And Here Comes Genetically Engineered IT

Hold your breath, we might be in for a paradigm shift in the domain of Information Technology.     If you give it a bit ( pun intended) of thought, Genetically Engineered Information Technology,     is not new at all, and in fact is  as old as  life itself. Sixty years ago,  Watson and Crick unraveled the mystery of the  DNA double helix,  its enormous capacity  for information coding as well as storage and replication.   So technically speaking you and I are Dynamic  Information Storage,  Retrieval,  Application  Systems. Yes, Dynamic indeed; information is constantly being upgraded; reprocessed, put into use...............  without  even having  to press any UPDATE/ delete  button.  . Of course there is a hitch:     convenient and  selective  loss of memory. 

DNA Double Helix 

Quite a lot happened during  the last 60 years. We were initially quite taken aback to note that a mere 4 letter code says all that is to be said in the Universe.  Strange indeed,  but haven’t we ourselves admitted long back that Truth is stranger than Fiction ? Speaking, reading and writing  a language requires increasing levels of  capability and sure  enough we  mastered the DNA  language, learned to decode  the mysterious messages   and and write  some of our own.  Genetically modified  brinjal being an example.  And now we are all set to  exploit this new method in the IT world.  We  have  learned that DNA is practically indestructible  and even after millions of  years the stored  information can be retrieved.  Logically , then  why can't we do away with the current data storage devices  and switch to DNA ?   

With this idea in mind,  Nick Goldman  with his team at the European Bioinformatics Institute at the  European Molecular Biology Laboratory,  Hinxton U.K  collaborated  with  those at the Agilent Technologies Genomics Lab at Santa Clara, California.   They  have come up with a practical guide to exploiting the universality  and robustness of   DNA as an information storage system. To prove beyond doubt the versatility and efficacy of their method the team chose 5 different forms of data:  ASCII text  of all of Shakespeare’s sonnets, MP3 format of the  26 minute’s speech of Martin Luther King’s I have a dream speech,   and .pdf format of Watson & Cricks famous 1953 Nature paper on DNA double helix  and a .jpg photo file of the EMBL  building summing upto little less than 800 kilobytes.  Nick Goldman  told BBC  that one gram of DNA can store up to 2 petabytes of information the equivalent of 3 million CDs.   Their research  paper is published in Nature Magazine online on 23 January 2013.  As Dr Ewan Birney  another team member opined to the BBC “ One of the great properties of DNA is that you don’t  need any electricity to store it. If you keep it cold dark and dry, DNA lasts for a very long time” –  Didn’t Jurrassic Park tell us precisely that?  So unlike  the conventional  storage devices  DNA  storage system will not demand constant attention.

Can this synthetic IT DNA t in anyway interfere with Nature’s life code? The team sets at rest, our   apprehensions. Goldman told the BBC that  though it uses the  4 letters ATGC,  “ The IT DNA  uses a completely different  code to what the cells of living bodies use”    
References : 
Nature Magazine published online 23rd January 2013. 

Ageing Gracefully

Ageing Gracefully

“Lived happily ever after “ is stuff of  fairy tales, no doubt.  However,  advances in biomedical sciences have done exceedingly well to improve longevity.   Well,  as of now “ever” is timed and the maximum is capped at 122 years. Human  curiosity  to understand and  thereby suppress the onset of   senescence  has been   historical and  science  has always helped in clearing the path forward.  Imagine Cinderella to be  at the  over super ripe  age of  120.  She  would have excellent eyesight, thanks to the  jelly like  intraoccular  lens inserted after the  cataract surgery,   would most probably be agile enough with   brand new knee / hip joints,, a few transplanted  organs….etc….   Sure she will  still recognize her Prince charming, would remember the glass slippers that shaped her life,  but  would be unable  to remember why just then she summoned  her maid.  ( Well all these  are applicable to Prince too.)

Amour (Love)    a film  by director Michale Haneke could very well be the story of Cinderella and her Prince. The film, which won Palme d’ Or  at the 2012 Cannes Festival,  was screened during the  recent  international  film festival at  Bangalore.  It is the story of an elderly couple, Anne and Georges. Pathos of  unstoppable old age and  the accompanying  trauma which can’t be wished away .  

 6^th December issue of Nature   has a special section  , sponsored by Nestle,  on Ageing.   A cluster of nine articles spread over 25 pages  explore   multiple aspects of ageing.   Quite interesting is the COBRA ( short for , Cognition, Brain and Ageing ) project, which  aims to monitor the ageing process of senior citizens for at least a decade. .  Volunteers for the study are in the 60+ age group. The study is prompted by the undeniable demographic data.  50 years ago age versus   population   plot looked like an upside down ice cream  cone, but now it is more like an upside down  Chinese soup bowl.  Average age of the global population is increasing  and more specifically population density in the 60+ segment is increasing even faster.  Naturally, both science and society need to be conscious about this  fact and take measures to confront. Professor  Lars Backman who leads the COBRA program at the Karolinska Institute in Stockholm   is confident, even if the path forward is arduous, the effort will be fruitful. His focus is “ Healthy Cognitive Ageing”  One of the key factors he is focusing on is  dopamine, a very important  neurotransmitter equally important in  physical   agility and learning. Dopamine level dip with age. He is asking the most important question:  Are there ways and means to push it up?  

Is old age inevitable ? Professor Caleb Finch Director of the Gerontology Research Institute at the University of Southern California  and his team are  enamored  with turtles and tortoises which  can live close to 200 years. Perhaps they might yield a clue?

The Centre for Eldercare and Rehabilitation Technology at the University of Missouri is focusing on user friendly gadgets  to assist  and enable  people to age gracefully, without having to compromise too much on the quality of life. Professor Eva Kahana  Director of the Elderly Care Research Center at the Case Western Reserve University would like to describe it rather as Ageing Proactively.

All said and done, perhaps  there is an age old recipe for longevity, and that is   starving ( or fasting, if you prefer it that way) .  Professor Luigi Fontana  is convinced that reducing  calorific  intake is the best way to interfere with ageing. This has been proved in laboratory animals.  Are we humans ready to retry this way  out  ?

Goodbye, Mr Chimps

Historical Mansion of Lin An Tai, Taipei ( Taiwan)

I am at the lab usually by 8.00 AM. There are several others who work in shifts to observe and to be observed  because we conduct high end experiments and   hence the need for a 24/7 vigil. Parking lot is visible through the window and Chimps can see me  getting out of my car. He knows that   I get in early so that  I can get a spot  close to this building.  If it were in his power, he would  have ensured that this spot is reserved for me permanently. He is my best friend for the past several years, he has been here longer than me and knows  more than me about the lab and the people.  He grunts when I make mistakes, grins when my experiments are successful.  Usually as soon a  he hears my footsteps in the corridor, he gets up and, swings hanging onto the iron door frame. What a grip, it never slips, at least so far. I admonish him for such acrobatics “ You are getting old, be careful” , but he gives me a huge grin  and reaches for  the breakfast packet.  We split the breakfast – I always carry enough for two-  but not the banana, that is  for him only.

But today he seems  different,  gloomy   and withdrawn. Idiosyncrasies of old age?  Of late he doesn't like me spending too much time with others, did I stop in the corridor too long to exchange a few words with  M.?  You know he notices every single detail. I ask my colleague who was in the night shift and now busy packing up to leave, "What happened? He isn’t  feeling well, looks like .  Or you chided him for something  silly ?" 

“Oh you don’t know?  The authorities are planning to retire him”

“Retire? What  would he do ? At this age? And he has nowhere to go either” I am aghast. "But how did he come to know about it ,I mean did someone tell him specifically ?"

“Oh Come on, He has been here for the past 30 years and he is intelligent enough to understand the goings on. Did we not panic last year, when the talks on downsizing  where in the air ,without being told point blank?”

“Well, but he is a bit different, isn't he? But what would he do ? How will he survive? We can just turn him out “

“He is entitled to  receive full retirement benefits , including medical, I believe.  Better than what most  us can expect.  You know his entire family has  dedicated their lives from day one,  for scientific research.  Elder siblings Rita and Theresa were adopted by the NASA, a few others  were with the  health programs on infectious diseases, HIV/AIDS, cognitive and behavioral sciences …….....  Only the AIDS research didn’t lead anywhere, because they didn’t respond at all.    All of them- they are all much  older than Chimps - have now been retired and  you know what and are being rehabilitated in a resort. “

“You are kidding,  a resort? “

“No! this is not a joke. Chimps  too will be taken there. I hear it is a fantastic place with all modern  fittings, almost like a spa.  Chimps can finally be reunited with his family there. But alas, they may not recognize one  other."

"What do you mean, they won’t recognize?”

“Ha! You are really ignorant.  Chimps,  was  separated from  his biological mother the moment he was born,  just like Rita and Theresa and dozens of  others before them. They were all  bred for  very specific causes by different adoption  agencies.  So  there has been no family bonding whatsoever”.

 “Oh ,then  indeed poor darling will be miserable at the resort.”

“ You know, but that will be best for him, to be with his kith and kin at least   during  the sunset years, they are all very  intelligent, they  will get used to one another . That is the best  we can do for them, after all they dedicated their body and soul for scientific research. I don't mind a bit that we need to foot their retirement and medical benefits bill  ”

“Perhaps you are right, but  we must  visit him every week, how about every Saturday?  By the way what is name of this resort ? “

“ Chimp Haven, the National Chimpanzee Sanctuary, just 22 miles off Shreveport, in Louisiana. Not very far from here. It will be a nice picnic for the whole  family". 

Deeply moved by  a  report that  the National Institute of Health (USA)  is attempting  to rehabilitate  about a 100 chimpanzees, who are no longer of research value , since invasive research on Chimpanzees has become irrelevant. 

 “ NIH faces Chimp housing quandary “:Nature 491, 2012, page 18. 

Treading the middle path

Controversies are part of public life.  Allegations and assertions fly in from multiple sides. Media   committed to   Breaking News every second,  is no help either. Common man is left too astounded at the revelations and too confused  to choose between true and false.   One knows truth is somewhere in between or everywhere, but  nebulous and evasive.

One would have thought  things are very different in the scientific world. After all, science is the pursuit of truth and scientists are driven by hard data alone, not mere speculations. So there should  be just black and white with sharp boundary and  no intervening grey area. If only this were true! State of things are no different in the scientific world either. Only difference is it rarely spills out  into daily newspapers or news channels.  For example the controversy about the genetically modified crops.(1-4) While one group is ready to wager  everything to advocate that  GM crops are man’s best answer to the impending global food crisis, their opponents would leave no stone unturned to prove the opposite. The huge chasm between this divide is filled by  the “maybe/may not be” population  who would keep on  demanding more proof to decide one way or the other.

Another debate which rages on endlessly is the climate change. Well, everybody agrees that  global climate is  changing, but not on the causes,  consequences nor on the urgency to confront the issue.  Of course there is a tendency to link  the occurrence of every natural disaster to climate change has resulted in the trivialization of the issue.   Kerry Emmanuel of MIT has done a detailed study  on the occurrence of hurricanes in the US  and remarks  that  “anthropogenic climate change may have a substantial influence on tropical cyclone activity around the world ” (5).  No conclusive reports have appeared as yet on the genesis of Hurricane Sandy that lashed the US east coast last week.  

These are only minor aberrations. Scientists have always taken decisions, one way or the other. Or else man wouldn't have stepped on the moon, nor  polio vaccine  made.

Tailpiece:  
L’Aquilla (Italy) is  an earthquake prone city, the residents are  aware of that. During March-April 2009, seismologists detected spikes in the activity of Earth’s underbelly, but top scientists of the   NCFPMR (National Commission for the Forecast and Prevention of Major Risks, Italy) reassured the public not to worry,  nothing out of ordinary would happen.  But alas on 6^th April 2009,   at about 3.00 AM the town experienced one of the worst earthquakes ever in the last 30 years.  Seven members of the Commission now stand convicted of manslaughter though not willful.  Their crime, not that they misread the signals , but that they mislead the residents into a false sense of “ all is well”, one of them  even suggesting that they relax with a glass of wine.

.

Sunset  from the shores of  Tungabhadra

References:

1.    Rat study sparks GM furore: Butler, Nature 27^th September,2012 489,page484

2.    Hyped GM maize study faces scrutiny: Butler  Nature 11^th October,2012, 490, 158

3.    Genetically modified plants and human health, Royal Society of Medicine 2008 vol. 101(6) .  290-298, Key et al

4.    Global Warming Effects on US Hurricane Damage: Kerry Emmanuel ftp://texmex.mit.edu/pub/emanuel/PAPERS/wcas_2011.pdf

TWAS 2012@ Tianjin

Science took me to Tianjin, a city, southeast of Beijing  in Mainland China during the  second half of September.

The  occasion was the 23rd General Meeting of the TWAS.  The acronym, TWAS, originally stood for the  Third World Academy of Sciences, with headquarters in Trieste Italy.  Formed in 1983, this started of as an excellent platform  for the   practising scientists and science & technology policy makers of the developing world to meet annually. Perhaps, members felt, the qualifier Third World had an archaic ring to it, so   in 2004, the name was changed to  Academy of Sciences of the Developing World,  though the acronym didn’t match.  But now in   a move to expand the boundaries  ( or rather remove it altogether) TWAS takes on a new avatar,   The World Academy of Sciences, and well  the acronym suits and hence  stays.). Anyway there are several   associate fellows   from the developed world. 

This year’s theme was  science, technology and innovation for economic growth. Chinese President Hu Jintao gave the keynote address. He mentioned that  China drew a  15 year roadmap in 2004, identifying activities and projects that would propel China to the frontiers in that time frame. He  promised 1.5 million US$ to the Academy  to boost  scientific cooperation and collaboration among the member countries. The Ministerial session that followed  had either the S&T minister himself or a top representative from S & T Ministry of   several of  the developing countries  addressing the audience. Mr Vylar Ravi, Minister for Science and Technology, India  also spoke. Particularly heartening was to listen to  efforts of Rwanda, Nigeria and Zimbabwe to alleviate poverty and improve quality of life  through innovations in S&T.  

Scientific sessions were  quite exciting and informative.  TB or not TB by Prof Richard N. Zare of  the Dept. of Chemistry, Stanford University covered his attempts to diagnose one of  most infectious diseases as early as possible.  Interested in the Life and Times of Dinosaurs? Anusuya Chinsamy-Turan of the Department of Zoology, University of Cape Town South Africa, analyses the microstructure of fossil bones to unravel the mysterious world of dinosaurs.

Tailpiece

What did a Bengali and a Keralite do when  they got some  free time in Tianjin?

While the rest went for shopping/site seeing, they visited the Zhou Enlai Memorial Museum. Here are some rare photographs from the museum 

Zhou Enlai & wife Den

May 4th Movement : A painting

Zhou Enlai's Appointment letter signed by Mao

A Copy of Red China

Zhou's letter to Chiang Kaishek

Art and Science of Hunger

Knut Hamsun  wrote  Hunger in 1890(1).  This Norwegian novel, set in Kristiania( modern day Oslo) , recounts the wretchedness of an aspiring  writer caught in the clutches of hunger. His unsolicited  essays are more often than not rejected    by  the publishers, and even on the rare occasions when accepted the reward is just  enough to cover food for a couple of days.   Poverty forces him to pawn every possible material possession he owns.  Partly autobiographical, the tortuous feeling of  hunger,  what it can do to  the physical and mental state of a human being, is splashed across the pages in vivid shades. His mind is at once delirious and sober, indulging  in snobbish fantasies  while still being acutely aware of the stark reality around.  Traumatized by hunger he even takes to chewing bark.   Thirty years later Kafka sketched the  " Hunger Artist"(2)  For Kafka's protagonist abstaining from food is an art and  he does it willingly out of no compulsion whatsoever. Proud of his skill, he is ever ready to demonstrate it under the watchful eyes of the  public ,   seeks no reward and ultimately  fades into oblivion.

Experts say that  one’s daily energy need could be as low as 1600kcals or as high  as 6000 kcals depending upon how heavily one sweats it out. (3) Coupled activity of two key hormones, at the hypothalamus,  ghrelin at the opening ceremony and leptin  during the closing ceremony,   orchestrates our feeding pattern(4). In other words, ghrelin is the start signal and leptin is the stop signal.   It indeed isn’t surprising at all that intense research in the area of obesity  has been instrumental in unraveling the intricate biochemical and neural pathways of hunger. Friedman (5)   and his colleagues at the Rockefeller Institute were doing precisely the same in obese mice population,   when they confronted  leptin  It is astounding that the amount of  leptin generated is proportional to the fat stored in the adipose tissue. That means there is a dynamic inventory going on.

Mutations in the leptin gene or lesions in the hypothalamus regions where leptin is supposed to exert its influence could lead to hyperphagia, a state where the body is in perpetually hungry mode leading  to overeating and obesity. Ghrelin the hunger hormone too acts at the hypothalamus, specifically  on a set of neurons called Agrp neurons.  If the AGRP neurons are provoked into frenzied activity   then again  hyperphagia develops. However,  if somehow  AGRP neurons can be sedated, then  the result is aphagia, loss of appetite and abstention from food.  August 9^th issue of Nature carries a research paper by   Sternson and his team at the Janelia Farm Research Campus, Howard Hughes Medical Institute, Virginia, (USA), which tries to map the   neural circuitry of hunger.(6)  Their findings,  team hopes would prove helpful in  overeating disorders.

At the  Museo Nacional Centro de Arte Reina Sofia, Madrid  

1. Hunger by Knut Hamsun

2. Hunger  Artist  in Selected Short Stories of Franz Kafka, Srishti Publishers, New Delhi 

3. Biochemistry of Hunger 

4.  The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review Klok  Jakobsdottir  Drent ,  Obes Rev. 2007 Jan;8(1):21-34.

5. JeffreyFriedman 
6.The Deconstruction of a neural circuit for hunger : Atasoy, Betley and Sternson, Nature vol. 488, 9^th August, 2012, pages 172-177

Our Microbial Secrets

Microbiologists and those who intently study the origin and spread of infectious diseases are dismayed. millions of people, drawn from  widely different  geographical locations  gather together for sports events like the Olympics or  World Cup , or religious events like the Haj or Kumbh Mela   yet, no major outbreak of infectious diseases has been reported. The Hindu religious festival Kumbh Mela where over 70 million people reportedly gather  and  dip into the same ( albeit, flowing ) waters, is another such unique event. Though there are stringent  guidelines regarding vaccinations against varieties of infectious diseases, the health hazards can never be undermined. Hence there is a new interest on closely monitoring  such " Global  Mass Gatherings" and scientists put their heads together  recently  during a three day conference in Jeddah, Saudi Arabia, Oct 23—25, 2010 

Scientists are divided on their opinion.  The argument that sports events usually draw together hale and healthy youngsters with the best  built-in  immunity profiles, and hence the chances of infections are rare could indeed be valid. However,  that is not the demographic profile at religious gathering. So there is something hidden from view, which guards against. Kamran Khan a specialist in Infectious Diseases, at St. Michaels Hospital, Toronto, Canada, has been collecting data for quite some time on the Haj pilgrims. He admits, tha the Saudi Government  indeed went to great lengths to prevent any kind of human disaster by insisting on the necessary immunizations as part of the pilgrims travel plans, screening pilgrims  at the arrival points, quarantining and treating the sick at lightening speed.  He quotes figures for 2009,  at the peak of  H1N1 scare,  2.5 million pilgrims visited Mecca, and less than 100 were diagnosed with flu.  Could it be that we are too paranoid about microbes and infectious diseases?  ( I can’t help but drawing your attention to an earlier piece  “Befriending Allergens”, where we discussed the benefits of being  on "Hello, How are you?" terms with  other life forms and  chemicals)

So a new project has been initiated,  Human Microbiome Project.(HMP). This is along the lines of the   Human Genome Project ( HGP) initiated about two decades ago, to unravel the locational and functional  mysteries of the genes encoded along the length of the human DNA chain. That exercise is complete, and we have plucked all the low hanging fruits. However  lot more remains elusive and enigmatic and scientists are in pursuit. It is altogether another matter that the HGP also dealt a rather a severe blow to our vanity that less than 25000 genes are enough to define a human being, and that is as much as the mouse needs too. 

What does the HMP endeavor to achieve? Scientists are already aware that the human   body is  literally the universe for  trillions of microorganisms  that coexist within us and on us,  Extensive studies have been carried out on the microbial communities in the gut  and have necessitated  that we do acknowledge the service they render to us. The HMP, intends to go beyond the gut microbiota, and do the  microbial mapping of the entire human body. Known for the precise and systematic methods, scientists  are  being site specific: Ear, nose,  mouth, throat,  under arms, inside elbows………………

Initial results have shown that the the microbiota map is very different from individual to individual  and then  within each individual there are umpteen site specific variations, too. Are we gearing up for another blow? The HMP might reveal that " We are, but what our microbes make us to be.!"

Tailpiece
Robert Hook (1635-1703)( of course,  the Hook's Law fame)  gave us the first concise book on the minute bodies.  Armed with just  a microscope, he explored the realm of  micro dimensions.  The book was published in 1666 by Royal Society of London. And then in 1675, Antonie  Van Leeuwenhoek  (1632–1723) established that there are life forms, so small that they are not visible to the naked eye.  

http://en.wikipedia.org/wiki/File:Micrographia_title_page.gif

References:

1. Reflection and reaction The Lancet Copnference on Mass Gathering Medicine ,

      Lancet Infectious Diseases pp 818-819,  vol.10, 2010, McConnel and Memish

2. Infectious disease surveillance and modelling across geographic frontiers and scientific   

    specialties  The Lancet Infectious Diseases,  pp 222-230, Vol. 12(3).2012     

    Dr Kamran Khan MD, and others

3. Tackling the Microbiome, (Editorial, L Hood), Science , 1209 vol.336, 2012

4.  Do Sports Events Give Microbes a Chance to Score?, Kupferdchmidt. Science 1224- 

    25, vol.336 2012

5.  Science, All articles in the  special section 1245– 73 , Vol  336, 2012.