemotaxis and phagocytic activity of polymorphonuclear leukocytes.28,29 Past studies have shown that the short-term use of lithium leads to diminution of intracellular cAMP, but long-term lithium treatment causes just the opposite response through a compensatory mechanism.30,31 The current belief is that lithium causes depletion of inositol monophosphatase resulting in alterations in calcium homeostasis and seritonergic function.5,3234 Inositol is an intracellular second messenger system linked to neurotransmitters affecting cell function, growth, and differentiation.5 The association between the blockade of the phosphatidyl inositol pathway and lithium-provoked psoriasis is through the release and depletion of intracellular calcium.5 Low intracellular calcium levels cause increased proliferation of keratinocytes and affect terminal differentiation.11 Lithium inhibits the enzyme inositol monophosphatase, necessary for the recycling of inositol.11 The inhibition of the intracellular release of calcium appears to be the mechanism in which lithium provokes the development of a psoriasiform eruption.35 The support for the inositol depletion hypothesis comes from the clinical observation that inositol supplementation can reverse the exacerbation of lithium-provoked psoriasis.16 In addition, studies have shown that lithium increases the production of interleukin-2 (IL-2), tumor necrosis factor- (TNF-), and interferon-gamma in psoriatic keratinocytes.11 The dysregulation in the production of these cytokines has been linked to the induction of psoriatic lesions.11 Lithium also increases intracellular tyrosine phosphorylation in psoriatic T cells but not in control T cells, with a possible implication to psoriasis lesion development.16

Clinical manifestation of lithium-provoked psoriasis. Reports of lithium-provoked psoriasis in the literature include new onset of pustular psoriasis, palmoplantar pustulosis, erythroderma, psoriasiform dermatitis, psoriatic arthropathy, and psoriasis involving the nail and scalp.36 The most common presentation of lithium-provoked psoriasis is the classic plaque-type lesions.5 Clinically and histologically, there is little difference between psoriasis vulgaris and lithium-provoked psoriasis.37 In addition, elevated plasma concentrations of lithium have been found in patients with psoriasis who have never been treated with lithium compounds, suggesting a possible environmental factor.38 There may be inherent factors that influence the induction or aggravation of psoriasis with lithium.11 When plaque-type psoriasis develops with lithium therapy, it may take longer to resolve compared to pustular psoriasis.37 It has been suggested that exacerbation of pre-existing psoriasis is more common than induction of new psoriatic lesions.3940 While in some patients, there is a definite temporal relationship between aggravation of psoriasis with the initiation of lithium and improvement with discontinuation of the drug, this is not always the case.27,41 The refractory period for the development of psoriatic lesions after the initiation of lithium treatment is variable and ranges from a few weeks to several months.36 There have also been reports suggesting that production of psoriatic lesions can be temporally related to the improvement in mood symptoms due to cellular saturation with lithium ions.36

Management of lithium-provoked psoriasis. Supplementation with inositol in dietary consumption has sparked an interest in the treatment of psoriasis associated with lithium therapy. Peripheral inositols received in the form of dietary consumption do not cross the blood-brain barrier and therefore do not alter lithium effects on mood stabilization.42 Studies have shown that patients with psoriasis on lithium therapy experience significant improvement after 6g of daily inositol supplementation by mouth with dramatic improvement within 48 to 72 hours.43 A double-blind, randomized, placebo-controlled, crossover trial showed that inositol supplementation significantly improved the Psoriasis Area and Severity Index (PASI) scores in psoriasis patients on lithium compared to placebo.5 In another double-blind, placebo-controlled trial, 4 to 6g/day of omega-3 fatty acid was found to be very useful in clearing acute lithium-induced psoriasis.44 In addition, there has also been success with TNF- inhibitors, such as etanercept, in the treatment of severe, recalcitrant, lithium-provoked psoriasis.4445 However, there are new reports suggesting the onset or exacerbation of psoriasis with TNF- inhibitors possibly through elevation of cytokines or due to increased susceptibility to infections.46 In evaluating lithium-provoked psoriasis, the role of stress and other psychological factors, as well as current medications, must be evaluated. Lithium-provoked psoriasis can be controlled with conventional treatments, such as topical corticosteroids, keratolytics, vitamin D analogues, oral retinoids, psoralen plus ultraviolet A (PUVA) therapy, and methotrexate.36 Psoriatic lesions generally disappear within a few months after discontinuation of lithium treatment.36 In some cases, patients can develop treatment-resistant psoriasis, which may warrant discontinuation of lithium with change to another mood-stabilizing agent (under close supervision of a psychiatrist) depending on the severity of cutaneous involvement.40,47,48 Reduction in dosage of lithium is an additional option for treatment-resistant cases.36 Yet, lithium-provoked psoriasis has been reported to occur at varying therapeutic levels and is not believed to be dose related.49 It is advised that not all patients with psoriasis will have a flare-up with the initiation of lithium therapy, and psoriasis is not considered a contraindication to lithium use.50

The synthetic oral antimalarial (AM) agents are 4-aminoquinolone compounds that have been used in the prophylaxis and treatment of malaria and several dermatological disorders for many years.11 The most commonly used oral AMs are chloroquine and hydroxychloroquine.11 The exacerbation and induction of psoriasis during treatment with AMs has been widely acknowledged.4 One mode of action of AMs is through the inhibition of transglutaminase in the skin, which is thought to influence cellular proliferation.11 The inhibition of this enzyme can induce de-novo pustular psoriasis, which is notably uncommon compared to aggravation of pre-existing psoriasis.51 Some patients may have minimal presence of pre-existing psoriatic lesions without being aware that these minor skin changes constitute psoriasis.11 It has been shown that patients with psoriatic skin lesions after use of AMs had exacerbation of their psoriasis in 31 percent of cases.52 The same study also reported the induction of psoriasis and pustular psoriasis during chloroquine therapy.53,54 In another group, 42 percent (20/48) of American soldiers with psoriasis given chloroquine for the prophylaxis of malaria had exacerbation of psoriasis, which was treatment resistant.55 Exacerbation of psoriasis has been reported with chloroquine treatment for psoriatic arthritis.5657 Psoriatic skin lesions most often occur with a latency of 2 to 12 weeks (average of 3 weeks) after starting AMs, with some patients exhibiting durations longer than 40.5 weeks, especially in cases of pustular eruptions occurring in those with pre-existing psoriasis.4 Clinicians may be faced with a difficult decision in patients with simultaneous collagen vascular disease, such as progressive discoid or subacute cutaneous lupus erythematosus and psoriasis.4 Resolution of psoriatic lesions usually occurs within one month of discontinuing the AM agent.11 The use of chloroquine and hydroxychloroquine in patients with psoriasis is considered by some to be a contraindication.11

A relationship between systemic antibiotics and drug-provoked psoriasis remains controversial. The tetracyclines are one group of antibiotics that have been described in association with psoriasis with no definitive latency period.58 Tetracyclines may theoretically provoke psoriasis through reduction of intracellular cAMP and by the interaction with arachidonic acid and its metabolites.59 It has been theorized that tetracyclines accumulate in higher concentrations in psoriatic lesions compared to uninvolved skin.60 Some tetracyclines may cause photosensitization, which may result in predisposed patients with psoriasis to experience exacerbation through the Koebner phenomenon secondary to phototoxicity.6163 In one study, investigators reported that 4.11 percent (19/462) of patients experienced exacerbation of psoriasis as a consequence of tetracycline use.4 It has also been suggested that tetracyclines should be avoided in patients with clinical evidence of psoriasis, as well as in healthy individuals with a genetic predisposition for psoriasis, such as in those with a positive family history or with HLA-B13, B17, and B27 genotypes.4 The validity, practicality, and clinical relevance of these suggestions remain uncertain.

Reports suggest that exacerbation of psoriasis by penicillin derivatives is rare and may actually represent acute generalized exanthematous pustulosis and not true drug-provoked psoriasis.6566 Macrolides and penicillin derivatives were associated with psoriasis in one multivariate case-control model in patients less than 50 years of age.64 Whether the actual drug intake or the infection itself is the inciting agent is still uncertain.4 Therefore, clinicians should keep in mind that antibiotics may have been given as a treatment for presumed streptococcal infection, a known trigger of psoriasis development or exacerbation.64

NSAIDs are a class of medications used for treatment of pain and arthritides. NSAIDs are frequently used by patients who have psoriasis as well as psoriatic arthritis. NSAIDs are available by prescription and over the counter. NSAIDs inhibit the metabolism of arachidonic acid by the cyclo-oxygenase (COX) pathway leading to accumulation of leukotrienes, which has been postulated to aggravate psoriasis.11 According to one study, both topical and systemic NSAIDs were the most common cause of both exacerbation and induction of psoriasis.11 Of the NSAIDs, naproxen was the most common culprit.67 Six patients had exacerbation of psoriasis after taking oral NSAIDs in a large study of 462 patients.68 In another study, topical 1% indomethacin cream exacerbated psoriasis in 14 of 20 patients with known disease.69 In case-controlled and case-crossover studies, there have been adverse side effects of NSAIDs reported in patients with psoriasis, particularly with proprionic acid derivatives.69 The effects of NSAIDs have a short latency period (1.6 weeks on average) without significant variations between the different subsets of drug-provoked psoriasis.4 Considering that patients with psoriasis can have associated arthropathies, it is important for clinicians to recognize NSAIDs as potential exacerbators of psoriasis. Nevertheless, in some patients, exacerbation of psoriasis and arthritis may coincidently occur simultaneously with the use of NSAIDs.

Angiotensin-converting enzyme inhibitors (ACEI) are widely used to control hypertension. In an analysis of case-controlled and case-crossover studies, ACEIs were associated with psoriasis in patients greater than 50 years of age.64 Although there are no current studies confirming a causal relationship between the two, ACEIs are considered to be possible triggering/exacerbating agents of psoriasis.64 Recent studies suggest that patients with a history of familial psoriasis and a specific ACE genotype exhibiting low ACE activity are more susceptible to developing psoriasis after initiation of therapy.70

Drugs with considerable data in the induction/ exacerbation of psoriasis include interferons, terbinafine, and benzodiazepines.64,69 There have also been reports of generalized pustular psoriasis in association with phenylbutazone.4 Other miscellaneous drugs with a reported association with psoriasis include digoxin, clonidine, amiodarone, quinidine, gold, TNF-alpha inhibitors, imiquimod, fluoxetine, cimetidine, and gemfibrozil.11 With an ever-expanding list of medications, investigators have suggested using the Adverse Drug Reactions Probability Scale in assessing the relationship between drugs and adverse reactions if a clinician is faced with a difficult decision in high-risk psoriasis patients on multidrug regimens.71

Several drugs have been associated with drug-provoked psoriasis (). Understanding the pathogenesis of drug-provoked psoriasis not only helps to achieve a greater appreciation of the disease process, but is also useful in providing guidance for treatment methodologies. In certain cases of drug-provoked psoriasis, lesions may become resistant to treatment and hence early recognition and management can help avoid issues of nonadherence. In general, most drugs tend to exacerbate psoriasis rather than induce it.11 In cases where psoriasis is induced, one should question if this is truly a first-time occurrence or if previous subclinical signs may have gone undetected. Why provocation of psoriasis occurs in some individuals and not others who are exposed to a specific drug remains unclear. The absence of additional triggering factors should always be ruled out first. Patients should be encouraged to avoid alcohol, excessive sun exposure, smoking, and stressfactors that can all affect the clinical course of the disease. Management of drug-provoked psoriasis includes detailed personal, social, and family history. Provocation testing is also an option if a definitive relationship cannot be established. Drugs that are considered to have a strong potential risk factor for psoriasis development should be avoided after weighing the risk and benefits of the agent.64 Fortunately, there are only a few drugs that demonstrate a well-documented, direct, causal relationship with the development of psoriasis or psoriasiform eruptions, and alternative therapeutic options are frequently available.

Drug-provoked psoriasis: Reported agents

3. Zahl V, Gerdes S, Mrowietz U. Co-medication in patients with severe psoriasis: first results of a retrospective analysis in 1203 hospitalized patients in Germany. Presented at: the 4th International Congress-The Royal College of Physicians; December 13, 2005; London, England.

58. Botev-Slatkov N, Tsankov N, Tonev S, et al. Drug therapy deteriorates the course of psoriasis. Presented at: 17th World Congress of Dermatology, Part II; West Berlin: Springer; 1987:216.

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Drug-Provoked Psoriasis: Is It Drug Induced or Drug Aggravated?

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Artemis is our first step toward space colonization – Big Think

Posted: November 21, 2022 at 2:47 am

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Ancient DNA and Neanderthals | The Smithsonian Institution’s Human …

Posted: November 16, 2022 at 11:29 pm

DNA (deoxyribonucleic acid) is arguably one of the most useful tools that scientists can use to understand living organisms. Our genetic code can tell us a lot about who we are, where come from, and even what diseases we may be predisposed to contracting and acquiring. When studying evolution, DNA is especially important in its application to identifying and separating organisms into species. However, DNA is a fragile molecule, and it degrades over time. For most fossil species, there is essentially no hope of ever acquiring DNA from their fossils, so answers to questions about their appearance, physiology, population structure, and more may never be fully answerable. For more recently extinct species scientists have, and continue to, extract ancient DNA (aDNA) which they use to reconstruct the genome of long-gone ancestors and relatives. One such species is Neanderthals, Homo neanderthalensis.

Neanderthals were the first species of fossil hominins discovered and have secured their place in our collective imagination ever since. The first Neanderthal fossils were found in Engis, Belgium in 1829, but not identified as belonging to Neanderthals until almost 100 years later. The first fossils to be called Neanderthals were found in 1856 in Germany, at a site in the Neander Valley (where Neanderthals get their name from). Neanderthals diverged from modern humans around 500,000 years ago, likely evolving outside of Africa. Most ancestors of Homo sapiens remained in Africa until around 100,000 years ago when modern humans began migrating outwards. In that time, Neanderthals evolved many unique adaptations that helped them survive in cold environments of Europe and Asia. Their short limbs and torso help conserved heat, and their wide noses helped warm and humidify air as they breathed it in. Despite these differences, modern humans and Neanderthals are very closely related and looked similar. We even overlapped with each other-living in the same place at roughly the same time in both the Middle East and Europe. If this is the case, why did Neanderthals go extinct while we survived? We can use DNA to help to answer this question and others, including:

Scientists answer these questions by comparing genomes as whole, as well as specific genes, between humans and Neanderthals. Before getting into the specifics of Neanderthal DNA, it is important to appreciate the structure of DNA itself, why it is so important, and why aDNA can be so difficult to work with.

Fast Facts

You may recognize the basic structure of DNA: two strands arranged in a double-helix pattern with individual bases forming rungs, like a twisting ladder. These bases are adenine (A), thymine (T), guanine (G), and cytosine (C). They form complementary pairs on opposite ends of each ladder rung: adenine across from thymine and cytosine across from guanine. For example, if one side of the twisting ladder reads AATG, the opposing side will read TTAC. It is the sequence of these individual base pairs that makes up our genetic code, or our genome. Errors can occur when DNA is unwound to be replicated with one or more bases being deleted, substituted for others, or newly added. Such errors are called mutations and range from being essentially harmless to deadly.

The main function of DNA is to control the production, timing, and quantity of proteins produced by each cell. This process is called protein synthesis and comes in two main stages: transcription and translation. When the cell needs to produce a protein, an enzyme called RNA polymerase unzips the DNA double-helix and aids in pairing RNA (ribonucleic acid, a molecule related to DNA) bases to the complementary DNA sequence. This first step is called transcription, the product of which is a single-sided strand of RNA that exits the cell. This messenger RNA, or mRNA, goes into the cells cytoplasm to locate an organelle called a ribosome where the genetic information in the mRNA can be translated into a protein. The process of translation involves another kind of RNA, transfer RNA or tRNA, binding to the base sequences on the mRNA. tRNA is carrying amino acids, molecules that will make up the final protein, binding in sequence to create an amino acid chain. This amino acid chain will then twist and fold into the final protein.

Base pairs are arranged in groups of three, or codons, on the mRNA and tRNA, Each codon codes for a single amino acid. Each individual amino acid can be coded for by more than one codon. For example, both AAA and AAG code for the same amino acid lysine. Therefore, a mutation changing the last A to a G will be functionally meaningless. This is known as a silent, or synonymous change. If that last A in the codon mutated to a C, however, the codon AAC codes for asparagine, a different amino acid. This new amino acid could lead to the formation of a completely new protein or make the amino acid chain unable to form a protein at all. This is known as a nonsynonymous change. Nonsynonymous changes are the basis for diversity within a gene pool on which evolution acts.

The total DNA sequence is made up of base pairs, but not all sequences of base pairs serve the same function. Not all parts of the DNA sequence directly code for protein. Base pair sequences within DNA can be split into exons, sequences that directly code for proteins, and introns, sequences that do not directly code for a specific protein. The exon portion of our genome is collectively called the exome, and accounts for only about 1% of our total DNA. Exons and introns together form genes, sequences that code for a protein. On average there are 8.8 exons and 7.8 introns in each gene. The noncoding, or intron, parts of DNA used to be called junk DNA, random or repeating sequences that did not seem to code for anything. Recent research has shown that the majority of the genome does serve a function even if not coding for protein synthesis. These intron sequences can help regulate when genes are turned on or off, control how DNA winds itself to form chromosomes, be remnant clues of an organisms evolutionary history, or serve other noncoding functions.

Most of our total genome is made of up nuclear DNA, or the genetic material located in the nucleus of a cell. This DNA forms chromosomes, X-shaped bundles of DNA, that separate during cell division. Homo sapiens have 23 pairs of chromosomes. Nuclear DNA is directly inherited from both parents with 50% each coming from an organisms biological male and female parents. Therefore, both parents lineages are represented by nuclear DNA with one exception. One of those pairs of chromosomes are called sex chromosomes. Everyone gets some combination of X (male female parent) and Y (male parent only) chromosomes that determine an organisms biological sex. These combinations can come in a variety of possible alternatives outside of XX and XY including XXY, X, and others. Because the Y chromosome is only inherited from a biological male parent, the sequence of the Y chromosome can be used to trace patrilineal ancestry.

DNA is also found in the mitochondria, an organelle colloquially referred to as the powerhouse of the cell. This mitochondrial DNA or mtDNA is much smaller than the nuclear genome, only composing about 37 genes. mtDNA is only inherited from an organisms biological female parent and can be used to trace matrilineal ancestry. Because both Y-chromosome DNA and mtDNA are smaller and inherited form only one parent, thus less subject to mutations and changes, they are more useful in tracing lineages through deep time. However, they pale in comparison to the entire nuclear genome in terms of size and available base sequences to analyze.

Fast Facts

Recall that DNA is made up of base pair sequences that are chemically bonded to the sides of the double-helix structure forming a sort of twisting ladder. As an organic molecule, the component parts of that twisting ladder are subject to degradation over time. Without the functioning cells of a living organism to fix these issues and make new DNA, DNA can degrade into meaningless components somewhat rapidly. While DNA is abundant and readily extracted in living organisms (you can even do your own at-home experiment to extract DNA! https://learn.genetics.utah.edu/content/labs/extraction/howto/) finding useable DNA in extinct organisms gets harder and harder the further back in time that organism died.

The record for the oldest DNA extracted used to go to an ancient horse, dating to around 500,000-700,000 years old (Miller and Lambert 2013). However, in 2021 this was blown out of the water with the announcement of mammoth DNA extracted from specimens over 1 million years old found in eastern Siberian permafrost, permanently frozen ground (van der Valk et al., 2021). These cases of extreme DNA preservation are rare and share a few important factors in common: the specimens are found in very cold, very dry environments, typically buried in permafrost or frozen in caves. The oldest hominin DNA recovered comes from a Neanderthal around 400,000 years old (Meyer et al. 2016), near the beginnings of the Neanderthal species. Finding older DNA in other hominins is unlikely as for most of our evolutionary history hominins lived in the warm, sometimes wet, tropics and subtropics of Africa and Asia where DNA does not preserve well.

When scientists are lucky enough to find a specimen that may preserve aDNA, they must take the utmost care to extract it in such a way as to preserve it and prevent contamination. Just because aDNA is preserved does not mean it is preserved perfectly; it still decomposes and degrades over time, just at a slower rate in cool, dry environments. Because of this, there is always going to be much less DNA from the old organism than there is in even the loose hair and skin cells from the scientists excavating it. Because of this, there are stringent guidelines in place for managing aDNA extraction in the field that scientists must follow (Gilbert et al., 2005 for example). In hominins, this is even more important since human and Neanderthal DNA are so similar that most sequences will be indistinguishable from each other.

Challenges in Sequencing aDNA

When aDNA does preserve, is often highly fragmented, degraded, and has undergone substantial changes from how the DNA appeared in a living organism. In order to sequence the DNA, or read the base pair coding, these damages and changes have to be taken into account and fixed wherever possible. aDNA comes in tattered, fragmented strands that are difficult to read and analyze. One way scientists deal with this is to amplify the aDNA that is preserved so that it is more readily accessible via a process known as polymerase chain reaction (PCR). PCR essentially forces the DNA to self-replicate exponentially so that there are many more copies of the same sequence to compare. Due to the exponential duplication, it is especially important for there to be no contamination of modern DNA in the sample. The amplified sequences can then be compared and aligned to create longer sequences, up to and including entire genes and genomes.

The component parts of DNA also degrade over time. One example is deamination, when cytosine bases degrade into a thymine molecule and guanine bases degrade into an adenine. This could potentially lead to misidentification of sequences, but scientists have developed chemical methods to reverse these changes. Comparison between closely related genomes, such as humans and Neanderthals, can also identify where deamination may have occurred in sequences that do not vary between the two species. Deamination can actually be useful because it is an excellent indicator that the sample you are looking at is genuine aDNA and not DNA from a contaminated source.

aDNA extraction and sequencing is inherently destructive and requires destroying at least part of the fossil sample you are attempting to extract DNA from. That is something that paleoanthropologists want to avoid whenever possible! To rationalize destroying a fossil to extract aDNA, it is common practice to first test this technique other non-hominin fossils from the same site to first confirm that DNA is accessible and in reasonable quantities/qualities. Testing aDNA form other sources, such as a cave bear at a Neanderthal site, can also identify any potential sources of contamination more easily since cave bears and humans are more distantly related.

Fast Facts:

DNA preserves best in cold, dry environments

aDNA must be destructively sampled, amplified, and analyzed prior to looking at the sequence

Neanderthal skull La Ferrassie 1 from La Ferrassie, France

The first analysis of any Neanderthal DNA was mitochondrial DNA (mtDNA), published in 1997. The sample was taken from the first Neanderthal fossil discovered, found in Feldhofer Cave in the Neander Valley in Germany. A small sample of bone was ground up to extract mtDNA, which was then replicated and analyzed.

Researchers compared the Neanderthal mtDNA to modern human and chimpanzee mtDNA sequences and found that the Neanderthal mtDNA sequences were substantially different from both (Krings et al. 1997, 1999). Most human sequences differ from each other by an average of 8.0 substitutions, while the human and chimpanzee sequences differ by about 55.0 substitutions. The Neanderthal and modern human sequences differed by approximately 27.2 substitutions. Using this mtDNA information, the last common ancestor of Neanderthals and modern humans dates to approximately 550,000 to 690,000 years ago, which is about four times older than the modern human mtDNA pool. Since this study was completed, many more samples of Neanderthal mtDNA have been replicated and studied.

Sequencing the Complete Neanderthal Mitochondrial Genome

After successfully sequencing large amounts of mtDNA, a team led by Svante Pbo from the Max Planck Institute reported the first complete mitochondrial DNA (mtDNA) sequence for a Neanderthal (Green et al. 2008). The sample was taken from a 38,000 year old Neanderthal from Vindija Cave, Croatia. The complete mtDNA sequence allowed researchers to compare this Neanderthal mtDNA to modern human mtDNA to see if any modern humans carried the mtDNA from a related group to the Neanderthal group.

Later, Svante Pbos lab sequenced the entire mitochondrial genome of five more Neanderthals (Briggs et al. 2009). Sequences came from two individuals from the Neander Valley in Germany and one each from Mezmaiskaya Cave in Russia, El Sidrn Cave in Spain, and Vindija Cave in Croatia. Though the Neanderthal samples came from a wide geographic area, the Neanderthal mtDNA sequences were not particularly genetically diverse. The most divergent Neanderthal sequence came from the Mezmaiskaya Cave Neanderthal from Russia, which the oldest and eastern-most specimen. Further analysis and sampling or more individuals has led researchers to believe that this diversity was more closely related to age than it was to population-wide variance (Briggs et al. 2009).On average, Neanderthal mtDNA genomes differ from each other by 20.4 bases and are only 1/3 as diverse as modern humans (Briggs et al. 2009). The low diversity might signal a small population size.

There is evidence that some other hominin contributed to the Neanderthal mtDNA gene pool around 270,000 years ago (Posth et al., 2017). A femur discovered in Germany had its mtDNA genotyped and it was found that there was introgression from a non-Neanderthal African hominin, either Homo sapiens or closely related to us, around 270,000 years ago. This mitochondrial genome is also highly divergent from the Neanderthal average discussed previously, indicating that Neanderthals may have been much more genetically diverse in their more distant past.

As for Neanderthal introgression into the modern human mtDNA genome, it is possible that the evidence of such admixture is obscured for a variety of reasons (Wang et al 2013). Primary among these reasons is sample size: There are to date only a dozen or so Neanderthal mtDNA sequences that have been sampled. Because the current sample of Neanderthal mtDNA is so small, it is possible that researchers simply have not yet found the mtDNA in Neanderthals that corresponds to that of modern humans.

Map of Neanderthal extent througout Eurasia.

There have been many efforts to sequence Neanderthal nuclear genes, with an eventual goal to sequence as much of the Neanderthal genome as possible. In 2014, the complete genome of a Neanderthal from the Altai Mountains in Siberia was published (Prufer et al., 2014). This female individuals genome showed that her parents were likely half siblings and that her genetic line showed evidence of high rates of incestuous pairings. It is unclear whether this is due to her living in a small and isolated population or if other factors may have influenced the lineages inbreeding. Their analysis also showed that this individual was closely related to both modern humans and the Denisovans, another ancient human population. By their analysis, there was only a very small margin by which Neanderthal and Denisovan DNA differed exclusively from modern humans.

Fast Facts:

Neanderthals are genetically distinct from modern humans, but are more closely related to us than chimpanzees are

The Neanderthal and modern human lineages diverged about 550,000 years ago

So far, we have no evidence of Neanderthal mtDNA lineages in modern humans

Neanderthals were not as genetically diverse as modern humans were at the same period, indicating that Neanderthals had a smaller population size

Neanderthal nuclear DNA shows further evidence of small population sizes, including genetic evidence of incest

As technology improves, researchers are able to detect and analyze older and more fragmentary samples of DNA

Scientists have also found DNA from another extinct hominin population: the Denisovans. The first remains of the species found were a single fragment of a phalanx (finger bone) and two teeth, all of which date back to about 40,000 years ago (Reich et al., 2010). Since then, a Denisovan mandible, or lower jaw, has been found in Tibet (Chen et al., 2019) and a Denisovan molar has been found in Laos (Demeter et al., 2022). Other fossil hominins, such as the Homo longi remains from northern China (Ji et al., 2021) and the Dali cranium from northwestern China may belong to the Denisovans, but without comparable fossils and genetics it is difficult to know for sure.

This species is the first fossil hominin identified as a new species based on its DNA alone. Denisovans are close relatives of both modern humans and Neanderthals, and likely diverged from these lineages around 300,000 to 400,000 years ago; they are more closely related to Neanderthals than to modern humans. You might be wondering: If we have the DNA of Denisovans, why cant we compare them to modern humans like we do Neanderthals? Why isnt this article about them too? The answer is simply that we dont have enough DNA and fossils to make a comparison. The single-digit specimen pool of Denisovans found to date is statistically far too small a data set to derive any meaningful comparisons. Until we find more Denisovan material, we cannot begin to understand their full genome in the way that we can study Neanderthals. The lack of more (and more morphologically diagnostic) Denisovan fossils is the reason why scientists have not yet given them a species name.

Fast Facts:

Homo sapiens and Homo neanderthalensis are different species, yet you are reading this webpage about them potentially interbreeding with each other. So, what does that mean, exactly? Modern humans and Neanderthals lived in separate regions evolving along separate evolutionary lineages for hundreds of thousands of years. Even so, Neanderthals are still our closest currently known relative. Because of that evolutionary proximity, despite being recognized as different species, it is still possible that members of our two species exchanged genetic information. This exchange of DNA is called introgression, or interbreeding.

When looking for evidence of interbreeding, scientists do not search billions and billions of base pairs. Instead, there are specific regions of the genomes that are known to be highly variable in modern humans along with several million single nucleotide polymorphisms (SNPs), where the given base at a single location can vary among people. The difference between the total genome and these specific regions/sites can lead to some confusion. In terms of the total genome, humans and chimpanzees are 98-99% similar. Yet, it is possible for individuals to have up to 4% Neanderthal DNA. That difference is accounted for in that 4% of the highly variable genome is inherited from a Neanderthal source, not 4% of the entire genome. If one was to look at the modern human genome as a whole, at least 98-99% is the same, inherited from our common ancestor with Neanderthals.

Neanderthals are known to contribute up to 1-4% of the genomes of non-African modern humans, depending on what region of the word your ancestors come from, and modern humans who lived about 40,000 years ago have been found to have up to 6-9% Neanderthal DNA (Fu et al., 2015). Because Neanderthals likely evolve outside of Africa (no Neanderthal fossils have been found in Africa to date) it was thought that there would be no trace of Neanderthal DNA in African modern humans. However, a study in 2020 demonstrated that there is Neanderthal DNA in all African Homo sapiens (Chen at el., 2020). This is a good indicator of how human migration out of Africa worked: that Homo sapiens did not leave Africa in one or more major dispersals, but that there was gene flow back and forth over time that brough Neanderthal DNA into Africa.

The evidence we have of Neanderthal-modern human interbreeding sheds light on the expansion of modern humans out of Africa. These new discoveries refute many previous hypotheses in which anatomically modern humans replaced archaic hominins, like Neanderthals, without any interbreeding. However, even with some interbreeding between modern humans and now-extinct hominins, most of our genome still derives from Africa.

For many years, the only evidence of human-Neanderthal hybridization existed within modern human genes. However, in 2016 researchers published a new set of Neanderthal DNA sequences from Altai Cave in Siberia, as well as from Spain and Croatia, that show evidence of human-Neanderthal interbreeding as far back as 100,000 years ago -- farther back than many previous estimates of humans migration out of Africa (Kuhlwilm et al., 2016). Their findings are the first to show human gene flow into the Neanderthal genome as opposed to Neanderthal DNA into the human genome. These data tells us that not only were human-Neanderthal interbreeding events more frequent than previously thought, but also that an early migration of humans did in fact leave Africa before the population that survived and gave rise to all contemporary non-African modern humans.

We previously mentioned the lack of genetic contributions by Neanderthals into the modern human mtDNA gene pool. As we have shown that Neanderthal-human interbreeding did occur, why wouldnt we find their DNA in our mtDNA as well as our nuclear DNA? There are several potential explanations for this. It is possible that there were at one point modern humans who possessed the Neanderthal mtDNA, but that their lineages died out. It is also highly possible that Neanderthals did not contribute to the mtDNA genome by virtue of the nature of human-Neanderthal admixture. While we know that humans and Neanderthals bred, we have no way of knowing what the possible social or cultural contexts for such breeding would have been.

Because mtDNA is passed down exclusively from mother to offspring, if Neanderthal males were the only ones contributing to the human genome, their contributions would not be present in the mtDNA line. It is also possible that while interbreeding between Neanderthal males and human females could have produced fertile offspring, interbreeding between Neanderthal females and modern human males might not have produced fertile offspring, which would mean that the Neanderthal mtDNA could not be passed down. Finally, it is possible that modern humans do carry at least one mtDNA lineage that Neanderthals contributed to our genome, but that we have not yet sequenced that lineage in either modern humans or in Neanderthals. Any of these explanations could underlie the lack of Neanderthal mtDNA in modern human populations.

Given that scientists have DNA evidence of another hominin species, the Denisovans, is there any evidence for interbreeding among all three species? Yes! Comparison of the Denisovan genome to various modern human populations shows up to 4-6% contribution from Denisovans in non-African modern human populations. This concentration is highest in people from Papua New Guinea and Oceania. It makes sense that interbreeding would appear in these Southeast Asian and Pacific Island communities, as their ancestors migrated from mainland Asia where Denisovan fossils have been found. There is also substantial evidence for Denisovan-Neanderthal interbreeding, including one juvenile female that appears to be a fist generation hybrid of a Neanderthal female parent and Denisovan male parent (Slon et al., 2018). Finding more Denisovan fossils will hopefully mean developing a more complete picture of Denisovan genetics so that scientists can explore these interactions in more detail.

Fast Facts:

Homo neanderthalensis, adult male. Reconstruction based on Shanidar 1 (artist, John Gurche)

While much of the genetic diversity discussed above came from inactive, noncoding, or otherwise evolutionarily neutral segments of the genome, there are many sites that show clear evidence of selective pressure on the variations between modern humans and Neanderthals. Researchers found 78 loci at which Neanderthals had an ancestral state and modern humans had a newer, derived state (Green et al 2010). Five of these genes had more than one sequence change that affected the protein structure. These proteins include SPAG17, which is involved in the movement of sperm, PCD16, which may be involved in wound healing, TTF1, which is involved in ribosomal gene transcription, and RPTN, which is found in the skin, hair and sweat glands. Other changes may not alter the sequence of the gene itself, but alter the factors that control that genes replication in the cell, changing its expression secondarily.

This tells us that these traits were selected for in the evolution of modern humans and were possibly selected against in Neanderthals. Though some of the genomic areas that may have been positively selected for in modern humans may have coded for structural or regulatory regions, others may have been associated with energy metabolism, cognitive development, and the morphology of the head and upper body. These are just a few of the areas where we have non-genetic evidence of differentiation between modern humans and Neanderthals.

While the study of DNA reveals aspects of relatedness and lineage, its primary function is, of course, to control the production of proteins that regulate an organisms biology. Each gene may have a variety of genotypes, which are the variances that can occur within the site of a particular gene. Each genotype codes for a respective phenotype, which is the physical expression of that gene. When we study Neanderthal DNA, we can examine the genotypes at loci of known function and can infer what phenotype the Neanderthals mutations may have expressed in life. Below, explore several examples of Neanderthal genes and the possible phenotypes that they would have displayed.

Ancient DNA has been used to reconstruct aspects of Neanderthal appearance. A fragment of the gene for the melanocortin 1 receptor (MRC1) was sequenced using DNA from two Neanderthal specimens from Spain and Italy: El Sidrn 1252 and Monte Lessini (Lalueza-Fox et al. 2007). MC1Ris a receptor gene that controls the production of melanin, the protein responsible for pigmentation of the hair and skin. Neanderthals had a mutation in this receptor gene which changed an amino acid, making the resulting protein less efficient and likely creating a phenotype of red hair and pale skin. (Thereconstruction below of a male Neanderthal by John Gurche features pale skin, but not red hair) .How do we know what this phenotype would have looked like? Modern humans display similar mutations of MC1R, and people who have two copies of this mutation have red hair and pale skin. However, no modern human has the exact mutation that Neanderthals had, which means that both Neanderthals and humans evolved this phenotype independent of each other.

If modern humans and Neanderthals living in Europe at the same time period both evolved this reduction of pigmentation, it is likely that there was an advantage to this trait. One hypothesis to explain this adaptations advantage involves the production of vitamin D. Our bodies primarily synthesize our supply of vitamin D, rather than relying on vitamin D from food sources. Vitamin D is synthesized when the suns UV rays penetrate our skin. Darker skin makes it harder for sunlight to penetrate the outermost layers and stimulate the production of vitamin D, and while people living in areas of high sun exposure will still get plenty of vitamin D, people who live far from the equator are not exposed to as much sunlight and need to optimize their exposure to the sun. Therefore, it would be beneficial for populations in colder climates to have paler skin so that they can create enough vitamin D even with less sun exposure.

The FOXP2 gene is involved in speech and language (Lai et al. 2001). Mutations in the FOXP2 gene sequence in modern humans led to problems with speech, and oral and facial muscle control. The human FOXP2 gene is on a haplotype that was subject to a strong selective sweep. A haplotype is a set of alleles that are inherited together on the same chromosome, and a selective sweep is a reduction or elimination of variation among the nucleotides near a particular DNA mutation. Modern humans and Neanderthals share two changes in FOXP2 compared with the sequence in chimpanzees (Krause et al. 2007). How did this FOXP2 variant come to be found in both Neanderthals and modern humans? One scenario is that it could have been transferred between species via gene flow. Another possibility is that the derived FOXP2 was present in the ancestor of both modern humans and Neanderthals, and that the gene was so heavily favored that it proliferated in both populations. A third scenario, which the authors think is most likely, is that the changes and selective sweep occurred before the divergence between the populations. While it can be tempting to infer that the presence of the same haplotype in Neanderthals and humans means that Neanderthals had similar complex language capabilities, there is not yet enough evidence for such a conclusion. Neanderthals may also have their own unique derived characteristics in the FOXP2 gene that were not tested for in this study. Genes are just one factor of many in the development of language.

The gene that produces the ABO blood system is polymorphic in humans, meaning that there are more than two possible expressions of this gene. The genes for both A and B blood types are dominant, and O type is recessive, meaning that people who are type A or B can have genotypes of either AA or AO (or BB and BO) and still be A (or B) blood type, but to have type O blood one must have a genotype of OO. Various selection factors may favor different alleles, leading to the maintenance of distinct blood groups in modern human populations. Though chimpanzees also have different blood groups, they are not the same as human blood types. While the mutation that causes the human B blood group arose around 3.5 Ma, the O group mutation dates to around 1.15 Ma. When scientists tested whether Neanderthals had the O blood group they found that two Neanderthal specimens from Spain probably had the O blood type, though there is the possibility that they were OA or OB (Lalueza-Fox et al. 2008). Though the O allele was likely to have already appeared before the split between humans and Neanderthals, it could also have arisen in the Neanderthal genome via gene flow from modern humans.

The ability to taste bitter substances is controlled by a gene, TAS2R38. Some individuals are able to taste bitter substances, while others have a different version of the gene that does not allow them to taste bitter foods. Possession of two copies of the positive tasting allele gives the individual greater perception of bitter tastes than the heterozygous state in which individuals have one tasting allele and one non-tasting allele. Two copies of a non-tasting allele leads to inability to taste bitter substances.

When scientists sequenced the DNA of a Neanderthal from El Sidrn, Spain for the TAS23R38 gene, they found that this individual was heterozygous and thus was able to perceive bitter taste - although not as strongly as a homozygous individual with two copies of the tasting allele would be able to (Lalueza-Fox et al. 2009). Both of these haplotypes are still present in modern people, and since the Neanderthal sequenced was heterozygous, the two alleles (tasting and non-tasting) were probably both present in the common ancestor of Neanderthals and modern humans. Though chimpanzees also vary in their ability to taste bitterness, their abilities are controlled by different alleles than those found in humans, indicating that non-tasting alleles evolved separately in the hominin lineage.

The microcephalin gene relates to brain size during development. A mutation in the microcephalin gene, MCPH1, is a common cause of microcephaly. Mutations in microcephalin cause the brain to be 3 to 4 times smaller in size. A variant of MCPH1, haplogroup D, may have been positively selected for in modern humans and may also have come from an interbreeding event with an archaic population (Evans et al. 2006). All of the haplogroup D variants come from a single copy that appeared in modern humans around 37,000 years ago. However, haplogroup D itself came from a lineage that had diverged from the lineage that led to modern humans around 1.1 million years ago. Although there was speculation that the Neanderthals were the source of the microcephalin haplogroup D (Evans et al. 2006), Neanderthal DNA sequenced does not contain the microcephalin haplogroup D (Green et al. 2010).

While changes to the genome can directly affect the phenotypes displayed in an organism, altering the timing mechanism of protein production can cause very similar effects. MicroRNA (miRNA) is one such mechanism: a cell uses miRNA to suppress the expression of a gene until that gene becomes necessary. One miRNA can target multiple genes by binding its seed region to messenger RNA that would otherwise have carried that information to the ribosome to be transcribed into proteins, preventing transcription from taking place. In hominins, one particular miRNA called miR-1304 is exhibited in both an ancestral and derived condition. The derived condition has a mutation at the seed region which allows it to target more mRNA segments but less effectively. This means that in the derived state, some genes will be more strongly expressed due to a lack of suppression. One such trait is the production of enamelin and amelotin proteins, both used in dental formation during development. The suppression of production in Neanderthals, and subsequent lack of suppression in modern humans, could be a contributing factor to some of the morphological differences between Neanderthal and modern human dentition.

Research shows that Neanderthal DNA has contributed to our immune systems today. A study of the human genome found a surprising incursion of Neanderthal DNA into the modern human genome, specifically within the region that codes for our immune response to pathogens (Dannemann et al 2016). These particular Neanderthal genes would have been useful for the modern humans arriving in Europe whose immune systems had never encountered the pathogens within Europe and would be vulnerable to them, unlike the Neanderthals who had built up generations of resistance against these diseases. When humans and Neanderthals interbred, they passed this genetic resistance to diseases on to their offspring, allowing them a better chance at survival than those without this additional resistance to disease. The evidence of this genetic resistance shows that there have been at least three incursions of nonhuman DNA into the genes for immune response, two coming from Neanderthals and one from our poorly understood evolutionary cousins, the Denisovans.

While many of the genes that we retain for generations are either beneficial or neutral, there are some that have become deleterious in our new, modern lives. There are several genes that our Neanderthal relatives have contributed to our genome that were once beneficial in the past but can now cause health-related problems (Simonti et al 2016). One of these genes allows our blood to coagulate (or clot) quickly, a useful adaptation in creatures who were often injured while hunting. However, in modern people who live longer lives, this same trait of quick-clotting blood can cause harmful blood clots to form in the body later in life. Researchers found another gene that can cause depression and other neurological disorders and is triggered by disturbances in circadian rhythms. Since it is unlikely that Neanderthals experienced such disturbances to their natural sleep cycles, they may never have expressed this gene, but in modern humans who can control our climate and for whom our lifestyle often disrupts our circadian rhythms, this gene is expressed more frequently.

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Lopez-Valenzuela M., Ramrez O., Rosas A., Garca-Vargas S., de la Rasilla M., Lalueza-Fox C., Espinosa-Parrilla Y., 2012. An ancestral miR-1304 allele present in Neanderthals regulates genes involved in enamel formation and could explain dental differences with modern humans. Molecular biology and evolution. mss023.

Mackelprang, R., Rubin, E.M., 2008. New tricks with old bones. Science 321: 221-212.

Meyer M., Arsuaga J.L., De Filippo C., Nagel S., Aximu-Petri A., Nickel B., Martnez I., Gracia A., de Castro J.M.B., Carbonell E., Viola B., Kelso J., Prfer K., Pbo S. 2016. Nuclear DNA sequences from the Middle Pleistocene Sima de los Huesos hominins. Nature 531, 504507.

Millar CD., Lambert DM., 2013. Ancient DNA: Towards a million-year-old genome. Nature 499, 3435.

Noonan, J.P., Coop, G., Kudaravalli, S., Smith, D., Krause, J., Alessi, J. Chen, F., Platt, D., Pbo, S., Pritchard, J.K., Rubin, E.M., 2006. Sequencing and analysis of Neanderthal genomic DNA. Science 314: 1113-1118.

Pennisi, E., 2009. Sequencing Neandertal mitochondrial genomes by the half-dozen. Science325: 252.

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Biological Influences on Human Behavior: Genetics & Environment

Posted: at 11:29 pm

Twin Studies

Because identical twins have the same DNA, they are often used to help scientists understand which behaviors may be determined by genetics and which may be influenced by our environment. As exact copies of each other, sets of identical twins can be compared with other sets of identical twins to see how the environment affects their individual behaviors.

For example, scientists may compare identical twins that were separated at birth to identical twins that grew up in the same household. This allows them to examine how different environments influence the same genetic makeup. Other studies may compare identical twins that were raised together to fraternal twins, who, like normal siblings, only share about half of their DNA.

While there are no definitive answers, what these studies do generally show is that neither genetics nor the environment is more important than the other when it comes to some of the more complex behaviors. For example, genetic makeup accounts for about half of the variation we see in human personalities and intelligence. But this means that the other half of the variation we see in people comes from their environmental surroundings. So for some behaviors, both our genes and the environment play an equally important role.

It may be tempting to think that genetically influenced behaviors come from specific genes. However, just because a behavior has a genetic basis doesn't mean that there is a gene that 'controls' that trait. Genes don't actually control behaviors, they just facilitate certain reactions to our environment.

For example, many animals in nature are monogamous, which is a genetically influenced behavior. But there is no specific gene that causes monogamous behavior in these animals. Instead, certain genes produce proteins with receptors that respond positively to the scent of their mate. And it's this positive response that began with genetics and then is triggered by the environment that keeps the couple close to each other.

Humans have similar responses to other people; we like being around others for a reason! Human brains are genetically programmed to respond to social recognition and bonding with others. We are a very social species and we form complex relationships with friends and family. However, what we don't know much about is how our brains do this. Hormones and hormone receptors are major players, but the jury is still out on just how those mechanisms are involved in forming relationships and bonding with others.

One thing that separates us from other animals is how much longer it takes us to develop after we're born. We spend a very long time learning how to talk, walk, and interact with the world around us. During this time we are involved with many different people: our parents, siblings, and schoolmates, just to name a few. This allows us to be involved in a variety of complex social networks, which scientists think may have led to our unique success in the Animal Kingdom. As you can see, even from very early in life, both our environments and our genetics are important factors in determining how we behave.

Human behaviors are complex. Our social networks, personal interactions, and relationships are determined by both our genes and the world around us. Some behaviors may have a genetic basis, but genes do not actually control behavior. Rather, our genetic makeup influences how we interact with and respond to our surroundings.

While we do not fully understand the mechanisms behind human behaviors, we do have some insight into whether certain behaviors are influenced more by our genes or our environment. Twin studies are helpful for this because identical twins have the same DNA. Comparing sets of identical twins in different environments allows scientists to more closely examine how genetics and the environment shape us as individuals.

After completing this lesson, you should be able to:

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The Missing Plan for Alien First Contact to Pro-and-Anti-UFO Factions in U.S. Government (Planet Earth Report) – The Daily Galaxy –Great Discoveries…

Posted: November 8, 2022 at 11:20 pm

The Missing Plan for Alien First Contact to Pro-and-Anti-UFO Factions in U.S. Government (Planet Earth Report) The Daily Galaxy --Great Discoveries Channel

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The Bill of Rights: A Transcription | National Archives

Posted: November 7, 2022 at 10:39 am

Note: The following text is a transcription of the enrolled original of the Joint Resolution of Congress proposing the Bill of Rights, which is on permanent display in the Rotunda at the National Archives Museum. The spelling and punctuation reflects the original.

On September 25, 1789, the First Congress of the United States proposed 12 amendments to the Constitution. The 1789 Joint Resolution of Congress proposing the amendments is on display in the Rotunda in the National Archives Museum. Ten of the proposed 12 amendments were ratified by three-fourths of the state legislatures on December 15, 1791. The ratified Articles (Articles 312) constitute the first 10 amendments of the Constitution, or the U.S. Bill of Rights. In 1992, 203 years after it was proposed, Article 2 was ratified as the 27th Amendment to the Constitution. Article 1 was never ratified.

Congress of the United States begun and held at the City of New-York, on Wednesday the fourth of March, one thousand seven hundred and eighty nine.

THE Conventions of a number of the States, having at the time of their adopting the Constitution, expressed a desire, in order to prevent misconstruction or abuse of its powers, that further declaratory and restrictive clauses should be added: And as extending the ground of public confidence in the Government, will best ensure the beneficent ends of its institution.

RESOLVED by the Senate and House of Representatives of the United States of America, in Congress assembled, two thirds of both Houses concurring, that the following Articles be proposed to the Legislatures of the several States, as amendments to the Constitution of the United States, all, or any of which Articles, when ratified by three fourths of the said Legislatures, to be valid to all intents and purposes, as part of the said Constitution; viz.

ARTICLES in addition to, and Amendment of the Constitution of the United States of America, proposed by Congress, and ratified by the Legislatures of the several States, pursuant to the fifth Article of the original Constitution.

Article the first... After the first enumeration required by the first article of the Constitution, there shall be one Representative for every thirty thousand, until the number shall amount to one hundred, after which the proportion shall be so regulated by Congress, that there shall be not less than one hundred Representatives, nor less than one Representative for every forty thousand persons, until the number of Representatives shall amount to two hundred; after which the proportion shall be so regulated by Congress, that there shall not be less than two hundred Representatives, nor more than one Representative for every fifty thousand persons.

Article the second... No law, varying the compensation for the services of the Senators and Representatives, shall take effect, until an election of Representatives shall have intervened.

Article the third... Congress shall make no law respecting an establishment of religion, or prohibiting the free exercise thereof; or abridging the freedom of speech, or of the press; or the right of the people peaceably to assemble, and to petition the Government for a redress of grievances.

Article the fourth... A well regulated Militia, being necessary to the security of a free State, the right of the people to keep and bear Arms, shall not be infringed.

Article the fifth... No Soldier shall, in time of peace be quartered in any house, without the consent of the Owner, nor in time of war, but in a manner to be prescribed by law.

Article the sixth... The right of the people to be secure in their persons, houses, papers, and effects, against unreasonable searches and seizures, shall not be violated, and no Warrants shall issue, but upon probable cause, supported by Oath or affirmation, and particularly describing the place to be searched, and the persons or things to be seized.

Article the seventh... No person shall be held to answer for a capital, or otherwise infamous crime, unless on a presentment or indictment of a Grand Jury, except in cases arising in the land or naval forces, or in the Militia, when in actual service in time of War or public danger; nor shall any person be subject for the same offence to be twice put in jeopardy of life or limb; nor shall be compelled in any criminal case to be a witness against himself, nor be deprived of life, liberty, or property, without due process of law; nor shall private property be taken for public use, without just compensation.

Article the eighth... In all criminal prosecutions, the accused shall enjoy the right to a speedy and public trial, by an impartial jury of the State and district wherein the crime shall have been committed, which district shall have been previously ascertained by law, and to be informed of the nature and cause of the accusation; to be confronted with the witnesses against him; to have compulsory process for obtaining witnesses in his favor, and to have the Assistance of Counsel for his defence.

Article the ninth... In suits at common law, where the value in controversy shall exceed twenty dollars, the right of trial by jury shall be preserved, and no fact tried by a jury, shall be otherwise re-examined in any Court of the United States, than according to the rules of the common law.

Article the tenth... Excessive bail shall not be required, nor excessive fines imposed, nor cruel and unusual punishments inflicted.

Article the eleventh... The enumeration in the Constitution, of certain rights, shall not be construed to deny or disparage others retained by the people.

Article the twelfth... The powers not delegated to the United States by the Constitution, nor prohibited by it to the States, are reserved to the States respectively, or to the people.

ATTEST,

Frederick Augustus Muhlenberg, Speaker of the House of RepresentativesJohn Adams, Vice-President of the United States, and President of the SenateJohn Beckley, Clerk of the House of Representatives.Sam. A Otis Secretary of the Senate

Amendments 11-27

Note: The following text is a transcription of the first ten amendments to the Constitution in their original form. These amendments were ratified December 15, 1791, and form what is known as the "Bill of Rights."

Congress shall make no law respecting an establishment of religion, or prohibiting the free exercise thereof; or abridging the freedom of speech, or of the press; or the right of the people peaceably to assemble, and to petition the Government for a redress of grievances.

A well regulated Militia, being necessary to the security of a free State, the right of the people to keep and bear Arms, shall not be infringed.

No Soldier shall, in time of peace be quartered in any house, without the consent of the Owner, nor in time of war, but in a manner to be prescribed by law.

The right of the people to be secure in their persons, houses, papers, and effects, against unreasonable searches and seizures, shall not be violated, and no Warrants shall issue, but upon probable cause, supported by Oath or affirmation, and particularly describing the place to be searched, and the persons or things to be seized.

No person shall be held to answer for a capital, or otherwise infamous crime, unless on a presentment or indictment of a Grand Jury, except in cases arising in the land or naval forces, or in the Militia, when in actual service in time of War or public danger; nor shall any person be subject for the same offence to be twice put in jeopardy of life or limb; nor shall be compelled in any criminal case to be a witness against himself, nor be deprived of life, liberty, or property, without due process of law; nor shall private property be taken for public use, without just compensation.

In all criminal prosecutions, the accused shall enjoy the right to a speedy and public trial, by an impartial jury of the State and district wherein the crime shall have been committed, which district shall have been previously ascertained by law, and to be informed of the nature and cause of the accusation; to be confronted with the witnesses against him; to have compulsory process for obtaining witnesses in his favor, and to have the Assistance of Counsel for his defence.

In Suits at common law, where the value in controversy shall exceed twenty dollars, the right of trial by jury shall be preserved, and no fact tried by a jury, shall be otherwise re-examined in any Court of the United States, than according to the rules of the common law.

Excessive bail shall not be required, nor excessive fines imposed, nor cruel and unusual punishments inflicted.

The enumeration in the Constitution, of certain rights, shall not be construed to deny or disparage others retained by the people.

The powers not delegated to the United States by the Constitution, nor prohibited by it to the States, are reserved to the States respectively, or to the people.

Amendments 11-27

Note: The capitalization and punctuation in this version is from the enrolled original of the Joint Resolution of Congress proposing the Bill of Rights, which is on permanent display in the Rotunda of the National Archives Building, Washington, D.C.

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The Bill of Rights: A Transcription | National Archives

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‘Centre, states need to work together for a developed India’: FM Sitharaman on ‘Atmanirbhar Bharat’ – The Economic Times

Posted: at 10:39 am

'Centre, states need to work together for a developed India': FM Sitharaman on 'Atmanirbhar Bharat' The Economic Times

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Biden Signs Executive Order Designed to Unleash "Transhumanist Hell" on …

Posted: at 10:29 am

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Important article first published on September 19, 2022

***

If anyone needed proof that the powers pushing the levers behind the mindless moron who sits in the Oval Office are fully on board with the World Economic Forum/United Nations agenda of biomedical tyranny and transhumanism, look no further than the executive order that Joe Biden signed on Monday, September 12.

By quietly getting Bidens signature on this document, his handlers may have given us the most ominous sign yet that we stand on the threshold of a technocratic one-world beast system. Prepare to make your stand because its about to get much more intense.

This documents Orwellian title, Executive Order on Advancing Biotechnology and Biomanufacturing Innovation for a Sustainable, Safe, and Secure American Bioeconomy, will assure that its significance will fly right over the heads of 99 percent of the media, even the conservative media.

They will read it and yawn. I plead with everyone reading this article to please not make that same mistake.

Because of the arcane scientific language in which this document is written, even most of those who take the time to read and study it (I assure you Biden did not) will not fully grasp what is being ordered by the White House.

Thats where we strive to help.

Karen Kingston, a former Pfizer employee and current analyst for the pharmaceutical and medical-device industries, helps us decipher whats going on in this executive order.

Kingston stated in a Twitter post:

Let me read between the lines for America. Bidens Sept. 12, 2022, executive order declares that Americans must surrender all human rights that stand in the way of transhumanism. Clinical trial safety standards and informed consent will be eradicated as they stand in the way of universally unleashing gene-editing technologies needed to merge humans with A.I. In order to achieve the societal goals of the New World Order, crimes against humanity are not only legal, but mandatory. (emphasis added)

Here is one of the most disturbing excerpts from Bidens executive order:

We need to develop genetic engineering technologies and techniques to be able to write circuitry for cells and predictably program biology in the same way in which we write software and program computersincluding through computing tools and artificial intelligence

Patrick Wood, an economist and author of several books on technocracy, has been following the transhumanist and global technocracy movements for four decades. He told me that Kingston is not overstating the issue.

He said this E.O. is proof that the executive branch is now owned lock, stock and barrel by the biomedical/pharmaceutical industry. It will be Katy bar the door from here on out.

The transhumanists within Big Pharma have completely taken over government policy and taxpayer funds to promote their own anti-human agenda of hacking the software of life, Wood told me. It also clearly demonstrates who has the power, and who sets the policies in America.

The mRNA injections that have already gone into the bodies of at least 70 percent of adults in the U.S. (and a smaller percentage of its children) mark the gateway to transhumanism. We have been told this by Kingston as well as by the late Dr. Zev Zelenko and Dr. Robert Malone, a co-inventor of the mRNA platform.

LeoHohmann.com was one of the first sites to blow the whistle on Modernas former chief medical officer, Tal Zaks, who told the world straight up in December 2017 that We have hacked the software of life, and that this mRNA gene-editing biotechnology would be incorporated into vaccines to treat and prevent all manner of illnesses. Weve seen how well they work, with millions getting sick and tens of thousands dying after getting two or more doses of the Covid injections offered up by Moderna and Pfizer. With the FDA and CDC now totally on board, this mRNA technology is being included in scores of other vaccines, including flu shots.

The September 12 executive order was no doubt put in place as back up for the continued experimentation on the human population, and I expect the vaccine industry will exploit it to the max. Soon we will see the return of vax mandates, this time more ferociously policed and enforced than before.

This E.O. may also have been timed at least partly in anticipation of the new pandemic treaty that the Biden administration is hoping to get passed through the United Nations World Health Organization next year. This treaty will transfer sovereignty over matters of health emergencies from the national level to the WHO.

Wood said the E.O.s intended consequences is to push the frontier of genetic modification of all living things and especially humans. He believes this will ultimately spark the biggest public backlash in modern history.

Biden pledges not only funding but an all-of-government transformation to support this anti-human scheme from top to bottom, Wood writes. It also automatically blocks any agency or department from dissent.

Below are just a few of the highlights quoted directly from the document:

What this means is that human beings will be data mined for their most personal possession, their DNA and genomic properties, and the government will offer no protection.

It will actually be encouraged and seen as a green light for biomedical practitioners worldwide. It is the goal of the technocratic proprietors of Agenda 2030 to catalogue, map out, and monitor every living thing on earth.

This was spelled out in the early 2000s by the late researcher Rosa Koire and put into book form in 2011 with Behind the Green Mask: U.N. Agenda 21. Koire was a Democrat, but she understood that the takedown of America and indeed every nation of the formerly free world, would not be accomplished by the left or the right but by supranational globalists with an allegiance to no particular nation. In fact, these globalists detest the nation-state model that has dominated the world for thousands of years. Their goal is global governance and they say it out loud in their own documents.

Have no fear.

Do not be intimidated.

Truth will not be defeated.

Humanity will prevail against these anti-human eugenicist monsters because we have living souls and are created in the image of a Holy God with individual free wills.

Because of that, we humans are capable of having a personal relationship with Jesus Christ and the one and only triune God of the Bible. Those who take the bait of the globalists and submit to the world system will in essence be handing over their humanity in exchange for empty promises of safety and security. They will become transhumans, thus foregoing, at some point, their ability to connect with God. Thats a very big step and a decision that will face every human being sooner or later as this technology ramps up. Your very soul will depend on the choice you make. Will you follow God or will you follow man?

Above all, this is a spiritual battle.

We must continue to expose the sinister transhumanist agenda that these globalist predators did their best to keep hidden within a scientific vernacular that they know will wow and mystify the average person. We have decoded it for you in this article from two of the best Christian experts on the topic available in the world today Karen Kingston and Patrick Wood.

Note to readers: Please click the share buttons above or below. Follow us on Instagram and Twitter and subscribe to our Telegram Channel. Feel free to repost and share widely Global Research articles.

Leo Hohmann is an investigative reporter on globalism, Christianity, Islam, Judaism and where politics, culture and religion intersect.

Featured image is fromLeoHohmann.com

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Biden Signs Executive Order Designed to Unleash "Transhumanist Hell" on ...

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Biden transhumanist executive order: We need to program biology …

Posted: at 10:29 am

Mon Sep 19, 2022 - 8:35 pm EDTTue Sep 20, 2022 - 7:26 pm EDT

(LifeSiteNews) The Biden administration issued an executive order calling for biotechnology that can predictably program biology in the same way in which we write software and program computers, a transhumanist practice, in service of human health.

As an example of such biotechnology, Executive Order 14081 included by implication the COVID-19 mRNA injections, citing the COVID-19 pandemic as demonstrating the vital role of biotechnology in developing and producing life-saving vaccines that protect Americans and the world.

The mRNA jabs are an example of what has been described as the most prominent area of biotechnology: The production of ostensibly therapeutic proteins and other drugs through genetic engineering. However, while the proteins produced by the mRNA shot were touted as beneficial, evidence has emerged that they are toxic to humans. In fact, as StatNews noted in 2016, mRNA experiments were abandoned by several pharma groups before the COVID-19 outbreak over concerns about toxicity.

In support of its proposal to use biotechnology to aid human health, the order called upon the Secretary of Health and Human Services (HHS) to submit a report assessing how to use biotechnology to achieve medical breakthroughs, reduce the overall burden of disease, and improve health outcomes.

RELATED: Biden admin reportedly pressuring FBI to target conservatives in bid to justify anti-MAGA rhetoric

Efforts to program biology in human beings not only present further potential dangers to health, such as those shown by the mRNA shots, but they would also increasingly open up the possibilities of eugenic enhancement, which is why gene editing has often been described as a Pandoras Box, potentially creating classes of genetic haves and have-nots in society.

In fact, the use of such technology has been underway for years. For example, the gene editing tool CRISPR has been used in China to alter the DNA of babies to apparently eliminate susceptibility to HIV.

According to Bidens executive order, while the power of biotechnology is most vivid at the moment in the context of human health, it can also be used to achieve our climate and energy goals, improve food security and sustainability, secure our supply chains, and grow the economy.

Biden accordingly calls for the use of biotech to sequeste[r] carbon and reduc[e] greenhouse gas emissions, as well as increas[e] and protec[t] agricultural yields; protec[t] against plant and animal pests and diseases; and cultivat[e] alternative food sources.

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The G20 meeting this October will see the most powerful nations in the world - the U.S., Canada, the U.K., the E.U., Australia, India, China, Russia and Brazil among others -discuss climate policies that are already affecting billions of people around the world.

Thispowerful cadre of international leaderswants the world torun on solar and wind power, forcing an end tothe use of gas, oil and nuclear power, as well as crushing beef farmers because of supposed methane emissions.

But the harsh impact of such policiesis already being felt, with energy blackouts and soaring inflation hammering people around the world, making it beyond timefor all of us tospeak out.

SIGN: Tell G20 leaders that their radical climate policies are making basic foods,fuel, heating and electricityincreasingly unaffordable for normal citizens.

As western leaders turn off the oil spigots and impose draconian restrictions on farmers, we've all experienced the pain of increased prices, not least at the pump and the grocery store.

This inflation was entirely avoidable if onlyour politicians prioritized food and energy security over climate theories, but instead they have succumbed to radical environmentalists whose agenda would cripple the livelihoods and living standards of muchof the globe.

Communities all around you are feeling the weight of crushing price hikes, which will soon reach your own food isles and gas pumps if it hasn't already.

The effects of inflation are being felt in the developing world most, as fuel and food prices sky rocket, making even worse poverty an inevitabilty for hundreds of millions of people.

Reality will hit home for us soon.

The harshest effects of energy shortages will be felt this winter in the west, when our leaders' decisions to cut oil supplies and reject Russian natural gaswill:

The media are already preparing people for rolling blackouts. States like California and countries like England arewarning citizens that they face severe electricity and gas shortages.

Now is the time to speak out and be part of a movement that can prevent this disaster spreading.

SIGN the petition calling on international leaders to abandon their reckless energy agenda and return the world to economic stability.

The entire climate change industry is based on models that have been consistently inaccuratefor decades, with Al Gore among the most infamous prophets of doom to be proven wrong.

In 2009 Gore told theCOP15 climate change conference in Copenhagen that the North Polewould be ice-free by 2014, a claim that remains wildly off the mark.

Al Gore is not alone in getting things wrong however, as this brief timeline ofscaremongering headlines proves:

The world needs to wake-up to what's really happening: our lives are being upended on the basis of climate theories and models that have been consistently wrong for decades.

It's time to stop the scaremongering and push back against the radical agenda of international elites.

SIGN & SHARE: Tell G20 leaders that their radical climate policies are making basic foods,fuel, heating and electricityincreasingly unaffordable for normal citizens.

Thank you.

As an example of biotech that could reduce carbon dioxide, commonly demonized as a major culprit of global warming, the U.S. Department of Agriculture (USDA) has proposed solutions such as the use of trees and microbes to draw excess Co2 out of the atmosphere. The U.S. Department of Energy has also proposed the use of a process to convert waste gases into important chemicals, which captures more carbon gases than it releases.

More controversial is the use of biotech to assist farming, such as by increasing crop yields and protecting against disease through the use of genetically modified (GM) foods, which have been shown to have toxic effects on the human body.

Raising further privacy-related questions is Executive Order 14081s establishment of a Data for the Bioeconomy Initiative, which calls for biological data sets, to include genomic (gene-related) information deemed critical for societal advances.

The Executive Order further calls for a plan to fill any data gaps and make new and existing public data findable and accessible. This proposal raises the question of whether and how individuals genomic information might be publicly disclosed, and whether it would be done so only with informed consent.

Bidens call for the programming of biology the way we program software, if applied to humans, would facilitate transhumanists vision of the creation of superhumans through various kinds of technology, including biotechnology.

In anticipation of major transhumanist developments, including biotech advances, World Economic Forum (WEF) adviser Yuval Noah Harari has gone so far as to declare that we are one of the last generations of homo sapiens, and that within a century or two, earth will be dominated by entities that are more different from us than we are different from chimpanzees.

Well soon have the power to re-engineer our bodies and brains, whether it is with genetic engineering or by directly connecting brains to computers and these technologies are developing at breakneck speed, Harari explained to CNNs Anderson Cooper on 60 Minutes in October 2021.

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Meaning of life – Wikipedia

Posted: at 10:29 am

Philosophical and spiritual question concerning the significance of living or existence in general

The meaning of life, or the answer to the question: "What is the meaning of life?", pertains to the significance of living or existence in general. Many other related questions include: "Why are we here?", "What is life all about?", or "What is the purpose of existence?" There have been many proposed answers to these questions from many different cultural and ideological backgrounds. The search for life's meaning has produced much philosophical, scientific, theological, and metaphysical speculation throughout history. Different people and cultures believe different things for the answer to this question.

The meaning of life can be derived from philosophical and religious contemplation of, and scientific inquiries about existence, social ties, consciousness, and happiness. Many other issues are also involved, such as symbolic meaning, ontology, value, purpose, ethics, good and evil, free will, the existence of one or multiple gods, conceptions of God, the soul, and the afterlife. Scientific contributions focus primarily on describing related empirical facts about the universe, exploring the context and parameters concerning the "how" of life. Science also studies and can provide recommendations for the pursuit of well-being and a related conception of morality. An alternative, humanistic approach poses the question, "What is the meaning of my life?"

Questions about the meaning of life have been expressed in a broad variety of ways, including:

These questions have resulted in a wide range of competing answers and explications, from scientific theories, to philosophical, theological, and spiritual explanations...

Many members of the scientific community and philosophy of science communities think that science can provide the relevant context, and set of parameters necessary for dealing with topics related to the meaning of life. In their view, science can offer a wide range of insights on topics ranging from the science of happiness to death anxiety. Scientific inquiry facilitates this through nomological investigation into various aspects of life and reality, such as the Big Bang, the origin of life, and evolution, and by studying the objective factors which correlate with the subjective experience of meaning and happiness.

Researchers in positive psychology study empirical factors that lead to life satisfaction,[15] full engagement in activities,[16] making a fuller contribution by utilizing one's personal strengths,[17] and meaning based on investing in something larger than the self.[18] Large-data studies of flow experiences have consistently suggested that humans experience meaning and fulfillment when mastering challenging tasks and that the experience comes from the way tasks are approached and performed rather than the particular choice of task. For example, flow experiences can be obtained by prisoners in concentration camps with minimal facilities, and occur only slightly more often in billionaires. A classic example[16] is of two workers on an apparently boring production line in a factory. One treats the work as a tedious chore while the other turns it into a game to see how fast she can make each unit and achieves flow in the process.

Neuroscience describes reward, pleasure, and motivation in terms of neurotransmitter activity, especially in the limbic system and the ventral tegmental area in particular. If one believes that the meaning of life is to maximize pleasure and to ease general life, then this allows normative predictions about how to act to achieve this. Likewise, some ethical naturalists advocate a science of moralitythe empirical pursuit of flourishing for all conscious creatures.

Experimental philosophy and neuroethics research collects data about human ethical decisions in controlled scenarios such as trolley problems. It has shown that many types of ethical judgment are universal across cultures, suggesting that they may be innate, whilst others are culture-specific. The findings show actual human ethical reasoning to be at odds with most philosophical theories, for example consistently showing distinctions between action by cause and action by omission which would be absent from utility-based theories. Cognitive science has theorized about differences between conservative and liberal ethics and how they may be based on different metaphors from family life such as strong fathers vs nurturing mother models.

Neurotheology is a controversial field which tries to find neural correlates and mechanisms of religious experience. Some researchers have suggested that the human brain has innate mechanisms for such experiences and that living without using them for their evolved purposes may be a cause of imbalance. Studies have reported conflicting results on correlating happiness with religious belief and it is difficult to find unbiased meta-analyses.[19][20]

Sociology examines value at a social level using theoretical constructs such as value theory, norms, anomie, etc. One value system suggested by social psychologists, broadly called Terror Management Theory, states that human meaning is derived from a fundamental fear of death, and values are selected when they allow us to escape the mental reminder of death.

Alongside this, there are a number of theories about the way in which humans evaluate the positive and negative aspects of their existence and thus the value and meaning they place on their lives. For example, depressive realism posits an exaggerated positivity in all except those experiencing depressive disorders who see life as it truly is, and David Benatar theorises that more weight is generally given to positive experiences, providing bias towards an over-optimistic view of life.

Emerging research shows that meaning in life predicts better physical health outcomes. Greater meaning has been associated with a reduced risk of Alzheimer's disease,[21] reduced risk of heart attack among individuals with coronary heart disease,[22] reduced risk of stroke,[23] and increased longevity in both American and Japanese samples.[24] In 2014, the British National Health Service began recommending a five-step plan for mental well-being based on meaningful lives, whose steps are:[25]

The exact mechanisms of abiogenesis are unknown: notable hypotheses include the RNA world hypothesis (RNA-based replicators) and the iron-sulfur world hypothesis (metabolism without genetics). The process by which different lifeforms have developed throughout history via genetic mutation and natural selection is explained by evolution.[26] At the end of the 20th century, based upon insight gleaned from the gene-centered view of evolution, biologists George C. Williams, Richard Dawkins, and David Haig, among others, concluded that if there is a primary function to life, it is the replication of DNA and the survival of one's genes.[27][28] Responding to an interview question from Richard Dawkins about "what it is all for", James Watson stated "I don't think we're for anything. We're just the products of evolution."[29]

Though scientists have intensively studied life on Earth, defining life in unequivocal terms is still a challenge.[30][31] Physically, one may say that life "feeds on negative entropy"[32][33][34] which refers to the process by which living entities decrease their internal entropy at the expense of some form of energy taken in from the environment.[35][36][37] Biologists generally agree that lifeforms are self-organizing systems which regulate their internal environments as to maintain this organized state, metabolism serves to provide energy, and reproduction causes life to continue over a span of multiple generations. Typically, organisms are responsive to stimuli and genetic information changes from generation to generation, resulting in adaptation through evolution; this optimizes the chances of survival for the individual organism and its descendants respectively.[38]

Non-cellular replicating agents, notably viruses, are generally not considered to be organisms because they are incapable of independent reproduction or metabolism. This classification is problematic, though, since some parasites and endosymbionts are also incapable of independent life. Astrobiology studies the possibility of different forms of life on other worlds, including replicating structures made from materials other than DNA.

Though the Big Bang theory was met with much skepticism when first introduced, it has become well-supported by several independent observations.[39] However, current physics can only describe the early universe from 1043 seconds after the Big Bang (where zero time corresponds to infinite temperature); a theory of quantum gravity would be required to understand events before that time. Nevertheless, many physicists have speculated about what would have preceded this limit, and how the universe came into being.[40] For example, one interpretation is that the Big Bang occurred coincidentally, and when considering the anthropic principle, it is sometimes interpreted as implying the existence of a multiverse.[41]

The ultimate fate of the universe, and implicitly humanity, is hypothesized as one in which biological life will eventually become unsustainable, such as through a Big Freeze, Big Rip, or Big Crunch.

Theoretical cosmology studies many alternative speculative models for the origin and fate of the universe beyond the Big Bang theory. A recent trend has been models of the creation of 'baby universes' inside black holes, with our own Big Bang being a white hole on the inside of a black hole in another parent universe.[42] Many-worlds theories claim that every possibility of quantum mechanics is played out in parallel universes.

The nature and origin of consciousness and the mind itself are also widely debated in science. The explanatory gap is generally equated with the hard problem of consciousness, and the question of free will is also considered to be of fundamental importance. These subjects are mostly addressed in the fields of cognitive science, neuroscience (e.g. the neuroscience of free will) and philosophy of mind, though some evolutionary biologists and theoretical physicists have also made several allusions to the subject.[43][44]

Reductionistic and eliminative materialistic approaches, for example the Multiple Drafts Model, hold that consciousness can be wholly explained by neuroscience through the workings of the brain and its neurons, thus adhering to biological naturalism.[44][45][46]

On the other hand, some scientists, like Andrei Linde, have considered that consciousness, like spacetime, might have its own intrinsic degrees of freedom, and that one's perceptions may be as real as (or even more real than) material objects.[47] Hypotheses of consciousness and spacetime explain consciousness in describing a "space of conscious elements",[47] often encompassing a number of extra dimensions.[48] Electromagnetic theories of consciousness solve the binding problem of consciousness in saying that the electromagnetic field generated by the brain is the actual carrier of conscious experience; there is however disagreement about the implementations of such a theory relating to other workings of the mind.[49][50] Quantum mind theories use quantum theory in explaining certain properties of the mind. Explaining the process of free will through quantum phenomena is a popular alternative to determinism.

Based on the premises of non-materialistic explanations of the mind, some have suggested the existence of a cosmic consciousness, asserting that consciousness is actually the "ground of all being".[9][51][52] Proponents of this view cite accounts of paranormal phenomena, primarily extrasensory perceptions and psychic powers, as evidence for an incorporeal higher consciousness. In hopes of proving the existence of these phenomena, parapsychologists have orchestrated various experiments, but successful results might be due to poor experimental controls and might have alternative explanations.[53][54][55][56]

Reker and Wong define personal meaning as the "cognizance of order, coherence and purpose in one's existence, the pursuit and attainment of worthwhile goals, and an accompanying sense of fulfillment" (p.221).[57] In 2016, Martela and Steger defined meaning as coherence, purpose, and significance.[58] In contrast, Wong has proposed a four-component solution to the question of meaning in life,[59][60] with the four components purpose, understanding, responsibility, and enjoyment (PURE):

Thus, a sense of significance permeates every dimension of meaning, rather than standing as a separate factor.

Although most psychology researchers consider meaning in life as a subjective feeling or judgment, most philosophers (e.g., Thaddeus Metz, Daniel Haybron) propose that there are also objective, concrete criteria for what constitutes meaning in life.[61][62] Wong has proposed that whether life is meaningful depends not only on subjective feelings but, more importantly, on whether a person's goal-striving and life as a whole is meaningful according to some objective normative standard.[60]

The philosophical perspectives on the meaning of life are those ideologies that explain life in terms of ideals or abstractions defined by humans.

Plato, a pupil of Socrates, was one of the earliest, most influential philosophers. His reputation comes from his idealism of believing in the existence of universals. His theory of forms proposes that universals do not physically exist, like objects, but as heavenly forms. In the dialogue of the Republic, the character of Socrates describes the Form of the Good. His theory on justice in the soul relates to the idea of happiness relevant to the question of the meaning of life.

In Platonism, the meaning of life is in attaining the highest form of knowledge, which is the Idea (Form) of the Good, from which all good and just things derive utility and value.

Aristotle, an apprentice of Plato, was another early and influential philosopher, who argued that ethical knowledge is not certain knowledge (such as metaphysics and epistemology), but is general knowledge. Because it is not a theoretical discipline, a person had to study and practice in order to become "good"; thus if the person were to become virtuous, he could not simply study what virtue is, he had to be virtuous, via virtuous activities. To do this, Aristotle established what is virtuous:

Every skill and every inquiry, and similarly, every action and choice of action, is thought to have some good as its object. This is why the good has rightly been defined as the object of all endeavor [...]Everything is done with a goal, and that goal is "good".

Yet, if action A is done towards achieving goal B, then goal B also would have a goal, goal C, and goal C also would have a goal, and so would continue this pattern, until something stopped its infinite regression. Aristotle's solution is the Highest Good, which is desirable for its own sake. It is its own goal. The Highest Good is not desirable for the sake of achieving some other good, and all other "goods" desirable for its sake. This involves achieving eudaemonia, usually translated as "happiness", "well-being", "flourishing", and "excellence".

What is the highest good in all matters of action? To the name, there is an almost complete agreement; for uneducated and educated alike call it happiness, and make happiness identical with the good life and successful living. They disagree, however, about the meaning of happiness.

Antisthenes, a pupil of Socrates, first outlined the themes of Cynicism, stating that the purpose of life is living a life of Virtue which agrees with Nature. Happiness depends upon being self-sufficient and master of one's mental attitude; suffering is the consequence of false judgments of value, which cause negative emotions and a concomitant vicious character.

The Cynical life rejects conventional desires for wealth, power, health, and fame, by being free of the possessions acquired in pursuing the conventional.[63][64] As reasoning creatures, people could achieve happiness via rigorous training, by living in a way natural to human beings. The world equally belongs to everyone, so suffering is caused by false judgments of what is valuable and what is worthless per the customs and conventions of society.

Aristippus of Cyrene, a pupil of Socrates, founded an early Socratic school that emphasized only one side of Socrates's teachingsthat happiness is one of the ends of moral action and that pleasure is the supreme good; thus a hedonistic world view, wherein bodily gratification is more intense than mental pleasure. Cyrenaics prefer immediate gratification to the long-term gain of delayed gratification; denial is unpleasant unhappiness.[65][66]

Epicurus, a pupil of the Platonist Pamphilus of Samos, taught that the greatest good is in seeking modest pleasures, to attain tranquility and freedom from fear (ataraxia) via knowledge, friendship, and virtuous, temperate living; bodily pain (aponia) is absent through one's knowledge of the workings of the world and of the limits of one's desires. Combined, freedom from pain and freedom from fear are happiness in its highest form. Epicurus' lauded enjoyment of simple pleasures is quasi-ascetic "abstention" from sex and the appetites:

"When we say ... that pleasure is the end and aim, we do not mean the pleasures of the prodigal or the pleasures of sensuality, as we are understood to do, by some, through ignorance, prejudice or willful misrepresentation. By pleasure, we mean the absence of pain in the body and of trouble in the soul. It is not by an unbroken succession of drinking bouts and of revelry, not by sexual lust, nor the enjoyment of fish, and other delicacies of a luxurious table, which produce a pleasant life; it is sober reasoning, searching out the grounds of every choice and avoidance, and banishing those beliefs through which the greatest tumults take possession of the soul."[67]

The Epicurean meaning of life rejects immortality and mysticism; there is a soul, but it is as mortal as the body. There is no afterlife, yet, one need not fear death, because "Death is nothing to us; for that which is dissolved, is without sensation, and that which lacks sensation is nothing to us."[68]

Zeno of Citium, a pupil of Crates of Thebes, established the school which teaches that living according to reason and virtue is to be in harmony with the universe's divine order, entailed by one's recognition of the universal logos, or reason, an essential value of all people. The meaning of life is "freedom from suffering" through apatheia (Gr: ), that is, being objective and having "clear judgement", not indifference.

Stoicism's prime directives are virtue, reason, and natural law, abided to develop personal self-control and mental fortitude as means of overcoming destructive emotions. The Stoic does not seek to extinguish emotions, only to avoid emotional troubles, by developing clear judgment and inner calm through diligently practiced logic, reflection, and concentration.

The Stoic ethical foundation is that "good lies in the state of the soul", itself, exemplified in wisdom and self-control, thus improving one's spiritual well-being: "Virtue consists in a will which is in agreement with Nature."[68] The principle applies to one's personal relations thus: "to be free from anger, envy, and jealousy".[68]

The Enlightenment and the colonial era both changed the nature of European philosophy and exported it worldwide. Devotion and subservience to God were largely replaced by notions of inalienable natural rights and the potentialities of reason, and universal ideals of love and compassion gave way to civic notions of freedom, equality, and citizenship. The meaning of life changed as well, focusing less on humankind's relationship to God and more on the relationship between individuals and their society. This era is filled with theories that equate meaningful existence with the social order.

Classical liberalism is a set of ideas that arose in the 17th and 18th centuries, out of conflicts between a growing, wealthy, propertied class and the established aristocratic and religious orders that dominated Europe. Liberalism cast humans as beings with inalienable natural rights (including the right to retain the wealth generated by one's own work), and sought out means to balance rights across society. Broadly speaking, it considers individual liberty to be the most important goal,[69] because only through ensured liberty are the other inherent rights protected.

There are many forms and derivations of liberalism, but their central conceptions of the meaning of life trace back to three main ideas. Early thinkers such as John Locke, Jean-Jacques Rousseau and Adam Smith saw humankind beginning in the state of nature, then finding meaning for existence through labor and property, and using social contracts to create an environment that supports those efforts.

Kantianism is a philosophy based on the ethical, epistemological, and metaphysical works of Immanuel Kant. Kant is known for his deontological theory where there is a single moral obligation, the "Categorical Imperative", derived from the concept of duty. Kantians believe all actions are performed in accordance with some underlying maxim or principle, and for actions to be ethical, they must adhere to the categorical imperative.

Simply put, the test is that one must universalize the maxim (imagine that all people acted in this way) and then see if it would still be possible to perform the maxim in the world without contradiction. In Groundwork, Kant gives the example of a person who seeks to borrow money without intending to pay it back. This is a contradiction because if it were a universal action, no person would lend money anymore as he knows that he will never be paid back. The maxim of this action, says Kant, results in a contradiction in conceivability (and thus contradicts perfect duty).

Kant also denied that the consequences of an act in any way contribute to the moral worth of that act, his reasoning being that the physical world is outside one's full control and thus one cannot be held accountable for the events that occur in it.

The origins of utilitarianism can be traced back as far as Epicurus, but, as a school of thought, it is credited to Jeremy Bentham,[70] who found that "nature has placed mankind under the governance of two sovereign masters, pain and pleasure"; then, from that moral insight, he derived the Rule of Utility: "that the good is whatever brings the greatest happiness to the greatest number of people". He defined the meaning of life as the "greatest happiness principle".

Jeremy Bentham's foremost proponent was James Mill, a significant philosopher in his day, and father of John Stuart Mill. The younger Mill was educated per Bentham's principles, including transcribing and summarizing much of his father's work.[71]

Nihilism suggests that life is without objective meaning.

Friedrich Nietzsche characterized nihilism as emptying the world, and especially human existence, of meaning, purpose, comprehensible truth, and essential value; succinctly, nihilism is the process of "the devaluing of the highest values".[72] Seeing the nihilist as a natural result of the idea that God is dead, and insisting it was something to overcome, his questioning of the nihilist's life-negating values returned meaning to the Earth.[73]

To Martin Heidegger, nihilism is the movement whereby "being" is forgotten, and is transformed into value, in other words, the reduction of being to exchange value.[72] Heidegger, in accordance with Nietzsche, saw in the so-called "death of God" a potential source for nihilism:

If God, as the supra-sensory ground and goal, of all reality, is dead; if the supra-sensory world of the Ideas has suffered the loss of its obligatory, and above it, its vitalizing and up-building power, then nothing more remains to which Man can cling, and by which he can orient himself.[74]

The French philosopher Albert Camus asserts that the absurdity of the human condition is that people search for external values and meaning in a world which has none and is indifferent to them. Camus writes of value-nihilists such as Meursault,[75] but also of values in a nihilistic world, that people can instead strive to be "heroic nihilists", living with dignity in the face of absurdity, living with "secular saintliness", fraternal solidarity, and rebelling against and transcending the world's indifference.[76]

The current era has seen radical changes in both formal and popular conceptions of human nature. The knowledge disclosed by modern science has effectively rewritten the relationship of humankind to the natural world. Advances in medicine and technology have freed humans from significant limitations and ailments of previous eras;[77] and philosophyparticularly following the linguistic turnhas altered how the relationships people have with themselves and each other are conceived. Questions about the meaning of life have also seen radical changes, from attempts to reevaluate human existence in biological and scientific terms (as in pragmatism and logical positivism) to efforts to meta-theorize about meaning-making as a personal, individual-driven activity (existentialism, secular humanism).

Pragmatism originated in the late-19th-century US, concerning itself (mostly) with truth, and positing that "only in struggling with the environment" do data, and derived theories, have meaning, and that consequences, like utility and practicality, are also components of truth. Moreover, pragmatism posits that anything useful and practical is not always true, arguing that what most contributes to the most human good in the long course is true. In practice, theoretical claims must be practically verifiable, i.e. one should be able to predict and test claims, and, that, ultimately, the needs of humankind should guide human intellectual inquiry.

Pragmatic philosophers suggest that the practical, useful understanding of life is more important than searching for an impractical abstract truth about life. William James argued that truth could be made, but not sought.[78][79] To a pragmatist, the meaning of life is discoverable only via experience.

Theists believe God created the universe and that God had a purpose in doing so. Theists also hold the view that humans find their meaning and purpose for life in God's purpose in creating. Some theists further hold that if there were no God to give life ultimate meaning, value, and purpose, then life would be absurd.[80]

According to existentialism, each person creates the essence (meaning) of their life; life is not determined by a supernatural god or an earthly authority, one is free. As such, one's ethical prime directives are action, freedom, and decision, thus, existentialism opposes rationalism and positivism. In seeking meaning to life, the existentialist looks to where people find meaning in life, in course of which using only reason as a source of meaning is insufficient; this gives rise to the emotions of anxiety and dread, felt in considering one's free will, and the concomitant awareness of death. According to Jean-Paul Sartre, existence precedes essence; the (essence) of one's life arises only after one comes to existence.

Sren Kierkegaard spoke about a "leap", arguing that life is full of absurdity, and one must make his and her own values in an indifferent world. One can live meaningfully (free of despair and anxiety) in an unconditional commitment to something finite and devotes that meaningful life to the commitment, despite the vulnerability inherent to doing so.[81]

Arthur Schopenhauer answered: "What is the meaning of life?" by stating that one's life reflects one's will, and that the will (life) is an aimless, irrational, and painful drive. Salvation, deliverance, and escape from suffering are in aesthetic contemplation, sympathy for others, and asceticism.[82][83]

For Friedrich Nietzsche, life is worth living only if there are goals inspiring one to live. Accordingly, he saw nihilism ("all that happens is meaningless") as without goals. He stated that asceticism denies one's living in the world; stated that values are not objective facts, that are rationally necessary, universally binding commitments: our evaluations are interpretations, and not reflections of the world, as it is, in itself, and, therefore, all ideations take place from a particular perspective.[73]

"... in spite of or in defiance of the whole of existence he wills to be himself with it, to take it along, almost defying his torment. For to hope in the possibility of help, not to speak of help by virtue of the absurd, that for God all things are possibleno, that he will not do. And as for seeking help from any otherno, that he will not do for all the world; rather than seek the help he would prefer to be himselfwith all the tortures of hell if so it must be."

Sren Kierkegaard, The Sickness Unto Death[84]

In absurdist philosophy, the Absurd arises out of the fundamental disharmony between the individual's search for meaning and the apparent meaninglessness of the universe. As beings looking for meaning in a meaningless world, humans have three ways of resolving the dilemma. Kierkegaard and Camus describe the solutions in their works, The Sickness Unto Death (1849) and The Myth of Sisyphus (1942):

Per secular humanism, the human species came to be by reproducing successive generations in a progression of unguided evolution as an integral expression of nature, which is self-existing.[86][87] Human knowledge comes from human observation, experimentation, and rational analysis (the scientific method), and not from supernatural sources; the nature of the universe is what people discern it to be.[86] Likewise, "values and realities" are determined "by means of intelligent inquiry"[86] and "are derived from human need and interest as tested by experience", that is, by critical intelligence.[88][89] "As far as we know, the total personality is [a function] of the biological organism transacting in a social and cultural context."[87]

People determine human purpose without supernatural influence; it is the human personality (general sense) that is the purpose of a human being's life which humanism seeks to develop and fulfill:[86] "Humanism affirms our ability and responsibility to lead ethical lives of personal fulfillment that aspire to the greater good of humanity".[88] Humanism aims to promote enlightened self-interest and the common good for all people. It is based on the premises that the happiness of the individual person is inextricably linked to the well-being of all humanity, in part because humans are social animals who find meaning in personal relations and because cultural progress benefits everybody living in the culture.[87][88]

The philosophical subgenres posthumanism and transhumanism (sometimes used synonymously) are extensions of humanistic values. One should seek the advancement of humanity and of all life to the greatest degree feasible and seek to reconcile Renaissance humanism with the 21st century's technoscientific culture. In this light, every living creature has the right to determine its personal and social "meaning of life".[90]

From a humanism-psychotherapeutic point of view, the question of the meaning of life could be reinterpreted as "What is the meaning of my life?"[91] This approach emphasizes that the question is personaland avoids focusing on cosmic or religious questions about overarching purpose. There are many therapeutic responses to this question. For example, Viktor Frankl argues for "Dereflection", which translates largely as cease endlessly reflecting on the self; instead, engage in life. On the whole, the therapeutic response is that the question itselfwhat is the meaning of life?evaporates when one is fully engaged in life. (The question then morphs into more specific worries such as "What delusions am I under?"; "What is blocking my ability to enjoy things?"; "Why do I neglect loved-ones?".)[92]

Logical positivists ask: "What is the meaning of life?", "What is the meaning in asking?"[93][94] and "If there are no objective values, then, is life meaningless?"[95] Ludwig Wittgenstein and the logical positivists said:[citation needed] "Expressed in language, the question is meaningless"; because, in life the statement the "meaning of x", usually denotes the consequences of x, or the significance of x, or what is notable about x, etc., thus, when the meaning of life concept equals "x", in the statement the "meaning of x", the statement becomes recursive, and, therefore, nonsensical, or it might refer to the fact that biological life is essential to having a meaning in life.

The things (people, events) in the life of a person can have meaning (importance) as parts of a whole, but a discrete meaning of (the) life, itself, aside from those things, cannot be discerned. A person's life has meaning (for themselves, others) as the life events resulting from their achievements, legacy, family, etc., but, to say that life, itself, has meaning, is a misuse of language, since any note of significance, or of consequence, is relevant only in life (to the living), so rendering the statement erroneous. Bertrand Russell wrote that although he found that his distaste for torture was not like his distaste for broccoli, he found no satisfactory, empirical method of proving this:[68]

When we try to be definite, as to what we mean when we say that this or that is "the Good," we find ourselves involved in very great difficulties. Bentham's creed, that pleasure is the Good, roused furious opposition, and was said to be a pig's philosophy. Neither he nor his opponents could advance any argument. In a scientific question, evidence can be adduced on both sides, and, in the end, one side is seen to have the better caseor, if this does not happen, the question is left undecided. But in a question, as to whether this, or that, is the ultimate Good, there is no evidence, either way; each disputant can only appeal to his own emotions, and employ such rhetorical devices as shall arouse similar emotions in others ... Questions as to "values"that is to say, as to what is good or bad on its own account, independently of its effectslie outside the domain of science, as the defenders of religion emphatically assert. I think that, in this, they are right, but, I draw the further conclusion, which they do not draw, that questions as to "values" lie wholly outside the domain of knowledge. That is to say, when we assert that this, or that, has "value", we are giving expression to our own emotions, not to a fact, which would still be true if our personal feelings were different.[96]

Postmodernist thoughtbroadly speakingsees human nature as constructed by language, or by structures and institutions of human society. Unlike other forms of philosophy, postmodernism rarely seeks out a priori or innate meanings in human existence, but instead focuses on analyzing or critiquing given meanings in order to rationalize or reconstruct them. Anything resembling a "meaning of life", in postmodernist terms, can only be understood within a social and linguistic framework and must be pursued as an escape from the power structures that are already embedded in all forms of speech and interaction. As a rule, postmodernists see awareness of the constraints of language as necessary to escaping those constraints, but different theorists take different views on the nature of this process: from a radical reconstruction of meaning by individuals (as in deconstructionism) to theories in which individuals are primarily extensions of language and society, without real autonomy (as in poststructuralism).

According to naturalistic pantheism, the meaning of life is to care for and look after nature and the environment.

Embodied cognition uses the neurological basis of emotion, speech, and cognition to understand the nature of thought. Cognitive neuropsychology has identified brain areas necessary for these abilities, and genetic studies show that the gene FOXP2 affects neuroplasticity which underlies language fluency. George Lakoff, a professor of cognitive linguistics and philosophy, advances the view that metaphors are the usual basis of meaning, not the logic of verbal symbol manipulation.[citation needed] Computers use logic programming to effectively query databases but humans rely on a trained biological neural network. Postmodern philosophies that use the indeterminacy of symbolic language to deny definite meaning ignore those who feel they know what they mean and feel that their interlocutors know what they mean.[citation needed] Choosing the correct metaphor results in enough common understanding to pursue questions such as the meaning of life.[citation needed] Improved knowledge of brain function should result in better treatments producing healthier brains. When combined with more effective training, a sound personal assessment as to the meaning of one's life should be straightforward.[citation needed]

The Mohist philosophers believed that the purpose of life was universal, impartial love. Mohism promoted a philosophy of impartial caringa person should care equally for all other individuals, regardless of their actual relationship to him or her.[97] The expression of this indiscriminate caring is what makes a man a righteous being in Mohist thought. This advocacy of impartiality was a target of attack by the other Chinese philosophical schools, most notably the Confucians who believed that while love should be unconditional, it should not be indiscriminate. For example, children should hold a greater love for their parents than for random strangers.

Confucianism recognizes human nature in accordance with the need for discipline and education. Because humankind is driven by both positive and negative influences, Confucianists see a goal in achieving virtue through strong relationships and reasoning as well as minimizing the negative. This emphasis on normal living is seen in the Confucianist scholar Tu Wei-Ming's quote, "We can realize the ultimate meaning of life in ordinary human existence."[98]

The Legalists believed that finding the purpose of life was a meaningless effort. To the Legalists, only practical knowledge was valuable, especially as it related to the function and performance of the state.

The religious perspectives on the meaning of life are those ideologies that explain life in terms of an implicit purpose not defined by humans. According to the Charter for Compassion, signed by many of the world's leading religious and secular organizations, the core of religion is the golden rule of 'treat others as you would have them treat you'. The Charter's founder, Karen Armstrong, quotes the ancient Rabbi Hillel who suggested that 'the rest is commentary'. This is not to reduce the commentary's importance, and Armstrong considers that its study, interpretation, and ritual are the means by which religious people internalize and live the golden rule.

In the Judaic world view, the meaning of life is to elevate the physical world ('Olam HaZeh') and prepare it for the world to come ('Olam HaBa'), the messianic era. This is called Tikkun Olam ("Fixing the World"). Olam HaBa can also mean the spiritual afterlife, and there is debate concerning the eschatological order. However, Judaism is not focused on personal salvation, but on communal (between man and man) and individual (between man and God) spiritualised actions in this world.

Judaism's most important feature is the worship of a single, incomprehensible, transcendent, one, indivisible, absolute Being, who created and governs the universe. Closeness with the God of Israel is through a study of His Torah, and adherence to its mitzvot (divine laws). In traditional Judaism, God established a special covenant with a people, the people of Israel, at Mount Sinai, giving the Jewish commandments. Torah comprises the written Pentateuch and the transcribed oral tradition, further developed through the generations. The Jewish people are intended as "a kingdom of priests and a holy nation"[99] and a "light to the Nations", influencing the other peoples to keep their own religio-ethical Seven Laws of Noah. The messianic era is seen as the perfection of this dual path to God.

Jewish observances involve ethical and ritual, affirmative, and prohibitive injunctions. Modern Jewish denominations differ over the nature, relevance, and emphases of mitzvot. Jewish philosophy emphasises that God is not affected or benefited, but the individual and society benefit by drawing close to God. The rationalist Maimonides sees the ethical and ritual divine commandments as a necessary, but insufficient preparation for philosophical understanding of God, with its love and awe.[100] Among fundamental values in the Torah are pursuit of justice, compassion, peace, kindness, hard work, prosperity, humility, and education.[101][102] The world to come,[103] prepared in the present, elevates man to an everlasting connection with God.[104] Simeon the Righteous says, "The world stands on three things: on Torah, on worship, and on acts of loving kindness." The prayer book relates, "Blessed is our God who created us for his honor ... and planted within us everlasting life." Of this context, the Talmud states, "Everything that God does is for the good." including suffering.

The Jewish mystical Kabbalah gives complementary esoteric meanings of life. As well as Judaism providing an immanent relationship with God (personal theism), in Kabbalah the spiritual and physical creation is a paradoxical manifestation of the immanent aspects of God's Being (panentheism), related to the Shekhinah (Divine feminine). Jewish observance unites the sephirot (Divine attributes) on high, restoring harmony to creation. In Lurianic Kabbalah, the meaning of life is the messianic rectification of the shattered sparks of God's persona, exiled in physical existence (the Kelipot shells), through the actions of Jewish observance.[105] Through this, in Hasidic Judaism the ultimate essential "desire" of God is the revelation of the Omnipresent Divine essence through materiality, achieved by a man from within his limited physical realm when the body will give life to the soul.[106]

Christianity has its roots in Judaism, and shares much of the latter faith's ontology. Its central beliefs derive from the teachings of Jesus Christ as presented in the New Testament. Life's purpose in Christianity is to seek divine salvation through the grace of God and intercession of Christ.[108] The New Testament speaks of God wanting to have a relationship with humans both in this life and the life to come, which can happen only if one's sins are forgiven.[109]

In the Christian view, humankind was made in the Image of God and perfect, but the Fall of Man caused the progeny of the First Parents to inherit Original Sin and its consequences. Christ's passion, death and resurrection provide the means for transcending that impure state (Romans 6:23). The good news that this restoration from sin is now possible is called the gospel. The specific process of appropriating salvation through Christ and maintaining a relationship with God varies between different denominations of Christians, but all rely on faith in Christ and the gospel as the fundamental starting point. Salvation through faith in God is found in Ephesians 2:89 "[8]For by grace you have been saved through faith; and that not of yourselves, it is the gift of God; [9]not as a result of works, that no one should boast." (NASB; 1973). The gospel maintains that through this belief, the barrier that sin has created between man and God is destroyed, thereby allowing believers to be regenerated by God and to instill in them a new heart after God's own will with the ability to live righteously before him. This is what the term saved almost always refer to.

In Reformed theology it is believed the purpose of life is to glorify God. In the Westminster Shorter Catechism, an extremely important creed for Reformed Christians,[110] the first question is: "What is the chief end of Man?" (that is, "What is Man's main purpose?"). The answer is: "Man's chief end is to glorify God, and enjoy him forever". God requires one to obey the revealed moral law, saying: "Love the Lord your God with all your heart, with all your soul, with all your strength, and with all your mind; and your neighbour as yourself".[111] The Baltimore Catechism answers the question "Why did God make you?" by saying "God made me to know Him, to love Him, and to serve Him in this world, and to be happy with Him forever in heaven."[112]

The Apostle Paul also answers this question in his speech on the Areopagus in Athens: "And He has made from one blood every nation of men to dwell on all the face of the earth, and has determined their preappointed times and the boundaries of their dwellings, so that they should seek the Lord, in the hope that they might grope for Him and find Him, though He is not far from each one of us."[113]

Catholicism's way of thinking is better expressed through the Principle and Foundation of St. Ignatius of Loyola: "The human person is created to praise, reverence, and serve God Our Lord, and by doing so, to save his or her soul. All other things on the face of the earth are created for human beings in order to help them pursue the end for which they are created. It follows from this that one must use other created things, in so far as they help towards one's end, and free oneself from them, in so far as they are obstacles to one's end. To do this, we need to make ourselves indifferent to all created things, provided the matter is subject to our free choice and there is no other prohibition. Thus, as far as we are concerned, we should not want health more than illness, wealth more than poverty, fame more than disgrace, a-long life more than a short one, and similarly for all the rest, but we should desire and choose only what helps us more towards the end for which we are created."[114]

Mormonism teaches that the purpose of life on Earth is to gain knowledge and experience and to have joy.[115] Mormons believe that humans are literally the spirit children of God the Father, and thus have the potential to progress to become like Him. Mormons teach that God provided his children the choice to come to Earth, which is considered a crucial stage in their developmentwherein a mortal body, coupled with the freedom to choose, makes for an environment to learn and grow.[115] The Fall of Adam is not viewed as an unfortunate or unplanned cancellation of God's original plan for a paradise; rather, the opposition found in mortality is an essential element of God's plan because the process of enduring and overcoming challenges, difficulties, and temptations provides opportunities to gain wisdom and strength, thereby learning to appreciate and choose good and reject evil.[116][117] Because God is just, he allows those who were not taught the gospel during mortality to receive it after death in the spirit world,[118] so that all of his children have the opportunity to return to live with God, and reach their full potential.

A recent alternative Christian theological discourse interprets Jesus as revealing that the purpose of life is to elevate our compassionate response to human suffering;[119] nonetheless, the conventional Christian position is that people are justified by belief in the propitiatory sacrifice of Jesus' death on the cross.

In Islam, humanity's ultimate purpose is to worship their creator, Allah (English: The God), through his signs, and be grateful to him through sincere love and devotion. This is practically shown by following the divine guidelines revealed in the Qur'an and the tradition of the Prophet (with the exception of Quranists). Earthly life is a test, determining one's position of closeness to Allah in the hereafter. A person will either be close to him and his love in Jannah (Paradise) or far away in Jahannam (Hell).

For Allah's satisfaction, via the Qur'an, all Muslims must believe in God, his revelations, his angels, his messengers, and in the "Day of Judgment".[120] The Qur'an describes the purpose of creation as follows: "Blessed be he in whose hand is the kingdom, he is powerful over all things, who created death and life that he might examine which of you is best in deeds, and he is the almighty, the forgiving." (Qur'an 67:12) and "And I (Allh) created not the jinn and mankind except that they should be obedient (to Allah)." (Qur'an 51:56). Obedience testifies to the oneness of God in his lordship, his names, and his attributes. Terrenal life is a test; how one acts (behaves) determines whether one's soul goes to Jannat (Heaven) or to Jahannam (Hell).[121][citation needed] However, on the day of Judgement the final decision is of Allah alone.[122]

The Five Pillars of Islam are duties incumbent to every Muslim; they are: Shahadah (profession of faith); Salat (ritual prayer); Zakat (charity); Sawm (fasting during Ramadan), and Hajj (pilgrimage to Mecca).[123] They derive from the Hadith works, notably of Sahih Al-Bukhari and Sahih Muslim. The five pillars are not mentioned directly in the Quran.

Beliefs differ among the Kalam. The Sunni and the Ahmadiyya concept of pre-destination is divine decree;[124] likewise, the Shi'a concept of pre-destination is divine justice; in the esoteric view of the Sufis, the universe exists only for God's pleasure; Creation is a grand game, wherein Allah is the greatest prize.

The Sufi view of the meaning of life stems from the hadith qudsi that states "I (God) was a Hidden Treasure and loved to be known. Therefore I created the Creation that I might be known." One possible interpretation of this view is that the meaning of life for an individual is to know the nature of God, and the purpose of all of creation is to reveal that nature and to prove its value as the ultimate treasure, that is God. However, this hadith is stated in various forms and interpreted in various ways by people, such, as 'Abdu'l-Bah of the Bah Faith, and in Ibn'Arab's Fu al-ikam.[126]

The Bah Faith emphasizes the unity of humanity.[127] To Bahs, the purpose of life is focused on spiritual growth and service to humanity. Human beings are viewed as intrinsically spiritual beings. People's lives in this material world provide extended opportunities to grow, to develop divine qualities and virtues, and the prophets were sent by God to facilitate this.[128][129]

Hinduism is a religious category including many beliefs and traditions. Since Hinduism was the way of expressing meaningful living for a long time before there was a need for naming it as a separate religion, Hindu doctrines are supplementary and complementary in nature, generally non-exclusive, suggestive, and tolerant in content.[130] Most believe that the tman (spirit, soul)the person's true selfis eternal.[131] In part, this stems from Hindu beliefs that spiritual development occurs across many lifetimes, and goals should match the state of development of the individual. There are four possible aims to human life, known as the purusharthas (ordered from least to greatest): (i) Kma (wish, desire, love and sensual pleasure), (ii) Artha (wealth, prosperity, glory), (iii) Dharma (righteousness, duty, morality, virtue, ethics), encompassing notions such as ahimsa (non-violence) and satya (truth) and (iv) Moksha (liberation, i.e. liberation from Sasra, the cycle of reincarnation).[132][133][134]

In all schools of Hinduism, the meaning of life is tied up in the concepts of karma (causal action), sansara (the cycle of birth and rebirth), and moksha (liberation). Existence is conceived as the progression of the tman (similar to the western concept of a soul) across numerous lifetimes, and its ultimate progression towards liberation from karma. Particular goals for life are generally subsumed under broader yogas (practices) or dharma (correct living) which are intended to create more favorable reincarnations, though they are generally positive acts in this life as well. Traditional schools of Hinduism often worship Devas which are manifestations of Ishvara (a personal or chosen God); these Devas are taken as ideal forms to be identified with, as a form of spiritual improvement.

In short, the goal is to realize the fundamental truth about oneself. This thought is conveyed in the Mahvkyas ("Tat Tvam Asi" (thou art that), "Aham Brahmsmi", "Prajnam Brahma" and "Ayam tm Brahma" (This tman is Brahman)).

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