Tuesday, August 1, 2023

The Sixth Scientific Revolution Transforming Humans as Context Bound

All scientific discoveries contribute towards a better understanding of the universe that we live in. All of this knowledge reinforces our belief that the universe is orderly and that we are at the center. In contrast, there are some scientific revolutions that change how we think about ourselves, as humans. There are some discoveries that shake up our complacency about our importance in the grand scheme of the universe. Such scientific revolutions deserve special merit since by removing our self-centered bias, we get closer to a more universal truth about us and the universe we inhabit. Since our bias for self-centeredness is strong, so are these scientific revolutions. This paper examined five such scientific revolutions and postulates a sixth one that is emerging.


It is easy to define the first of such revolutionary thinking. Thales of Miletus 6th century BCE argued that we should observe physical events without assigning the cause to "god." He argued that there is an underlying process that causes the world to behave the way it does and that we need to work out these hidden processes rather than simply call it the will of god. This revolutionary thinking caused the birth of science. 

The second scientific revolution was by the 16th  century Nicolaus Copernicus., who in astronomy, removed the earth from the center of the universe and placed it among other planets revolving around the sun. By doing this Copernicus also moved humankind, and not just Earth, from being at the center of the universe and we attained a more peripheral place in the universe.

The third revolution that continued to move humans away from being the center of the universe was by the 19th century Charles Darwin. By publishing his The Origin of Species, Darwin pushed humans off the throne of superior beings and back into our mammalian lineage. The theory asserts that like all other beings, we evolved and share lineage with lower primates and other living things. Like all other animals, we are a work in progress. 

The 20th century brought the fourth revolution with Sigmund Freud who emphasized the concept of an unconscious mind. The notion of the unconscious can be traced back to ancient civilizations when dreams were considered to be messages from the gods. Even early philosophers like Plato and Aristotle explored the idea of unconscious mental processes. At the turn of the century, scientists such as Franz Anton Mesmer, Pierre Janet, Alfred Adler, and Carl Jung all worked on this unconscious mind that hid thoughts and decisions from consciousness and therefore from us. But it was Freud that took this concept further and developed a theory of the mind that argued that the unconscious mind is the primary motivator for behavior. The theory put forward the interpretation that we are not in conscious control of our actions.

The later part of the 20th century brought us the fifth revolution with Albert Einstein and his colleagues who developed the idea that the matter is relative. This theory of relativity postulated that gravity and acceleration are indistinguishable, that mass and energy cause gravity and time to curve, and that the acceleration of massive objects causes ripples in spacetime. All of this makes our natural world less rigid, and our reality is determined by context by the locality of the event. 

These theories have one thing in common, what we believe about who we are, as humans on Earth, is not true. That we are part of a larger universe, that we evolved from other life forms, and that how we see the world is relative to our position in the universe. There is a locality in our reality. Where we are is important. The sixth revolution takes all these concepts of moving humankind away from being to the center of the universe as it argues that even our body is part of such a locality. That the biological and chemical context that we reside in determines how we function and behave. This environmental physiology, where the environment changes our physiology proposes that although we see ourselves as sovereign entities we are in reality a conglomerate of different processes that are influenced by the world we live in. As such, under this environmental physiology, there is no “us” and “them”, no “me” and the “environment”, as both converge. Environmental physiology highlights the malleability of our physiology. Richard Rorty said this beautifully: “…had physiology been more obvious psychology would never have arisen…if the body had been easier to understand, nobody would have thought that we had a mind.” (p 239). 

Most of the developments in environmental physiology highlight human intervention in modifying the body. However, equally impressive, and more instructive, is the evidence showing how nature itself manipulates our bodies. By observing how nature manipulates and modifies our bodies, scientists have learned new techniques that emulate nature. Despite the impressive nature of these technological advances, the underlying theme is how nature has such a powerful force on us by constantly changing and modifying our bodies. 

Technological advancements include: 
Genetic Engineering and Recombinant DNA technology led to the creation of genetically modified organisms (GMOs); 
Polymerase Chain Reaction (PCR) amplified specific DNA segments, making it possible to study and analyze genes and their functions more easily;
Gene Sequencing has led to insights into genetic variations, disease mechanisms, and personalized medicine; Stem Cell Research that promoted regenerative medicine, and tissue engineering; 
CRISPR-Cas9 Gene Editing technology allows precise modification of DNA sequences, making gene editing faster, and more accessible; 
Synthetic Biology of new biological components, systems, and even entire organisms, with varied applications; 
Omics Technologies advancements in how molecules interact within living organisms resulting in contributions to genomics, proteomics, and metabolomics; 
Human Embryonic Stem Cells that repair specific damaged organs; 
Induced Pluripotent Stem Cells (iPSCs) takes adult cells and reprogram them to an embryonic stem cell-like state; Immunotherapy such as immune checkpoint inhibitors and CAR-T cell therapy, harness the immune system to target and eliminate cancer cells; 
Microbiome Research that evaluates the bacterial makeup of the stomach enabling the development of probiotics; 
Nanobiotechnology that promotes targeted drug delivery, biosensors, and imaging technologies; 
Neuroscience and Brain Imaging such as functional MRI (fMRI), provide insights into the brain's structure and function; and 
Artificial Intelligence and Machine Learning in Biology accelerate data analysis, drug repurposing, protein folding predictions, and diagnostics.

Such advancements, impressive as they may seem, are just a small insight into the way that nature itself behaves. Scientists have used this limited knowledge about what we know about how the environment influences our bodies to experiment with coming up with technologies in a short span of time. But it would express a special kind of hubris if we forget to add how nature itself manipulates “us.” There is a vast number of unknown-unknowns, but what we have learned provides enough substantiating evidence to affirm that our context, our environment, changes us. This knowledge has taught us that we are more malleable and receptive than we believe. Nature manipulates our bodies on a daily basis. The sixth revolution in science is knowledge about how nature influences and changes our genes, how genes are expressed, how our body processes food, how we uptake nutrients, how we age, how we think, and how we behave.

Natural influences on the body include: 
Epigenetic modifications that determine the expression of specific genes, subdue some and excite others without altering the underlying genetic sequence. Environmental factors, such as diet, stress, and exposure to toxins, can lead to epigenetic modifications, influencing health outcomes; 
Plasmids, are small, circular DNA molecules in humans that come from bacteria and archaea and become inserted in human cells. They often carry genes that provide selective advantages, such as antibiotic resistance, leading to the spread of antibiotic resistance genes; 
Horizontal Gene Transfer (HGT) is the transfer of genetic material between different organisms, typically bacteria can exchange genetic material-- share beneficial genes, such as antibiotic resistance genes--through processes like conjugation, transformation, and transduction; 
Jumping Genes (Transposons) are segments of DNA capable of moving within a genome. They can "jump" from one location to another, potentially affecting gene regulation and function, playing a significant role in shaping the human genome's evolution and diversity; 
Retroviruses are individual strands of RNA viruses that can multiply into human cell DNA by integrating their genetic material into the host genome; 
Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections in our ancestors' germ cells; MicroRNAs (miRNAs) play a crucial role in post-transcriptional gene regulation by binding to messenger RNAs (mRNAs) and either degrade them or inhibit their translation into proteins;
Dysregulation of miRNAs has also been linked to the progression of diseases, such as cancer and neurodegenerative disorders; 
Prions are misfolded proteins that can induce the misfolding of other normal proteins, leading to a chain reaction that can propagate disease in the brain and nervous system, such as Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy (mad cow disease) in cattle; 
Endocrine Disruptors such as Bisphenol A (BPA) are chemicals that can interfere with the endocrine system, disrupting hormonal regulation reproductive and developmental abnormalities; 
Gut bacteria break down complex carbohydrates, producing essential vitamins, and regulating immune responses affecting weight, inflammatory bowel disease, and allergies. which can influence our metabolism, immune system, and overall health; 
RNA editing such as Adenosine-to-inosine (A-to-I),  is a process that alters the nucleotide sequence of RNA after transcription. It is modified by enzymes called ADARs (adenosine deaminases acting on RNA and can impact gene expression, particularly in the nervous system, and is essential for normal brain function;
Genetic recombination is the process of exchanging genetic material between two DNA molecules during meiosis (cell division), homologous chromosomes exchange genetic material through crossing over. It occurs during sexual reproduction and contributes to genetic diversity; 
DNA Repair Mechanisms correct errors that arise during replication or as a result of external factors. For example,  Nucleotide excision repair (NER) is a DNA repair pathway that removes and replaces damaged nucleotides caused by exposure to ultraviolet radiation;
Hormesis where exposure to low or moderate levels of a stressor or toxin can result in a beneficial or stimulatory response, leading to improved health, resilience, or longevity. In other words, "What doesn't kill you makes you stronger." Hormesis can occur in various biological contexts such as Radiation Hormesis, Exercise Hormesis, Caloric Restriction Hormesis, and Phytochemical Hormesis.


All of these processes, and many others that we still have not discovered, interact. For example, exposure to low or moderate stressors that trigger hormetic responses may lead to epigenetic modifications. A hormetic response could activate specific cellular pathways that, in turn, influence epigenetic modification that changes how some genes are expressed (Vaiserman, 2011). The relationship can also be reciprocal where epigenetic modifications can regulate genes involved in stress response pathways or cellular repair mechanisms. Specific epigenetic changes may enhance or dampen hormetic responses, affecting the magnitude of the beneficial effect elicited by the stressor. In some cases, epigenetic changes induced by hormetic responses may be heritable. Offspring could inherit the altered epigenetic marks from their parents, potentially passing on the beneficial effects of hormesis to subsequent generations (Xavier, et al, 2019). Both hormesis and epigenetics have been linked to aging and longevity (Vaiserman, 2011). Moderate stressors that induce hormetic responses are believed to contribute to lifespan extension in various organisms. Epigenetic changes, on the other hand, can influence the aging process by regulating genes involved in cellular senescence and age-related diseases.

The Sixth Revolution in science moves humans from a homo-centric view of the world to one that places humans as more malleable and porous, allowing for the context, and the environment, to influence and change us.


REFERENCES

Rorty, R. (1979). Transcendental arguments, self-reference, and pragmatism. Transcendental arguments and science: Essays in epistemology, 77-103.

Vaiserman, A. M. (2011). Hormesis and epigenetics: is there a link?. Ageing research reviews, 10(4), 413-421.

Xavier, M. J., Roman, S. D., Aitken, R. J., & Nixon, B. (2019). Transgenerational inheritance: how impacts to the epigenetic and genetic information of parents affect offspring health. Human reproduction update, 25(5), 519-541.

TECHNOLOGICAL INNOVATIONS
Genetic Engineering and Recombinant DNA Technology:
Watson, J. D., & Crick, F. H. (1953). Molecular structure of nucleic acids: A structure for deoxyribose nucleic acid. Nature, 171(4356), 737-738.
Cohen, S. N., Chang, A. C., Boyer, H. W., & Helling, R. B. (1973). Construction of biologically functional bacterial plasmids in vitro. Proceedings of the National Academy of Sciences, 70(11), 3240-3244.

Polymerase Chain Reaction (PCR):
Mullis, K. B. (1986). The unusual origin of the polymerase chain reaction. Scientific American, 262(4), 56-61.
Saiki, R. K., Scharf, S., Faloona, F., Mullis, K. B., Horn, G. T., Erlich, H. A., & Arnheim, N. (1985). Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science, 230(4732), 1350-1354.

Gene Sequencing:
Sanger, F., Nicklen, S., & Coulson, A. R. (1977). DNA sequencing with chain-terminating inhibitors. Proceedings of the National Academy of Sciences, 74(12), 5463-5467.
Venter, J. C., Adams, M. D., Myers, E. W., Li, P. W., Mural, R. J., Sutton, G. G., ... & Zhu, X. (2001). The sequence of the human genome. Science, 291(5507), 1304-1351.

Stem Cell Research:
Evans, M. J., & Kaufman, M. H. (1981). Establishment in culture of pluripotential cells from mouse embryos. Nature, 292(5819), 154-156.
Takahashi, K., & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126(4), 663-676.

CRISPR-Cas9 Gene Editing:
Doudna, J. A., & Charpentier, E. (2014). Genome editing. The new frontier of genome engineering with CRISPR-Cas9. Science, 346(6213), 1258096.
Jinek, M., Chylinski, K., Fonfara, I., Hauer, M., Doudna, J. A., & Charpentier, E. (2012). A programmable dual-RNA–guided DNA endonuclease in adaptive bacterial immunity. Science, 337(6096), 816-821.

Synthetic Biology:
Gibson, D. G., Glass, J. I., Lartigue, C., Noskov, V. N., Chuang, R. Y., Algire, M. A., ... & Venter, J. C. (2010). Creation of a bacterial cell controlled by a chemically synthesized genome. Science, 329(5987), 52-56.
Khalil, A. S., & Collins, J. J. (2010). Synthetic biology: applications come of age. Nature Reviews Genetics, 11(5), 367-379.

Omics Technologies:
Aebersold, R., & Mann, M. (2003). Mass spectrometry-based proteomics. Nature, 422(6928), 198-207.
Lander, E. S., Linton, L. M., Birren, B., Nusbaum, C., Zody, M. C., Baldwin, J., ... & Bouvrette, S. (2001). Initial sequencing and analysis of the human genome. Nature, 409(6822), 860-921.

Human Embryonic Stem Cell Research:
Thomson, J. A., Itskovitz-Eldor, J., Shapiro, S. S., Waknitz, M. A., Swiergiel, J. J., Marshall, V. S., & Jones, J. M. (1998). Embryonic stem cell lines derived from human blastocysts. Science, 282(5391), 1145-1147.
Yu, J., Vodyanik, M. A., Smuga-Otto, K., Antosiewicz-Bourget, J., Frane, J. L., Tian, S., ... & Thomson, J. A. (2007). Induced pluripotent stem cell lines derived from human somatic cells. Science, 318(5858), 1917-1920.

Immunotherapy:
Hodi, F. S., O'Day, S. J., McDermott, D. F., Weber, R. W., Sosman, J. A., Haanen, J. B., ... & Urba, W. J. (2010). Improved survival with ipilimumab in patients with metastatic melanoma. New England Journal of Medicine, 363(8), 711-723.
Maude, S. L., Laetsch, T. W., Buechner, J., Rives, S., Boyer, M., Bittencourt, H., ... & Wood, P. (2018). Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. New England Journal of Medicine, 378(5), 439-448.

Microbiome Research:
Turnbaugh, P. J., Ley, R. E., Hamady, M., Fraser-Liggett, C. M., Knight, R., & Gordon, J. I. (2007). The human microbiome project. Nature, 449(7164), 804-810.
Qin, J., Li, R., Raes, J., Arumugam, M., Burgdorf, K. S., Manichanh, C., ... & Wang, J. (2010). A human gut microbial gene catalogue established by metagenomic sequencing. Nature, 464(7285), 59-65.

Nanobiotechnology:
Farokhzad, O. C., & Langer, R. (2009). Impact of nanotechnology on drug delivery. ACS Nano, 3(1), 16-20.
Sweeney, S. M., & Wooley, K. L. (2005). Self-assembling polymers for gene delivery: from laboratory to clinical trial. Advanced Drug Delivery Reviews, 57(15), 2075-2087.

Neuroscience and Brain Imaging:
Ogawa, S., Lee, T. M., Nayak, A. S., & Glynn, P. (1990). Oxygenation-sensitive contrast in magnetic resonance image of rodent brain at high magnetic fields. Magnetic Resonance in Medicine, 14(1), 68-78.
Kandel, E. R., Schwartz, J. H., & Jessell, T. M. (2000). Principles of neural science (Vol. 4). McGraw-Hill, Health Professions Division.

Artificial Intelligence and Machine Learning in Biology:
Alipanahi, B., Delong, A., Weirauch, M. T., & Frey, B. J. (2015). Predicting the sequence specificities of DNA- and RNA-binding proteins by deep learning. Nature Biotechnology, 33(8), 831-838.
Topol, E. J. (2019). High-performance medicine: the convergence of human and artificial intelligence. Nature Medicine, 25(1), 44-56.

NATURAL INFLUENCES
Epigenetics
Jirtle, R. L., & Skinner, M. K. (2007). Environmental epigenomics and disease susceptibility. Nature Reviews Genetics, 8(4), 253-262.

Plasmid 
Modi, S. R., Lee, H. H., Spina, C. S., & Collins, J. J. (2013). Antibiotic treatment expands the resistance reservoir and ecological network of the phage metagenome. Nature, 499(7457), 219-222.

Horizontal Gene Transfer
Thomas, C. M., & Nielsen, K. M. (2005). Mechanisms of, and barriers to, horizontal gene transfer between bacteria. Nature Reviews Molecular Cell Biology, 6(9), 711-721.

Jumping Genes
Chuong, E. B., Elde, N. C., & Feschotte, C. (2017). Regulatory evolution of innate immunity through co-option of endogenous retroviruses. Science, 351(6277), 1083-1087.

Retroviruses
Grandi, N., & Tramontano, E. (2018). Human endogenous retroviruses are ancient acquired elements still shaping innate immune responses. Frontiers in Immunology, 9, 2039.

MicroRNAs
Bartel, D. P. (2009). MicroRNAs: target recognition and regulatory functions. Cell, 136(2), 215-233.

Prions
Prusiner, S. B. (1998). Prions. Proceedings of the National Academy of Sciences, 95(23), 13363-13383.

Endocrine Disruptors
Diamanti-Kandarakis, E., Bourguignon, J. P., Giudice, L. C., Hauser, R., Prins, G. S., Soto, A. M., ... & Zoeller, R. T. (2009). Endocrine-disrupting chemicals: an Endocrine Society scientific statement. Endocrine Reviews, 30(4), 293-342.

Gut Bacteria
Sender, R., Fuchs, S., & Milo, R. (2016). Revised estimates for the number of human and bacteria cells in the body. PLOS Biology, 14(8), e1002533.

RNA Editing
Nishikura, K. (2010). Functions and regulation of RNA editing by ADAR deaminases. Annual Review of Biochemistry, 79, 321-349.

Genetic Recombination
Hunter, N. (2015). Meiotic recombination: The essence of heredity. Cold Spring Harbor Perspectives in Biology, 7(12), a016618.

DNA Repair
Lehmann, A. R., & McGibbon, D. (2006). Xeroderma pigmentosum. Orphanet Journal of Rare Diseases, 1(1), 27.

Radiation Hormesis, 
Macklis, R. M., & Beresford, B. (1991). Radiation hormesis. Journal of Nuclear Medicine, 32(2), 350-359.

Exercise Hormesis, 
Ji, L. L., Kang, C., & Zhang, Y. (2016). Exercise-induced hormesis and skeletal muscle health. Free Radical Biology and Medicine, 98, 113-122.

Caloric Restriction Hormesis, 
Turturro, A., Hass, B. S., & Hart, R. W. (2000). Does caloric restriction induce hormesis?. Human & experimental toxicology, 19(6), 320-329. 

Phytochemical Hormesis
Son, T. G., Camandola, S., & Mattson, M. P. (2008). Hormetic dietary phytochemicals. Neuromolecular medicine, 10, 236-246.

Tuesday, August 23, 2022

Summary of "Politics of Anguish" (book)

Chapter 1 : The Creation of a New Disease

Feared more than cancer or heart attack, Alzheimer’s disease has now capture people’s fears and worries. But finding how the disease develops and then progresses has eluded scientists. Going back in time when Dr. Alois Alzheimer observed the new disease provides some evidence and clues to why we have failed to control this disease. 

Finding that there were some clamping of neurons, plaques and tangles, in the brain was not a new discovery. But the creation of this new disease relied on other issues at the time. It relied on a belief that certain people are inferior, that politically it was beneficial for the Munich clinic to define this new disease to compete with the Prague clinic, and the belief that old age is a dustbin of medical problems. The motivation for creating this new disease was not only scientific but also political in 1900 Germany.

Alzheimer’s disease stayed dormant until the 1950s when American scientists started looking at diseases of older age and searching for cures. By the 1970’s the zeal of searching for a pill to cure all maladies, including Alzheimer’s disease, blinded researchers and they lost focus on how the disease develops and progresses.

The foundation of the science is however unstable. The initial observations that Alzheimer observed, the plaques and the tangles, were common, not just for Alzheimer’s disease but also for many other diseases including neurosyphilis (Dr. Alzheimer’s speciiality.) The plaques and the tangles did not directly cause the disease as many people had these in their brain but never developed the disease. This is a story of how the most frightening disease in the world was created by a perfect storm. Today we are left with disorganized research and a 100% failure of finding a cure or a way of slowing the disease. The future looks bleak and we can only understand this present situation by looking back in history. 


Chapter 1: The Creation of a New Disease 

What Alois Alzheimer identified more than a century ago was an early onset dementia that was important, but not for the reasons he and his clinic director Emil Kraepelin presumed. Initially Alzheimer saw a pattern that fit the biological proof in support of the clinical observations—plaques and tangles and early-age of onset. Subsequent researchers fell into the same pattern: a habitual research method of finding proof.  We now know that these criteria are not discrete enough to both define and predict Alzheimer’s disease. 

And we know this because of the ambivalence of the neurobiology, of how the plaques and tangles relate to the disease. Questions arose from the beginning, which to this day we still cannot answer, because there is a problem with what we are trying to explain. Other than familial Alzheimer’s disease, the remaining paths of the disease  are random and cannot be measured reliably. 

Clinicians remain dependent on prognostic tools that are unreliable. There remains a healthy discussion about the validity of the diagnosis. Research on the clinical features of Alzheimer’s disease is based on combining many short–term, specific, small, cross-sectional study samples. As a result research is fragmented and confusing. Whether by choice or chance we are told that the salvation to this disease will come from a cure. But this construct contains a falsehood. A similar search for laboratory proof is currently being undertaken for Alzheimer’s disease. But how did this state of disorganization in research come about? To find an answer we have to move away from science and look closer at the politics of the disease.

Chapter 2: Politics 

Only tenuous evidence existed that separate Alzheimer’s disease from senile dementia. The current consensus among researchers is that Alzheimer’s disease and senile dementia are indistinguishable in contrast to Alzheimer’s belief. 

The imperative to promote a more biological psychiatry was a paradigm-changing endeavor in the 20th century. Alzheimer’s disease played a major role in contributing to psychiatry’s reliance on neurobiology, biology, chemistry and genetics. Because of its prominence, Alzheimer’s disease will likely play a large role in the future of psychiatry. This prediction is being realized with the introduction in 2010 of the NIH-sponsored Research and Domain Criteria (RDoC) which integrates biomarkers, genomics and clinical observations to define both normal and abnormal behavior. Alzheimer’s disease is the proving concept for this new U.S. federally-funded nosology.

The fact that in the 1900s the Munich laboratory competed with the Prague laboratory was also a factor. Even today, biomedical research remains a highly competitive field. Nowadays biomedical research seems particularly prone to fraud because of the level of competition among clinics. Back in the 1900s Kraepelin understood this competition which played a significant role in the scramble to be the first to define Alzheimer’s disease. The belief that some people are different from others because of genetics may have also helped Kraepelin assert the distinction between Alzheimer’s disease and senile dementia. The eugenics argument is rarely mentioned in the literature despite the importance of the philosophy in academic circles at the turn of the 20th century. The fact that most of Kraepelin’s perceived competitors were Jewish—at a time when Jews were considered inferior by some groups—could not have been a small consideration. As an example, Fischer’s obscurity and his early demise in prison because of his Jewish beliefs, is another indication of the strong undercurrent of racist beliefs at the time. Although Fischer’s insights into dementia have now been vindicated his legacy remains obscured.  But of all these factors, the central issue was—and still is—ageism. If Alzheimer could not argue that this new disease was not just for older people, there would be no classification of a new disease. 

Diseases of old age are not news. For most of the past century, it was assumed that old age is a stage of dying and therefore associated with decrepitude. Older adults were meant to have diseases and die. No medical interest exists to subvert  such inevitability. The reason why Alzheimer’s disease gained traction is because, for the first time, the disease was affecting younger people. The importance of these prejudices are present with us today.  

The birth of Alzheimer’s disease as we know it today, was more than simply a new clinical observation it also had political overtones. It reflected the stereotypes of the time. In 2011, the NIA changed the definition of Alzheimer’s disease to allow the pharmaceutical industry to experiment with a clinical disease before it becomes diagnosed (pre-clincial). But this is creating costly and divergent research. After a century of research we are still unclear about the diseases that come under Alzheimer’s diseases and sadly, we are not closer to understand what causes Alzheimer’s disease or its many variants. 

Chapter 3: Disorganized research

Several major sources of confusion remain in Alzheimer’s disease research. The primary confounder comes from the fact that we do not know what Alzheimer’s disease is, and even if we did, we cannot reliably diagnose it, either clinically or neurobiologically. Even if we accept the NIA’s pre-clinical stage of Alzheimer’s disease, the validity and reliability of pre-clinical data is poor at best, and contradictory at worst.  

The varied causes of cognitive diseases are not well understood. Gaining knowledge about chemical, neurological and biological pathways and processes does not directly contribute to our understanding of behavioral or clinical disorders. After more than a hundred years of research, there remains a lack of understanding of whether one disease has different expressions—Alzheimer’s disease, Lewy Body Dementia, Vascular dementia—or whether different disease processes lead to the same pathway of expression—Alzheimer’s disease caused by physical trauma, bacteria, virus or vascular disease.  Therefore, it is difficult to make distinct and accurate diagnoses. 

The concept that Alzheimer’s disease is not a disease but a syndrome provides an impetus for more research by examining the process of the disease, rather than investing all research efforts in finding a cure. The cause/s of the disease are still unknown. Correlational studies might imply causation but this is psychology, not science. Researchers need to admit that the results are puzzling because we are working from an incomplete theory—one that we need to update.

The second source of confusion comes from the great variance among older adults—heteroscidasticity. Even among identical twins, this drift can result in one twin getting Alzheimer’s while the other escapes. This relates to epigenetic changes that influence both brain plasticity and neurogenesis. This variance, that increases among individuals as they age, will continue to dilute the linear association between a specific neuropathology and its expression, especially among older adults. 

Although researchers look for genetic markers that will eliminate all these epigenetic or environmental factors, so far The Alzheimer’s forum has identified more than 1,395 studies working on 695 genes that account for up to 0.5 percent of Alzheimer’s disease. If 695 genes account for half of one percent of Alzheimer’s disease, then even if researchers can identify and manipulate all of these genes the disease will not be cured. This criticism, that genetic studies cannot explain all the variance of Alzheimer’s disease, can be applied to the search for biomarkers, both biological and chemical. The only challenge to the current expression of biological determinism is the fact that there is no competing paradigm to guide research. 

The deduction is that confusion becomes a ploy, not a failure or an expression of incompetence. Confusion as a method allows a small research group connected with the NIA to dictate and continuously change the meaning of the disease. Regardless of the intention, the result is obvious. Confusion and uncertainty have created great fear. This confusion unfortunately spills over into clinical practice as well, affecting patients, their families and their rights as citizens. Alzheimer’s disease is over-registered and over-diagnosed with consequential wasted health care costs and undue stress to the family. Perhaps the confusion is that we did not understand that our fear of Alzheimer’s disease has become a neurobiolgical playground where we have feverishly worked ourselves into a research cul de sac. 

Chapter 4: Research cul de sac

The inductive method of observing a disease to learn what people have in common creates a false syllogism—a fallacy. Just because everyone with dementia has the neuropathology, we cannot logically argue that everyone with the neuropathology will have dementia.  Because science should also be based on a deductive model, where theory directs the line of investigation, researchers need to conduct more theory-driven hypothesis testing. A mounting body of evidence does not support the theoretical construct that a linear causal pathway exists between a biomarker, causing MCI that then matures into a dementing illness. Infact a systematic review of the literature agues for broad use of techniques to counter MCI. Partly for this reason, we see very little deductive reasoning in research on Alzheimer’s disease, although it is evident in neurobiological studies. The two worlds of neuroscience and clinical services that are evident in Alzheimer’s disease remain distinct, separate and divorced. 

The lack of validity, across a whole spectrum of issues in Alzheimer’s disease research is a negative statement. The anomalies point to the necessity of expanding the concept of biomarkers to explain how they might be moderated or mediated by other, as of yet unexplored factors. It could be that the plaques and tangles are like scarring on a wound—indicative of a trauma but serving as a protective feature. Clearing the scab will not change the underlying trauma and might even be detrimental to the healing process. We are leading to potential situations where despite being competent and having normal memory and behavior, a patient might still be diagnosed with dementia. Such is the mission of the Research Domain Criteria. We need to resist this biological determinism mode of thinking, which is becoming more and more prevalent, and which has negative repercussions on our relationship with our medical and legal institutions. Alzheimer’s disease is playing a major role in persuading researchers to adopt such a system of biological determinism. 

The relationship between Alzheimer’s disease and changes in the normal aging processes need to be distinguished. One possible clue could be the speed of attrition. Even though we still do not know enough about normal aging processes, sudden attrition might be indicative more of disease pathology. A longitudinal perspective is crucial for elucidating such a distinction. Despite all the ambiguity surrounding the disease, we see the disease as very real and very frightening. We remain fixated on it because it feeds a very personal and intimate fear. We accept a fanciful process of causation because it is safe to assume that we know how to approach the problem and possibly find a cure. But if we reinterpret the philosophy behind our fear of Alzheimer’s disease we might arrive at some basic understanding that might help in defining a new, badly-needed research paradigm. 

Chapter 5: Philosophy of Alzheimer’s disease

People need a consistent, stable sense of self throughout their lifetimes, including when they self-project into future situations. This is the essence of being, of Dasein. A purely neurobiological model of cognition cannot explain some basic anomalies in research. For example, a woman misdiagnosed with Alzheimer’s disease nevertheless makes herself believe that she has the disease; men who pretend to be 20 years younger become younger; and clusters of people who have very long lives age well without Alzheimer’s disease but these clusters are found only in small geographic areas. All these events can help us understand the dynamics of our reality, our being. This is the study of ontology. Such preoccupations have also received validation from neurological studies. The next frontier involves accepting a broader definition of being—of Dasein—that includes others, the environment and our geography. It is not biological determinism, because the biology/genetics is determined by the environment and our interpretation of that environment. We own the biology as well as the environment.

There is a cultural condition of the fear of Alzheimer’s disease. That there is an element of self–limitation, of  a self-fulfilling prophecy and it may be time to question our own mindsets. Older adults report that their fear of Alzheimer’s disease has increased from the second most feared disease to the most feared disease. Fear of dementia is now so strong that there is a new term: “Dementiaphobia”. This alone represents significant condition of our Dasein—both in terms of what we care about (gaining ownership of beliefs and ideas), the Facticity (we have no control over whether we get Alzheimer’s disease), and also in our personal projections of the future (the likelihood that we are going to get Alzheimer’s disease). 

In this context, fear has already limited our ability to deal with negative cognitive episodes. This is a constant in our lives. Many opportunities exist to misinterpret cognitive decline as both long-term and Alzheimer’s disease-related. Fear is nuanced. A family member suffering Alzheimer’s disease creates a template for us to follow, a mindset, especially if we provide care for them. There is significant deterioration in the health of caregivers when compared to a similar group of non-caregivers. Caregiving becomes more stressful the longer one does it. The stress does not stop when the care recipient dies. Also seen in the  “widowhood effect”—where the surviving spouse dies soon after their partner—exemplifies how intimate relationships define what is important in life. Death following spousal death among older adults has been estimated at between 30 percent and 90 percent in the short term, and around 15 percent in the long term. 

Not only are we led to believe that Alzheimer’s disease is random without any control, caring for a loved one with Alzheimer’s disease magnifies this as a likelihood in our future. This association might contribute more to familial dementia then genetic factors. Because we learn by experience we are sensitized to look for “signs” of the disease that we then use to promote the likelihood that we will get the disease. “We have nothing to fear but fear itself” is the new watchword for Alzheimer’s disease. 

Chapter 6: Complexity Theory of Dementias

The brain is the most complex organ in the universe. Nothing else is more complex. The simple theory that two misfolded proteins by themselves create a breakdown of thinking is not accurate. Theories based on the Amyloid Cascade hypothesis are incomplete. Emerging evidence points to a more complex process. There are many possible causes of dementia. The initial injury might or might not progress.  The neurological disease might or might not affect cognition. 

These considerations are valid and have been left out of the new research agenda. Our conventional reliance on genetic causes is similarly simplistic. Accepting the evidence that external injury (viral, bacterial, biological, chemical, environmental, behavioral) can initiate dementia reframes the disease as a public health issue. In this case, we can alleviate or minimize some of these causes. We are already doing this with head trauma in sports with new protocols for diagnosis and treatment. Other injuries that are shown to contribute to dementias should be similarly addressed. By addressing potential traumas, perhaps we could eventually prevent most of the initial causes of the disease. Such an approach opens the door to positive, creative prevention. Adjusting the focus to include the study of multiple causes also brings the disease squarely into the public health field. 

A central puzzle of dementias is the penumbra. Also, a feature of stroke, the penumbra or shadow that accompanies the surrounding dead tissue in the brain might explain why some stroke victims experience the growth of the penumbra that eventually leads to dementia. The process of penumbra raises radical scientific questions about the progression of dementias and whether or not the neuropathology can be contained. 

Perfusion (blood circulation) and the role of vascular conditions play a major role in dementias. Emphasizing the roles of an active lifestyle, healthy diet, and awareness of vascular issues moves the discussion further into the public health realm. Within Complexity Theory, the concept of the brain functioning as a machine is incorrect. Even dementia patients learn new things, and they sometimes forget things then remember them, or have episodes of clarity. How can we explain this fluctuation through neuronal death? Appreciating that parts of the brain can continue to grow, switch capacity from left to right and back to front, and vice versa, and acknowledging that cognition might be an assimilation of different systems within the same brain, will help researchers ask more incisive questions about the role of the brain. 

Acknowledging that the brain is always changing, neurons and glial cells constantly die and get replaced, where more than 30,000 proteins constantly misfold and get degraded, where constant injuries to the brain are accommodated, where memories are constantly re-imaged and prioritized, where cognitive functions are shifted from one area of the brain to another, all of these events define the daily functioning of our brain. The question that needs to be asked is why does this constant maintenance stops or becomes overwhelmed?

Science will benefit from a resurgence of sociological and philosophical discussion about the role of cognition in the mind, the distinction between mind and brain, and the concept of self. All these broad discussions have been rejected in preference for the more simplistic explanation. So far, after a century of confusion, it is time to stop repeating the same mistakes in the hope of coming up with new results. We need a new methodology that might provide different results. 

Chapter 7: Synthesis

A more inclusive approach allows diverse literature to be included rather than ignored. The body as a sovereign entity a self-willed, independent, exclusive and free agent is an illusion. Ample evidence now shows that our body—meaning our brain and body—not only respond to external activity but also mirrors these activities. External influences—of which we are unaware most of the time—affect how we think, behave and feel. Social constructs, memes, and stereotypes affect us because we internalize and operationalize them within us.  There is no impermeable barrier between our external environment and our body; an illusion of the mind creates this duality. No better example exposes this illusion than dementias and aging. The crescendo of fear of dementias affects us. We often live trapped in a world where fear dictates our future.  Fear of dementia as represented by Alzheimer’s disease now represents perhaps the penultimate disease meme of the 21st century.  To combat this we need to expand our study of dementias to include social and psychological factors, otherwise, we will remain in our current research cul de sac. We need to shift from a hypercognitive model to a caring model. Care might lead to a cure. 

Chapter 8: Epilogue

This is as far as science can take us. Criticism of dementia research dictates a number of changes that need to be made at the Federal level to promote a healthier and more inclusive scientific debate. Scientists need to be very sure of what they are studying and to emphasize the validity and reliability of their subject matter. Such recommendations are necessarily abstract, nuanced, and academic. But on a more personal level, I can identify the basic parameters of the data and conjecture how I see this Complexity Theory apply at an individual level. This is not prescriptive in any way but the start of a discussion away from the neurobiology. 


Recommendation for self-help


Summary and Class Discussion Points




Older Smell

On their return from visiting a nursing home, my children when we were in kindergarten happily shared with me their impression that the residents “smell.” A nursing home is not the best place to get to know older adults, but the stereotype remains. There are even some fancy scientific theories to explain why this is so. We know that taste and smell diminish with age, but that older people also have a distinct odor is worth exploring.

Visiting Japan, one is immediately faced with the strict culture of washing and bad odor is frowned upon. The Japanese even have a distinct name for the body odor of older people Kareishu. After conducting a poll of 150 men and women, the Japanese Shiseido Group found that odor from older people is the second most offensive scent behind bad breath. We will return to this study later on. 

Body odor in humans is determined by various factors, including genetic background, physiological conditions, behavioral patterns, food ingestion, and disease types, but most often there is a stereotype that it relates to getting old. The theory is that older people smell because of their aging biology. One theory suggests that aging causes hormonal imbalances resulting in more lipid acid in our skin. And as skin matures, its natural antioxidant protection decreases, resulting in greater oxidation of this lipid acid resulting in Nonenal. The smell of this chemical compound is similar to oil that goes rancid when left out. This chemical is more common among people over 40 years of age. Another biological theory is that the major contributor is the bacterial activity in skin gland secretions. Numerous skin bacteria help produce smelly substances and as we get older this bacteria seems to be more common. 

It could also be related to diet. In 2017 Jun Nishihira with Hokkaido Information University and his colleagues reported that eating a mushroom extract (Champignon) was found to improve body smell, as well as bad breath and smelly poo. The idea that perhaps we can counteract this Kareishu was explored by Dae Youn Hwang with Pusan National University, Republic of Korea, and his colleagues. They found that extracts of Spiraea Japonica—a deciduous, perennial shrub native to Japan—reduced the odor of older adults. 

Developing products to counteract Kareishu opens the market to businesses making money off older people’s fears and stereotypes. Shiseido Group at one point developed a perfume "Harmonage Fragrance" specifically formulated to neutralize older people’s body odor. Then there is the line of anti-age-stench soaps by Mirai Clinical that this time uses persimmon extract as a natural deodorizer. The issue is not that body odor changes with age, it does, the issue is whether this smell is bad. 

Researchers have shown that the body odors of some animals—including mice, black-tailed deer, otters, owls, and rabbits—change with age and that animals can distinguish their young and old peers by smell. Even people can tell the difference between old and young otters and rabbits by how they smell. 

Older people might smell differently from younger people, but this is not always a bad smell. We know for example, that some frail older people experience difficulties in mobility and getting washed, but those that are still functional and maintain good hygiene might be different.

Johan Lundström and his colleagues at the University of Pennsylvania stitched absorbent pads into the armpits of T-shirts and asked volunteers of different ages to sleep in the shirts for five consecutive nights. During the day, the volunteers stored the T-shirts in sealed plastic bags; avoided spicy foods, cigarettes, and alcohol; and showered with odorless shampoo and soap. After the fifth night, blindfolded volunteers rated the pads and found elderly people's odors both less intense and less unpleasant than odors from young and middle-aged people. Middle-aged men had the most unpleasant odor while the odors of middle-aged women were judged to be the most pleasant. Old people's smell was often instantly recognizable and not necessarily in a bad way. The result from this study is different from the earlier study by the Shiseido Group. But then again if I am selling a fragrance I want to create a market of smelly older adults so that they will buy my fragrance. In reality, older adults might smell differently but not in a bad way. The lesson is how easily we accept the negative stereotype of older people smelling.


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References


Nishihira, J., Nishimura, M., Tanaka, A., Yamaguchi, A., & Taira, T. (2017). Effects of 4-week continuous ingestion of champignon extract on halitosis and body and fecal odor. Journal of Traditional and Complementary Medicine7(1), 110-116.


Kim, J. E., Choi, Y. J., Lee, S. J., Gong, J. E., Seong, J. E., Park, S. H., & Hwang, D. Y. (2022). Evaluation of Deodorizing Effects of Saccharina japonica in 10-Month-Old ICR Mice Using a Novel Odor Marker Associated with Aging. Evidence-Based Complementary and Alternative Medicine2022.



https://www.scientificamerican.com/article/old-person-smell/


Mitro, S., Gordon, A. R., Olsson, M. J., & Lundström, J. N. (2012). The smell of age: perception and discrimination of body odors of different ages. PloS one7(5), e38110.

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0038110


Hospice

When talking about gerontology—the study of older people—most people assume that it is a new study as they have not heard of it. The same goes for hospice. If you bring it up in a conversation most people will know of someone who went through hospice, but again they think that this is a current trend, something new. So, it comes as a bit of a shock when people learn that gerontology is as old as writing itself. The first known record of writing is the Sumerian Saga of Gilgamesh about 4,000 years ago. The most famous of the five poems is "Gilgamesh, Enkidu, and the Netherworld." a poem that describes the love that King Gilgamesh has for Enkidu, a half-god when he tragically dies. An event that sets Gilgamesh on a search to find a cure for aging and to death in order to bring his friend back from the dead. The story has spawned many others, and there are traces of this story everywhere, including in the bible. It is important to understand that the first evidence we have of literature dealt with getting old and dying. 

Even the term “gerontology” was used in 1903 by Ilya Mechnikov, an immunologist who with Paul Ehrlich was jointly awarded the 1908 Nobel Prize in Physiology or Medicine. Gerontology even fathered the discipline of endocrinology (the study of hormones) and transplantation (transplanting organs). A hundred and twenty years later, people still think that gerontology is new because they do not want to think about aging and about dying. This is very much true in Japan as well. In 2016 Mitsunori Miyashita with the University of Tokyo asked Japanese people about a ‘good death’ and showed that they tended to avoid thinking about it. The study also found that they gave their family a large say in how they should die. We do not want to think about death. 

Hospice provides care for people who are dying. Such care was first established during the Crusades in the years after 1000 and became widespread in the Middle Ages. It formally became a branch of medicine when Cicely Saunders founded St. Christopher’s Hospice in London in 1967. This first hospice set the stage for other hospices throughout the world. In Japan, the first systematic palliative care service was launched at Yodogawa Christian Hospital, Osaka, in 1973, and then in 1981, the first palliative care unit (PCU) was opened at Seirei Mikatahara General Hospital, Shizuoka. After 1990 when insurance started covering PCU treatment, hospice grew into a national service that covered all of Japan. By 2017,  there were 394 PCUs with 8,068 beds. All of the designated cancer hospitals have PCUs. 

In Japan, like in every other country, most people want to die at home and a third want to die at PCUs. However, the reality is that most die in hospitals. Masanori Mori and Tatsuya Morita have identified the need for more training and better specialization in Japan to promote better and more accessible care for the dying. And there have been great advances. By 2015 there were more than 50,000 physicians trained in palliative care. While a study that started in 2008 to monitor palliative care in Japan called the Outreach Palliative Care Trial of Integrated Regional Model (OPTIM) has recently found that Nurses' palliative care knowledge, and practice improved with more training. 

The fundamental problem with hospice relates to what we discussed earlier in the introduction, people do not want to talk about it, and that includes physicians and nurses. Health care workers do not want to go into hospice. If you are part of a profession of saving people’s lives then helping them to die seems contradictory. Most people leave hospice till the very end. Others shy away from contacting hospice, even though most hospice services can be delivered to your home. The only way to change this is to accept death as part of the cycle of life. Talking about death does not have to be sad as it can highlight the privilege of being alive. By appreciating that having a good death needs to be planned. We have known this for centuries perhaps now is the time to accept it for ourselves.


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References


Mori, M., & Morita, T. (2016). Advances in hospice and palliative care in Japan: A review paper. The Korean Journal of Hospice and Palliative Care19(4), 283-291.


Nakazawa, Y., Kato, M., Miyashita, M., Morita, T., & Kizawa, Y. (2018). Changes in nurses' knowledge, difficulties, and self-reported practices toward palliative care for cancer patients in Japan: an analysis of two nationwide representative surveys in 2008 and 2015. Journal of pain and symptom management, 55(2), 402-412.


What are the main challenges facing palliative/end-of-life care today in relation to Japan’s ageing society

Posted on January 31, 2018 by pallcare

Mariko Masujima, Principal Investigator, and Zaiya Takahashi, Core Promoter, the Center of Excellence for End-of-Life Care at Chiba University, describe the present situation, policy and cultures about end-of-life care in Japan.

Accessed: https://eapcnet.wordpress.com/2018/01/31/what-are-the-main-challenges-facing-palliative-end-of-life-care-today-in-relation-to-japans-ageing-society/


Drugs and Older Adults

America is the country for sex, drugs, and rock and roll….well maybe just drugs and rock & roll.  Americans can be very traditional when it comes to discussing sex, but as for drugs we use medication as much as the Japanese. Most Americans are on some kind of medication or illicit drug. During 2015–2016, almost half of the U.S. population, including children, used one or more prescription drugs.  If you include recreational drugs, alcohol, and tobacco then you can assume that nearly everyone is on some kind of mood-altering drug. In addition, nearly everyone takes caffeine, either from coffee, soft drinks, or tea. Drugs are everywhere and they are differentiated only by whether they are legal or not and whether they are prescribed by a doctor or self-administered.

When discussing the problem of drugs, most people fall into the habit of automatically blaming recreational drugs. There is a long-standing myth that drug abuse is rare among older adults. The belief was that long-term drug addicts either recovered or died, and that addiction and use of illegal drugs by older adults were restricted to a small group of older criminals. But when we look at reality a different picture emerges. It is prescription medication among older people that is a primary concern. It is legal medications that cause more harm--those prescribed by your doctor--or those that you can buy from a pharmacy off-the-shelf. Prescription drugs are more popular with older people, especially older women. Pain relievers remain the most popular drug for the last two decades. Nearly a third of adults over 65 are on prescription medication. Most of these are not addictive, but the most popular medicines are, especially those for pain relievers.

While we see older men being addicted to alcohol and illicit drugs, older women are more likely to be addicted to pain medication like sedatives, hypnotics, and anxiolytics for anxiety. One type of anxiolytics is Benzodiazepines, which treat anxiety, pain, or insomnia, and are highly addictive and common. There are also common medications that older adults should not be taking. These drugs are updated every year under the BEERS criteria. 

Some medications might also be used inappropriately either intentionally or through forgetfulness. Older adults forget what medications they are on, and when and how to take them. Even though the US spends more on medications than any other country—mainly because we pay more for drugs than most countries—Japan leads the world in prescribing medications for older adults. 

When the world saw a decline in life expectancy for the first time this century in 2014, that was not due to wars, in the US this was attributed to the over-prescription of opioid medication. Promoted by big pharma, opioids were sold with the lie that they were not addictive. There was a fivefold increase in prescription opioid overdose deaths from 1996 to 2016 in the US. While newspapers focused on younger adults who misused prescription opioids, it was middle-aged and older adults between 50-64 years and older that use prescription opioids at a higher rate than any other group.

Combined with alcohol, prescription drug abuse among older adults is one of the fastest-growing health problems in the US. Alcohol and prescription drug abuse affect up to one in six older adults. Since older adults have a decreased ability to metabolize chemicals, the drugs stay in the body longer and our brains seem to get more sensitive to these drugs. This makes it dangerous for older adults to use any drug, even if the person is not addicted. On top of this, there is self-abuse. One-tenth of all older adults are also binge drinkers—five or more drinks at a time. Binge drinkers were more likely to be male and more likely to also use tobacco and/or cannabis. In the US cannabis use among older adults increased to one in twenty people, especially among older men younger than 69. Prescription medication combined with other drugs does not mix well.  With increasing access to geriatric doctors, nurses, and gerontologists we see a reduction in prescriptions and an overall improvement in life. In a complex world, having someone help you to navigate around these many drug options will benefit you to get the most from medications.


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References

Han, B. H., Moore, A. A., Ferris, R., & Palamar, J. J. (2019). Binge drinking among older adults in the United States, 2015 to 2017. Journal of the American Geriatrics Society, 67(10), 2139-2144.


Han, B. H., Sherman, S. E., & Palamar, J. J. (2019). Prescription opioid misuse among middle-aged and older adults in the United States, 2015–2016. Preventive medicine, 121, 94-98.


TsujiHayashi, Y., Fukuhara, S., Green, J., & Kurokawa, K. (1999). Use of prescribed drugs among older people in Japan: association with not having a regular physician. Journal of the American Geriatrics Society, 47(12), 1425-1429.



https://www.addictioncenter.com/addiction/elderly/


https://acpinternist.org/archives/2021/03/cannabis-use-increasing-among-older-adults.htm


https://www.verywellmind.com/us-has-highest-levels-of-illegal-drug-use-67909


https://www.cdc.gov/nchs/products/databriefs/db334.htm#:~:text=During%202015%E2%80%932016%2C%20almost%20one,the%20pattern%20varied%20by%20age.


https://rehabs.com/blog/most-popular-drug-in-us-by-decade/


Ending our Story

We have an image in our minds of how our life will progress. This is usually formed when we were children, so it is simplistic. It goes something like this: we grow up, make lots of money, get married, have kids, and live happily ever after. We quickly find that this story might not be true for us. But even though we might be disillusioned, what this tells us is that with these stories we like to predict. We like to tell a coherent story about our lives. It is part of how we are designed and we like to guess what will happen in the future, and we seem to do it for our own death as well.

When we ask people how long they expect to live they will be surprised to learn that they are fairly accurate. We tend to underestimate how long we live but otherwise, it is fairly accurate. It is so accurate that statisticians who work with life insurance (actuaries) use this to adjust how long they expect us to live and therefore adjust how much we pay for life insurance.

David Phillips, with the University of California San Diego, has been looking at this phenomenon.  In 1992 Phillips and his colleagues examined three million deaths from natural causes.  Women are more likely to die in the week following their birthdays than in any other week of the year. It seems that females are able to prolong life enough it seems until they have reached a positive, symbolically meaningful occasion—their birthday. For women a birthday seems to function as a “lifeline.” In contrast, male deaths peak shortly before their birthday, suggesting that their birthday functions as a “deadline” for males. Older men are more likely to experience their looming birthday as a negative sign. The importance of a “lifeline” or a “deadline” also works for other significant days.

In 2016 Andrew Stickley and his colleagues looked at over 27,000 suicides in Japan between 2001–2010. What they found was that males were more likely to commit suicide around their birthday—5 days before and a week after their birthday. While females, they committed suicide 7–11 days before their birthday. In Japan, birthdays seem to be a deadline for both males and females. We find cultural variations throughout the world.

David Phillips and Elliot King showed that in a small Jewish group death declines by about a third below normal before the Jewish holiday of Passover and then peaks by the same amount the week after. It seems that Jewish people hold on to life a little bit longer to celebrate Passover. In contrast, non-Jewish deaths showed no such pattern around the same period.

The same is found for the Chinese who are less likely to die the week before the Harvest Moon Festival but peak the week after. In the West deaths spike during Christmas and New Year’s holiday period possibly because these periods are both stressful and indulgent. Also, people might delay seeking medical treatment during the festive season. 

Another interesting observation centers around Tetraphobia, the fear of the number “4”  that is common in Japan, as well as in China, Taiwan, Singapore, Malaysia, Korea, and Vietnam. This superstition seems to have arisen from the similarity of the pronunciation of the word “four” and “death” in Japanese as well as in Mandarin and Cantonese. When looking at death from heart disease among Japanese and Chinese Americans we find that there are extra deaths on the fourth of the month. No such increases showed up among other populations. 

It is difficult to make any conclusions. Certain days such as our birthdate can have significance. We might see it as an accomplishment (for women) or as a deadline (for men), or as evidence of loneliness among suicidal Japanese.  Some festivities which are stressful likely to hasten our demise (Christmas and New Year) while other holidays we might withstand till after they pass (Passover for Jews and Harvest Moon Festival for Chinese.) Then there are days that we fear that act as a self-fulfilling prophecy (the 4th of each month). What seems to emerge is that how we think about death influences when we die, at a minimum by a few days and at a maximum by some years.


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