Reductionism and holism in the history of aging and longevity research: Does the whole have parts?

Ilia Stambler

Summary

The research of aging and life extension has been notoriously characterized by a multitude of often contradictory approaches, both in terms of theoretical concepts as well as possible practical interventions. This work will explore a general taxonomy of these approaches that seems to be ubiquitous in the history of aging and longevity research. The taxonomy will juxtapose between reductionist/therapeutic and holistic/hygienic approaches to potential life-extending interventions. Both approaches sought to achieve biological equilibrium and constancy of internal environment, yet emphasized diverging means and diverging perceptions of what constitutes equilibrium and constancy. The reductionist approach saw the human body as a machine in need of repair and internal adjustment and equilibration, seeking to achieve material homeostasis by eliminating damaging agents and introducing biological replacements, in other words, working by subtraction and addition toward balance. The holistic approach, in contrast, focused on the equilibration of the organism as a unit within the environment, strongly emphasizing the direct sustaining and revitalizing power of the mind and hygienic regulation of behavior. In the holistic approach, internal equilibrium was sought not so much through calibrating intrusions, but through resistance to intrusions. The apparent relative weight of each approach in public discourse will be shown to change with time, in several western countries, with a special focus on France in the first half of the twentieth century, reflecting the initial hopes, disappointments and reactions to those disappointments in a variety of scientific programs. The potential benefits and drawbacks of both the reductionist and holistic approaches to the problems of aging and longevity will be thus exemplified.

Introduction: Reductionism vs. Holism – a major dichotomy among potential life-extension methods

The history of biomedical research of aging and longevity has been an integral part of general medical history, though this relationship is not always acknowledged. Yet, in fact, studies, explicitly aiming to ameliorate the degenerative aging process and prolong human life, often constituted a formidable motivation for biomedical research and discovery. Arguably, at least several modern biomedical fields have originated directly from aging and life extension research. Some examples include hormone replacement therapy born in Charles-Edouard Brown-Séquard’s rejuvenation experiments with animal gland extracts (1889), probiotic diets originating in Elie Metchnikoff’s conception of radically prolonged “orthobiosis” (c. 1900), the cell therapy and tissue replacement therapy methods now currently referred to as “regenerative medicine” owing a lot to the experiments on cell and tissue culture and replacement by Eugen Steinach, Serge Voronoff, Alexis Carrel, Paul Niehans and others.^1,2 Yet, the field has also been notoriously controversial and diverse concerning the prospective actual or potential methods that should be pursued for the amelioration of aging and achievement of life extension, their scientific, methodological and practical merits. Historically, the research of aging and life extension has been teeming with a multitude of often contradictory approaches, both in terms of theoretical concepts as well as possible practical interventions. The present work will attempt to provide an over-arching categorical dichotomic framework for those diverse approaches.

I argue that, despite the great diversity of suggestions for possible methods and research directions toward life prolongation, a major basic dichotomy transpires: between what can be termed the “holistic/hygienic approaches” that emphasized the importance of psychological environment and hygienic regulation of behavior to maintain the harmony of the whole vs. the “reductionist/therapeutic approaches” which sought ways to eliminate damaging agents and to introduce biological replacements to maintain the human machine in good working order. Apparently, these approaches have always coexisted side by side, though it may be possible to observe that the ostensible relative weight of each approach in public discourse (in terms of notoriety and prestige, funding, amount and dissemination of relevant publications) changed with time, reflecting the initial hopes, disappointments and reactions to those disappointments in a variety of scientific programs in particular local contexts.  The distinction between holistic and reductionist approaches has been definitive for the history of modern medicine³, and the history of longevity research illustrates and foregrounds this distinction.

France – a seedbed of modern aging and longevity research. The reductionist roots of this research

France represents probably one of the best examples of this distinction. France was a fertile, perhaps even a primary ground for the research of aging and longevity since the Enlightenment and even earlier. In mid-19th century, profound contributions to the practical treatment of the elderly were made by the founders of Médecine de Vieillards (medicine of the aged), in particular Charles-Louis-Maxime Durand-Fardel, Jean-Martin Charcot and others. Pioneering contributions were made to the theory of aging by Marie-Jean-Pierre Flourens (1794-1867) and Édouard Robin (c. 1859).¹ In the late 19th – early 20th century, the pursuit of human life extension was encouraged by peaceful and prosperous social conditions, and by the philosophical traditions of positivism, liberalism and progressivism. In this period, France produced some of the world’s ground-breaking advancements in the theory of aging, methods of rejuvenation and life-extensionist philosophy. This is epitomized by the works of Elie Metchnikoff (1845-1916), a vice director of the Pasteur Institute in Paris, the Nobel Laureate in Physiology/Medicine of 1908 and the author of the concept of “gerontology”.⁴ Another crucial figure was Charles-Édouard Brown-Séquard (1817-1894), the President of the French Biological Society, Chair of Medicine at Collège de France in Paris and the founder of therapeutic endocrinology that emerged from a “rejuvenation” experiment. Other prominent figures included Serge Voronoff (1866-1951) – one of the pioneers of xeno-transplantation born of rejuvenation attempts, Jean Finot (1856-1922) – the author of the “philosophy of long life” and more. In this formative period of the French school of aging and longevity research, reductionist and mechanistic proclivities were unmistakable.

Notably, since the mid-19th through the early 20th century, reductionism and materialism, essentially viewing the human body as a machine in need of repair, underscored most of the ground-laying works of French researchers of aging and longevity. Thus, the primary methodology of the French founders of “medicine of the aged” and aging-ameliorating interventions in the mid-19th century – Charles-Louis-Maxime Durand-Fardel, Jean-Martin Charcot and others – was dissection. Through the autopsy dissection, they established the age-related pathological changes in separate organs and tissues, in fact, reducing the entire process of aging to these specific organ changes. Though Durand-Fardel spoke of the life-span being determined by a holistic “vital principle of limited duration”⁵ – finding tissue-specific degeneration was for him by far more determinative. One of the most prominent French researchers of longevity of the mid-19th century, Marie-Jean-Pierre Flourens (1794-1867), asserted that “Just as the duration of growth, multiplied a certain number of times, say five times, gives the ordinary duration of life, so does this ordinary duration, multiplied a certain number of times, say twice, give the extreme duration. A first century of ordinary life, and almost a second century, half a century (at least) of extraordinary life, is then the prospect science holds out to man” (1854).⁶ He thus determined that human longevity is preset by a mechanical body buildup, as if by winding of a clock-work. And the main line of Flourens’ research on the localization of brain functions (the field he in fact founded) was an epitome of reductionism. Furthermore, one of the first modern scientific theories of aging, proposed by Édouard Robin of the French Academy of Sciences in 1858, posited that aging is due to body “mineralization” or accumulation of “alkaline residues,” “calcification” or “ossification.” Robin’s theory considered lactic acid and “vegetable acids” as possible means to dissolve the “mineral matters” and thus prolong life.^7,8 Thus, the body was essentially viewed as a rusting and clogging machine subject to a cleanup. (Unlike otherwise specified, hereafter all the excerpts are in my translation.)

The teachings of the most authoritative figures in aging and longevity research of the late 19th-early 20th century – the founder of therapeutic endocrinology Charles-Edouard Brown-Séquard and the founder of modern gerontology Elie Metchnikoff – were profoundly materialistic and reductionist. Brown-Séquard suggested that through the supplementation of deficient hormones, bodily equilibrium can be restored, youth returned, and life prolonged. In Brown-Séquard’s seminal experiment of 1889 with self-injections with animal (dogs’ and guinea pigs’) sex gland extracts for rejuvenation (which laid down the foundation for modern therapeutic endocrinology), a chief concern was to rule out any psychosomatic influences and to reduce medical intervention to a subtraction or addition of matter.⁹ Metchnikoff, in turn, in his foundational theory of aging (perhaps the first truly scientific theory of aging based on histological observations) divided the body into “noble” or “functional” elements (mainly the parenchymal tissues, such as the heart and the brain) and “primitive” or “harmful” elements (such as the “devouring phagocytes” and intoxicating putrefactive microflora). The former needed to be strengthened or replenished, the latter destroyed or attenuated. Thus the body was seen as a sort of a mechanical balance, with weights added or removed as needed to keep the balance steady. According to Metchnikoff, the direct effects of the mind on the body were limited to “some nervous disorders.”¹⁰

Materialism and reductionism underwrote the work of yet another prominent fin-de-siècle French proponent of healthy longevity, the social scholar Jean Finot. In The Philosophy of Long Life (1900), Finot did speak of “Will as a means of prolonging life,” yet for him reductionism held the key for understanding, manipulating and extending life. In Finot’s philosophy, biology is reducible to chemistry and physics, and the complexity of a living organism is reducible to an interrelation of its components. Such a reduction, according to Finot, opens the possibility for engineering life, and eventually for life’s prolonged maintenance:¹¹

“What is the life of a man? The result of the lives of millions of plastides. For each plastide lives its own life, and there are even cases in which the man dies whilst the plastides composing him continue to live. Now, biology proves to us that among the phenomena observable at a given moment in a living plastide there is none which has no affinity to physics and to the chemistry of inert bodies. Nothing in them permits us to separate them from the body of elements already studied and possible of reproduction.”

Equally in favor of materialism and reductionism were Metchnikoff’s French followers, the physiologists Albert Dastre and Sergey Metalnikov. According to Albert Dastre (1844-1917), Claude Bernard’s pupil and Chair of the Department of General Physiology at the Sorbonne, reductionism opens the possibility to profoundly manipulate life’s components, since biology “is a particular chemistry, but chemistry none the less. … The vital action is not distinct in basis from physicochemical action, but only in form.” Subjected to physicochemical manipulation, human beings may “remain forever in full health and guarded from disease.”¹² And according to Metchnikoff’s pupil at Institut Pasteur, Sergey Metalnikov (1870-1946), senescence and death arise from a disharmony of differentiated body components. (This fundamental tenet was shared by the majority of fin-de-siècle theorists of aging, from August Weismann to Metchnikoff.) The basic unit of life, the cell, however was seen as potentially immortal. Therefore, according to Metalnikov, the body, composed of such potentially immortal units, can be made potentially immortal, if only learning to bring the components into harmony.¹³

Essentially, reductionism formed the theoretical basis for the rejuvenation experiments in humans at that period. The “father” of rejuvenative hormone replacement therapy, Brown-Séquard, vigorously defended the specificity of sex hormone injections and countered critics (such as Dr. Amédée Dumontpallier, 1826-1899) who argued that their effects are due to auto-suggestion or non-specific stimulation (i.e. that any injection would produce the same stimulating effect on the body). Brown-Séquard’s follower, the Russian-born Parisian surgeon Serge Voronoff, famous for the transplantation (“grafting”) into humans of animal (mainly male ape) sex gland tissues for “rejuvenation,” continued in his master’s footsteps. Voronoff recapitulated the basic theoretical premise that the deterioration of aging is due to an imbalance of the components comprising the body machinery, and that the balance can be restored through supplementing or replacing failing components.^14-16 Voronoff’s methodology of “rejuvenation” by sex gland “grafting” was reductionist almost by definition: by substituting (grafting) a single crucial element in the body mechanism (the sex gland tissue), the machine’s ‘run-time’ could be increased. The grafting did affect the whole body, but the effect was believed to be analogous to replacing an energy carrier (a principal component or a “battery”) to sustain the operation of the entire machine.

Voronoff’s reductionist and mechanistic views were explicit. He spoke of the “essential mechanism of our body” where “each organ performs its part,” the thyroid gland provides “the brain-motor’s ignition spark,” all the endocrine glands are “wonderful little factories” that “regulate the action of each organ” and, when some of these controls fail, the body is “put out of gear” and disintegrates. The sex glands, the main object of rejuvenating interventions, are akin to a battery, supplying the body with “vital energy.” The removal of particular parts brings about disarray and death, while their replacement provides new “sources of energy,” reestablishes the “controls” and restores the body’s “equilibrium of functions.” Hence, a major task of rejuvenative medicine is to establish “a stock of spare parts for the human machine.” A central place in Voronoff’s writings was reserved for anatomical and histological examinations, for detailing the surgical technique intended to rearrange the parts of the mechanism.^14-16 Indeed, Voronoff attributed great importance to the “psychic” effects of the grafting operation, but only to demonstrate how a material, “mechanistic” interference positively affects the mental sphere: improving intelligence, productivity, interest in life. But the opposite influence, from the mind onto the body, was thoroughly depreciated. Such mind-over-body effects would obscure the results of treatment and had to be ruled out.

The grafting appeared to be a novel, unorthodox intervention, but Voronoff’s central claim was that the operation restored the natural equilibrium of the body. The ultimate aim of rejuvenation techniques was, in accordance to Claude Bernard’s dictum, to achieve “the fixity of the internal environment” which is “the condition for free life.”¹⁷ And the means to attain this fixity were through supplementing or replacing those components whose deteriorative change would otherwise threaten the overall body stability. Reductionism might thus be pivotal for the rejuvenation enterprises of the early 20th century: the supplementation or replacement of an isolated component appeared to the rejuvenators a feasible task, perhaps more feasible than attempting to comprehend and/or manipulate the whole of the human reaction to the whole of the external environment. Beside Voronoff, the cohort of French pioneers of rejuvenation (mainly practicing sex gland tissue transplantations and various other means of endocrine rejuvenation) included Placide Mauclaire, Lois Dartigues, Raymond Petit, Léopold Lévi, Henri de Rothschild, and others, forming a “school”.

In later assessments, however, reductionist rejuvenation techniques did not appear to live up to their promise.¹⁸ With regard to Voronoff’s method, the problem of graft rejection by the host organism appeared almost insurmountable. Replacing or supplementing a single gland did not appear to durably forestall the deterioration of the entire organism, and no conclusive evidence for extending the life-span by such means was offered. Consequently, a recoil from immediate rejuvenation attempts occurred, accompanied by a recoil from their underlying mechanism and reductionism.

The research of aging and longevity in France in 1930-1950. The strengthening of the holistic approach

In the 1930s-1940s, an increasing number of French researchers of aging and longevity began to espouse holistic perceptions of the unity of the mind and body, and the subordination of an individual to society, gradually replacing the earlier prevalent notions of reductionism, physicalism and individualism. The holistic tone in French research of aging of the 1930s-1940s was set by the leading French longevity researcher, one of the pioneers of tissue culture and regenerative medicine, Alexis Carrel (1873-1944).² Echoing Auguste Comte, who asserted that “No sound treatment of either body or mind is possible, now that the physician and the priest make an exclusive study, the one of the physical, the other of the moral nature of man,”¹⁹ Carrel urged:²⁰

“Man is much more than a sum of analytical components. One has to embrace at the same time both the parts and the unity of man, because he reacts like a unit, and not like a multiplicity, to the cosmic, economic and psychological milieu. The solution of grand problems of civilization depends on the knowledge not only of different aspects of humanity, but of the human being as a whole: as an individual within a group, a nation and a race. This is the true science of man…. The conquest of health is not sufficient. It is the progress of a human person that is sought, because the quality of life is more important than life in and of itself.”

Such a holistic vision moved away from the earlier materialistic and reductionist proclivities of French life-extensionists.

The recoil from reductionist rejuvenation took many forms. First and foremost, since immediate rejuvenation appeared at the time untenable, the scholarly focus seems to have shifted to basic research of aging, predicated on the assumption that only after a comprehensive, lengthy and costly investigation, the complexity of the aging processes can be gradually unraveled, and consequently, in some distant future, actual life-extending interventions may be found. The concepts of bodily “equilibrium” of the early rejuvenators were rather qualitative and vague, and it was necessary to establish precisely what components and quantities constitute “steady states” or deviations from them. The practical aims of aging research became more modest: rather than attempting to effect an immediate and thorough rejuvenation, it became more presentable to seek a thorough understanding of the aging process and perhaps some mitigation of age-related diseases. Such an emphasis on basic research and caution in goals have been expressed by many researchers of aging, in particular in France, since the late 1930s through the early 1950s.¹ Another form of withdrawal was a rejection of “surgical” means of rejuvenation, in favor of more “natural” improvements in the life style.

Yet perhaps one of the central forms of withdrawal from rejuvenation attempts appears to have been a movement away from their underlying reductionism, and toward a more holistic perspective. This trend seems to have been salient in the “post-Voronoff” French longevity research community, and was epitomized by the work of Auguste Lumière, the crusader for the revival of “humoralist” medicine, among many other contemporary French physicians and biologists.

Auguste Lumière (1862-1954) could be considered as one of the leading actors in the “holistic turn” in French research of aging and longevity of the 1930s-1940s. Auguste and Louis Lumière (1864-1948) are renowned for the creation of cinematography in 1895. Perhaps less known is their deep involvement in biomedical research, especially that of Auguste.²¹ Thus, during WWI Louis constructed articulated arm prostheses for amputees, while Auguste developed a non-adherent anti-septic bandage (tulle gras) that dramatically reduced the time of wound healing, introduced oral anti-typhoid vaccination, anti-tetanus serum booster (sodium persulfate), and more. While Louis concentrated more on research and development of photographic technology, Auguste fully dedicated his efforts to biomedical research proper, with a notable emphasis on aging, rejuvenation and life-extension.²²

Lumière’s medical theory and practice were based on the most ancient and widespread holistic medical tradition of all – the “Humoralism.” For thousands of years, the balance and stability of different body liquids (or “humors”) was seen as the necessary condition for health and longevity. Auguste Lumière’s most ambitious and pervasive project was “The Renaissance of the Humoral Medicine.”²³ It was Lumière’s task to revive the humoralist tradition, to create a new “scientific humoralism” that would focus on establishing the balance of all types of liquids throughout the body, especially intracellular and interstitial liquids. As for the earlier “humoralist” theories, for Lumiere the key concepts were “balance,” “equilibrium,” “stability” and “fixity.” He just introduced other constituents of “equilibrium,” different from the equilibrium of “essential elements” in Roger Bacon, Paracelsus and other alchemists, or the equilibrium of “cell types” in Metchnikoff, Steinach, Voronoff and great many other life-extensionist physiologists in the first quarter of the century. Instead, Lumière’s theory considered the equilibrium and stability of cell colloids – dispersed liquid suspensions of macro-molecules (particularly proteins), or micelloids (colloid droplets). And this is the gist of his theory: When the colloids are stable and balanced (maintained dispersed in suspension), this state is characteristic of health and vitality; but when the colloids become unstable or imbalanced, they precipitate and flocculate – and this is the state of pathology and aging.²⁴ For Lumière, at the infancy of molecular biology, the colloids were essentially blobs of matter that “congest” or “dissolve,” with molecular composition and mechanisms unknown. Nonetheless, he was able to detect the colloids’ “stability” or “perturbations” and incorporated that knowledge into a vast explanatory apparatus and therapeutic methodology, including anti-aging strategies aimed to “stabilize the cell colloids”.

One of Lumière’s favorite “stabilizing substances” (essentially emulsifiers) was Magnesium Hyposulfite (Mg-S₂O₃), an anti-shock substance, capable of “reestablishing humoral equilibrium” and “inhibiting the disorganization of colloids, with all the cortege of disorders this entails.” It was also supposed to exert a general “desensitizing” (immunizing or tempering) effect on the entire body.²⁵ A wide variety of other “desensitizing” and “stabilizing” agents were tested and clinically applied by Lumière: “Anti-bacterial desensitization” (the regular immunization by specific antigens, e.g. Koch bacillus extracts), “Auto-hemotherapy” (injection of the patient’s own blood, presumably exerting “desensitizing” effects), as well as a wide assortment of metal compounds: magnesium benzoate, copper glycocholate, sodium undecylate, etc. etc. A special place was reserved for compounds of gold, partly realizing the ancient dream of alchemists. Chrysotherapy, using salts of gold, such as Allochrisine, was employed to stabilize innumerable “humoral imbalances” (and gold particles are still used today in the treatment of rheumatoid arthritis and other diseases, even in “nanomedicine”²⁶). “Granulotherapy” or “Anthrotherapy” employed small carbon or other particles, not just to absorb toxins, but to produce a “mild mechanical irritation” in order to achieve general desensitization and stimulate phagocytosis (also reminiscent of some more recent “nanomedicine” experiments²⁷). Changing the blood volume was yet another mechanical means to influence the colloidal state. Changing fluid pressure would change the vasomotor sensitivity to the pressure of flocculates, and consequently affect the sensitivity or immunity to shock. Accordingly, the most ancient methods of “balancing the humors” – the blood-letting or water intake – remained in the arsenal and were given a new rationale. Yet another therapy dear to Lumière’s heart was “negative ionization,” using the “aero-ionization lamp” introduced by the Russian biophysicist Alexander Chizhevsky in 1919. In Lumière’s view, negative ions presumably stabilize the colloids’ electrical charge. Endocrine extracts too were employed for colloids’ stabilization, for maintaining the “equilibrium of humors,” continuing the studies of “endocrine rejuvenation” started by Voronoff and others.

Despite some similarities of methodology, Lumière in fact broke away from the “rejuvenators” of the 1920s, such as Voronoff. The dissent manifested in the criticism and skepticism of the actual effectiveness of their methods, and in the fact that hormone replacements played only a very minor part in Lumière’s clinical practice. But perhaps the strongest point of departure was Lumière’s withdrawal from the mechanistic reductionism that underscored the majority of rejuvenation techniques. Not only did he emphasize the importance of purely psychological motivation for longevity, but the body itself was seen as much more than a combination of its parts. In Sénilité et Rajeunissement (Aging and Rejuvenation, 1932, pp. 94-95), Lumière wrote:

“The most important [characteristic of living beings] consists in the prodigious faculty of synthesis that only the living cells possess and that does not appear in any measure and in any degree in other molecular arrangements… Experience and observation, unaffected by all the reasoning of logicians, demonstrate that the properties of a substance essentially depend on the arrangement, the assemblage, the aggregation of atoms and molecules that compose it, and that these assemblages give birth, out of all the pieces, to novel properties that are present in no way and in no degree in the constituent parts.”

Lumière’s model of the body just could not be easily broken down into parts, because it was mainly composed of “balanced fluids.”

The therapeutic implications of this “holistic” theory followed. As Lumière insisted, all therapy should be combined, multi-faceted or “polyvalent” (Les Horizons de la Médecine, 1937, p. 60):

“One grand principle must dominate the methods of treatment of chronic functional afflictions: in pathological states, the disequilibrium and the instability of humors depend on accidents that have multiple causes; with rare exceptions, the stabilizing and curative therapy directed against them cannot achieve its goal except when it addresses simultaneously all the causes, that is to say, it must be “polyvalent” in order to be completely efficient….  [It is necessary] to remedy, in the same time, all the dysfunctions and eliminate all the factors that are involved in their production.”

Furthermore, he strove to provide a unifying framework for the phenomena of therapeutic non-specificity that may explain many therapeutic and rejuvenative effects (La Renaissance de la Médecine Humorale, 1937, p. 267):

“This conception [of humoral destabilization through flocculation of colloids] allows us to understand medical mysteries that would remain impenetrable without it. This notion explains to us why a single agent can cause diverse afflictions; why a multiplicity of essentially different agents can generate the same disease; why a single remedy can cure multiple distinct afflictions; why many completely different medications can cure the same syndrome; and why the major symptoms of acute maladies present a remarkable similarity. This is because all these phenomena share one common factor – the flocculate.”

Both Voronoff and Lumière sought “equilibrium” and “fixity.” According to Lumière, “the great principle of life appears to be fixity” that must be maintained in all life forms, from individual cells to organisms, to species to societies (La Vie, La Maladie et La Mort, Phénomènes Colloïdaux, 1928, pp. 66-67). The task of therapy, for Lumière as well as for Voronoff, consisted in maintaining the fixity, safeguarding it against catastrophe or degenerative change. But, paradoxically, in the quest for “fixity,” in the struggle against formidable change, both scientists became great medical innovators, introducing new “stabilizing” treatments that may appear unorthodox even by contemporary standards.

Yet, an important difference may be pointed out between Lumière and Voronoff. In Lumière, the “vital equilibrium” appears to be much more complex than Voronoff’s “human machine.” In Lumière’s vision, the equilibrium must involve the responses of the body as a whole, including diverse environmental and psychological factors. Compared to Voronoff, Lumière was much more willing to admit to his almost complete ignorance of these intricacies. In Sénilité et Rajeunissement (p. 91), he stated:

“If, generally, we perceive the existence of a relation between matter and intelligence, we are completely ignorant of the mechanisms that govern this relation, and the cause for psychic equilibrium completely evades us. Not only in this order of phenomena has the vital equilibrium remained an enigma: the processes of the regulation of all organic functions, the thermal, the respiratory, the cardiac, etc…. remain entirely obscure. We are ignorant!”

It was perhaps this realization of the immense complexity of the “vital equilibrium,” of integrating elements that could not be readily “removed” or “supplemented,” that contributed to Lumière’s withdrawal from the current rejuvenation methods, and caused him to seek solace in anticipating the results of “future research.”

Intriguingly, despite the humility before the grandeur of the “organism as a whole,” Lumière remained a “therapeutic activist” and “scientific optimist” to the end of his nonagenarian life. A similar coexistence of therapeutic and scientific optimism with the great “holistic” awe before the complexity and wholeness of the human being, in his/her infinite connectedness to the society and the universe, is salient in the work of other French contemporary longevity researchers and seekers of “equilibrium”, members of the so called “Neo-Hippocratic” holistic movement. After his return to France from the US in 1939, Carrel became one of the leaders of this movement. Yet many other prominent figures supported the movement. The supporters included prominent physicians, some of them members of the French Academy of Sciences and the Medical Academy, heads of medical departments. They were united against the “analytical,” “materialistic,” “mechanistic” and “dehumanizing” approaches in medicine, and unanimous in their advocacy of “synthesis,” treating the human being as “a whole,” with due consideration of his mental or “psychic” activities, “imponderable” factors in healing, the recognition of the patients’ individuality, the integration of an individual with the grander social and physical environment. These emphases are now firmly associated with a “holistic” medical paradigm.

The proponents of the movement did not use the term “holism,” but rather saw themselves as “Neo-Hippocratists.” From the teachings of Hippocrates, they derived the basis for considering the human being as a “whole” in an unbreakable rapport with the environment, with season and place. Following Hippocrates, they sought to maintain a physiological and mental equilibrium, never considering a disease as an entity, but as a temporal imbalance of the equilibrium. The equilibrium, according to them, could be restored not so much by chemicals and operations, but rather by a more “natural” and “moderate” way of life. Depreciating heroic interventions, they strove to assist the “healing power of nature” through adjusting the life-style, and most of all, by cultivating the healing power of the mind. These principles were, according to them, neglected by the “official” or “materialistic” medicine and must be restored.

In the 1930s-early 1940s, France was at the forefront of the “Neo-Hippocratic” and “Naturist” movement, upheld by such prominent physicians as Jean Poucel, Claude Sigaud, Paul Carton, René Biot, Louis Corman, Pierre Winter and others.²⁸ In 1933, the world’s first journal dedicated to natural and integrative medicine – Hippocrate – was inaugurated by Prof. Maxime Laignel-Lavastine of Paris. In the same year, on the initiative of Dr. Jérome Casabianca, there was organized in Marseille “La Société de Médecine Naturiste de Marseille – Médecine Préventive et Néo-hipppocratique” (the Marseille society for naturist, preventive and neo-Hippocratic medicine). The first International Congress on Neo-Hippocratism was held in July 1937 in Paris, under Laignel-Lavastine’s presidency. Then, the first grand, national conference in the field took place in Marseille in November 1938, presided over by Prof. Lucien Cornil, dean of the Marseille medical faculty. In 1939, there was founded the “Union pour la defense de l’espèce” (“The union for the defense of the species”) dedicated to developing agriculture “conforming to our physiological needs.” At the time, these were pioneering institutions on the world scale, and they manifest a “holistic turn” in French medical science generally,²⁹ and in the approach to aging-related ill health in particular.

After the “holistic turn” France seems to have lost its leading position in the life-extensionist movement. The diminishing impact of French life-extensionists after the departure from reductionist rejuvenation endeavors is understandable, as it signified a departure from daring interventions toward a more protective and conservative attitude. Since the 1930s through the 1950s, the (predominantly critical and cautious) discussions of rejuvenation continued in France, notably by the founders of the French Society of Gerontology (formed in 1939) – Leon Binet (1891-1971) and Francois Bourlière (1913-1993). Leon Binet, who became president of the French Academy of Sciences in 1957, focused on clinical geriatrics and experimented with oxygen therapy and embryonic extracts. Francois Bourlière, who became the founding director of the Claude Bernard Center of Gerontology in Paris in 1956, conducted comparative studies of average longevity from various animal species and supported the use of hormones (mainly sex hormones) in geriatric therapy.³⁰ In the late 1940s, Michel Bardach of the Pasteur Institute in Paris advanced a “rejuvenative”/“orthobiotic”/”stimulating” cytotoxic serum.³¹ In the 1950s and 1960s, the biologist and philosopher of science Jean Rostand (1894-1977) was an outspoken supporter of radical life-extension and pioneer of cryo-preservation.³² But none of these researchers seems to have had the notoriety and ambition of the French “founding fathers” of life-extensionism – Brown-Séquard, Metchnikoff and Voronoff. Was the therapeutic optimism “dissolved in the whole”?

A similar trend in the German-speaking aging research community

A very similar change of attitudes and approaches occurred in the German-speaking world, mainly in Austria and Germany (to a lesser extent in Switzerland). In the 1920s, “endocrine rejuvenation” became a world wide movement, spreading from the US to Russia and Japan. Yet, France and Austria emerged as the primary and competing rejuvenation superpowers. Beside the Parisian Voronoff and his “sex gland transplantations,” a crucial figure in the rejuvenation movement was the Viennese physician Eugen Steinach (1861-1944), famous for the “Steinach operation”, first performed in a human patient on November 1, 1918, which involved the ligation of seminal ducts (“vasoligation” or vasectomy). The theory behind the operation was quite reductionist and mechanistic. The vasoligation was supposed to suppress the sperm-producing activity and thereby to stimulate the hormone-producing activity of the “interstitial tissue” of the testis. Such enhanced sex hormone production was assumed to effect “rejuvenation,” “revitalization” or “reinvigoration.” The general rejuvenating effects were ascribed by Steinach to the whole-body increase in the blood flow (hyperemia) produced by the sex hormones (though Steinach recognized other methods of blood flow increase, such as diathermy, massage, exercise and baths). To avoid infertility, the operation was commonly performed only on one of the two spermatic ducts.  Simply put, the operation was supposed to tweak and boost the energy supply mechanism.

Under Steinach’s leadership, Austria (beside France) became a world leader in all matters of endocrine rejuvenation, renowned by the works of Erwin Last, August Bier, Karl Doppler, Emerich Ullmann, Paul Kammerer, Robert Lichtenstern, Otto Kauders, Gottlieb Haberlandt and others. Sigmund Freud (1856-1939) was enthusiastic enough about Steinach’s rejuvenating operation to have it performed on himself in 1923 by the surgeon Victor Blum. In Germany too, in the first quarter of the century, the rejuvenation movement boomed, though perhaps to a lesser extent than in Austria. The German physiologist Jürgen Harms (1885-1956) performed the first testis transplantations in guinea pigs at about the same time as Steinach, in 1911, while Voronoff conducted the first testis transplantations in animals (he-goats and rams) only in 1917. In the 1920s, Harms was one of the most active proponents of sexual rejuvenation in humans, though Voronoff’s work stirred a much greater sensation. One of the most energetic practitioners of Steinach’s procedure in Germany was Peter Schmidt, having performed hundreds of operations in his clinic in Berlin. Other Berlin practitioners, such as Richard Mühsam and Ludwing Levy-Lenz, followed suit. Indeed, in the 1920s, Steinach’s procedure was widely applied all across the world. In Germany, however, the application of Steinach’s operation was among the widest. Beside operative interventions, by the late 1920s, hormonal preparations for rejuvenation became an object of keen interest in Germany. Sex gland extracts and stimulants became widely available for men and women: Testiglandol from Grenzach and Testifortan from Promonta, Novotestal from Merck and Plazentaopton from Kalle, Pituglandol and Neosex, Testogan and Yohimbin, Progynon and Menformon, Follikulin and Unden, dried ovaries, testis and erectile tissue powder. The majority of German founders of endocrinology (many of whom incidentally were Jewish) actively researched, developed and advertised the rejuvenating and eroticizing effects of such supplements. The proponents included Magnus Hirschfeld (the founder of the Institut für Sexualwissenschaft – the Institute for Sex Research in Berlin, and one of the first gay rights activists), Bernhard Schapiro (Hirschfeld’s co-worker and co-developer of Testifortan), Max Hirsch (editor of the monumental Handbuch der Inneren Sekretion – Handbook of Inner Secretion, 1926-1933), Bernhard Zondek and Selmar Ascheim (developers of the first reliable pregnancy test), and Hermann Zondek (Bernhard’s older brother, also a prominent endocrinologist) and others. In summary, in the 1920s the rejuvenation through “artificial” operative or pharmacological/organotherapeutic interventions flourished in Germany and Austria, and from this intertwined research into sex and rejuvenation a large part of modern endocrinology was born.³³

Yet, similarly to the French-speaking scientific community, also for the German-speaking researchers of aging and longevity, by the early 1930s it was becoming increasingly clear that the “rejuvenation” methods did not quite live up to their promise. A corresponding recoil from the underlying reductionism occurred. A striking testimony to the disenchantment with “rejuvenation” and its underlying reductionism can be found in Altern und Verjüngung. Eine Kritische Darstellung der Endokrinen “Verjüngungsmethoden,” Ihrer Theoretischen Grundlagen und der Bisher Erzielten Erfolge (Aging and Rejuvenation: A Critical Presentation of Endocrine “Rejuvenation Methods,” Their Theoretical Foundations and Up-to-Date Successes), by Benno Romeis (1931).³⁴ Prof. Dr. Benno Romeis (1888-1971), at the time director of the Department of Experimental Biology of the Institute of Anatomy at the University of Munich, was an active member of the rejuvenation movement, having conducted in the 1920s extensive original studies on the effects of rejuvenating interventions (particularly Steinach’s operations and hormonal supplements). Altern und Verjüngung (initially published as a part of Max Hirsch’s Handbuch der Inneren Sekretion) was one of the most authoritative and thorough accounts of the worldwide rejuvenation research up-to-the-date, a watershed monograph, summarizing the rejuvenators’ successes and failures and pointing out possible directions for future study. For most instances, Romeis’s criticisms were devastating. Perhaps most importantly, the extensive anatomical and physiological data on age-related changes of various endocrine organs (thyroid, parathyroid, pituitary, adrenals, testes and ovaries) did not permit to ascribe to any of these organs the predominant or primary causative role in senescence, as many reductionist rejuvenators would have liked to believe. The whole appeared to be bigger than any particular component or the simple sum of them.

Generally, the rejuvenation methods were found thoroughly wanting methodologically. They did not fulfill the high popular expectations associated with them. Indeed, these methods demonstrated “some effects,” such as increased appetite, improved libido and work power, in a large percentage of cases. Yet, these effects were mostly temporary and unpredictable, confounded by an immensity of other contributing factors and relativized by (mostly unknown) individual idiosyncrasies of each and every patient, under particular environmental circumstances and conditions. The evidence presented was often doctored or even falsified, and in any case contradictory and inconclusive. Neither operative nor supplementary rejuvenating methods provided any real evidence for a significant life-extension or long-lasting health improvement. The effects of the “rejuvenation therapies” were shown to be usually of short duration, and stronger in younger patients (due to their generally better reactivity and reserves) rather than in the older patients for whom those therapies were presumably intended. The dominant reductionist theories of aging that underwrote those therapies, emphasizing the primary role of particular (mainly endocrine) organs in the aging process and in the reestablishment of organic equilibrium upon rejuvenation, were also found to be too rudimentary and restricted, requiring a profound elaboration.

Hence the strong disappointment with the therapeutic effectiveness of the rejuvenation methods was also accompanied by the disappointment with their underlying reductionist theories. And hence, similarly to France, the discussion of life-extension in Germany in the 1930s showed a notable shift of emphasis from “materialistic-reductionist” or “artificial” rejuvenation toward more “natural” and “holistic” macrobiotic hygiene.³⁵ A good example of this shift of attitude can be seen in the book Lang leben und jung bleiben! (Live long and stay young!) (1937)³⁶ by Dr. Gerhard Venzmer (1893-1986) of Stuttgart, one the best known popularizers of life sciences in Germany, since the 1920s well into the 1950s, having written many books on diverse aspects of biomedicine, with a peak of acclaim during the Nazi period, with hundreds of thousands of copies in circulation. Venzmer’s attitude to “rejuvenation” may be a prime example for the valorization of “natural” holistic hygiene over “artificial” and reductionist rejuvenative surgery and pharmacology. The very term “rejuvenation” was vilified: “The word ‘rejuvenation’, Venzmer wrote, “was earlier severely abused. Overreaching reports, much more ‘sensational’ than factual, awakened false hopes, which were necessarily followed by bitter disappointments. All the endeavors to fight premature aging were thereby made ‘unsavory’” (pp. 147-148).

In place of the “unsavory” (anrüchig) rejuvenation procedures, there comes the “natural” and holistic self-help, particularly emphasizing the health improvement systems practiced in Germany. Among the many German life-extending projects promoted in the work, the anti-tobacco campaign was waged by Fritz Lickint. The life-prolonging breathing exercises or “gymnastics of the cardiovascular system” were recommended by Lothar Tirala and Ludwig Roemheld. The importance of physical exercise (particularly walking) against age-related cardiovascular diseases was emphasized by Julius Hermann Greeff. (Greeff was the author of apparently one of the world’s first dedicated studies of centenarians, published in 1933.³⁷) Relaxation techniques against cardiovascular and nervous diseases were suggested by Karl Fahrenkamp.³⁸ All these means were recommended by Venzmer as essential props to strengthen the vitality of the individual, and to maintain the entire “National Body” (Volkskörper). The emphasis on “natural” and holistic preventive measures was overwhelming. Several other examples of this trend of recoil from reductionist rejuvenation toward holistic life style improvement in Germany may be cited.^39-41 In Austria, the former seedbed of rejuvenation research, following its “Anschluss” (annexation) to Germany in 1938, the attitudes to rejuvenation became hardly distinguishable from those in Germany, as can be exemplified by the work on aging and longevity by the Austrian neurologist, president of the Austrian League for National Regeneration and Heredity, Julius Wagner-Jauregg (1857-1940).⁴² This shift of attitudes to rejuvenation and life-extension may have corresponded to the more general trend toward naturism and holism that was noted with reference to medicine in Nazi Germany in that period.⁴³

With the “holistic” and “naturist” turn, it seems, the German-speaking aging and longevity research community also lost much of the pioneering drive that characterized the earlier “rejuvenators”. It may be argued that the rise and fall of interest in rejuvenation attempts and their underlying reductionism was a global trend. After a surge of publications in the 1920s, in the 1930s the very term “rejuvenation” was rapidly disappearing from the scientific literature. According to Nathan Shock’s Classified Bibliography of Gerontology and Geriatrics (1951, 1957, 1963), the number of publications on “rejuvenation” dropped from a maximum of 27 in 1928 to a minimum of 2 in 1940.⁴⁴ Yet, France alongside Austria and Germany represent perhaps the most salient examples of this trend. The scope of this work does not allow going into further details regarding other contexts.

Conclusion: Reductionism and Holism – which is “better”?

Admittedly the above examples are limited, and the scope of this work does not permit a more extensive further elaboration. For example, a thorough analysis of changes of attitudes in other national contexts or periods, especially after WWII until the present time, would go beyond the scope of this illustrative work. Yet, the examples above may serve well to illustrate the paradigmatic opposition and temporal succession between “reductionist” and “holistic” approaches in aging and longevity research. What philosophical or practical lessons can be learned from the examples of this opposition?

First of all, it is rather difficult to set in stone any definitive “oppositions” or temporal and local “trends” and “periods” in the pursuit of life-extension. Just some apparent trends and predominant emphases can be observed. It should be noted, for example, that even at the peak of the “rejuvenation boom” in the 1920s, the reductionist endocrine rejuvenation was practiced by only a negligible proportion of the population (perhaps thousands operated and tens of thousands taking organotherapeutic supplements worldwide), leaving the rest of the world unaffected or even unfamiliar with these methods. In contrast, some forms of holistic physical culture and “healthy diet” could always be practiced by almost anybody. Thus “natural” and holistic means could have always predominated over the “artificial” and reductionist ones in popular practice. In the literature, however, the trends might be different. Indeed, in the scientific and popular-scientific literature, the “reductionist methods” may “leap to the eye” in the 1920s and disappear from view later on. Thus, the “reductionist” approach may be in a sense more “elitist,” with a stronger appeal for the scientific community, perhaps even more fruitful for the development of science. After all, the reductionist understanding of the “mechanism” may require more intellectual rigor than the rather vague discussions of “wholeness”. In contrast, holistic approaches may be more “populist,” more easily accessible to lay audience and perhaps even more practical, following a set of rather simple and traditional recommendations for a healthy life style (such as cheerful attitude, rest and sleep, exercise, moderate and balanced nutrition). On the other hand, with all the valorization of holistic life style improvements, hormonal and other pharmacological supplements for rejuvenation and life-extension have not vanished, but in fact formed the foundations for therapeutic endocrinology which became a part of massive healthcare practice. The balance and tradeoffs concerning the broadness of appeal and applicability of the different approaches should be kept in mind.

Another potential lesson is the suggestion of a strong relation between scientific perceptions and general social perceptions. It may not be an accident that many proponents and researchers of aging and life extension in Nazi Germany weighed heavily (though not exclusively) in favor of “natural” and holistic macrobiotic health regimens, despite many antagonistic undercurrents. The “natural” hygienic life style improvements were emphasized, as the German society was supposed to be reverting to a “natural” and therefore “healthy” state of the nation.⁴⁵ Moreover, the fear of reductionist intervention may have been a part of the general fear of any intervention into the “national body” from within or from without. In France, ideological parallels are more difficult to find. Nonetheless, it may not be accidental that the “holistic shift” occurred concomitantly with the strengthening of the so-called French political “traditionalism,” reinforcing in the 1930s and culminating during the Vichy regime. The term “traditionalism” (traditionalisme) generally refers to an attempt to return to pre-Enlightenment values, for example, replacing the values of “Liberty, Equality, Fraternity” with “Labour, Family, Fatherland.”⁴⁶ Yet, its extension into the field of longevity research is conceivable. It is difficult to speculate whether the attempts of rejuvenators to dissect and make far-reaching “progressive” intrusions into the “human nature” became increasingly suspicious within the political “traditionalist” paradigm; or whether the failure of the “rejuvenative” intrusions somehow contributed to the general rise of “traditionalism.” In any case, the concomitance of the “holistic shift” with the rise of “traditionalism” may be significant. The same underlying psychological factors of populism and suspicion of “excessive” intellectualism, valorization of simplicity, alongside the fear of intrusion, and rejection of “modish” and presumably unsubstantiated novelty, may be implicated. Of course it would be a grave injustice to claim that all proponents of holism must necessarily also tend to nationalism and traditionalism, nonetheless, a significant correlation can be observed with reference to the specific historical examples.

The temporal succession of the trends may also be significant. The “strain” of reductionist analysis may be followed by a period of holistic “relaxation” (it may not be accidental that during relaxing meditation, unity and wholeness are commonly envisioned). The period of holistic relaxation may then again be followed by a period of reductionist effort. Though not elaborated here, a “comeback” of reductionist medical thinking may be observed after WWII in several national contexts, in particular with the development of “transplantation medicine”.¹ The periodic change of attitudes may also point to a certain cyclicality in scientific thought, rather than unidirectional upward march of scientific progress. Such a cyclicality was noted earlier with reference to social structure and ideology, with analogies in human physiology. Thus, one of the prominent Russian longevity researchers of the early 20th century, Alexander Bogdanov (1873-1928, b. Alexander Malinovsky) – the creator of the science of “tectology” or the “universal science of organization” (1913-1928), a leader of the “Scientific Organization of Labor” movement in Russia, and the founding director of the State Institute for Blood Transfusion in Moscow, apparently the first such dedicated institute in the world – wrote in Tectology:⁴⁷

“The increasing complexity of life’s relations, the increase of their heterogeneity – decrease the harmonious order and stability of the entire system… In all such cases, sooner or later, the accumulated instability leads to crisis. … Those crises that arise as a result of positive selection (and it must be remembered that this is not the only type of crisis) are usually accompanied by a change in the very direction of selection, which then becomes negative. … It manifests in destruction of those elements, connections or groups that are the least stable and vital, that in the largest measure disturb the internal organization of the whole. There takes place the simplification of the system, and increase of its harmonious order. Therefore, if the negative selection does not lead to a complete or profound destruction of the system, but is again followed by positive selection, then the subsequent growth and development of the system assume the characteristics of greater organization, the viability of the society increases, similar to how it happens under analogous cases concerning the viability of the organism.”

The strengthening of reductionism may correspond to a period of “increasing complexity” or “heterogeneity”, while holism may become more prevalent at the period of “simplification”.

A question may arise: Which approach, the reductionist or the holistic, is conceptually “better”? Many clarifications are required to such a question. That is to say, “better” for which purposes? What is “better” – “the trees” (reductionism) or “the forest” (holism)? And can one see the forest for the trees, or the trees for the forest, or both at the same time? Presumably, at any given moment, one may either perceive “the whole” or “the parts”, but not both at the same time. In this sense, what would be the meaning of “parts” within the “whole”? Perhaps some kind of “time-sharing” or “zooming” faculty is involved in shifting from reductionist analytical thinking to holistic synthetic thinking. These questions are rather speculative and hypothetical, yet hopefully they will encourage additional consideration. More rigorous definitions of medical “holism” and “reductionism” may be required to address these questions.

A more practical question may be: Which approach is “better” for therapy? Some authors argue against the predominance of “reductionism” in current medical thought, particularly in aging research, as being too limited, with its focus on selected mechanisms being too narrow and thus fraught with the danger of one-sided and partial, and therefore ineffectual and even potentially harmful treatment.⁴⁸ Yet, the impression that the reductionist method is completely without merit when attempting to understand and intervene into the aging process, in fact elevating the aging process above reductionism, may also be one-sided and ineffectual. The relative merits and shortcomings of reductionist vs. holistic thinking may be considered in a more balanced way. Thus, even when valorizing the wholeness, the unity of the mind and the body, highlighting “synthesis,” and criticizing the limited mechanistic, materialistic, deterministic or reductionist views, we perhaps should not discard the reductionist, “analytical” approach altogether. The anti-reductionist, anti-mechanistic views often mask lacunas in the understanding of physiological processes, and sometimes amount to vagueness and superstition. On the other hand, with all its drawbacks, the conquests of “materialist,” “quantitative” and “analytical” medicine, include veritable life-saving and life-prolonging means (for example, consider transplantation as a reductionist “engineering” approach⁴⁹). Arguably, reductionism should not be discarded simply because we do not yet understand completely the mechanisms of aging. But the mechanisms of aging should not be the exclusive focus either, when devising therapy for the aging individual, at the risk of discarding a vast array of emerging, environmental and social properties and factors. Rather, analysis must be complemented by synthesis, or some “time sharing” may be employed. Reductionism and holism may have their specific indications and uses for particular therapeutic circumstances and purposes. Hopefully, the search for such indications and uses will continue.

Perhaps an even more pressing question is how the choice of either reductionist or holistic perception affects the actual choice of therapy in each particular case. As this work has argued and exemplified, both approaches sought to achieve biological equilibrium and constancy of internal environment. Yet, their implied perceptions of what constitutes equilibrium and constancy were diverging. The reductionist approach saw the human body as a machine in need of repair and internal adjustment and equilibration, seeking to achieve material homeostasis by eliminating damaging agents and introducing biological replacements, in other words, working by subtraction and addition toward balance. The holistic approach, in contrast, focused on the equilibration of the organism as a unit within the environment, strongly emphasizing the direct sustaining and revitalizing power of the mind and hygienic regulation of behavior. In the holistic approach, internal equilibrium was sought not so much through calibrating intrusions, but through resistance to intrusions. These approaches may in fact entail conflicting therapeutic strategies – the valorization vs. prevention of intrusions! How can these be reconciled, or how can the physicians and patients be empowered to make an informed and most therapeutically beneficial choice? And what are the biological equilibrium, balance or stability that are being sought in the first place?! Instead of “equilibrium” or “balance,” sometimes the terms “homeostasis” or “homeodynamics” are used, with reference to the stability of particular tissues or the entire organism, at particular moments or during the entire life course. But how can these concepts be quantitatively and formally defined, and how would these definitions apply for particular clinical cases? How much is “too much” that needs to be removed, and how much is “too little” that needs to be supplemented to maintain “balance”? Or when does the equilibrium need to be preserved by avoiding disturbances, or when does it have to be rescued by interventions? Without a formal and mathematical definition of stable biological balance or equilibrium it may be difficult to answer these questions.⁵⁰ Hopefully, such agreed definitions and practicable suggestions could be elaborated in time.

 

References and notes

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5. Charles-Louis-Maxime Durand-Fardel, Traité clinique et pratique des maladies des vieillards (Clinical and practical treatise on the diseases of the aged), 1854, quoted in Joseph T. Freeman, “The History of Geriatrics,” Annals of Medical History, 10, 324-335, 1938, and in Ignatz Leo Nascher, Geriatrics, the Diseases of Old Age and their Treatment. Including Physiological Old Age, Home and Institutional Care, and Medicolegal Relations, P. Blakiston’s Son & Co, Philadelphia, 1914, p. 41.
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45. Adolf Hitler, Mein Kampf, 1923, translated into English by James Murphy, 1939 by Hurst and Blackett, NY, Reprinted in Project Gutenberg of Australia, esp. Vol. 2, Ch. 1 “Weltanschauung and Party”, Vol. 2, The National Socialist Movement, Ch. 2 “The State”, Vol. 1, A Retrospect, Ch. 4 “Munich”, Vol. 1, Ch. 11 “Race and People”, http://gutenberg.net.au/ebooks02/0200601.txt.
46. René Rémond, Les Droites en France (The right-wingers in France), Aubier, Paris, 1982, pp. 473, 493.
47. Alexander Bogdanov, Tektologia: Vseobshaya Organizatsionnaya Nauka (1913-1928), “4. Ustoychivost i organizovannost form, 1. Kolichestvennaya i strukturnaya ustoychivost” (Tectology: the universal science of organization (1913-1928), Ch. 4. Stability and organization of forms, Section 1. Quantitative and structural stability), Economica, Moscow, 1989.
48. Marios Kyriazis, “Third phase science: defining a novel model of research into human ageing,” Frontiers in Bioscience, 22, 982-990, 2017.
49. Ilia Stambler, A History of Life-Extensionism in the Twentieth Century, Longevity History, 2014, Ch. 4, Section 16, “The 1950s-1960s. The evolution of rejuvenation methods: From organotherapy to replacement medicine. The cycle of hopefulness,” pp. 215-217, http://www.longevityhistory.com/. The issue was partly raised at the presentation: Ilia Stambler, “On the history of life-extension research: Does the whole have parts?” Sixth SENS Conference (SENS6). Reimagine Aging. Queens’ College – Cambridge UK, September 3-7, 2013, proceedings at Rejuvenation Research, 16, S41, 2013, http://www.sens.org/videos/history-life-extension-research-does-whole-have-parts-ilia-stambler; https://www.youtube.com/watch?v=EoBkf8rEGOo.

50. David Blokh and Ilia Stambler, “The application of information theory for the research of aging and aging-related diseases,” Progress in Neurobiology, 2016, http://dx.doi.org/10.1016/j.pneurobio.2016.03.005.