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

Identification of Genetic Loci Underlying the Phenotypic Constructs of Autism Spectrum Disorders". Xiao-Qing Liu et al. Journal of the American Academy of Child and Adolescent Psychiatry, Vol. 50 No. 7

Ceyhan M, Kanra G, Erdem G, Kanra B Immunogenicity and efficacy of one dose measles-mumps-rubella (MMR) vaccine at twelve months of age as compared to monovalent measles vaccination at nine months followed by MMR revaccination at fifteen months of age.Vaccine. 2001 Aug 14;19(31):4473-8.

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.

No comments:

Post a Comment