NEUROTICS-DE-KASHIF

UCSF Brain Tumor Stem Cell Grant

2009-12-12T15:35:00.002-05:00

UCSF Brain Tumor Stem Cell Grant to Drive Development of Novel Therapy

A team of scientists representing 5 California-based institutions have received a grant from the California Institute for Regenerative Medicine (CIRM) to advance stem cell based strategies for treating brain tumors. The objective of the grant is to file a new drug application with the U.S. Food and Drug Administration within four years, driving a stem cell-associated therapy towards clinical trial.

The brain tumor team is led by Mitchel Berger, MD, chair of the UCSF Department of Neurosurgery, and includes collaborators at the Ludwig Institute for Cancer Research at UCSD (Webster Cavenee, PhD and Co-PI, and Frank Furnari, PhD), UCLA (Paul Mischel, MD, PhD, Tim Cloughesy, MD, and Linda Liau, MD, PhD), the Burnham Institute for Medical Research (Evan Snyder, MD, PhD and Co-PI), and the Salk Institute (Inder Verma, PhD). Other key investigators for the UCSF group include C. David James, PhD, Tomoko Ozawa, MD, PhD, Russell Pieper, PhD, Mei-Yin Polley, PhD, Michael Prados, MD, and Elizabeth Read, MD.

The brain tumor team will receive $19,162,435 to genetically engineer stem cells that home to and deliver products resulting in cell death specific to glioblastoma multiforme (GBM). The concept is based on the team's discovery that neural stem cells naturally seek out brain tumor cells. If the product of this research is approved by the FDA, it would be tested first in patients with recurrent GBM.

* Currently 5/5

Genomics Research Lends Support to Brain Tumor Stem Cells

2009-11-13T22:21:00.000-05:00

Voltaire had once said, “doctors give drugs of which they know little, into bodies, of which they know less, for diseases of which they know nothing at all".

Not as radically, however, this likely is the case for brain tumors.

If you repeat something so many times, the expression becomes trite. However to say that brain tumors such as glioblastomas are an extremely fatal disease, every times raises a red flag sign. Every paper begins with, despite advances in adjuvant therapies the population overall survival remains less than a year. I don't think statements like, the current regimen of care involves resection of as much of the tumor as possible followed by chemotherapy and radiotherapy, will ever be cliched because they deal with patient's lives. To add further, at majority of the centers, now, immunotherapy is also being increasingly offered as an adjuvant.

Modern genetics tools like microarrays and comparative genomic hybridization have given us insights into the biology of brain tumors that we weren’t familiar with before. Patterns have emerged with regards to brain tumor treatment across all adjuvant therapies, that brain tumor is a heterogeneous disease. With the help of these tools, scientists have identified subset of patients, harboring tumors of the same grade (WHO type IV; glioblastomas), that respond differentially to therapies, including immunotherapy; some respond while others do not. In “escapers” there occurs progression of disease, the timing of which is variable and the tumor claims the life of the patient, ultimately. These techniques have revolutionized the field of genetics including cancer genomics to the extent that some of the established lines of research in brain tumor field seem otiose. A recent study by Radlwimmer et al. published in Clinical Cancer Research [15 November 1, 2009] overhauls some of the established cell lines which even today are being used as models for studying brain tumors, in vitro. This and many other similar studies set the stage that these advanced genomic tools would become the standard of investigation from now onwards.

Jadus et. al. [Clin Cancer Res 2007;13(2) January 15, 2007] have reported that there exist around 27 tumor associated antigens that could potentially be used for devising immunotherapy against tumors. However, this study is limited by the fact that many of these antigens were from cell lines which were grown in serum which is known to destabilize the genetic signatures of the tumors thus producing variants not reminiscent of the original tumor. Secondly, many of the reported antigens are also expressed on normal brain tissue and they are not specific for brain tumors. However, there have emerged some interesting associations as well; IL-13Rα2 is a tumor associated antigen that is uniformly expressed in 100% of the original tumor samples. Among other antigens that are also highly expressed are survivin, hTert, Mage-1, Gage-1, Sart-1, and Aim-2. Except IL13Rα2, little is known about others in this list whether they are present on normal brain tissue or not. On the other hand antigens which have been in clinial trials for immunotherapy against brain tumors include, EGFRVIII, CMV, and some of the ones from the previously mentioned list.

In the light of recent evidence, the above study needs to be repeated, and high throughput genomic analysis of original tumor grown in serum free medium must be carried out, and it must include normal brain tissue as controls to see which are the antigens unique to the tumor. Additonally, a new set of cell lines need to be developed or better yet spontaneously brain tumor models that are available, at present, need to be utilized and improved further to study the disease in laboratory.

The study by Radlwimmer and colleagues [Clinical Cancer Research ( 2009; 15 November 1, 2009] which professes that tumors grown under serum free stem-like spheroids conditions tend to preserve genetic signature of the original tumor is a land mark one. It not only proves the existence of stem like cells in brain tumors, it also point towards the cells that feed the brain tumor in toto. Scientist like Peter Dirk, Angelo Vescovi, Eric Holland, Alvarez Buyella, Robert Weinberg, Luis Prada, just to quote a few of the many, have been asserting for years about the existence of tumor initiating, radio- and chemo- resistant stem-like cells [Holland et. al. Expert Reviews Neurotherapeutics, 9 (10) 1447 – 1449 (2009)] that get enriched following treatment. Keeping in touch with surgeons is the best way to re-evaluate the ongoing research because ultimately the goal is to heal the patients whichever way possible.

Glioblastoma Claims Senator's Life

2009-08-27T20:28:00.004-04:00

The death of senator Kennedy, who was treated for GBM at Duke fifteen months back, raises further concerns on progress against brain tumors.

Itasca & Cajal

2009-08-05T13:52:00.003-04:00

So, I am at this beautiful place learning and doing the science which I like the most, of course. "We walk on the shoulder of giants" is such a true satement as on our very first day, there was mention of Dr. Santiago Ramon Y Cajal, whose work we continue to appreciate since he was awarded Nobel Prize in 1906. Dr. Lorene Lanier while referencing to his work compiled in a two volume book that contains the origional drawings of Dr. Cajal of the central nervous system histology which stands as accurate a depiction today, even with technological and scientific advancements, as it was over a century ago. Soon after the lecture was over, I couldn't help but flip through the initial pages of the book and I found this statement by Dr. Cajal himself really moving."I finally chose the cautious path of histology, the way of the tranquil enjoyments. I knew well that I should never be able to drive through such a narrow path in a luxurious carriage; but I should feel myself happy in contemplating that captivating spectacle of minute life in my forgotten corner and listening, entranced, from the ocular of the microscope, to the hum of the restless behive which we all have within us." The irony of this humble choice did not escape Cajal's attention on winning the Nobel Prize little more than 20 years later.

This is the science at its best, nothing more captivating than the science itself.

The Maze of Brain Tumors

2009-06-08T14:12:00.006-04:00

In this long hiatus from writing some interesting findings in the science of brain tumors have surfaced. But it demands some background information first. A year into 21st century i.e. 2001, we were introduced to a book entitled "Brain tumor Immunotherapy" written by Linda M. Liau, M.D.,PhD., a faculty at UCLA. The idea indeed is novel, and may potentially lead to a break through in finding a cure for this ravaging disease. Whereas many of the Phase II and Phase III clinical trials on brain tumor immunotherapy are underway, we have still a long way to go, says John S. Kuo,M.D.,PhD. of University of Wisconsin in, "Tumour vaccine approaches for CNS malignancies: progress to date", published in Drugs 2009;69(3):241-9

It was in 2004 that Sheila K. Singh M.D.,PhD., now a faculty at McMaster University, discovered a population of cells within primary brain tumors that mimicked stem cell-like characteristics. She was under training at Hospital for Sick Children at University of Toronto then, under the supervision of Dr. Peter B. Dirks, M.D., PhD. The publication made it to Nature, and thus began the era of brain tumor stem cells. A year before that, in 2003, Dr. Harley L. Kornblums lab had already identified brain tumor stem cells from pediatric brain tumors. The publication appeared in PNAS. The number of publications that have followed, in just five years, are enormous. It can be judged from the fact that a simple keyword search for "brain tumor stem cells" through pubmed yields more than 2191 articles, published to date.

The modern practice of neurosurgery didn't begin until 1879 when the first meningioma was surgically excised by Dr. William Macewen of Glasgow. More than one and a quarter of a century in, with all the technological and scientific advancements, the outcome for patients with brain tumors hasn't still changed much. There have, of course, been cases where, with the help of immunotherapy, a longevity of, maximum, 36 months have been achieved (Please refer to Dr. Linda M. Lau's presentation on google). However, such cases remain few in number. For the majority, however, outcome remains dismal, with the average progression free survival of 9-12 months post surgery. I must emphasize here that this statement might seem overly simplified, the actual outcomes might vary with respect to centers at which patient is being treated and with regards to the treatment regimen being practiced by the neurosurgeon. However the typical route taken by a neurosurgeon, at any center today is to excise as much of the tumor as possible, give radiotherapy and chemotherapy, and then administer immunotherapy. For the most part these therapies are "adjunct", and none of them is effective, singly.

Given the excess of information that is available on brain tumor stem cells, however, alternative hypothesis are also actively and rigorously being explored. Charles S. Cobbs M.D., a neurosurgeon at California Pacific Medical Center firmly believes that during developmental years our brains get infected with CMV. A sequence homologous to CMV genome have been found in the genome of brain tumor cells which has convinced Dr. Cobbs to pursue this path of investigation. By exploring into immunotherapy options, in collaboration with brilliant Dr. Linda M. Lau, Dr. Cobbs has witnessed that in one patient immune response against CMV antigen was extremely strong such that that patient remains disease free, so far. But, how such an immune response gets mounted isn't known entirely, yet. Further research is being carried out, to extend the therapy to other patients.

Animal models that have long been used to study different diseases have been promising in areas for brain tumor immunotherapy, nanoparticles based chemotherapy, or chemotherapeutic agents alone etc. but most success have come through in canine models; Dr. John Ohlfest PhD., of University of Minnesota have been very active in developing immune therapies for canine brain tumors, and he believes one day it would lead to a break through in treating human disease. Batman, the dog, which received this therapy remains disease free and active, to date. There are clinical trials going on that combine the science of stem cells with brain tumor immunotherapy. Dr. Mitchell's group, from Duke University, who is actively exploring such therapies, is just one such example, out of the many. However, the story isn't as simple, again, as it might have seemed. When Shinya Yamanaka M.D.,PhD., published his induced pluripotent stem cells paper, he also wrote a commentary on using immunotherapy against epitopes of brain tumors. Peter Dirks M.D.,PhD., also concurred on the idea by writing a similar paper although his main area of focus remains brain tumor stem cells. Technically speaking, these hypotheses are sound but somehow the findings from animal models have failed to translate onto human subjects, says John S. Kuo, M.D.,PhD., of University of Wisconsin in his publications, " Tumour vaccine approaches for CNS malignancies: progress to date", and there is still a long way to go.

This brings me to the point that I had mentioned to my mentor few months back that we need to actively explore into this area by using real human tissues from the operating room. It is not surprising that Dr. Alfredo Quinone Hinojosa M.D., a neurosurgeon at Johns Hopkins University who also runs a Brain Tumor Stem cell Laboratory has presented this perspective in his latest article entitled, " Intra-operatively obtained human tissue: protocols and techniques for the study of neural stem cells", published in J Neuroscience Methods 2009 May 30;180(1):116-25. Aside from making the point that one has to move quickly in science this article genuinely underpins to the fact that if a real progress has to be made in brain tumor field, we need to study the normal and abnormal tissue of the patient rather than rely heavily on animal models which no doubt are important in increasing our understanding but that is the tissue we are devising therapies against, after all, hence that should be the focus of our attention.

But what I find even more interesting is the fact that even the most celebrated ones are coming back to the basics. Dr. Linda M. Liau who has been a great proponent of Immunotherapy for brain tumors has finally succumbed to the seductions of brain tumor stem cells as manifested by her latest publication in J Neurooncol. 2009 May 26, entitled, " Molecular properties of CD133+ glioblastoma stem cells derived from treatment-refractory recurrent brain tumors". The point that this article makes is that if we identify the intrinsic and extrinsic cues that regulate these CD133+ brain tumor stem cells, we might be better equipped in devising strategies to curb the recurrence of these highly malignant tumors. Dr. Peter Dirks, on the other hand, is focussing on establishing the hierarchy of brain tumor stem cells to neural stem cells. But these latest advancement in science are hardly surprising, infact these were the most logical ones to begin with. After surgery, when exposed to radiotherapy and chemotherapy, CD133+ positive cells are the ones that get most resistant to both these adjuvant therapies. It is because of these cells that the cancer recurs. If we have to check that growth, we have to strike that Achille's tendon. Our arrow could be a vector, an immune cell or some miracle drug but a thorough understanding, as highlights Dr. Lau's paper, of the regulatory mechanisms of BTSCs must come first.

Not to complicate this any further, Dr. Austin Smith PhD., of Cambridge University, has picked up the most obvious point whether CD133+ cells are the only progenitor cells in developing brain. Not so surprisingly, a population of CD133- cells with a different set of progenitor markers was identified by his team that also shows stem cell characteristics. But the simple point that emerges from this discussion is that CD133+ cells closely correlate with disease severity, recurrence, early progression to advanced disease that is responsible for high mortality in brain tumors.

On Doing Science - Advice from the Expert!

2009-04-08T23:48:00.004-04:00

You should be doing experiments because you want the answer. You shouldn't be doing it looking over your shoulder that someone might beat you to the answer, says John Dick, the scientist who first identified cancer stem cells from AML.

Questioning Sociability in Science?

2009-04-07T01:28:00.002-04:00

Dr. Sosumu Tonegawa October 13, 1987.

The science that inspires!

2009-03-28T01:45:00.003-04:00

The last page of the MIT TechTalk,-Volume 53, No. 17, March 4, 2009-displays the photograph of a smiling young man. The wall behind and the floor below him, are both chalked with seemingly esoteric inscriptions . This is Geoffrey von Maltzahn, the winner of this years Lemelson-MIT student Prize, an accolade that recognizes an outstanding inventor who proposes sustainable and innovative solutions to the worldly problems. "The $30,000 Lemelson-MIT Student Prize is awarded annually to an MIT senior or graduate student who has created or improved a product or process, applied a technology in a new way, redesigned a system, or demonstrated remarkable inventiveness in other ways. A distinguished panel of MIT alumni including scientists, technologists, engineers and entrepreneurs chooses the winner."

The "Gold Star" as the article is titled reporting Geoff's contribution is actually a pithy expression of his innovative approach in fighting, the scourge of all diseases, cancer. What made him the most deserving candidate for the prize were his two remarkable achievements; the development of new class of cancer therapeutics and establishment of new paradigm to enhance drug delivery to tumors.

I had reported in one of my previous posts about Dr. Sangeeta Bhatia who had developed nanoparticles that could precisely home in on tumor cells and deliver drugs specifically while convecting heat to the malignant cells at the same time when being subjected to microwaves. Geoff had been working with Dr. Bhatia on these "nano antennas" as they are named that made from gold particles that when injected in blood localize to the cancerous tissue by passing through the leaky blood vessels in tumor niches. Once there, the antennas are heated by non-invasive near-infrared radiations. This approach kills 100% of tumors in mice, says Dr. Bhatia, in preclinical trials.

His second invention is the efficient drug delivery to tumors by first sending in the benign particles that "locate" the tumors. These navigator particles then send signals to what he calls "assassin" particles that then home in on the tumor and deliver the drug at concentrations that would otherwise be toxic to the normal tissues if administered systemically.

At age 28, Geoff, a Harvard-MIT Health Sciences and Technology graduate student, has 8 patent applications, 19 publications and two companies, Nanopartz Inc. (www.nanopartz.com) and Resonance Therapeutics, to his credit.

Massry Prize-2008

2009-01-25T16:14:00.006-05:00

In words quite clear,"our thought is that we should recognize it before the Nobel Prize did" Dr. Shaul G. Massry, a professor emeritus of medicine at the University of Southern California has predicted the future Nobel Laureate trio of Dr. James A. Thomson, Dr. Shinya Yamanaka and Dr. Rudolf Jeanich who shared the Massry Prize for the year 2008.

Eight of its 21 recipients, since its establishment in 1996, have gone on to win the Nobel Prize. That highlights the significant contribution to science that this prize recognizes.

The three recipients reversed the differentiated skin cells to obtain iPS cells. Dr. Jeanich, however, has used these cells to successfully treat Parkinson's disease in mouse model.

The full story can be read here.

There is much hope in this science of transdifferentiation. A team of researchers from University of Bath, center for Regenerative Medicine that includes Dr. Jonathan Slack who is currently the head of the Stem cell Institute at University of Minnesota have already used the technique to transdifferentiate liver cells to pancreatic Beta-cells that carries the promise of helping diabetic patients.

Cancer Stem Cells

2009-01-03T18:01:00.011-05:00

The much talked about paper by Quintana et al (Nature 2008(Dec 4); 456(7222): 593-8.) brings into question the rarity of existence of cancer stem cells and a detailed analysis of this publication has been made on various sites, including the Nature Publishing Group's blog, "The Niche". Jim Till, who is a member of the Board of Directors of the Cancer Stem Cell Consortium (CSCC), based in Ottawa, Canada, does a comprehensive review of literature on the topic and the implication of this particular study. Another comprehensive blog run by Alexey Bersenev of Children's Hospital of Philadephia summarizes the findings on the topic with a stem cells perspective in hematological malignancies.

There are few points that emerge from these discussions:

Cancer stem cells don't necessarily have to be rare.

The results of this particular study can not be generalized to all malignancies.

The most important point that emerges from these exhaustive discourses of the subject is that there is a need to identify and understand that population of cells which is resistant to therapy. This unequivocally points towards cells which we now label as cancer stem cells, be it the hematological malignancies or of solid tumors like breast or brain tumors.

This particular study doesn't imply in any way to reject the well established stem cell hypothesis, for example, in the case of brain tumors. It would not have any implications what so ever, admits Dr. Peter Dirks whose team first identified brain tumor stem cells. He professes that the results in the case of brain malignancies would not change much as immune responses are already crippled in brain milieu against tumors. Further readings about lowered immune reactivity against malignant cells, from an earlier, though unethical, study are available here.

In case of brain tumors, the question is not whether CD-133 is a marker for brain tumor stem cells but it is more of this marker being necessary and sufficient. There is little doubt about it being sufficient as xenografting of cells expressing CD-133 were able to recapitulate tumor characteristics at numbers as low as 100 whereas even 100,000 of CD133 negative cells were not able to initiate tumors. It is not by chance that the same cells expressing this marker happen to be resistant to chemotherapy and radiotherapy. It is also not serendipitous for these cells to be present at lower proportions in low grade gliomas and at higher numbers in high grade tumors like glioblastomas. So from a purely translational-research perspective, and borrowing from Jim Till's argument and from Jenny Chang's argument that in the clinical setting, the only importance is ‘what are the characteristics of the resistant population that appear to be able to make new cancers, we can conclude that this should be our main point of focus.

All these observations point towards, though an obvious, fact that cancers comprise of very heterogeneous population of cells. A recent BMC article by Zhang et al (J Exp Clin Cancer Res. 2008 Dec 24;27(1):85.) addresses their significance by using a combination makers such as Nestin and CD-133 by employing immunohistochemistry to positively identify brain tumor stem cells. The use of more than one marker should suffice in addressing the controversy surrounding any single marker, and there should be an active search for newer more specific markers.

Finally, coming to the debate of "cells of origin" and CSCs, many points have been made in both of these blogs about not confusing the two, though indirectly hardly any ambiguity remains as to what would the cells of origin for tumors and of stem cells present in these tumors be. Much indirect evidence comes from studies in mouse models and Dr. Alvarez-Buylla and Dr. Luis F. Parada just published their finding in Cancer Cell. 2009 Jan 6;15(1):45-56, lending further support to the already accumulating evidence that tries to answer the cells of origin question, at least in part for brain tumors. Here is what John Dick, who identified for the first time human CSCs from leukemic patients, says about the "cells of origin" dilemma that should clarify some of the ambiguity:

"As a final point, we would like to re-iterate the distinction between the concepts of CSCs (cells within a tumor that possess stem-like properties) and “cell of origin” (the normal cell type in which the tumorigenic process is initiated, whether a stem cell or progenitor). The CSC model does not make any assumptions regarding the origins of CSCs – indeed, there is now abundant evidence that CSCs in mice may arise from either normal stem or progenitor cells depending on the specific transforming events, although evidence in human cancers is still lacking."

Transcriptomic, proteomic, bioinformatics, nanotechnology or systems biology etc, whatever the means may be, a better understaning of the resistant population of cells is necessary if only we are to eradicate brain tumors. Equally important is the understanding of approaches, for example immunological, pharmacological, osmotic, oncolytic viruses, gene therapy, microRNA or nanotechnology based approaches that employ various combinations of available technique, in order to get rid of brain tumors, after all responses tend to stall after some time following exposure to these therapeutic strategies. The goal is to ameliorate human suffering, decrease morbidity and mortality, improve quality of life, and increase longevity with the ultimate aim to cure the disease. What, therefore, matters is the end, not the means to an end but equally important are the resources that remain limited, thus dictating us further in allocating them wisely.

Peter Doherty

2008-12-21T01:59:00.005-05:00

I usually don't skim books. It spoils the ending but that generalization is hardly applicable to genres other than fiction or plays, may be. Autobiographies are exceptions, in particular. But the reason why I skipped pages of this book was the dictatorial nature of the title which obviously stirred some expectations.

The 1996 winner of Nobel Prize in Physiology or Medicine, a scientist of humble origins from Australia recounts his unlikely path to becoming a Nobel Laureate in his, much acclaimed and an instructive autobiography,"The Beginner's Guide to Winning the Nobel Prize, a Life in Science". The book is available at Columbia University Press. Fortunately, we happen to be at the Society for Neuroscience 2008 Conference in Washington DC where at the CUP stall, I picked two of these books, the other one being "In search of Memory, the Emergence of New Science of Mind" signed by Dr. Eric Kendal himself.

As I begin reading Dr. Doherty's autobiographical account, I instinctively find myself skipping to the pages where he advises novice minds the following lessons that he learned through his lifelong scientific pursuits:

1. Try to solve major problems and make really big discoveries
2. Be realistic and play to your strengths
3. Acquire the basic skills, and work with the right people
4. Work in an appropriate field
5. Find and cultivate your true passion
6. Focus and don't be a dilettante
7. Be selective about where you work
8. Value evidence and learn to see what's in front of your nose
9. Think outside the box
10. Talk about the problem
11. Tell the truth
12. Be generous and culturally aware
13. Be persistent and be tenacious, but be prepared to fail
14. Your time is precious
15. Avoid prestigious administrative roles
16. Take care of yourself, and live a long time
17. Have fun, behave like a winner

But these seventeen principles come with a disclaimer.

"So you want to win a Nobel prize, says Dr. Doherty; to become famous, powerful and maybe even very wealthy? If that's your ambition I can't help you. There is no instruction manual or course that can guide you to a Nobel Prize and, numerically speaking, most of us have more chance of winning an Olympic gold medal. There is also another difference; an Olympic medalist might go on to win a Nobel, but can you imagine Albert Einstein or Bertrand Russell competing in the decathlon? I was brutally reminded of this when I had to present a large cheque to Michael Chang for winning St. Jude Tennis Classic in Memphis. We were both winners in one sense or another but, though Michael might conceivably change his life at some stage to become a great scientist or writer, there is no way that I could ever beat an 85 year-old Chang or Sampras on the court".

Dr. Doherty along with Dr. Zinkernagel were awarded Nobel Prize for their discovery of how immune system works against virus infected cells.

Perfection in Imperfection

2008-09-18T18:31:00.004-04:00

Looking back now on the long path my life has followed, on the lives of my peers and colleagues, and on the briefer ones of the young recruits who have worked with us, I have become persuaded that, in scientific research, neither the degree of one's intelligence nor the ability to carry out one's tasks with thoroughness and precision are factors essential to personal success and fulfillment. More important for the attaining of both ends are total dedication and a tendency to underestimate difficulties, which cause one to tackle problems that other, more critical and acute persons instead opt to avoid.

An excerpt from "In Praise of Imperfection; My life and Work" by Rita Levi Montalcini, 1988.

Solution in Integration

2008-08-22T06:57:00.006-04:00

The TechTalk that got me thinking that in integration lie the solutions of many medical problems. Few precedents are cited below.

1. MIT radar technology fights breast cancer.
2. Preset patterns discovered in neuronal stem cells could complicate therapy.
3. Remote-control nanoparticles deliver drugs directly into tumors.
4. Interdisciplinary cancer study cited.
5. The David H. Koch Institute for Integrative Cancer Research to be launched in 2010 at MIT.

5. The last one, an institute, is infact a five prong strategy launched towards countering the most feared of all diseases, the cancers.

4. In the Interdisciplinary cancer study, scientists find that with the help of nanotechnology they can detect cancer from bodily fluids at early stages. The case studied is of liver cancer. The malignant cells are much loose compared to their normal counterparts and their dissociation begins much earlier in the disease. Nanoparticles have been designed to detect these malignant cells early.

3. Dr. Sangeeta Bhatia, another engineer and a professor at the Harvard-MIT research program, have developed nanoparticles that can safely home in and deliver drugs to the tumors. This is an ingenious work because the nanoparticles are attached to DNA probes; the length of the DNA probe determines the melting point of the particles, hence the delivery of the drug is controlled using electromagnetic waves, the trascripts to which these particles "talk back" amazingly.

1. Focussed microwave heat treatment along with cancer chemotherapy can shrunk as much as 50% of the breast tumors, a study cited in the November, 2007 issue of Cancer Therapy.

2. Carlos Lois, a neuroscientist at MIT is skeptical of using neural stem cell therapy for various CNS disorders, including storkes and neurodegenerative disorders. His findings render him so; he has discovered that each neural stem cell is preset to formulate only a specific set of neuronal connection, hence taking any of the adult neural stem cells, proliferating them in vitro and then transplanting them into any site of injury within CNS, he says, might not work. The scientist need to figure out how to manipulate these NSCs genetically to help figure out how to stop the preset differentiations of NSCs and then push them into formulation of cells of choice before using them for therapy.

Milestones in Developmental Neurobiology

2008-07-24T11:34:00.005-04:00

The field of Developmental Neurobiology, within the umbrella of Developmental Biology, has grown in parallel with the parent discipline. The following milestones have been sifted only to highlight the significant achievements in Developmental Neurobiology*.

1907. R. Harrison shows that axons grow out from neuronal cell bodies, founding the field of developmental neurobiology, and invents tissue culture in the course of these experiments.

1917. S. Detwiler studies the origin of the neural crest and the mechanisms of spinal nerve development.

1924. H. Spemann develops microsurgical techniques for embryos and with H. Mangold, discovers the organizer and the phenomenon of neural induction.

1933. C. H. Waddington discovers that Hensen's node is equivalent to Spemann's organizer, and shows that the role of the organizer in neural induction is conserved across species.

1934. Using limb bud ablations, V. Hamburger shows that survival of motor neurons within the spinal cord depends on interactions with the periphery. This insight leads to the discovery of NGF and to the 1986 Nobel Prize to S. Cohen and R. Levi-Montalcini.

1965. R. Watterson shows that cells undergo interkinetic nuclear migration within the wall of the neural tube. It was later shown that this phenomenon occurs throughout development as neurons and glia are born, and that cells migrate within the wall of the neural tube to occupy new locations (P. Rakic and co-workers).

1966. G. Rosenquist generate more accurate fate of blastula, gatrula and neurula by using triated labelled thymidine in unlabelled embryos. This technique was used by J. Weston and D. Noden to map the fate of neural crest cells.

1971. T. Schroeder proposes that neurulation involves the constriction of apical bands of microfilaments within the neural plate.

1976. A.G. Jacobson and R. Gordon show that shaping of the neural plate and closure of the neural groove require convergent extension movements.

1980. G. Schoenwolf and co-workers study the cellular basis of morphogenetic movements of neurulation, showing that bending of neural plate requires intrinsic and extrinsic forces.

1985. R. Keller and co-workers use the so-called "Keller sandwiches" to study the morphogenetic movements of gastrulation. T. Doniach, J. Gerhart and C. Phillips used the same model to study planar signalling during neural induction.

1989. T. Jessell and co-workers' cellular and molecular studies of dorsoventral patterning (especially of the spinal cord), show the importance of the notochord and floor plate in dorsoventral patterning, and the role of sonic hedgehog in floor plate and motor neuron induction.

1990. Knockout mice are used to study dorsoventral patterning of the neural tube by P. Beachy and co-workers; T. Jessell and co-workers; M. Tessier-lavigne and co-workers.

1990. Knockout mice are used to study rostrocaudal patterning in hindbrain by M. Capechhi and co-workers; D. Wilkinson and co-workers, in midbrain by A. Joyner and co-workers; A. McMahon and co-workers; G. Martin and co-workers, and in forebrain by J. Rubenstein and co-workers.

1990- 2001. G. Schoefnwolf and co-workers and C. Stern and co-workers determine cell-fate mapping using flourescent dye injections.

Early 1990-2001. Molecular markers are used to identify the subpopulations of cells, reducing reliance on morphology and increasing specificity and resolution of the experimental analysis. These markers are used simultaneously in chick, mouse and zebrafish embryos.

1990-2001. Rostrocaudal patterning is established using cellular and molecular studies; by R. Krumalauf and co-workers, and A. Lumsden and co-workers in hindbrain; by R. Alvarado-Mallart, L. Bally Cuif and M. Wassef; D. Darnell and G. Schoenwolf in midbrain, and by L. Puelles and J. Rubenstein in forebrain.

Late 1990s-2001. Mutant fish are used to study neural induction, rostrocaudal and dorsoventral patterning, and axonal guidance by W. Driever, J. Eisen, M. Halpern, P. Ingham, C. Kimmel, C. Nusslein-Volhard.

1992. J. Eisen, D. Raible, J. Weston and co-workers map neural crest migration through injection of the single cells and time lapse videomicroscopy, and subsequently in 1996 screen embryos for mutations that affect neural crest migration.

1993. R. Harland and co-workers identify noggin, the first candidate neural inducer, by taking advantage of animal cap assays.

1993. Dr. Turner and H. Weintraub show that basic Helix Loop Helix (bHLH) achaete scute-like gene (NeuroD) induce ectopic neurons when overexpressed, as they do in drosophila.

1994. A. Hemmati-Brivanlou and D. Melton identify follistatin, a candidate neural inducer known to inhibit activin. By inactivating TGF-β signalling, they further show that default state of the extoderm is neural, not epidermal as previously believed.

1994-1996. E. DE Robertis and Y. Sasai identify chordin, a candidate neural inducer that binds to BMPs to block their signalling.

1994. R. Beddington shows that the node induces a secondary body axis that lacks a head when transplanted to an ectopic site in the gastrula.

1995. Molecular and cellular organization of the organizer by G. Schoenwolf and co-workers and C. Stern and co-workers.

1995. A. Chitnis and co-workers show that lateral inhibition acts in the vertebrate neural plate through Notch-Delta signalling in a manner similar to that found in the invertebrate ventral nerve cord.

1998. R. Beddington, E. Robertson and their co-workers identify the anterior visceral endoderm as a signalling centre equivalent to the head organizer of amphibians.

1998. C. Nusslein-Volhard and co-workers use a large-scale mutagenesis screen to identify genes that have unique and essential functions during development.

A cursory look at these achievements tells us that earlier discoveries within developmental neuroscience were widely spaced. However, the decade of 1990-2001 saw many more of these discoveries. The discipline's progress paralleled with significant developments in technology. As the tools to study the developmental processes got sophisticated, we saw more and more new findings in almost every existing discipline of biology including developmental neuroscience. Dr. Fiona Watt, the current chairperson of International Society for Stem Cell Research asserts that we are sitting on an information gold mine. We need the tools to analyze that data in a comprehensive fashion. Systems Biology has already revolutionized many fields of biological research. The reductionist approach that has been our main tool to study biological phenomenon is being reinforced by this emerging science. I can foresee the day, that I think isn't far now, when we will have a complete picture of processes that once considered to be isolated which, infact, are very intricate, interwoven and interdependent.

* Nat. Rev. Neurosci. 2, 763-771 (2001).
* Nat. Rev. Neurosci. 5, S526-527 (2004).

Adult Neurogenesis

2008-07-21T01:46:00.005-04:00

The book is finally out, and I am anxious to get my hands on it. Dr. Fred Gage has summarized the concepts of neurogenesis with a comparative analysis of the phenomenon in various species. The thirty chapters that the book contains are contributed by the leading scientists in this discipline such as Dr. Pasko R. Rakic, Dr. Arturo Alvarez-Buylla, Dr. Alfredo Quinones-Hinojosa, Dr. J. W. Schneider including Dr. Gage himself, to mention a few. The monograph is available at the Cold Spring Harbor Laboratory Press.

Another Milestone in Stem Cell Research

2008-07-14T09:05:00.005-04:00

This year only 33% of the submitted proposals for generating new cell lines got funded by the California State. California Institute of Regenerative Medicine initially rejected the proposal of Dr. Fred Gage of Salk Institute, an affiliate of the University of California, San Diego. Only upon receiving a letter from the great scientist about why that particular proposal was important, Dr. Gage won the funding. I haven't seen his manuscript, and I haven't even read the reviewers comments about why the proposal was rejected in the first place but that does raise some curiosity and suspicion about the review process at CIRM.

On another note, few months back I had the opportunity to meet with a Harvard professor who was trained by Dr. Rudolf Jaenisch at MIT. We discussed his work for a while before discussing different projects. Dr. Jaenisch had discovered a glitch in the apparent flawless discovery of the Dr. James A. Thomson and Dr. Shiniya Yamanaka that the induced Pleuripotent Stem Cells (iPS) obtained from mouse fibroblasts didn't actually yield an embryo. In order for them to become true embryonal stem cells certain factors must be activated in exact chronological sequence. Earlier, Dr. Jaenisch had done that successfully and he was able to generate mice using that technique. The July 1 issue of Nature Biotechnology now reports another marvelous achievement by the genius of Dr. Janisch. This time Doxycyclin has done the trick, obviating the need for further genetic manipulation of iPS cells. All scientists need to do now is to add those four factors to obtain iPS cells and with the addition of the drug, Doxycyclin they can obtain cells that can give rise to embryonal stem cells or become the source of tissue specific embryonic stem cells from any tissue within body. Isn't that amazing?

Stereotypes-The Two Edged Sword

2008-06-02T08:08:00.004-04:00

We all have heard the fable of a young child who rides a bicycle uphill.

He begins with a determination, "I know I will, I know I will". He continues reciting these words to himself while climbing upwards and he finishes by expressing, " I knew I can, I knew I can". Many years ago when I had first heard this fable, I wasn't aware of the meaning it carries but today I do.

I, for some reason, had issues with the word "stereotype". To me it has always been that shoe in which we deliberately try to fit everybody, sometimes to the extent of being forceful. Whereas this approach helps us to classify individuals and societies, the inherent fallacy with this approach is that it fails to acknowledge individual differences. There result too many false negatives or equivocally, false positives. Stereotypes become extremely dangerous or in simpler words, they feed on your anxieties especially when one is on the receiving end of a negative perception about the group one belongs to. The result could remarkably be different, in boosting ones morale for example, if you are from the group for which there exists a positive stereotype. This was precisely the theme of the article published in the April Issue of the Scientific American-Mind entitled "How stereotyping yourself contributes to your success or failure".

The research in this area began in 1970's under the theme of "Social Psychology". The purpose was, and I quote verbatim, "to identify ways of addressing the problems they cause so that human talent and potential is not neglected or squandered". It is a bitter truth but frankly this ailment is and has always been quite rampant in all the societies of this world, although I find it to be more common here.

The pioneering studies were published, in this regard, from Stanford University by Claude Steele and Joshua Aronson. They concluded that “in situations where the stereotype is applicable, one is at risk of confirming it as a self-characterization, both to one’s self and to others who know the stereotype", a finding which has been replicated by many groups. For instance, if a female is made aware of the stereotype that woman in general tend to perform lower on mathematical skills than men, is likely to do worse on a mathematics test than a woman who wasn't told of this stereotype. The reason cited for such underperformance is "enhanced cognitive load". These woman experience more recurrent intrusive negative thoughts and they find themselves thinking such thoughts, " These exercises are too difficult for me, I am not good at math". Exposing people to stereotypes about groups to which they belong increases their anxiety and stress when performing tasks related to that stereotype. Such anxieties use up the information-processing resources that are required to carry out the task, as is evident from the work of Beilock. It also demonstrated that woman don't succumb to the consequences of the stereotype if they learn to perform the task such that they are not mentally demanding, for example learning the math problems by rote which relies solely on long term memory.

But stereotypes aren't as bad as we think them to be. The supporting evidence in this regard came from Harvard University when Asian Woman were included into the study group. One group was informed of the woman stereotype (that woman being poor in math) whereas the other was told of their Asian origin (Asians being good in math). The results were strikingly different. The former group, as was anticipated, performed poorly in Mathematics, the latter, on the other hand, passed it with flying colors. The explanation, for this discrepancy however, is far from simple cognitive-load. The answer really lies in "Self and Identity".

"People generally tend to advance the interests of their in groups and to see it positively". If their social identity conflicts with their motivation to do well in a given area, they feel identity-related psychological conflict. In summary, people perform poorly in tasks when they have a conflicted sense of self. When the social identity is in harmony with individual aspiration, they achieve mightily. Based upon these observations, we are bound to conclude that great achievements are infact the result of a harmonious relationship of an individual with its environment. The conflict, no matter of what sort, would enhance cognitive load, interfere with ones concentration, increase anxieties and lead to an inferior outcome than expected. The question then remains, are we really controlled by our environment or there is a way out, to prove ones individuality, after all history is replete with so many such examples.

Three strategies have been identified that people use to come out of this fix, "social mobility" being the first one. Here individual effort is made to deflect the impact of the group on oneself. The second, named "social creativity" changes the different in-group stereotypes that deflect the impact of belonging to a disadvantaged group. Evidence points that stereotypes are not fixed but rather flexible. The third and seemingly the most important one though not always feasible, is to engage in social competition and to launch an active resistance against the legitimacy of the conditions. " Thus work to counter the stereotypes that are tools of their repression with stereotypes that are tools of emancipation."

Of the many conclusive remarks in this article, the one that resonates closely with the theme of the fable above is "In short, who we think we are determines both how we perform and what we are able to become".

Given above is the brief summary of the article. For a complete read please see“How Stereotyping Yourself Contributes to Your Success (or Failure),” By S. Alexander Haslam, Jessica Salvatore, Thomas Kessler and Stephen D. Reicher; Scientific American Mind; April 3, 2008.

The 2008 Kavli Prize in Neuroscience

2008-05-30T14:13:00.002-04:00

Pasko Rakic, of the Yale University School of Medicine, Thomas Jessell, of Columbia University, and Sten Grillner, of the Karolinska Institute in Sweden, who collectively have deciphered the basic mechanisms that govern the development and functioning of the networks of cells in the brain and spinal cord, shared the $ 1 million prize this year.

iMusic-A Myth or a Reality?

2008-04-20T22:13:00.007-04:00

If what the makers of iMusic claim is true, they have certainly unlocked the true potential of human brain, and thus of mind. I find some of their claims rather amusing, and I would like to mention few of them here.

The Premise:

Fact 1: Your brain's performance levels and your overall mental abilities are largely governed by your state of the mind, which is determined by your brainwaves.

Fact 2: Science has uncovered which brainwaves create peak performance mental states for learning, thinking, studying & virtually every mental task.

Fact 3: Listening to iMusic, an advanced acoustic technology, "automatically" dials your brain waves into a peak performance state for situation or environment.

The extrapolations:

1. Enhance memory for numbers, names and places.
2. Feeling mentally crisper and clearer.
3. Experience more energy and vitality throughout the day.
4. Better communicate your ideas and thoughts to others.
5. Elevate mood and emotional stability.
6. Increased focus at work, school & while driving.
7. Quicker thought speeds and memory recall.
8. Less study time and better grades.
9. Improved writing ability and greater creativity.
10. Greater skills at chess, card games and brain puzzles.

These are rather big claims, but let me take each of them, one by one. Music certainly influences your mood, as says Daniel J. Lavitin, in his acclaimed book, This is Your Brain on Music. Infact, this technique has long been in practice in the motion pictures industry where music has been used to invoke feelings of love, remorse, jubilation, fear, and anticipation etc.

Can there be a simple explanation?

Imagine if the played music can elevate your mood, wouldn't your mental abilities be more enhanced. You'll feel revitalized, mental fog would be lifted, you will be more focused at your work, your memory would improve, recall would be better, with less distractions thought speed would be quicker, less study time and then better grades at school. Chess, card games, and brain puzzles like sudoku are themselves known to improve your analytical abilities and keep your brain sharper.

A different kind of doping and the evidence behind:

I remember reading in Nature sometimes back about the debate on "cognitive doping". If this new technique is for real, then there begins an era of different type of cognitive doping. The only apprehension I have about iMusic is that most of the data they base their claims on is actually on school children or people who had Attention Deficit Hyperactivity disorder (ADHD). Based upon these findings, will they be justified in generalizing the findings to everybody? Will the Parkinson's, Huntington's or Alzheimer's patient who have moderate to severe cognitive decline benefit from this music? Will this music help the patients who had transient ischemic attacks that lead to decrease in their mental capabilities?

Price to get smart:

Anyways, these claims are rather varied and there happens to be different music "products" for every skill that you desire; to make you more intelligent, to unleash your creativity, to enhance your energy, and many more... There is definitely a price tag to each of these keys offered to unlock a certain potential that lies dormant inside your brain .

Being skeptical:

So my question, you are a forty something individual, you have finally given up on your writing career, the passion you had for painting has slowly vanquished, you despise the job that you currently hold, you are constantly depressed because of your failures (and use your imagination for an even grimmer picture), will iMusic's different products help this man? Will he turn into an artist he always wanted to be, will he be that accomplished writer he dreamt of once and will he be a successful professional, within just 25 days of using iMusic as are their claims.

The music no doubt is very pleasing to ears, try the sample one, you'll like it.

Achieving Your Dreams

2008-04-08T15:53:00.004-04:00

The "last lecture" of Dr. Randy Pausch of Carnegie Mellon University on "Really Achieving Your Childhood Dreams" is truly inspirational. He is keeping his priorities straight, even at the end. Having diagnosed with a terminal pancreatic cancer he has already outlived the period proposed by his doctors. He, nonetheless seems awfully cheerful, and more optimistic and content with his life than any of us could ever be. The conclusive slides of his lecture are truly impressive and instructive as well. This lecture is a must watch if you are a dreamer.

Brain, Heal Thyself

2008-04-03T13:47:00.003-04:00

If you are an avid reader, perhaps this time when you are at Barnes & Nobles, you should ask the person standing at the help desk to direct you to the Cognitive Neuroscience Section. When there, you are not just looking for any book but the one entitled, "The Best of The Brain From Scientific American" by Floyd E. Bloom . The reason why you'd want to pick this book is simple. Whereas other books in that section touch upon an aspect or two of the recent developments in neuroscience, this book, however, gives a comprehensive overview of what has been achieved and what we are expecting, in neuroscience, in the coming years. It is written such that a layman and a professional would equally be fascinated by it contents.

The book is divided into three main sections; Mind, Matter and Tomorrow's Brain. Each section is further divided into chapters, contributed by Neuroscientists of such caliber as Eric R. Kandel, Antonio R. Damasio, to name a few. The chapters discuss, in detail, various topics relevant to each theme. I, however, would like to quickly skip to the one within the Matter section entitled, "Brain, Repair Yourself" contributed by Fred H. Gage, an eminent Neuroscientist at Salk Institute, San Diego, California.

"Try not to damage your brain, because there is no way to fix it", has been the implicit advice given to patients by their neurologists for most of the 100 years history of neuroscience. The dogma that dominated neuroscience during that period was that adult brain doesn't have the capability to regenerate and repair itself after an insult unlike many other organs of the body. The resultant approaches to fix disorders of central nervous system have, thus, all been directed towards the delivery of deficient substances, resulting from a loss of neuronal cells, to the nervous system. Administration of L-dopa to persons suffering from Parkinson's disease is a prime example. These approaches helped only to ameliorate the symptoms of the disease than to actually cure it.

The demonstration of axonal repair in the 1960s and 1970s opened up the possibility that there might be repair processes going on within nervous system to which science hasn't had the access as yet. In the later years scientists like Fred Gage and many others discovered that there is, infact, neurogenesis taking place, though to a limited extent, in certain areas within brain. Scientists, therefore, began to wonder why is it that despite the occurrence of neurogenesis brain is unable to fix itself?

The answer lies in understanding the birth of new neurons which happens to be a tightly regulated process. The neural stem cells which are abundant in the areas of subventricular zone and the dentate gyrus of hippocampus gives rise to new cells, following an insult to the brain, a stroke, for example. Whereas for them to develop into fully functional neurons or glial cells which in turn depends upon where they end up, they must migrate away from their niche to the site of injury and be successfully incorporated at the new location. This migration seems to be limited which results in the senescence of almost half of the newly formed "injury bound" stem cells. This whole process is so tightly regulated that different signaling molecules take active part in each step of the way, from the proliferation of NSCs to their migration to the site of injury and their successful incorporation, the environment there contributes to the differentiation of newly arrived progenitor cells. Much of the insight into the molecular processes occurring at each step, the signaling molecules involved, the promoters and inhibitors of replication, migration, incorporation and differentiation, that remains to be explored is whats hindering the scientist of today to fix a damaged brain in various disorders of central nervous system.

But the situation isn't as dismal as it seems. The observations from patients suffering from depression who were given Prozac for the treatment of their symptoms that seems to trigger neurogenesis and allieviates symptoms of the disease almost a month after administeration, the same period that it takes for newly produces progenitor cells to arrive at a distant location within brain and start functioning fully. The molecular biology research has given further insight into various factors, such as growth factors like EGF and FGF which can boost the brain's ability to enhance the process of regeneration, as has been observed by Dr. Gage and his colleagues in laboratory animals. The breakthroughs in stem cells research has prompted the scientists to replace the dead cells by injecting adult or embryonal stem cells to the site of injury. All these approaches, are nonetheless limited due to our sparse understanding of the exact process involved in brain repair. Therefore, Dr. Fred Gage contends that the real answer might lie in activating the inherent ability of the brain to repair itself using its own raw ingredients; the NSCs, growth factors, sonic hedghogs, notch signalling, BMPs, BDNF, NT3 and NT4, and many more that still needs to be explored.

Philosophers and scientists have long been supportive of the notion, "Mens sana in corpore sano" In healthy body lies a healthy brain. Dr. Gage closes his article on the same theme that though most of the above mentioned process might give a boost in brain repair, they might actually tip the balance to the other side and may result in uncalled for problems. He therefore asserts that the simplest and probably the cheapest approach, in short term, would be to keep yourself and your brain healthy is to exercise regularly, eat a balanced diet and get good sleep; all of which have been found to increase neurogenesis, decrease stress, consolidate memories and make their recall easier, till scientists are able to figure out and control the process of brain repair. The production of new neurons, as mentioned above has been found to alleviate depression symptoms whereas the survival of the neurons can be enhanced by their constant stimulation such as by doing active brain exercises apart form the physical ones, reading extensively, keeping yourself involved through innovative approaches and doing out of routine mental tasks, some of these have also been considered to be protective against the early onset of diseases like Alzheimer's, mainly by increasing the cognitive reserve of the individual.

For a detailed account on how to keep your brain active, Sharpbrains offers a good repository of information and suggest various brain workouts.

Eric Kandel

2008-04-02T23:54:00.006-04:00

As I read through "In Search of Memory: The Emergence of New Science of Mind". I find the following paragraph to be particularly moving. Whereas the context of relationship between Eric Kandel and Denise Bystryns, his wife, clarifies only after reading the entire second chapter, "An American Education", I quote the following paragraph mainly to emphasize on being orgional in science and not feeling constrained by physical means, as is evident from the following excerpt.

"Denise sensed, perhaps more than I did, that my idea of examining the biological basis of mental function was original and bold, and she urged me to explore it. I was concerned, however. Neither of us had any financial resources, and I thought it essential to have a private practice in order to support us. Denise simply gave the issue of money short shrift. It was of no importance, she insisted. Her father, who had died a year before I met her, had advised his daughter to marry a poor intellectual because such a man would value scholarship above all and would strive to pursue exciting academic goals. Denise believed she was following that advice (she certainly married someone who was poor), and she always encouraged me to make bold decisions that favored my doing something genuinely new and original".

If you ever want to read on the life of a Nobel Laureate which captures biology with a mix of history and where origionality of ideas and their development is at its peak, I would highly recommend that you pick Eric Kandel's "In Search of Memory: The Emergence of New Science of Mind". You'd definitely feel inspired by it.

Motif

2008-03-01T22:59:00.002-05:00

Back in yore (actually not so long ago) when I had picked the name for my blog, I wanted to capture my "eccentricities". "Neuro-tics-de-Kashif" seemed to rightly capture my quirks. "Neurotics"were then my peculiarities, however the "Neuro", pointed to my inclination for this subject. Followed it was "de" which portrayed my love for romantic languages, and not just for French only. But there is only so much a title could tell. My crotchets, as variegated as they were, all seem to run through this rubric. With passage of time, however, I have come to respect human limitation that you can't master them all. One can only maintain a level of interest that makes ones life beautiful that otherwise faces the risk of being banal.

I can't be a political activist, for my countrymen. It seems to me a dead end and an utter waste of energy which, in broader sense, is very limited in today's world. Dr. Read Montague, a neuroscientist at Baylor College of Medicine writes in his book, ."Your Brain is (Almost) Perfect: How We Make Decisions" that efficiency is when you get the most with the least investment. Politics thus appears to me a highly inefficient activity to be indulged in, even just writing about it. I enjoy reading good books, perhaps even write a review about them sometimes but again literature is not my forte. I read books only to appreciate the beauty, love, remorse, anarchy, creativity, realism, idealism that existed or still prevails in this world, and in the process be a little wiser myself. I can't be an authority on poetry although I love the archaic expressions of thee, didst or doth, for example. Similarly, I can't be a Environmentalist, though I love spending time in the lap of nature which sooths my riling nerves. I prefer that whatever volume of air that enters my lungs be a little over the cleanest, and I don't think it is too much to ask for. I enjoyed playing football back in school, and I still do whenever I am back in my town but I have to face the fact that I can never be a professional football player. I only play it now for physical fitness, avoiding whenever possible, any contact that risks an injury. My interest in Badminton, Swimming and Jogging, thus, remains only to the extent that these sports help boost my capabilities to perform better on the task I cherish the most.

The question, thus, I really asked myself was of "committedness". Like an embryonal stem cell, beginning life at birth to the gradual differentiation that paralleled my institutional and social education rendering me a little more committed, with every passing moment, by paring away apparently unrelated activities. I very well might have been an Engineer, had I not taken Biology as my major or I could have been an English professor because I loved the language. Long before this stage, I could have been a painter if only our arts teacher had stayed in school. Dr. Daniel J. Lavitin of McGill University in "This is Your Brain on Music, The Science of a Human Obscession" writes that with every decision made, we loose a certain broader perspective on things. He talks about differentiation while expressing his love for music. He says that being an expert, in the context of music, robs us of that innocent amusement that one has as a novice.

I have come to formulate a much too obvious theory about life; that it is short. Transitory than we expect it be. So fleeting in fact that to achieve even a single remarkable thing, said, of course, in strictly "perfectionist" terms, is mostly impossible. By that I mean to do that one thing such that in your heart you know that’s how you wanted to it to be. When many years down the lane you look back, you only feel complacent thinking that there is not a single thing you could improve on any aspect of it, and that what you had done was flawless. Something we only wish. Minutes after I write this post, I will find many thoughts that need rearrangement, many words to be replaced with more suitable ones and many appearing out of place and context. That, perhaps, is basic to human nature. Of course, I am a firm believer that with enough dedication and perseverance there is little that can't be achieved. Light rays when focused, through a convex lens, onto a piece of paper can ignite fire. The brain, a miracle in itself, can do wonders when its faculties are combined to perform a single task.

It may seem apparent now that I am heading towards neuroscience, the theme that could rightly capture my interests but I still face the challenge of being too broad. Many subdivisions within neuroscience such as Cognitive Neuroscience, Computational Neuroscience and Nanotechnology, Behavioral Neuroscience, Cellular and Molecular Neuroscience and Developmental Neurobiology are areas that one could write about. But I can't possibly know and write about all of them then will I be too narrowed in my approach towards this science by writing only about topics that interest me or the ones I will be working on. The risk, is, thus, of being too broad or too narrow but that's a risk one must take.

Commenting further on the evanescing life, consider a ten minute lifespan. Your task, to do the most of those ten minutes. You plan, and try to squeeze everything possible. There is a maxim that it always takes longer than you expect, so leave some leeway. Even with the leeway, you were unable to finish you first minute life task, it now impinges onto the second minute which in turn encroaches onto the third and so on. In the end, of life, then, there will always be somethings that remain unfinished.

Ghalib had once said:

Hazaron khwahishain aiseen keh har khwahish pe dam nikle
Bahut nikle mere dil ke arman, magar phir bhee kam nikle

This further stresses the need to focus and most importantly, prioritize. If a person is able to make a difference in just one area, I believe he served the purpose of his existence. Only that is the path to immortality otherwise we are very transitory beings. We can do more than just eat, sleep, reproduce and die.

Focus in an Intricate Yet Interconnected World

2008-02-13T04:47:00.007-05:00

Where are we heading, as a nation, is a question that surfaces in my mind every now and then, and alongside rush volleys of many more questions, most, too often, centered around the theme of "self" which, quixotically, is deeply tethered to every idea, physical or metaphysical, in one's life, on this planet earth and in the great cosmos, all around. Finding no reasonable answer, as expected, given the complexity of our interactions with the universe and of minds blind sight to foresee everything, I tend to matters at hand. To an eye which harbors chromatic aberrations, the images appear hazy. Similarly a life lacking direction, dabbled in every event that sparked even a little interest, gets oneself no where, hence my pursuit to focus on aspects that intersect my interests of leading a purposeful life, in a much intricate world that we inhabit. Dr. Joseph Murray, a Nobel Laureate in Physiology or Medicine, 1990, expressed some similar thoughts in his autobiography. He, quite pedantically, captures the need to attain focus yet highlighting the varied interests that one develops during ones life.

"We have been blessed in our lives beyond my wildest dreams. My only wish would be to have ten more lives to live on this planet. If that were possible, I'd spend one lifetime each in embryology, genetics, physics, astronomy and geology. The other lifetimes would be as a pianist, backwoodsman, tennis player, or writer for the National Geographic. If anyone has bothered to read this far, you would note that I still have one future lifetime unaccounted for. That is because I'd like to keep open the option for another lifetime as a surgeon-scientist".

Health, perhaps, is one topic which, as declared in Alma-Ata in 1978, bears the impact of every factor, one could ever think of, on one's wellbeing. The plummeting of stock market affects economy, the earnings are decreased, GDP's goes low, household income is decreased and there is a rise in psychological problems, apart from a zenith in the unmet necessicities. A staggering nation like Pakistan which, so far, has not been able to stand on her feet, due to a lack of political stability is under the same threat, once more. Politics affects development through lack of social stability which in itself is an umbrella term just like health, that alters available resources which affects a nations growth in avenues of investment that in turn is dependent upon literacy which no doubt is a hallmark of sustainable economy. Take the case of environment, for example; the improved understanding of issues of global concern, an outcome of excellent education, would help solve the problem of pollution and do away with factors that contribute to it. Finding alternative sources of fuel requires abundant resource allocation in areas of research, the undertaking of which requires trained individuals which in turn is dependent upon a country's good education that ultimately comes down to a stable economy and a sustainable development. It doesn't take a rocket scientist to figure out that we, infact, are paralyzed by so many variables, the mere though of them is enough to make us go raving mad. The hour demands focus and division of labor.

As to my countries politicians who, at the moment, are very busy reciting slimy speeches to their countrymen, just to win a seat to the paradise of national treasure, to buy properties in every corner of the world, to fill their abyss of an appetite for worldly pleasures and in the wake dupe the innocent, impoverished nation once more, I urge them, though hopelessly, that, for God's sake, just for once, do something for the welfare of the emaciated, worn out and educationally starved "nominal future" of this country.

My only interest lies in the fact that they:

- Live a healthy life
- Breath a clean air
- Drink clean water
- Eat a balanced diet
- Be free from financial worries
- Get a decent education
- Reciprocate a better future to this country by acquiring one for themselves
- Have liberty to carry out the good works they intend to do,
- Live a life filled with peace of mind in the "safe confines" of their homes
- And, to say the least, they should have stakes in the betterment of this nation, not the urge to flee this land when any such opportunity comes by.

I don't care which faction you belong to, I give no credence to which caste you were born with, I have no interest in your religious affiliations, and I particularly share no preference for what you are; a Chaudhary, a Vadera, a Peasant or, for that matter, a Fille.

Quite humorously, but deep from the heart, if you can't focus and do the work you seduced us with your promising words, then for heaven's sake do us all a favor and die, for purely evolutionary needs, and we would honor you postmortem.

"We salute the improvement of the human genome by honoring those who remove themselves from it. Of necessity, this honor is generally bestowed posthumously".

While I wait for the aforementioned ideas to sink in the heads of my soon to be "leader" politicians (if for some startling luck they ever get to read it), the brain storming on how to concatenate my earlier and future posts towards their unification to a single theme continues…Till then adios!

2008-01-29T21:58:00.005-05:00

"Mens Sana in Corpore Sano"

-Latin quote