Hair raising experiments

Who isn’t worried about hair? Age and gender  take a  united stand against this common enemy.   And what challenges!    Either it is too oily or too dull;  too thin or  too bushy;  too curly or too straight to be styled;  greying too fast or too dark to take up any color!  Every third commercial in the TV suggests solutions with desirable outcomes. Pick your choice.

Besides being the crowing glory, body hair as an integral part of skin plays  an important  role in maintaining homeostasis. The hair that sticks out of the skin is actually a string of dead cells. But can there be death without birth?  Indeed hair  too goes through a birth and  growth period before embracing death.

Life cycle of the hair is actually   the  life cycle of  the hair follicle.  No new hair follicles are made postnatally, the lower portion of the follicle goes through cycles of regeneration  to produce new hair to replace the old.  For this  we are born with a storehouse of stem cells  Anatomically this storehouse is  called the “bulge” ( a rather unscientific term, I agree) at the base of the hair follicle.  These stem cells  are pluripotent, means they can   differentiate into adult hair follicles, epidermis or  sebaceous glands.  Because of the pluripotency  and also because they can be easily cultured in the lab,  skin stem cells  have attracted considerable scientific curiosity.  Several laboratories  around the world are  actively involved in  unravelling the mysteries of the skin and hair.   

Anagen and Telogen are the active and resting phases of the hair follicle  cycle.  The dynamic transition from growth state to rest state is the catagen phase.  During the anagen phase the hair follicle sports  vigorous growth and hair forms.  How long the anagen phase prolongs decides how long the hair will be. But this is genetically predetermined. At the end of the growth phase,  the blood and nutrient supply to the follicle is cut off and it  shrinks and shrivels.  The nascent   hair is pushed up to replace the old one. The shrivelled follicle rests before getting rejuvenated for the next cycle.  Every single hair follicle goes through these three stages albeit  not at the same time.  The  green, amber and red signals  during the hair  life cycle is definitely not synchronised. Imagine  shedding all our sclap hair in one go! What a disaster. Likewise hair on the scalp  has a different  cycle time than the one on the eyebrow or for that matter hair on the hands.  There are instances of synchronized seasonal  cycles.  For example it has been reported that in several breeds of  sheep  the hair is in the telogen phase during winter months. When the ambience warms up in spring the follicles move into anagen phase and  get  ready to shed the old hair.  

Sure enough there is a circadian rhythm at work and scientists  had recognized this very early. The biological  Master clock is in the hypothalamus, (suprachiasmatic nuclei to be precise) but then there are a few autonomous ones scattered elsewhere in other tissues, skin being one among them.  The circadian rhythm is implemented through  a very intriguing interplay among   sets of proteins called, CLOCK, BML1, CRYs and PERs.  The dancers frequently change partners,  take quick  forward and backward steps, ( positive and negative feedbacks)   to  regulate the anagen, catagen, telogen phases.      

Janich et al (3)  conducted in vivo and in vitro studies on special breed of rats. They focussed on the  “bulge” stem cells.  The stem cells have two classes of population: one group  in an “Ever Ready to Go” state, while the remaining   lazily dozing off.    What causes this class divide.  isn’t yet clear. But      Janich et al observed that by disrupting circadian rhythm  they could either increase or decrease the population ratio.    However   upsetting the circadian rhythm  proved  detrimental because it  led to premature aging.

1. Epidermal stem cells: Properties, markers, and location

Robert M. Lavker  and Tung-Tien Sun

PNAS December 5, 2000 vol. 97 no. 25 13473-13475

2. Epidermal stem cells of the skin.Blanpain C, Fuchs E.  Ann. Rev. Cell Dev Biol  2006;22:339-73.

 

3. The circadian molecular clock creates epidermal stem cell heterogeneity.

Jannich et al Nature Vol. 480, 209-214, 2011.

4. Clock genes, hair growth and aging

Mikhail Geyfman and Bogi Andersen AGING, Vol 2, No 3 , pp 122-128, 2010

 

Science and Technology for the Developing World

 Earlier  published in  JFWTC Journal, Volume 5, Issue 2, 2009

With the developing countries increasingly poised to dictate the global market trends and growth potential, it is only appropriate that focus shifts to their specific needs. So what exactly are the specific needs of the developing world? Topping the list are obviously clean water, energy and healthcare at affordable costs. The qualifier “at affordable costs” has a universal appeal not just restricted to developing nations. Human mind is tuned to equate low cost with low (read less efficient) technology; a grave misconception indeed. High tech and low cost are not necessarily mutually exclusive as the cell phones technology has proved admirably. So the need of the hour is innovative ideas. Governments in the developing countries are getting sensitized on the power of science and technology as strong enablers for national progress and are open to ideas from all segments of the society.

Govt of India, for example, has floated several platforms for the collaboration of scientists and technologists with entrepreneurs to fast track “an innovative idea to market”. The Techno Entrepreneurial Promotion Program (TEPP) is one such initiative under the Department of Scientific and Industrial Research, Ministry of Science and Technology, Government of India. TEPP recently came forward to partner with the GE Edison Challenge, the annual technical challenge for students organized collectively by GE India Technology Centres and hosted by JFWTC, Bangalore.

This year students were challenged to come up with a technical solution, practical and sustainable for the energy needs of a small Indian rural community. TEPP volunteered to award Rs. 20,000/- as seed money for each of the 18 finalists to build models prototypes to substantiate their ideas. Subsequently each team will get to interact with a business incubator cell to prepare a strong business case. They could then approach the TEPP for the second phase of funding to translate their ideas into reality. As Dr A.S. Rao, former Director of TEPP puts it “Of course this is investing in risk. Perhaps less than 1% of the funded projects will mature into successful products / business. But it is worth the risk .”

Other devloping countries are not lagging behind either.Last year in Mexico and this year in Durban, I got the privilege (Accompanying Person, as the Academy puts it ) of seeing at close quarters the workings of the Academy of Sciences for the Developing World (TWAS). The events th th were the 10 and 11 Annual General Conferences of the Academy respectively.

TWAS is a consortium of distinguished scientists and engineers founded in 1983 with head office in Trieste,

Italy. Late Nobel Laureate Abdus Salam was instrumental in this intiative. One of the focus areas of the organization is sustainable development through science and technology, a common thread linking ~900 members across 100 countries: 85% of them from developing countries. TWAS firmly believes cultivating scientific temper is key to alleviating the miseries of the developing world and works very closely with Science and Technology Ministries to promote scientific research in key areas. Besides, the Academy has in place a host of other programs and activities too. For example (TWOWS) is a platform exclusively for women in science and engineering, while Inter Academy Panel (IAP) focuses on International Issues. The IAMP (InterAcademy Medical Panel) and the Consortium on Science, Technology and Innovation for the South (COSTIS) have broader playing fields.

More often Science and Technology per se cannot provide complete solutions. Efficient management is equally important. A case in study is eThekwini; the Water and Sanitation Services for the city of Durban. To begin with Government of South Africa treats water as a human right and provides 200 litres of water to every household every day free of charge. This is the baseline. Any requirement above this threshold is charged on a well defined slab system. EThekwini has 29 decentralized waste water treatment plants (DEWATS) in which it treats 500 million litres of waste water per day.

Tailpiece

While at Durban, I visited the Phoenix farm, the first ashram Mohandas Karamchand Gandhi founded in 1904. Most of the original buildings were destroyed in ethnic violence in the 80’s but the house and an office have now been rebuilt on the same site. The building which originally accommodated the printing press is currently a school and the house, a simple structure, a sort of museum. It was here that Gandhiji gave definite shape to building an egalitarian society based on the principles of nonviolence; it was here his ideas on satyagraha took root. It was electrifying to touch the printing press which must have churned out copies of Indian Opinion. Photographs and original letters are displayed on the walls of the house; many of them rare and precious. These bring into focus momentarily the man and the workings of his noble mind. For example the one Gandhi wrote to his elder brother regarding a family feud. 

Outside the mango trees were heavy with fruits and of course the fruits tasted divine

Of Microbes and Men

 Earlier published in JFWTC inhouse Journal  

A microbial power plant?   Concept is not new, has been bouncing around for almost 100 years.  Bruce Sterling’s science fiction “Distraction” set in the year 2044 does allude to it.  A series of articles in a recent issue of Nature ( 18^th May 2006)  focuses on microbial capabilities and efforts to harness them for serving mankind.  A team of   electrical engineers, microbiologists, biotechnologists and environmental chemists spread across globally, definitely see  a possibility, albeit  not immediate. There are several hurdles to overcome before  the lab  model becomes a commercial reality.

The focus is on the oxidative metabolic pathway of the microbes.  Chemically oxidation is stripping of electrons and reduction is gaining of electrons.  The essential consequence of the oxidative metabolic pathway is an electron transport chain which begins with  the nutrient  and after several steps  ends at oxygen.  Flow of electrons means passage of current.  So in a microbial soup if you can siphon off the electrons onto a suitable anode instead off to oxygen,  while continuously replenishing the nutrient medium then you have a fuel cell.

Yuri Gorby¹ and his team have put to work photosynthetic bacteria Synechosytis in a microbial fuel cell.  Central to this set is Gorby’s observation that the bacterial surface has thin whiskers of nanometer dimensions which together with cytochrome  facilitates conductivity.

At Penn State University Bruce E. Logan² and his colleagues are using these miniature power plants to clean wastewater and also to generate hydrogen.  By blocking the supply of oxygen and a meagre input of 0.25 volt, the team could achieve four fold increase of hydrogen production. 

The current per se might be infinitesimally small, but the potential?  That is what  Prof. Peter Girguis’³ team at  Harvard  is interested in.  But the problem is to make the electrodes “ bacteriophilic” or coax the bacteria to get closer and adhere to the electrode.

A couple of years earlier Schroder etal⁴ from Institute for Chemistry and Biochemistry, University of  Greifswald, Germany used platinum with a coating of poly (tetrafluor aniline) to  improve electrode/bacterial interface.  They reported Clostridium butyricum or Clostridium beijerinckii with   carbohydrates as nutrients could  generate  current densities between 1 and 1.3mA/sqcm. 

Recently Willy Verstraete and his team⁵ (Laboratory of Microbial Ecology and Technology,   Belgium) demonstrated that when microbial fuel cell units are stacked together the power output could be multifold. They reported a  “Maximum hourly averaged power output of 258 W m^-3 using a hexacyanoferrate”. Their observation that in an MFC, the microorganisms colonise  as a biofilm and live in close contact with the electrode  is a crucial piece of information.   Because biofilms  are the toughest architecture of bacterial colonies and might be the surest way to improve the electrode-microbe interface. 

Kolter and Greenberg⁶ report that when bacteria opt  to settle down as a biofilm it secretes a glue which holds the colony together and also helps the film  cling  firmly onto the substrate surface.   Biofilms of microbial colonies  are tough, mutate quickly and become drug resistant.   Naturally    Kolter’s   interest is in rupturing the  film  so as to  break up the colony and subdue the microbes on a one to one basis.    But from the MFC  perspective   important question to ask is can we facilitate the secretion of that glue  selectively so  that the MFC microbes  adhere more firmly to  the electrode surface ?

1.      Batteries not included : News Feature ,  Lane, Nature 441, p274 (2006)

2.      Increased power and Coulombic efficiency of single-chamber microbial fuel cells through an improved cathode structure, Logan etal.  Electrochem. Comm. 8:489 (2006).

3.      Circuits of slime:   News feature,  Schibert,  Nature 441, p276 (2006)

4.      Electrochemistry Communications, Schroder et al   6, p955 (2004)

5.      Continuous electricity generation at high voltages and currents using stacked microbial cells,  Verstraete et al  Env. Sci. Techn 40, 3388   (2006)

6.      Superficial Life of microbes: Kolter and Greenberg,  Nature 441, p 300 (2006)

                                                                                                             

Through the Eye of a Needle

Published in JFWTC  inhouse Journal Vol 4 Issue 3 2008 

Years ago de Gennes addressed an interesting  situation in polymer physics. Suppose a sufficiently long polymer chain in a viscous solution, has  one end anchored to the wall.   How  fast  will the free end of  chain find its way to the surface?

He  referred to this as “ Ariadne’s thread’.  The allusion was to Greek mythology, of Ariadne helping her friend Theseus to enter and escape  from the infamous maze.  The maze (Labyrinth) was  built by Daedalus the architect  to entrap the dreaded monster Minataur.  Once inside one would go endlessly along the twists and turns without ever finding the exit.  Ariadne gave a ball of thread to   Theseus  and he was to tie one end of the thread to the door post as he entered and unwind the ball as he moved straight ahead  and down (and never  be tempted to turn left  or right or up).  Theseus  thus came  to the the heart of the Labyrinth where he encounters and kills the sleeping Minotaur and  retraces his way along the threadline back to the doorpost  ( read safety and freedom) .

Well, de Gennes didn’t put any condition on where exactly the polymer terminal should appear on the surface.   What if he had?   This would have  changed a “random walk” process to a  more purposeful errand.  Any such  process then would need the machinery of “ molecualr recognition” for successful accomplishment.  This exactly is being addressed  in  the December 12^th issue of Science by  Deutman et al.    The challenge is to   coax  the   free end of a long polymer chain to thread itself through a molecular ring. 

Even in the macroscopic world it is not an easy proposition to thread a needle (especially if you wear bifocals).  You need to perfectly align the eye of the needle against the stiff tip of the thread to make the process easy and smooth.   Now you need to accomplish this at molecular level  and on top of it  the thread must find the eye of the needle  on its own ! This  has multiple biological implications  such as translocation of proteins and viruses across cell membranes.   The paper aptly titled “Mechanism of Threading a Polymer Through a Macrocyclic Ring” demonstrates this in a synthetic system.

For the eye of the needle, the team chose macrocycles  of varying ring size ( 5 to 22 atoms).   The threads were polymer chains (upto 440 atoms in length).   The threads were special in that they were knotted at one end. ( one terminal had a a bulky end group, while the other terminal was free).  Closer to the bulkier end, the chain carried a special affinity group  which could selectively recognize  and latch onto   companion group on  the outer rim of the macrocycle.   Complexation between the two groups  leads to a fluorescence signal and the team used this to monitor the kinetics of  threading.

Deutman et al have proposed possible threading mechanisms.   The  intramoleular insertion  model actually suffers a little  too much from steric  and process complexity : initial complexation of the thread and the ring and  then  looping of the chain followed by  insertion of the free end and then  the chain unlooping to stretch  and straighten out.  The thermodynamic calculations  are given,  but it isn’t very clear whether this multistep process  will pass the free energy and entropy audits.   It would be interesting to explore  the possibility of the   free terminal being  the guiding factor, rather than having the recognition site somewhere along the chain.  Another  twist to the challenge will be if  the macrocycle could sport a  molecular slit  through which the thread could  slip itself inside at  any point along the chain length.

In the same issue,  we get a peep into the  behaviour of a complex family  of  trans membrane proteins called secondary transporters,  which facilitates the passage of  small molecules and ions across the lipid bilayer.   While  substrate  molecules smoothly   roll to  the other side by  a mechanism  reminiscent of  peristaltic movement; the inhibitor moiety is stuck at the front gate itself.  Singh et al have  provided crystallographic data to support the same.

References :

1.Reptation of a polymer chain  in the Presence of Fixed Obstacles

de Gennes Journal of Chemical Physics, Vol. 55, p.572-579; 1971

2. Mechanism of Threading a Polymer Through a Macrocyclic Ring

Deutman et al Science Dec. 12, 2008   1668-1671

3. A Competitive Inhibitor Traps LeuT in an Open-to-Out Conformation.

Singh et al Science 12 December 2008: Vol. 322. no. 5908, pp. 1655 - 1661

Crossing the Frontiers

Published in JFWTC inhouse journal  Vol.4 Issue 1-2 (2008)

That geographical boundaries are never  barriers in the pursuit of science is once again  reinforced  in the  12^th June issue of Nature.  This issue  carries a  very important paper  by    29 scientists  from 4 nations on  how Gama Secretase Modulators ( GSM)  act  (1).    Gama secretase  is the   key  enzyme  which chops up the  Amyloid Precursor Protein (APP)  into  fragments.   Of these fragments,   the 42 residue long beta amyloid peptides  cling together  to form the debris patches responsible for  Alzheimers’s disease.  The shorter fragments are (as of now) considered harmless because they don’t lump together .

Modulators  are small chemical molecules which  as the name implies, influence the activity of an enzyme. For example  ibuprofen  modulates gama secretase to preferentially produce only the  short fragments.   The global team had a very clear objective in mind: to find out the mode and site of action of  ibuprofen like  modulators.   This then could pave for the design/identification  of more powerful modulators to effectively counter the progress of Alzheimer’s disease.   Usually, molecules such as modulators, inhibtors or enhancers,  bind to the  enzyme itself and alter its  ability to bind to substrate.   However  the team was surprised to find that the  GSMs actually  sat at strategic positions on the  substrate APP and prevented  the  enzyme from making larger cuts!   So now there is a rush to screen and identify  the best of the lot and pharmaceutical firms are already smelling  billions of  dollars in profit.

The same issue of Nature describes the possibility of pH imaging of tissues in vivo (2).   GE Healthcare is an industry partner in this work done in collaboration with University of Cambridge.  The assumption here is that tissue pH is  indicative of  the tissue health. So can we measure or map it ?  The team injected  hyperpolarized ¹³C enriched bicarbonate solution into mouse having subcutaneous lymphoma. They then   measured the signals of  H ¹³CO₃ ^-  and  ¹³CO₂  using  MR .  pH could then be calculated from the age old Henderson-Hasselbalch equation.   This paper  has  two significant take aways   yes  the tumor pH is lower than the surrounding tissue pH and  yes, it is possible to measure tissue pH in a quick,  noninvasive way.

The 8^th World Congress on Biomaterials held at Amsterdam from 29^th May till 1^st June had an apt subtitle: Crossing of Frontiers.  The Congress, held once in 4 years facilitates  interactive sessions not only on Biomaterials  but also on all relevant adjoining scientific disciplines.  It was indeed a crossing of frontiers of materials, medicine and biology on one hand and academy and industry on the other.  The wide range of  perspectives that these  groups brought to the discussion table  facilitated innovative collaborations.

The Congress was just intense. I have never poured over a conference abstract book with so much thoroughness.  With 9 parallel oral presentation sessions from  8.45 AM till 5.30PM and  15 clusters displaying close to a total of  1600 posters,  it was necessary to do some homework.     Sitting  late into the night  I marked  the specific oral and poster presentations  I must not miss at any cost.   

“Layer by layer nanoassembled biomaterials”  was one such  theme.     Often referred to as LBL , this technique  is an area of intense research today because of the  innumerable possibilities it offers,  in terms of  structure and function of the ultimate product.   Akashi’s  group from Osaka University  presented the their elegant work on the fabrication of  cellular multilayers on  gelatin and fibronectin  films. 

On Nanopatterning    IBM research group at Zurich  in collaboration with  Georgia Tech,  demonstrated  how the simple technique of microcontact printing   could be used to get not only  protein arrays but  entire  protein libraries on a  substrate surface.    MAPS (Microstamping onto an Activated Polymer Surface)   a new acronym  that caught on fast,   refers to  the process of  patterning  biological ligands and proteins onto the surface of polymers.

 Three dimensional scaffolds for tissue engineering  was another actively deliberated  theme.  Spanned across  several sessions  participants presented new data on  synthetic and natural polymers, composites, hybrid hydrogels,  electrospun systems,  etc. with spherical and cylindrical geometries getting special attention.  The symposium on “ what intrinsic information content is required of the scaffold  in the tissue engineered constructs” was an attempt to set  some guidelines on the selection of the scaffold chemistry and geometry depending on what needs to grow on it.

Hydrogels  continue to be  the most preferred  biomaterial  for many applications.  I was pleasantly surprised and indeed proud  when several of our papers  published a decade ago were cited  in connection with synthesis and characterization of Polyethyleneglycol  hydrogels.  

Tail piece :

The  Biomaterials Congress  opened with the enactment of Rembrandt’s “Night Watch”.  The characters marched to the stage to the accompaniment of the drum beat and took up their positions as if ordained by Rembrandt.  For a moment we were transported to the Rembrandt era  till we saw one of them easing out of the cluster and go to  the mike to address the audience.  There is an interesting addendum to the “Night Watch”.  History states that  all those in the  painting actually paid Rembrandt  to be there, except perhaps  the drummer.

1.Substrate targeting g Secretase Modulators:

   Kulkar etal  Nature 453,  925- 929  ( 12 June 2008)

2. Magnetic resonance imaging of pH using hyperpolarized ¹³C labeled bicarbonate

   Gallagher et al  Nature 453, 940-943 (12 June 2008)

3. World Biomaterials Congress   http://www.wbc2008.com/

Climate Change : Are we prepared?

Published in JFWTC inhouse Journal Vol3 Issue 4 2007

Whichever way we look at it, the picture is dismal.  In a single stroke “climate change” has turned the picture of future  bleak  with just grey and black.  Be it the Amazonian forests in South America or the e Western Ghats in south western India,  experts say we are on the brink of losing it all.  Minute upward variations in temperature  portend cataclysmic  consequences.

Malhi etal in the 11^th January issue of Science analyzes the combined effects of climate change and deforestation on the precious  ecoheritage of Amazonian forests.  These forests are essential drivers  of the hydrological cycles over the whole of northern hemispheres in particular and global in general (the  El Nino effect).  If  climate change  is the sum of multiple activities not easily comprehended, contained or controlled, could we at least  put a check on defrorestation?  Malhi et al give us  alarming figures arrived at in 2001.    837,000km²  of forests cleared for pastures, soybean production and other human activities.  Containing deforestation alone thus looks to be the immediate first step.   But  how effectively can we do it?

Some of our good intentions could actually bring about alarmingly opposite results. For example the effort to switch to biofuels to contain emissions.  The case for greener biofuels   seems to be  actually askew.  Benefit calculations of biofuels  are based on  greenhouse gas emissions  alone  and don’t take into consideration the entire crop cycle and its effect on the ecosystem.  William Laurance  of  Smithsonian  Tropical research Institute, Balboa, Panama, describes a rather convoluted situation.   Governmental subsidies are luring American farmers to  switch  from Soy to Corn.   Result ?  Scarcity in the global market place drives Soy prices high and Brazilian farmers with an eye for profit  are losing no time in  clearing large stretches of Amazonian forests for cultivating soy.  So when we complete a full circle are we really achieving what we intended to achieve?  Is there a real winner?  

Two very recent publications in the 29^th Feb. issue of Science  confirm our worst fears.  Calculations done by  Timothy Searchinger  of Princeton University  and his team show that we will be very much in the red if  crop lands become biofuels farms. It would take  us upto several centuries to pay up for this “carbon debt.”   In the same issue  Joseph Fargione  and his team  presents results  which  concur  with this observation.

That brings us  to the question of how climate change would affect the food situation.

Here we have an added challenge: increasing population. We are perhaps fast approaching the Malthusian limits.  Urbanization is progressively encroaching into land available for cultivation.   Food crops will take time to adapt to variations in temperature and rain fall and the immediate result would be a decline in the production.   Lobell et al  cautions that by 2030 we will be in a critical situation with respect to food security.  The  situation in the geographical regions of    South Asia, China and South East Asia  collectively with  a total of over 500 million malnourished people  is at a greater risk.   Rice is the staple food in this region.  Rice cultivation requires plenty of water and is heavily dependent on seasonal rains.  With temperature on the upward trend, rains are bound to be erratic.    A streak of rosy paint here is that the rice genome has been completely mapped.  Scientists should feel the urgency in genetically engineering rice and other crop varieties that could withstand higher temperature and drought, the inevitable consequences of climate change. 

Another ray of hope : Geneticist Craig Venter   is  absolutely convinced that  his  “Fourth generation fuel” project   will be ready  in about 18 months.  He is focused on genetically  modifying  mictobes  to accept  CO₂   and give out  octane in return.  Not that such microbes don’t exist.  They do, but   octane yields are  pitifully low, nowhere near the needs of humankind. Venter is confident  that   genetic engineering is the answer. His own words  "We have 20 million genes which I call the design components of the future. We are limited here only by our imagination."

Prabha R. Chatterji

1. Climate Change, Deforestation and the Fate of  the Amazon

    Malhi et al Science, 2008,  319 p 169-172

2. Switch to corn promotes Amazon Deforestation

    W. Laurence  Science 2007,  318, 1721

3. Land clearing and biofuel  Carbon debts.

   Fargione et al Science 2008, 1235

4.Use of US  cropland  for biofuels increases greenhouse gases through emissions 

    from land use change

    Searchinger  et al Science  2008, 319, 1238

5. Prioritizing Climate Change Adaptation Needs for  Food security in 2030

    Lobell et al  Science 2008, 319 p607-610

6. Craig Venter at the Technology, Entertainment and Design conference in Monterey, California. Feb. 2008

Virtually There !

Published in JFWTC   inhouse journal Vol3 Issue 3 2007

Two articles in two separate issues of Science,   constitute very captivating reading.  July 27^th issue of Science carries a  review on the enormous possibilities  a  Virtual World can provide. William Sims Brainbridge, the author  is with the Information and Intelligence systems Division of the National, Science Foundation, USA.  Aug.24^th issue has a scientific report on “Video ergo sum: Manipulating bodily self consciousness”,  in simple terms “ out of body experience”. The authors  Bigna Lenggenhager  and Tej Tadi  are from Laboratory of Cognitive Sciences, EPFL, Lausanne Switzerland Thomas Metzinger has affiliations with both Guttenberg and Goethe Univ., Maiz and  Olaf Blanke is from the Dept. of Neurology University Hospital, Geneva.

The first article deals with “Virtual World”.  Most of us have had a dose of this  through “Matrix “a movie which powerfully presented  this concept. The story is set in the 2199   when mankind is reeling under the threat of  a complete take over by intelligent machines.  The machines, in an effort to subjugate the mankind,  have designed the Matrix, a virtual world and the trapped, hapless humans believe that they are living in the real world. The saviour Neo, fights against odds to snap the spell and bring deliverance to all. Much earlier in  a Walt Disney movie, TRON,  an Master Control Program (MCP) digitizes  Flynn, the slighted scientist and the MCP condemns  him to play virtual games   till death. But ultimately Tron rescues Flynn by destroying the MCP.  Even prior to this we have had glances of a virtual world in “Alice in Wonderland”.

Currently World of Warcraft (WoW) and Second Life (SL) are the popular online role-playing  internet games set in virtual world.  Bainbridge argues that virtual world need not be confined to cybergames and science fiction, but can be effectively used to  generate quantitative data for social , behavioral and economic sciences. In fact National science Foundation, USA has provided support to set up two educational virtual worlds “River City” and “Quest Atlantis”.  Stretching further, Bainbridge suggests that one could, perhaps   get a peep into elusive concepts such as “Self and identity” by cleverly manipulating the various “avtars”. 

And that is where the  investigations of  “Video  ergo sum” team snugly fit in. Simulating an expansive three dimensional  ambience is one thing and being in there as a “virtual body” is altogether different matter. How does self awareness manifest itself in such ambience? The team set out to seek answers through  a  carefully  designed clinical experiment,. They simulated a virtual reality around participants and  conducted a modified version of the “rubber hand  Illusion” experiment. (A cleverly designed  experiment which tricks the brain into accepting the rubber hand as one’s own). 

The present  experiment involved a three dimensional  rear view   of the  participant himself and synchronous and asynchronous multisensory inputs such as vision and touch.  The experiments per se were very simple; but had to be carefully  conducted. Analysis of participants’ responses has led the team to conclude that  the brain can be cleverly tricked into being in an “ out of body” state.  Conflicting  multisensory signals led the  participant to feel the image seen in front is the  real self.  The team believes the temporo-parietal junction in the brain  has a big role to play in inducing the  “out of the body experience”. 

But what is relevant here is the fact that  through conflicting sensory signals and appropriate imagery  “there, that is me”  feeling can be generated.  As Bainbridge suggested, the potential lies far beyond the boundaries of the entertainment  zone.   Are we getting closer to understanding ourselves through a virtual presence in a virtual ambience?

References:

1.      The scientific research potential of virtual worlds;    William Sims Bainbridge Science 27^th July Vol. 317, pages 472-476

2.      Video Ergo Sum : manipulating bodily self consciousness;  Bigna Lenggenhager, Tej Tadi, Thomas Metrzinger, Otaff Blanke , Science 24^th August 2007, Vol. 317, pages 1096-1099

  

Octopus shows the way

Published in   JFWTC in house Journal Vol.1 Issue 1 2005


Biological species are a perennial source of inspiration to scientists and engineers: be it  developing  a new material , fabricating a smart device or  designing a  more versatile robot.

Prof Binyamin Hochner, a biologist at Hebrew University in Jerusalem,  Albert H. Titus assistant professor in electrical engg.dept.  at the State University of New York,  Buffalo and Eric Baer Professor in Polymer science at the  Case western University have one thing in common: all three are totally captivated by  the Octopus.

An octopus, of course  has several fascinating  features.   To begin with it is a truly blue  blooded animal because  copper rich hemocyanin flows  through its veins. Anatomically it is a mass of soft flesh with no internal  skeleton.  It manages to keep its eight long dangling  arms  free from entanglement.  It can regrow  an arm if one is  severed.  At times  it resorts to  this trick willingly to escape from  a fearsome predator.  It has other escape modes too: several hidden sacks of  thick blackish ink  which  can be  sprayed  to confound enemies Its  specialized skin cells are capable of  color changing as well as  reflection and refraction  of light. Octopus uses this in multiple ways :  to camouflage themselves with the ambience, to  communicate with other octopuses, or as a warning signal.

Binyamin Hochner, heading the Octopus lab  at Hebrew University in Jerusalem is eager to learn a few things from the octopus  to design the  next generation  robots with flexible arms. It is the neurophysiology of the  arm that  amazes Hochner’s  group. Not only the  arm has seemingly infinite degrees of freedom, it can almost do the great Indian rope trick. For example, when in demand, the soft supple  arm  can turn into  a segmented semirgid structure. 

So how does the Octopus do it ? The answer lies in  the structural features of the arm which anatomically falls in the class of muscular hydrostat, a hydrostatic system where the fluid ( water)  is within muscle cells.  Since water is incompressible, contraction of the muscles in one dimension causes expansion of the hydrostat in an orthogonal direction. The production of movement and force is dictated by the constant-volume constraint in these structures.  Elephant trunks and tongues are other examples of a muscular hydrostat.  

The muscles themselves are special and made up of  longitudinal,  transverse  and helical  fibres.  A fibre reinforced   hydro or organo gel composite is the  closest approach to a muscular hydrostat. Karra from the dept. of Computer science and applied mathematics is working with  the team  trying to unravel the complex  biomechanics and movement control strategies by developing a physical 3D dynamic arm model and simulations.  

Titus, the Optical engineer at the State University of New York  finds  the octopus eye to be  an amazing organ.  The most  unique being.

Octopus eye is fitted with a biological lens that rolls  in and out  of the socket to focus close up, and distant objects respectively.  Titus has an NSF funded research project  to  replicate an octopus retina in a silicon chip,    Titus has  built into his  O-retina chip  the capability to distinguish objects on the basis of brightness, size, orientation and shape.  Titus hopes to incorporate polarized vision as well as edge recognition in future versions. Polarized vision   enables  the octopus to spot  otherwise transparent prey such as jellyfish.  Edge detection is  a data compression feature very special to biological eyes. Edge information usually is sufficient for detecting and tracking objects.  In robots, this chip could thus allow for faster processing of visual data. O- retina chips will be low in power consumption because  it uses analog circuitry. Ideal for  autonomous robots or other devices that need to work overtime.

Eric Baer and his team  are  trying to mimic  the focusing power of the octopus eye. The octopus eye,can focus light five times more strongly than a human eye s. Many biological lenses consist of several nanolayers  and form a smooth gradient that helps to focus light.  Baer’s team picked two commonly available polymers:  poly (methylmethacrylate) and poly(styrene-co-acrylonitrile). These polymers have different refractive indices (1.4893 and 1.5700 respectively),  By varying the number of polymer nanolayers in each film, the researchers varied the final resultant  refractive index.   One such set when  rolled  into a sphere  had a focusing ability equivalent to that of the octopus eye. Baer is optimistic, that  this paves the way for  designing lenses with almost any desired focusing power. He has already made for  himself a pair of reading glasses.

Courtsey : National Geographic News   February 9, 2005  Optical Engineering  August 2003  and Nature Dec. 7, 2004

One hundred years of Alzheimers disese

Published in   JFWTC in house Journal Vol.2 Issue 3 2006

Nov. 3^rd issue of Science carries several interesting articles on  Alzheimer’s disease.  It was exactly 100 years ago on 3^rd Nov. 1906 that  Dr Alois Alkzheimer  presented a detailed  paper on this   bewildering  disease. The occasion was the  37^th meeting of the German psychiatrists  in Tubingen, Germany. The papers collectively   read almost like “One hundred years of solitude” by Garcia, peep into the developmental biology of this debilitating disease.  

As the head of the anatomical laboratory of a psychiatric clinic, Alzheimer and his team had  observed  intriguing   protein patches  in   epilepsy patients during brain histopathology studies.   In April  1906 one of his female patients  afflicted with  progressively deteriorating  mental faculties   died and the subsequent neuro pathological studies revealed the presence of patches and tangles  in her brain.  This was a sort of clinching evidence for Alzheimer , whose notebook contained entries  after entries of  mentally ill and epileptic patients  and their brain histopathology reports.  He now had enough proof to make the connection: accumulation of debris in the brain to deteriorating mental faculties.

But that was 1906 and only the beginning of understanding Alzheimer’s disease.   While it might have been easy to identify the chemical nature of the protein, b amyloid,  ( now we know it a short polypeptide 40 or 42 residues long , trimmed to size from a larger  precursor) , it has taken several  decades to understand  “how” and the “why” is still shrouded in mystery.  Besides the b amyloid protein  which deposits as the patches, our current knowledge implicates another candidate:  the highly phosphorylated forms of t (Tau) protein which forms the fibrillar tangles.  But there are several unanswered questions. Brain has at least 6  forms of t protein and all six  have other essential functional responsibilities as  stabilizing agents for   “ microtubular assembly” which are structural components of a cell.. So when does Dr Jekyll become Mr Hyde? And more importantly what is the   link  between b amyloid and t proteins.  Do they work independently or in collusion?

Age appears to be the major predisposing  factor while inherited forms  of the disease  are rather rare,  less than 1% . Statistics paints a horrifying picture of the disease spreading like wildfire. Already we are being challenged with a physically  aging population, add to that dementia.   Scientists are pushing hard for a weapon to face and subdue disease. Blocking the overproduction of the causative proteins using drugs could be one way  which is the current method.   However, it has also been noticed that this blocking upsets several other delicate biological balances within the body.  That calls for more elaborate efforts in drug design. Time is not on our side here given that each drug has to go through several phases of testing, often spanning several years before it is certified

Of course the best  remedy is to spot the patches and fibrils at the molecular level and contain it then and there. We are not there yet, but soon will be.   Or perhaps one could use cleverly the “ silencer genes” ( Nobel Prize 2006 for Physiology & Medicine) to turn off  (and on as often as necessary) the  b amyloid  and t protein genes. 

Befriending the Allergens

Before ordering  Chinese food at least some of us  put in a  rider, to the cook,  "No MSG please".  And  then there are others who  would stay away from peanuts or egg.   Few others  move around with a swollen face and leaky nose during spring.  Ah we are facing  ALLERGY 

So what causes of allergy?  Allergy is human body's natural and immediate reaction  when it spots  something foreign/ alien ( technical term Allergen) in its radar screen, be it air borne or food borne. A whole battalion of defense forces roll out of their resting dens and unleash their weapons and the body suffers.

Allergies of all types are on the rise in the West and billions of dollars are being provided as support grants to scientists to unravel the enigma.  Progress has indeed been made but more needs to be done.  Thus we now know that . while  leucocytes might be the common term for the defense force,  there are very  specialized warriors like the neutrophils , eosinophil, basophils, lymphocytes, the T cells, natural killer cells ..................  Checks and counter measures are also in palce. For example another set of cells  called Regulatory T cells  ( or Suppressor T cells )  sees to it that this  killing spree  doesn’t go unchecked and helps to bring about some sort of   peaceful coexistence between the warring groups. 

There have been umpteen discussions on whether allergies are  inherited or acquired  at a later stage in life  as a consequence of life style, eating habits etc.  Well  it could be both. If there is a family history sure enough  there indeed  is a predisposition.  After all  isn’t the  foetus   protected  by the  antibodies  present in  mother's blood?  

November 24th issue of Nature magazine carries a special section on Allergies.  The demographic analysis brings in interesting results.

·         Allergies in general are on the rise in the developed world

·         Asthma is extremely common in North America, Australia & South America

·         Asthma is lowest in parts of Russia,  China

·         Food allergies are  negligible in India though asthma is prevalent.

To get a better perception of the Nature Vs Nurture argument we need more information on the subsets: such as how do the first, second and third generation immigrants in the developed world fare?.  This is awaited.

But the first  bullet is intriguing. Why the West is more prone to allergic diseases?  With cleaner living conditions and higher standards of living  one would have expected  the  West to have healthier trends?  That,  too much hygiene could indeed be an issue was first pointed out in 1989 by Doctor David  Strachan (Department of Public Health Sciences, St George’s Hospital Medical School, London, UK). Since then this is known as the  Hygiene Hypoythesis . 

Too much of antibacterials and antibiotics  eliminate not only the pathogens but also the good ones.  The human body,  thus robbed off the  opportunity to make an acquaintance with the microbial  community,   classify and confront them en masse as aliens/antigens. So the need of the hour is to strike a balance.  Shutting off the enemy completely may not be such a good idea; instead confront them early on so that  we can get to know them, devise a strategy and suitable weapons. [ Isn't  this the very  idea behind  vaccination?]

  

Studies are on to introduce allergy sufferers to miniscule amounts of the allergen and thus slowly develop their immunity.     Duke University Medical centre at Durham, NC USA and University of Cambridge, UK conducted independent experiments on peanut allergy.   In both studies  (groups size of 20-25)  kids   prone to allergic reactions with peanuts were  encouraged to eat   minute amounts of peanut  flour , the dose increasing daily over a 30 week period. At the end of the trial period  several of them could eat upto  30 peanuts without any harmful side effects. 

Though  this trick is known for centuries , it will take time  to transform this into a proper form of  therapy.   But for the time being,  what is your peanut tolerance? 

REFERENCES

Nature  24 November 2011 pages S1- S27.

David P Strachan Family size, infection and atopy: the first decade of the “hygiene hypothesis” Thorax 2000;55(Suppl 1):S2–S10