CROSSWORD PUZZLE: SCIENCE AND TECHNOLOGY

Enrich your knowledge bank with this crossword puzzle on Science and Technology

ACROSS

1. These bright & energy-saving white light sources won them a Nobel Prize (4,4)

5. Largest transporter protein family utilizing ATP; associated with chemoresistance in cancer (3)

7. Mutations in this mitochondrial protein can cause hereditary spastic paraplegia (4)

8. This ‘intergenic’ region gives E. coli resistance to beta lactamases (3)

9. Crucial for environmental monitoring, map making and meteorology (Acr.) (3)

11. ATP + AMP ⇋ 2ADP – This gene is essentially expressed here (2)

13. Second most traded currency in the world (3)

14. Automatic Image Segmentation algorithms used in MRI; especially to localize cancers (5)

15. RNA quality control autoantigen (2)

16. Carbon copy (Acr.) (2)

17. Lighter OWL axiomatization of DOLCE & DnS ontologies (3)

18. ERDA can detect this of heavy ions; legally entitled in simple English (4)

19. Effective gene therapy injection technique (3)

20. Have 2 copies of Val734lle variant of ABCC9 gene? You’ll no longer need this in the morning (5)

21. Fixed the arbitrary stakes (5)

23. When French Police taps your phone, it may be just a Monday morning drill for this coordination intelligence unit. (5)

25. With axe in his head (5)

27. An allergic response can definitely raise this (Acr.) (4)

28. This Israel based computing services hold the majority of voice data in the world (4)

29. This second largest whale is a razorback (3)

30. Antibody associated with Rheumatoid Arthritis and Sjogren’s syndrome (2)

31. WHAT __ - protein structure analysis platform for mutant prediction (2)

32. In 2000, this Act put regulations on electronic communications and surveillance (5)

33. Basic unit of information (3)

34 & 38. Y- Axis acceleration (2)

35. Blistering of skin when genes of Keratin 5/14 get mutated (Acr.) (3)

36. Contingency table of small sample size? Find the exact p- value for significance (Acr.) (3)

39. PI3K related serine threonine protein kinase mutated in Seckel Syndrome (3)

40. Poly (A) independent sequencing method to sequence both polyadenylated and non polyadenylated RNAs (8)

DOWN

1. German database of enzymes (6)

2. Youngest high impact crater in Titania, the moon of Uranus (6,6)

3. Caused White Leprosy/ Black Fever in Paleotropics (10)

4 & 37. The type of borosilicate glassware used in science labs (2)

5. DNA profiling pioneer (4,8)

6. 45 tera Watt hour? They definitely need these specialized circuits for the Deuterium Uranium nuclear plants in Canada (5,2,3)

10. The first consumer targeted virtual reality head mounted display (6,4)

11. Acts with neuroregulins in Ach receptor development (4)

12. DNA, RNA and the flow of info earned this family three Nobel Prizes (8)

22. This circular plasmid makes Agrobacterium a natural genetic engineer (2)

24. This gene family is defensive against insect attacks in rice (4)

26. Method of choice for complete snapshot of all transcripts available at one precise moment in a cell (6) 

Crossword answers

The Loyalty Factor

They say stay close to your friends and closer to your enemies. But the irony is we often fail to recognize who is who for us. Blame it on the complexly intertwined concepts of loyalty and betrayal in the present world.

Here’s a quick thought. There was Mumbai, the then Bombay, with rich oil reserves and a favorable coastal line to augment business interests. There was Delhi. Centrally placed, easily accessible from across India, a highly sought after nodal point to mediate internal and external diplomatic traffic. However, the British chose geographically relatively isolated Calcutta to establish The East India Company and start off their political, economic and cultural invasion of the Indian Empire spanning over four million square kilometers. Calcutta is still the true Victorian city. It bore the brunt of British looting and gradually withered in later years of British imperialism. Ever wondered why the British had their initial yet strongest foothold in Calcutta of all Indian cities? All because one person put a price tag on loyalty, traded his selfish interests with the freedom of Mother India.

In 1756, when King George II commanded Major-General Robert Clive to spot the ideal fertile land for establishing a trading company with ulterior motives, the shrewd British informants found an apt candidate to crack an entry. Mir Jafar. The disloyal Army Chief of Siraj Ud Daulah, the then Nawab of Bengal. On offering the prospect of being the next Nawab of Bengal, Mir Jafar kept aback the entire left wing of Bengal Army comprising 15000 infantry, 35000 cavalry and 59 field pieces idle. The figuratively handicapped army, without any lateral protection or a commander succumbed to a trivial British force of just 2100 infantry and 6 field pieces. Standing shoulder to shoulder with the Nawab, who was oblivious to the treachery brewing around him, Jafar devised and designed the whole military operation of Bengal Army in the Battle of Plassey in 1757. He thus ensured the surety of British victory in the battle, killing hundreds of Indian Army men. Needless to say, this paved way to the very first establishment of East India Company in Calcutta and the rest of British domination is history.

Life often puts us in this difficult situation when we have to choose between gains and loyalty. But, in sooth, such a situation becomes a difficulty only because we consider loyalty to be one of many choices. It is never a choice. Loyalty is a necessity, it should rather be the central axis of our virtues. Betrayal may, sometimes, be the easier route to momentary gains. But staying true to our words, deeds, peers and leaders can definitely give us lasting results. Moreover, momentary gains only make us obliged to unworthy forces. We grew up hearing stories of Casabianca and Japanese Samurais; of Hanuman and Karna. It is of no doubt that the indispensable virtue of loyalty is deep rooted within us. It is just a matter of discovering it within us and hold on to it tight, irrespective of any persuasions and hurdles. Believe in ourselves, stand by virtuous principles, and be loyal to causes of nobility. The one single thing that cannot be compromised in our voyages in Science. Rewards will certainly come searching for us.

Breast Cancer Research Update

A quick peek into some of the promising studies from around the world on breast cancer diagnostics and therapeutics from last week.

Diagnostic

In vitro and in vivo studies by Singh et al published in Nanomedicine have shown that covalently linked glucosamine and non-covalently phospholipids- glucosamine coated carbon nanotubes called glycol- MWCNTs have preferential accumulation in breast tumor tissue through a specific interaction with glucose receptors. This is promising in developing more accurate diagnostic tools as well as improved targeted therapy by molecular radiotherapy.

An interesting study from China by Jun Yan et al showed that  1ml suspension of carbon nanoparticles when injected into the body had excellent tissue retention specifically in axillary lymph nodes. Hence, it can be used 10-15 minutes before surgery to exclusively target axillary lymphnodes for sentinel node biopsy and dissection. The tissue targeting and identification rate is proven to be significantly higher than conventional blue dye.

Prognostic

Tumor Infiltrating Lymphocytes (TILs) have always been an enigma for cancer biologists. A review by Ahn et al on the subject throws light on the increased prognostic evidence and predictive potential of TILs in triple negative and Her2 positive breast cancers. 

Deregulation of TET1 and 3 under hypoxia in tumor tissue is of high prognostic value in tumor progression and aggressiveness. Belmonte et al studied the DNA hydroxymethylation associated with these genes during hypoxia to effectively explain the downstream mediation of p38-MAPK pathway in breast tumors with poor outcome.

Therapeutic

In silico analyses have opened up new insights into the binding and downstream signaling contribution of Protease activated receptor 2 (PAR2). Though specific ligand binding sights have not been explored, putative ligand specific conformations of PAR 2 are analyzed more in this study by Kakarala et al. It is quite interesting to note that there is a bias in the binding of PAR 2 to different receptors and this gives agonistic action with serotonin type 1, β adrenergic type 1 and antagonistic action with substance K (NK1), serotonin type 2, thromboxane and dopamine type 4 receptors.

Poly-ADP-ribose polymerase (PARP) mediated signaling pathways play significant role in breast cancer cells that PARP inhibition to silence homologous recombination is a hot topic in developing new therapeutic agents. But the sensitivity of cancer cells especially in TNBC is not sufficient enough to propagate this idea further. Wiegmans et al’s study from the Signal Transduction Laboratory in Queensland have shown positive results that if combined with histone deacetylase inhibitors like SAHA and ROMI, with PARPinhibitors, effective HR pathway silencing mediated by RAD51, BARD1, and FANCD2 takes place. Optimistic for adjuvant therapy in breast cancer especially TNBC.

This is giving the preliminary basis towards a more rational drug design in metastasizing breast tumors.

When tearing down effectively helps in building up

To all intents and purposes, strategic analysis for the means to a goal often takes a system back to the point of introspection and finding the means right within it.

This story dates back to 1863. He was a perfectly ordinary young boy, born to a farmer in rural Michigan. An apt pupil at school, fascinated by machines, he started tinkering on his own. Unwilling to settle as a farmer, he spent more than ten years of his youth job-hopping. Finally, he joined Edison Illuminating Company in Detroit as a night engineer to learn more about electricity. Thanks to his dedication and perseverance, he was promoted to the position of Chief Engineer in just two years. Knowing each of his employees personally, it didn’t take much time for Thomas Edison himself to befriend him and encourage his tinkering and innovative potential. He started experimenting on self-propelling gasoline engines envisioning an era of horseless carriages. After many attempts he finally perfected his automobile engine and started a motor company with one of his good friends. In 1908, the first commercial vehicle for common man started rolling out of his company at a price of just $825 (~ $21,600 2015 USD). A group of workers drudged on one car at a time, assembling the parts by hand. And it took nearly two days for each group to assemble a car. In the first month of production, only eleven cars rolled out. The workers had to literally drag the parts from one place to another in the factory to get different parts assembled. As his company moved forward in this way for four years, he came up with a master plan to improve efficiency and productivity. He deconstructed the whole assembly into 84 core areas, trained a group of workers dedicatedly in one area each. He adapted the idea of steamrollers and leather conveyor belt from the meat packing industry and recreated an automated assembly line. Each worker sat in his position with his part of the whole automobile. The assembly line brought the core assembly towards them at fixed time intervals and all that they had to do was fix their particular part on to the assembly within the stipulated time and let it move to the next worker. In the following year, 9000 cars per day rolled out of his company with an average of merely 93 minutes for assembling one car. The cost of production became so manageable that he could sell his cars for $260 (~ $3,200 2015 USD) less than a third of the initial cost. This brought cars up from the luxury of affluent society down to a necessity of common man’s day-to-day lives. In the coming years, his company produced not less than 2 million cars annually and owned more than 50% of the global automobile market. Any guesses on whose story this is? It was none other than the master team player Henry Ford with his first car Ford Model T that ruled the automobile market for 64 years without even a single advertisement of promotion. And his good friend/ business partner was none other than William Murphy, the founder of Cadillac, the luxury motorcar division of General Motors.

With less manpower and more efficiency, Henry Ford revolutionized the concepts of mass production with two key strategies: deconstruction of the task and teamwork. Nobody can be a master of all trades. But everybody invariably is a master of at least one. The proficiency of a system depends on how well the expertise of each component of the system is explored and utilized best towards a common goal. No system can thrive in solitude. Henry Ford did not invent automobile engines or assembly lines. But he utilized both in the most effective manner possible to bring out the best out of his team. And the best part is, unlike all the contemporary automobile companies of his time, his team was never over worked. Each of them enjoyed the simplicity of the part of work undertaken while getting the returns of the accomplishment of the team as remuneration and job satisfaction. We often meet with not so satisfactory results of our efforts after exhaustively carrying the whole burden of a task ahead on a single shoulder. Flourishing systems do not claim to have components that excel in every aspect, but they positively and absolutely claim utilizing the excellent aspect of every single component of it as a team.

RGCB News: Onam Celebrations and Sadbhavana Diwas

നന്മയുടെ മറ്റൊരോണം കൂടി.....

RGCB hosts the higher education and exploration platform for students and staff from across India. So we feel it is of prime priority that there should be an event to proclaim the unity in our cultural diversity. Every year we choose a day around the regional festival of Onam to celebrate harmony and creative artistic talents of RGCB. On 20^th of August, the staff and students of RGCB gathered together for the festive occasion this year. An exquisite ‘Athapookkalam’ adorned the atrium of the main building welcoming everyone with vibrant colors and floral fragrance. Lighting the lamp of prosperity and good fortune, the senior personnel of the institute started off the day’s events in grandeur. The packed M R Das Convention Centre witnessed a three-hour long cultural extravaganza by the staff and students of RGCB under the commendable leadership of Dr. Ruby John Anto and the student coordinators. Professor M Radhakrishna Pillai, the Director of RGCB symbolically offered a delectable feast to Gods and invited his team to enjoy a traditional ‘Onasadya’ in the in-house cafeteria. Everyone gathered at the courtyard for an afternoon of traditional ‘Onakkalikal’ too. A memorable day of ebullience indeed.

Sadbhavana Diwas 2015

The 71^st Birth Anniversary of Rajiv Gandhi, the former Prime Minister of India was commemorated by observing Sadbhavana Diwas nationwide and at RGCB. Vowing to the very noble cause of national integrity for which this great soul existed, an oath of commitment led by Dr. Satish Mundayoor, the Dean of RGCB was taken.

“I take this solemn pledge that I will work for the emotional oneness and harmony of all the people of India regardless of caste, region, religion or language. I further pledge that I shall resolve all differences among us through dialogue and constitutional means without resorting to violence.”

From the Director’s desk.

We are quite fortunate to be born in that part of earth enriched with unparalleled natural and cultural treasures. Nevertheless, this part of earth is quite unfortunate to be enriched in a subset of people who exploit that. Onam, the occasion reminding us of our glorious past, is the best opportunity to rethink and resolve for a better tomorrow. Let the spirit of Onam be that of sterling joy, prosperity and optimism. Let not the neo modern mechanistic world change our traditions into another feigned obligatory gesture lest the fears of renowned poet Sugathakumari might come true in future not so far away. 

"എങ്കിലുമേതോ വിദൂരസ്മരണതൻ സങ്കടദീർഘമാം പാതയിലൂടവേ

പണ്ടേ മരുവായി മാറിക്കഴിഞ്ഞൊരു സങ്കേതഭൂവിൽപഴയശീലത്തിനാൽ 

കാലം മുടങ്ങാതെ വന്നു പോകും പക്ഷി ജാലങ്ങളെപ്പോലെ ആരോ നയിപ്പതാം
ഒന്നുമറിയാതെ യാന്ത്രികമായ്ത്തന്നെ വന്നുപോകുന്നതാം നീയുമെന്നോണമേ 

അല്ലാകിലെന്നേ വരാതിരുന്നേനെ നീ അല്ലിനെ സ്നേഹിക്കും എങ്ങൾതൻ നാടിതിൽ"

Caenorhabditis elegans: The model system that transformed research strategies worldwide.

Many heard about Caenorhabditis elegans (C. elegans) when they survived even as space shuttle Columbia was ripped apart in its final flight in 2003. But the legacy of this tiny nematode dates back to early 1960s.

Approximately 25,000 peer reviewed publications have used C. elegans as an experimental model organism. More than a thousand research papers have already been published in 2015 with work revolving around C. elegans.  It was the first multi cellular organism to have its entire genome sequenced and the only organism to have its neural connectome fully mapped. Between 2002 and 2008, three of the Nobel Prize winning discoveries were on C. elegans. Two encyclopedias on this organism have been published in 1988 and 1997 with numerous reprints which still serve as invaluable resources for researchers worldwide. Moreover, an online review portal, WormBook consolidates all the works done on C. elegans. There is even an extensive repository of the genomic, transcriptomic and proteomic data of C. elegans, WormBase, accessible globally to scientific curators. This is updated fortnightly, more frequently than any other molecular biology database in the world. Thousands of scientists and hundreds of millions of dollars are involved in C. elegans work around the globe. National Institutes of Health has a dedicated initiative for C. elegans research. For a 1mm non-parasitic nematode feeding on bacteria in rotten organic matter, it is an insignificant organism in nature. But why does the scientific community of life sciences and chemistry work so profoundly on it?

It was in 1963 that Sydney Brenner first proposed C. elegans as the model organism for his studies on the molecular and developmental biology of neural systems. The choice was very crucial. Brenner chose C. elegans for many reasons. He was immensely attracted by the very fact that thousands of this soil-dwelling nematode could be easily grown in a bed of E. coli in a petri dish within the laboratory unlike mouse, rats or higher animals. Moreover, being a hermaphrodite, these organisms self-fertilized and inbred 300-350 offspring per reproductive cycle of just three days. The added advantage came with the knowledge that, they could even be cross-bred with male worms for genetic hybrids. Only plant geneticists enjoyed the convenience of crossing and selfing till then. The total number of cells in the body of this worm is always fixed at 959 in an adult hermaphrodite and 1031 in the adult male. Of these 302 cells are consistently neurons. They form a primitive nervous system with a ‘brain’ of circumpharyngeal nerve ring. This can be easily traced with the contrast optics of serial section electron microscopy. The organism is thus equidistant from complexity and simplicity. The transparency of body gives the unique opportunity to track cellular differentiation and developmental processes even in the intact organism under a simple microscope. Anatomic simplicity, short life span of less than three weeks, fully sequenced 20,470 distinct genes with 50% homology to human genome and long term storage feasibility and easy transportability; C. elegans is one of the best model systems in experimental cellular biology.

Sydney Brenner, H Robert Horvitz and John E Sulston received the Nobel Prize in Physiology or Medicine in 2002 for their work in “genetic regulation of organ development and programmed cell death”. They found out that 131 cells present during the early embryonic stages of the worm were absent in the adult and traced these cell lineages throughout the life span of the worm to postulate their theories on the programmed cell death or apoptosis. Starting from the discovery of nuc-1 by Sulston and ced-3 and ced-4 by Horvitz, this paved way to the identification of many pro and anti apoptotic genes. Later, asymmetric cell division and the fate of each cell during embryogenesis was extensively mapped using C. elegans. DNA recombinations as well as DNA repair mechanisms have been described using the same model organism. Andrew Fire and Craig C Mello worked extensively on genetic interference by hybridization of exogenous double stranded RNA with endogenous mRNA transcripts (RNA interference; RNAi) in C. elegans which earned them the Nobel Prize in Physiology or Medicine in 2006. In fact, C.elegans is one of the first multi cellular transgenic animals created in laboratory settings. Peculiar gut granules of C. elegans emit fluorescence and even cause a fluorescence burst at the time of death of the worm. Martin Chalfie was awarded the Nobel Prize in Chemistry in 2008 for his work on green fluorescent proteins as a marker of gene expression. He did much of his work using C. elegans. From nucleotide base pairing in DNA to genetic basis of muscle atrophy in zero gravity space, C. elegans is helping researchers worldwide to understand the intricacies of molecular biology and genetics.

Interestingly, WormBase has declared prize worth $5000 to anyone who comes up with a better model organism than C. elegans!

RGCB News: Independence Day

Every year RGCB observes the Independence Day of India with nationalism and discipline. Today, the staff and students gathered in the courtyard of the Jagathy campus of RGCB. At 8.30 in the morning, Professor M Radhakrishna Pillai, the Director of RGCB hoisted the National Tricolor Flag. With a salute to the thousands who sacrificed their lives and existence to earn us the freedom we enjoy today, ‘Jana Gana Mana’, the National Anthem was sung. Symbolizing the unity we stand for, everyone sat together for a modest breakfast at the in-house cafeteria. Dr. K Santhosh Kumar, Senior Scientist who hosted the Indian National Flag led the observance at the BIC campus. The National Anthem was sung with due respect and in proper decorum. The staff and students of BIC campus also sat down in the campus cafeteria to enjoy a breakfast together.

From the Director’s desk.

As we enter the 69^th year of being free, we have a long story of ups and downs in Indian history to remember. Much water has flown under the bridge after the midnight when India was finally declared free. The day wasn’t just marking the elimination of the physical presence of a medieval colonialist governing power; it marked the beginning of the end of cultural depreciation, economic exploitation and suppression of free thoughts in Mother India. With freedom come great responsibilities. Today, we are free to express our thoughts, to practice what we preach and stand by our values without an authoritative system imposing undue restrictions on us. We have the social obligation to put our collective efforts for a better tomorrow. Not everyone can simulate a Dandi March to fight for our principles. But as model citizens of this great nation, we should not forget to do our little part. Keeping India clean, not looting public resources, paying taxes, not taking law in our hands, preserving our rich traditional art forms, respecting social justice and striving for technological and scientific self-reliance could be a good start. As Dr. Rajendra Prasad mentioned in the foreword of M K Gandhi’s India of My Dreams, “Freedom is only the means to a greater and nobler end.” Let’s all stay together, walk together, work together towards that nobler end.

Six things to learn from the Indians who made it to the top.

Indian names have been adorning the headlines of world news recently by making it to the top of the multinational entrepreneurships that figuratively rule our day-to-day lives. What can we learn from them?

The morning routine of an average man in any nation in the world is almost the same these days. Waking up to a preset alarm, rushing to the office clad in the metro sexual executive attire in his car, grabbing a go-cup of coffee from a café on the way using his credit card, catching up with the news of the day in the car stereo, returning calls and emails in his phone, to reach office and log in to his computer to work on the documents and work sheets that define his job. But have you noticed that the corporate offices of more than 80% of these quintessential things that cater our needs in a day are globally headed by people of Indian origin? Is it just a coincidence as the wheel of time turns or is it because people of Indian origin actually deserve to be at the top for their unique qualities?

1. Believe in Karma. Ambition and perseverance are not specific to Indians. But the track records of Indians who made it to the top of tech giants show it could be of a higher degree in Indians. Unlike the Chief Executive Officers who founded their parent companies, Indian CEOs invariably started their journeys at the bottom of the tech ladder. Each of them has a long story of perseverance and untiring efforts to their credentials. Satya Nadella joined Microsoft as a technological assistant in 1992. He strived for his goals for 22 long years to ascend through the steps of Project Head, Vice- President, Senior, Executive and Corporate Vice- President to finally reach the coveted position of the Chief Executive Officer of Microsoft. Indra Nooyi started with a strategy position in Pepsico in 1994 and through her master game plans directed the restructuring of the company to its current global status through over-a-decade’s effort to finally be the CEO of Pepsico and #15 in the Forbes list of The World’s 100 Most Powerful Women. Shantanu Narayen toiled as the creative head of Adobe Systems in the company’s journey to the frontlines of digital marketing for ten long years before his current position as the CEO and the President of Adobe Foundation. Anshuman Jain, the co-CEO of Deutsche Bank and Ivan Menezes, the CEO of the London- based distillery giant were also taken up by the respective companies in early 1990s as non-executives. None of them had the privilege of inheritance, pedigree or social dominion to bypass their long journey. None of them sought shortcuts in their race to supremacy. The only tools they utilized were perseverance and aspirations.
2. Communication Skills. Though one should never say this out aloud, it is no secret that we have to thank the British rule for one thing in particular. Our education enterprise. Every single kid who goes to school in India gets a formal education in the global language, English. Most of the schools in India have chosen English as the medium of instruction. With 122 vernacular languages and more than 2000 dialects, English rose up as the one strong unifying element for the 1.2 billion Indians to express their thoughts. When Chinese, Koreans, Germans and Japanese capture the markets with their technological advances, the positions of power and governance seek Indian technological experts with eloquence. Nobody forgets the awkward English speech of Lei Jun at Xiaomi’s launch in India. It is not necessarily excellent oration, but the right choice of words and the right way to speak realistically that can build a good rapport with colleagues and clients. The fine line between firmness and harshness is always crucial for a leader.
3. Academic Competence. It has become a trump card for the youth to quote the stories of Bill Gates, Steve Jobs and Mark Zuckerberg dropping out from their schools yet succeed big time in life ultimately. The world is changing. It is not the same world when they started their journey. Everyone is competent and resourceful. To get an opening in this juncture, we need world class training as well as the name of an alma mater. Most of the Indian executives, after graduating from ace schools in India, had higher education with esteemed fellowships from world class institutions and Ivy Leagues. Though grades actually don’t matter in the future prospects of one’s career, to break into a system one needs strong academic credentials today.
4.  Be the Heart.  Darwin could easily agree that his theory of ‘Survival of the fittest’ suits best to today’s merciless, cut-throat competition than millions of years of evolution. Every system is striving towards stability and has backup plan Bs and Cs if plan A fails just like how the body adapts and functions in congruence by the compensatory performance of the counterpart organ when a kidney, lung or eye fails. We cannot afford to lag behind even an inch lest equally qualified and skilled would replace us. So the key is ‘Be the heart’, be indispensible to the system we thrive in. Then the system will definitely nurture us and our growth. Think about Google without Gmail, Google Maps, Google Chrome, Chrome OS, Google Drive and of course Android. No wonder when Larry Page, the co- founder of Google, decided to form Alphabet Inc, a conglomerate of all the companies owned and  tied up to Google, he didn’t think twice in making his Product Chief Pichai Sundararajan as the new Chief Executive Officer of Google.  With 70 patents on non-volatile memory design and flash storage systems, can anyone but Sanjay Mehrotra compete to the position of the CEO of SanDisk?
5. Humility. “This is a very humbling day for me”, was the email that Satya Nadella sent to Microsoft employees the day after he was appointed the CEO of the company. Thanks to the long journey from middle-class families in semi-urban India, the technological executives from India always stay down-to-earth. They move with the team as one of them. If the absolutely non-geeky Padmashree Warrior could make Cisco into a $135 billion multinational technology company in just seven years through genuineness and team playing, basic humane virtues should be still the fore-runner in the game.
6. Advantage India. Multiethnic background, regional imbalances, economic inequalities, overpopulation and unemployment. The very factors that we point out as India’s major hurdles in progress actually play the key role in making Indians understand the problems of the third world better and customize and emerge with products to feed the needs of the needy. With surging globalization, each system should satisfy every subset of population in the world. This was the very thought behind Android One, the economy line of electronics running Android OS conceived by Sundar Pichai of Google for the less developed countries. Understanding the high cost of overseas phone calls, Gurdeep Singh Pall, the Senior VP of Microsoft came up with Voice over Internet Protocol through Skype. None but Rajeev Suri could play the instrumental role in making Nokia Siemens Network to be the pioneer in consumer electronics hardware market by establishing its service hub in India where 900 million people use mobile phones. As Salman Rushdie once said, “You can take the boy out of Bombay; you can’t take Bombay out of the boy, you know.” Knowing the core India is, in fact, very rewarding.

 Well, these qualities are not just for techies. Think about it.

Stem Cells: The storehouse of potency and potentials

Bridging the gap between bench and bedside, stem cell research is showing promising results in clinical trials worldwide.

There is only one set of circumstances where man puts his effort, energy, time and money to get the less specialized, the less differentiated, the less evolved. And that is Stem Cell Research. Stem cells are the unspecialized cells with the potential to divide continuously to self-replenish and under certain circumstances can differentiate into specialized cells of characteristic phenotype and function. During embryonic stage and early periods of growth, embryonic stem cells divide and differentiate to form the entire body of the organism with all its extremely intricate organ systems. Whereas in the adult organism, somatic stem cells maintain an internal repair mechanism by constantly replenishing and replacing aging cells. Scientific research is gearing towards utilizing stem cells as an elixir for degenerative and autoimmune diseases. Under controlled conditions in laboratory, genetic reprogramming can generate pluripotency in differentiated cells (induced pluripotent cells; iPSCs) which have extensive medical and commercial prospects in drug therapeutics and stem cell therapeutics.

In the February of 2015, a stem cell based therapeutic product was approved for commercial marketing for the first time in the world as The European Medicines Agency approved Holocar for the treatment of blindness caused by limbal stem cell deficiency post physical or chemical burns. Boasting a struggle of 25 long years to bring this product from bench to bedside, researchers, industrialists and clinicians behind the scenes  have opened a wide arena of therapy and hope to common man. The International Society for Stem Cell research (ISSCR) consolidates stem cell research around the globe through updated publications, funding resources, annual meetings, international symposiums and the ‘Guidelines for Stem Cell science and Clinical Translation’. Clinical trials using bone marrow, umbilical cord blood, placental and mesenchymal stem cells for cardiac repair, neurodegenerative diseases, hematological disorders and autoimmune diseases is showing promising results worldwide. Stem Cell Technologies have an online tool for finding the stem cell clinical trials going on in hospitals for various diseases which will help patients to access the facilities under strict regulations. This is adapted from the clinical trial registry maintained by National Institutes of Health (NIH).

Growing at a rate of 30% per annum, the stem cell industry is expected to hit a turnover of $1.2 billion by 2017 worldwide. Forbes reports that the Indian industry is estimated to hold a significant proportion of this market with a worth of $600 million by then. Basic and translational research in this field is funded by funds worth more than three hundred crore rupees mobilized by Department of Biotechnology (DBT) and Indian Council for Medical Research (ICMR) over the past seven years under the supervision of dedicated Task Force teams. But as the research in this field is still crawling in its bassinet, the use of stem cells for therapy in patients may pose grave risks with our relative ignorance about adverse effects. Stem cells, with their immense potential to divide and differentiate in the body, require close monitoring and extremely tight management conditions to be used in patients in a hospital set up. To curb the chances of malpractice in the field, ICMR Department of Health Research and DBT have revised and published the ‘National Guidelines for Stem Cell Research’ in 2013. These guidelines encourage stem cell research at basic and applied levels with adequate regulations but strictly prohibit stem cells for therapy other than the hematopoietic stem cells transplantation (HSCT) for hematological disorders in India. The National Apex Committee for Stem Cell Research and Therapy (NAC-SCRT) monitors the regulatory approvals for clinical trials involving stem cells. Numerous companies in private sector like Lifecell, Stemade (India) and Bioeden (U.S.) offer cord stem cell storage facilities in India at affordable costs today. Let us hope that the new generation, with the privilege of its own stored stem cells, gets the opportunity to address and contain diseases with the commendable progress in stem cell research.

Remembering Dr. A P J Kalam

Rajiv Gandhi Centre for Biotechnology and Swadesi Science Movement organized a gathering to remember Dr. A P J Kalam at M R Das Hall in the Campus I of RGCB at 11 in the morning of August 10, 2015. Dr. G Madhavan Nair, the former Chairman of Indian Space Research Organization, Professor M Radhakrishna Pillai, the Director of RGCB, Dr. Suresh Das, Executive Vice President of KSCSTE and Mr. A Jayakumar, Secretary General of Vijnana Bharati were kind enough to share their very close interactions with Dr. Kalam on personal and professional grounds.

Professor Pillai reminisced Dr. Kalam’s words during his visits to RGCB in 2002 and 2005 during his presidential tenure that he had shared with RGCB blog before. Dr. Suresh Das mentioned how moved he was with the various anecdotes validating Dr. Kalam’s simplicity, humility, leadership qualities and team spirit over and again. Dr. Kalam always wanted his team to be very productive for which he ensured that his team members always had the best environment to work. “There couldn’t be a much better way for Dr. Kalam to leave this earth but while talking to youth about saving earth and making this planet a better place to live in.” He mentioned how once Dr. Kalam sent his manager to take the kids of one of his team members to a carnival when their father couldn’t turn up in time, as he was engrossed at work.

Mr. Jayakumar, having interacted with Dr. Kalam on many personal and official occasions, recalled how powerful a thinker he was and how hopeful he always was of India rising up to the most prosperous nation in the world. He made his wonderful observation that Dr. Kalam started his foresighted journey of interacting with the young minds of India, motivating them, guiding them from north-east India in 2002 and by destiny, ended his circle right there itself after traveling all over India with his visions and dreams for over a decade. He urged each and everyone not to just remember Dr. Kalam by repeating his words or remembering his deeds, but to rise above the conventionalities and put his words into practice, materialize his dreams and bring the prosperity, peace and progress to Mother India that Dr. Kalam envisioned.

Dr. Madhavan Nair, who started his career in the team of Dr. Kalam at Vikram Sarabhai Space Centre in 1967, recollected how Dr. Kalam nurtured him into an exemplary technologist. “He always gave us much more work than what we could accomplish in a given time, but always showed us the right path to travel through to achieve those goals on time”; he told why he never had regrets working in Dr. Kalam’s team. Despite unhealthy competition from his contemporaries, Dr. Kalam rose to be an indispensible part of India’s space and defense programs through sheer perseverance, leadership skills and visions. He always ensured an ideal working environment for his team. While working on a high profile project-nearing deadline, Dr. Kalam made all the arrangements for proper medical attention to Dr. Nair’s son who fell ill and calmly broke the news to him only when his son was safe. He emphasized how much more each of us had to learn from the principles and ethics of Dr. Kalam. Even as the President of India, he did not use a penny from the government to entertain his personal guests in Rashtrapathi Bhavan nor did he recommend any of his acquaintances to any jobs, but rather paid his bills from his pocket and urged everyone to earn a job through good education. He concluded with mixed emotions that Dr. Kalam couldn’t be better described with any words but with the verses of “Endaro Mahanubhavulu”, Tyagaraja’s famous Cranatic kriti that Dr. Kalam always used to play on his Veena.

Procrastination: The Robber of Time

All of us procrastinate. Yet all of us deny it. We often overlook this problem only to land in the mire of unaccomplished goals.

Leonardo da Vinci. The High Renaissance Man. Painter. Scientist. Engineer. Sculptor. Architect. Inventor. Astronomer. Writer. Historian. Anatomist. Words often fail to do justice to what he was. Daydreaming to fly, he designed the very first prototypes of parachutes, helicopters and airplanes centuries before modern aviators could even conceive the idea of flying.  He envisaged exquisite designs of robots, armored tanks, assault rifles, swinging bridges, submarines, motorcars, solar panels and alarm clocks. He is regarded as the most creative and versatile genius in the history of mankind. But in his deathbed at the age of 67, this gifted human being apologized to God and mankind for the offence of his "work not reaching the quality it should have". Why?

Leonardo was an extreme procrastinator. If he had taken the effort to finish any of his ideas on technology, 1500s would have been the modern 1900s. If he had published his findings of Sun being the center of solar system and of the planetary motions, it wouldn’t have taken another forty years for Copernicus to initiate the Scientific Revolution. One shouldn’t be surprised to know that he never finished his masterpiece ‘Mona Lisa’ even after working on it for twenty years. It took him nearly ten years to finish the lips of Mona Lisa. Like majority of his works and notebooks, the painting saw sunlight only after his death when his pupil Salai inherited it. He worked on ‘The Virgin of the Rocks’ for twenty-four years against a seven-month deadline to fulfill the commission and turned in the painting to the church only when his patrons threatened to stop paying him. Though known as world-class painter he was, he only had less than fifteen completed paintings to his name. His biography enlists his countless unfinished projects than his achievements. If he had published ‘The Vitruvian Man’ in 1490 (the date in his notebook), the basic foundation of anatomy and architecture would have been restructured two hundred years earlier. He admitted having flight of ideas so frequently that he thought about at least nine possibilities of addressing a problem within two minutes challenging himself to be productive and effective but seldom could he actually solve the problem as he procrastinated on practicing any of his ideas. He always found his own reasons and justifications to procrastinate and block his epoch-making works.

For the relentless thinker, ever-curious inventor, uncompromising perfectionist, time was the biggest enemy. Even when procrastinating to utmost levels, Leonardo could accomplish more in his life than what we can ever imagine because of his incomparable dimensions of dexterity and versatility. But for us, while swimming in mediocrity, the penalty for procrastination could be huge enough to affect our career, success and reputation. Though International Classification of Diseases has not included procrastination as a behavioral disorder, it is worthwhile to analyze this as a major malady of creative minds. Researchers and students often face this ailment, comprehend the issues of lacking well-timed schedules and agonize over consequential inefficiencies. The degree of procrastination is not usually proportionate to the complexity or gravity of the job to be done. Repeated acts of procrastination eventually make it a part of the person’s character that it starts to span from trivial things to works requiring much time, effort and creativity. It could range from filing tax returns, registering for a conference, uploading a file, writing an article, designing an experiment or analyzing data before a deadline. Many a time we fail to efficiently complete this on time because of congested internet traffic or crashed servers due to innumerable procrastinators rushing at the last moment or unusable samples or data. It even extrapolates to various tiers of personal and social lives too when returning a phone call or email or even planning a vacation stays undone forever. But mere analysis of the problem of procrastination cannot save us from its adverse effects, as even a neurosurgeon can get a stroke. The best way is to identify the problem ourselves, tackle it through our own means and overcome it with diligence. Conquering procrastination is a tedious task but it is worth all the efforts to free us the burden of unfinished tasks and unaccomplished goals.

Personalized Medicine: Where do we stand today?

With major advancements in diagnostic and therapeutic modalities, we are progressing towards an era where each individual gets treatment specifically for the disease in him.

Ten years ago, if a person walked into any hospital in India with a disease, the chances of getting diagnosed and treated by a set of arbitrary protocols were extremely high. The diagnostic tests were meant to confirm the etiology and determine the severity of illnesses. The treatment strategies were meant to address diseases as issues at a social tier. Gone are the days of conventional management tactics and regimens. Today, we are fortunate to avail the benefits of evidence based and personalized medicine. Diagnostic methods investigate beyond simple identification of illness at the generic level. Analysis of a disease to decipher the specificities to genomic level in a particular individual is the focus of diagnosis these days so that therapies can be tailored to address the problem right at its crux.

Skala et al from Vanderbilt University showed promising results of growing organoids in a petri dish from tumor cells harvested from patients to simulate the actual tumor. Fluorescence based quantitative optical imaging was used to measure NADH and FAD in 3D tumors in dish to analyze the drop in cellular metabolic level with each chemotherapeutic agent. This helps to identify drug sensitivity and resistance within 48 hours of culturing the cells, well before the actual treatment is started in patients. Researchers and clinicians in The Institute of Cancer Research and The Royal Marsden Hospital in London used the cutting edge 3D printing technology to “print” phantom tumor models of individual patients and used this to guide them in molecular radiotherapy and fine tuning the radiation dosage. We have grown past conventional radiotherapy too. The Proton Therapy with better tumor targeting has been boasting good recovery with least adverse effects of irradiation in Head and Neck, chest and abdominal tumors over these years in Prague prompting more centers in UK to utilize this technique by 2017. In United States, the Federal Government has undertaken a $215m Precision Medicine Initiative , a bold enterprise coordinated by National Institutes of Health (NIH) to comprehend diseases to the extent of customizing discrete preventive and therapeutic strategies. The initiative proposes near- term focus on cancers and long- term focus on a wider range of diseases.

In India, the disciplines of Basic Science research, Molecular Biology, Genomics, Bioinformatics are being brought together harmoniously by Government and Corporate resources. Council for Scientific and Industrial Research (CSIR) mediates the Indian Genome Variation (IGV) multi centric project to bring to light Single Nucleotide Polymorphisms (SNPs), Copy Number Variations (CNVs) and repeats of 1000 shortlisted genes in Indian population deemed biomedically significant and pharmacogenetically relevant. This information is consolidated into a database freely accessible to researchers and clinicians. The cardinal genomics and drug response studies in India were led by Indian Council for Medical Research (ICMR) Center for Advanced Research in Pharmacogenomics at Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry till 2012 and continued by CSIR Institute of Genomics and Integrative Biology (IGIB). ICMR has been implementing newer task forces on pharmacogenomics to steer studies on pharmacokinetics, dynamics and genomics in Indian population. Department of Biotechnology (DBT) and Central Drug Research Institute (CDRI) have various initiatives towards this cause. Advancing one step forward at a time, the biotechnology industry in India has translated many of the genomic level studies to drug selection tools. The Imatinib Resistance Mutation Analysis (IRMA) for detecting 90 mutations in ABL domain to predict the efficacy of Imatinib in Chronic Myeloid Leukemia (CML) developed by OncQuest Lab is propitious now. Collaborating with international diagnostic majors, Indian companies like Avasthagen, Action Biotech and TCG Life Sciences have brought genomic, transcriptomic and metabolomic testing panels for virulence in Tuberculosis (TB) and drug efficacy prediction in TB, SLE, Glaucoma, Coronary Artery Diseases and Neuropsychiatric disorders.

Rajiv Gandhi Centre for Biotechnology (RGCB) has been a trailblazer in advocating and materializing personalized medicine through various projects involving diseases posing a burden in Indian health scenario.  Multifactorial chronic diseases are dealt with studies on monocyte protein markers in Type II Diabetes Mellitus, metabolomic profiling to predict the risk of onset of Type II DM, neurodegenerative disorders, gut microbiome in malnutrition and Type II DM. Tailored therapy in Oncology is a promising and fast progressing arena with studies on Nanoparticle mediated targeted drug delivery, chemotherapy efficacy and BRCA1/2 in prostate cancer, induced Pluripotent Stem Cells (iPSCs) for in vitro drug testing, epigenetic landscape in endocrine resistance in breast cancer, prognostic markers for oral squamous cell carcinoma, PAK1 and MTA targeted therapy in breast cancer, cancer informatics and disease prediction modeling tools. With the high incidence of infectious diseases in India, the studies like immune profiles in measles vaccine immunogenicity in selected cohorts in India, virulence studies in Chikungunya and Dengue virus, Tuberculosis, Cholera, Malaria and Leptospirosis are very pertinent. The Laboratory Medicine and Molecular Diagnostics in RGCB provides extensive diagnostic and prognostic platforms for cancer, infectious diseases and cardiovascular genomics with dedicated services accessible to public at affordable costs.

The major hurdle in practicing personalized medicine in India is the lack of awareness of its significance among researchers and clinicians. Pharmacogenomics is complicated, time consuming and exorbitant. The positive results obtained under controlled conditions within the four walls of laboratories can be replicated at a community level only if the markers and platforms are extremely robust. Moreover, prescribing and dispensing customized medicines is a huge burden for clinicians unless patients are very well aware of the consequences.  Let us hope for healthy changes in basic research and clinical practices in India to bring forward better clinical outcome through emerging tools in Biotechnology.