Shades of Gray

Interrelated phenomenon Shades of Gray – Gene Manipulation to establish hegemony, Drug Hoarding and Vaccine Nationalism,

It is understandable, the US started vaccine and drug hoarding, contrary to the principles of humanitarian values and ethics. Hegemony and lack of transparency from China and other power are adding towards a heady mix. This initiated a sense of self.

However, scientific pursuit falls within the realms of humanitarian traits, it is not nation-specific, or unique to any ethnicity, and definitely not the fiefdom or expertise of any ideology or religion.

Having said this, despite the attitude of select countries, we should keep humanity and altruism as our highest pursuits and avoid getting muddled in the politics of nationalism, ethnicity, ideology, or religion.

Every country should attempt in advancing science, however, we should not succumb to vaccine nation, drug hoarding, or manipulating the genome of the wild viruses and or bacteria for usurping our hegemony to advance our nationalistic endeavors. We all know, Science is a double-edged sword, used rightly will lead to evolution, and unlikely use to destruction.

Dr. Shashank Heda,
Dallas, Texas

COVID & Spanish Flu – Comparison and Contrast

102 Not out – Approximately 102 years back, the world was ravaged by Spanish Flu (a misnomer) and today, we are reeling under COVID-19. Both pandemics caused significant pandemonium, and share a common pattern. While it is understandable to see an intermittent new ‘human – microbe’ interaction, going awry, the current pandemic has exposed our fault lines and our preparedness after 102 years. It is not about microbes and our immunity, it is a testimony of our (un)evolved human journey or rather stagnation of evolution in the last 102 years.

102 Not Out, provides a succinct comparison and contrast between the Spanish Flu and COVID-19 and a poignant story of our collective failure.

Background

1918-19 – That period must be the one coinciding with your grandparents or great parent’s birth. So, memories are only through archival records. The global toll was almost 50-100 million, whereas the US lost some 685000 people (a very high percentage for the population at that time). India had 5% mortality with over 12 million succumbing to Spanish Flu.

Spanish Flu – What is that?

Is it truly Spanish flu? It started in France and England. However, they both were at war and wanted to keep this covered. However, Spain being neutral, and news being public, it was reported transparently. It is a misnomer to call it Spanish flu. That is derisive, as Spain was neutral during WW I. It was World War I and soldiers were living in overcrowded barracks. It started in Etaples, France in 1916. It will similarly be wrong to construe that it was an element of French warfare because a similar disease was also observed in 1917 at Aldershot, England. Then too, it was commonly thought to have jumped the animal-human borders as pigs and poultry were a mainstay at these hospitals.

It never occurred to them that they would take the Influenza bug along with them while traveling back home. A disease that once was restricted to specific geography quickly became ubiquitous and spread out indiscriminately. As John Barry said, in New York Times, “None alone provides great protection, but the hope was that if most people followed most of the advice most of the time, the interventions could significantly reduce the spread of the disease, or “flatten the curve,” a phrase now all too familiar. This may sound simple, but it is not. As with a diet, people know what to eat but often stray; here straying can kill”.

3D_Influenza_transparent_key_pieslice_med

(Picture Credit – CDC illustration on influenza virus. Influenza A viruses are classified by subtypes based on the properties of their hemagglutinin (H) and neuraminidase (N) surface proteins. There are 18 different HA subtypes and 11 different NA subtypes. Subtypes are named by combining the H and N numbers – e.g., A(H1N1), A(H3N2). Click on the image to enlarge the picture).

It almost engulfed an entire then connected globe. However, the definition of connectedness, which was ignored then and which is ignored now too, is common to both the Spanish Flu and COVID-19. An estimated 500 million people worldwide were affected. It was a rudimentary period in the evolution of medicine and of course, there were no vaccines or medicines to treat the patients. The findings were, as usual, generally, healthy young adults succumbed to the illness, contrary to most diseases that took the life of the young and old. Today, we call this onslaught of infection against those with a mature immune system as Cytokine Storm. Then, we only knew it killed the young. Then too, people used hand washing, isolation, masks, avoiding public places, and quarantining those ill/suspected ill. It ravaged the economy and disrupted public life, basic civic services like garbage clean up, and postal delivery government services etc. were compromised. There was no one to cremate dead bodies; garbage was flying astray across the streets, no one to light neither lamp posts nor sufficient people to deliver the mail. City offices started digging mass graves, closed schools, public places including theaters. The truth was not transparent, trust in authorities deprecated. Then too, there was a lurking fear that ““civilization could easily disappear from the face of the earth.” Reopening then was marked by a rebound in cases.

Rebound after Reopening

Spanish Flu Rebound

In its intense and acute form, the malady lasted for almost 15 months, from the spring of 1918 to the summer of 1919. It is said that this pandemic Flu almost killed 50-100 million people. Today, we call that Influenza A or H1N1 flu. H1N1 kept lingering, again due to mutations, for 38 years until it was controlled with specific therapies.

Antigenic Shift versus Antigenic Drift

Influenza A and B, each has 8 genes and a variation keeps happening to make a combination each year. As investigations reveal, the 1918 pandemic started with an H1N1 strain, that kept mutating. At this moment, it is wise to understand the meaning of H and N, H stands for those proteins which are required to latch on the cell (inside) and release themselves (N proteins) when mature to infect other cells. This protein structure keeps changing slightly, called antigenic drift. Sometimes, the virus mutates significantly with major changes in the structure of the H and N proteins, called an Antigenic shift.

fcimb-08-00343-g0001

Fast Forward 2019-20 – Comparison and Contrast

It is commonly accepted believe that SARS CoV2 jumped the animal-human barrier. It too spread out from densely populated places. Like COVID-19, it took the world by surprise. No one anticipated that the global burden of death would be over 250, 000 in just 4 months. Then, there was no medicine and here again, we have no specific remedy. The mechanism of death was the same, cytokine storm prevailed then and it is reigning now. It took away the young healthy adults then, however, it is incapacitating for those young adults now, though the mortality is very high in the elderly. Then too, we used masks, isolation, and barrier protection, which we see as the mainstay of stopping the virus within the communities. We call it social distancing, back then, they called it crowding control.

What have we learned?

We see a commonality in the pattern. The biological behavior of the bugs is not changeable. The human response was almost the same. We respond exactly the same way how we responded then. We distanced from each other, we realized, it was spreading through our breath and mouth, so we used masks in 1918 and again, we are using masks. Is there anything wrong with this?

Quotable quotes from Christopher Nichols, Associate Professor of History at Oregon State University –

“The questions they asked then are the questions being asked now,”

“And while it’s very rare that history provides a simple straightforward lesson for the present, this is one of those instances. The Spanish flu tells us that social distancing works. And it works best if we act early, act fast and stick together — and base our decisions not on social or economic concerns, but on science and data and facts.”

References:

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1997248/
https://www.nytimes.com/2020/03/17/opinion/coronavirus-1918-spanish-flu.html
https://www.webmd.com/lung/news/20200420/four-lessons-from-the-1918-spanish-flu-pandemic#4
https://www.cdc.gov/flu/about/viruses/types.htm
https://www.cdc.gov/flu/about/viruses/change.htm

 

https://interactives.nejm.org/iv/playlist/index.html?media_id=siCcYW3U&pcs=sidebar

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1997248/https://www.nytimes.com/2020/03/17/opinion/coronavirus-1918-spanish-flu.htmlhttps://www.webmd.com/lung/news/20200420/four-lessons-from-the-1918-spanish-flu-pandemic#4https://www.cdc.gov/flu/about/viruses/types.htm

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1997248/https://www.nytimes.com/2020/03/17/opinion/coronavirus-1918-spanish-flu.htmlhttps://www.webmd.com/lung/news/20200420/four-lessons-from-the-1918-spanish-flu-pandemic#4https://www.cdc.gov/flu/about/viruses/types.htm

Tribal Instinct & COVID

This is the story of two tribes who want to seclude themselves to prevent coronavirus. Irrespective of whether the strategy works, State cannot impose its will on the people. It is interesting to know that the Cheyenne River Sioux Tribe had rejected an ultimatum by South Dakota’s governor to remove checkpoints on state highways within tribal reservations or risk legal action. According the head of the Tribe, the checkpoints are built to save life, not faces.

‘Individual Identity to Protect’

This becomes important for two reasons –

1) The Tribes have a right to their reservations. In an informal sense, they are a country on their own and the will of the state cannot be imposed unilaterally upon the tribal reservations.

2) Proponents of Herd Immunity insists that isolation will deprive the development of resistance to the virus. Isolation, Social Distancing and ‘Shelter-in-Place’, are social mechanism contrary to herd immunity. It is worth noting that absence of herd immunity makes the population vulnerable to further waves of COVID. Whereas, the detractors persists saying that the innate immune arm serves as the logical arm to counter new infections.

I agree, one of the strategies for countering bugs is to make them commensals and coexisting with them. However, this cannot be enforced. When the state decides to impose its will on the minority, it infringes not just on their rights but their existence.

Excerpts from National Geography

Native Americans are especially vulnerable to COVID-19 due to underlying health issues such as diabetes and heart disease, as well as crowded multigenerational homes. On reservations, where roughly half of Native Americans live, not everyone has indoor plumbing or electricity, making it difficult to follow the guidelines to wash hands regularly in hot water. As a result, Navajo Nation, the largest reservation in the United States, has an infection rate nearly as high as that of New York and New Jersey. As of May 11 there have been 102 confirmed deaths.

‘Blood memory’

The indigenous Native Americans from several states have truly bloody memory from the past panemics. Smalpox is an example, during which their tribes lost significant number of natives. Some elderly haven’t yet come to terms with those deaths yet.

When you have social structure that is so intricate, interrelated and interwoven, it is necessary to create checkpoints to isolate. 

Contagion and Contact

History has ample examples of secluded cultures, ethnicities, and congregations being wiped out after interaction with those having an advantage of a wider swath of commensals. If we understand history, we understand the reason for this tribal instinct. If we lose the context of history, an unilaterally impose our will of integration, we will lose them again.

The entire civilization in the Americas was lost to guns and bugs. The Incas, the Mayas, Aztec, and the other smaller tribes. We know how the Spanish conquistador bought plague and other diseases from the then most filthy continent on the face of the earth. Another example is the now reigning tribes in the Amazon. And the most notable are the tribes from the Andaman, an archipelago in the Indian Ocean.

Is it our tribal instinct to expose the entire population to SARS CoV2 better or is there tribal instinct better in safeguarding their cluster and ethnicity?

Shashank Heda,
Dallas, Texas

https://www.nationalgeographic.com/history/2020/05/indigenous-spiritual-leaders-offer-wisdom-during-the-pandemic/

South Dakota governor tells Sioux tribes they have 48 hours to remove Covid-19 checkpoints
https://www.cnn.com/2020/05/09/us/south-dakota-sioux-tribes/index.html

New Hypothesis for Cause of Epidemic among Native Americans, New England, 1616–1619 ; Emerg Infect Dis. 2010 Feb; 16(2): 281–286; John S. Marrcorand John T. Cathey;  doi: 10.3201/eid1602.090276; PMCID: PMC2957993; PMID: 20113559

https://www.nativewellness.com/

Indian mortality in northwestern

2011_vol_2 SAARC Cultures

Prehistoric and Historic Interface

depopulation_of_native_america

‘Catch 22’ with COVID

Covid-19 has pushed us into a situation of ‘Catch 22’, it has exposed the fault lines on several facets on which our modern society, and especially the 21st century, are built. It has questioned the entire edifice of the foundation of humanity, especially as it exists in an integrated global dependent economy.

Covid-19 has pushed us into a situation of ‘Catch 22’, it has exposed the fault lines on several facets on which our modern society, and especially the 21st century, are built. It has questioned the entire edifice of the foundation of humanity, especially as it exists in an integrated global dependent economy.

We have polar perspectives – on one side, we have New Zealand, a small nation, that stopped everything including the virus. New Zealand is not alone state, most smaller well-managed nations were able to thwart the wave of pandemic including Romania, Japan, etc.

On the other end of the polar extreme, we have huge behemoths like the US and China, where despite the controls, the pandemic has been difficult to control.

Of course, economies suffer and to speak the ideal, mankind cannot be restricted to isolation, from itself (social network, families snd friends) and from nature. That has not been, and for millennia has never been the lifestyle irrespective of the civilization. We are definitely in a quagmire, a piquant situation of making a choice, and irrespective of the choice we opt for, we will have to pay collateral value.

That’s why I call it ‘Catch 22’, a situation that has exposed our fault lines.

Planners and politicians are facing this dilemma and resolve but none of our intelligence, native natural or artificial, will help us through this. I remember an important saying by Albert Einstein, that this problem cannot be solved with the same mindset that created it. We have to rise and evolve to a different plane to understand and solve this. (Shashank Heda, Dallas, Texas).

We cannot solve our problems with the same thinking we used when we created them.

Albert Einstein

You may well ask, is this the toughest challenge in the evolution of mankind? Well, I can say with confidence that we as mankind, have evolved through millennia and one thing is clear, this too shall pass.

Every day, I struggle to find, what’s the positive message for today. And I circle back to our inbuilt resilience. How do we strengthen and enhance, visit my next blog on road to resilience during pandemic and stress?

Jugad is not Innovation

Jugad is a reckless exploration of expedient solutions with no or minimal disregard for the system. Whereas Innovation is a novel way of solving a problem, oftentimes it is in the context, e.g. saving money, getting things done at a faster pace, etc. However, innovation never disregards society at large or compromises the existing structure. It encompasses both business and technical problem-solving. Another term, Technology Debt, is used for faster Go-To-Market development of code and is prominently used in software parlance. In this article, I have taken a dig at a common tendency to blatantly brandish our attitude towards scrupulous things with total disregard for laws or norms.

Words 1006, reading time 4 – 5 minutes.

What is Jugad?

 Jugad can colloquially and loosely be defined as a practice of getting things done by investing minimal efforts and getting the desired outcome with an element of exigency attached to getting things done with least care for the system. Whereas, optimization is doing things with minimum cost/efforts/time in getting it done. Often, the later is used in situations to showcase early results but not at the cost of compromising or impacting the system adversely. In Jugad, there is an element of recklessness, lack of concern for the system and accountability. Often it involves dubious methods and approaches. Jugad is when someone gets the license after flouting the system in a spurious way.

 

Introspection

Jugad is not Innovation

Innovation is deeply embedded in the common mind of most amongst us, we call it common sense. Most citizens have a healthy dose of common sense, that is often used in our day to day life. It brings a fundamental advantage in several ways. However, Jugad has a negative connotation and it is self-defeating, for the person and indirectly for the wider society. Despite, like an addiction, we believe it is a great attribute of smartness and keep indulging in it with pride, at the cost of crumbling character. The invention is when Tara Shinde (Vidya Balan) suggests an innovative idea to push the satellite into outward orbits with limited energy (as in Mission Mangal).

Jugad is not Technical Debt

Often a similar term is used in Information Technology (IT) Programming wherein a feature has to be pushed into production at the desired date to achieve a Go-To-Market objective. Yes, it does result in fallacies in the code and does involve a lack of diligent testing beforehand, but it is not at the cost of overall system compromise. It underpins an Agile methodology for code development. Below examples will illustrate Technical debt, and I have taken little extra deep dive to explain the different types of technical debts.

Carnegie Mellon University defines it as “a conceptualizes the trade-off between the short-term benefit of rapid delivery and long-term value”. A design or construction approach that is expedient in the short term but that creates a technical context in which the same work will cost more to do later than it would cost to do now (including increased cost over time) whereas Gartner defines technical debt “as the deviation of an application from any nonfunctional requirements”. What does this have to do with our ordinary “Jugad”? Technical debt emphasizes two paths to choose:

The easier route – made up of messier code or design, will get you there faster.

The harder route – made up of cleaner code and design that takes a lot more time.

It is unavoidable, unintentional and planned. It expedites pushing code but never with malicious intent.

Technical Debt 1

So What Is Jugad?

I will cite an example. Never have I felt good after receiving a traffic citation. I complained but realized, that citation has always helped me reduce my speed and be more attentive. No one will disagree that this effect was everlasting. It might have prevented untoward incidences. However, I always grumbled for getting a citation. In the US, the only way to redress the citation is by legal means, any other means is counterproductive. However, in India, other means can be adopted for faster redressal.

Recently, there was a huge fire in Delhi (Dec 8, 2019) with a death toll of over 35. It is definitely a somber and tragic event. I am sure, the City Corporation of Delhi must be having its own fire rules and regulations. However, I am also sure that those might have been intentionally overlooked. A post facto analysis may reveal the truth later.

In a nation where bridges and buildings keep falling like a pack of cards, it is only newsworthy to read such death tolls and we feel the pain and despair only for a few moments. We lament express shock and get back to our work. However, the underlying phenomenon is our own fallacy and lack of commitment and abject ignorance of true empathy. Incidences like the huge fire in Delhi, the crumbling bridges and buildings or the smog in Northern India are tragic outcomes of a Jugad attitude. It is painful to see recurrent high death toll from such incidences. Unfortunately, we need incidences like this to learn reactively. Of course, some learning will definitely be an outcome, policy books will be updated by city planner, corrupt official, and expediency by owners will override these, NGOs may criticize and some matters will go to courts while others will be pushed beneath the rug.

Indians often pride expediency and leverage our capabilities in getting things done, hardly ever realizing that every moment, every incidence of individual contribution, adds to this Jugad character of the national identity.

There is a great deal of criticism about India as a $5 Trillion economy. People are a skeptic but India is already beyond $5 Trillion Economy. I am taking a futuristic view. According to PwC and the World Economic Forum, India is bound to be a $28 Trillion Economy and China a $50 Trillion Economy. I have an even better prediction about that but first, India needs to fix the parallel process, commonly called ‘Jugad’.

As a rising nation, Indians have to abandon this parallel process (Jugad) mindset. Like it is imperative to dismantling a parallel economy, so is it equally important to dismantle this Jugad mindset and commit to hardship and build a character. Finally, every country has a character and characteristics and this is one character that will lampoon India as trailing Pakistan in the future.

Summarily, I can say with a lot of certainty that almost everyone indulges in Jugad frequently, if not the least evert now and then. However, some pride themselves only on Jugad. If only we can stop our temptation and fix our attitude of falling for short cuts at the cost of the system that would be best application of introspection.

https://medium.com/existek/what-is-technical-debt-and-how-to-calculate-it-80193e4e746d

View at Medium.com

https://insights.sei.cmu.edu/sei_blog/2015/07/a-field-study-of-technical-debt.html

https://www.thehindu.com/news/cities/Delhi/many-dead-and-injured-in-fire-at-delhis-anaj-mandi/article30236267.ece

https://www.bmc.com/blogs/technical-debt-explained-the-complete-guide-to-understanding-and-dealing-with-technical-debt/

View at Medium.com

— — —

Additional Illustration on technical debt –

Technical Debt 2

Demystifying Fasting and Cancer

All faiths across the globe different faith from Zoroastrians, Buddhism, Christianity, Islam, Judaism, Taoism, Jainism, and Hinduism advocate fasting. Fasting is definitely helpful for health and longevity. Social media is abuzz with Fasting and how it treats cancer. There is a sudden surge of colloquial and rudimentary messages on health. Often, these are relied with credence when it comes especially from revered spiritual leaders. One such message is from Sadhguru, a highly respected spiritual leader. In this video, Sadhguru is talking about the ubiquitously presence of cancer cells in our body. To deter the spread of these cancerous cells, he is recommending fasting.

First and foremost, we need to visit the definition of cancer cells. A key characteristic of cancer cell is uncontrolled growth of cells that have accumulated genetic changes (mutations) due to a carcinogen (a cancer causing agent). Second, cancer cells are not goondas that collect in one place as they advance. In fact, as the cancer stage advances these cells spread across their site of origin. Third, fasting is helpful only in select cases, not every cancer. Also, fasting is helpful beyond cancer, however it depends upon the state of metabolism, activities, age, at the least.

While we need people like Sadhguru to bring the social transformation, we definitely want these messengers to provide a solid rationale that is resting on scientific pedestals, devoid of which we will create confusion and loss of credibility. In this article, I have provided a scientific rationale for understanding the causes of cancer and if fasting can help stop the development or progression of cancer.

Words 2492, reading time 9 – 12 minutes. Background in Medicine helpful.

This 2.34-minute video from Sadhguru is truly insightful.  In the below article, I provided the rationale for reconciling scientific understanding of Cancer and Diet with those Vedic practices that are proposed by Sadhguru. More importantly, scientific literature provides a mixed body of the rationale for dietary practice for cancer prevention and or treatment. To rephrase, dietary restrictions can be a feasible option for select cancers, NOT ALL the types of cancer.

I got this video from Singapore, from a good colleague with whom I worked several years ago. With deep respect and reverence to Sadhguru. I listened to this video wherein Sadhguru talked about cancer as –

1) Always present within the body and get stimulated because of stimulants and intoxication.

2) They get organized into one place and later become overwhelming for the body to counter.

3) That these cancer cells consume 27-28 times the normal calories.

His solution according to Yogic culture is –

1) Spacing meals 8 – 12 hours a day

2) Fasting once or twice a month

It immediately drew my attention to the landmark paper by Hanahan and Weinberg, in which the authors talked about ‘The Hallmark of Cancer”. As an Oncology fellow, I remember having read it at least 2-3 times as it was foundational and disruptive in 2000.

As undergraduates, we were tutored on the existence of Oncogenes (1970) and Tumor Suppressor Genes (1986) and Knudson’s two-hit hypothesis (1971). Then, it might have not had such a reminiscent influence on my mind, until I started my post-graduation in pathology. However, Hanahan and Wienberg’s paper was a step ahead in explaining the different pathways for cancer. It served me when I lead the exploratory search for the epigenetics (methylation of TSG) and downregulation of several caspases (genes) in the apoptotic pathway.

I was definitely perplexed when I read the version of Sadhguru on the existence and or progression of cancer for several reasons –

 

  1. I mentioned the key developments in cancer as a stepwise accumulation of mutations in the genes of the cancer cell. These mutations occur due to several factors called carcinogens – viruses, chemicals, hormones, persistent inflammation, UV radiations, etc. We also know that cancer can occur de novo due to improper repair mechanism or existence of germline mutation (mutation inherited from parents). However, stimulants and intoxicants (especially the former), are definitely not carcinogenic and intoxicants like alcohol are considered co-carcinogens, not directly implicated in the development of cancer causation. I especially exclude the 300 plus carcinogens found in cigarettes as a stimulant and include nicotine as the stimulant, which is not a carcinogen, as proven by ‘comet assay’.

I realized, like thousands of other researchers across the globe, that tumorigenesis is a multi-step process and follows a multistep pathway. Germline mutations (those acquired from parents) like BRCA1, BRCA2 or RB genes occur in hereditary cancers. We can call these as existing in all cells in folks who inherit them from parents. However, the percentage of germline mutations are minuscule, possibly representing less one percent of the population. For these hereditary acquired cancers, one single hit drives a normal cell towards cancer progression. Where, in a normal population, any mutation has to hit two times to drive the cells to cancer progression. This Two hit hypothesis was proposed by Knudson in 1971 and is the underlying mechanism for most genetic aberrations occurring in a normal population. Of note, cancer cells do not exist universally in our bodies unless those are inherited from our parents (a less than 1% probability).

TSG and Cancer

 

  1. Though we know that cancer cells consume most of the host nutrition, it is hard to believe that these (cancer) cells organize (like gangs of Goondas) and rob the body of the nutrition. In fact, it is the other way around. Cancer cachexia, a state common in terminal cancer, is primarily due to diversion of nutrition towards metastasized (spread out) cancer cells, not when they come together.

 

  1. The solution offered by Sadhguru, that we should fast at least once or twice to avoid cancer is so much inadequate if not wrong,  as we all know that those who fast frequently have cancer and those obese who are voracious eaters don’t necessarily have cancer (but other metabolic diseases).

 

I specifically mentioned ‘The Hallmark of Cancer” that was published in 2000. This paper made a major stride in advancing our understanding of cancer (the paper was revised by Hanahan and Weinberg in 2011). It is worth revisiting the 6 facets of the hallmark in the above illustration.

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Warburg Effect

Recently, a debate is intensifying on the existence of the mechanism of cancer causation other than carcinogen-induced genetic abnormalities. Immune modification and metabolic abnormalities have also been implicated. The later is called the Warburg effect. Warburg effect proposes that the cancer cells metabolize via the glycolytic pathway even in the presence of aerobic state instead of the much more efficient oxidative phosphorylation pathway.

Let us understand two aspects –

1) Does fasting help the initiation of cancer and

2) Once established and or advanced, will fasting help cancer to regress and or get into control?

Does fasting help cancer?

Recent Geroscience literature reveals that cancer and aging are characterized by dysregulated metabolism consisting of upregulation of glycolysis and down-modulation of oxidative phosphorylation. Based on the research on Geriatric patients, metabolic interventions have been explored as promising strategies to promote longevity and to prevent or delay age-related disorders including cancer.

Will fasting help regression and or control of Cancer?

Select metabolic intervention approaches include chronic calorie restriction, periodic fasting/ fasting-mimicking diets, and pharmacological interventions mimicking calorie restriction.  These are considered as adjuvant anticancer strategies, not the mainstay of cancer therapeutics. By adjuvant, I mean they are supplemented along with standard cancer therapy (chemotherapy, radiation, and targeted therapy). However, to summarize, calorie restriction is subjective and second, where it is effective, it has an adjuvant effect.

Animal studies (in rodents) have shown that chronic caloric restriction reduces and delays cancer incidence, and inhibits tumor progression and metastasis. Also, there is mounting evidence that cancer incidence and mortality are strongly reduced in chronic calorie-restricted non-human primates. Studies of long-term calorie-restricted human subjects have shown a reduction of metabolic and hormonal factors associated with cancer risk. However, chronic caloric restriction is not a feasible clinical intervention. Evident difficulties, such as the long period required to be effective, and unacceptable weight loss, hamper clinical application in cancer patients.

Autophagy: definition and mechanisms

In the 1990’s Yoshinori Ohsumi first proposed autophagy. He received a Nobel Prize in 2016 for Physiology or Medicine for his seminal work in establishing a morphological and molecular mechanism of autophagy.

Autophagy is an evolutionarily conserved lysosomal catabolic process by which cells degrade and recycle intracellular endogenous (damaged organelles, misfolded or mutant proteins, and macromolecules) and exogenous (viruses and bacteria) components to maintain cellular homeostasis. The specificity of the cargo and the delivery route to lysosomes distinguishes the three major types of autophagy –

  • Mircroautophagy involves the direct engulfment of cargo in endosomal/lysosomal membrane invaginations.
  • Chaperone-mediated autophagy (CMA) recycles soluble proteins with an exposed amino acid motif (KFERQ) that is recognized by the heat shock protein hsc70; these proteins are internalized by binding to lysosomal receptors (LAMP-2A) 6.
  • Macroautophagy (herein referred to as autophagy) is the best-characterized process; in this process, cytoplasmic constituents are engulfed within double-membrane vesicles called autophagosomes, which subsequently fuse with lysosomes to form autolysosomes, where the cargo are degraded or recycled. The degradation products include sugars, nucleosides/nucleotides, amino acids and fatty acids that can be redirected to new metabolic routes for cellular maintenance.

Autophagy occurs at basal levels under physiological conditions and can also be upregulated in response to stressful stimuli such as hypoxia, nutritional deprivation, DNA damage, and cytotoxic agents. Autophagy has attracted considerable attention as a potential target of pharmacological agents or dietary interventions that inhibit or activate this process for several human disorders, including infections and inflammatory diseases, neurodegeneration, metabolic and cardiovascular diseases, obesity and cancer.

Autophagy and cancer
The role of autophagy in cancer is complex, and its function may vary according to several biological factors, including tumor type, progression stage, and genetic landscape, along with oncogene activation and tumor suppressor inactivation. Thus, autophagy can be related either to the prevention of tumorigenesis or due to the enabling of cancer cell adaptation, proliferation, survival, and metastasis. The initial indication that autophagy could have an important role in tumor suppression came from several studies exploring the essential autophagy gene BECN1, which encodes the Beclin-1 protein that is frequently deleted in ovarian, breast and testicular cancer.

BECN1 is located adjacent to the well-known tumor suppressor gene BRCA1, which is commonly deleted in hereditary breast cancer. These deletions are generally extensive and affect BRCA1 along with several other genes, including BECN1, suggesting that the deletion of BRCA1, not the deletion of BECN1, is the driver mutation in breast cancer. Furthermore, the activation of oncogenes (e.g., PI3KCA) and inactivation of tumor suppressors (e.g., PTEN and LKB1) are associated with autophagy inhibition and tumorigenesis. Animal models note that the tumor suppressor function of autophagy is associated with cell protection from oxidative stress, DNA damage, inflammation and the accumulation of dysfunctional organelles. Collectively, these phenomena are important factors that could trigger genomic instabilities leading to tumor development.

However, the loss of function of autophagy genes has not yet been identified and demonstrated in humans, raising doubts about the relevance of autophagy to tumor initiation in different types of cancer. In addition, the autophagic machinery is not a common target of somatic mutations, indicating that autophagy may have a fundamental role in the survival and progression of tumor cells.

Once the tumor is established, the main function of autophagy is to provide a means to cope with cellular stressors, including hypoxia, nutritional and growth factor deprivation, and damaging stimuli, thus allowing tumor adaptation, proliferation, survival, and dissemination. Autophagy, by degrading macromolecules and defective organelles, supplies metabolites and upregulates mitochondrial function, supporting tumor cell viability even in constantly stressful environments. Studies have demonstrated that autophagy increases in hypoxic regions of solid tumors, favoring cell survival (a factor that does not favor fasting to help cancer regression and or cure).

The inhibition of autophagy leads to an intense induction of cell death in these regions. Moreover, tumors frequently have mutations or deletions in the tumor suppressor protein p53, which also favors autophagy induction to recycle intracellular components for tumor growth. Although the basal autophagy rate is generally low in normal cells under physiological conditions, some tumors show a high level of basal autophagy, reinforcing the prosurvival role of autophagy in cancer. RAS-transformed cancer cells undergo autophagy upregulation to supply metabolic needs and maintain functional mitochondria, which in turn favors tumor establishment. Autophagy also has a supportive role in metastasis by interfering with epithelial-mesenchymal transition constituents to favor tumor cell dissemination. Finally, studies have demonstrated that autophagy is commonly induced as a survival mechanism against antitumor treatments, such as chemotherapy, radiotherapy and targeted therapy, contributing to treatment resistance.

How does dietary restriction modulate autophagy and cancer therapy?

Autophagy and cancer therapeutics have a mixed relationship. Because autophagy can inhibit tumor development or favor tumor growth, progression, invasion and treatment resistance, researchers proposed that autophagy modulation could be a new therapeutic strategy in the treatment of some malignancies. In preclinical studies, dietary restriction (DR) has been shown to extend the lifespan and reduce the development of age-related diseases such as diabetes, cancer, and neurodegenerative and cardiovascular diseases. DR promotes metabolic and cellular changes in organisms from prokaryotes to humans that allow adaptation to periods of limited nutrient availability. The main changes include decreased blood glucose levels and growth factor signaling and the activation of stress resistance pathways affecting cell growth, energy metabolism, and protection against oxidative stress, inflammation, and cell death. Nutrient starvation also activates autophagy in most cultured cells and organs, such as the liver and muscle, as an adaptive mechanism to stressful conditions.

Studies demonstrate that dietary interventions can reduce tumor incidence and potentiate the effectiveness of chemo- and radiotherapy in different tumor models, highlighting dietary manipulation as a possible adjunct to standard cancer therapies. Among the many diet regimens that have been assessed, caloric restriction (CR) and fasting are the methods under intense investigation in oncology. CR is defined as a chronic reduction in the daily caloric intake by 20-40% without the incurrence of malnutrition and with the maintenance of meal frequency. In contrast, fasting is characterized by the complete deprivation of food but not water, with intervening periods of normal food intake. Based on the duration, fasting can be classified as –

(i) intermittent fasting (IF—e.g., alternate day fasting (≥16 hours) or 48 hours of fasting/week) or
(ii) periodic fasting (PF—e.g., a minimum of 3 days of fasting every 2 or more weeks).

Conclusion

Every stride in translational medicine helps in advancing our understanding of cancer and subsequently, the management of this malady. However, when a person of Sadhguru’s respected stature talks about fiction based on Yogic culture, we tend to degrade our Yogic culture and deprive the credibility of our repute.

However, as stated earlier, there is a mixed bag of information on dietary restriction and cancer prevention or treatment. 

There is a perfect need for interpreting a way of life (Sanatan Dharma and its various plural forms of ideologies for a living). I accept and understand that ancient Vedic science stood on significantly advanced scientific thinking, however, our times are different and we should rely on the current body of knowledge and refine our thinking of ancient yogic culture.

Note: I believe in providing direct feedback. I made an attempt to reach Sadhguru’s office at Coimbatore. No one answered. Possibly, I will make a few more attempts.

Citations:

http://cubocube.com/dashboard.php?a=1582&b=1585&c=1

Effect of short term fasting on cancer treatment https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530042/

Autophagy and intermittent fasting: the connection for cancer therapy? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6257056/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3608686/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648937/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5442682/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5107564/

Nicotine: Carcinogenicity and Effects on Response to Cancer Treatment – A Review (2015)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4553893/

https://www.britannica.com/topic/fasting

 

Consciousness, Death, and Persistent Vegetative State

Background

Consciousness, Death, Coma and Persistent Vegetative State

John Paul II Institute has organized a symposium on Death and Organ Donation. Dr. Coimbra, a neurologist, has shared a video opposing the idea of organ harvesting and donation. Below, is the link on that discourse along concerning the John Paul II symposium (the link is included at the end of the blog). I differ with Dr. Coimbra and have provided a justification for my perspective. 

Dr. Coimbra raised an interesting question – not alone in medicine but one that touches spirituality and philosophy and extends to encompasses life and living. These questions have been an enigma ever since mankind has been dabbling cognitively exploring to understand it.

However, let us discern select issues at first. At the center of the debate is the definition of death and a downstream question, after objectively defining death, is harvesting and or donating the organs. The discussion rests on a select premise and some experiments. Also, it exists in a milieu of ethics and moral values. Let me take this opportunity to untangle the issues in a reverse chronology as that helps discern and render the problem space in a simpler light.

Ethical Milieu and the Messiah Syndrome

Generally, I am averse to the idea of a conspiracy being unleashed on mankind unless it is by a select group of corporate interests or a select few individuals. I hate to consider an idea wherein, someone questions the ethical and moral commitment of a hoard of well-meaning high caliber individuals and their intellect and commitment, especially when these are not connected and/or affiliated, except for the cause and dedication to their quest for scientific (systemic) understanding. To rephrase, it is hard for me to question the integrity of these folks if these people have no common thread, except a persistent quest to unravel science. Especially, when this cohort is not bound by country, religion, business, generations, ethnicity, ideology, etc. Generally, I don’t subscribe to the ‘Messiah’ ideology. So, I would debunk this Messiah Syndrome at the outset. Calling it ‘Conspiracy’ is unjust and uncalled for. Let us not subscribe to questioning the ethical and moral commitment of all these independent contributors.

Scientific Design and Validation

Experiments have validity if the design and or collection of data is methodical, unbiased and satisfies statistical and or inferential framework. Dr. Coimbra has not substantiated his observations with adequate scientific findings and their correlations except inferences based on his precepts and biased beliefs. This defeats the purpose of any scientific study and helps his contentions to falls from the high scientific pedestals.

Conscious Connectedness

Death and Persistent Vegetative State are inextricably related to consciousness. For any discussion on the death to proceed, we need to understand, the very abstract concept of consciousness and its finite and sublime association with organ(ic) rhythmicity and the circadian cycle. The finite but abstract state of consciousness has always endured cognitive and spiritual interests for generations of the elite and of intellectuals. Suffice it to say that with humility, I am attempting to articulate ideas in this subtle and undefined area. Definitely, I want to stay away from sounding like an authority, which I am not except in my capacity as a sincere contemplative scientific seeker.

Consciousness is a culmination of awareness, cognitive interpretation, and our own limited potential to respond to the inputs from the senses and the surrounding we exist. A vegetative state is the loss of this connection between soma and conscious awareness. At times, it is transient and sometimes, it is permanent and irreversible. Loss of connection does not necessarily mean loss of somatic function. We have had several anecdotes wherein, people have risen after long durations of disconnect if their bodies are kept functional. We know that the duration of brain death is longer in frigid conditions or in infants. Similarly, we also know that sages have practiced an extended ‘state of mind and body’ dissociation during their trance phases. We have seen them reverting to normal bodily functions after reversing the soma – conscious association. Their experiences have been very different. We also have heard patients going through the near-death phenomenon, experiencing those bright flashes of light. These are just a few select examples. However, based on all these, it is evident that this is as intriguing an area as ever. However, one thing is clear that once that association between soma and conscious is irreversibly broken, we can closely approximate it with death (exception is Locked-In Syndrome, wherein, the patient is awake and conscious but disconnected with the body.

Consent and Compliance

Under these circumstances, it is best to go by the consent or implied consent of the individual (best interest standards/Substituted judgment). If those are not available, family discretion comes into play. However, religion, culture, and laws of countries define and influence this space of ethics and compliance. Evidently, we see several versions that act out, depending upon the circumstances.

Inference

Labeling this complex cornucopia of facts and diverse facets into a generalized assumption of the immorality of harvesting organ post-death is grossly inadequate if not possibly wrong.

References

Persistent Vegetative State
https://www.sciencedirect.com/topics/neuroscience/persistent-vegetative-state

The Challenges of Defining and Diagnosing Brain Death
https://www.hopkinsmedicine.org/news/articles/the-challenges-of-defining-and-diagnosing-brain-death

The Legal Definition of Death and the Right to Life
https://link.springer.com/chapter/10.1057/978-1-137-58328-4_8

Neuroethics of death in the United States – PeerJ

Click to access 2890.pdf

Spiritual  –

Kundalini Yoga
https://en.wikipedia.org/wiki/Kundalini_yoga

Advaita Vedanta
https://en.wikipedia.org/wiki/Advaita_Vedanta

 

Our Obsolete ‘Fairy Model’

The “Fairy Model”, is embedded as a class effort. Islam has humane cause and healthy tenets, however, the clerics and the religious guardians have become too strong, authoritarian and harsh to let any intellectual individual let it evolve. Islam is not an exception, followers of any faith, not just Islam but Hindus, Christian and Jews etc., all have to reconcile to the concept of change and get rid of the obsolete ideas and evolve. Today, we need religious change more than any technology. The chasm is widening everyday. Evolving religious ideologies to match the changing world alone will solve the problem created by this chasm.

“You would be in Jannat (heaven)” with those multiple fairies. Those are the promises made to several of the Jihadist on multiple occasions, umpteen number of time.

Utter nonsense for four obvious reasons –

  1. This presumes carnal life extends to Jannat. In true spiritual sense, if Jannat has to exist, will it be with those material trapping? Great food, sex, pleasure? Utter nonsense taught to gullible and innocents who cannot think through.
  2. That Jannat is also the place where Lord enjoys carnal moments. Wow! So those who prophesies also awaits the moments to indulge in material pleasure? Surprising that the spiritual leaders are ever bonded and never rise and evolve (those interested may read Maslow’s hierarchy of needs).
  3. The perpetrators forget that the victim, after their death, too enjoys similar benefits in Jannat.
  4. Islam has no place for ladies in Jannat, except serve these youngster, who have just achieved martyrdom. Well, that is against ‘equal opportunities’? A review of history shows countless women having led countries, religion and ideologies. It is a great insult to womanhood when their participation is not extolled.

My request to those prophesying terrorism, please change or update your model, it truly sounds dumb because everyone gets the same treatment – The Lord, The Victim and the Perpetrator. It is little old fashioned and outdated. Unlike old fashioned communism, during these times, everyone would like to be treated differently, not the same.

The concern is not about dedicating for religion or its ideologies, it is about having sane ideas and devoting for those. Finally, every religion has artifacts, and I consider this as one of those artifacts. However, truly speaking, enticing young gullible youngsters with a ‘Fairy Model’, sounds really outdated and obsolete.

Every religion is bound with emotions and artifacts but deep inside, there is a rationale and a message for humanity, often in the context when those tenets were laid. However, over a period, those who are expected to safeguard those tenets, either ends up evolving it or denigrating and exploiting it. Evolution generally is forwarded by singular efforts, whereas devolution or exploitation is generally a class effort. An outside-in view will always provide a rationale and reasoning and remove those emotional epithets.

In this case, the “Fairy Model”, is embedded as a class effort. Islam has a humane cause and healthy tenets, however, the clerics and the religious guardians have become too authoritarian and harsh to let any individual let its ideology evolve. Followers of any faith, not just Islam, but Hindus, Christian and Jews etc., all have to reconcile to the concept of change and get rid of the obsolete ideas.

Assimilating change is challenging, especially within the realms of religion. Change is challenging because it is difficult to understand the change since we are moribund to the status quo, and then to assimilate and drive that change within the context of the religion and finally, to contextualize it to make it relevant. Changing the Fairy Model is not just important but an existential reality for not just one religion but pretty much all religion or ideologies.

Kashmir attack: Tracing the path that led to Pulwama

https://www.bbc.co.uk/news/world-asia-india-47302467

Why am I blogging on health and diet?

For most healthy living is having a balance between eating and exercise. Well, it goes beyond that one will eventually comprehend the importance of spirituality and expand the dimension of health. Suffice it to say that, the most elementary blocks of health starts with Diet and Exercise and this blog is focused on diet and exercise.

Because it is core and critical to our efforts and initiatives in life.

Generalizing from decades of observations, understanding the molecular mechanism that cascades the physiologic pathways, and adding an angle of a spiritual journey to our living, I too believe that the source is within us. We pamper ourselves with indulgence and defend it with reason. That in itself is a root cause for systemic illnesses such as for overweight/obesity, insomnia, hypertension, and diabetes (well in exceptional cases, we do have hereditary, genetic and developmental factors that contribute).

However, once these systemic maladies set in, it takes a long time to revert to the original baseline. Here again, we try indulging in radical results with resultant generalized impact. Liposuction, extreme diets, such as keto diets, etc. cause untoward effects on the body. Dependence on drugs such as antidiabetic or antihypertensives keeps increasing, partly because of tolerance and mostly because the root cause is not addressed.

Restoring health is a discipline, not a snapshot event in time. It needs a comprehensive multidimensional change. I know if I haven’t slept adequately how that affects my work. Some maladies have an evident outcome, others have a long-lasting impact. Let’s have that balanced perspective to dart towards achievements.

I am often reluctant towards opting for radical options such as surgery (with exception), so also I am against drugs/medicines.

Every life journey is unique, complicated by a confluence of conscious and subconscious flows, that we alone can decipher and discern. Those moments of reflection should ideally help in putting up a roadmap towards the restoration of health. While that is the permanent way, we can and should rely on drugs or other means, while transiting towards that phase.

However, jumping directly to radical options is ill-founded and deficient. A gradual incremental reversal, though difficult, can be achieved through consistent behavior with discipline. Well, it is easy to say but difficult to implement. However, that’s the test of your grit and determination, that we all are born with.

Celibate Life for Serving the Lord?

Celibacy and renounciation is not a prerequisite to service of Lord or to mankind. Yes, it is a distraction from devotion but it is not absolutely required. Many religions consider it is a must, possibly because life and normal living itself is a beyond distraction from the path of spiritual service. How best can we confluence these divergent tracks?

Not that atrocities towards women in places of beliefs are uncommon amongst at Hindu Temples or and Muslim Madrassas. We commonly see religion asking for renouncing celibate life to be a guardian or evangelize religion.

The key question is –
Do we have to renounce normal living and be celibate for the service of our Lord and to run the religious institutions? Celibacy is not an absolute criterion but a matter of choice, inner decision, and personal philosophy. This ensures less abuse of fair gender within their ecosystem.

Some religious practices have institutional stipulations that enforce celibacy. However, human nature and natural instincts fight back. The guardians of religion eventually, succumb to their internal material instincts and end up abusing and covering for their crimes. We see such abuses that later get institutionalized.

The report below talks about the Pope allowing for marriage for the priests. Only if the Pope opens the door for the clergy to be married and start a normal life, that we will see a true decrease in such incidences.

Let me change the topic to Hinduism and its evolutionary traits and practices. Hindu priests have always had the option to marry and accept a normal life. Reflecting upon how Hinduism has evolved after adopting such practices, provides credence that this is a philosophy in evolution and has a longer life than predicted by most western historians.

It is important to keep our ideas open and align with nature. Freezing change is counterproductive. The day we freeze evolution, we stop growing though and the only way to keep vibrant and dynamic is to keep listening, debating, and evolving with a sense of accommodation and assimilation. Sometimes back, during the medieval period, Hinduism froze varna and subdued our women. We wiped out meritocracy by institutionalizing nepotism and feudalism. We created a majority that was subservient to those who captured the institutions – religious, social, family, political, etc. thus weakening our institutions.

It takes time to dismantle but the time we unfreeze and evolve, we will see a spurt in our spiritual and ideological growth. To those who say Hinduism is under attack, I agree. But it is not an external element, but our own internal shackles.

Pope admits clerical abuse of nuns including sexual slavery
http://www.bbc.co.uk/news/world-europe-47134033