A wound that never heals- Cancer

Generations of scientists have been tirelessly looking for a cure, to what appears to be public enemy number one- cancer. Cancer, is not one “disease”, its causes are even more variable than the variety of organs and cells types within those organs it can affect. Accumulated “mutations” or errors in genes, to inherited genetic conditions or exposure to tobacco or asbestos can cause cancer, that can arise anywhere in the body from the skin, colon, stomach, lungs, oesophagus, pancreas to the lymph nodes and the brain. Neither is cancer a modern disease, the oldest documented case dates as far back as 2500 B.C, found in Egyptian inscriptions on papyrus ( the precursor to paper), where incidents of breast tumors are reported.

Aiding the journey towards cancer- when our defenses betray us

There is a well characterized route of cancer progression from when cells give rise to “benign” or non cancerous tumors to “malignant” or cancerous tumors that have the property of invading other tissues and spreading throughout the body. However, only some key points or stop-overs and the final destination in the route are constant, like going from Delhi to Chennai. The possibilities to actually make the trip are numerous, one can fly, take the train, go by car or on a Harley – Davidson. The routes a cell can take to become a cancerous tumor are even more diverse. Now, since the cell on its way to becoming a tumour, is acting against the body- it is more like a terrorist, and what does our body do to contain a stray cell? Same as what the international police would do to contain a terrorist and to capture him. There are curfews and checkpoints and the wanted person’s photographs or sketches are circulated at every port of entry to another country, with special surveillance in areas he was last seen. Similarly, our body has surveillance mechanisms that look for abnormally acting cells, that form a part of our immune system. As is imaginable, escaping the surveillance is possible either through conning or conniving with, the system. That is essentially what the cancer cell does.

Mammalian defense mechanisms have evolved to fight germs and heal wounds in a concerted way because both external and internal injuries increase the risk of infection to vital organs. Therefore, the initial reaction of our body to a pathogen, like bacteria or virus, is the same as after a broken bone or a bruise. Remember the burning, redness and swelling that came soon after the cut in your hand? That is the first stage of ‘inflam’-mation. This is the body’s normal response designed to heal afflicted tissue. The main types of cells involved are the white blood cells (WBCs) or leukocytes. Only recently has there been an increasing acceptance of the role of inflammation in cancer.

What makes the inflammatory response a mechanism for cancer progression? Coming back to wound healing, it is apparent that there is a need for increase in cell number to replenish the cells that were lost, additionally an open wound gives an invitation to external bacteria and other parasites, therefore some immunologically active WBCs called monocytes also enter the wounded region. So, inflammation creates an micro-environment, around the afflicted region, conducive to cell proliferation and increases access of WBCs normally floating around in the blood to enter the site of injury. The WBCs secrete proteins called cytokines that are responsible to accentuate cell proliferation. These are the most obvious parallels to cancer, cell proliferation and an increasing permeability of the tissue which can allow cells to enter or exit the boundaries of the tissue or metastasize and then spread throughout the body.

“ Over 2 million people in the world have inflammation associated cancer. That can be because of acquired infections like Hepatitis B or C viruses in the liver and bacterial infections of the stomach,” said Dr. Curtis C. Harris, chief of lab of human carcinogenesis at the National Institutes of Health, in a podcast from the 2010 Frontiers in cancer prevention research conference.

Hepatocellular carcinoma (HCC), or cancer of the liver cells can arise due to several causes and is the third most common cause of cancer associated death. Epidemiological studies to look at environmental causes of HCC led to a very unique finding. It was already known that the Hepatitis B virus causes chronic inflammation in liver, that as explained above, preordains cancerous growth. “Looking at the incidence of HCC in regions prone of Hepatitis B viral infections, an immediate disconnect was detected. While regions with high HCC also had a incidence of Hepatitis B infections, the corollary was not true. This indicated that an additional factor might increase the progression to cancer, post viral infection”, said Dr. John D. Groopman, Chair, department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, at the 2010 conference for Frontiers in Cancer Prevention Research. “ This led to a multi-institutional and multi- disciplinary study in Eastern China. The study established that a Hepatitis B infection in addition to exposure to aflatoxin, synergistically increases the likelihood of HCC,” he added. Dr. Groopman was awarded the 2010 American Association for Cancer Research Award for Excellence in Cancer Prevention Research. His lab has been intensively involved in the studying the affects and mechanism of action of aflatoxin- a toxin produced by a mould called Aspergillus flavus, a common contaminant found in wheat, corn and other food crops and is a potent carcinogen ( an agent that can cause cancer). His research has previously shown that aflatoxin, binds DNA and causes a mutation in one of the most important tumor suppressor genes- the p53 gene, this makes a liver cell capable of crossing an intra- cellular check- point, that would normally restrict its proliferative capacity.

The recent endeavours by NGOs in India to ban the use of asbestos is definitely warranted. Inhalation of asbestos causes mesothelioma, which is inflammation of the lining of the lung and is a causal factor for lung cancer. The apparent paradox between the cytotoxic effects of asbestos and its involvement in lung cancer was solved when inflammatory cells, called monocytes were brought into the picture. As they get activated following exposure to asbestos, they release cytokines in an attempt to heal the tissue injury. But chronic exposure leads to mesothelioma and cancer.

Being your own enemy- addicted to cancer?

Another inflammatory response that increases the chances of liver cancer is cirrhosis a chronic inflammatory disease, that is known to be caused by alcoholism. The International Agency for research on cancer (IARC) is a part of World Health Organization (WHO) and recruits international expert working groups to evaluate the scientific evidence, from epidemiological and experimental studies, of carcinogenicity of specific exposures. Their 2010 monograph on Alcohol consumption evaluated scientific evidence from the past couple of decades from all over the world and grades alcoholic beverages as carcinogenic to humans ( Group 1- scientific evidence confirms carcinogenicity). Alcohol consumption was found to causally relate to malignant tumors (cancers) of the mouth, neck, oesophagus, colorectum and the female breast, in addition to liver cancer. The monograph states that the primary component in alchoholic beverages- ethanol is carcinogenic because of its metabolism produces acetaldehyde, which is genotoxic or causes DNA damage. Additionally, other components of the beverages may also be carcinogenic.

The most common and widely known environmental carcinogen associated with increasing the risk for lung and oral cavity cancers by about 20 times, is tobacco smoke. Additionally, it increases the risk for pancreatic, stomach, liver, cervical and colorectal cancer. It is also a Group 1 carcinogen identified as far back as 1986. Between one-fifth and two thirds of men in most populations still smoke one or the another form of tobacco. Lung cancer is the most common cause of death from cancer in the world. Many components of tobacco smoke are carcinogenic, including benzene, polycyclic aromatic hydrocarbons, nitrosamines etc. These organic compounds can cause DNA damage by binding to DNA ( forming DNA- adducts) and causing errors during DNA replication. Exposure to these foreign agents also activates the immune system and lung cancer is often predated by chronic inflammatory diseases like emphysema and asthma (yes, asthma is an inflammatory disorder).

Dr. Avrum E. Spira, Director of translational bioinformatics program, at Boston University school of medicine, calls the oral cavity, wind pipe, nasal passage and the lungs a “ molecular field of injury” prone to accumulated genomic alterations because of increased exposure to toxins from tobacco smoke. In 2008, his lab published a very interesting way to identify people with a high risk of developing lung cancer. Smoking changes the pattern of gene expression in all smokers' and profiling these biomarkers from cells in the lining of the nose, mouth and airways from people diagnosed with lung cancer could be used to test if a patient with a history of smoking, showing abnormalities in CT scans are on the way to develop cancer or not. As with all forms of cancer, the earlier the detection the better the prognosis.

Dr. Spira advocates non invasive techniques like bronchoscopy to remove cells that are used for looking for biomarkers. A thought echoed by Dr. Mary Reid, Associate Professor at Roswell Park Cancer Institute, Buffalo. Dr. Reid's laboratory is trying to establish new autofluorescence techniques to detect premalignant tumors in the lung, head and neck regions. Autofluorescence is an inherent property of biological tissue that makes them glow, and can be used to observe tissue architecture without the use of any dyes, if the right wavelength of light is used on them. Abnormal tissue architecture indicates the presence of premalignant tumors in many cases. “ This technique can complement CT scans and even detect lesions not seen on CT in the central airway and oral cavity,” she said.

The role of lifestyle and behavior reaches beyond tobacco smoking and drinking, to eating. Obesity has also been recognized as a chronic inflammatory disorder that also predisposes to many types of cancer. IARC recognized being overweight ( BMI of 25-30 kg/m^2) and obese ( BMI of 30kg/m^2 or higher) as conditions increasing risks for several types of cancer, like colon and breast. Chronic inflammation results in the presence of sustained levels of cytokines in the blood. A recent study published in American Society of Neurochemistry (ASN) Neuro, July 2010, conducted in the laboratory of Dr. Thomas N. Seyfried, at Boston College, Massachussets, in mice, which had glioblastoma (the most aggressive type of human brain cancer) showed that reducing calorie intake could reduce malignant brain tumour growth and metastasis. American cancer society estimates that 14% of all cancer deaths in men and 20% in women are attributable to excess body weight. A possible mechanism by which fat tissue can cause cancer progression was investigated in Dr. Charles Vinson's laboratory at Center for Cancer research in the National Cancer Insitute, Bethesda. They used fat less mice to study the mechanism linking obesity and cancer. The initial hypothesis had been that the white fat tissue (adipose tissue) secretes adipokines , that increase formation of tumours. However, the fat less mouse does not have any white adipose tissue or adipokines and still was found to have enhanced tumor development in some tumour types, except breast tumours. These mice are diabetic and have high circulating levels of insulin and insulin like growth factors, and proinflammatory cytokines, characteristics they share with obese people. The group concluded that these mice demonstrate the dissociation of the role of adipokines and chronic inflammation in obese people that makes them prone to cancer.

Preventing cancer progression, natural and chemical agents

Now that one of the aides of cancer has been recognized, what do we do about it? The old Indian home remedy for a fever or sore throat come to mind, turmeric in hot milk. Curcumin, the active ingredient derived from turmeric has been shown in a series of study conducted in the laboratory of Dr. Marc Diederich, Professor at the laboratoire de Biologie Moleculaire et Cellulaire du Cancer, Luxembourg to be anti-inflammatory and recently to be an effective chemopreventive agent for prostrate cancer. However, because of low bioavailability ( remember that turmeric is not water soluble) requires curcumin intake to be in several grams (8-16g) a day in tablets, for it to show any preventive effects.

“ Characteristically, epithelial cancers, like prostate and pancreatic cancer, have a long incubation period and are more amenable to chemopreventive intervention. Our lab is pioneering studies that would lead to the use of antibodies against epidermal growth factor receptor (EGFR) as a chemopreventive agent for cancer. EGFR levels are known to be upregulated in many types of cancer including lung, colorectal and pancreatic cancers. A sub- clinical dose is being tried at an ongoing clinical trial to see the efficacy of the antibodies in preventing invasive cancer development,” said, Dr. C. V. Rao, professor of medicine at the Oklahoma cancer center, Oklahoma city. EGFR antibodies have been used for a long time in treating last stage cancers of the lung, colon, breast etc. “ More than 70% of epithelial cancers are preventable using vaccines, prophylactic chemoprevention and life style changes.” he added. Vaccines for hepatitis B, human papilloma virus that causes cervical cancer in females, have been available for decades and the WHO widely recommends systematic increase in their distribution and use.

Note: Cancer was called a “wound that never heals” by a renowned pathologist, Rudolf Virchow, in 1863.

Accomplishments

Why is it that people want different things? Why is it more accepted to want what everyone wants? We are likely to have a genetic composition that predisposes us towards wanting social approval, or society can't have evolved to the extent it has.
We are even now constantly selecting for such combination of genes, as getting married and having kids is, perhaps the most universal social conduct gaining high approval.
Working as a volunteer for the rights of adivasis or minorities, going around the world, discovering a drug, appear far, far down in the list of approved activities, if they appear at all.
In most countries, joining the army, working for the government also make it high on the list.
What about death? Of course, I am not talking about approval here, I am talking about acceptance. In the US, death is considered to be bad, in fact any american reading this, will probably exclaim, who doesn't think death is bad? And how could it not be bad?

Well, there are in fact plenty of scenarios when death could be preferable. Abject poverty, for one, where one is realistic enough to know that there is no way out. No light at the end of the tunnel. Or when life has taken every glimmer of hope or happiness.
And of course the obvious matter of matter- maintaining the cycle of nutrients and life.
In fact, the charm of life is that it won't last forever. Otherwise, what little motivation people have, to be a better person, learn a little more, see or think or do more, would be successfully procrastinated to never getting done.
I do believe that most cultures, living close to nature have a much higher acceptance of death. It doesn't make them uncivilized. According to me, that is something to emulate.
Many religions also view death as bad, apocalypse promises to kill all the non- believers. Others escalate death in the name of a religious empowerment as a sure shot way to eternal happiness. But then, I don't believe God made religion anyway.
The other most socially approved act is to have children, the opposite or the beginning leading to death, depending on who is thinking about it. Someone once said that having a child is an act of very high optimism. One must be optimistic enough to believe in the best possible future for their children, obscuring all mishaps and unpleasantness that must have befallen them, while growing up. Perhaps magnifying the happiness children bring, to overshadow the essential sacrifices for bringing up children. We must be evolutionarily wired to achieve that level of obscuring as well. Or perhaps the need to be needed is powerful enough to overcome everything else.
So what is an individual's contribution to society, children? some skilled labor? Is it overreaching to want to do something meaningful that outlasts your generation and want a family? Or is it even possible to do many things well? Bringing up children well, is no small task, somehow our parents managed it well enough, but as technologies bring in more negative forces to take away the innocence from our children, it is getting harder and harder. Maybe only in my imagination. But game-boy, definitely doesn't make friends, or improve imagination, when a short answer to everything is easily available on the internet, why read a book?
Is that where, some socially incompetent geniuses come in, who are responsible for the few breakthroughs that can occupy whole generations in their repercussions?
But if you haven't had time or the thought to read about everything that can affect your child, not limited to good parenting books, who let us all admit it, have nothing to do with the real world after the child is born. Everytime something bad happens to your child, you will blame yourself and not without reason.Unless, you are reading real child psychology, which if you have time to read, after your child is born, you belong to a tiny elite percentage of the world population. You have also probably read economics, art and literature that can give the rounded development a child would need. You may also have achieved the level of meaningful success in your field of choice, enough to be an expert who is valued and can keep up with little effort. Well, you may well be fictitious. And still not be able to change the course your children's lives take.
What do you want your child to be?

So, what do I want to be?

George Orwell and Charles Darwin

Ahem, what do Orwell and Darwin have in common? (Some people may ask) Well, this is actually about how those two geniuses can be so different and yet lead to the same dictum. Darwin led the revolution in scientific thinking of how all the diversity in nature was the product of "natural selection" and Orwell is one of few who wrote with certainty the doubtless evolution of society towards evil oligarchy. Oligarchy of the few smart or priviliged ones , the faces of who may change following "revolutions", but the end is always the same balance in society.

Masses of creatures allow variations to accumulate, such that should some of them move to a different place, or the climate change a little, some of them survive better than the others and the species survives and maybe gives rise to a new one. However, all species, do the same thing, live, eat,reproduce, fight and die. So Orwell says, the result of variations in the human population are always the same. Ignorant masses, easily hypnotized by speeches and grandeur,are used by the few powerful leaders, through smart talkers. As those in power constantly create diversions that either terrify or make deliriously happy the people they "rule" such that the real issues are neither discussed nor solved or even thought about. What is the real issue for a species : to survive. And there, even the most evolved, like the cockroach, are at mercy of nature. So, they at least take reassurance in that mother nature is always looking to keep the smartest or the strongest of them, for the future, for their own good. Sounds like the theme from Animal Farm and 1984. So, who is big brother? Is that God? Well, no, God is good. Omnipresent, pray and you shall be heard. He will give you what you deserve and if you don't get that, then you didn't deserve it in the first place. Or you can wait, the time isn't right, not just yet, look at all those around you, suffering, aren't you better off from those dying of starvation and yellow fever or some other color fever? And yet you ask for more!! Pray, because He has been kind enough to let you be disease-free and fed.

Darwin talks about the requirement of variation in the populations of species, for natural selection to act on and favor one over the other, under changing conditions. Orwell, thinks that conditions might change, revolutions may happen, but the "social "order of things will stay the same. In some cases man is big brother, as we exploit the environment for first our good and then because there is no other way. Then we exploit each other, again using the same excuses, why, the "American"Indians have been moved to reservations for the sake of development. The naxalites are terrorists and hinder economic development of our great nation. The nation that ignores its people, because they have always been hidden in forests minding their own business, is in turn ignored or exploited for its own good. It is told, you are too unstable to harbor nuclear weapons and how are we going to maintain world order if every little third world country wants to go to the moon and have nuclear energy, what next? Next they will all want food and water for everyone! Let us take your minerals and cheap labor and we will show you how to live.
But there is poetic justice, what was once Great Britain, is not so great anymore and what now is the United States may well end up someone else's bitch.

Hence, all is in order. The names in that order change, maybe there is a God after all. As some of us gaze in awe at the diversity of life and how much we don't know about so much and how much we will never know about, say dinosaurs. How we all started from a single-celled organism- a point in dispute and will remain so , it seems, now and forever. The more things change the more they remain the same. Someone will soon find a better way to find fault on some minor detail in a way a small snail evolved, or even better in human paleontology. And the masses needing some way to stay hopeful will throw evolution out of books. Because isn't it a threat to the existence God?However,if He exists , then is He not big brother incarnate, for tortured creatures dying all the time without having had a life cannot be for the good of all. And if He is making it hard for our own good, because He knows best.We may write books and have theories and find a cure to cancer, make electrons and protons clash at the speed of light, if He in fact is in control then all that doesn't mean anything.He can make all that a lie in a whiff of smoke All that makes life easier for a few, interesting for a few more. But most of the proles-masses, just barely exist and couldn't care less. A large number of them pray for His kindness and mercy way more than the ones that seem to be under His special care. The concept of heaven or hell,makes their harsh realities bearable, but the mere concept of a heavenly abode in the sky is even more ludicrous than animals taking over a farm and making a windmill. Therefore the smart ones, play demigods and pull strings wherever possible. Exploit and brain wash whoever possible to try and get to the top of the order, be closer to big brother in spirit.

In the end, our evolution, if indeed we are evolving, is not in our control . We keep on endlessly cycling and recycling thoughts that have always existed in different minds.

So do Darwin and Orwell have a common thread? Yes, that the order of things as they are, has existed well before mankind and will continue to exist through the time alloted to mankind and well beyond.

Never Enough

In the last few days of my trip to India, I thought, Oh! if only I could have stayed a little longer. And then I realized,it's what I would think even if I had stayed a year. No amount of time is enough to soak up all the love and attention ( though it does tend to slack off a bit after a month or two) Then I started to think when was the last time that I thought, alright, this is enough of ........, I am happy with it. Well, maybe my time at IISc. But in the end, I hadn't really wanted to leave so many things undone even there.
So my conclusion was, there will never be enough time or love or success that will make me think it was enough. I will have to strive to achieve the contentment, from as much as I have been endowed with. And of course, as is usually the case, all that deep thinking , wasn't really required to arrive at this conclusion. Everyone already knows this and if I were Shakespeare, I would have been able to put this common wisdom into better prose.
Taking a macroscopic view, the world will never have neough of Nelson Mandelas, Mother Teresas maybe even Einsteins, Isaac Newtons, J.B. Haldanes ( though, being in the scientific field, I have come to accept that all of the big scientists were not indispensable, someone would have figured it out anyway, maybe not with the same flare, but eventually..). I have started to think that while science maybe a hard conceptually and not everyones cup of tea , plus the ultimate thing that will help mankind in the end ( I don't mean the biblical end), being a politician can't be a cake walk either. And in terms of what the politicians ( and here I include thefreedom fighters, and the Hitlers) have "achieved" or have the power to achieve, scientists mostly because of how removed we are from reality ( needing clairvoyance to justify our existence) don't do so much for an average person. I know, I know, what about all the cures and the vaccines ?? well, I would think they rank much lower than freedom of movement and thought. Because while there can be enough freedom( Oh yes!! there is atleast one such thing) there shouldn't be too little of it. And I would prefer to die of a disease than live in a coercive and unjust society.

Maybe I am underplaying the scientists because I am one of them. Maybe towards the bottom rather than the top of the pile, but still. I think while we enjoy glorifying ourselves ( there can never be enough publications) the real world doesn't figure into our image of self. For as many of them as I have met atleast. I am sure, there are a lot of them into social work, but there is a reason we don't immediately think of a socially active or aware person when we think about scientists. They will all have opinions ( or else what use are their brains), but what they do with that.. is in short , not enough.

Missing the absence

I have been here in the states for more than three years now (if you ask my dad he would tell you the exact number of days). I had somehow felt a strange sense of deja vu when I came here, it was as if I had walked on the streets before, seeing strange people with of various colors ( not just skin color) walk by me and say things in the hope of exchanging pleasantries didn't seem strange at all. I know the source of that, after all I knew since I was about 13 yrs old that I would do a PhD in biology in the US. ( At least, I knew what I wanted when I was 13, I must be a specimen of reverse metamorphosis). And that, from the kid I used to be who refused to acknowledge adults ( friends of my mom's) on the street like other well- mannered kids would. Though, I should say that the exchanges of pleasantries with people here, was rather one sided, I merely smiled then and now I smile and nod.
Everyone here wants to know everyone else at some level or atleast wants to announce there own presence, while I have always wanted to be a part of the wood-work or concrete or whichever object that blends in with the surroundings. Though, wanting something rarely precedes getting it and unfortunately I have always attracted attention and usually of the wrong kind.
Except here, where I think I would have been the least conspicuous person had I not been an "Indian girl" (no, she is not mexican) . But I am okay with that, as long as people announce their presence and other than the nod don't really expect anything more. Or am I?
Well, scientifically I am certainly not okay with not knowing enough people. It used to be much easier in India, just walk out of your lab and you have the option of talking to anyone from any field you like. Not that there aren't people here, or that there isn't variety ( which I already mentioned exists). After all, its a famous university full of brilliant people (I am sure). But I don't know any of them. In fact, I might not even know most of their names, let alone know them personally. So I have like three people I can talk about my work, unless you count the other three I talk long distance with. But what can you do if you are reserved, can't drink coffee or beer. Where in my last institute I just had friends who had been with me since college and I was in a big lab and a big department so I had never needed to find a reason, place and time to talk about work.
But as far as the anonymity being here provides me, I haven't been able to decide whether I absolutely like it or not. I don't dislike it. But for some times..

Sometimes I wish I could hear my favorite song being played inside shops or you know how that right song, coming from the neighbors' windows can cheer you up unexpectedly. When I hear a familiar language (Hindi or Bengali) being spoken somewhere around me, my ears sort of get entrained towards it and I strain to catch a few words. This, when I used to block out all conversations, including the ones I was supposed to be involved in.

I still have some time to decide what I want for a future (since I haven't decided yet it must mean I have time). And that would include in which continent, should I get the luxury to get picky, I would like to live for the next ten years or for the rest of my life. The longing to belong somewhere or to be where you belong is, surprisingly, overpowering my focus on science. I hadn't anticipated that. I have always been able to put work before everything (even then, the status of my PhD is laughable) and technically the genetic system that I want to work in, is nearly impossible to maintain and run in India, we are still more than a decade behind and will probably continue to lag for some time. I would like to think that I could actually take that a step ahead. But I am not very confident of being able to be that "leader". My one hope is to get that confidence and then it would be a straightforward choice. I may not actually miss the convenience of getting everything I need in a day, and OMG if its really late and too expensive it will have to be six weeks. Compare that to the once in a couple of years that we used to order from Sigma, from literally the richest lab of the time, at IISc, Bangalore. We will have to see. Maybe I will be a scientific writer and get to bring minds together and connect things, which by far interests me more than even complex genetic diseases. That would be ideal, who wants to run a lab?

All these disjointed thoughts and I know it is about something that's missing.. I think I was better without these thoughts, then I could focus on the work at hand and take it a step at a time. Not worry about things way beyond my control. Where did this confusion come from? I want it to go.. find someone else. I was much better without it.

Thanks

Thank you people for your sincere concern .. And to others who read the post and got to know him a little.

For Divesh Thimmaiya, till we meet again..

I never thought I would start a blog, though writing is something I have even considered to take up as a profession. But there is nowhere else I can tell people about the friend I lost this saturday. The friend I had not even seen in 4 yrs but it feels like just yesterday he was grinning at me from the side of the street and saying "I like it... (pause) I like it". Someone who could make even the grouchiest person (that would be me) smile at any time of the day or night. I want to know what he had been planning , because he always had plans, on friday , or last week or last month. Not just plans that people make and never carry out, he made plans that he would make work. I want to know what were the things that had made him smile recently, because , as I told him frequently, his was one winning smile. And those eyes, I will never forget them. They were one of the brightest I have ever seen. Moreover, I want to know what he wants me to do now. I don't want to forget anything he ever said to me. And that is not a problem, I have an excellent memory ( which is why I am grouchy) but at least this time, it will serve a good purpose. I remember he said that honesty is overrated, noone can be honest all the time, lies save people, there are things you should be able to lie about , it is integrity that is important. He must have been 23 when he said that and I have never had anyone say something that profound. He had a big heart that could hold hundreds of people in it and still remember all their names and interests. When he walked into a room, people turned to look. He worked hard and partied harder. He was opinionated and didn't pull the punches, if thats what he thought was needed.
The last time I talked to him I was complaining about how I had no results and he had said that " Bada kaam kar raha hain bachcha, time to lagega" . I don't think I am doing anything big, but that sure made me feel a hundred times better and all important all of a sudden.
I wish I had called him, but my preoccupations seemed so important at the time and the fact that I knew he had many many friends and wasn't exactly waiting by the phone for my call, had me delay that indefinitely. What I hadn't realized was, that I needed to talk to him, I needed him to bring back clarity of thought using his unmatched sense of humor. I needed him. I still do. And he is gone. The one guy I knew who could actually bring change ( ask anyone at IISc, who was there before he came and since..) is gone. I was one of the privileged people who knew him. And God knows that if he hadn't been such an incorrigible flirt I wouldn't have known him at all. Thank God he drove his bike at my pace beside me around the M - Block hostel till I got on it finally. His "Oye Soniye!!!" which he used on as many females as he knew, I think, could still flatter all of them . I apparently blushed. Thats something, I never blush and to this day I would contest his observation. Maybe not.

I never knew anyone from his family, but I want them to know that not only did their son live life to the fullest making each day count, he left a mark on everyone whose life he touched. I didn't even know him for more than 6 - 8 months before I left IISc, and then India. But distances didn't matter with him. I always imagined him busy doing something interesting or annoying. And in my dreams he will continue to do that always. And till we meet again, I will live like he would have, or at least try to. But Divesh, you nut, wait till I get my hands on you ... Just you wait.

Ishita