Saturday, December 31, 2011

Infinite Causal Regress ~ Back to the Future

What will I be tomorrow?
I am me!
The state of flux manifests
I change from Being to Becoming ~ a cumulative discourse between content and context.
Is it fantasy that leads the imagination with its requisite abstraction?
I begin to write ~the call from the past?
I practice Medicine ~ a privilege to care for and nurture others
I educate myself in the field of Physics and Mathematics ~Does Lamarck press?
The mind is freed to grasp the abstract
Two new beautiful beings inherit the earth ~ our children
I marry my sweetheart
Sleepless nights, worry-filled days and joyous recoveries!
I am a physician ~ with a devotion to the craft
I educate myself in the field of Medicine ~love it
I go to Medical School
I prefer the idea of helping sick people ~has Darwin overcome Lamarck?
I want to be a physicist ~is this the Lamarckian influence?
I go to High School
I want to be a doctor ~is this the primary dictate of the Darwinian influence?
Different ideas roil inside and around me, 
I go to intermediate school
My friends advocate their ideas and plans to influence me
I advocate my future ~ that no one hears
I write a short story ~ that no one reads
I go to grade school
I read my first book called Fuzz and Buzz
I am a child tempered with introversion ~exerting my independence
I am an infant with all the assembled parts of a male ~ a miracle
The genes exert their Darwinian pressures ~ a tug here and a push there
I am a fetus ~ with cellular replication in full fury
The genetic materials unite ~ from Morula to Blastula
I am conceived ~ an army brat
My parents get married.

Monday, December 26, 2011

Funny How The World Changes

A funny thing happened this Christmas eve, watching Eddie Murphy clown around in “delirious” and I was in stitches. Now I have watched this episode many times and except for a snicker, a smile and a “heh” there was little in the way of expression that escaped my lips. By little, I mean nada. But the other day in the company of some other family members, the same episode had me doubled over in delirious laughter and pain in my sides. A nuance here and a word or action by the funny man there and nothing but, total loss of all composure. My family members enjoyed my discomfiture more than what was on the screen and through the loudspeakers.

The DVD played out and I was exhausted from the exercise of lost control. We sat around for a while and it began to dawn upon me the very nature of our day-to-day existence. How our lives are governed by our inner states of being. The emotions that captivate us, draw us, temper our behavior and then play out our senses to their extroverted outcomes are what create our reality.

The product of our being resides as much in the externals that continue to haunt us from every aspect of our lives: the negative barrage of the television, or the provocative words of the newspapers, the misguided anger and disgust of others, but also by the very nature of our own thoughts. We perceive through the color of our intent. We live our lives under the shadows of our fears, angers and assumptions. Reality changes to the color of our “sunglasses.”

It was an interesting self-discovery. This was not earth shattering by any means. And I am sure others have come to this conclusion at some point or another, but for me this was an “Ah-hah” moment. What made this moment special was not the funny man on the screen, but my complete submission to the nature of that moment. The firewalls of the “self” were down, completely unguarded, there was nary a filter of “control”. The self was exposed!

It is funny how moments shape and transmogrify the understanding and how moments collapse into one other to further the thought, as happened next.

My 16-year old niece came in after the deluge of the laughter had subsided and I had once again settled into the norm of “controlled expressions.” But what was “funny” was the conversation that flowed.

We were discussing what she wanted to do in her future. Now, let me preface that with the fact that she is a beautiful person inside and out. Her face lights a million smiles and her words are ancient with respect and love. She is one extraordinary child of this human race. The conversation turned into what she wished to do in her future. It was an implicit inquiry rather then a statement.

She loves the field of medicine, “I want to help people in some way.” She said, “but I don’t necessarily want to be a doctor.” Oh? This was new to me.
“You know, do something useful.” She reflected for a moment, “Time passes by so quickly.” This from a 16-year old girl can be quite discombobulating.
“What is it that you like?”
“Right now, I want to get into photography.” That was more like it. We seem to be moving into a stream of self-reflection on her part.
“That’s great!”
“But how does that help people?” she asked with half a smile and an equal measure of doubt.
“Do what you love to do.”
“But…” she quizzed, “how does it help others?”
“It will come to you.”
“Photos and medicine?” She paused.
“Maybe…” She stopped and her face lit up. I knew she had figured out something and she was mulling it over.
“You know, as a physician, it is more like a hand-to-hand combat. It is caring for one person at a time. But when you create something that by virtue of its inception is guaranteed to help tens, hundreds, thousands or even millions, that is a dream worth having.” My vocal chords betrayed my own thoughts.

“Thank you!” She jumped up, gave me a hug and off she went bustling with the energy of her thinking, leaving in her wake, the few snow flakes falling from winter loaded clouds overhead and an uncle’s pride.

It is possible that this desire will change as equally as it will stand throughout her lifetime. But however it is and whatever it is, if it is with passion and desire, it will color her world with joy. Even though that is my, philosophizing! It is a 180-degree directional change for me. I mean previously, all I would say, “do something meaningful, worthwhile to support yourself.” Now, not so! The preface changes but the meaningful part, the content and context, comes packaged within, loaded with passion.

I was always the practical one, but not this time, not that moment. My thinking was clear, composed and assured. All practicality had been laid at the altar of passion. It is after all the one thing that moves mountains, builds railroads that crisscross the nation, fire rockets that reach outer space and beyond, build skyscrapers that face the gale force winds way above where the crows fly and create tiny robots that swim inside of us peering within at the intricacies of our internal universe. Yes! It is that very passion that conceives of the impossible and gives it form and substance.

I remember the glow in her eyes as they lit up, her face blossomed into a beaming smile and I knew she understood. She never told me how she had merged the two concepts, but we will find out in the future. Now won’t we?

Funny, how it all started with the “funny man.” When the façade of what should be, suddenly changed into what can be, the entire message of life changed. It is funny how things change. It is funny how the future changes to a newer perceived reality. It is funny how the shell that deflects, protects, reflects, modifies our behaviors and actions sometime also keeps us from our better angels.

Funny, how things change.
Funny, how the mind perceives,
Funny, how perceptions fade.
Funny, how the vision grows.

And the world changes! 

Sunday, December 18, 2011

Social Media and I

It happened one afternoon. It was quite simple, you see, I love to write stuff, you know. Yet the only writing that I could force onto paper was either medical or related to aviation. The force, or whatever you want to call it, inside of me, wanted to just release the energy that was confined and needed to find an outlet. In fact one of the editors that I had submitted my “stuff” to, said maybe I should “Blog” it. Blog? What was that? Never heard of it. Anyway after sifting through some books from the bookstore, I found out that there was an easy way to put my thoughts in a “Blog.” And thus sprang the spring of thoughts culminating in editable, bright letters.
Self-expression must pass into communication for its fulfillment.~Pearl S. Buck

I learned that sometime one has to stop pushing the concept of rejection, driving up the tautological pole of determination and find a medium conducive to share and pair with people of the same ilk – the vast majority, us!

As I started this foray into penning ethereal issues onto digital domains, I quickly realized that there were others who had the same drive and purpose. Some have successfully negotiated paths into brand name recognition while others like me just float about from one “Blog” to the next, caught in the wave of back and forth sludge at the end of the pier. Yet it was and remains to this day, liberating.

The old saying goes that to see farther one has to stand on the shoulders of giants. Well, I tried climbing those shoulders. There are some luminaries that stand out in the twitter-verse who focused my thoughts and attention. Their names need mention:
@drjohnm who writes about cardiac electrophysiology. Well he was kind enough to include me in one of his Grand Rounds. His posts are complex issues in cardiology reduced into bite-sized ingestible morsels for the rest of us. And then there is @jordangrumet. he is an internist by trade and has a life full of experiences. He writes heart warming and true to life experiences. They are from the heart and chock full of emotions. I also gravitate to @doctorwes a cardiologist, whose writing speaks volumes about the current trends in medicine and the fallacies ingrained within the healthcare system. Equally of great import is the well known @kevinmd who hosts articles/opinions from a diverse group of physicians and submits many of his opinions too. The articles represented on his site are well written and thought through. Some other physicians who post regularly include @LindP_MD  and @Doctor_V. I am missing a whole host of other wonderful bloggers and I apologize for that. There are many organizations that have excellent information that wake my senses and challenge my thoughts. These include; @NISSSAMSI posts about mathematics and all the nuances of probabilities, @ASCOPost  and @OncologyTimes that deal with cancer related topics, @AACR that deals with Cancer research and @Athletesheart that deals with human activities and the human heart.

The diversity of thought in the social media is so grand, it reminds me of an ancient oak tree with a trunk centuries old, roots that have spread over a vast geography searching for new aquifers and the deciduous branches in the thousands reaching out for new space sprouting fountains of knowledge and disseminating terabytes of new ideas. Imagine the possibilities!

And there is more to this tweet thing and the chat thing; something called the “Hash-tag chats or #”. This is another medium of interesting communication between likeminded individuals. These hash-tag denominated chats occur on specified days of the week at a given hour and all you have to do to participate in it is, well simply show up, search under the respective hash-tag, chat using that hash-tag and there you are. You get to hear other’s sentiments related to the discussion at hand and they get to hear your 140 character laden thoughts. Several ones that I participate are #MDchat: this one is a bunch of docs communicating ideas about the future of medical care and how to modify it for the better. #Cmechat:  discussion relates to nuances of teaching and learning in medical education, with some great insights into human and group behavior, #hcsm: is an excellent discussion for all, regarding healthcare and how to enhance it via social media. There are some free-flowing moments that bring a unique shade to the discussions and #bcsm: is about patients with breast cancer to join up with others and find a forum to discuss issues relating to the adversity they face and the available options of care, including nuances of medical are rendered and available. There are many more that you can participate in and enjoy the camaraderie. Just search!

In the end it is about expressing one's thoughts and learning from those of others. It is about communicating. I foresee for those with the desire to learn a bonanza through the social media. For some it may present a medium of self-expression, for others a universal medium of discussion and for the marketers a tool for misuse (warning: interfering in other’s private space with marketing will lead to unintended consequences - Guaranteed), but for the majority it will be an ideal ocean, colored in shades of blue by a rainbow of ideas. From the grids of a Mondrian painting to the lush spotlit grandeur of a Vermeer, the transition from the Tweet galaxy to the Blog universe, both, delight and intrigue us with their splendor.

So there you have it. Take from this, all, any, or none of its intended measure, then measure it to your own needs. If it helps, the universal energy (e of the mc^2) will put a smile on my face. If it doesn’t, I’ll try harder next time.

Heres to you dear friends!

Lets learn from that tree and explore that ocean!

Thursday, December 15, 2011

Vitamin D

Curious as it might seem, it was. He was a short guy, reminded me of Danny Devito ,   about four feet nine, with a balding head and thick grey side burns. You would think from his facial profile that he had just emerged from a movie set. His skin was a whiter shade of pale, powdered for effect and the stubble of the five-o-clock shadow stood out in stark relief. He carried a great set of laryngeal chords though. A certain boom in his voice more than made up for his height and pallor.
‘Sir, can you get that for me.” He asked, as I passed by him in the aisle. The “that” was a bottle of 300 pills of Vitamin D3 on the top shelf, much beyond his reach.
“Sure.” I said and gathered the bottle and handed it to him.
“Vitamin D, I see…” I said, hoping to get a response.
But he was not interested in my comments. “Thanks,” he said and pushed his cart in the opposite direction.

It happened again a few months later at a seminar related to over the counter medicines. He was there and after the lecture his voice boomed from the back of the room.
“I have to take issue with you about the Vitamin D.”
The back and forth that followed lasted about fifteen minutes and what was especially interesting was that not a single participant left. Everyone was rooted to the seats, as if spellbound by the dialogue. It turns out our guy is a doctor who had more than a firm conviction in the magical powers of Vitamin D.

Magic or not, there is something to be said about this supplement. Vitamin D has generated a significant amount of literature in the recent past 5-10 years. So, equally the number of proponents have grown with the literature.

Is it magical?

Not really. It is a supplemental vitamin, fat soluble in its characteristics and found abundantly in nature. So what of this recent shine?

Lets look at the basic function first.

Vitamin D functions:

Simply stated the Vitamin D regulates the calcium levels in the blood for both calcific and non-calcific functions. By calcific function, I mean the bones. Vitamin D regulates the calcium homeostasis. The major function at a visible level of calcium is to fill the hollow matrix of collagen tissue of the bones and to render them strong, weight bearing, as armor, as tools for transmission of sound, and as hollow arches and tunnels for transference of air. At the microscopic and invisible level calcium performs admirably in regulating heart function and inter and intra cellular transport networks.

We all know about Rickets, a bone deformity that occurs due to Vitamin D deficiency.

Vitamin D and infection and inflammation:

Looking at the cellular network function we find that Vitamin D is intimately involved with the process of inflammation, and repair of wounds. Its function is to hold the initial repair mechanism to proceed to completion and prevent it from continuing beyond. To understand what that means, consider this: A wound is a breach of tissue. To repair that wound the body brings in an armada of cells that both, put in place a scaffolding to bridge the breach and then remove the dead and effete material (cells) and then put a “coat” of normal layers of skin above the breach so that the trauma appears only as a minor scar.  Now suppose that the process of repair continued beyond that, the cellular machinery would be growing cells on top of each other into clumps of tissue that also had admixed within them dead and dying cells and a chaotic growth would follow. One can safely assume this chaotic cellular behavior would create a tumor-like growth following each traumatic breach of the skin or any tissue. A sort of an "unrestrained Keloid” in medical parlance.

Vitamin D has the property of stopping that over-growth. And that is a good thing! Too little would have the opposing effect; delayed healing and infection susceptibility.

Vitamin D and Mortality:

A Chochrane review of 50 randomized controlled trials with 94,000 elderly women showed that Vitamin D3 supplementation reduced all-cause mortality, but most especially supplementing with Vitamin D also reduced the morbidity from vertebral fractures and other skeletal related events with better quality of life. Additionally there is emerging data that deficient individuals also have a higher risk of Type I and II diabetes.
The Cochrane review showed benefits only with Vitamin D3 and not with plain Vitamin D or any of the metabolites taken orally. Of note is that the darker skin (African American blacks) does not allow the UV rays to perform the chemical magic of converting the sterols into Vitamin D3 that is then bound to DBP or Vitamin D binding protein for initiating its functions upon the cells (elicited below).

Consuming more Vitamin D?

Extrapolating on the issues mentioned above, let us look at what would happen if we started chewing on Vitamin D in excess:
The calcium levels would rise dramatically in the blood stream. With the rise of calcium in the blood, more will be excreted via the kidneys through urine leading to stone formation in the urinary tract. That is a painful scenario worth an “ouch.” The high calcium levels would also play havoc with all the organ cellular networks; the heart would suffer cardiac arrhythmia and show on the electrocardiogram initially as prolonged Q-T intervals, the colon would slow down in its motility causing constipation and the brain cells would not be able to maintain their function at higher levels of calcium causing a decay in neural transmission and thus in thought and action.

Vitamin D and Cancer

Now for the good part that we all have been waiting for. What and how does it protect us from cancer?

Fair enough! Vitamin D has been shown to have some beneficial effects against at least four types of cancers; breast, colon, ovary and prostate. Other potential malignancies where it might have the benefit include, osteosarcoma (bone cancer) Glioma (brain tumor) and with “additive” (synergistic) effects to chemotherapy regimens against a whole host of other cancers.

How? How? You say.
Elementary, my dear, elementary!

We are now embarking on a journey into the known. Much remains unknown and therefore subject to reversal in the future.  But the path so far traveled is interesting to say the least. To know the bad, we should know the good. To know cancer we have to know the normal physiological and mechanistic functions of the cells. In knowing the normal function any disarray will become obvious as a wayward and ungainly behavior. .

Cells divide for an organism (human, animal most life) to grow. Similarly cells divide in a cancer for it to grow. In that division, there are many stories. We will tackle just a few:

Cell Division and Switches:

For cells to divide they need a “kick-start” that seems to come from a genetic dictate predicated on a physical need, which is, strangely decided upon by a primary genetic calling. Take for instance the male and female germ cells that merge and then the logarithmic division that occurs to create a baby. The cells within the baby grow and then stop and then grow as the needs of the body dictate to keep up with the overall growth. These on-off switches are embedded in our DNA.

 Based on the prevailing state of the cell certain genes become over-expressed while others under-expressed. It is the way to control cell function and behavior, almost like having a brake and the accelerator, each applied sequentially as needs arise. There are specific genes that tell cells when they should and should not divide. Remember, I said “switches” well there are a host of known switches and others that we know not of yet.

“Ligand binding causes receptor dimerization and subsequent autophosphorylation of their intracellular tyrosine residues, which in turn phosphorylate other intracellular proteins thereby forming the signal transduction cascade leading to formation of cell cycle regulators which control cell proliferation, differentiation and division. One such signal transduction system involves Ras/ Raf pathway (Ras is a proto-oncogenic product and Raf is a serine/ threonine kinase) which activates the kinase cascade by sequential phosphorylation of the kinases like Raf, Src, MAP (Mitogen-activated protein) and ERK 1/ 2 (Extracellular signal-regulated kinases 1 and 2) leading to gene expression resulting in the progression of the cell cycle and ultimate cell division. It has been observed that constitutive activation of RTK as well as other nonreceptor kinases do occur in many cancers in association with mutations in the genes coding for proteins involved in the kinase cascade.”

(Translation) The switches cause transmission of signals to travel from the cell surface via receptors, through the cytoplasm of the cell, activating pathways, subsequently riding into the nucleus of the cell where the decision to divide takes place. Mutation of any component of the pathway leads to either an abrogation of the signal or amplification of it –to the detriment of the cell and the organism. If the brakes fail or the accelerator is constantly applied.. you get the message.

What is interesting is that cancer cells as well as normal cells express a surface receptor called the Vitamin D Receptor or VDR (How original!), that binds to a metabolite of Vitamin D called calcitriol “When bound to VDR, calcitriol has been found to regulate the activity of more than 60 genes leading to prodifferentiating, antiproliferative and antimetastatic effects on cells in addition to effects on cell cycle and angiogenesis (antiangiogenic).” In other words calcitriol shuts down the proliferative (growing ability) of the cell to multiply/divide and spread..

One comprehensive gene product that keeps cells in check is the Rb gene. This gene has to remain in a hypo(low)phosphorylated state (inactive) Vitamin D (calcitriol) keeps it so. Rb gene in a hypo(low)phosphorylated state, binds with the E2F transcription factors and arrests the cell cycle growth phase.

In cancers of the breast, prostate, colon and ovaries calcitriol is known to dephosphorylate the Rb gene product leading to a blockade of cancer cells at a checkpoint-1 in the cell cycle. Conversely Phosphorylation of the Rb gene has the opposite effect and leads to unchecked cell growth. Speaking about the cell cycle, one is reminded of an oxen-driven water well. Consider the owner as the p53 gene (p53 another very important gene is considered  as the Guardian of the Genome”), the oxen as the power source, the mechanical brake as the Caspase system and the cans of water on the metal wire containing the new dividing cells.

The p53 gene/protein product determines when the oxen start and stop. The Oxen (hormones, protein and the process of phosphorylation) have to be fed to work and the cans bring up the water (newly divided cells). If brackish water comes up in the cans, the owner investigates the well and either applies a brake, puts a filter or digs the well deeper to get to the newer water stratum for cleaner supply. So in this thought process, onsider Vitamin D as one of the brake/filter in the oxen driven well water system.

This downregulation of the various pathways is inherent to the Vitamin D byproducts such as calcitriol that mates with the VDRs to induce a “downstream” signal to the center of the aberrant (cancer) cell nucleus and tells it to stop growing. In other words, Vitamin D “may” bring(s) sanity to potential chaos.

Another mechanism used by Vitamin D (known via basic hard science) is creating an over expression of a protein called cystatin-D:

“Cystatin-D is antitumorigenic and antimetastatic. It inhibits these endogenous cysteine proteases (endosomal/ lysosomal), has some modulatory role in cell proliferation, differentiation, survival and migration in addition to interleukin and nitric oxide production. It also inhibits migration and anchorage - independent growth, antagonizes Wnt/β-catenin signaling pathway (Wnt is an oncogene which codes for the growth factor Wnt), represses c-myc and expression of a number of epithelial-mesenchymal transition inducers (SNAI1, SNAI2, ZEB1 and ZEB2) which are involved in the progression of primary tumors towards metastasis. The protein (cystatin D) induces E-cadherin expression which is repressed during epithelial-mesenchymal transition period.”

(Translation) Cystatin-D prevents cellular differentiation and migration of the cell and inhibits certain key genetic promoters to cause a phase-transition, eg EMT (Epithelial-Mesenchymal Transition). EMT is known to occur in malignancies allowing cells to co-opt normal cells to allow tunneling and escape into the open.

Additionally Cystatin-D also (upregulates ) jazzes up the BAX system (that promotes bad cell apoptosis/death) and (downregulates) mutes  the BCL2 system (that prevents cell apoptosis/death). This inverse underpinning keeps the bad/cancer cell growth from achieving out of control proliferative state. This mechanism has been contemplated to help reduce the risk of Non Hodgkin Lymphoma.

Interestingly Calcitriol also has some of these “magical” properties of enhancing the VDR on the cell surface for increased binding and thus increased influence on cellular behavior (One might consider the role of the lobbyists in determining policy in Washington).

Before you go running to your garage and speeding in your car to the local drug store, let me mention a few caveats: The determination of these mechanistic actions have been seen in-vitro studies (in the Petri dish in the labs, that is) Large scale studies in humans have been done using retrospective (looking backwards into the past) epidemiological and case controlled studies. There is a wide gulf between the “this” and the “that.” The correlative forces between what has been seen in human studies seem likely to be compliant with the lab studies for they seem to confirm the mechanism underlying the overall findings, yet a word of caution here it seems is prudent: In a multivariate system a univariate determination for causation is fraught with pot holes. The bird eye view looking down on the entire premise is virtuous. We are beginning to peer down into this microscopic cellular fiefdom and it has some strange stories to tell.
p53 gene

So allow me to throw a cautionary tale in here: Vitamin D3 inside the body can also be co-opted by the cancer cell to convert its signal from one enforcing “proapoptosis” or forcing death of bad cell into an “antiapoptotic” signal as Duque et al suggest in their 2004 paper:
“Perhaps the most significant finding is that mutp53 can convert vitamin D3 from a proapoptotic agent into an antiapoptotic one. In support of this notion, vitamin D3 suppresses death receptor-mediated apoptosis in OVCAR3 ovarian carcinoma cells (Zhang et al., 2005b), which harbor endogenous mutp53. Conceivably, some cancers might have evolved a mechanism that allows them to capitalize more efficiently on the survival route of VDR while evading its proapoptotic effects. Our data suggests that acquisition of gain-of-function p53 mutations may constitute one such mechanism. Obviously, p53 mutations alone are not sufficient to drive the conversion of the VDR pathway into an antiapoptotic one, as not all mutp53-expressing tumor-derived cell lines are equally protected by vitamin D3. Thus, additional alterations most likely cooperate with mutp53 to orchestrate the antiapoptotic response to vitamin D3. Identification of such cooperating factors remains an important challenge. However, in addition to the well documented proapoptotic effects, there are circumstances where vitamin D3 exerts antiapoptotic effects, including increased cell survival following UV trauma and protection of some cancer cell lines from killing by cytotoxic drugs. An inhibitory effect of vitamin D3 on TNFα-induced apoptosis and on TRAIL and Fas ligand-induced apoptosis, accompanied by a decrease in Bax and upregulation of Bcl2 and p21, has also been described.”
Translation: Vitamin D3 can be co-opted by a mutated p53 into doing exactly the opposite of what it does in normal circumstance. So different scenarios may breed different results. Thus high levels may actually in an underlying mutated gene scenario create a monster that we have been trying to avoid facing. That is why being extra caution is indeed the right way to proceed, lest we broadcast the wrong message to everyone.

Vitamin D and individual Cancers:

Breast Cancer:

Vitamin D and Breast Cancer studies have revealed several interesting features. The most recent one presented at the San Antonio Breast Conference in December 2011, Hates, showed in a retrospective analysis that the size of the initial presentation of the breast cancer was inversely associated with the level of the Vitamin D in the blood. The correlation was significant to a high degree level at p-value=0.0063.
“In a retrospective study, lower vitamin D levels were significantly associated with larger tumor size (P=0.0063), Barbara Brouwers, PhD, of the University of Leuven in Belgium, reported during a poster session at the San Antonio Breast Cancer Symposium.”
 Looking back at other studies there are other associative features, including the risk reduction between high levels of Vitamin D and lower risk of Estrogen Receptor Positive and negative breast cancer models (Jin Lee Hong et al.).
“In conclusion, we investigated the in vivo effect of certain Gemini vitamin D analogs on mammary tumor growth in a chemically-induced breast cancer model and in a xenograft model. We report here that Gemini vitamin D analogs significantly inhibit both ER-positive and ER-negative mammary tumor growth without increasing serum calcium levels. Mechanistic studies showed that the inhibitory activity was associated with the induction of IGFBP-3 and the CDK inhibitor p21 in both animal models.”
 Using age as a defining criterion, the postmenopausal breast cancer patients who had a high level of Vitamin D level also had a lower risk of aggressive disease. (Robien et al) These data suggest some degree of correlation between the cancer of the breast and some modulating features of Vitamin D. One of the etiologies of this suppressive pressure seems to be the anti-inflammatory effect of the disease through the induction of the NFkB (Nuclear Factor kappa B), which is intimately involved with inflammation and may be the driving force as a promoter of the disease in malignancies. More data will have to be gathered for confirmation. The authors caution: “Changes in vitamin D intake over time might have contributed to the diminished association observed in later years” The word “May” stands out in stark contrast, doesn’t it? We seem to be looking for answers and finding them. “Seek and ye shall find!”

Prostate Cancer:
Prostate cancer cell

Kovlenko et al show the importance of VDR in prostate cell growth and the risks of procancerogenic events related to low VDR either to lower dietary intake or subsequent deletion by other factors. While this data is suggestive of the promissory intent of the VDR, it is at best a correlation. Similarly Yang et al, found; “that inhibition of Snail-1 signaling by transfection could increase the expression of VDR, enhance the anti-proliferative activity of 1,25(OH)-D(3) in osteosarcoma cells, and induce apoptosis and lower invasion in vitro.
Therefore, strategies to suppress Snail-mediated signaling may lead to the better action of 1,25(OH)-D(3) as an anti osteosarcoma treatment.”


In Melanoma cell lines the Vitamin D3 acts protective against cancer via the fas-mediated pro-apoptotic pathway via the immunogenic Natural Killer (NK) cells. However moderate to sever exposure to the sun in people who have a preexisting history of at least one skin melanoma show an association with VDR gene polymorphism (Bsml). In other words there appears to be an underlying damaged gene that transposes the risk for future occurrences by making Vitamin D ineffective due to the inherent VDR (polymorphism) mutation. (Mocellin et al and Mendelcorn-Monson et al)  What that means simply is that even Vitamin D polymorphism (mutation) make the function of Vitamin D in protecting health moot. However this is a relatively infrequent occurrence.

(Translation) A messed up VDR by virtue of a messed up gene makes Vitamin D therapy ineffective.

Bone Metastasis:

As mentioned previously, since Vitamin D plays a major role in the homeostasis of calcium and the maintenance of normal bone structure and remodeling, it has been shown that deficiency of Vitamin D leads to growth of metastases from prostate cancer into the bone. Zheng et al suggest through experimentation: “At endpoint, osteolytic and osteosclerotic lesion areas, total tumor area, and tumor mitotic activity were all significantly increased in vitamin D deficient mice compared to controls. Vitamin D deficiency stimulates prostate cancer growth in bone through modulating the bone microenvironment.”
Translation not needed. This might be as a result of the structural porosity caused by the low calcium level and lack of protection of pathway inhibition by the low levels of Vitamin D.

While on the subject of Prostate Cancer another study shows a direct relation between VDR expression, Vitamin D and a reduced risk of progression, reiterating the finding that the VDR when joined with the Vitamin D promote cellular restraint and slow down the rate of progression of disease. Prospective studies need to be done to confirm the VDR levels, Vitamin D3 levels and the rate of spread of Prostate Cancer for further proof.

Colon Cancer:

In Colon Cancer Davis et al suggest: “A wealth of scientific evidence supports a role for vitamin D in decreasing colorectal cancer incidence, and possibly mortality. This reduction in risk is related to inhibition of cellular proliferation and stimulation of differentiation”
Remember the Wnt pathway, I mentioned earlier in this discourse and its relation to VDR and Vitamin D. Well here it is again. Apparently there is some control of the Wnt pathway inhibition exercised by the VDR and calcium. The result is that B-Catenin does not accumulate in the nucleus to send a message to the genes to become active and tell the cell to grow.  However if this allowed to proceed, then B-Catenin binds to TCF4 that activates another gene product “myc” that allows entry into the nucleus promoting the cancer cell through cell cycle advance and division.
“Binding of WNT to FZ activates one of two pathways: the canonical pathway, which involves β-catenin  and controls cellular proliferation; and the planar pathway, which involves Ca2+ and is important in cellular movement and polarity. Briefly, in the canonical pathway, in the absence of WNT, cytosolic β-catenin, which is normally bound to membranous E-cadherin, interacts with the 'destruction complex', which is composed of the tumor-suppressor protein APC (adenomatous polyposis coli), glycogen synthase kinase 3β and axin. This results in serine phosphorylation of β-catenin, its recognition by an E3 ubiquitin ligase, and its degradation. If, however, WNT is present it binds to FZ, the kinase activity of the destruction complex is blocked, and β-catenin remains unphosphorylated, resulting in accumulation of β-catenin in the nucleus. This enables β-catenin to bind to the transcription factor TCF4 that can activate downstream target genes such as the proto-oncogene MYC that promotes entry of the cell into the S-phase of the cell cycle. The small intestine of mice lacking a functional Tcf4 gene is populated only by cell-cycle-arrested, differentiated epithelial cells, the nuclei of which have accumulated β-catenin.”

Non-Hodgkin Lymphoma:

Now before your eyes cross and your teeth chatter, let me also mention that Vitamin D seems to have a protective effect on Non Hodgkins Lymphoma. This data is garnered from epidemiology studies only and subject to criticism. However what is not prone to ridicule is the fact that Vitamin D3 potentiates the effects of chemotherapeutic agents such as Gemcytabine and Cisplatin when used in bladder cancer cell models in vitro (lab) and in vivo (in animal models). These studies presage the next experimental protocols utilizing studies in humans for corroboration.

I find it important to mention the strong language used by Ma et al in his support for Vitamin D and its protective effects: “Calcitriol elicits anti-tumor effects mainly through the induction of cancer cell apoptosis, cell cycle arrest, differentiation, angiogenesis and the inhibition of cell invasiveness by a number of mechanisms. Calcitriol enhances the cytotoxic effects of gamma irradiation and certain antioxidants and naturally derived compounds. Inhibition of calcitriol metabolism by 24-hydroxylase promotes growth inhibition effect of calcitriol. Calcitriol has been used in a number of clinical trials and it is important to note that sufficient dose and exposure to calcitriol is critical to achieve anti-tumor effect.”

Vitamin D Testing:

Vitamin D testing has come under a lot of scrutiny. Since methodologies differ and the exact needs of an individual person remain unknown, people have  extrapolated the blood levels empirically. Real hard facts remain still enshrouded in mystery, although we are peeling the onion layers diligently. The bare facts about its mechanism are fairly well known:  The Vitamin D is called a "vitamin" because of its availability from an exogenous source, predominately from oily fish in the form of cholecalciferol, vitamin D3. Plant-based vitamin D is in the form of ergocalciferol, D2.It is really a hormone, as it is synthesized by the skin and metabolized by the liver and then, the kidney to an active hormone, calcitriol, which then acts in its classical action to absorb calcium from the intestine, and promote bone mineralization. In the skin, 7-dehydrocholesterol is converted to vitamin D3 in response to sunlight, a process that is inhibited by sunscreen with a skin protection factor (SPF) of 8 or greater. Once in the blood, vitamin D2 or D3 from diet, or D3 from skin production are carried by an alpha-2-globulin, vitamin D binding protein, and are carried to the liver where they are hydroxylated to yield 25-hydroxyvitamin D (25OHD; calcidiol). 25OHD then is converted in the kidney to 1, 25(OH)2D (calcitriol) by the action of 25OHD-1-alpha hydroxylase (CYP27B1). The CYP27B1 in the kidney is regulated by nearly every hormone involved in calcium homeostasis, and its activity is stimulated by PTH, estrogen, calcitonin, prolactin, growth hormone, low calcium levels, and low phosphorus levels. Its activity is inhibited by calcitriol, thus providing the feedback loop that helps regulates its synthesis.”

Heart Disease:

Q: So what is the ideal level of Vitamin D in the blood? 
A: Some profess 50 nMol/ml. Others are not sure. The problem is that the value is extrapolated from data gathered via epidemiological studies. A prospective large cohort study has yet to be undertaken. The dilemma of recommending the real dosage and trying to achieve the “real right level” in the blood is difficult.
Q: Is more Vitamin D intake safe?
A: No! absolutely not, as previously articulated.
Q: Is a Vitamin D deficiency a potential source of bad health?
A: Seems so, based on the previous discussion.
Q: Does the right amount prevent against various cancers?
A: Strongly suspected but not confirmed.
Q: Does the right level of Vitamin D protect against heart disease?
A: Yes it seems so! Vacek et al conclude from their single institution study spread over 5 years and 8 months They use the cutoff value at 30 nMol/ml: Vitamin D deficiency was associated with several cardiovascular-related diseases, including hypertension, coronary artery disease, cardiomyopathy, and diabetes (all p <0.05). Vitamin D deficiency was a strong independent predictor of all-cause death (odds ratios 2.64, 95% confidence interval 1.901 to 3.662, p <0.0001) after adjusting for multiple clinical variables. Vitamin D supplementation conferred substantial survival benefit (odds ratio for death 0.39, 95% confidence interval 0.277 to 0.534, p <0.0001). In conclusion, vitamin D deficiency was associated with a significant risk of cardiovascular disease and reduced survival. Vitamin D supplementation was significantly associated with better survival, specifically in patients with documented deficiency.”

Mechanism of action in Heart Disease:

Although the mechanism of action in the relationship between heart disease and Vitamin D deficiency remains elusive, preliminary data seem to show that it causes inhibition of cardiomyoblasts (primitive heart cells) growth, reduces inflammation (considered a precursor to coronary disease) expresses the production of cardiomyotubes which direct nutrients to the cells and stabilizes the cardiac cells themselves.
And so, you don’t get too comfortable in your pajamas reading this, guess what? One of the hallmarks of testing for heart disease event risk is the “calcification” found in the coronary arteries. The issue then arises; does the calcification occur because of too much calcium (related to Vitamin D?) in the blood (metastatic) or due to preceding damage with atherosclerosis of the blood vessels, caused as a result of inflammation and calcium deposition is secondary (dystrophic). You see the “head-scratching” that goes on in real science! Answer still eludes us. In fact recent data in another meta analysis failed to show any benefits in heart disease or cancer. So there!

This discourse is a nonlinear multi-directional attempt at relegating, the mysteries of Vitamin D and its many nuances in the life of a living cell, to knowledge. Its effects on humans translated axiomatically via basic science. Prospective studies have yet to show the benefits proposed and thus are eagerly sought. Human epidemiological studies are fraught with risks in correlating assumptions with causations and thus the warnings and disclaimers. What the epidemiological studies do is, set the stage for confirmatory data. The problem is often in the eye of the beholder. The experimentalist who sets out to prove the epidemiological data will most likely, through his “rose-colored glasses” find identity with the preceding study. Unless, that information is vouched for by basic experimental science, shards of untruths maybe in store to prick the balloon of gathered information.

There are many rungs to this ladder. We have just stepped on the very first rung. What we may find on the next one and the one after is something new that may change our entire viewpoint, or confirm without a shred of doubt the premise we seek to annul or uphold. For truth in real science is to shed individual and prevalent bias and arrive at an understanding.

Where can we find Vitamin D? You ask. Oh it is everywhere. Go outdoors and bask in the sun each day and your body will produce enough of it to keep your levels within norm. And Oh by the way, spending the entire day under fluorescent lights and then running off to the beach to get cooked is damaging to the skin. Moderation is called for as in all other aspects of life. But if you must live in the glare of the computer screen under artificial life eating bonbons then there are Vitamin D pills available.

I wonder how the pale-faced doctor with the grey sideburns we met earlier, is holding up?  An outdoor walk might help. Don’t you think?

  1. Vitamin D is involved with the Homeostasis of Calcium in the bones and soft tissues
  2. Cells express VDR or Vitamin D Receptors that merge with Vitamin D to signal into the cell.
  3. Byproduct of Vitamin D promotes more VDR as need arises.
  4. Once the VDR merges with Vitamin D the signal goes through the cytoplasm of the cell into the nucleus to cease extravagant proliferation.
  5. Cancers use various pathways to bypass the growth restraints. Vitamin D seems to reaffirm those restraints.
  6. Studies suggest Vitamin D protects the heart in some manner the exact mechanism still remains unknown.
  7. Vitamin D testing and actual threshold value of protection remains elusive.
  8. We can all get plenty of Vitamin D by frequently taking a walk in the sun.
A man only becomes wise when he begins to calculate the approximate depth of his ignorance.
~Gian Carlo Menotti


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Tuesday, December 13, 2011


I wonder at what it is
What it takes and what it gives

I wonder at the beautiful rose
Where it ends after the glow

I wonder at the piece of straw
Where the genesis and where its flaw

I wonder at each thought I have
What will it create or why not

I wonder at the air I breathe
Where it is and why cant I see

I wonder at the sun that shines
How it warms, colors and blinds

I wonder at the moon above
How it lays on this earth its silver glove

I wonder at the roar of fire
At why it glows with the color of sky

I wonder at the past I had
All those memories buried to last

I wonder at the future to come
What it will hold and what I become

I wonder at the birds that fly
Defying gravity into the sky

I wonder at each form of life
How vigorous and full it is in strife

I wonder at all that there is
It is all grandeur, it is pure bliss!

Saturday, December 10, 2011

Science is Elegant

"The Diaphanous Frippery of Science" Part 3 of 3

In matters of truth and justice, there is no difference between large and small problems, for issues concerning the treatment of people are all the same~ Albert Einstein

 Science is simple. It is elegant. It is uncomplicated. It is harmonious. It is also the cornerstone to all that you see. It is the scaffolding that holds the skyscraper, the bridge that bridges the gulf, the boat that floats and sails, the airplane that flies without a visible moving part, the rocket ship that visits distant planets, the pacemaker that paces the heart, the mechanical heart that pulses the beat, the blind eye that visits the sights for the first time, the artificial legs that keep pace with the thoughts and the brain that moves inanimate things without a tether. Such is science; the truth, the fact and at its basic state the very essence of glorious simplicity.

Simply is that I am, shall make me live ~ Shakespeare

We glide smoothly over the water with nary a wake like the swans, carrying the placards of our prejudices, while below the water the vigorous paddling creates eddies of confusion and activity. It is neither in the smoothness of the glide nor in the turbulence beneath the surface that the answers lie, but in the constructive work to grasp the truth through reason.

The Turbulent Life of Vaccines

You know, back when I was young, naïve, full of an idealized promise, I had an objective in mind; to cure human diseases. It was a simple inner directive. Why the suffering? Why the cries of pain, why the loss and why the glacial gain? Somehow through the aegis of this freeze dried world of horse-traders, bartering-buddies and smoke-filled room negotiators, I learned the yellow-brick-road was actually made of asphalt replete with potholes. I came across the simplest of all solutions against most diseases and that was in the form of vaccination. After all hadn’t that very premise saved millions. Alas that turf was taken and won many decades before. So I set out to cure cancer. I did. But working on the Salamander and its cell polarity changes by severing the tail before it grew back was a promising start into how cells grow, only to come to an abrupt firewall. So from a mass life-saving promise, I decided to tackle the cancer on a one on one basis. And yet the vaccine-feet kept tripping me again and again. So here are a few words on the Vaccine debate, for that fills the void when other news is slow. There is much good for humanity and an equal measure of rhetoric from it, that fills the vacuum of knowledge. Speaking about the good, there is no question about the benefits of Polio vaccine (Polio cases have decreased by over 99% since 1988, from an estimated 350 000 cases world-wide then, to 1 349 reported cases in 2010. The reduction is the result of the global effort to eradicate the disease). Similarly, smallpox vaccine has saved countless of lives around the world (Smallpox was responsible for an estimated 300–500 million deaths during the 20th century (yeah read that one more time before proceeding). As recently as 1967, the World Health Organization  (WHO) estimated that 15 million people contracted the disease and that two million died in that year. After vaccination campaigns throughout the 19th and 20th centuries, the WHO certified the eradication of smallpox in 1979). That my friends is no small feat!

So the incontrovertible evidence of vaccine superiority in these two diseases remains unchallenged.

Yet one name associated with vaccination constantly comes up:  Dr. Andrew J. Wakefield. Was he the evil doctor that created this stir against the MMR? Why would he do that? Before, I go on, maybe it is time for you, dear reader, to read his paper (it is not so well written at that and remains officially retracted), published in Lancet and determine his motive for yourself.

Dr. Wakefield makes these two assertions in response to a criticism:

"Hypothesis testing and presentation of the outcome—either positive or negative—is a fundamental part of the scientific process. Accordingly we have published studies that both do,1 and do not2 support a role for measles virus in chronic intestinal inflammation: this is called integrity. The latest of these studies was strongly positive,3 and was accepted by the MRC Review in February, 1998"
"However, it pales into insignificance compared with their failure to declare the fact of an MMR catch-up campaign that was initiated in 1988 with the introduction of this vaccine. This campaign was targeted at children, whatever their age, who presumably had not received either monovalent mumps or rubella vaccine whatever their exposure status. As such it was a novel and, in terms of safety, untested policy. On the basis of Taylor and colleagues' inclusion criteria, and taking account of the catch-up campaign, then those first birth cohorts who actually received MMR (circa 1986) were precisely those in whom a doubling of the numbers of cases of autism were seen. Thereafter these numbers continue to increase strikingly. Omission of this essential fact—the catch-up campaign—requires explanation lest it be misconstrued."

In it he seems to show a correlation between MMR and gastrointestinal symptoms, associated with signs of autism and suggests via time-line the use of MMR and the sudden explosive rise of Autism.

He suggests more research to study this correlative possibility further. I think that journalistic imprudence and media blitz that followed, served up a promotion for countless so-called journalists to the upper editorial staff level and destroyed this man’s professional and personal life by driving him out of his native North-West London. This was done both at the outset when the bandwagon got rolling and then again at the fork in the road, when they started to cook his goose as the first contradiction came. The British press turned on a dime and racked up enough pools of venom forcing the political hand against Dr. Wakefield and his professional life. Dr. Wakefield (I don’t know the doctor, only about him) is to my knowledge not another Anil Potti, MD from Duke whose infamous genetic work led to at least three clinical trials (now curtailed) and hundreds of articles used his now defunct premise as the reason for their study.

Equally, the psychology professor Dr. Marc Hauser, from Harvard, who seemed to have falsified data to fulfill his personal need rather then the cold hard treasures of science, also created a buzz in the field of evolutionary biology.

 However, Dr. Wakefield, it appears was following an innate concern. His hunch. The problem that ensued was a firestorm of publicity generated by his original paper that led many parents to boycott the vaccine for fear of inducing autism in their children. The ill-informed populace propagated the story, as did the journalistic zeal and feeding frenzy that multiplied it many fold. The media experts obligingly for their own selfish needs hop-skipped-and-jumped, tripping over each other to carry a story that they little understood, much less comprehend. The result is a present day filled with warring factions. Was this his personal motive? Not based on the documents in the digital domain (I am not privy to legal documents and therefore my version is incomplete on this issue). The man it appears had a hunch found some correlation and wished more scrutiny. Yet here as is the prevailing trend today, where correlation was implied, causation was magnified. This is sad, truly sad, about the vile and ignorant nature of the self-promoters and the ignorant media.

Does MMR vaccine work 100% of the time? No. Here is an excerpt from an NCBI article:
“seroconversion and clinical protection rates were significantly higher in children who received only MMR at 12 months of age than in children revaccinated at 15 months of age. Seroconversion rate for measles was 69.9% in children who received MMR at 12 months of age and 90.3% in children revaccinated at 15 months of age (P=0.0003). While there was no measles case in children who were revaccinated, 12 (2.7%) children in the first group acquired measles during the follow-up period.”

 As a matter of fact neither does the Flu vaccine. Although MMR has superior efficacy than the Flu vaccine.

“A total of 1952 subjects were enrolled and received study vaccines in the fall of 2007. Influenza activity occurred from January through April 2008, with the circulation of influenza types A (H3N2) (about 90%) and B (about 9%). Absolute efficacy against both types of influenza, as measured by isolating the virus in culture, identifying it on real-time polymerase-chain-reaction assay, or both, was 68% (95% confidence interval [CI], 46 to 81) for the inactivated vaccine and 36% (95% CI, 0 to 59) for the live attenuated vaccine. In terms of relative efficacy, there was a 50% (95% CI, 20 to 69) reduction in laboratory-confirmed influenza among subjects who received inactivated vaccine as compared with those given live attenuated vaccine. The absolute efficacy against the influenza A virus was 72% (95% CI, 49 to 84) for the inactivated vaccine and 29% (95% CI, -14 to 55) for the live attenuated vaccine, with a relative efficacy of 60% (95% CI, 33 to 77) for the inactivated vaccine.” – NEMJ October 2009.

Clearly the antibodies directed against the Influenza virus must find that single strain or known multiple strains of the Flu virus to be effective for the exposed community, otherwise, no dice. The problem is that the flu virus has the innate ability to mutate rapidly and the selective immunogenic response forces the specious mutation for survival. We have been burnt by the Influenza outbreak of the 1918 when millions died and never wish to relive it again, rightly so. And the knee-jerk reaction to the H1N1 “pandemic” of 2009 that followed.

Looking back at the MMR vaccine effectiveness in the majority to prevent measles, mumps and rubella? Data suggest~Yes! (See Cochrane review-ref below) Does it cause autism? There is much doubt on that issue. The anti-vax crowd and the pro-vax crowd are hinged as the front and back covers of a heavy tome. Instead of adding more pages to it, my thinking is let’s settle the debate scientifically and independently, so more lives are not lost from ignorance or stubborn stupidity. The passion that drives both sides is more than a little interesting -it is fervent belief! There is a dire need to address the “might” to alleviate a fear, and turn the tide with scientific proof,  from  “cannot” to “should not” to “does not,” in context of causation (if that can be done). It is that nebulous gray that continues to cloud the black and white. Epidemiology as a “science” will NOT/NEVER resolve this.

Now before some of you still reading this, run out and put me in the anti or pro crowd. I am not a zealot in either. I believe in prevention. I believe in protection. I merely wish to confirm via solid evidence and not be emotionally roiled by loud voices. By the way both my kids had the full complement of vaccines as youngsters.

Thought Experiment on MMR and Autism:

You know what might be an interesting test?

Say you have some neural (brain) cells lying around in the lab and some unused MMR vaccine, well here goes a concept; We know that ASD (Autism Spectrum Disorder) has several CNVs (Copy Number Variation) including known NLGN3 and NLGN4 gene aberrations (in about 60% of cases). So here is the proposed recipe: Take a few of those normal neural (brain) cells, culture them with the MMR vaccine in fetal calf serum in the lab (incubate for 72-96 hours) and then put the neural cell DNA through Genome Wide Analysis to determine the above mentioned genetic mutations. If the DNA aberrancies match with the known mutations, then well-designed studies (lab) need to be done prospectively, independently and by multiple institutions for confirmatory proof, so this idiocy can stop! If not then move on. Oops, me thinks, I stepped into the tar-pit.

(You may wish to stop at this point: But those stalwarts pursuing may find a few issues that might crop up with this form of experiment):


  1. The viral penetration into the neural cells, if at all possible, maybe linked to some in-vivo selective bias unknown to us – Another experiment to conform that can be undertaken. Yet we know the virus penetrates cells for its own survival.
  2. The before and after Genome Wide Analysis performed on the experimental neural cells.
  3. What if a susceptibility locus or loci in the neural cells are needed before the viral products induce the CNAs and other genetic anomalies etc. then, the pre-viral incubate GWAS would show such changes in those cells where the DNA mutates.
  4. Different neural cell lines from different patients may be needed.
  5. A single cell line has the Hayflick Limit to contend with thus after a few divisions, the cell line will be apoptotic (dead). Therefore from each cell line we may only have the ability to test three or four generations.
  6. Since we are enhancing the immune surveillance cellular network, jazzing up the immune system so to speak also causes significant gene amplifications, so we need to be cognizant of that too. What genes are being over expressed for the immune network and what if any for ASD.
  7. One more thing, one will have to do multiple experiments at least about a 100 times and plug that data into the computer to perform the Monte Carlo Analysis for good measure to see the (million iterative process) computed output.

You see the dilemma with these few questions and there are many more under my sleeve. And I hope someone will send me a note, saying "you are WRONG!” with verified facts, or just bully to get a dialog going. I remain open to education. Never said real experimentations are easy, did I? But the thought is simple, maybe all wet but still worth contemplating, don’t you think?

Back it up, I say. Back it up with basic science. Prove it, not through the junk of epidemiology and statistical maneuvering but by the essence of the basic scientific curiosity itself. Use the epidemiological/statistical data if you must, but then confirm it and then re-confirm it with HARD scientific evidence.

Vaccines are being employed in cancer prevention also. I love this concept. Even though this concept had fallen onto hard times with the failed trials in Melanoma cell lines. There is now new vigor as we come to know more and more about the nuances of the immune network and its functional capabilities. There is ample opportunity to treat cancer, by allowing the Dendritic Cells to co-opt the antigenic expression of the cancer cell and then utilizing (triggering) the natural “Killer T-Cells” to do their job in cancer destruction. This methodology was tried with modest success in prostate cancer in the past. Simple as the premise seems, there are still many issues that plague the premise. Baby steps of success have been advanced, but much needs to be (re)solved. There is a trial based on Breast Cancer patients whereby those with HER-2neu positive cancers are treated with an li-Key modulated vaccine (AE7) directed against the tumor associated antigen Her-2. Initial results seem to show some promise. What may appear as small steps is actually huge windfall of data that at present may not seem to bear fruit, but might be a game-changer at some time in the future. There are many Edward Jenners and Salk and Sabin’s at work in small and large labs across the globe. Stay tuned. Time and diligence is on the scientist’s side. Diligence cannot be rushed, nor hopped over. Natural Immunity plays a heavy role in maintaining health and an overactive one can cause untold miseries also (eg. RA, Lupus etc.). it is therefore of significant import to be cognizant of all potential unintended consequences that one can foresee in the crystal ball. Heather Lankes from the Feinberg School of Medicine at Northwestern University in Chicago wrote a provocative paper published November 2009 between the Flu Vaccination and risk of Non Hodgkins Lymphoma, that bears scrutiny (Referenced). Below is an excerpt:

"We found that risk of NHL was inversely associated with a history of a polio and smallpox vaccination and positively associated with ever receiving an influenza vaccination. These patterns of association were similar between men and women.factors for NHL"

From anatomy we know that, “the head bone is connected to the neck bone …” we must take into account all the variables, variances and vagaries of nature -the bridges and the quick sand. You cannot forget to put sugar in a pecan pie or a little salt in boiling spaghetti, can you? The end result is a difference between a masterpiece spread or just plain blah dinner. Everything has a reason and a purpose in nature. But never forget,  Simplicity is the ultimate sophistication.” Leonardo DaVinci.

Damn it “burn that midnight oil” until “the cows come home,” for a change!

Worth a shot, don’t you think?


Andrew J. Wakefoield. The Lancet, Volume 354, Issue 9182, Pages 949 - 950, 11 September 1999

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Jefferson TO, Rivetti D, Di Pietrantonj C, Rivetti A, Demicheli V. Vaccines for preventing influenza in healthy adults. Cochrane Database Syst Rev. 2007 Apr 18;(2):CD001269.