Fingers of Instability ~ In Life and Nature

An Honest tale speeds best, plainly told. Shakespeare - King Richard (Act IV, Scene IV)

Self-Organized Criticality

We’ve all heard about the “Straw that broke the Camel’s back.” Indeed every extra weight wears on the back support of the camel's spine until the burden is too much and the ligaments rupture, the muscles fray, bones fracture and the sinews give out. The cascade is not a sudden departure but a slow progressive instability that ensues leading to the catastrophic failure.


When sorrows come, they come not single spies, but in battalions ~Shakespeare -Hamlet (Act IV, Scene V)


 Sand-Pile Self-Organized-Criticality

To articulate it better, let us look at an avalanche, you know one of those 180 miles per hour gigantic clouds of ice and snow running down the mountainside, demolishing all the trees and structures in its path? Yes that one. Well it turns out that there are progressive “fingers of instability” present there too. 

The compressed ice over the previous layer of snow/ice via the power of thermodynamics liquefies the boundary layer. The snow layers above slip and slide and start the avalanche. 

It can manifest as a snow, slab or water flow state depending on frigidity of the moisture. 

A similar phenomenon is implicated in the pyroplastic nightmare of a volcanic lava flow and the geological weakened anchors in land-slides; the latter is a progressive system of instability that allows small pebbles to create the sliding mechanism leading to years of uninhabitable space.

 The Bak-Tang-Weisenfel Sand pile Model reiterates the meaning of a progressive building instability and the cataclysm that follows with “one more grain of sand.” This is termed as a Self-Organized Criticality.

 The Sand Pile Experiment essentially determines that critical juncture of stability vs. instability. As the sand is piled on the surface and the slope builds up, the grains of sand are poured onto the pile, one by one, until the slope exceeds a specific threshold value and the site collapses transferring sand into the adjacent sites, increasing their slope. During the build-up of the sand-pile there are small unstable elements within the pile. As more and more unstable elements form, a critical threshold once transgressed leads to the collapse.


 Genes and Mutations

The Knudsen One-Two Hit Hypothesis in Heritable and Non-Heritable Cancers

Changing gears and reflecting about the human body one finds the same fingers of instability present. Ever hear about a Knudsen’s Hypothesis. Well, the hypothesis states that since there are two alleles of each gene one on each arm of the chromosome, therefore it takes two hits in sequential order or concurrently to dislodge a gene function via mutation. One allele mutation weakens the gene but does not alter the function. However loss of both alleles disrupts that gene's function. If the targeted gene is a tumor suppressor gene then that suppression will be circumvented and any (promoter) oncogene can have a field day in initiating and promoting cancer. A case in point is the BRCA1 gene that is a tumor suppressor gene. Its normal functioning protects against malignant transformation of cells in various organs. A mutated/damaged BRCA1 gene leads to a propensity for breast, ovarian, colon and prostate cancers, to name a few. Its like granny driving a red Ferrari with one foot on the brake pedal and other on the accelerator, easing on the brakes, look out! So if those tiny fingers of instability exist as a loss/damage of one allele during birth or via inheritance, followed by a second blow from an external source such as consumed chemicals or exposure to radiation fields etc. then the cancer cascade begins.

Multi-lineage Hits on the Retinoblastoma Gene

 The Linear Logic of Colon Cancer Genetic Mutation

Taking the theme further, let us look at the phenomenon of Colon Cancer. Here the initial “finger “ is the APC gene mutation. Again the gene carries two alleles and each of them has to be knocked out to start the process of initiating a polyp in the colon. This gene then governs the initial process, failing APC mutation the process does not move ahead. In other words if the APC gene mutation is prevented then colon cancer may not form or even propagate. Aspirin and NSAIDs seem to work through the COX-2 mechanism that shuts down the polyp formation. In fact current data suggests a 60% reduction of colon cancer in people taking Aspirin or NSAIDs. It remains unknown whether the mutated gene is dysregulated or whether it’s effect is marginalized by Aspirin. So, here we have the first finger of instability in relation to the colon malignancy. We now add to that another gene called DCC gene that allows the polyp to grow bigger. There are cases and gastroenterologists will share this with you, that they have seen; large poypoidal non/pre-cancerous growths obstructing the colon but these growths never converted to cancer. There, is the non-random linear stream of genetically mutated continuity that drives the malignant process. In other words, if the next sequence of genetic events in the polyp’s history does not take place, the transformation into cancer is arrested. Moving on, now lets add the p53 gene mutation into the mix and voila, the “avalanche” starts and cancer begins. The last step in this unholy  process is the H-Ras gene. Add this into the cauldron of this “Hubble, Bubble, Boil and Trouble” witches brew and now the fully formed colon cancer acquires the ability to spread across many planes, in other words metastasize. So as it is abundantly clear, the fingers of instability exist in the genome and each change adds to the certainty of the outcome but not the time.

Wild-Type Gene Insertions

I might be taking a less traveled path here, but the fingers are going and if you have the patience to read, come along for the ride. Picturing the dynamics of this eventuality one finds the system can be arrested at various levels of the growth phase. Aspirin as I mentioned has been shown in many studies to prevent polyp formation- the precursor to the colon cancer, and equally, adding a “Wild-Type” (Wild-Type means a fully functional unmutated form of the natural gene product) DCC gene or a fully functional “wild-type” p53, where a mutated p53 exists,  might also arrest the course of the disease. In fact studies have been done in prostate cancer where “wild-Type” p53 gene infused via viral vectors, resulted in abrogation of a rapid growth phase in the prostate cancer cells. Food for thought and further research!

 Malignant Lymphoma

Let me take you into another scenario that was developed back in the 1970s by two US pathologists R.J. Lukes and L.D. Collins who devised a classification of Non Hodgkins Lymphoma based on immune nature of the lymphocytic cell line (Lymphomas arise from the white cells called lymphocytes and these cells are responsible for humoral and cellular immunity in the body). This was a tedious task that won over many hearts. In fact at the core of the classification was the premise that cell growth arrests at various stages of growth of a lymphocytic cell leading to an over abundance of the arrested cell population that leads to malignant Lymphoma. The earlier the phase-arrest occurs, the greater the chance of a more aggressive Lymphoma and the later the blocked growth, the more timid the disease with a slower biological growth rate and a longer life span for the individual so afflicted. The classification was based on the morphological views of the cell. The fingers of instability in the Lymphoma are like the “arresting cables,” that are genetically determined. These mutations it is believed can occur from many determined and indeterminate environmental sources such as fertilizers and benzoate compounds. So as the genes play out their drama ( in this case the BCL2, or via Chromosomal translocations like 11:14 etc.), the time of arrested development determines the viciousness of the disease. 

Chromosome 11:14 Translocation in Lymphoma

Life, therefore is lived with these fingers of instability. We are always teetering on the edge of survival. Science estimates that about 10,000 hits occurring on our DNA is a daily affair. It is the built-in mechanism of safety with the DNA-Mismatch repair mechanism that keeps us embroiled in the dynamics of living. Failing this mechanism the DNA takes a hit at a single nucleotide or multiple nucleotide levels and that leads to a  change and the Mismatch repair mechanism unable or overwhelmed by the suddenness leads to a formative DNA change and causes unholy hell. The plot thickens, the pulse races, be still my heart.

Rhythms of the Heart

Sino-Atrial and A-V Node

Speaking of the heart, now here is a crafty four chamber hollow organ that evolves from a tube and continues it's rhythmic beat for 3 billion times in a 80 year old life span.  Match that to a Chevy, Benz or Lamborghini or for that matter even the Ford Model A and the simple answer is "No maas." In that history of time the heart suffers so many whips and scorns and as many winks and smiles that the accumulated physical and emotional stress takes it's toll.  From the sludge of the  excess food deposits, the trauma of the minor inflammations and compromised blood supply to the organ, the constant A-V Node that synchronizes the pulse and rhythm of the heart may with deprived nourishment, abrogate it's authority  to other competing minor neural node stakeholders in the atria or the ventricles. 

Thus the drama of irregular heart rhythm begins. Since the quivering organ does not carry the same "push" to disperse the blood through hundreds of miles of capillaries, "heart failure results. Each extra grain of insult added to the pile of time ultimately collapses the synchronicity of the A-V Node and that sudden departure from rhythm takes a life. The Self-Organized Criticality finds a new victim, proceeding from the ignorance in innocence, through ignorance of change to a loss of human life. Not only the rhythm but the damaged muscle function can bleed strength away, leading to the euphemistic term "Cardiomyopathy." Whatever the ultimate  pathology that grates this organ is, the ultimate race is towards a congested heart state leading to heart failure.

 Aviation

Aloha Airline Decompression and Metal Fatigue

Disparate groupings of animate and inanimate issues show the relevance of this Instability concept in other walks of life. I will take you to another realm called aviation. Airplanes fly, we know that, you can drive them on the roads too if you prefer, but at greater fuel costs and traffic tickets. They (the airplanes) too are subject to these invisible but certainly palpable “fingers of instabilities.” Let me explain further. Remember Aloha Airlines in the 1990s with the fuselage ripped off from the multiple compression/decompression phases of pressurization from thousands of flights, as it landed in Alaska and presented an awesome photo opportunity with passengers alive and seat-belted in their seats. What happened there was metal fatigue. 

US Airways Skin Rupture

A similar event happened to a US Airways airplane recently when a 3-foot piece of aluminum plate was blown off just in front of the rear vertical empennage. No injuries were reported, except rapid decompression. Metal fatigue at vulnerable joined surfaces was blamed. This of course led to a NTSB and FAA requirement for annual survey of the weak points in all commercial aircraft. Early discovery of fracture lines leads to proactive replacement of the piece in qiestion. The instability is thus checked. Damage contained.

 Economic Fingers of Instability and the Crash

And one last bastion of instability, to no one’s surprise is the Economy. Add to the normal barter system of, “I have what you need, but it will cost you…” the dynamics of leveraged arbitrage where the buyer does not know the seller and the seller who bought it from some one else at a lower price, does not know the initial product seller. This is the very crux of the CDS debacle that usurped trillions of dollars in equity around the world. The smarty-pants, mathematically oriented “Quants” added one Ponzi scheme atop another and the fingers of instability lost traction. The net result is a world in chaos. While the blame game continues and the finger pointing gets more intense with the passage of each day as the financial system contracts from its mythical rarified peaks, the regression to the mean follows that will level the field for all, over time. The high-flyers will trim their assets as will everyone else. Thus with such extravagance of hi-falutin words rendered as evidence from economists and deeds by their minions, instability is created and when it does exceed the threshold, please remember when you hear this, “It can’t happen.” means, it will! As Benjamin Zhang explains in his article referenced below; “Moreover, the marginal impacts of volatility and jump measures increase dramatically from investment grade to high-yield entities.” Meaning the higher the yields (return) the greater the risk on the opposite side: loss, for instance! He further goes on to state, “Historical skewness is an indicator of asymmetry in asset returns. A large and positive skewness means that extreme upward movements are more likely to occur. Nevertheless, skewness is not a sufficient indicator of jumps. For example, if upward and downward jumps are equally likely to occur, then skewness is always zero. However, jump volatility RV(J) and kurtosis are direct indicators of the existence of jumps in the continuous-time framework, but the fact that both measures are non-negative suggests that they are unable to reflect the direction of jumps, (my emphasis) which is crucial in determining the pricing impact of jumps on CDS spreads.”  Meaning that the Jumps occur on both sides of the coin, High net returns and high net losses. Try trillions of dollars of loss since the 2007-2008 window period and counting. The United States financial system has faced many downturns, a total of 21 Recession, the current one being the 22nd  since 1900. What is interesting is that of the 21, only two others have been this deep. The other two were The Great Depressions of 1921-1922 and 1929-1933. The Self-Organized Criticality also suggests that there are many more fingers of instability in smaller sand-piles then there are in larger ones. Smaller sand-pile breakdowns are easily recovered from, yet the smaller ones if they remain organized and stable, can temporarily withstand the critical factor of breakdown towards a larger window of time until the combined criticality is reached in the larger sand-pile, a power-law distribution related chain reaction occurs and the back of the banks really breaks!

 Moderation

So what do we learn from this: Moderation. Moderation is tolerated for a much longer time in life and living, then is excess. Building taller castles real and or imagined have more fingers of instability automatically included in their structure. Surprised at that? You shouldn’t be, if you had followed the logic. The larger the structure created, the more spectacular the fall. Remember Bernie Madoff? Anyway, history is replete with examples but we humans beings constant in our habits, categorize events, itemize them and cubby-hole them for posterity in minimalistic fashion. Never do we relate them to each other and to others for grasping the essence of the universal truth. What the Self-Organized Criticality shows us that a small wave is easily deflected while a tsunami has gross devastation written all over it. A single economic system collapse is weathered easily but subjecting the entire world to a global single unitary system of economics and culture is tantamount to annihilation. Similarly a single mutation in an individual can lead to an unfortunate loss of one life but modulating the genome of a large populace is looking for unmitigated disaster ~extinction.

 The Cosmic Rip

Speaking of extinction. The question of the cosmic Self-Organized Criticality lies in the Universe’s  infinite expansion. As the universe expands and the galaxies drift further apart, eventually as one Cosmologists Robert Caldwell of Dartmouth explains, the fabric of the universe will rip (didn't know there was a fabric surrounding the universe) and so will all the heavenly bodies that comprise it. Shudder! Ok now don’t get all jittery about it and build bunkers in your basements (they wont help anyway). That won’t happen for another 22 billion years according to his calculations. Until then as Mr. Spock says, “Live Long and Prosper.”

 References:

Per Bak, Chao Tang and Kurt Wiesenfeld (1987). "Self-organized criticality: an explanation of 1/ƒ noise". Physical Review Letters 59 (4): 381–384.



Naoto Yoshioka . A sandpile experiment and its implications for self organized criticality and characteristic earthquake Earth Planets Space, 55, 283–289, 2003



http://www.bis.org/publ/work181.pdf

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61049-0/fulltext


http://www.nature.com/scitable/topicpage/Tumor-Suppressor-TS-Genes-and-the-Two-887

LONELINESS: The Sense of One

Ever hear about the man who committed suicide? No, you probably did not. On his chest was a soiled piece of paper that had one word written in bold letters “LONELY.” It was striking. It was curious. It was a subject of conversation for several days. What had he meant? Was he lonely or was he implying that everyone else is. Or was he simply expressing an opinion about the state of mind of a society?

Well, whichever point of view one chooses to affirm, one is left with this empty feeling of guilt, compassion, and a repressive sense of being. You see, here I am contemplating something that happened almost a decade ago and yet the memory steals its way back, confounding the present thought and essence of this moment.

I turn my mind to my iPad and click on the Twitter app and off I go into a different universe. A world imagined. A world filled with 140 or less characters expressing a thought or even multiple ones. There is a craze in trying to mash the words, use numbers and via a colon, dash and a bracket create a smile. It is a whole new world. A little upside-down; Sadness is the open bracket while smile is just the opposite, the transition, a click of the key. I look at the steady stream of thoughts that percolates from diverse minds from places far and near. There are people wrestling with their demons and diseases, anger and frustration, fear and strength. Some have ideas to govern the ungovernable and others have ideas to change the world, a much loftier enterprise. And some just rattle on about a sneeze, a cough or simply nothing. It is a steady stream of chaos. It is fascinating! Compelling to say the least. Every nuance and action is shared. Some send pictures of the foods they enjoy, while others send pictures of themselves. Some intellectualize and others try to dumb everything down. It is a sea of humanity and what makes it happy and sad and angry and frustrated and just “be,” is individualism.

I ask myself the question what is driving all of us into this common pathway of word-stream? I am here too. What makes me do something like this? Why, when I can read a book, listen to music or chat with my family, why, oh why must I want to click into being, these electronic energies and time-robbing gremlins of the twitterverse? Why indeed?

Maybe it is the embedded knowledge in other people’s expressed opinion, I try to rationalize. Maybe it is the diversity of thought. Or maybe it is the exact opposite and their implied disdain for my thoughts or its acceptance or complete lack of interest or whatever, but whatever it is, it is magnetic like bees to a flower. What alerts my senses is when my @JediPD button is lit up and I know that some one has communicated with me. I realize then, that there is a need, in me and possibly as in most others, to communicate. To have a sense of belonging, a sense of togetherness, a sense of communication, a camaraderie of sorts, a dialog full with meaning-something that twitter simply cannot provide but only infers. But on the converse side there are scores of people right next to me who easily fill that need already. What gives?

Maybe it is in the loneliness of this electronic togetherness, in this quasi-communicative form, filled with numbers, letters and ampersands that a desire to create another world of free-floating thought amongst a diverse group of individuals represented by avatars and pseudonyms that drives this thought train- to feel the pulse of the unmet, unknown, and unseen. Strange psychology of the mind this is, a corrupted sense of being and existence, don’t you think? It reminds me of that train ride again when, I saw several kids clumped together in two opposing seats. All of them spent the two-hour ride peering at the glow of their smart phone screens. They never said, “boo” to each other. All the while there were snickers, giggles and outright laughter from amongst them but nary a word shared. Have I become one of them?

Maybe, I have because, another event unfolded in front of me, while walking the street in Manhattan the other day, a woman caught my attention. No, no she was very much alive. She was disheveled. Her hair grayed and knotted fell to her shoulders. The clothes, if one can call them that were a rag tag collection of sewed together pieces of fabric, misshapen, misaligned and with the only purpose to cover her boney body underneath. You got the view of her slender arms as they shot out from beneath her cloaked body touching anyone nearby. She had a frown on her face mostly. She was asking anyone near her, “can you please tell me what time it is?” The concern on her face deep with anxiety as if she was missing an important meeting or catching a train. Her face changed for a fraction of a second when someone looked at her and then their watch and answered her. She would then repeat the procedure to the next passerby. One would think she needed a psychiatric evaluation and maybe she did but what got me was that fleeting smile or smirk or whatever it was that graced her unwashed face for that brief moment, when she made a connection with another human that changed her momentarily. Was she lonely. I think so. Don’t you?

Is that the message that man was trying to communicate? We are alone, in thought, in ideas, and fears and frustrations of the mind and we only fill one side of the dialog when we communicate. We are hoping for the other side to respond and in that response is the pull, the need and the magnetism that compels us. We fill our days to belong, to be together, knowing that life even with the closest of companions and soul mates is lived in the isolation of thought, which remains singular. That we are indeed alone and that we try to create new worlds to fill that emptiness is the crushing sense of loneliness that man who committed suicide must have felt. I hope not for all our sakes. Ok enough, let me get back to my tweeting.

Dimitri's Lair

Strange though it seems, but the other night the entire weight of the concerns and fears about medical care were revealed in a small family owned off-road rural restaurant. It sits nondescript and shaded by an oak tree at the road bend. If you blink, you can miss it. I was there.

The owners are Greek, hard working, dedicated to the spirit of providing the best faire to their customers and for that they have earned a loyalty, it seems, of the many that visit them daily. More come here for their meals and a lively discussion of current affairs then in most other places. Don’t get me wrong, the food is phenomenal and the establishment super clean and sparkling with images of care and concern for the patron.

The owners are an interesting pair. The wife is a tall woman with a quick and easy smile and the husband has a perpetual frown that falls heavily on his bushy moustache. His girth belies the enjoyment he gets from his own cooked meals. Graying at the temples, he looks more like someone who should be in a pinstriped suit in Manhattan, but no, this is a quiet, intelligent man, enjoying the fruits of his toils. Their two sons help manage serving and bussing needs in their restaurant, both with the same easy smile as their mother. The restaurant is a tiny haven, a pastiche of bucolic long-ago rural countryside hospitality.

I sit down on the wooden chair next to the wall waiting for my take-out Gyros and watch the wife deftly arrange the meats, greens, onions and tomatoes on the pita bread. Nothing spectacular but oh so delicious! My mouth waters as she delicately places each element in just the right proportion before layering the surface with the home made sauce. If the aroma had calories then all patrons would be walking out as calorie filled

Humptey Dumpteys. Thankfully it only causes sprinkles of digestive juices.

“I come to this country ten years ago, to start a new life with just a few dollars and a dream.” The owner/husband now straddling the wooden chair facing the two guests at a table. He is within earshot, but his voice carries, after all this is his domain.

“You did a wonderful job, Dimitri,” the thin man with a balding head, answers.

“But look at what we got now. It is like my homeland all over again.”

“Not that bad, Dimitri?” The man’s heavy-set wife asks with concern.

“Yes this is how it started.” He muses for a moment. “The same, everyone wants something for Nothain.” He exaggerates the “nothing,” and shakes his head in disgust.

“You know Dimitri,” the woman chimes in, “You are right, look at what they are doing to our health care here.”

“That is a part of it.” Dimitri answers.

“I was at my doctors the other day, you know. Well he wanted me to have a CT scan of the chest because of a chronic cough, I have and some fuzzy stuff on the chest X-Ray that no one can figure out.” She exaggerates her cough for emphasis and without missing a beat goes on, “but then his secretary told me the other day that the insurance would not cover it.”

“Ah ha.” Dimitri is able to get an acknowledgement in.

“So my doctor, God Bless his soul, says to me, you know, Anna, we might have to code you with a higher diagnosis so you can be covered for this test.” She is now fully animated, “But wont that stay with me as a diagnosis? I asked him. No! he says, we are sending it as a suspect diagnosis.” Her face now contorted in abject alarm. “He sat and explained to me the games the insurance companies play to reduce their costs…”

“But sometime the doctors do order a lot of tests?” her male companion interjected.

“Yes, but my doctor explained all that. He said if we don’t do this test, we can continue to monitor with six monthly chest X-Rays.” Her eyes dart from Dimitri and now to me trying to engage anyone who will listen. “And a CT scan can pick up any problem earlier.”

“But now, I read somewhere, they say CT scans can cause harm, even cancer.” Dimitri professes.

“Yes, and I asked my doctor that. He said, that it is the same amount of radiation as one would get flying from the East Coast to the West Coast, or something like that.” She answered.

“So what happened?” Dimitri is inquisitive as another patron enters the restaurant and the tiny bell atop the entrance door jingles his attention.

“I finally got the CT scan two weeks ago after weeks of phone calls and letters from my doctor to my private insurance company.” Anna quietly eyes Dimitri and with the emotions of a motionless rock she says, “They found a shadow!”

“What is it?” Dimitri asks.

“My doctor says, he will need a biopsy next week, but he suspects cancer.”

“I am so sorry, Anna.” Dimitri puts his large hands on hers in sympathy. “Maybe it will turn out to be nothing. Don’t worry, half the time it can be a pneumonia or something like that.” He offers.

“I don’t think so. My doctor wants me to see a surgeon. He says that if it is cancer they can get rid of it” Anna falls silent.

Dimitri pushes back his chair, ready to leave. “That is good!”

“Imagine, if my doctor had not pursued? Just Imagine!” Anna says.

“He is a good doctor.” Dimitri answers. “But soon they will take that responsibility away from him and people over a certain age may not get any treatment for cancer at all!” he waves his hands with a finality. “It happened to my father in Greece. The government disallowed his treatment and then he had to pay a doctor from his own pocket to get the chemotherapy. Now he can’t even get the medicine anymore because the government is so deep in debt, the companies wont supply the medicienes!” His face turns red and his bushy eyebrows narrow and meet in the middle of his forehead. He becomes for that brief moment, all eyebrows, nose and a mop of salt and pepper head of hair. Dimitri pushes back, shakes his head and goes behind the counter to assist his wife.

“Sad. I say, real sad!” Anna says shaking her head. “It can’t happen here?” she asks with her eyes screwed in close together, her face contorted and a forehead lined with deep wrinkles of worry.

Or can it?

I feel a tap on my shoulder. Dimitri’s wife is standing with a plastic bag filled with stacked Styrofoam boxes in it. I must have lost a few moments somewhere. The smell inundates my senses and momentarily, I am wheeled back into my reality. I look back at Anna and our eyes meet. She smiles, a concerned half-smile and our paths diverge..

Dimitri’s wife remarks as she swipes the credit card, “Oh those two are the most negative people on this earth!”

Are they?

I exit the restaurant cajoled with the temper and tantrum of life’s vicissitudes. The insolence of every falsehood and every entrenched thought is cascading through my mind. We have succeeded in burying ourselves in all forms of despair, under every constraint and behind every discipline. While Dimitri was concerned about the entitlements and their devastating effects, Anna was angered about services expected but being denied, both frustrations finding a voice in that fraction of a quiet evening. Life has become the lockbox of anger, dissent and inaction. The past does suddenly look greener. And yet, my hope in our humanity and its resilience still remains firm. We shall overcome!

And we will!

Now More Than Ever...

 In essentials, unity; in differences, liberty; in all things, charity~ Philipp Melanchthon

Doctors are a quiet lot. They reside in their own private worlds. Individualism is bred, since decisions have to be made in real time when lives are at stake. Individualism also espouses the strength of the many minds to meet and discuss the disease riddled human body, leading to a confluence of thoughts for a proper management of an illness. This precise individualism is the reason that many doctors do not ascribe to a united front. They also don’t have the time or inclination to merge in social format to promote a cause. Most leave the social interactions to the bean counting beavers that have risen to the top in various circles of Management of Medical Care. In fact when only 18% of the doctors have membership in the AMA a society that purportedly speaks for physicians, that should tell you that something is not quite right with the state of that art.

Now however things are about to change. What is becoming clearer over the past year or so is that many doctors are using different forms of social media to communicate with others. It seems to have brought a new religion into the field of medicine. A fractured coalition of similarly thinking individuals is about to find a common thread. This thread will change the color of the fabric in the very near future. The benefit will be felt in the larger context of the society. Patients will learn and be educated, families will learn how to monitor their loved ones and each individual will be empowered to take better care of him or herself. Now that is a worthy cause. A platform to do good, that will vacate the ignorance of one and challenge the many that aspire to prey upon the vulnerable. Yes there is hope! Yes there is a way! And yes it will be done. And interestingly there will be no monetary strings of control attached. It will be a human to human connection for promoting and enhancing life.

Commonality in thinking leads to a common purpose. As physicians, that purpose is to provide the best and most efficient health care for the patients. This time, hopefully the unity will be bereft of all the “movers and shakers” the “advisory committees’ and the “money changers.” A direct communication at all levels will create a social network amongst the physicians that will propel the banner of “Good Health.” Unity of thought occurs when ideas are discussed in the light of the day and not behind closed doors in the ivory towers and beside expensive lamplights either. A social network fits the menu perfectly! And in that union of thought the physician will learn, what is perceived as lacking; to know the mind of a patient.

When 22% of all online experience is shared via Social Media and 40 million tweets a day exchanging glances, 750 million faces glaring through Facebook and 75% of the population over 13 years of age just in the US wirelessly connected, the moment is well past inception. It is now!

It is time! Social Media or So Me as it has come to be known, is calling all physicians. One can choose from a potpourri of chat lines scheduled at different hours on different days of the week to communicate with fellow-common-thinkers. Participate, communicate and learn from others the nuances of how the society unlocks its barriers in lockstep with each expression. Now more then ever…

The “chat” list is long but here are a few, worth considering: #hcsm, #bcsm, #MDchat, #meded, #mhsm, #RNchat to start with. 

But the perception of life as an organic unity is a slow achievement, and depends for its growth on a people's entry into the main current of world-events. M Iqbal

PLACEBO

"He that cannot reason is s a fool. He that will not is a bigot. He that dare not is a slave." ~ Andrew Carnegie

Do you know what a placebo is? Of course you do. It is that sugar locked up in the form of a pill or a saline solution in a syringe mocking the pharmaceutical realm of a parenteral agent for improving health. The question that arises then is why do we have a placebo when we have such wonderful medicines available today that can lower blood pressure, lower the sugar in the blood, eat, chew and spit out the cancer cells, thin the blood and thicken it, make more blood, or make less, diminish an element/chemical or raise it in the serum, cleanse the kidneys and also the liver, give brain food for thought and sex up the food of love, I mean we’ve got it all. This is modern day society. Something hurts and a pill will make it go away. Something doesn’t feel right and we make it harmonize. We can get rid of infections, hot flashes, cold sweats, feeling alarmed or feeling nothing at all. We can take the body temperature down and raise the awareness of the mind, or raise the threshold for alarm and drop the bar on fright. So then, you might ask if we can do all that, what is this placebo and why do we need it?

The human body has a built in system of controls. It is a remarkable piece of machinery. It truly is. I mean, where else would you come across this wonderment of trillions of pieces that fit together in such awesome and perfect harmony to create a masterpiece called the human body. Imagine creating multi-terabytes of memory that can be parallel processed into a decision that changes the course of human history. A heart that can beat for 3 billion times in a 80 year human lifetime, an eye that can spot a color from miles away, a nose that can differentiate between a filet mignon and a fried chicken, an arm that can lift hundreds of kilos and a leg that can outrun most animals. You get the drift, don’t you? Well in this wonderful contraption wouldn’t you think there would be a mechanism to fix any potential harm that might come about? Your guess is correct, it does! Given the complexity of this prudent concoction of diverse cellular automata there are mechanisms available to rid the “self” of any harm.

Let us see how that would be so. Imagine when you were a kid, a real kid and you might still be if you are lucky, when the world was large and the trees outside looked like a forest, the staircase never ended and the tiny hill you climb with a few steps seemed to loom large, it was your personal Everest, that kind of kid. Now remember if you do, that you had a fever from acquiring the rotten virus from another of your ilk. You may have shared an ice cream float gazing into that someone’s eyes or bitten off a chocolate bar or even heavens forbid, kissed someone whose blue eyes rattled your hormonal sense of existence. That virus, she or he gave you now flourished inside unbeknownst to you until one day it had overtaken your body’s mechanism of self-preservation temporarily. You got a fever, a headache and chills to boot. You stayed away from school and developed the art of communicating via telephone without using your hands. Your mother brought you some cold moist towels as you milked the system for some more entitled sympathy and made her promise to allow you to do things that would under normal circumstances be considered taboo. And a day later the fever was all gone, the headache dissipated and the chills no longer lingered. You felt a little tired but all in all, almost back into the adolescent race of “that one is mine, this one is yours.”

What happened in that 24-hour period? That is the wonder of the human body’s genius. Upon being attacked by the virus, the immune surveillance found out about the invader. It liberated agents into the blood stream called interferons to destroy the virus. The Interferons also have the innate ability to raise the body temperature and all the while the defensive white cells marched and devoured the virus wherever it had been multiplying. The immune cells also took an imprint of the virus and stored it in its memory-banks so that should the virus ever attack again, it would harness the soldiers immediately and prevent breaches in the first line of defense. So while your mother or grandmother crushed leaves and mint to inhale and loaded you up with pills that were essentially ineffective against the virus, taking them fulfilled the prophecy that doing something actually did something. But really it did not. She might as well have given you a sugar pill at that and taken the victory lap in her mind. But let us not disappoint such loving care and desire to do good with such careless remarks. Your body did all that, minus the interfering pills that assuaged the fearful, concerned and troubled minds. By the way, on a side bar, the entire vaccination concept for infectious disease and to extent in cancer is based on exploiting the immune cellular network to the attenuated, dead or live virus or cancer cell antigen in measured doses so that the immune surveillance can develop a memory for the same and ward off future attacks. So even though the attempt was to rid the viral infection with a pill, the effort was more of nebulous thought of efficacy rather than efficacy itself. The pill that your mother/doctor prescribed for your cold was a placebo, a sugar pill! She still swears by it many years later. She claims she saw the concoction in some reputable magazine.

Now where else have I heard this song before? Oh, I know, I know, you raise your hand. In the various medical journals! You say. You would be right, because most well thought of studies have usually undergone the rigor of experimentation. By that, let me explain, I mean the medicine being developed for a certain disease is compared to a placebo so as to evaluate the real benefit of the medicine. Why placebo? You ask. Why does one have to compare to a sugar pill? Good question. Remember if your mother had done nothing for your viral fever and your body fixed the problem wouldn’t that suggest that the body would take care of the malady? Yes of course it would. So the innate ability of the body to fix is a self-fulfilling prophecy. Adding to that the mother lode of the mind now furthers the “cause-celebre”. Remember mind over matter. And what is even more intriguing and well documented is the fact that if you were to choose a pill or an injection, both placebos, the injection has a better impact in relieving the pain. Funny how our mind and body plays tricks. Your mind tells your body what to do all the time. It is a subjective process. So now lets venture into another thought experiment, to differentiate the efficacy between a “blue” pill and a “red” pill, knowing the color of the pill would change your perceptions towards the benefits of that pill, especially if you had heard that red was better than blue or vice versa. 

Morpheus in Matrix with the red and blue pills

Knowing the potential benefit between two sets of criteria, color the thinking so much as to yield a potential benefit of up to 14% in a statistical modeling. And this statistical modeling renders results in “p-values” of probable significance. In other words, knowing the end result changes everything. This placebo effect is an internal bias of the human body to fix itself. If either the experimenter or the person being tested knows the color of the pill, the bias thus built in the experiment can yield results to suit and confirm the premise undertaken. By that I mean the system is “Rigged” from the beginning. So both parties have to be blinded for a thorough and clear unbiased experimentation ~ therein lies the concept of the “Double-Blinded” Studies. Here is where the placebos come in. The placebos are contained in exactly the same container and look identical to the experimental drug, so the patient does not know the “color of the pill.” The inherent benefit from placebo is therefore contained on both sides of the experiment, thus negating that particular bias. Everything else would then be considered the real, real result - maybe. The experimenter also does not know which patient is getting what and neither does the patient have any clue. The patient’s own immune system, through the power of his or her mind, is invoking the placebo effect of gaining benefit from the “pill”/therapy and on the other side of the equation, the experimenter being blinded as to which patient is being treated, cannot stack any favors (like, younger patients against older, or more women against men or white against color, or gymnasts against sedentary slobs) on the experimental drug side to arm it with better outcomes. However based on the fact that on both sides, the patients are getting something and thus their mental gymnastics will produce the “placebo-effect” and render any such bias moot. In today’s world, only the computer knows and is un-blinded to the experiment. It fills in the numbers of patients on both sides of the aisle to balance the scales between the experimental medicine and the placebo. So if the result after the study has accrued enough numbers of patients it isthen  un-blinded to the experimenter, the statistics will show the real value or lack thereof! Any untruths by omission or commission are betrayals of the self. There is a part of me that wants to address the Confidence Interval and Probability in Statistics, but maybe save it for another day. Suffice to say that the most commonly used CI (Confidence Interval) is at 95%, which means the measure of success is based on 95% accuracy, or putting it another way that equates to a 2 Standard deviation disregarding the impact of the five-percentages. And to get to a Six Standard Deviation or Six Sigma the numbers of patients to be tested in an experiment would rise to 1,000,000,000 or One Billion and that will test accuracy to a value of 99.7% CI!

Venturing further, if you really wanted to see the “placebo effect,” you could divide one group into receiving a “placebo” pill and the other nothing. At the end of the study you would magically and miraculously prove to your non-believing self that the “placebo” group received some benefit that they imagined while the other group did not. 

Snake Oil Pills

The placebo pill grew more hair, less hair, could see better and farther, hear the high “C-Note” or felt stronger, nimbler and could articulate better. Placebos have been known to benefit many an unsuspecting individual against a slew of maladies in various experiments through time. That is what gave rise to the largest industry of the Snake-Oil Salesmen. Fascinating, don’t you think? That something can be had from almost nothing but from the pure distillation of a thought. Some of those fascinating examples are listed below in references.

Given such an impressive array of benefits from taking “sugar pills” the charlatans as I just mentioned, never stay far behind. In fact they, unfortunately will cast larger shadows over crystal clear reason and muddy the waters of logical thought by spreading the myth of their latest “wondrous” drug or concoction that can cure such things as cancer. I’ll take you back a few years and maybe you might remember an actor Steve McQueen with his rugged smirk, who developed cancer (Mesothelioma) and decided to spend his waning months trying to recoup life through the use Laetrile manufactured and promoted in Mexico. 

Steve McQueen

Vitamin-17 they called it and touted it’s benefits, saying that modern medicine did not want to use the product because the pharmaceutical industry was heavily vested in promoting their own drugs. They had ginned up testimonials from fictitious patients about their miraculous cure from using Laetrile. Oh what a travesty that was for the many people who were seduced into spending their fortunes finding the elusive nonexistent cures. But those kinds of shenanigans are not limited solely in the purview of snake-oil salesmen. A similar circumstance would be if an industry crafted an “observer-biased” experimental study to promote a product. Don’t hold your breath and gasp, it does go on in today’s world. It would impact a large group of vulnerable patients at the mercy of greed. It is therefore paramount for physicians to understand the experiment performed, the methodology utilized, the statistical manipulations used, the criteria established and whether or not there is a “moving percentage” to qualify for a benefit or not. Some of you might be surprised with that latter statement. But it is true. Let me explain: Previously the definition of a Partial Response or PR in the field of oncology (cancer care) was that the verifiable disease by clinical or radiological evaluation had to have resolved by more then 50% with an experimental drug under study. Simple enough! Then some one decided to change the PR criteria to a resolution of equal or more than 30%. Now what gives? Essentially by changing that criterion the author was able to upstage response number by migrating “minimal responses” (or responders with less than 50% resolution) into partial responders. Here suddenly the drug effect appeared huge. They could not tinker with the “complete response” which means complete disappearance of the disease and thus is not modifiable. So what was left then, was a smaller group of minimal responders tied with “stable disease” and voila the magic of statistics did the rest by enhancing the numbers of partial responders. Not only that they then started lumping the complete responders with the now magnified numbers of partial responders to compare with a previous study that used a different set of rules. So essentially they were comparing data of different drugs that would otherwise be considered non-equivalent and asserting that the new drug was a potential blockbuster drug of the future, since it gave so many more responders. Abominable to say the least! While we are on the subject, let me state quite unequivocally something that most of the oncologists agree upon. The best response criterion in oncology is the overall survival. Really simple! If the drug A makes you live longer then Drug B (previously tested against a placebo without any of the said statistical and marketing manipulation) then you may have a better product. Using Progression Free Survivals, Disease Free Survival, Time to Progression and all such terminologies indicate a sub-par benefit to the patient, especially if any morbidity is associated with the product in use. We must critically read and learn to understand the nuances of all scientific “experimental-studies,” teach ourselves the techniques to understand the difference between a good and a not so good scientific study and then come to our own conclusion. A snake-oil salesman will sell you his wares if you have the unsuspecting and an incurious mind.

White cells and Red Cells (EM)

So how does “placebo” really work? Using inferences from various studies it appears that positive imagery leads to an up-regulated immune systems that drives the mechanics of white cells (Lymphocytes: T, B, Dendritic and Macrophage cells) into interacting with the invading agent; such as a virus, bacterium or even cancer cell and render them impotent. 

Dendritic Cell

In addition a much slower mechanism is also in place for example Sickle Cell Anemia is a genetic mutation in the African community as a mode of preservation against Malaria. Since there is a prevalence of the Anopheles Mosquitoes that is ubiquitous to the region the population has the predilection for the red cell genetic mutation to prevent itself from being hijacked by the (Malaria) disease. In essence the evolutionary forces forced a gene mutation to create a circumstance that prevents falling prey to a deadly disease. And another issue that you may be familiar with is “Spontaneous Resolution.” Spontaneous resolution does occur in cancer and the mechanism is believed to be also via the immune pathway. Placebo, it is believed works through a similar mechanism of positive imagery that is used as a rallying cry against the “non-self” enemy. In the end, the human body remains the ingenious enterprise, crafty, plastic and changeably protective of self.

Lets raise a glass to that best of the best in defense against all humans being scourges. For in that defense lies our superiority against illness and disease. In that defense lies the virtue of our being!

I think a small dose of what makes the “placebo-effect” tick would be in order, don’t you think? How can we marshal such defenses? Simple really!

1. Imagine good health! (A corollary in baseball would be for a batter to concentrate on the gaps between the fielders rather than the fielders themselves if he/she wishes to enhance his/her hitting percentage.)

2. Incorporate the wellness you feel from exercise on a daily basis. If you can sit, don’t lie down. If you can stand, don’t sit, if you can walk don’t stand and if you can run don’t walk. Amplify your behavior. The Endorphins released in your brain through exercise will enhance the sense of “Well-being.” A healthy body nourishes a healthier mind and thus creates a positive “feed-back loop.”

3. Eat to live and not live to eat. Excess food is stored as fat and forms the bases of diminished activity as a result and ultimately leads to limited activity that leads to less endorphin release and neuro-psychochemical induced depression. The feeling of lack of wellbeing ensues and that ultimately hurts the so-called viable “placebo-effect.” Depression can also lead to chronic disease as a self-fulfilling prophecy.

4. Limit Stress!

5. Take time to enjoy little things in life.

Okay, enough proselytizing the demons out of our existence for now.

Placebo is music for outsiders, by outsiders and our gigs are like conventions of outcasts, which is cool~ Brian Molko ~ Placebo (Musical Group)

References:

Benedetti F, Pollo A, Lopiano L, et al. Conscious expectation and unconscious conditioning in analgesic, motor, and hormonal placebo/nocebo responses. J Neurosci. 2003;23(10):4315-23.

Boström H. Placebo -- the forgotten drug. Scand J Work Environ Health. 1997;23 Suppl 3:53-7.

Haour, F. Mechanisms of the placebo effect and of conditioning. Neuroimmunomodulation. 2005;12:195-200

Hrobjartsson A, Gotzsche PC. Is the placebo powerless? Systematic review with 52 new randomized trials comparing placebo with no treatment. Journal of Internal Medicine. 2005;257:394-396.

Kaptchuk TJ. The placebo effect in alternative medicine: Can the performance of a healing ritual have clinical significance? Ann Intern Med. 2002;136:817-825.

Wampold, BE, Minami T, Tierney SC , Baskin TW, Bhati, KS. The placebo is powerful: Estimating placebo effects in medicine and psychotherapy from randomized clinical trials. Journal of Clinical Psychology. 2005;61:835-854.

Wager TD, Rilling JK, Smith EE, et al. Placebo-induced changes in fMRI in the anticipation and experience of pain. Science. 2004;303:1162-1167.

Young JH. Laetrile in historical perspective. In Merkle GE, Petersen JC, editors. Politics, Science, and Cancer: The Laetrile Phenomenon. Boulder, CO: Westview Press, 1980.

Relman A. Closing the books on Laetrile. New England Journal of Medicine 306:236, 1982.

Friedman MJ. 1978. Erythrocytic mechanism of sickle cell resistance to malaria. Proc Natl Acad Sci U S A 75: 1994-1997.

Fleming AF, Storey J, Molineaux L, Iroko EAm, Attai ED. 1979. Abnormal haemoglobins in the Sudan savanna of Nigeria. I. Prevalence of haemoglobins and relationships between sickle cell trait, malaria and survival. Ann Trop Med Parasitol 73:161-172.

Boecker H, Sprenger T, Spilker ME, Henriksen G, Koppenhoefer M, Wagner KJ, Valet M, Berthele A, Tolle TR (February 2008). "The Runner's High: Opioidergic Mechanisms in the Human Brain". Cerebral cortex (New York, N.Y. : 1991) 18 (11): 2523.

Jillian R. Satin, Wolfgang Linden, and Melanie J. Phillips. Depression as a predictor of disease progression and mortality in cancer patients: a meta-analysis. Cancer, 2009