Praxeology: A holistic approach to human behaviour

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In philosophy, praxeology or praxiology (/ˌpræksiˈɒlədʒi/; from Ancient Greek πρᾶξις (praxis) ‘deed, action’, and -λογία (-logia) ‘study of’) is the theory of human action, based on the notion that humans engage in purposeful behavior, contrary to reflexive behavior and other unintentional behavior.

French social philosopher Alfred Espinas gave the term its modern meaning, and praxeology was developed independently by two principal groups: the Austrian school, led by Ludwig von Mises, and the Polish school, led by Tadeusz Kotarbiński.

Origin and etymology

Coinage of the word praxeology (praxéologie) is often credited to Louis Bourdeau, the French author of a classification of the sciences, which he published in his Théorie des sciences: Plan de Science intégrale in 1882:

On account of their dual natures of specialty and generality, these functions should be the subject of a separate science. Some of its parts have been studied for a long time, because this kind of research, in which man could be the main subject, has always presented the greatest interest. Physiology, hygiene, medicine, psychology, animal history, human history, political economy, morality, etc. represent fragments of a science that we would like to establish, but as fragments scattered and uncoordinated have remained until now only parts of particular sciences. They should be joined together and made whole in order to highlight the order of the whole and its unity. Now you have a science, so far unnamed, which we propose to call Praxeology (from πραξις, action), or by referring to the influence of the environment, Mesology (from μεσος, environment).

However, the term was used at least once previously (with a slight spelling difference), in 1608, by Clemens Timpler in his Philosophiae practicae systema methodicum:

There was Aretology: Following that Praxiology: which is the second part of the Ethics, in general, commenting on the actions of the moral virtues.

It was later mentioned by Robert Flint in 1904 in a review of Bourdeau’s Théorie des sciences.

The modern definition of the word was first given by Alfred V. Espinas (1844–1922), the French philosopher and sociologist; he was the forerunner of the Polish school of the science of efficient action. The Austrian school of economics was based on a philosophical science of the same kind.

With a different spelling, the word was used by the English psychologist Charles Arthur Mercier (in 1911), and proposed by Knight Dunlap to John B. Watson as a better name for his behaviorism. Watson rejected it. But the Chinese physiologist of behavior, Zing-Yang Kuo (b. 1898) adopted the term in 1935. It was also used by William McDougall (in 1928 and later).

Previously the word praxiology, with the meaning Espinas gave to it, was used by Tadeusz Kotarbiński (in 1923). Several economists, such as the Ukrainian, Eugene Slutsky (1926) used it in his attempt to base economics on a theory of action. It was also used by Austrian economist Ludwig von Mises (1933), Russian Marxist Nikolai Bukharin (1888–1938) during the Second International Congress of History of Science and Technology in London (in 1931), and Polish scholar Oscar Lange (1904–1965) in 1959, and later.

The Italian philosopher, Carmelo Ottaviano, was using the Italianised version, prassiologia, in his treatises starting from 1935, but in his own way, as a theory of politics. After the Second World War the use of the term praxeology spread widely. After the emigration of Mises to the US his pupil Murray Rothbard defended the praxeological approach. A revival of Espinas’s approach in France was revealed in the works of Pierre Massé (1946), the eminent cybernetician, Georges Théodule Guilbaud (1953), the Belgian logician, Leo Apostel (1957), the cybernetician, Anatol Rapoport (1962), Henry Pierron, psychologist and lexicographer (1957), François Perroux, economist (1957), the social psychologist, Robert Daval (1963), the well-known sociologist, Raymond Aron (1963) and the methodologists, Abraham Antoine Moles and Roland Caude (1965).

Under the influence of Tadeusz Kotarbiński, praxeology flourished in Poland. A special “Centre of Praxeology” (Zaklad Prakseologiczny) was created under the organizational guidance of the Polish Academy of Sciences, with its own periodical (from 1962), called at first Materiały Prakseologiczne (Praxeological Papers), and then abbreviated to Prakseologia. It published hundreds of papers by different authors, and the materials for a special vocabulary edited by Professor Tadeusz Pszczolowski, the leading praxeologist of the younger generation. A sweeping survey of the praxeological approach is to be found in the paper by the French statistician Micheline Petruszewycz, “A propos de la praxéologie”.

Ludwig von Mises was influenced by several theories in forming his work on praxeology, including Immanuel Kant’s works, Max Weber’s work on methodological individualism, and Carl Menger’s development of the subjective theory of value.

Philosopher of science Mario Bunge published works of systematic philosophy that included contributions to praxeology, and Bunge dismissed von Mises’s version of praxeology as “nothing but the principle of maximization of subjective utility—a fancy version of egoism”. Bunge, who was also a fierce critic of pseudoscience, warned that when “conceived in extremely general terms and detached from both ethics and science, praxiology has hardly any practical value”.

Austrian economics in the tradition of Ludwig von Mises relies heavily on praxeology in the development of its economic theories. Mises considered economics to be a sub-discipline of praxeology. Austrian School economists, following Mises, use praxeology and deduction, rather than empirical studies, to determine economic principles. According to these theorists, with the action axiom as the starting point, it is possible to draw conclusions about human behavior that are both objective and universal. For example, the notion that humans engage in acts of choice implies that they have preferences, and this must be true for anyone who exhibits intentional behavior.

Advocates of praxeology also say that it provides insights for the field of ethics.

Source: en.wikipedia.org/wiki/Praxeology

Albert Pike’s vision of three world wars (1871)

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en.wikipedia.org/wiki/Albert_Pike

“The First World War must be brought about in order to permit the Illuminati to overthrow the power of the Czars in Russia and of making that country a fortress of atheistic Communism. The divergences caused by the “agentur” (agents) of the Illuminati between the British and Germanic Empires will be used to foment this war. At the end of the war, Communism will be built and used in order to destroy the other governments and in order to weaken the religions.”

“The Second World War must be fomented by taking advantage of the differences between the Fascists and the political Zionists. This war must be brought about so that Nazism is destroyed and that the political Zionism be strong enough to institute a sovereign state of Israel in Palestine. During the Second World War, International Communism must become strong enough in order to balance Christendom, which would be then restrained and held in check until the time when we would need it for the final social cataclysm.”

“The Third World War must be fomented by taking advantage of the differences caused by the “agentur” of the “Illuminati” between the political Zionists and the leaders of Islamic World. The war must be conducted in such a way that Islam (the Moslem Arabic World) and political Zionism (the State of Israel) mutually destroy each other. Meanwhile the other nations, once more divided on this issue will be constrained to fight to the point of complete physical, moral, spiritual and economical exhaustion…We shall unleash the Nihilists and the atheists, and we shall provoke a formidable social cataclysm which in all its horror will show clearly to the nations the effect of absolute atheism, origin of savagery and of the most bloody turmoil. Then everywhere, the citizens, obliged to defend themselves against the world minority of revolutionaries, will exterminate those destroyers of civilization, and the multitude, disillusioned with Christianity, whose deistic spirits will from that moment be without compass or direction, anxious for an ideal, but without knowing where to render its adoration, will receive the true light through the universal manifestation of the pure doctrine of Lucifer, brought finally out in the public view. This manifestation will result from the general reactionary movement which will follow the destruction of Christianity and atheism, both conquered and exterminated at the same time.”

Hail Hydra (Hydra vulgaris)

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“As far as we can tell, it doesn’t age or die,” says Assistant Professor Celina Juliano, Department of Molecular and Cellular Biology. “You can cut little pieces out of the animal and it will regrow and maybe the most amazing thing is that you can dissociate the animal into single cells, mix them all up, put them back in a ball and a new Hydra will just grow out of it.”

biology.ucdavis.edu/research/model-organisms/hydra

en.wikipedia.org/wiki/Hydra_(comics)

Prof. Noam Chomsky on the State-Corporate Complex: A Threat to Freedom and Survival

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Abuse of authority by the UN: Sexual exploitation and abuse of children covered up

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In reviewing the UN’s response to the Allegations on the ground, the Panel finds that the head of HRJS and the SRSG of MINUSCA both committed an abuse of authority. As head of the mission and the most senior UN official in CAR, the SRSG of MINUSCA was the person most able to intervene with officials to hold the perpetrators accountable and to stop the abuses from reoccurring. Yet despite being made aware of the Allegations on a number of occasions, he took no steps to ensure that follow up occurred. The security situation in CAR and the absence of clear guidelines with respect to non-UN command troops provide some context to the SRSG’s conduct. However, they do not justify his persistent failure to take action in the face of the seriousness of the Allegations. Rather, his failure to take steps to prevent the sexual abuse of children or to ensure the accountability of the perpetrators was a total abdication of his responsibility to uphold human rights in the implementation of MINUSCA’s mandate. Similarly, the actions of the head of HRJS show an outright disregard for his obligations as head of the human rights component of the UN mission in CAR. For example, he neither considered that protection of the children at risk was his responsibility nor acknowledged that the Allegations brought to light what could potentially be systematic violations which required urgent action to halt further abuse, identify the perpetrators, and ensure that they were held accountable. He also failed to follow up with other children who were allegedly abused. Instead, he appears to have been preoccupied by the political sensitivity of the Allegations.
Taking Action on Sexual Exploitation and Abuse by Peacekeepers

Humes’ is-ought problem

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The is–ought problem, as articulated by the Scottish philosopher and historian David Hume, arises when one makes claims about what ought to be that are based solely on statements about what is. Hume found that there seems to be a significant difference between descriptive or positive statements (about what is) and prescriptive or normative statements (about what ought to be), and that it is not obvious how one can coherently move from descriptive statements to prescriptive ones. Hume’s law or Hume’s guillotine, is the thesis that, if a reasoner only has access to non-moral and non-evaluative factual premises, the reasoner cannot logically infer the truth of moral statements.

A similar view is defended by G. E. Moore‘s open-question argument, intended to refute any identification of moral properties with natural properties. This so-called naturalistic fallacy stands in contrast to the views of ethical naturalists.

The is–ought problem is closely related to the fact–value distinction in epistemology.

Further References

Mooya, M.. (2022). Hume’s guillotine – the ‘is-ought’ problem in property valuation theory. Journal of Property Research

Plain numerical DOI: 10.1080/09599916.2021.1918222
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“This paper introduces hume’s law (the fulcrum of the ‘is-ought’ problem of moral philosophy) into the property valuation literature, and uses it as a prism to reflect on the nature and limitations of standard valuation theory. the paper shows how a consideration of hume’ thesis can help to clarify and solve some specific practical problems in property valuation. the opportunity presented by the subject of property valuation is, in turn, used to reflect back on hume’s thesis itself, to show conditions under which hume’s law may be said to be false. the paper makes important contributions both to the property valuation literature and to the literature on moral philosophy. with respect to property valuation, it proposes a change in the manner conclusions of valuations are reported, and the replacement of the notion of valuation accuracy by the wider and more socially appropriate concept of reasonableness.”

Spielthenner, G.. (2017). The Is-Ought Problem in Practical Ethics. HEC Forum

Plain numerical DOI: 10.1007/s10730-016-9318-8
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“This article is concerned with the role empirical research can play in normative practical ethics. there is no doubt that ethical research requires some kind of collaboration between normative disciplines and empirical sciences. but many researchers hold that empirical science is only assigned a subordinate role, due to the doctrine that normative conclusions cannot be justified by descriptive premises. scientists working in the field of ethics commonly hold, however, that the empirical sciences should play a much bigger role in ethical research. the aim of this paper is to show that empirical sciences can play a substantive role in normative ethics, with no illicit inferences from is to ought. to achieve this aim, i explain (in ‘the is-ought problem explained’ section) hume’s thesis. in the following sections, i am concerned with different uses of empirical data that do not imply an illicit inference from descriptive premises to a normative conclusion. the article demonstrates that there are many modes of ethical reasoning that allow for a substantive use of empirical data, and it also shows the importance of hume’s thesis for clarifying ethical reasoning.”

Hapla, M.. (2020). Justification of human rights and is-ought problem. Casopis pro Pravni Vedu a Praxi

Plain numerical DOI: 10.5817/CPVP2020-1-3
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“Clarifying the transition from facts to norms is one of the key issues of legal philosophy and ethics. in the article, the author analyzes how various theories of justification of human rights attempt to solve it. he first characterizes human rights as critical moral rights and clarifies in what sense we can say that they exist. he then describes the is-ought problem and analyzes why some approaches cannot deal with him adequately. at first, he focuses on human rights justification through the concept of basic needs and capabilities, later on robert alexy’s explicative-existential justification. however, the greatest attention is paid to the justification theory, which was constructed by alan gewirth, one of the main representatives of ethical rationalism. according to the author, this is the most sophisticated attempt to deal with this problem in the field of human rights. in the last part of the article, the author formulates his own opinion on it. according to him, the solution is to stop imposing absolute demands on the justification of these rights, but to start assessing its strengths and weaknesses in relation to the concepts that compete with it.”

Pigden, C.. (2001). The Is-Ought Problem: An Investigation in Philosophical Logic. Australasian Journal of Philosophy

Plain numerical DOI: 10.1080/713659291
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Iwasa, N.. (2011). Sentimentalism and the is-ought problem. Croatian Journal of Philosophy

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“Examining the moral sense theories of francis hutcheson, david hume, and adam smith from the perspective of the is-ought problem, this essay shows that the moral sense or moral sentiments in those theories alone cannot identify appropriate morals. according to one interpretation, hume’s or smith’s theory is just a description of human nature. in this case, it does not answer the question of how we ought to live. according to another interpretation, it has some normative implications. in this case, it draws normative claims from human nature. anyway, the sentiments of anger, resentment, vengeance, superiority, sympathy, and benevolence show that drawing norms from human nature is sometimes morally problematic. the changeability of the moral sense and moral sentiments in hume’s and smith’s theories supports this idea. hutcheson’s theory is morally more appropriate because it bases morality on disinterested benevolence. yet disinterested benevolence is not enough for morality. there are no sentiments the presence of which alone makes any action moral.”

de Vries, R.. (2011). The Uses and Abuses of Moral Theory in Bioethics. Ethical Theory and Moral Practice

Plain numerical DOI: 10.1007/s10677-011-9290-y
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“Moral theory is an important guide to bioethical decision-making, but it can confuse and mislead those who offer ethical advice to clinicians and researchers, delaying decisions that must be made in a timely fashion. in this paper i examine the ways moral theory can lead bioethicists astray. absent a sensitivity to the empirical realities of ethical problems, moral theory 1) contributes to the disappearance of the persons caught in an ethical quandary, 2) focuses on the puzzle-solving rather than examining the conditions that generate moral problems, and 3) universalizes ethical dilemmas, overlooking local processes for resolving moral questions. taken together, empirically informed moral theory and theoretically informed empirical research can help bioethicists transcend the is/ought problem in ethical work. © 2011 springer science+business media b.v.”

Sisk, B. A., Mozersky, J., Antes, A. L., & DuBois, J. M.. (2020). The “Ought-Is” Problem: An Implementation Science Framework for Translating Ethical Norms Into Practice. American Journal of Bioethics

Plain numerical DOI: 10.1080/15265161.2020.1730483
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“We argue that once a normative claim is developed, there is an imperative to effect changes based on this norm. as such, ethicists should adopt an ‘implementation mindset’ when formulating norms, and collaborate with others who have the expertise needed to implement policies and practices. to guide this translation of norms into practice, we propose a framework that incorporates implementation science into ethics. implementation science is a discipline dedicated to supporting the sustained enactment of interventions. we further argue that implementation principles should be integrated into the development of specific normative claims as well as the enactment of these norms. ethicists formulating a specific norm should consider whether that norm can feasibly be enacted because the resultant specific norm will directly affect the types of interventions subsequently developed. to inform this argument, we will describe the fundamental principles of implementation science, using informed consent to research participation as an illustration.”

Hormesis in toxicology

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Hormesis is a characteristic of many biological processes, namely a biphasic or triphasic response to exposure to increasing amounts of a substance or condition. Within the hormetic zone, the biological response to low exposures to toxins and other stressors is generally favorable. The term “hormesis” comes from Greek hórmēsis “rapid motion, eagerness”, itself from ancient Greek hormáein “to set in motion, impel, urge on”, the same Greek root as the word hormone. The term ‘hormetics’ has been proposed for the study and science of hormesis.

In toxicology, hormesis is a dose response phenomenon to xenobiotics or other stressors characterized by a low-dose stimulation, with zero dose and high-dose inhibition, thus resulting in a J-shaped or an inverted U-shaped dose response (e.g. the arms of the “U” are inhibitory or toxic concentrations whereas the curve region stimulates a beneficial response.) Generally speaking, hormesis pertains to the study of benefits of exposure to toxins such as radiation or mercury (perhaps analogous to health paradoxes such as the smoker’s paradox, although differing by virtue of dose-dependent effects). Microdosing, and to some extent homeopathy, are often regarded as applications of hormesis.

In physiology and nutrition, hormesis can be visualized as a hormetic curve with regions of deficiency, homeostasis, and toxicity. Physiological concentrations deviating above or below homeostasis concentrations adversely affects an organism, thus in this context, the hormetic zone is synonymously known as the region of homeostasis. In pharmacology the hormetic zone is similar to the therapeutic window. Some psychological or environmental factors that would seem to produce positive responses have also been termed “eustress”.

In the context of toxicology, the hormesis model of dose response is vigorously debated.The biochemical mechanisms by which hormesis works (particularly in applied cases pertaining to behavior and toxins) remain under early laboratory research and are not well understood. The notion that hormesis is an important policy factor for chemical risk regulations is not widely accepted.

Further References

Calabrese, E. J., & Baldwin, L. A.. (2002). Defining hormesis. Human and Experimental Toxicology

Plain numerical DOI: 10.1191/0960327102ht217oa
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“Much confusion surrounds the concept of hormesis and what its biological meaning represents. this paper provides a definition of hormesis that addresses its historical foundations, quantitative features, and underlying evolutionary and toxicologically based mechanistic strategies. hormesis should be considered an adaptive response characterized by biphasic dose responses of generally similar quantitative features with respect to amplitude and range of the stimulatory response that are either directly induced or the result of compensatory biological processes following an initial disruption in homeostasis. given the limited magnitude of the stimulatory response (i.e., usually 30-60% greater than controls at maximum), heightened study design and replication requirements are often necessary to ensure reliable judgments on causality. even though hormesis is considered an adaptive response, the issue of beneficial/harmful effects should not be part of the definition of hormesis, but reserved to a subsequent evaluation of the biological and ecological context of the response.”

Mattson, M. P.. (2008). Hormesis defined. Ageing Research Reviews

Plain numerical DOI: 10.1016/j.arr.2007.08.007
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“Hormesis is a term used by toxicologists to refer to a biphasic dose-response to an environmental agent characterized by a low dose stimulation or beneficial effect and a high dose inhibitory or toxic effect. in the fields of biology and medicine hormesis is defined as an adaptive response of cells and organisms to a moderate (usually intermittent) stress. examples include ischemic preconditioning, exercise, dietary energy restriction and exposures to low doses of certain phytochemicals. recent findings have elucidated the cellular signaling pathways and molecular mechanisms that mediate hormetic responses which typically involve enzymes such as kinases and deacetylases, and transcription factors such as nrf-2 and nf-κb. as a result, cells increase their production of cytoprotective and restorative proteins including growth factors, phase 2 and antioxidant enzymes, and protein chaperones. a better understanding of hormesis mechanisms at the cellular and molecular levels is leading to and to novel approaches for the prevention and treatment of many different diseases.”

Ullman, D.. (2021). Exploring Possible Mechanisms of Hormesis and Homeopathy in the Light of Nanopharmacology and Ultra-High Dilutions. Dose-Response

Plain numerical DOI: 10.1177/15593258211022983
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“Serially diluted succussed solutions of a suitable drug/toxic substance can exhibit physicochemical and biological properties even far beyond avogadro’s limit defying conventional wisdom. they can show hormesis, and homeopathy uses them as medicines. many studies confirm that they can have an impact on gene expression different than controls. water in the exclusion zone phase can have memory but for a short period. however, the nanoparticle as the physical substrate can hold information. nanoparticle and exclusion zone duo as nanoparticle-exclusion zone shell can provide a prolonged memory. the nanoparticle-exclusion zone shell model may be an important step toward explaining the nature and bioactivity of serially diluted succussed solutions used as homeopathic medicines. this model may also provide insight into the workings of hormesis. hormesis is the primary phenomenon through which homeopathic phenomenon may have evolved exhibiting the principle of similars. hahnemann exploited it to establish homeopathy. the nanoparticle-exclusion zone shells present in the remedy, selected on the principle of similars, can be patient-specific nanoparticles in a symptom syndrome-specific manner. they can carry the drug-specific information for safer clinical applications in an amplified form for high yielding. it suggests homeopathy is a type of nanopharmacology.”

Calabrese, E. J.. (2014). Hormesis: A fundamental concept in biology. Microbial Cell

Plain numerical DOI: 10.15698/mic2014.05.145
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“This paper assesses the hormesis dose response concept, including its historical foundations, frequency, generality, quantitative features, mechanistic basis and biomedical, pharmaceutical and environmental health implications. the hormetic dose response is highly generalizable, being independent of biology model (i.e. common from plants to humans), level of biological organization (i.e. cell, organ and organism), endpoint, inducing agent and mechanism, providing the first general and quantitative description of plasticity. the hormetic dose response describes the limits to which integrative endpoints (e.g. cell proliferation, cell migration, growth patterns, tissue repair, aging processes, complex behaviors such as anxiety, learning, memory, and stress, preconditioning responses, and numerous adaptive re-sponses) can be modulated (i.e., enhanced or diminished) by pharmaceutical, chemical and physical means. thus, the hormesis concept is a fundamental concept in biology with a wide range of biological implications and biomedical applications.”

Calabrese, E. J.. (2020). Hormesis and ginseng: Ginseng mixtures and individual constituents commonly display hormesis dose responses, especially for neuroprotective effects. Molecules

Plain numerical DOI: 10.3390/molecules25112719
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“This paper demonstrates that ginseng mixtures and individual ginseng chemical constituents commonly induce hormetic dose responses in numerous biological models for endpoints of biomedical and clinical relevance, typically providing a mechanistic framework. the principal focus of ginseng hormesis-related research has been directed toward enhancing neuroprotection against conditions such as alzheimer’s and parkinson’s diseases, stroke damage, as well as enhancing spinal cord and peripheral neuronal damage repair and reducing pain. ginseng was also shown to reduce symptoms of diabetes, prevent cardiovascular system damage, protect the kidney from toxicities due to immune suppressant drugs, and prevent corneal damage, amongst other examples. these findings complement similar hormetic-based chemoprotective reports for other widely used dietary-type supplements such as curcumin, ginkgo biloba, and green tea. these findings, which provide further support for the generality of the hormetic dose response in the biomedical literature, have potentially important public health and clinical implications.”

Mcclure, C. D., Zhong, W., Hunt, V. L., Chapman, F. M., Hill, F. V., & Priest, N. K.. (2014). Hormesis results in trade-offs with immunity. Evolution

Plain numerical DOI: 10.1111/evo.12453
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“Many have argued that we may be able to extend life and improve human health through hormesis, the beneficial effects of low-level toxins and other stressors. but, studies of hormesis in model systems have not yet established whether stress-induced benefits are cost free, artifacts of inbreeding, or come with deleterious side effects. here, we provide evidence that hormesis results in trade-offs with immunity. we find that a single topical dose of dead spores of the entomopathogenic fungus, metarhizium robertsii, increases the longevity of the fruit fly, drosophila melanogaster, without significant decreases in fecundity. we find that hormetic benefits of pathogen challenge are greater in lines that lack key components of antifungal immunity (dif and turandot m). and, in outbred fly lines, we find that topical pathogen challenge enhances both survival and fecundity, but reduces ability to fight off live infections. the results provide evidence that hormesis is manifested by stress-induced trade-offs with immunity, not cost-free benefits or artifacts of inbreeding. our findings illuminate mechanisms underlying pathogen-induced life-history trade-offs, and indicate that reduced immune function may be an ironic side effect of the “elixirs of life. © 2014 the author(s).”

Zimmermann, A., Bauer, M. A., Kroemer, G., Madeo, F., & Carmona-Gutierrez, D.. (2014). When less is more: Hormesis against stress and disease. Microbial Cell

Plain numerical DOI: 10.15698/mic2014.05.148
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“All living organisms need to adapt to ever changing adverse conditions in order to survive. the phenomenon termed hormesis describes an evolutionarily conserved process by which a cell or an entire organism can be preconditioned, meaning that previous exposure to low doses of an insult protects against a higher, normally harmful or lethal dose of the same stress-or. growing evidence suggests that hormesis is directly linked to an organ-ism’s (or cell’s) capability to cope with pathological conditions such as aging and age-related diseases. here, we condense the conceptual and potentially therapeutic importance of hormesis by providing a short overview of current evidence in favor of the cytoprotective impact of hormesis, as well as of its underlying molecular mechanisms.”

Calabrese, E. J., & Mattson, M. P.. (2017). How does hormesis impact biology, toxicology, and medicine?. Npj Aging and Mechanisms of Disease

Plain numerical DOI: 10.1038/s41514-017-0013-z
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“Hormesis refers to adaptive responses of biological systems to moderate environmental or self-imposed challenges through which the system improves its functionality and/or tolerance to more severe challenges. the past two decades have witnessed an expanding recognition of the concept of hormesis, elucidation of its evolutionary foundations, and underlying cellular and molecular mechanisms, and practical applications to improve quality of life. to better inform future basic and applied research, we organized and re-evaluated recent hormesis-related findings with the intent of incorporating new knowledge of biological mechanisms, and providing fundamental insights into the biological, biomedical and risk assessment implications of hormesis. as the literature on hormesis is expanding rapidly into new areas of basic and applied research, it is important to provide refined conceptualization of hormesis to aid in designing and interpreting future studies. here, we establish a working compartmentalization of hormesis into ten categories that provide an integrated understanding of the biological meaning and applications of hormesis.”

Calabrese, E. J.. (2018). Hormesis: Path and progression to significance. International Journal of Molecular Sciences

Plain numerical DOI: 10.3390/ijms19102871
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“This paper tells the story of how hormesis became recognized as a fundamental concept in biology, affecting toxicology, microbiology, medicine, public health, agriculture, and all areas related to enhancing biological performance. this paper assesses how hormesis enhances resilience to normal aging and protects against a broad spectrum of neurodegenerative, cardiovascular, and other diseases, as well as trauma and other threats to health and well-being. this paper also explains the application of hormesis to several neurodegenerative diseases such as parkinson’s and huntington’s disease, macrophage polarization and its systematic adaptive protections, and the role of hormesis in enhancing stem cell functioning and medical applications.”

Brain Science from Bench to Battlefield: The Realities – and Risks – of Neuroweapons | CGSR Seminar

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Dr. James Giordano: clinicalbioethics.georgetown.edu/jgiordano/
Animated version: cognitive-liberty.online/the-matrix-agent-smith-and-dual-use-neuroscience/

James Giordano, PhD, MPhil, is Chief of the Neuroethics Studies Program, Scholar-in-Residence, leads the Sub-Program in Military Medical Ethics, and Co-director of the O’Neill-Pellegrino Program in Brain Science and Global Health Law and Policy in the Pellegrino Center for Clinical Bioethics; and is Professor in the Departments of Neurology and Biochemistry at Georgetown University Medical Center, Washington, DC, USA. He is also Distinguished Visiting Professor of Brain Science, Health Promotions and Ethics at the Coburg University of Applied Sciences, Coburg, Germany, and was formerly 2011-2012 JW Fulbright Foundation Visiting Professor of Neurosciences and Neuroethics at the Ludwig-Maximilians University, Munich, Germany.

Prof. Giordano currently serves as Chair of the Neuroethics Program of the IEEE Brain Project, and an appointed member of the Neuroethics, Legal and Social Issues (NELSI) Advisory Panel of the Defense Advanced Research Projects’ Agency (DARPA). He has previously served as Research Fellow and Task Leader of the EU Human Brain Project Sub-Project on Dual-Use Brain Science; an appointed member of United States Department of Health and Human Services Secretary’s Advisory Council on Human Research Protections (SACHRP); and as Senior Science Advisory Fellow of the Strategic Multilayer Assessment Branch of the Joint Staff of the Pentagon.

Further References

Year	Citation	Score
2020	DeFranco J, Rhemann M, Giordano J. The Emerging Neurobioeconomy: Implications for National Security. Health Security. 18: 267-277. PMID 32816585 DOI: 10.1089/Hs.2020.0009	0.322
2020	Ramirez-Zamora A, Giordano J, Gunduz A, Alcantara J, Cagle JN, Cernera S, Difuntorum P, Eisinger RS, Gomez J, Long S, Parks B, Wong JK, Chiu S, Patel B, Grill WM, et al. Proceedings of the Seventh Annual Deep Brain Stimulation Think Tank: Advances in Neurophysiology, Adaptive DBS, Virtual Reality, Neuroethics and Technology. Frontiers in Human Neuroscience. 14: 54. PMID 32292333 DOI: 10.3389/Fnhum.2020.00054	0.33
2019	Shook JR, Giordano J. Ethical Contexts for the Future of Neuroethics. Ajob Neuroscience. 10: 134-136. PMID 31361203 DOI: 10.1080/21507740.2019.1632969	0.328
2018	Giordano J. Looking Ahead: The Importance of Views, Values, and Voices in Neuroethics-Now. Cambridge Quarterly of Healthcare Ethics : Cq : the International Journal of Healthcare Ethics Committees. 27: 728-731. PMID 30198475 DOI: 10.1017/S096318011800021X	0.355
2017	Kraft CJ, Giordano J. Integrating Brain Science and Law: Neuroscientific Evidence and Legal Perspectives on Protecting Individual Liberties. Frontiers in Neuroscience. 11: 621. PMID 29167633 DOI: 10.3389/Fnins.2017.00621	0.344
2017	Akram F, Giordano J. Research Domain Criteria as Psychiatric Nosology. Cambridge Quarterly of Healthcare Ethics : Cq : the International Journal of Healthcare Ethics Committees. 26: 592-601. PMID 28937340 DOI: 10.1017/S096318011700010X	0.34
2017	DiEuliis D, Giordano J. Why Gene Editors Like CRISPR/Cas May Be a Game-Changer for Neuroweapons. Health Security. 15: 296-302. PMID 28574731 DOI: 10.1089/Hs.2016.0120	0.336
2017	Becker K, Shook JR, Darragh M, Giordano J. A four-part working bibliography of neuroethics: Part 4 – Ethical issues in clinical and social applications of neuroscience. Philosophy, Ethics, and Humanities in Medicine : Pehm. 12: 1. PMID 28569221 DOI: 10.1186/S13010-017-0043-Y	0.371
2017	Giordano J, Bikson M, Kappenman ES, Clark VP, Coslett HB, Hamblin MR, Hamilton R, Jankord R, Kozumbo WJ, McKinley RA, Nitsche MA, Reilly JP, Richardson J, Wurzman R, Calabrese E. Mechanisms and Effects of Transcranial Direct Current Stimulation. Dose-Response : a Publication of International Hormesis Society. 15: 1559325816685467. PMID 28210202 DOI: 10.1177/1559325816685467	0.329
2016	Wurzman R, Yaden D, Giordano J. Neuroscience Fiction as Eidolá: Social Reflection and Neuroethical Obligations in Depictions of Neuroscience in Film. Cambridge Quarterly of Healthcare Ethics : Cq : the International Journal of Healthcare Ethics Committees. 1-21. PMID 27852344 DOI: 10.1017/S0963180116000578	0.313
2016	Martin A, Becker K, Darragh M, Giordano J. A four-part working bibliography of neuroethics: part 3 – “second tradition neuroethics” – ethical issues in neuroscience. Philosophy, Ethics, and Humanities in Medicine : Pehm. 11: 7. PMID 27646569 DOI: 10.1186/S13010-016-0037-1	0.335
2016	Giordano J. Commentary: The Value of Patient Benefit: Consideration of Framing Contingencies to Guide the Ethical Use of DBS-a Case Analysis. Cambridge Quarterly of Healthcare Ethics : Cq : the International Journal of Healthcare Ethics Committees. 25: 755-8. PMID 27634728 DOI: 10.1017/S0963180116000530	0.317
2016	Shats K, Brindley T, Giordano J. Don’t Ask a Neuroscientist about Phases of the Moon. Cambridge Quarterly of Healthcare Ethics : Cq : the International Journal of Healthcare Ethics Committees. 25: 712-25. PMID 27634722 DOI: 10.1017/S0963180116000438	0.352
2016	Giordano J. Toward an Operational Neuroethical Risk Analysis and Mitigation Paradigm for Emerging Neuroscience and Technology (NeuroS/T). Experimental Neurology. PMID 27468658 DOI: 10.1016/J.Expneurol.2016.07.016	0.319
2016	Armon E, Kohls NB, Giordano J. On the viability of neurotechnology and mind–body methods in pediatric mental health: Perspectives on integrating new tools to complement old techniques European Journal of Integrative Medicine. 8: 137-140. DOI: 10.1016/J.Eujim.2015.12.011	0.33
2015	Shook JR, Giordano J. Principled research ethics in practice? Reflections for neuroethics and bioethics. Cortex; a Journal Devoted to the Study of the Nervous System and Behavior. 71: 423-6. PMID 25935658 DOI: 10.1016/J.Cortex.2015.03.017	0.304
2015	Giordano J, Shook JR. Minding Brain Science in Medicine: On the Need for Neuroethical Engagement for Guidance of Neuroscience in Clinical Contexts Ethics in Biology, Engineering and Medicine: An International Journal. 6: 37-41. DOI: 10.1615/Ethicsbiologyengmed.2015015333	0.315
2014	Buniak L, Darragh M, Giordano J. A four-part working bibliography of neuroethics: part 1: overview and reviews–defining and describing the field and its practices. Philosophy, Ethics, and Humanities in Medicine : Pehm. 9: 9. PMID 24885037 DOI: 10.1186/1747-5341-9-9	0.344
2014	Loveless SE, Giordano J. Neuroethics, painience, and neurocentric criteria for the moral treatment of animals. Cambridge Quarterly of Healthcare Ethics : Cq : the International Journal of Healthcare Ethics Committees. 23: 163-72. PMID 24495713 DOI: 10.1017/S0963180113000698	0.322
2014	Giordano J, Kulkarni A, Farwell J. Deliver us from evil? The temptation, realities, and neuroethico-legal issues of employing assessment neurotechnologies in public safety initiatives. Theoretical Medicine and Bioethics. 35: 73-89. PMID 24442931 DOI: 10.1007/S11017-014-9278-4	0.317
2014	Shook JR, Giordano J. A principled and cosmopolitan neuroethics: considerations for international relevance. Philosophy, Ethics, and Humanities in Medicine : Pehm. 9: 1. PMID 24387102 DOI: 10.1186/1747-5341-9-1	0.344
2014	Rossi PJ, Okun M, Giordano J. Translational Imperatives in Deep Brain Stimulation Research: Addressing Neuroethical Issues of Consequences and Continuity of Clinical Care Ajob Neuroscience. 5: 46-48. DOI: 10.1080/21507740.2013.863248	0.311
2013	Giordano J. Ethical considerations in the globalization of medicine–an interview with James Giordano. Bmc Medicine. 11: 69. PMID 23496884 DOI: 10.1186/1741-7015-11-69	0.307
2013	Giordano J, Rossi PJ, Benedikter R. Addressing the Quantitative and Qualitative: A View to Complementarity—From the Synaptic to the Social Open Journal of Philosophy. 3: 1-5. DOI: 10.4236/Ojpp.2013.34A001	0.358
2013	Rossi PJ, Novotny P, Paulick P, Plischke H, Kohls NB, Giordano J. Decision Technologies in Medical Research and Practice: Practical Considerations, Ethical Implications, and the Need for Dialectic Evaluation Ethics in Biology, Engineering and Medicine. 4: 91-102. DOI: 10.1615/Ethicsbiologyengmed.2013008091	0.305
2013	Giordano J. Unpacking neuroscience and neurotechnology – Instructions not included: Neuroethics required Neuroethics. 6: 411-414. DOI: 10.1007/S12152-011-9150-4	0.373
2012	Kawa S, Giordano J. A brief historicity of the Diagnostic and Statistical Manual of Mental Disorders: issues and implications for the future of psychiatric canon and practice. Philosophy, Ethics, and Humanities in Medicine : Pehm. 7: 2. PMID 22243976 DOI: 10.1186/1747-5341-7-2	0.331
2011	Jotterand F, Giordano J. Transcranial magnetic stimulation, deep brain stimulation and personal identity: ethical questions, and neuroethical approaches for medical practice. International Review of Psychiatry (Abingdon, England). 23: 476-85. PMID 22200137 DOI: 10.3109/09540261.2011.616189	0.316
2011	Kohls N, Sauer S, OffenbÃ¤cher M, Giordano J. Spirituality: an overlooked predictor of placebo effects? Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 366: 1838-48. PMID 21576141 DOI: 10.1098/Rstb.2010.0389	0.34
2011	Giordano J, Benedikter R. The shifting architectonics of pain medicine: toward ethical realignment of scientific, medical and market values for the emerging global community–groundwork for policy. Pain Medicine (Malden, Mass.). 12: 406-14. PMID 21332927 DOI: 10.1111/J.1526-4637.2011.01055.X	0.335
2010	Benedikter R, Giordano J, Fitzgerald K. The future of the self-image of the human being in the Age of Transhumanism, Neurotechnology and Global Transition Futures. 42: 1102-1109. DOI: 10.1016/J.Futures.2010.08.010	0.313
2010	Giordano J, Hutchison PJ, Benedikter RAJ. Culture, Sustainability, and Medicine in the Twenty-first Century. Re-grounding the Focus of Medicine Amidst the Current “Global Systemic Shift” and the Forces of the Market: Elements for a Contemporary Social Philosophy of Medicine International Journal of Politics, Culture and Society. 23: 29-41. DOI: 10.1007/S10767-009-9085-5	0.313
2009	Giordano J, Akhouri R, McBride D. Implantable nano-neurotechnological devices: consideration of ethical, legal, and social issues and implications. Journal of Long-Term Effects of Medical Implants. 19: 83-93. PMID 20402632 DOI: 10.1615/Jlongtermeffmedimplants.V19.I1.80	0.321
2009	Giordano J. Quo vadis? Philosophy, Ethics, and Humanities in Medicine preserving the humanistic character of medicine in a biotechnological future. Philosophy, Ethics, and Humanities in Medicine : Pehm. 4: 12. PMID 19682382 DOI: 10.1186/1747-5341-4-12	0.401
2009	Giordano J, Engebretson JC, Benedikter R. Culture, subjectivity, and the ethics of patient-centered pain care. Cambridge Quarterly of Healthcare Ethics : Cq : the International Journal of Healthcare Ethics Committees. 18: 47-56. PMID 19091145 DOI: 10.1017/S0963180108090087	0.306
2009	Loveless S, Giordano J. Erlebnis, Erwartung und Ethik (Experience, Expectation, and Ethics) Neuroethics. 2: 113-113. DOI: 10.1007/S12152-009-9035-Y	0.359
2008	Giordano J, Ives JA, Jonas WB. Hormetic responses in neural systems: consideration, contexts, and caveats. Critical Reviews in Toxicology. 38: 623-7. PMID 18709570 DOI: 10.1080/10408440802026356	0.31
2008	Giordano J. Complementarity, brain-mind, and pain. Forschende Komplementarmedizin (2006). 15: 71-3. PMID 18496019 DOI: 10.1159/000121106	0.317
2007	Ives JA, Giordano J. Unusual claims, normative process: on the use and stringency of the scientific method. Complementary Medicine Research. 14: 138-139. PMID 17596693 DOI: 10.1159/000103287	0.339
2007	Giordano J, O’Reilly M, Taylor H, Dogra N. Confidentiality and Autonomy: The Challenge(s) of Offering Research Participants a Choice of Disclosing Their Identity Qualitative Health Research. 17: 264-275. PMID 17220396 DOI: 10.1177/1049732306297884	0.331
2006	Giordano J, Engebretson J. Neural and cognitive basis of spiritual experience: biopsychosocial and ethical implications for clinical medicine. Explore (New York, N.Y.). 2: 216-25. PMID 16781644 DOI: 10.1016/J.Explore.2006.02.002	0.339
2005	Giordano J, Engebretson J, Garcia MK. Challenges to complementary and alternative medical research: focal issues influencing integration into a cancer care model. Integrative Cancer Therapies. 4: 210-8. PMID 16113028 DOI: 10.1177/1534735405279179	0.33
2004	Giordano J, Garcia MK, Strickland G. Integrating Chinese traditional medicine into a U.S. public health paradigm Journal of Alternative and Complementary Medicine. 10: 706-710. PMID 15353031 DOI: 10.1089/Acm.2004.10.706	0.336
2003	Giordano J, Garcia MK, Boatwright D, Klein K. Complementary and alternative medicine in mainstream public health: A role for research in fostering integration Journal of Alternative and Complementary Medicine. 9: 441-445. PMID 12816632 DOI: 10.1089/107555303765551660	0.321

Neuroweapons & neurohacking (dual-use neuroscience)

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Janus, Roman god of gates, doorways, beginnings, and endings, and Bellona, Roman goddess of war. Sculpture by Johann Wilhelm Beyer, 1773-80 CE, Vienna, Schönbrunn Garden.

Why Gene Editors Like CRISPR/Cas May Be a Game-Changer for Neuroweapons

“This year marks the Eighth Review Conference (RevCon) of the Biological Toxins and Weapons Convention (BWC). At the same time, ongoing international efforts to further and more deeply investigate the brain’s complex neuronal circuitry are creating unprecedented capabilities to both understand and control neurological processes of thought, emotion, and behavior. These advances have tremendous promise for human health, but the potential for their misuse has also been noted, with most discussions centering on research and development of agents that are addressed by existing BWC and Chemical Weapons Convention (CWC) proscriptions. In this article, we discuss the dual-use possibilities fostered by employing emergent biotechnologic techniques and tools—specifically, novel gene editors like clustered regular interspaced short palindromic repeats (CRISPR)—to produce neuroweapons. Based on our analyses, we posit the strong likelihood that development of genetically modified or created neurotropic substances will advance apace with other gene-based therapeutics, and we assert that this represents a novel—and realizable—path to creating potential neuroweapons. In light of this, we propose that it will be important to re-address current categorizations of weaponizable tools and substances, so as to better inform and generate tractable policy to enable improved surveillance and governance of novel neuroweapons.
The authors discuss the dual-use possibilities fostered by employing emergent biotechnologic techniques and tools—specifically, novel gene editors like clustered regular interspaced short palindromic repeats (CRISPR)—to produce neuroweapons. They posit the strong likelihood that development of genetically modified or created neurotropic substances will advance apace with other gene-based therapeutics and assert that this represents a novel—and realizable—path to creating potential neuroweapons.”
[…] “In the interim, it is likely that more indirect means of manipulating the brain and behavior will be developed. ‘‘Neurohacking’’ will increase, and biotechnology, such as CRISPR/Cas and novel gene editors, will provide tools to realize production of novel neuroagents with dual-use po-
tential. Simple acknowledgment of these facts, however, is insufficient. It will be essential to pursue and obtain a deeper and fuller understanding of the ways that genetic pathways to human cognitive and behavioral modification can be engaged for dual and direct use as neuroweapons, to
formulate policies based on this level of understanding, and to engage surveillance of the use of these technologies in various silos of development and application, so as to afford both preventive and more preparatory capabilities.”

DiEuliis, D., & Giordano, J.. (2017). Why Gene Editors Like CRISPR/Cas May Be a Game-Changer for Neuroweapons. Health Security, 15(3), 296–302.

Plain numerical DOI: 10.1089/hs.2016.0120
DOI URL
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“This year marks the eighth review conference (revcon) of the biological toxins and weapons convention (bwc). at the same time, ongoing international efforts to further and more deeply investigate the brain’s complex neuronal circuitry are creating unprecedented capabilities to both understand and control neurological processes of thought, emotion, and behavior. these advances have tremendous promise for human health, but the potential for their misuse has also been noted, with most discussions centering on research and development of agents that are addressed by existing bwc and chemical weapons convention (cwc) proscriptions. in this article, we discuss the dual-use possibilities fostered by employing emergent biotechnologic techniques and tools – specifically, novel gene editors like clustered regular interspaced short palindromic repeats (crispr) – to produce neuroweapons. based on our analyses, we posit the strong likelihood that development of genetically modified or created neurotropic substances will advance apace with other gene-based therapeutics, and we assert that this represents a novel – and realizable – path to creating potential neuroweapons. in light of this, we propose that it will be important to re-address current categorizations of weaponizable tools and substances, so as to better inform and generate tractable policy to enable improved surveillance and governance of novel neuroweapons.”

Janus and his two faces: past and future.

“There is a scientific race for decoding the human brain. current and near future technology will make it possible to not only merely influence the enemy’s mind and behavior, but to actually control it. breakthroughs in neuroscience will enable new types of non-lethal weapons for precise behavioral manipulation, for example through behavior-altering neurotropic drugs, through remote electromagnetic brain monitoring and stimulation, through acoustic weapons beaming voices directly into enemy heads, and even through holographic projections and other ‘complex battlefield illusions.’ within ten years soldiers could be equipped with transcranial magnetic stimulation devices or brain-computer interfaces, which would make it possible for their commanders to steer their emotions and to control their thoughts. this paper will discuss how the emerging sixth domain of warfare (the mind) is likely to transform military operations and profoundly change how wars are conducted. it is argued that military operations will be increasingly centered on achieving desired psychological effects, which will, on the positive side, reduce the need for physical destruction and killing. at the same time, ‘neuroweapons’ will also create new and unprecedented dangers, resulting from misuse and proliferation, which will need to be addressed through development of a concept of ‘neurosecurity’ that will be outlined.”

Krishnan, A.. (2014). From Psyops to Neurowar: What Are the Dangers?. Paper to Be Presented at the ISAC-ISSS Conference in Austin, 14-16 November 2014

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Further References

Bruner, R. C., & Lentzos, F.. (2019). Militarising the Mind: Assessing the Weapons of the Ultimate Battlefield. BioSocieties

Plain numerical DOI: 10.1057/s41292-018-0121-4
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“Advancements in behavioural neuroscience have revolutionised the treatment of mental illness by elucidating the mechanisms underpinning human behaviour and cognition. these advancements are not completely benevolent, but have dual-use potential which harkens back to a darker time when states sought to influence and control each other’s citizenry through psychological means. this article puts proposed behaviour-altering neuroscience weapons into their appropriate technical, historical, and geopolitical contexts to present a sober and critical analysis of the threat arising from the weaponisation of behavioural neuroscience. it argues that by using psychiatric drugs, brain stimulation, brain imaging or neurobiochemical weapons, states may be able to leverage neuroscientific advances to influence, control, and manipulate human behaviour and cognition. however, these approaches are extremely nascent and face technical and operational challenges that make their deployment difficult. despite this, in consideration of the rapid pace of scientific advancement, growing geopolitical instability, and ambiguities in international law, scientists and the international community must remain vigilant as these technologies become more refined and the practical barriers to use begin to lower.”

Evans, N. G.. (2021). Neuroweapons. In The Ethics of Neuroscience and National Security

Plain numerical DOI: 10.4324/9780429447259-6
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Dando, M.. (2015). Neuroscience and the Future of Chemical-Biological Weapons. Neuroscience and the Future of Chemical-Biological Weapons

Plain numerical DOI: 10.1057/9781137381828
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“This study is concerned with the potential misuse of advances in neuroscience. recently, fears surrounding the abuse of benignly-intended research in the life sciences –the dual-use problem — have focused on ‘Gain-of function’ experiments, in which deadly influenza viruses have been made transmissible through the air. however, many other aspects of the life sciences, besides the study of viruses, could be subject to hostile misuse. there is a century-long history of the development of novel neuroweapons, which is based on civil research and a vast, ongoing increase in research funding. these developments underpin an attempt to produce a mechanistic understanding of brain functions, which risk being subjected to misuse in the future. this study does not propose that this benignly-intended work be reined in, nor suggest that neuroscientists bear the sole responsibility for preventing the misuse of their work. however, they remain inextricably involved and should, one could argue, assume a certain level of accountability. thus, this book sheds light on how they, and international security specialists, can work to bolster efforts to minimise the potential for misuse of modern neuroscience research. part i: the past — 1. neuroscience and the developments of cbw — 2. the structure and function of the brain — 3. the cbw non-proliferation regime — 4. the dual-use challenge — part ii: the present — 5. modern civil neuroscience — 6. novel neuroweapons — 7. implications of advances in neuroscience — 8. the search for incapacitants — 9. bioregulators and toxins — part iii: the future — 10. the btwc and cwc facing scientific change — 11. where are we going? — 12. the governance of dual-use neuroscience.”

Dando, M.. (2015). Novel Neuroweapons. In Neuroscience and the Future of Chemical-Biological Weapons

Plain numerical DOI: 10.1057/9781137381828_6
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“In 2007 a set of lecture powerpoint slides and speaking notes appeared on the internet.1 they were titled ‘protecting our national neuroscience infrastructure: implications for homeland security, national security and the future of strategic weapons’. what was interesting for a start was that the lecture was written by dr. robert e. mccreight who has spent 35 years in the united states state department working on global security arms control, biowarfare, treaty verification and other related issues.2 ”

Giordano, J. J.. (2015). Neurotechnology in National Security and Defense: Practical Considerations, Neuroethical Concerns. Advances in neurotechnology

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“Neurotechnology in national security and defense: practical considerations, neuroethical concerns is the second volume in the advances in neurotechnology series. it specifically addresses the neuroethical, legal, and social issues arising from the use of neurotechnology in national security and defense agendas and applications. front cover; contents; series preface; foreword; acknowledgments; editor; contributors; chapter 1: neurotechnology, global relations, and national security : shifting contexts and neuroethical demands; chapter 2: transitioning brain research : from bench to battlefield; chapter 3: neural systems in intelligence and training applications; chapter 4: neurocognitive engineering for systems’ development; chapter 5: neural mechanisms as putative targets for warfighter resilience and optimal performance; chapter 6: neurotechnology and operational medicine; chapter 7: ‘neurint’ and neuroweapons : neurotechnologies in national intelligence and defensechapter 8: brain brinksmanship : devising neuroweapons looking at battlespace, doctrine, and strategy; chapter 9: issues of law raised by developments and use of neuroscience and neurotechnology in national security and defense; chapter 10: neuroscience, national security, and the reverse dual-use dilemma; chapter 11: neuroskepticism : rethinking the ethics of neuroscience and national security; chapter 12: prison camp or ‘prison clinic?’ : biopolitics, neuroethics, and national security; chapter 13: between neuroskepticism and neurogullibility : the key role of neuroethics in the regulation and mitigation of neurotechnology in national security and defensechapter 14: why neuroscientists should take the pledge : a collective approach to the misuse of neuroscience; chapter 15: military neuroenhancement and risk assessment; chapter 16: can (and should) we regulate neurosecurity? : lessons from history; chapter 17: engaging neuroethical issues generated by the use of neurotechnology in national security and defense : toward process, methods, and paradigm; chapter 18: postscript : a neuroscience and national security normative framework for the twenty-first centuryback cover.”

Dando, M.. (2015). Novel Neuroweapons. In Neuroscience and the Future of Chemical-Biological Weapons

Plain numerical DOI: 10.1057/9781137381828.0013
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Giordano, J., & Wurzman, R.. (2011). Neurotechnologies as weapons in national intelligence and defense – An overview. Neurogenetics

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“Advances in neuroscience and neurotechnology have necessitated discussions on the ways that such developments could be used as weapons in contexts of national security, intelligence, and defense. this paper defi nes the concept of neuroweapons, and elucidates operational issues associated with their use to aid informational and strategic intelligence, such as brain-machine interfaces to improve effi ciency in data analysis. as well, exploration of neuropharmacologic, neuromicrobiological, and neurotoxic agents are discussed relevant to their utility in combat scenarios. the limitations of emerging neurotechnologies as weapons are addressed, as both regards practical and operational frameworks, and implications relevant to formulation of ethico-legal guidelines and governance of research, development and potential use.”

Noll, G.. (2014). Weaponising neurotechnology: International humanitarian law and the loss of language. London Review of International Law

Plain numerical DOI: 10.1093/lril/lru009
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“In recent years, research on military applications of neuroscience has grown in sophistication, raising the question as to whether states using weapon systems that draw on neuroscience are capable of applying international humanitarian law (ihl) to that use. i argue that neuroweapons largely eliminate the role of language in targeting, render unstable the distinction between superior and subordinate, and ultimately disrupt the premise of responsibility under ihl. i conclude that it is impossible to assess whether future uses of these weapons will be lawful under ihl.”

DeFranco, J., DiEuliis, D., & Giordano, J.. (2020). Redefining Neuroweapons: Emerging Capabilities in Neuroscience and Neurotechnology. PRISM

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“As global conflicts assume increasingly asymmetric and gray zone forms, the ability to employ current and newly developing techniques and tools of neurocognitive science to manipulate human thought and behavior must be viewed as a present and increasing challenge. ongoing developments in neuroscience and technology (neuros/t), which trend toward 5- to 10-year trajectories of progression, make the brain sciences valid, viable, and of growing value for operational use in warfare, intelligence, and national security (wins) applications. historically, biochemical weapons have included incapacitating or lethal agents such as nerve gas, irritants, vesicants, and paralytics. numerous examples of such weapons can be drawn from world war i to the present. various forms of neuros/t have become available, and radical leveling and emerging developments in the brain sciences fortify and add to this current palette of weaponizable tools.”

Nørgaard, K., & Linden-Vørnle, M.. (2021). Cyborgs, Neuroweapons, and Network Command. Scandinavian Journal of Military Studies

Plain numerical DOI: 10.31374/sjms.86
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“In this article, we will explore the emerging field of military neurotechnology and the way it challenges the boundaries of war. we will argue that these technologies can be used not only to enhance the cognitive performance of warfighters, but also as a means to exploit artificial intelligence in autonomous and robotic weapons systems. this, however, requires the practice of a collaborative network command and a governing framework of cyborg ethics to secure human control and responsibility in military operations. the discussion of these governing principles adheres to the tradition of military studies. hence, we do not aim to present a neuroscientific research program. nor do we wish to embark on technical solutions in disciplines such as artificial intelligence and robotics. rather, the intention is to make the highly specialized language of these sciences accessible to an audience of military practitioners and policymakers, bringing technological advances and challenges into the discussion of future warfighting.”

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In vivo gene editing

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“In vivo gene editing in post-mitotic neurons of the adult brain may be a useful strategy for treating neurological diseases. Here, we develop CRISPR–Cas9 nanocomplexes and show they were effective in the adult mouse brain, with minimal off-target effects. Using this system to target Bace1 suppressed amyloid beta (Aβ)-associated pathologies and cognitive deficits in two mouse models of Alzheimer’s disease. These results broaden the potential application of CRISPR–Cas9 systems to neurodegenerative diseases.”

Park, H., Oh, J., Shim, G., Cho, B., Chang, Y., Kim, S., … Kim, J.. (2019). In vivo neuronal gene editing via CRISPR–Cas9 amphiphilic nanocomplexes alleviates deficits in mouse models of Alzheimer’s disease. Nature Neuroscience

Plain numerical DOI: 10.1038/s41593-019-0352-0
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“In vivo gene editing in post-mitotic neurons of the adult brain may be a useful strategy for treating neurological diseases. here, we develop crispr–cas9 nanocomplexes and show they were effective in the adult mouse brain, with minimal off-target effects. using this system to target bace1 suppressed amyloid beta (aβ)-associated pathologies and cognitive deficits in two mouse models of alzheimer’s disease. these results broaden the potential application of crispr–cas9 systems to neurodegenerative diseases.”

Further References

Gillmore, J. D., Gane, E., Taubel, J., Kao, J., Fontana, M., Maitland, M. L., … Lebwohl, D.. (2021). CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis. New England Journal of Medicine

Plain numerical DOI: 10.1056/nejmoa2107454
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“BACKGROUND: transthyretin amyloidosis, also called attr amyloidosis, is a life-threatening disease characterized by progressive accumulation of misfolded transthyretin (ttr) protein in tissues, predominantly the nerves and heart. ntla-2001 is an in vivo gene-editing therapeutic agent that is designed to treat attr amyloidosis by reducing the concentration of ttr in serum. it is based on the clustered regularly interspaced short palindromic repeats and associated cas9 endonuclease (crispr-cas9) system and comprises a lipid nanoparticle encapsulating messenger rna for cas9 protein and a single guide rna targeting ttr. methods: after conducting preclinical in vitro and in vivo studies, we evaluated the safety and pharmacodynamic effects of single escalating doses of ntla-2001 in six patients with hereditary attr amyloidosis with polyneuropathy, three in each of the two initial dose groups (0.1 mg per kilogram and 0.3 mg per kilogram), within an ongoing phase 1 clinical study. results: preclinical studies showed durable knockout of ttr after a single dose. serial assessments of safety during the first 28 days after infusion in patients revealed few adverse events, and those that did occur were mild in grade. dose-dependent pharmacodynamic effects were observed. at day 28, the mean reduction from baseline in serum ttr protein concentration was 52% (range, 47 to 56) in the group that received a dose of 0.1 mg per kilogram and was 87% (range, 80 to 96) in the group that received a dose of 0.3 mg per kilogram. conclusions: in a small group of patients with hereditary attr amyloidosis with polyneuropathy, administration of ntla-2001 was associated with only mild adverse events and led to decreases in serum ttr protein concentrations through targeted knockout of ttr. (funded by intellia therapeutics and regeneron pharmaceuticals; clinicaltrials.gov number, nct04601051.).”

Mills, E. M., Barlow, V. L., Luk, L. Y. P., & Tsai, Y. H.. (2020). Applying switchable Cas9 variants to in vivo gene editing for therapeutic applications. Cell Biology and Toxicology

Plain numerical DOI: 10.1007/s10565-019-09488-2
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“Progress in targeted gene editing by programmable endonucleases has paved the way for their use in gene therapy. particularly, cas9 is an endonuclease with high activity and flexibility, rendering it an attractive option for therapeutic applications in clinical settings. many disease-causing mutations could potentially be corrected by this versatile new technology. in addition, recently developed switchable cas9 variants, whose activity can be controlled by an external stimulus, provide an extra level of spatiotemporal control on gene editing and are particularly desirable for certain applications. here, we discuss the considerations and difficulties for implementing cas9 to in vivo gene therapy. we put particular emphasis on how switchable cas9 variants may resolve some of these barriers and advance gene therapy in the clinical setting.”

Plain numerical DOI: 10.1038/s41593-019-0352-0
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Jordan, B.. (2021). In vivo gene editing for gene therapy. Medecine/Sciences

Plain numerical DOI: 10.1051/medsci/2021140
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Yip, B. H.. (2020). Recent advances in CRISPR/Cas9 delivery strategies. Biomolecules

Plain numerical DOI: 10.3390/biom10060839
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“The clustered regularly interspaced short palindromic repeats (crispr)/cas9 system has revolutionized the field of gene editing. continuous efforts in developing this technology have enabled efficient in vitro, ex vivo, and in vivo gene editing through a variety of delivery strategies. viral vectors are commonly used in in vitro, ex vivo, and in vivo delivery systems, but they can cause insertional mutagenesis, have limited cloning capacity, and/or elicit immunologic responses. physical delivery methods are largely restricted to in vitro and ex vivo systems, whereas chemical delivery methods require extensive optimization to improve their efficiency for in vivo gene editing. achieving a safe and efficient in vivo delivery system for crispr/cas9 remains the most challenging aspect of gene editing. recently, extracellular vesicle-based systems were reported in various studies to deliver cas9 in vitro and in vivo. in comparison with other methods, extracellular vesicles offer a safe, transient, and cost-effective yet efficient platform for delivery, indicating their potential for cas9 delivery in clinical trials. in this review, we first discuss the pros and cons of different cas9 delivery strategies. we then specifically review the development of extracellular vesicle-mediated gene editing and highlight the strengths and weaknesses of this technology.”

Büning, H., & Schambach, A.. (2021). A first step toward in vivo gene editing in patients. Nature Medicine

Plain numerical DOI: 10.1038/s41591-021-01476-6
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Latella, M. C., Di Salvo, M. T., Cocchiarella, F., Benati, D., Grisendi, G., Comitato, A., … Recchia, A.. (2016). In vivo Editing of the Human Mutant Rhodopsin Gene by Electroporation of Plasmid-based CRISPR/Cas9 in the Mouse Retina. Molecular Therapy – Nucleic Acids

Plain numerical DOI: 10.1038/mtna.2016.92
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“The bacterial crispr/cas system has proven to be an efficient tool for genetic manipulation in various organisms. here we show the application of crispr-cas9 technology to edit the human rhodopsin (rho) gene in a mouse model for autosomal dominant retinitis pigmentosa. we designed single or double sgrnas to knock-down mutant rho expression by targeting exon 1 of the rho gene carrying the p23h dominant mutation. by delivering cas9 and sgrnas in a single plasmid we induced an efficient gene editing in vitro, in hela cells engineered to constitutively express the p23h mutant rho allele. similarly, after subretinal electroporation of the crispr/cas9 plasmid expressing two sgrnas into p23h rho transgenic mice, we scored specific gene editing as well as significant reduction of the mutant rho protein. successful in vivo application of the crispr/cas9 system confirms its efficacy as a genetic engineering tool in photoreceptor cells.”

Li, F., Wing, K., Wang, J. H., Luu, C. D., Bender, J. A., Chen, J., … Hewitt, A. W.. (2020). Comparison of CRISPR/Cas Endonucleases for in vivo Retinal Gene Editing. Frontiers in Cellular Neuroscience

Plain numerical DOI: 10.3389/fncel.2020.570917
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“CRISPR/cas has opened the prospect of direct gene correction therapy for some inherited retinal diseases. previous work has demonstrated the utility of adeno-associated virus (aav) mediated delivery to retinal cells in vivo; however, with the expanding repertoire of crispr/cas endonucleases, it is not clear which of these are most efficacious for retinal editing in vivo. we sought to compare crispr/cas endonuclease activity using both single and dual aav delivery strategies for gene editing in retinal cells. plasmids of a dual vector system with spcas9, sacas9, cas12a, cjcas9 and a sgrna targeting yfp, as well as a single vector system with sacas9/yfp sgrna were generated and validated in yfp-expressing hek293a cell by flow cytometry and the t7e1 assay. paired crispr/cas endonuclease and its best performing sgrna was then packaged into an aav2 capsid derivative, aav7m8, and injected intravitreally into cmv-cre:rosa26-yfp mice. spcas9 and cas12a achieved better knockout efficiency than sacas9 and cjcas9. moreover, no significant difference in yfp gene editing was found between single and dual crispr/sacas9 vector systems. with a marked reduction of yfp-positive retinal cells, aav7m8 delivered spcas9 was found to have the highest knockout efficacy among all investigated endonucleases. we demonstrate that the aav7m8-mediated delivery of crispr/spcas9 construct achieves the most efficient gene modification in neurosensory retinal cells in vivo.”

Lee, J., Kang, Y. K., Oh, E., Jeong, J., Im, S. H., Kim, D. K., … Chung, H. J.. (2022). Nano-assembly of a Chemically Tailored Cas9 Ribonucleoprotein for in Vivo Gene Editing and Cancer Immunotherapy. Chemistry of Materials

Plain numerical DOI: 10.1021/acs.chemmater.1c02844
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“Cancer gene therapy based on the clustered regularly interspaced short palindromic repeat (crispr) system has been challenging due to the poor delivery and efficacy in vivo. herein, we report the development of nanoassembled ribonucleoprotein complexes (nanornp), which can efficiently block the pd-l1 immune checkpoint and induce an anti-tumor effect in vivo. we utilize crispr-associated protein 9 (cas9) that is chemically derivatized with a low-molecular weight polymer, which condenses with single-guide rna and modified dna oligonucleotides to form stabilized nanornps. delivery of the nanornp into b16 melanoma cells in vitro leads to efficient internalization and gene disruption with low cytotoxicity, leading to sustained downregulation of pd-l1. in vivo delivery in a mouse melanoma model demonstrates that the nanornp can induce indels in the target cells of the tumor at high frequencies, resulting in major suppression of tumor growth, without involving combinatorial treatment. blockade of the pd-l1 checkpoint by the nanornp in tumor tissues promotes t cell infiltration and effector cytokine release, which are characteristics of the activation of anti-tumor immunity, and inhibition of immunosuppressive myeloid cells. the current system suggests a promising strategy as an in vivo gene editing platform for cancer immunotherapy.”

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