Its all about the "smelling the roses" ....

The wonderful thing about science is that it unweaves the fabric of the living world, warp by weft, for our understanding. It explores the world and brings to light these tiny facts, nuggets of information, these hypotheses and theories that give you wonderful explanations for your everyday observations. This is one reason which makes neuroscience, neurophysiology, neuroanthropology and neuropsychology (basically all these multiple disciplines beginning with neuro, as you may have validly surmised by now) particularly attractive to me !

The reason I say this is because, on so many occasions, i have read through articles on these and similar subjects and found wonderful insights into our everyday observations. These random explorations (basically an activity I indulge in when I am unable to focus on the job that i should legitimately be doing) have helped me sustain my fascination with science despite having completed a PhD (A PhD, as many of the graduates will agree is genuinely a degree in philosophy because it truly teaches you to accept failures and be philosophical about them :)). Anyways, getting back to the subject on hand, the most recent article to have caught my fancy in such a quest, is my discovery of a beautiful explanation for a common complaint of many women or rather of many chefs in general. Ever so often I have heard many of my friends complain that they feel satiated by the mere process of cooking. So much so that their appetite almost vanishes for the food that they have painstakingly cooked. This is a very common observation and for some reason i had always associated it with the smell of food activating the brain's satiation and pleasure centers before the actual food was partaken. This was of course just meaningless conjecture on my part, unsupported by any background search or review.

But then in a recent issue of the major science journal - Cell, I found a beautiful explanation for the above phenomena amply supported by evidence and not merely speculation. This chain of evidence, as I found out later, extends from times much earlier than now and in fact, the subject of olfactory perception and the activation of specific regions in the brain has been under study for many years now.

As some of the careful observers would have noticed in their life too, it is true that olfactory and visual, sensory signals do indeed contribute to our sense of satiation after or during a meal. A small portion of great looking and smelling food in a restaurant is much more pleasurable because of the sheer presentation, smell and ambience (even though the taste may not be dramatically different from a local take out place)! The importance of the aromas and the visual appeal of food in augmenting gastronomic pleasure has been duly stressed for several centuries now by both connoisseurs and lay men/women like me. I make special attempts at making the food atleast look good if not taste great... :)

Interestingly, I also learnt of one of the last diet fads, called the sensa diet, on the above hypothesis that enhancing the smell of foods (by sprinkling fragrant crystals of flavors and scents) decreases calorie intake by boosting the satiation signals in our central nervous system.

So, the first question that arises is - is their any merit to this observation ? What is the role of smell in altering our mind state ? Can food aromas increase our satiety ? How does this work ?

My brief search on some relevant literature led me to this paper by a research group in Yale, published in 2005 and which laid the foundation for the more recent finding.

I did realize a few interesting things through a perfunctory perusal of this manuscript. Interestingly, an odor molecule may reach the olfactory epithelium via the nose (called as orthonasal olfaction in technical jargon) or the mouth (called as retronasal olfaction). A smell is perceived as coming from the outer world when sensed through the nose whereas when sensed retronasally, it is perceived as arising from the mouth. In fact this illusion is so strong that people routinely mistake retronasal olfaction for "taste". So much so that even though our tongue is only capable of recognizing a limited palette of tastes - sweet, sour, salty, savory and bitter, we often can discern more complex tastes - medicinal, pleasant, fruity, rotten etc etc. And these "tastes" that we often sense are actually a result of the odors being sensed retronasally. Pinching the nose while eating or drinking is a simple experiment that will demonstrate this point. In fact, pinching the nose while drinking something distasteful / medicinal is a common strategy adopted by many, especially when dealing with kids.

A wise man called Rozin, had also observed that "olfaction" is the only dual sensory modality that senses both objects in the external world and inside (mouth). Based on this he further proposed that the same olfactory stimulation / smell may be perceived and evaluated in two qualitatively different ways depending on whether it is referred to the mouth or the external world.

Exploring this possibility the authors in 2005, showed through careful and controlled experimentation that although the smells traveling through the orthonasal or the retronasal route lead to the same olfactory receptors, they activate distinct regions of the brain. By delivering the aroma of chocolate (along with other chemicals about which i am not discussing now but which did yield interesting results) through distinct tubes that utilized the two distinct modes of olfactory perception, they studied the effect of the aroma and the mode of delivery on the brain activity. Monitoring the brain activation through functional MRI (fMRI), they clearly show that orthonasal delivery of smells activated the amygdala (which is involved in reward anticipation) while the retronasal mode of delivery triggered the activation of the medial orbitofrontal cortex, which is implicated in initiating the pleasure response upon the receipt of the reward. This was thus suggestive of the fact that retronasal olfaction possibly contributed more to satiation than the orthonasal route.



It was to test this hypothesis that the second group of researchers began their study. They used a special Mass spectrometry technique to quantify the aromas generated in an individual's retronasal passage. In their study asking volunteers to eat as much as they want to feel satiated, the experimenters found that the individuals who released more retronasal odorants tended to consume fewer calories. However, intriguingly, the authors also found that the total concentration of aromas released from a given food varies significantly among individuals. This is something i fail to understand but it does suggest that the complexity of a food's odor is only one component contributing to the satiation signals in the brain.

I wonder if there is any research on the visual component of the food... !!!

Meanwhile, this study does give some ray of hope for the foodies battling with weight loss plans.... You can make food smell great and end up eating less but still having the same pleasure index !!! So one can binge without a cringe !!

Refernces:
Small, D.M., et al. (2005). Neuron 47, 593–605.
Ruijschop, R.M., et al. (2009). J. Agric. Food Chem. 57, 9888–9894.

PS - Now, it does make me wonder though... it must be a tough choice for a restaurateur... Should he cut down on the aromas and the appearance of the food, so that people order more or should he allow people greater pleasure and satiation so that they come back again ? Guess that's why better restaurants cut down on the portions size and make great looking/smelling/tasting stuff... they make you want to eat more and let you eat more too !!!

Hype and hoopla - Much ado about nothing... !!

A glimpse at the Indian media last week would have definitely made everyone hear the victory bugles that were playing from every quarter. The reason being the supposed apology from the editor of Lancet - the medical journal where the article on NDM-1 super bug (New Delhi metallo lactamase) was first published. This super bug has become a celebrity of sorts as it is forever in the media limelight for all the wrong reasons! First, there was the super bug controversy subsequent to the publication of the article in Lancet and then there is another hullabaloo now about the "apology" from the editor.

For the uninitiated, the reputed British journal LANCET had published a collaborative work, involving several groups from India, Pakistan the UK, which claimed that a bacterial gene that confers resistance to practically all the β-lactam antibiotics was widespread across the Indian subcontinent. Furthermore, riding on carriers and patients, this “superbug” was traveling to other continents. Since most antibiotics, including the frontline carbapenems were ineffective against the bacteria that harbored this gene, it seemed to be an unstoppable medical crisis. This resistance conferring gene is mainly carried on plasmids and was called the New Delhi β-lactamase (NDM-1). It was named after New Delhi simply because it was first identified in european patients who had just returned from India (as medical tourists) and extensive molecular analysis suggested that the bug did originate on the Indian subcontinent. This was done probably without any great thought by simply following normal scientific convention for nomenclature of new discoveries especially the beta lactamases.

This article however created a frenzy in the Indian media. A normal thinking person would probably say that the frenzy is justified because after all you've discovered a bug which is resistant to all available antibiotics and India is a densely populated country with significant health care issues, so it is time that the government did something to control the spread. But, here is the TWIST !!!

Surprise Surprise, the media hype was not for the problem of the bug or the medical issues at the forefront but it was about the nomenclature !!!!

"Why was the bug called 'NDM-1'?" The entire country went on a hyper-emotive overdrive as it criticized the researchers, the journal, etc etc. The media and the government were quick to denounce the findings of the report. It was labeled unscientific and unacceptable in addition to being the handiwork of a pharmaceutical lobby! It was declared to be treacherous plot by the west to destroy our burgeoning “medical tourism industry”! This report was thus portrayed as an attempt by the West to paint a dirty and disease-spreading image of India, the rising economic power. Hence, it was implied, that it is the duty of every patriotic Indian to protest to this “national insult” towards restoring the “India shining” image.

I have already clarified the underlying dynamics of this issue in a previous post of mine but basically, it is imperative to remember that naming a new organism or enzyme after its source, site-of-first-identification or discoverer is part of scientific convention, specifically, with regard to this particular group of enzymes! Think Lyme disease, as in Lyme, Connecticut, or Norwalk virus, as in Norwalk, Ohio. Think of Clostridium botulinum strain Alaska and Anaplasma centrale strain Israel. And several other organisms have been named so - the banyan tree is named as Ficus benghalenesis ; one of the most virulent of pathogens, the causative agent for TB, is called Mycobacterium tuberculosis Beijing ; a new frog species found in Sahyadari (Western Ghats) has been named Nasikabatrachus sahyadrensis. In 1961, a dinosaur was named as Barapasaurus tagorei as its discovery coincided with the birth centenary of Tagore. All these were also named after India or other cities in the world. No one raised a hue and a cry then. Thus, there doesn't seem to be much of a case against the naming of the bug !!!

But clearly, the bug was a health hazard and there were other more important issues to consider than just focusing on the nomenclature. But thats what happened eventually, as everyone ignored the potential pandemics that could spread through this bug or the urgent need for the discovery of new antibiotics or even the need to cut down on unnecessary prescription and consumption of antibiotics (which has led to the development of such a strain in the first place... ). All that remained was this feeling of hurt and insult because a disease causing pathogen was named after New Delhi !!!

And then with time, as is true for most media frenzies, this controversy died a slow death and everyone forgot about it, till of course the editor of lancet decided to come to India to launch an India chapter of the journal. And then as journalists usually do for a scoop or two, they probed him on the past controversy and the editor - placed in the tough spot that he was, issued rather diplomatic (and meaningless in my opinion) apology. He said that he stood by the findings of the report but is sorry about how the organism was named after India. First of all, this was a diplomatic defense because the editor of a Journal really doesn't have any jurisdiction/opinion on the nomenclature issued by the writers. We all generate several plasmids during the course of our research and no editor can/does ever object to these names!! Secondly, there was no need to apologize because the nomenclature was as per normal scientific convention and there is no need for an entire country to get sentimental about something like this because it honestly doesn't mean anything. And more importantly, despite the apology, he does stand by the findings of the paper !! And thus, this apology is merely a gesture of politeness than of any merit. I guess, the editor, amidst all the media glare just chickened out of telling his host country that they should get over it and should focus on other pressing things.

And here I am, miles away from my country and all i can think is "Why?"...
Why do we as a country focus on appearances and verbal assurances than on the underlying truth and the facts ? It is far more important that we work of eradicating the threat of this super bug than on how and why it was named. Why are we as a country so insecure about ourselves and the worlds perception of us ??? We are a growing nation which is on the threshold of stepping on to the world stage and instead of solving our pressing problems like population, inflation, terrorism, naxalism, corruption, education, health and infrastructure, we are focusing on the name of a bug, on questions of national pride and respect. Ridiculous !!! If we as a people are proud of our nation, it truly shouldn't matter what the west thinks of us. We should have a sense of confidence in our worth which is independent of another view. And we should learn to be mature and self critical not for an award or a title but for our own self. Why doesn't anyone understand that in an increasingly competitive world market, sentiments hardly dictate anything. What matters is efficiency and cost effectiveness... and if we achieve this, the rest of the world will be playing in our backyard like they are in China's now... !!!

As for the editor while I do see his dilemma, i do wish that he was more forthright and had used his diplomatic tact elsewhere. Instead of chickening out he should have been honest and raised the very valid issues behind the naming of the organism and of the other concerns which are more important than the name. But I guess, its easy for me to comment when I am far away from the glares of a nation, seething with hurt and anger.

Through all this, all I see is the need for an effective media which can present news accurately and provide the right perspectives. A media which will responsibly use rationality and evidence to gain an audience than manipulating the sentiments of the masses to gain their petty ends.

Evolutionary drive towards greater complexity - fact or fable ??

"Life began in the primordial soup and the evolutionary drive has resulted in the origin of organisms of greater and greater complexity."
"Organisms get better as they evolve. They get more advanced, more modern and less primitive."
"From the first cell that coalesced in the primordial soup to the magnificent intricacies of the Homo sapiens, the evolution of life has been one long drive forward towards greater complexity."

True or False ?

Well, as far as I see, a lot of people would tend to agree to these statements...

But then once in a while you come across these books and authors who question such statements and our implicit acceptance of their veracity and they end up shattering many of the myths which we often accept unquestioningly ...

I haven't come across too many such people but one person who makes me think, question, argue and answer, as I read his thoughts is Stephen Jay Gould. SJ Gould is a famous naturalist and evolutionary biologist who has written several wonderful essays (more than 300 in fact, as a continuous monthly series over a period of several years) and quite a few books. While his essays are eye opening with their exquisite ability to interlink diverse events and delving into the depths of any subject to identify patterns and similarities, his books have this uncanny ability of exposing questions to which people have often assumed answers without rigorous questioning.

A good example would be the question of an increasing drive for complexity. Most people, even most biologists, would agree with the statements listed at the start of the post which suggest an inherent drive for complexity. In his book, "The Full House", Gould exposes this fallacy and attempts at convincing us of an alternate possibility.

"The Full house" is a beautifully written book and in true Gould style, it leads to a healthy argument in the minds of the reader as they battle against the statements made by him only to finally accept his logic and rationale. At many times, I have found Gould to be a Stickler for semantics while i have often prioritized and aimed at distilling the meaning implied without stressing on the actual words used. But I guess, in science, a field that deals with rational thought and empirical observations, it is important that one does use the right words to convey the right insight.

In this book, Gould leads us through the labyrinthine maze of statistics and their role in our understanding of this "evolutionary drive for greater complexity". He leads us through a step by step argument that finally leads one to accept that evolution in all likelihood does not have any inherent drive towards complexity. He uses two elegant examples to demonstrate the existence of a left and/or a right wall in various everyday phenomena i.e. a natural upper or lower limit that is inherent to the system under study. The human body, for example, has certain inherent physical limitations which ultimately determine the performance and improvement of athletes (this is an example of a right wall, which means that our physical performance can keep increasing with rigorous training, technology, dietary intake, lifestyle, drugs etc but only till we hit the right wall...which is determined by the limits of the human body). He demonstrates very convincingly that the existence of such left and right walls can actually bias the statistics and thereby our understanding of particular phenomena, leaving plenty of room for wrong interpretations.

The book begins with a succinct explanation of the three major statistical measures - the mean, the median and the mode, Gould first convinces us that the mean is the farthest from the truth (as even a single erroneous value can truly skew our perspective of a population), while the Mode is the closest to the truth as it depicts the most common value in a population.

1,2,3,2,4,100,2,4,5,2,1,1000

The mean for this series would be 98.3 while the median and the mode are 3 and 2 respectively. This clearly highlights the fact that the mode is the best representation of a population and therefore the most likely candidate to be used to study variations in a population.

Extending this point further, he makes the case that in the history of evolution, the bacterial mode of life remains the single most dominant life form that has populated the earth. Bacteria have been the oldest and most successful occupants of this planet as they are found in almost every habitat known to man - ranging from the bacteria that exist as parasites and symbionts to the autotrophic bacteria that are inhabitants of hot thermal springs and volcanic rocks. Thus, considering the long history of evolution and the predominance of bacteria, these tiny, microscopic organisms seem to form the "statistical mode" of life on earth. This line of thought leads us to explore the possibility that life is not an really exhibiting a drive for greater complexity through evolutionary history.

Also, importantly, he draws our attention to one fundamental question which needs to be addressed in the context of evolutionary progress and this is the question of the very definition of progress. What is considered to be more advanced and what is more primitive ? On what basis would one say that a particular lineage is more complex or more advanced ? Does a bacteria become more advanced and complex because it is better adapted to a diverse set of environmental conditions or do humans become more advanced and complex due to their conscious nature ? Or does a virus become more complex, because it has managed to evolve a basic minimal set of functions essential for its propagation and survival ? What defines evolutionary progress or complexity ?

An immediate thought would be to say that the evolutionary success of an organism is the true indicator of its progress and thereby of its complexity; and this is where the impact of bacterial abundance truly hits. Based on criteria such as numbers, abundance, evolutionary ancestry, biomass and adaptation, the bacteria truly seem to be "superior" to all other species including man.

Gould's argument is that this increase in "complexity", as we perceive in terms of multicellularity, physiology, life span, consciousness, etc, is not the result of an inherent drive but is rather a consequence of the existence of a left wall in the history of evolution of life. In the evolution of life, the simplest organisms arose first and things couldn't get any simpler from there. The existence of such a wall on the left of the evolutionary scale meant that things can only move in one direction - to the right. Thus, the origin of multicellular organisms and of sentient life is the result of random events which could only drive the evolution of life in only one direction. He cites the example of a drunk man walking whose left end is determined by the existence of a wall and the right by a ditch. Under the circumstances, there is a good chance that the man would end up in the ditch even though he is walking without an inherent drive because that's the only way open to him. Thus, he says that the evolution of human beings from the single celled organisms is not the result of an inherent drive in evolution towards greater complexity but rather, is the result of random events which cannot be expected to yield the same consequence upon another repetition. Gould also uses the example of parasites and simpler organisms like viruses to introduce the idea that organisms on the evolutionary scale could also tend towards simplicity rather than complexity.

Gould's primary idea of course is to convince the reader that the complexity in life as it exists today is not the result of a pre-ordained or inherent evolutionary drive towards greater complexity but rather the result of random events which have resulted in sentient beings like us, ruling the planet today! While the question of evolutionary complexity does make one think about the possible criteria that can be considered, the ultimate aim of this book is to convince us that evolution, in itself, lacks any inherent drive towards complexity; thereby stripping off any modicum of special ordainment that may be conferred on the reasons for human existence at this point in evolutionary history.

From my perspective, the definition of complexity seems like a question of semantics because i chose to interpret complexity as a reflection of the extent of specialization and adaptation. This is a criteria that Gould has not explored. I think that there has been an undeniable increase in the complexity of organisms since the origin of the first protocells. In the history of evolution, life has moved from the single celled bacteria to mutlicelled humans and the organisms have grown more and more specialized along the way. I do not suggest the existence of an inherent drive towards complexity but I do think, there is a trend towards greater complexity. This increased complexity, as interpreted as increased specialization and adaptation, could also address the existence of parasites and viruses whose existence was difficult to explain by the other definitions of complexity.

The underlying cause for this increased complexity could certainly be the existence of the left wall, as rightly suggested by Gould, but I am definitely, not completely convinced, by his arguments against an increase in complexity. I am also quite taken by his argument for the modal bacterial life and i think that it is a very good point to make. In fact, one rarely realizes the ubiquity and antiquity of bacterial life forms and going by these parameters, the entire history of the evolution of life would seem like the age of bacteria unlike the other ages which have named based on the predominant life forms seen in the period.

Thus, while I understand the case made my Gould in the book against the commonplace understanding of an inherent drive for increased complexity in the origin and evolution of life and I do espouse his view of our existence on this planet being a result of purely random events, which need not (and most likely will not) end the same way, if the history of life is replayed; I am however not prepared to say that over the entire evolutionary history known to us, there is no increase in the complexity of organisms.

On a parting note, I would like to present here a beautiful thought which was used as the opening for the book's second chapter:

"I have often had occasion to quote Freud's incisive, almost rueful, observation that all major revolutions in the history of science have as their common theme, amidst such diversity, the successive dethronement of human arrogance from one pillar after another of our previous cosmic assurance. Freud mentions three such incidents: We once thought that we lived on the central body of a limited universe until Copernicus, Galileo and Newton identified the earth as a tiny satellite to a marginal star. We then comforted ourselves by imagining that God had nevertheless chosen this peripheral location for creating a unique organism in his image - until Darwin came along and "relegated us to descent from an animal world". We then sought solace in our rational minds until, as Freud notes in one of the least modest statements of intellectual history, psychology discovered the unconscious."

A childhood lesson...

A brief glimpse walk down the memory lane made me recall this one sentence which was a constant companion through my school days. Hours were spent in the evenings, trying to write this sentence multiple times in cursive hand -

"A quick brown fox jumps over the lazy dog".

I was always amazed by the fact that this simple sentence contains all the alphabets in the english language which made it a pangram !

I used to still wonder how many of these are around...

And then a simple google search on a lazy morning yielded a huge list of pangrams none of which seem as elegant as this one simple sentence...

Here is a partial list that i came across.... Wonder if you have any ?

• Nymphs blitz quick vex dwarf jog. (27 letters)
• Big fjords vex quick waltz nymph. (27 letters)
• Bawds jog, flick quartz, vex nymph. (27 letters)
• Bawds jog, flick quartz, vex nymphs. (28 letters)
• Waltz, bad nymph, for quick jigs vex! (28 letters)
• Fox nymphs grab quick-jived waltz. (28 letters)
• Glib jocks quiz nymph to vex dwarf. (28 letters)
• Bright vixens jump; dozy fowl quack. (29 letters)
• Vexed nymphs go for quick waltz job. (29 letters)
• Jack fox bids ivy-strewn phlegm quiz (30 letters)
• How quickly daft jumping zebras vex. (30 letters)
• Two driven jocks help fax my big quiz. (30 letters)
• "Now fax quiz Jack!" my brave ghost pled. (30 letters)
• Vamp fox held quartz duck just by wing. (31 letters)
• Five quacking zephyrs jolt my wax bed. (31 letters
• The five boxing wizards jump quickly. (31 letters)
• Jackdaws love my big sphinx of quartz. (31 letters)
  
• Kvetching, flummoxed by job, W.zaps Iraq. (32 letters)
  
• My ex pub quiz crwd gave joyful thanks. (32 letters)
• Few quips galvanized the mock jury box. (32 letters)
• The jay, pig, fox, zebra, and my wolves quack! (33 letters)
• Quizzical twins proved my hijack-bug fix. (34 letters)
• The quick brown fox jumps over the lazy dog. (35 letters) (Used to test typewriters and computer keyboards, and as sample text; famous for its coherency, dating back to 1888)
• Wolf zombies spot the jinxed grave. (36 letters)
• Heavy boxes perform quick waltzes and jigs. (36 letters)
• A quick chop jolted my big sexy frozen wives. (36 letters)
• A wizard’s job is to vex chumps quickly in fog. (36 letters)
• Sympathizing would fix Quaker objectives. (36 letters)
  
• Pack my red box with five dozen quality jugs. (36 letters)
• Fake bugs put in wax jonquils drive him crazy. (37 letters)
• Woven silk pyjamas exchanged for blue quartz. (38 letters)
  
• Brawny gods just flocked up to quiz and vex him. (38 letters)
• My faxed joke won a pager in the cable TV quiz show. (39 letters)
• The quick onyx goblin jumps over the lazy dwarf. (39 letters)

Happily forgetful and forgetfully happy !!!

Memory - our ability to remember.
Who would not want more of it ? We all yearn to remember a little more - that one extra book, one more dialogue, another new name or that old wicked answer !! Intelligence is often understood to be linked with a sharp memory. Almost all of us would like to have a fabulous memory - to be able to recall every tiny detail, as we try and pack our brains with as many facts, figures and details as we possibly can. In our attempts to remember everything, we lose track of the fact that forgetting is no less important.

In fact, as someone rightly said - "What makes us human is not our ability to remember. It is our ability to forget."

Imagine remembering every tiny detail about every single day for years on end. An excess of memory and we would find our mind cluttered with the minutiae of everyday existence - the shape of the cup, the crack on the side, the level of the tea, the temperature outside, the day, date and time, the brand of tea, the texture of the scones, the colors, the smells, the feelings and the emotions - All this with one cup of tea. Imagine this on a daily basis. for every activity of the day and you can imagine the nightmare that it will be. It would become impossible to glean relevant information in a timely manner from these heaps of facts. It would be like fishing for a needle in haystack all the time.

Now, imagine surviving the horrors of the world with such tireless memory. Our adverse experiences haunting us forever with the same intensity as that of the initial experience. One's entire life would just become a ceaseless trauma. The past would haunt us forever simply because we remember it far too well, to let go.

And this is why forgetting is more important than remembering. The ability of our brain to weed out unnecessary information as it builds connections in the brain is what makes us human. It is indeed this so called "handicap" of ours, this inability to remember that becomes our true strength.
And thus, every time I feel like kicking myself for not recalling that book, that line or that story, and when i catch myself wishing for more hard disk in my head, i show myself the possible consequences of having a great memory.... :)

And then I am back to my happier forgetful self again... :)

The inheritance of time...

Of the many things that we inherit, I am most amazed by our ability to view the past and the future while still trudging through the present.

We get a glimpse of our future in the life of our parents.
It is amazing how, as we grow, we tend to become more and more like them. While the nature vs nurture debate is still on going, the fact of the matter is, that we inherit both of these from them in more ways than one. Appearances, mannerisms, attitudes, aptitudes, priorities are all inherited from them in some measure, modified by the ways of the world and then passed on further. And thus, as part of our true inheritance we can potentially visualize our future in the lives of our parents. Few rarely realize or appreciate this gift of foresight. Foresight, about the consequences of our actions and their impact on us and the world. If only we would learn the right lessons and remember them long enough, we could carve out a very different future for ourselves. The tragedy of life however is that in avoiding some mistakes, we end up making others but then at least one knows that "they tried" to make a difference.

We also get a chance to re-live our childhoods with a greater awareness of it through our children. It gives us the ability to peep into a past, to sit down and revisit our childhood for its simple pleasures, amidst the flurry of daily activity. Our children are an essence of us that we leave behind in the world. They give us an opportunity to make the changes that we desired. They give us an opportunity to revisit some experiences with greater clarity and experience. They provide us with an opportunity to rectify the errors of the past and to lay a better foundation for the future.

Thus, our true inheritance lies in our being able to view a glimpse of our future in our present and to revisit our past. I wish I am able to learn the right lessons and remember them too....

A tiny list that keeps me going... :)

Sitting by the window ledge sipping chocolate all snuggled in a blanket...Walking on the beach with the waves lapping at my feet... traveling the world to capture its glory through my lenses....translating the visions of my mind on to a blank paper.... Sitting by a brook listening to its heart beat.... walking on a long country road, smelling the grass... listening to the rain drops... walking on the dew drops... gazing at the night sky... sitting on an open lawn as the sun sleeps and the moon stays on guard with you by my side... hearing the silences that dwell in the heart of the mountain peaks... listening to the sounds of the jungle... making wood sing... reading by the lamp light in a place of my own... feeling the wetness on the nose of my favorite canine waking me up on a lazy morning... snuggling up in my blanket without a care in the world... playing with colors... walking like the roads never end... flying with the wind in my hair... gliding like a bird... swimming like the fish exploring the depths unseen...

A tiny list that keeps me going... :)

Adrift...

Farewells have always been difficult for me.
Unshed tears and unspoken words.
Words that always seem to fall short. Eyes that say it all. Embraces that you never want to end. Moments that keep running past the more you try and hold onto. Words that threaten to unleash the tears that you try lock away.

Farewells have always been difficult.

I thought it was difficult to be left behind but never did I realize how difficult it can be to actually move away, till I actually had to.

To move away from all that was known and certain. From all that was yours. From the anchors that held you in place to being adrift in a sea of change. To a place that feels alien. To people who seem distant. Trying to build a home so far away from home.

So much change and so much excitement that it actually leaves you yearning for some stability and some boredom !! Familiarity seems to give more comfort to the heart than the joy of new adventures. Such are the times as I look for an anchor to hold me in place in a world that seems to be moving too fast for me.

Fickle is the mind indeed as it craves for that which it does not have.

Gone with the wind...

In our lives, some times are more defining and more influential than the others. They change the course of our lives, the fabric of our being.
The last couple of months have been one such period for me.
They have just breezed past me and i was so busy that I could barely sit down and look at them. It felt like a giant roller-coster ride that has left me screaming my insides out due to fear, excitement, exhilaration and sadness.

They were filled with frantic activity that left behind frayed nerves. There was too much to be done and to be taken care of... so much so, that i didn't grant myself the time to just sit down and think, to assimilate, to register, to enjoy and to grieve. The days flew past in a haze and they left me wanting. Wanting for some quiet, some peace and some space.

I loved the rush and the excitement but I also missed the bigger picture. I missed being able to move one step at a time. To be able to grieve when the heart wanted to. To be able to rejoice when there was reason to. I missed not having opened my heart to have let those emotions out, simply because there was too much to do. I now wish to have been able to pause the roller coaster in motion just to get a snapshot in time for every moment in the past two months.

I've missed myself for so many days. The little girl in me who used to love staring at the stars had not gazed at the night sky for nearly two months because she was always too tired to keep her eyes open. The footloose nomad in me had not wandered off in a while because there were too many places to be at. The thinker in me had not thought for a while simply because there was too much to do.

The last few days have been filled with so many of these unfelt feelings, unshed tears, unspoken words and unspoken fears. The flurry of everyday activity had actually numbed my mind into unquestioning acceptance. And now when I sit down to think, the pain is too much to bear. The tears are too many to control and the words are too many to say.

The last few days have indeed gone with the wind as they brought me closer to Scarlett O Hara when she said - "Oh, I can't think about this now! I'll go crazy if I do! I'll think about it tomorrow."

But then now i also know that sometimes the pain doesn't diminish with time. All you manage to do is to push it under the rug till it resurfaces every now and then.

Some emotions are best dealt without procrastination.

Random patterns...

In a life that is fast rushing past us, we are forever trying to make sense. Trying to understand all that happens and all that does not happen. We are looking for causes, explanations, reasons and justifications. We are frantically searching. Searching, for a pattern, a cause or an explanation. Something to comfort us, something to give us hope. Hope for the future. Solace for the past. We are dazed by the world and we try to understand it by finding patterns - repetitive events which might help us know the future.

Like the constellations scattered in the sky, we imagine patterns in our everyday life. We assume causality and order on more occasions than one as we try to explain the world. We forget that the constellations in the sky are only products of random chance and not really organized structures and patterns. We forget that we are bound to find some order or pattern even though the world is driven by randomness. Our mind tricks us by locating these patterns in pure chaos. We then hold on to that pattern and build our lives on it. We forget that the pattern was nothing but our imagination. Our error lies not in perceiving the pattern but in ascribing more meaning to it than should be.

Most people believe in a grander scheme of events to unfold, giving purpose to their life, as they seek order in disorder. Some realize the force of randomness in their lives but do nothing as they hope that their understanding is indeed accurate. Some realize the truth and strive to over come the tricks that the mind plays.

As for me, from a child who believed in destiny to a hopeful skeptic now, I've been through the phases. And as i move ahead, I strive harder and harder to accept the role of randomness in shaping our lives.

A time to pause..

I think the things I own and love
Acquire a sense of me,
That gives them value far above
The worth that others see.
My chattels are of me a part:
This chair on which I sit
Would break its overstuffed old heart
If I made junk of it.

To humble needs with which I live,
My books, my desk, my bed,
A personality I give
They'll lose when I am dead.
Sometimes on entering my room
They look at me with fear,
As if they had a sense of doom
Inevitably near.

Yet haply, since they do not die,
In them will linger on
Some of the spirit that was I,
When I am gone.
And maybe some sweet soul will sigh,
And stroke with tender touch
The things I loved, and even cry
A little,--not too much.

Robert Service

Science is the answer for all problems .... True or False ???

This post takes off from a question and an ensuing argument that I had with a friend almost a year back. Posed with a question of what is science and whether science can explain everything, i ended up starting a trail of thought that i have nurtured for a year now...

Posed with the question of "What is science ?" over a simple lunch , I answered, science is a method of inquiry. From then on, I have wondered ever so often, if this is the right definition and every time i have concluded that this is the best i can come up with for now... Science is after all a method of inquiry where observation and hypotheses are used to arrive at a testable theory.

The next question is more tricky.

As a scientist my impulse "should have been" to say that science is indeed the answer to all our questions but then here i hesitated. This of course resulted in a tiff of sorts (because the poser of the question who was a true blue scientist and was certain that science is the answer to all questions)...

In the months that followed, I have tried to formulate my opinion and find my ground.

From my perspective, I see two schools of thought in addressing this question.

The first is of course is the line of thought that science is the answer to all our questions and that we must make it a way of life. This group is an unrelenting champion of the power of science and rationality. They want to rest their statements on objective facts, statistics and numbers and not on subjective observations and interpretations. Here the attempt is to explain every behavior, every like or dislike, every structure with a 'seemingly' rational thought. There is no place for feelings, instincts, biases etc etc.

The second school of thought is a rather convenient one... because, all it says is that science cannot possibly answer all questions. Questions pertaining to religion, morality, conscience and consciousness are beyond the purview of science and perhaps should be such. Science in this case becomes a mere tool to gain technology - a means of simplifying life. Science is not a way of life here and people are happy with terms like belief, faith, morals, unknown, too complex to understand, culture etc etc. This school of thought, implicitly supports a reliance on metaphysics and supernatural to "explain" everyday phenomena or call them as too complex to understand.

Now, where do I stand on these conflicting opinions and schools of thought ?
I think I have found a middle ground which in this case is a very thin line separating the two sides and a slight trip or slip on my part could very well push me to one extreme or the other. I however will attempt to present my case here.

Science is a method of inquiry - the best we have come up with so far!
It helps us develop a framework to arrive at universal facts and truths. It aims to remove subjectivity, and the bias that arises due to interpersonal variation, observation and interpretation. It tries to replace subjectivity with objectivity. But while the aim of scientific investigation is laudable, its means are flawed. They are flawed by their nature and this became clear to me when i read about the black swan paradox and Karl Popper's views of the fallibility of science.

What is the black swan paradox ?

"It is a demonstration of the fallibility of the empirical methods of scientific observation. Europeans for thousands of years had observed millions of white swans. Using inductive evidence, we could come up with the theory that all swans are white. However exploration of Australasia introduced Europeans to black swans. Poppers' point is this: no matter how many observations are made which confirm a theory there is always the possibility that a future observation could refute it. Induction cannot yield certainty."

The problem with science is that it is based on such empirical observations and these can never be absolutely certain. They can only increase the probability of you being right progressively. The method of science is what is flawed. I agree with Popper, when he was critical of the naive empiricist view that we objectively observe the world. Popper argued (and I agree) that all observation is from a point of view, and indeed that all observation is coloured by our understanding. The world appears to us in the context of theories we already hold: it is 'theory laden'. All our theories today are based on older theories. We are all standing on the shoulder of giants, as is often very rightly acknowledged. But this also means that using the wrong theory as the basis only weakens the whole infrastructure of science - it becomes akin to a house of cards.

The other problem one often sees especially in biological sciences is the problem of causation. It is difficult to say what is the cause and what is the effect with great certainty ? For example, does cancer lead to high levels of protein A or does high level of protein A lead to cancer ? This problem becomes more acute when one tries to decipher the past from traces buried in the dust of time as happens in the fields of evolutionary biology. In human evolution, did an increase in brain size result in an erect posture or did an erect posture, give the hands more to do and thereby result in an increase in brain size... ? Questions such as this and many more in evolutionary biology, sociobiology, evolutionary psychology etc border on pure speculation simply because evidence is scanty and incomplete.

Another limitation of science is technology. Science is heavily reliant on the available technology. Our investigations in science are limited by the available technology. In the last century, electrons, protons and neutrons seemed to be the indivisible components of all matter. But with the development of synchrotron and particle accelerators, we now have an ever growing list of sub-atomic particles. Technology has influenced what we know anD perhaps what we can know as well. This is also true in biology. In our attempt to understand a system, we tinker with the system, say for example, to understand the role of a protein, we over express or knock-it down in the cells and see how the system is altered. This approach again has inherent flaws. Removing a particular protein may not give an observable phenotype for many reasons :

- the protein can work even in very trace amounts
- there are other proteins (homologs) which could compensate
- the protein is essential only under particular conditions. And there can be many conditions here - embryonic state, high slat, low, salt, aging, high temperature, low temperature, dehydration, low nutrition, etc etc)... so, as can be seen, we can never be absolutely certain of all the functions of a protein through such approaches.
- proteins may have different functions under different conditions and in different organisms.
- a protein may behave very differently in an animals (in vivo as biologists like to call) than in the tissues and cells that are used as models in vitro

These simple examples, I hope do enough to elucidate the point that there are inherent caveats in the method of inquiry adopted by science.

Questions of the mind, such as consciousness, conscience, language, behaviour, binding, spatio-temporal integration, creativity, etc etc are all complex, open questions to which we dont have the answers still. In fact, there are also schools of scientists who that say that we cannot have answers to some of these questions.

But here I need to draw a line and state that this does not mean my implicit support to the second school of thought that holds science as only a source of technology. The inherent flaws in our method of scientific inquiry does not mean that "no inquiry" is better.

It does not mean that irrationality, superstition, dogma, speculation and faith should replace empirical testing. It just means, that we as scientists, should acknowledge the weaknesses in scientific method and work on correcting them. It means that we as scientists should be open to criticism and skepticism and we should work on strengthening our method.

So for now, I guess, the middle ground is where I am.

I see that science does not have all the answers, not now and maybe will never have.... but it is our best bet to get as close to truth as we possibly can. It is a method that aims to arrive at universal truths through empirical observation and rational thought. It is a method that has flaws but is definitely superior to reliance on pure speculation, faith and beliefs.

I guess, more than science, we should champion for a scientific temper, where people are open to alternative opinions, theories and paradigm shifts.... because thats what ultimately propels science forward.

Surprise...

It was a lazy morning,
that had me yawning...
I was on a bus ride from home,
that had me sitting like a lost gnome.

And then there was a harmless conversation,
that led to the inception of a plan beyond my wildest imagination.
It was a great conspiracy,
And so I found a partner to work with great secrecy.

The plan was made,
and the plot was laid...
Off we went on our tiny escapade,
from the everyday mundane, to form the surprise action brigade...

With a lot of excitement, and plans galore,
Off we went on the streets of Bangalore.
Armed with balloons and streamers,
we were two dreamers.
On the list, were also tiaras and wands,
To take two pretty angels to faraway fairy lands.
Next on the list was a chocolate cake,
which we couldn't wait to partake.

And then, at the appointed hour,
phone calls were made to the gang of four.
Lo and behold, there was a pop to surprise,
This was a party in disguise.

There was laughter and smiles with truck loads of fun...
All under the afternoon sun.
Candles were blown and cakes were cut,
It was a fabulous way to get out of the rut.

And then there followed a wild road chase
Through the city, we had a clock to race.
We landed in time, all jubilant and resplendent,
It was after all a dinner with a Rogue elephant...

It was night to remember,
with memories to cherish forever..
beautiful moments captured,
that left us all enraptured....

Oh what a day it was... :)



PS - It was a wonderful day. A day good enough to compel me into undergoing some public humiliation like this with such juvenile attempts at rhyming words... :-)

A memory trace and a bloodline...

She sat there in front of me, frail and tired after a day of ceaseless travel through a city that is bursting at its seams. She has traveled from the north to the south, and across, all over this city. She came back home, saw me and her face burst out into a gentle smile that did not disappear for a very long time.... A smile that came despite the weariness...

She was my surrogate grandmother.
I haven't seen my paternal grandmother since she died early - early enough, that she did get to see her eldest son (my dad) growing up from the young lad that he was then. This was my grandmother's sister. We've met them all through our travels in the summer vacations during school days... but these were all fleeting meetings which did not do much to leave a strong neural imprint in my mind.

But then this was a different meeting. I met them after sooo long and I felt their hand rise up to bless, and it was beautiful.... It seemed like the most natural thing in the world to have their hand on my head !! As she beamed on seeing me, I knew that some bonds just cannot be broken despite distances.

The ties of the bloodline are strong. They leave their seed and no matter how ill cared it may be, it grows into a tree. It has a resilience which is mind-numbing. There is a love which comes because of that knowledge of shared lineage.

It was a beautiful moment. A moment that made me want my grandparents to be there!
A moment that made all inconvenience disappear for me and for her.

She was hard on hearing as age was fast catching up with her, but her eyes were still burning bright. She still spoke nineteen to a dozen trying to convince me to not sleep on the floor and offering to sleep on the couch instead. She tried her best to convince me about getting married. She had ceaseless questions.

She was my surrogate grandmother.

She made me miss my grandmother. I missed having one to tell me stories, to narrate anecdotes, to play with me and to sleep on. To oil my hair and to cook all the wonderful things that grandmothers do...

I am not sure how it will be having a grandmother around full time (with the incessant marriage advice and the correcting) but i sure know that, for that one day, I wanted one too. She made me want to leave my head under her palm and to not let go. Frail, though she was, I felt protected by her. It was amazing and it is nothing but the wondrous ways of nature.

I sit her typing these words hours after they happened only to try and freeze the essence of that meeting into words, so that years from now, I can still pull on that same string and retrieve the same memory trace, not like a pensieve but hopefully not too far from it too.

Disconnect...

In a world that is fast shrinking, people are becoming farther and farther away. It is a conundrum that I fail to understand.

The World has become one in more ways than one. The diversity in culture, language, attires, festivals, food, music and literature is all coming to an end. We are building uniformity in every sense. Uniformity in abilities, in culture, in knowledge, in thought processes, in social structures, in amenities, in income groups and in living conditions. Happenings across the world are at our finger tips with the advent of technology. These are developments with their own brighter and darker sides... each one too complex to delineate from the others.

But despite so much connectivity and homogeneity, each man is an island today connected to the others through nothing but the World wide web. He is a rootless being as he is capable of going to any part of the world and feeling at home. Or perhaps, he never finds his true home! His life is nomadic, adrift with the tides of time and development.

He spends his days hooked onto the internet and his gadgetry updating his status and whereabouts ever so often... People like me end up writing about their thoughts and ideas on a public platform than just talking... :-)

This is something I fail to grasp. Despite the increasing connectivity on the internet, there is a sense of growing disconnect between people.

People are happy chatting over the internet and the phone than in person. It seems easy to laze around watching TV than to go for a social activity. Social gatherings have become a thing to endure than really a celebration that they once were. People are unable to sit with company without fidgeting with their PDA to update their status message or their blog. Be it a simple dinner, a pleasant sight or a wedding, we waste no time in sharing it with others. There is a need to connect with people but there is also a fear to really connect.

And what happens is that eventually, we end up connecting anonymously over the World Wide Web.

Why ?

Why are we letting this happen ? Why are our social structures disintegrating ? Is it the rapid pace of development which is pulling apart people and generations faster than they can come together. Why is there this constant need to stay in touch but still a little aloof, a little away ? Is our fear over powering our social nature ? What are we trying to achieve this way ?

Beats me...

The un-shed tears...

A sorrow melts into a tear drop and flows out of the heart into the universe...
But what happens to those unsaid sorrows and the un-shed tears ?

Do they well up inside to finally flood through your defenses ?
Or Do they percolate through our being to soak up our joys too ?

Do they just disappear with out a trace like a dew drop in morning sun ? Or
Do they fester inside like the pus in a boil ?

Do they drown your joys like the little paper boat sailing in the first rains ? Or
Do they just keep your withered heart tender and moist against the sun burning down on it ?

Do they flood through your being and ravage it like a savage beast ? Or
Do they quietly and silently seep within you to never resurface again ?

Are they strong like the waves of the ocean to leave you adrift ?
Or are they like the ripples on the pond that gently sway your way ?

Are they like the waters of the pond that are rustled by the slightest winds ?
Or do they stay frozen in the core of your being untouched and unaffected by all ?

Do they sweep you off your feet like an angry tornado ? Or
Do they leave you stagnant like a muddly puddle ?

Do they flow in your system like the slow poison that kills you over the years ?
Or do they, burst forth and spew out like an angry volcano ?

What happens to those un-shed tears ?

Thank you... :-)

Some one once said that all great things come in small packages. I knew it was true but I truly understood the saying over the last week as I found these tiny bundles of happiness and thoughts, left at my doorstep by a friend...

Tiny notes, post-its, tiny but thoughtful gifts, messages... they brightened up my day no matter what had happened before... !!! They were notes which told me someone cared... and that someone knew me for what I am...

This is a feeble attempt to express gratitude to the friends who've made my world a better place... who've been with me through thick and thin and who've made me believe in myself... Who've taught me to see the brighter side of things even when there is hardly any and who've made things better by just being there... :-)

Thank you by Dido...

"My tea's gone cold, I'm wondering why
I got out of bed at all
The morning rain clouds up my window
and I can't see at all
And even if I could it'd all be grey,
but your picture on my wall
It reminds me that it's not so bad,
it's not so bad

I drank too much last night, got bills to pay,
my head just feels in pain
I missed the bus and there'll be hell today,
I'm late for work again
And even if I'm there, they'll all imply
that I might not last the day
And then you call me and it's not so bad,
it's not so bad and

I want to thank you
for giving me the best day of my life
Oh just to be with you
is having the best day of my life

Push the door, I'm home at last
and I'm soaking through and through
Then you hand me a towel
and all I see is you
And even if my house falls down,
I wouldn't have a clue
Because you're near me and

I want to thank you
for giving me the best day of my life
Oh just to be with you
is having the best day of my life "

From the lasts to the firsts.....

It is a time for change and I see it knocking on my door.
As I pack one life into boxes to be stowed away, I pack another future into boxes to be carried with me.

Books, clothes, papers, cards, pictures.... each has a story associated with it.
A story that was a part of my life.
A story that led to another and finally brought me to where I am.
Stories of people, of ideas, of tales, of questions, of answers, of dreams and of conversations....
Stories of friends and strangers, of laughter and pain, of excitement and of despair, of the smiles and the tears... they all made me who i am.
They brought me to this day.

Stories... that I cherish but I am worried that I will forget, in the daily grind of the future. Stories that I want to hold onto for the rest of my life. People and memories, that I want to hold onto for the rest of my life.

As I pass through these days, I try and cram these moments of everyday mundane into my mind because i know not if and when things will be like this again....

I prepare for the future as I run through the days.
Everything feels like the last - the last meal with friends and family, the last Diwali, the last Puja, the last visit to the markets with a camera, the last home cooked meal, the last walk on campus... there is a sense of end associated with every good thing that even happy moments end with a tinge of sorrow... Every tick on the checklist only brings me closer to a future that takes me away from a past I cherish.

People say the future holds great promise and that I will meet more friends and that things will fall in place...

Maybe I will. But they don't realize that somethings cant be replaced. That somethings are an integral part of you and that when taken away, they leave you incomplete.

Maybe I will fill this emptiness eventually... maybe some parts will grow back...

But, one thing is for sure that the last five years of my life have redefined me and have helped me discover myself. And in these five years, I have become a part of somethings bigger than me and a lot of things have become a part of me...

And as I walk away from a past, I take these parts as the building blocks of a new future.

And very soon perhaps, the lasts will be replaced by the firsts... and perhaps, I will find my joys there too...

Expressions....

This is an era of expression. People are encouraged to express everything they feel no matter how transient or how permanent the thought or emotion maybe...

I however find myself a bit lost in this world simply because I am not a believer in words and words alone. To me actions always speak louder than words and so it is difficult to elicit words out of me... People keep telling me the value of expression ever so often. The constant refrain of friends is that I don't express myself enough... and that all the many things I think or feel are often lost in the unsaid.

I have come to accept the charge without protest simply because no matter how hard i try, I am not able to fit all my feelings and thoughts satisfactorily into words... actions always seem to do the job better. Some people learn to understand that actions speak louder than words and get used to the wordlessness from me, but some forever fail to grasp me or my mind...

People say, how hard can it be to say - "I care" or "I love you" or "I am sorry" and I feel like telling, that it is very hard... !!! It is easier to just implement what you feel... to do something for the special few, to let them peer into your mind and be privy to your thoughts and emotions, to let them see the real you with all your weaknesses and to be able to do anything for them, to listen to them because they are the most important people and to not hurt them.

How do words convey all this better ?

To a lot of people, words are just a means of communication. They are evanescent carriers of thought.

But, I am scared of the power of words. In relationships, our emotions are wrapped around our words and they have the power to mould our lives... Their power must be used with great care... and with this power comes great fear. Fear of being wrong, fear of saying too much, too soon or too little, too late... fear of not saying the right words or of saying the right words at the wrong time, fear of saying things which you do not mean... these fears thus paralyze me and I choose the easier, wordless way.

I'd much rather be around and DO the right things than just say the right things... but this is very difficult for most to accept.

And as I type these words, I understand the need for words... We all like to be told that we are liked, loved and cared for. Even though it is implicit in some actions, we'd much rather be told the obvious than be left with the fear that we are guessing wrong. Such wordless understanding only results from complete confidence in the relationship and a deep understanding, both of which do not come easy.

But today, as i write these words, I hope to say to the people that I care about, that I really do care for them. And also that my wordlessness is a part of me that I aspire for in every relationship. It suggests complete acceptance and implicit understanding. It places faith in relationships more than in words.

However, on this platform... I have taken my first baby steps at expression. I try to shed my fears and inhibitions to embrace words and I have made my first attempts at leaving my mind open to scrutiny. It still doesn't open my mind for the world to see, but, those who matter, manage to view the world inside through the tiny cracks that exist...

And as I choose my words here, I hope to make a beginning...

A beginning to be able to use words more often to say to the people I care about that "I really do care"....

And If I have stayed quiet and never said this before, its not because I don't care but simply because I find words insufficient at times.

Footloose... :-)

Traveling is something I have always fancied. It is a long standing dream of mine to travel the world. So when someone once asked my why I love traveling, the question sounded strange in a very big way. It was something I had so wanted for so long that I never questioned why I wanted it... ;)

Strange as it may sound, this question really made me ponder and every time i read a travelogue or wanted to visit a place, I tried questioning myself. At the end of nearly a month, I realized that every time I read about a place or a person, I wanted to see that place or person with my own eyes. I wanted to watch the world that groomed him and the world that he shaped. I was never happy with these second hand accounts of people and their places, of the food they had and of the experiences they had. The vignettes of the world only whetted my appetite for travel more than ever.

I never wanted to accept it when someone said that Venice is beautiful with its inland waterways that connect the city like the roads that do here. I wanted to experience the magic, the history and the romance of that city before I decide whether or not to like it.

I realized that i will never be happy with people and their experiences. I want to travel by the Gondolas, see the Venetians going about their business, traveling on boats. I want to experience the local history and the local cuisine. I want to live first hand everything that I have read and heard about this charming city.

I want to see and feel the pulse of the town which in someways is a depiction of man's victory over nature, of mankind's strength and intellect and perhaps mankind's eventual downfall (Venice is a rapidly sinking city and the recent green house effect is only hastening its demise).

Imagine a group of fleeing citizens deciding to build a new city on water to defend themselves and their property. Imagine them becoming a huge enterprising society of traders as they built a whole new city in the marshes by making wooden stilts all the way through. That is amazing ingenuity! Who at that time would have predicted that a group of people, escaping the raiders would end up becoming one of the richest states, supplying luxury goods to the whole of Europe and leaving their mark on world history for decades to come !! That is Venice, which is today called the romantic capital of the world. With its modest beginnings, Venice reached its peaks of glory and then succumbed to the vicissitudes of pleasure as it became the pleasure capital of the world and then disappeared of the world stage. Today it stands as a popular tourist destination due to its inland water ways... but people rarely find out about the beginnings of this city and its growth.

But this is the history that fascinates me.
The progress of a city from its birth on water through nothing but human skill and labor to its becoming the pleasure capital of the world and ultimately its slipping into oblivion (I mean Venice is not really a hot tourist destination... its popular but this popularity is nothing compared to its life in the last century!) .

I want to travel the world but not just to experience the Eiffel tower at night or the Swiss Alps in snow, but to live the world and to become one with the world. I want to travel through the streets of Morocco, through the ruins of Machu Pichchu and Mohenjodaro, through the wilderness of african grasslands to the present day bustling cities of New York and Manhattan. I want to see the world and the people that make it, in light of their past and their history.

I want to see the mountains and the hills, the seas and the oceans, the deserts and the oases, the grasslands and the forests... I want to make them all a part of me and I want to become a part of them.

Now, this question only left me wondering about how someone cannot want to see the world and know about all its peoples and cultures... But, i know people are different and this is just one of the many differences that can possibly be...

I guess, I am a traveler who revels in the learning and whose passion for photography only adds to the wanderlust. I guess, I am a little footloose in wanting to explore the world but it at least gives me a whole lot to look forward to. It gives me a dream and It makes the means worth the end... :-)

From the bench to the bedside...

I have spent a significant part of my doctoral work on the role and effects of a protein on the development and progression of a form of brain cancer called as "Gliomas". All this work of course was carried out in a premier research institute in India. Now, the work, since it involves a human disease, requires the involvement of patient samples, patient follow ups, tissue material, surgical intervention and a standardized treatment protocol. Unlike the west where medical research is carried out as part of a hospital and MD/PhDs constitute a large chunk of the researchers; In India the situation is quite different. Research in India is carried out with a complete disconnect from the medical community. Researchers and doctors have completely different training profiles and work platforms and there is minimal interaction between the two.

In this blog, I am trying to give a broad overview of this field and the work involved in it from the perspectives of all concerned. The intention of course is to highlight the fact that there is huge disconnect between the three groups of people involved in finding the cure to any disease - the researchers, the patients and the clinicians (I haven't yet involved the industry and the drug developers but they are a vital component of an translational research that needs to be taken from the bench to the bedside (as it is popularly stated!).

Now gliomas, as the name suggests are tumors of glial origin. The human brain is made up of billions and billions of neurons but these neurons cannot function and exist on their own. So the head on top that we all should be using (but are not always) is actually made up of billions of and billions of neurons and of many of these supporting cells called as astrocytes and glial cells. Now, as with any tumor, gliomas are named so because of their cells of origin - which are the glial cells. They arise because, somewhere deep in your brain, one cell is rebelling against the normal structure and has decided to be selfish and proliferate.

This errant cell, if left unchecked, will soon grow into a huge mass of cells all behaving the same way. A normal cell in the body becomes errant because it has accumulated some mutations - mutations which make some normal cellular proteins to lose their normal function or to alter their roles in the cell. A single cell usually requires multiple mutations before it gains the ability to proliferate uncontrollably - or as the scientists say to become transformed. This errant cells will now begin an epic journey as it divides and divides, ignorant of all other restrictive signals and indications. During these multiple rounds of divisions, more mutations are acquired all through the darwinian principle of evolution. Thus, a cancer cell, which acquires mutations favoring its growth and survival will multiply and give rise to more similar daughter cells. Like the parent cell, these progeny would also acquire the ability to migrate and move in search of better nesting grounds. But, we must not forget that this errant glial cell is actually in the brain and therefore cannot move out (for the novices, the brain, in view of its vitality has a impervious blood brain barrier which prevents the free exchange of materials from the rest of the body to the brain - this is one reason why not all chemicals and drugs will enter the brain). So what does it do ? It spreads its family through the existing brain and we will soon find that a widely infiltrating tumor will spread its way through the normal brain cortex. Soon however this massive proliferation will affect the normal brain and its functions.

The increasing intra-cranial pressure and destruction of the normal cortex ultimately result in multiple symptoms. Patients begin with symptoms like headache, nausea, weakness in extremities, dizziness, seizures, vomiting etc etc. Now we can all understand that all these symptoms can only arise pretty late into disease progression. By this time the brain is actually riddled with bad tissue arising from these errant clones. Patients also tend to ignore these symptoms till they are actually unbearable and things are not easy for a clinician too (I mean how many people immediately go for a doctor and an MRI when they have a headache - they suspect eye trouble, migrane, fatigue, stress etc etc till it becomes unbearable.

A clinician also has a number of possible neurological disorders to rule out before he can actually diagnose a tumor. An MRI needs to be done to detect and confirm the presence of a tumor and we all know that it is not an inexpensive proposition that will be one's first line of inquiry. Thus, by the time a glioma is diagnosed it is fairly advanced. Now once diagnosed, the first step is to remove the tumor mass but by this time large numbers of tumor cells would have actually infiltrated into the normal brain matrix thus making the excision very difficult.

Also making matters more difficult, the brain unlike the other organs of the body is a vital organ where complex functions are performed over very small regions. And we don't know with great clarity what all the functions are and where all they are localized? This is quite unlike other organs like the liver, the colon, the breast or the prostate. where we have more information and functions are redundant. So, now a surgeon is faced with the challenge of causing minimal invasion and removing the maximum tumor tissue possible. However, with great skill and with the aid of modern technology (like MRIs) a surgeon manages to pull out the tumor region from the brain to achieve what is called as a maximal safe resection.

Now this surgery is verified by an MRI (not the cheapest of techniques and noes not have a very good spatial resolution as well) and the solitary wandering cells will escape detection by this technique till they grow back as more vigorous tumors.... The next step after surgical intervention is radiotherapy. In this the patient is subjected to high doses of radiation to eradicate any errant tumor cells left behind. The last possible intervention in treating a glioma involves chemotherapy. This too is a tricky problem because the brain (being the special organ it is) is not freely accessible to all drugs and chemicals. Only a select family of drugs can actually access the brain through the blood-brain barrier - again limiting the treatment options. The current standard of care involves the use of Temozolomide, an alkylating agent (which adds alkyl groups to the DNA thereby damaging the DNA and the cell) as the single most commonly used chemotherapeutic agent for treatment of gliomas.

Now like all the other cancers, this toxic chemical will also cause multiple side effects as it will also affect normal brain tissue and other organs in the body. This is the extension of the agony for the patient and his family. Now depending on the severity of the disease, the time of diagnosis, the extent of infiltration, the effectiveness of the surgery, etc etc the tumor could respond differently to the different treatments in different patients. At this time now a pathologist needs to get a sample of the tumor to grade it such that the patient, his/her family can be informed of a predicted course of the disease to some accuracy. Every tumor is graded into different stages depending on how much the tumor has advanced. In an early tumor, the tumor cells would not have invaded deep into the normal brain and would be easy to resect. Also there will be lesser diversity in the types of tumor cells as they will be closer to the progenitor errant cell. These factors along with others make the low grade tumors easy to treat unlike the higher grade ones.

In gliomas, the tumors have been divided into 4 types according to the severity and the progression of the disease. Grade I and II tumors are the easiest to resect because they are still in the form of a compact mass. The cells in these tumors have still not started spreading and expanding their reach in the brain. Once resected mild chemo/radiotherapy can prevent the tumor from recurrance and patients are known to live for a very long time (atleast 10 years : While in absolute this is not a long time, considering the prognosis of a more malignant glioma this is actually really good). The grade III gliomas are more advanced and they show infiltration into the normal brain cortex which can be seen in an MRI as well. While surgery helps, further radio and chemotherapy only manage to provide a 2-3 year extension to the patient. The grade IV gliomas, on the other hand are the most malignant forms of this cancer. They show massive infiltration into the normal brain, extensive vascularization, nuclear atypia etc etc. Despite the extensive research happening in this field, the present day treatment only provides a median survival of a year to the patients and there are hardly any cases of complete remission. Even for the grade I and II tumors, the patients usually develop grade III or grade IV tumors within the next 5-10 years and succumb to the same fate. The disease thus only has a fatal prognosis and the only difference possible lies in the extent of fatality.

Imagine from the prospect of a family and an individual the kind of uncertainity and trauma that such a diagnosis can unfold. Imagine being told that you need to have a surgery the consequences of which can never be completely ascertained. And after the surgery, your system will be bombarded with toxic chemicals which will have side effects and all this will extend your life by a couple of years at max. The expense incurred is another aspect which takes the therapy beyond the reach of many in our country. To worsen the situation, its your brain which is targeted to all this trauma. The organ which defines you and your existence. Such massive invasion of the privacy of the brain only leaves behind side effects on the mind.... I am writing all this not to discourage people from undergoing a treatment because they should and at least it prolongs their life by a year to a decade. That can be valuable to any individual to organize their life and facilitate their family's existence.

In the present model, once diagnosed by a pathologist, the patient begins a standardized therapeutic regimen under the guidance of a qualified oncologist. His treatment is followed through a routine MRI imaging and the treatment is modulated accordingly. We as researchers access the tissue through the surgeons as part of single consortium. The tissue from the tumor is bisected into two halves and snap frozen. One half is used for the isolation of RNA, protein, DNA etc which enable us as researchers in molecular biology to study the disease. The other half is provided to the pathologist where the tissue is fixed and processed to develop tumor sections which can be used to grade the tumor and study the expression and localization of select proteins. The study begins with large scale profiling of RNA, DNA, proteins and microRNAs whose expression is compared across normal brain samples and the different grades of gliomas. The candidate genes are then studied in cell culture models to identify their functions in tumor development. The study is further extended to animal models of the disease where the role of the gene in the disease is studied and validated. The ultimate aim of us researchers is to try and identify novel methods of diagnosis and prognosis to predict the course of the disease and to identify novel molecular targets for therapy. The development of novel drugs based on these studies would be the ultimate and ideal culmination of an entire such study.

However as researchers, we need to be aware of this personal apsect of every disease all through our studies. For doctors, each individual should be a human being and not a mere case to follow a standardized treatment protocol. His needs, his comfort, his discomfort, his financial situation, family - all these aspects need to be considered as part of the treatment protocol. For researchers such as me, the disease, the patient and the prognosis should mean more than numbers, statistics, jargon and a degree at the end. The need of the hour is to develop treatment protocols and that cannot happen by pure research in a laboratory. What is needed is an inclusive interaction between the patients, the doctors and the research community.

I stress on the inclusion of the researchers because being one myself, I see that we are living a complete disconnect with the patients. For us the patients are cases who have died and whose tissue is what we need to work with. It is a sad spectre but it is true because unless an until there is an emotional connect, we tend to lose perspective in our mad rush for the end. A researcher aims for results, publications, patents, grants and degrees. He is untouched by the miseries that haunt the hospital corridors, the traumas that people have to face. True to human nature, we stay in a state of complete disconnect until forced to face reality by a personal experience.

Such a model also breeds differences between the clinicians and the researchers because both are unaware of each other's skills and both end up presuming their indispensability and supremacy to the task on hand. What is needed is a model like in the United states where research is carried out within or in close connect with the premises of a hospital. This will not only ensure a first hand understanding of the disease and its symptoms to the researchers but it will also ensure a real understanding of the problems plaguing the clinicians. It will also allow easy access to the patient resources to the researchers in addition to providing clinicians with greater access to the developments in the laboratory.

Light that shines...

In my search for the monologue of Roark (the main protagonist in the Fountainhead), I chanced upon this other conversation between Howard Roark (HR) and Gail Wynand (GW) .This is a glimpse of that conversation which these two very different men share on a yatch, under the blue skies, free from the presence of the rest of the world. A world which does not understand them and a world that does not accept them. They have both lived their lives their own ways... one indifferent to the world and one trying to fight the world by gaining more and more power. These two men share these very different approaches to world and the people in it and yet they have a common thread which binds them. Both share a complete disregard for the opinion of the masses and both have lived a life on their own terms. They share an understanding that is deep and all pervasive. There is a bond between the two men from when they meet for the first time. They share camaraderie and respect for each other that defines their friendship. The difference in their ideologies is very visible in the following conversation but there is also a great affection which binds them despite the differences.

Wynand is talking about Selflessness in the absolute sense as preached by Ellsworth Toohey. He is of the opinion that true selflessness does not exist and Roark contradicts him and the conversation that follows is a masterpiece in english writing.

HR: The thing that is destroying the world. The thing you were talking about. Actual selflessness.

GW: The ideal which they say does not exist?

HR: They are wrong. It does exist - though not in a way they imagine. Its what i couldn't understand about people for a long time. They have no self. They live within others. They live second-hand. Look at PK.

I've looked at PK - at what's left of him - and it's helped me to understand. He's paying the price and wondering for what sin and telling himself that he's been too selfish. In what act or thought of his has there ever been a self? What was his aim in life ? Greatness in other people's eyes. Fame, admiration, envy - all that which comes from others. Others dictated his convictions, which he did not hold, but he was satisfied that others believed he held them. Others were his motive power and his prime concern. He didn't want to be great, but to be thought great. He didn't want to build, but to be admired as a builder. He borrowed from others in order to make an impression on others. There's your actual selflessness. It's his ego that he has betrayed and given up. But everybody calls him selfish.

GW: That's pattern most people follow.

HR: Yes! And thats the root of every despicable action? Not selfishness but precisely the absence of a self. Look at them. The man who cheats and lies, but preserves a respectable front. He knows himself to be dishonest, but others think he is honest and he derives his self-respect from that, second-hand. The man who takes credit for the achievement which is not his own. He knows himself to be mediocre, but he's great in the eyes of others. The frustrated wretch who professes love for the inferior and clings to those less endowed, in order to establish his own superiority by comparison. The man whose sole aim to make money.Now, I don't see anything evil in the desire to make money. But money is only a means to some end. It man wants it for a personal purpose - to invest in an industry, to create, to study. to travel, to enjoy luxury, he's completely moral. But the men who place money first go much beyond that. Personal luxury is a limited endeavour. What they want is ostentation: to show, to stun, to entertain, to impress others.. They're second-handers. Look at our so called cultural endeavours. A lecturer who spouts some borrowed rehash of nothing at all that means nothing at all to him - and the people who listen and don' give a damn, but sit there in order to tell their friends that they have attended a lecture by a famous name. All second-handers.

GW: If I were Ellsworth Toohey, I'd say: aren't you making out a case against selfishness? Aren't they all acting on a selfish motive - to be notice, liked and admired.

HR: - by others. At the price of their own self respect. In the realm of greatest importance - the realm of values, of judgement, of spirit, of thought, they place others above self, in the exact manner which altruism demands. A truly selfish man cannot be affected by the approval of others. He doesn't need it.

I think Toohey understands that. Thats what helps him spread his vicious nonsense. Just weakness and cowardice. It's so easy to run to others. It's so hard to stand on one's own accord. You can fake virtue for an audience. You can't fake it in your own eyes. Your ego is the strictest judge. They run from it. They spend their lives running. It's easier to donate a few thousands to charity and to think oneself noble than to base self-respect on personal standards of personal achievement. It's simple to seek substitutes for competence - such as easy substitutes: love, charm, kindness, charity. But there is no substitute for competence.

That, precisely, is the deadlines of second-handers. They have no concern for facts, ideas, work. They are concerned only with people. They dont ask: "Is this true?" They ask:"Is this what others think is true?".

Not to judge, but to repeat. Not to do, but to give the impression of doing. Not creation, but show. Not ability, but friendship. Not merit, but pull. What would happen to the world without those who do, think, work, produce? Those who are the egotists. You don't think through another's brain and you dont' work through another's brain. When you suspend your faculty of independent judgment, you suspend consciousness. To stop consciousness is to suspend life. Second-handers have no sense of reality. Their reality is not within them, but somewhere in that space which divides one human body from another. Not an entity but a relation - anchored to nothing. That's the emptiness i couldn't understand in people. That's what stopped me when i faced a committee. Men without an ego. Opinion without a rational process. Motion without brakes or motor. Power without responsibility. The second-hander acts but the source of his actions are scattered in every other living person. It's everywhere and nowhere and you cat reason with him. He is not open to reason. You cant speak to him - he can't hear. You're tried by an empty bench. A blind mass running amuck, to crush you without sense or purpose.

GW: I think your second-handers understand this, try as they might not to admit it to themselves. Notice how they'll accept anything except a man who stands alone. They recognize him at once. By instinct. There's a special insidious kind of hatred for him. They forgive criminals. They admire dictators. Crime and violence are a tie. They've got to force their miserable little personalities on every single person they meet. The independent man kills them - because they don't exist within him and that's the only form of existence they know. Notice the malignant kind of resentment against any idea that propounds independence. Notice the malice towards an independent man. Look back at your life Howard, and at the people you ve met. They know. They are afraid. You're a reproach.

HR: That's because their sense of dignity always remains in them. They're still human beings. But they've been taught to seek themselves in others. Yet no man can achieve the kind of absolute humility that would need no self esteem in any form. He wouldn't survive. They're still human beings. But they've been taught to seek themselves in others. Yet no man can achieve the kind of absolute humility that would need no self esteem in any form. He wouldn't survive.

They're still human beings. But they've been taught to seek themselves in others. Yet no man can achieve the kind of absolute humility that would need no self esteem in any form. He wouldn't survive. So after centuries of being pounded with the doctrine that altruism is the ultimate ideal, men have accepted it in the only way it could be accepted. By seeking self-esteem through others. By living second-hand. And it has opened the way for every kind of horror. It has become the dreadful form of selfishness which a truly selfish man couldn’t have conceived. And now, to cure a world perishing from selflessness, we’re asked to destroy the self. Listen to what is being preached today. Look at everyone around us. You’ve wondered why they suffer, why they seek happiness and never find it. If any man stopped and asked himself whether he’s ever held a truly personal desire, he’d find the answer. He’d see that all his wishes, his efforts, his dreams, his ambitions are motivated by other men. He’s not really struggling even for material wealth, but for the second-hander’s delusion--prestige. A stamp of approval, not his own. He can find no joy in the struggle and no joy when he has succeeded. He can’t say about a single thing: ’This is what I wanted because I wanted it, not because it made my neighbors gape at me.’ Then he wonders why he’s unhappy. Every form of happiness is private. Our greatest moments are personal, self-motivated, not to be touched. The things which are sacred or precious to us are the things we withdraw from promiscuous sharing. But now we are taught to throw everything within us into public light and common pawing. To seek joy in meeting halls. We haven’t even got a word for the quality I mean--for the self-sufficiency of man’s spirit. It’s difficult to call it selfishness or egotism, the words have been perverted, they’ve come to mean Peter Keating. Gail, I think the only cardinal evil on earth is that of placing your prime concern within other men. I’ve always demanded a certain quality in the people I liked. I’ve always recognized it at once - and it’s the only quality I respect in men. I chose my friends by that. Now I know what it is. A self-sufficient ego. Nothing else matters."

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This is an ideal to aim for. This is a philosophy to live by but I am perhaps stuck somewhere in between. Stuck in transition. In between these two worlds, where I to care for the opinions of some people even as I try to build my life my way.

And then as Roark says, " I can die for my friends, but I can't live for them."