Friday, May 20, 2011


Oh Woe is me, T’have seen what I have seen, see what I see! ~ William Shakespeare

Where does reality end and fiction starts? Or is it a continuum of spectral shades? How can one tell the difference? Is there a dividing line somewhere?

Let me take you back to a time when things were not as complicated, a time when ease of understanding was based on the limited but growing food of knowledge. I call it food, for the simple reason that knowledge like food is what makes us grow. So then the subject, is too much knowledge, bad? The answer is the same as for food. In moderation and the right kind will keep us healthy and wise.
Berkley, Gloucestershire

It is 1796 and you are in the bucolic countryside of Berkley, Gloucestershire. The stories of people dying of this vicious disease have spread far and wide. The Variola vaccination practice imported from the Ottoman Empire in early 1700s by Lady Mary Wortley Montagu to Europe to help prevent the scourge of smallpox. Unfortunately the practice had far-reaching and damaging results with 20% of the 60% vaccinated with Variola ended up dying of smallpox. People now do not venture out of their houses much for fear of falling victim to the disease.
Edward Jenner

A country doctor named Edward Jenner has heard stories about milkmaids becoming immune to the disease and also about a farmer named Benjamin Jesty who has used the cowpox pustules to infect his wife and children rendering them immune to smallpox. Dr. Jenner is curious. He remembers the advice of William Harvey, “don’t think, try” and he is cautiously patient but scientifically anxious to see the results. His gardener brings his child named James Phipps, an 8-year old boy, to him to protect him from the scourge. Edward Jenner now fully convinced of the potential from all the anecdotes he has heard tries his method on a consenting parent's child. 

He takes the pus from the cowpox pustules off the udders of a cow (subsequently named Blossom) and with a piece of sharp-edged wood scratches the pus on to the child’s skin and then waits. He watches over the child recording all the pertinent findings of fever, malaise and sweats that the child expresses. The child recovers completely without any sequelae. So far so good, he thinks. He is concerned for the more difficult and potentially lethal part of his experiment, to use Variola specimen from a small pox victim and deliberately infect the child. He does that on two successive occasions and both times the child demonstrates immunity to smallpox. Dr. Jenner has thus for the first time in history successfully demonstrated the cause and effect of an experiment. Dr. Jenner goes on to demonstrate on thirteen more individuals and sends a one-page paper to the Royal Society of Medicine in London. The paper is rejected initially for want of more detail and substance.
Edward Jenner's dissertation regarding Cowpox vaccination

This then is the sequence of a thorough understanding of the question posed by Dr. Jenner to himself. Does Cowpox, as everyone seems to claim, protect against smallpox? His answer in the form of the experiments done initially on 13 and subsequently on 23 patients demonstrate that the scientific premise is correct. Going into the experiment with James Phipps, Edward Jenner had copious doubts and a kernel of hope for success. The dogged and clear scientific proof of immunity obtained from the cowpox vaccination that rendered the 23 people immune to smallpox was the glorious success obtained with rigorous scientific proof. The British Government ordered mandatory vaccination to the population and subsequently all over the world to the result that in 1976, smallpox was considered eradicated from the planet.

Here was a distinguished scientist operating on an assumption of benefit for his patient and with apprehension and careful follow up he determined the benefits of the treatment. Except for the Variola vaccination that had become commonplace and deadly no other knowledge was available save for the anecdotes. This then was the sunrise onto the hinterlands of medical science. A cause and effect had been proven to the benefit of the entire world. No wonder they call Edward Jenner the father of immunity.

Watson and Crick

Now let us venture into another successful scientific discovery that has revolutionized the current thinking and from which we will be reaping benefits for the foreseeable future.
It is April of 1953, James Watson and Francis Crick have just published a scientific paper that makes the following famous understatement,  "This structure has novel features which are of considerable biological interest."  The duo had been interested in the DNA molecule for some time. The race is on, in the scientific community, to be the first to decipher it. Linus Pauling Nobel Laureate in Chemistry had proposed a trihelical structure for the DNA. 
Rosalind Franklin

It was not until Watson and Crick had heard a lecture given by Rosalind Franklin and Maurice Wilkins where the latter showed an x-ray diffraction image of the DNA that Watson and Crick were convinced about their lingering impression that the DNA was a double helix and based on preexisting information, contained 30% adenine and Thymine and 20% Cytosine and Guanine. 
X-Ray Crystallography of DNA

Based on the stick-figure Watson and Crick used as their model the phosphate sugars would be the outside backbone of the DNA and the nucleic acids would be bound together by weak hydroxyl links. Unfortunately Rosalind Franklin died in 1958 and therefore was not nominated for the Nobel Priize in medicine that was subsequently shared by Watson, Crick and Wilkins.
The DNA Proposed Model

 This is a story of a relentless dedication based on axioms and hypothesis and fragmented knowledge that were painstakingly pieced together by scientists through hard work and imagination. "It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material,” wrote Watson and Crick in the scientific paper that was published in Nature, April 25, 1953. It didn’t escape the rest of the world either!

One more story of import hails back to the 1970s and 80s. It concerns a determined soul who spent 20 out of 24 hours a day feeding himself the knowledge of genetic damage as a causative agent for cancer. His name is Robert Weinberg. He pioneered the research of oncogenes and tumor suppressor genes in his Whitehead Institute
He gathered the brightest individuals from all over the world and gave them a clean slate with few signposts of the known and potential unknown.  He identified and characterized both the first oncogene and the first tumor suppressor gene and demonstrated how certain gene regulators, or transcription factors, contribute to cancer metastasis. These are far reaching discoveries in the field of cancer medicine. The fruits of his labor have enabled oncologists to question genetic traits leading to cancer and how tumor suppressor genes are equally as important as the promoter genes in the story of cancer.

Robert Weinberg is a jovial hearty kind of a guy who exemplifies the team spirit. It is his obsession to get to the root of the disease called cancer. His research is one of painstaking slow and methodical rigor with many failures that sometime come in like driving rain. There are no shortcuts. No trolling the scientific papers and creating a new paper by modifying a few sentences and paragraphs. His and his colleagues’ version of trutht finding is the real science. The science that creates value and is remembered long after the scientist is gone. As all scientists are, he is not one to shy away from controversy and he is not one to slink away from issues. He approaches them head on and is determined to be at the forefront of new discovery. It is simple for him, all rests on hard work and dedication.

Fast-forward to today where there is a plethora of journals and the scientific community is awash in scientific publications. Everyday the mail seems to bring in a bag full of journals and each has at least 12-18 or more “peer-reviewed” articles of "importance". Every day there is a new discovery that such and such medicine causes such and such result. If this could all be true we would be discarding cancer and some other diseases to the heap of “has-been” pile.

So what gives? Why are we inundated with literature about new discoveries and latest bonanzas of scientific acumen and yet life remains stunted by the same diseases as it has for quite a while. Oh, I am not saying that progress has not been made. Yes it has from 1940s to the present the life span of men and women have scaled up significantly. Now in relation to cancer almost 52-56% of all-comers with cancer live out their full lives. So yes we have cured malignancies and yet the pace is slower then the burgeoning libraries of scientific papers.

Could it be that the data that is being culled is a rehashing of material? Or could it be that we are using statistics in meaningful ways to promote a point of view through the arbitrariness of mathematics and statistics? How can Vitamin D one day be preventative for most solid cancers including Colon cancer and the next day it is not? How can drinking one glass of wine give you health one day and the next day half a glass of wine three-days-a-week is the maximum recommendation for women because it can cause breast cancer (lobular carcinoma variety)? How is it that the Cholesterol lowering agents Statins were suspected of increasing the risk of cancer and then later decreasing the same risk? And how about this one that Selenium reduces the risk of prostate cancer and recently it has been determined that it does not. How come smoking… No! No! I don’t think anyone would touch that one, not even Philip Morris and company. Anyway there is a large number of how comes out there and they pose a question that needs to be answered. What makes a “landmark” scientific study reverse its own conclusions?
Is it possible that the dependence on ancillary scientific techniques of probabilities with vague multivariate reference points through the wizardry of mathematics can transform a quasi scientific findings into a virtual etched-in-stone “evidence” that someone else the next day by juggling the same numbers, vilify? 

There is disruption in the medical care that patients receive as a result of such gimmickry.

Another method of how some of the “ivory-tower” gifted scientists use their magic is by analyzing multiple studies under the guise of “meta-analysis.” This method suffers from similar lack of fastidiousness as the epidemiological probability experiments. While the former rely on previous information by authors-other than the one writing, the latter relies on a small number of variables ignoring others that might have an impact on the outcome. The data obtained is tainted by the original author’s bias and opinion and the meta-analytical author is approaching at it with his own determined  bias. Meanwhile no new information is obtained only new “nuance” is gleaned. The prevalence of meta-analysis studies is alarmingly huge and growing and yet nothing new comes out of it most of the time except 15 minutes of fame. The reason this is accepted is because a new study requires enormous resources and consumes large costs for patient accrual, time and money. Why not try to manipulate old material into a newly transformed data. And then we go about using that data in other studies. “A lie told often enough becomes the truth.”

Pseudoscience comes in many shades of grey. It is labeled junk, if the data used is obscure and has little factual truths in it. Another form in this spectrum of pseudoscience is Defective Science where the authors hungry for celebrity allow a confirmation bias to cloud their sense of right and true.
Martin Fleischmann

Stanley Pons

Martin Fleischmann and Stanley Pons of Cold Fusion fame 

failed to procure their name in history and in the scientific community with a failed concept under bright lights of the media in 1989. And then there is fraudulent science and misconduct purely for ideological or personal reasons where reputable scientists succumb to the pressures of potential fame and fortune and make up data to suit the premise they wish to explore.

And there are legitimate scientists who have done significant work to great personal peril to prove a theoretical argument and base it on excellent science and these individuals have won scorn and ridicule from their peers for many years before finally finding the reputation they deserved. A well-entrenched thought is difficult to dislodge and garners a ton of support in its defense. The three names that come to mind are Barbara McClintock and her Transposons or "jumping genes", Barry Marshall and his discovery of Helicobacter Pylori as the cause of peptic ulcer disease (He had to drink water teeming with Helicobacter Pylori and get peptic ulcer for his scientific proof, since much of the gastroenterology establishment was mired in the multibillion dollar antacid industry and Lynn Margulis and her hard fought scientific battle to prove endosymbiosis and evolution took an equivalent amount of whips and scorn before finding her rightful place in history.

Unfortunately for the lay person who succumbs to the 10 second fragments of television  news where studies are bandied about as the gospel. Too many people believe in the hoaxes sponsored by various companies that are out to prove their point of view and call it scientific study. While the spokesperson uses phraseology that makes him or her look authentic, he or she doles out percentages and statistics to confuse and obfuscate reality. The premise of pseudoscience invokes a visceral response from the public where with crafty words and nuances of fully exploited rationalization traps are offered as evidence via a celebrity mouthing the paid words. Pseudoscience is like a sociopath gaining empathy with false words. Once the trap has been set the public will follow the lead until another roar of a new idea kindles their imagination. Humans have a desire to believe and pseudoscience has the false words to convince.

It has and should be said that sometime being first out of the gate even with pseudoscience wins the initial battle of money war since real science is time consuming and diligent and by then the looters have looted the kitty.

It might seem childish to say, “hey what about the truth?” And in a world revved up and strung tighter then an unplucked mandolin anything goes is the reality. The majesty of the reward lies at the other end of the lies. It is for us to know and understand and comprehend the nature and virtue of the written word.

Science is allowing itself to incorporate pseudoscience in its matter. The nucleus of such a deplorable apparition is one step away from the transduced signal of a fully depressed gas pedal of a runaway car like the cancer cell.  We are allowing such badly used information and calling it scientific rigor. The value of science is looking down the abyss and is tethered only to the single thread of truth holding it back. If too often science contradicts itself, the believability will suffer. We cannot allow the Galileo’s of the world to be hampered by the Ptolemy’s “The Almagest.” Rigorous science requires verifiable truth and not some shades in between. Scientists should be weary of methodologies, statistics and conclusions derived in the studies. Even arguments based on probabilities are like imposters strutting stuff built on ethereal foundation.

I started with food and so I shall finish with that concept. Excessive food is bad for health. Excessive pseudoscientific literature is equally bad for progress especially in medicine, where the patient and his physician get bloated with a sense of airy, unnatural view of the world that mitigates the harsh reality into a false sense of comfort ending in calamitous ruin. The Journals and their editorials should pay heed to what is said, how it is said and what is the premise behind the words before putting it to print. Sadly if they don’t do their job well they will eventually have no job at all. Printing journals for the sake of filling pages with nonsense is irresponsible to all science.

No profit grows where is no pleasure ta’en;

In brief, sir, study what you most affect.
Tranio, scene I Taming of the Shrew ~ William Shakespeare


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