Taming Hydrogen :Enzymatically

New Year ushers in new hopes and sets aggressive targets. 2014 is no different.   Toyota, the Japanese auto giant unveiled  the  concept version  of a  hydrogen car  or the FCV (fuel cell vehicle)  at  the Consumer Electronics show  currently being held at Las Vegas. The cars will be marketed in California next year and even  the blueprint  for Hydrogen gas stations are ready The car, it is claimed   can reach a maximum speed of 100mph and accelerate to 60mph in 10 seconds.Moreover a fulltank run of about 300 miles is assured. Toyota didn't specify a price , but a humble guess is:anywhere between 50,000  -100,000 USD. (1). Hyundai and Honda motors are also fast catching up

Hydrogen,is the  simple, unassuming numero uno of  the periodic table.  Henry Cavendish, the eighteenth century chemist was the  first  to identify  this colorless odorless gas  and realize that upon combustion it yielded  water. That is why Lavoisier later named it   Hydrogen  that which yields water.  With just one electron and one proton, how complex can it chemistry get? Sure it is simple but  explosive too. It can burst into flames at the slightest provocation. Now combustibility is the hallmark of fuels, and naturally questions popped up among scientific circles. Could hydrogen be the ultimate fuel, because the product of its combustion is the benign and benevolent  Water. Can there be a greener fuel? However easy  combustibility, though highly desirable for a fuel, makes its storage and handling extremely difficult and dangerous.  Scientists have been trying  for decades to tame hydrogen. Indeed  there are success stories, but the price tags are  so exorbitant  that hydrogen as a fuel isn't a commercial success yet .If storage, handling and transportation of hydrogen become  cheaper and viable (on par with that of the crude oil,) then FCVs,  will soon be within common man's reach. Persistent efforts at all levels are on to tackle issues.  It is in this context that we must once again acknowledge help from the   lowly microbes.   

In a recent issue of Science magazine Schuchmann and Muller (Molecualr Microbiology and Bioenergetics, Institute of Molecular Biosciences, Wolfgang Goethe University Frankfurt Germany)  report (2,3)a clever way of  restraining this mischievous molecule. The method may even be economically viable.  Schuchumann and Muller  found a perfect ally in Acetobacterium woodii. These microbes thrive at room temperature , need no oxygen (or in more scientific terms they are anaerobic. It contains an enzyme Hydrogen Dependent Carbon dioxide Reductase,(HDCR) which can chemically link hydrogen (hydrogenase ) to carbon dioxide or peel them off (dehydrogenase) if necessary. In  other words the reaction is reversible. The reaction as depicted  below is quite simple, and devoid of the usual complexities of enzymatic catalysis. Earlier Reda et al(4) reported the use of an electroactive enzyme to bring about the reversible reaction of formate , but  hydrogen molecule did not play any direct role there.

                 

                         

Formic acid is a liquid,and  noncombustible which solves the problem of  storage , handling and transportation.  Schuchmann and Muller point out an  additional advantage; possibility of using  syngas, as the input  stream. Syn gas  is a mixture of  carbon monoxide, carbon dioxide and hydrogen. (CO, CO2 and H2,)  and is produced in bio gas generators. 

The concept of trapping hydrogen in carbon dioxide is not new (4,5). There are chemical methods to do  it, however  they all suffer in one way or the other either  by way of low yields, high temperature requirements or expensive catalysts.   Schuchumann and Miller are hopeful that their discovery  could be a biotechnological breakthrough.

But there are more  road blocks in the path of FCVs :for example   industrial scale manufacture of hydrogen  may not be so green. 

 References:

1. Toyota's Hydrogen car 2014

2.Direct and reversible Hydrogenation of CO2 to formate by a bacterial carbon dioxide:

   Schuchmann and Muller, Science Vol 342, p 1382-1385 , 2013 

3.An enzymatic route to H2 storage  Pereira Science 342, p,1329-30, 2013 

4.Reversible Interconversion of  Carbon dioxide and formate by an electroactive enzyme:   Reda et al Proceeeding of the National academy of Scienes (USA) Vol. 105(31)  pages  10654-10658, 2008

5..Reversible hydrogen storage using CO2 and a proton switchable iridium catalyst in   

   aqueous media under mild temperatures and pressures:  Hull etal  Nature Chemistry : 

   Vol.4,    pages 383- 388,  2012

  

  

Evolution has no End point.

This is breaking news. Scientists have decoded the genomes of two types of snakes , the cobra and python. These results are published in  two separate papers in the recent issue of Proceedings of the National Academy of Sciences, U.S.A. (1,2) Both teams were seeking an "evolutionary" answer to  the peculiar eating habits of these snakes. How did one group develop poisonous venom to kill the prey  and the other acquire enough muscle power to swallow  the prey? 

According to  the tree of Life   the common ancestor of all snakes is the lizard. One school of thought  is that when circumstances forced the lizards to  live in water, evolution shaved off their legs to turn them into more efficient swimmers. Another group is the of the opinion that   at some point perhaps due to adverse climatic conditions, lizards had to take shelter underground and thus  burrowing sawed off the legs.  The verdict is not yet out, but  scales could be tilting a bit in favor of burrowing, because of Najash the Fossil. This fossil of a 90 million year old burrowing snake  sports  a pair of hind legs. Well, getting back to the  cobra- python story perhaps there is a clue in the comparative body sizes of the snake and its  prey;  small agile snakes developed the venomous route to shock and kill their small prey while  big snake like the python  relied more on its own muscle power to subdue  bigger prey. 

Tree of Life  by German Scientist Ernst Haeckel  in the Evolution of Man 1879
Courtsey : English Wikipedia Tree of life (Biology)

Vonk et al set out to understand the molecular biology  of cobra venom.  Venom  is  a concoction of toxic  peptides.  Which genes  code for these peptides? Perhaps that will yield an evolutionary  clue? They sequenced the genome of the king cobra  and  linked the toxic peptides to about 20 odd  genes. They found that the venomous pathway has a pancreatic origin. They also hint at the possibility that the potency of the venom must have increased over a period of time to compete with the prey's ever alert defense mechanisms. Surprisingly the research team found nothing extraordinary in the genes for specific  toxins. These were genes that coded for peptides  used for other bodily functions elsewhere, such as  blood clotting  or BP lowering...etc.  But what intrigued them was the presence of multiple copies of these genes;  perhaps ready for easy and potent mutations. Decoding the genes for venom is a great help to the pharmaceutical field where, be it from any source, venom is worth its weight in gold.  Because venom could hold secret formula for a variety of drugs. Several cardiovascular and CNS drugs are modeled on peptides found in snake venom which exhibit similar behaviour(3). In France, scientist Pierre Escoubas  has ventured to establish a company VenomeTech "to lead the development of new drugs in the area of of pain cancer and diseases of the central nervous system", as the company's website proclaims.  

The story is slightly different in the case of pythons. Pythons  can starve for months at a stretch. But then when they get to eat a sumptuous meal, their internal organs balloon to accommodate the prey and metabolic rate multiplies several fold .  How does this happen?    Castoe's team discovered "massive rapid  changes in the gene expression that coordinate  major changes in the organ size and function after feeding;"  corresponding genes in  humans  perform  rather insipid  jobs in the area of metabolism, development and pathology. Castoe and his team  went one step ahead and compared  the genomes of the python and the Cobra.  They found 7442 genes common for both as well as other vertebrates. They suggest that snake genomes have differentiated and evolved much faster in response to the  peculiar  constraints they encounter.  

That brings us to a curious question.  Does that mean cobras and pythons have reached the plateau  of their respective evolutionary process?  Like as some scientists  assume  Humans are the ultimate intelligent beings ? Far from it. Prof. Richard Lenski at Michigan State University, USA has been studying the evolutionary saga of Escherichia coli for the past two and a half decades.  His experiments demonstrate that evolution never stops; Oh yes, it might  accelerate or slow down , but never stops even in an unchanging environment .   




1. The king Cobra genome reveals dynamic gene evolution and adaptation in snake venom systems: Vonk et al PNAS 110 (51) pages   20651-20656, 2013

2. The Burmese python genome reveals the molecular basis for extreme adaptation in snakes. Castoe et al PNAS 110(51) 20645-2065, 2013. 

3. From toxins to treatment-  Kupferschmidt,  Science 342, 1162-1164, 6 Dec. 2013 

4.The Man who bottled evolution : Elizabeth Pennisi, Science 342 , 790-793, 15 Nov. 2013 

Shaping memories: in Men and Materials

Roshomon (1950) was a  unique film  in which Kurosawa artistically and  elegantly  showed     perceptions are  colored by  personal bias.  Eyewitness accounts could differ widely. Could it be that we see what we want to see? Or could it be that memory shapes and stores  events to suit individual tastes?  Elizabeth Loftus, (Professor at the Dept. of   Psychology  and Social behavior,  University of California, Irvine, USA) prefers to use the term "corrupted memory". Her research studies also suggest  that  human mind is capable of manufacturing memories and holding on to them as real.  Memory is not a "one time, one bit information filed and forgotten" It is  a dynamic  process, and involves  reconstruction and  reprocessing of data.  Many agree with Loftus when she insists that   "eyewitness accounts do not run like a video recording",  and "an individual's beliefs, desires and imagination can fuel misremembering and information from external sources will exacerbate false recollection". 

Having said that it is this very  same memory that guides you back home  in the evening after a day's hardwork. You never tend to lose the way. The route map is engraved in our memory, from home to school/office/market/busstop/ airport wherever you go, whatever be the distractions enroute,  guides you back to home again.  Fed up working with inert, dumb materials,  scientists asked the question: could we engrave such  route maps in materials? Can we enable them to  remember and respond? After all biological materials  demonstrate intelligence. Why can't we teach    a   diamond to turn   into a lump of graphite and back again when necessary?    And why not, after all both diamond and graphite are basically carbon, albeit in different avatars.

Well it is true that we haven't yet reached the diamond-graphite stage yet,  but scientists have been able to design other  intelligent materials.   Shape Memory (SM) materials belong to this class and as the name implies their memory is limited to shapes. They have the ability  to switch   from a permanent  to a temporary form and back again. This switch over could be triggered by a variety of agents: pressure,  heat, magnetic field, electricity or light.  SM  materials have wrought a revolution in  frontier technological applications such as space, robotics, bio medicine etc. The simplest and oldest member in this group is perhaps our humble rubber and its capabilities can be easily demonstrated with  a common rubber band.   Resilience,  the ability to accommodate strain without cracking or crumbling, is the key factor for  a  material  to exhibit SM behavior.  In polymers,  their long chain structure and viscoelasticity   are facilitators. In  alloys the  process is explained through alterations in crystal structure. Nitinol, an alloy of nickel and titanium was the first shape memory alloy to be designed.     

So far brittle materials such as ceramics couldn't be trained to remember their shapes because they crumbled under the burden  of (memory) strain.  But now Li et al have found a way to circumvent that. This collaborative work involves researchers from Massachusetts Institute of Technology, USA and Nanyang Technological University, Singapore.  Li et al report their finding in the 27th September issue of Science.  Their test material is polycrystalline zirconia with small amounts of intentional impurities such as cerium oxide  or yittrium oxide .  Zirconia  is known to undergo  transition from tetragonal to monoclinic form without diffusion.  The investigators  used micrometer size pillars as test samples as this enabled them   to get high surface area at the same time allowed them to  keep  the   volume low.  This is a small step leading to a giant leap because ceramics are ideal workhorses for high temperature applications. 



References:

1. Misinformation can influence memory for recently experienced highly stressful events 
    Morgan et al.,International Journal of Law and psychiatry 36, 11-17, 2013

2. Evidence based justice: corrupted memory,  
   Nature Vol. 500  268-270, Aug. 14, 2013

3. Eyewitness testimony in the Lockerbite bombing case 
    Elizabeth Loftus Memory, vo.21 584-590, 2013

3.Shape memory and superelastic ceramics at small scales 
    Lai et al., Science : Vo. 341,1505-1508 , 27 Sept. 2013

On the use of Pesticides

Silent Spring was published  in 1962. In it Rachel Carson   raised an accusing  finger at the indiscriminate use (often as an aerial spray) of the insecticide DDT, (dichloro diphenyl trichloroethane). She shook the  collective conscious of the society to take note of the environmental deterioration happening around; what the pesticide was doing to the bees and birds.  The use of  DDT as a pesticide  was finally banned in the US in 1972.  Half a century later we are still struggling  with pesticides; should we or shouldn't we?    In 2012 alone over 3500 research papers have been published on the lingering effects of pesticides  in the environment. Even so   in 2012 the pesticides' sale stood at several billion dollars ( the break up goes like this . Herbicides: 40%  , Insecticides: 33%, Fungicides: 10%, Others: 10%)
  
This is the current state with ~6 billion population. Another three and a half decades and human population will touch the 9 billion mark.  Farm lands  will shrink to yield space for   housing colonies and offices. With limited agricultural land,  how to feed  the 9 billion? Quite a challenge and many  living today will  get a chance to witness it, because 2050 is near future. The question is can we repose faith in fertilizers and pesticides alone  to double, triple or quadruple the farm output? As facts stand today this will be suicidal. Because fertilizers don't distinguish between crop and weeds and pests have developed resistance to several pesticides. Besides in many places environmental accumulation of pesticides have begun to spell disaster for human beings as well.    

What alternatives do we have? Or do we have alternatives? It is indeed true that science and technology have been our constant companions  helping us  to improve quality of life in many different ways.  However it is necessary that we exercise caution and discretion, or   else  we land up  in greater dangers.  August 16th issue of  Science has reviewed the current situation with respect to pesticides. Several articles reiterate the need to adopt  an Integrated Pest Management Program worldwide .Two reports one is from down under and the other from Vietnam,  are eye openers. 

Ryegrass
Courtsey : Wikipedia 

Ryegrass menace has been with us from biblical times.It is a persistent weed which grows alongside wheat crop. And the weed enjoys unhindered growth in Australia.  Initially Hoegrass, a herbicide  could contain  the weed. Then gradually the dosages had to be increased  and ultimately  the weed developed  resistance to the herbicide. Then farmers switched to other herbicides,  but to no avail, because continuous use and large doses again led to herbicide resistance. Then AHRI (Australian Herbicide Resistance Initiative), set up by Powles, himself a farmer,  took up the responsibility  to educate farmers.  First of all, the farmers were told that they MUST read the label and follow precisely the directions on the label regarding the  usage and dosage. They must not exceed the recommended doses.  Second, just like crop rotation, they must   keep changing the herbicide every year, so that the weed doesn't get time to develop  resistance. These steps together with mechanical destruction of the weed seeds have proved   immensely useful. 

Brown Planthopper
Courtsey:
RRI supports Thai move to stop insecticide use in Rice

The other story comes  from the lush green  rice fields of Mekong delta in Vietnam. With help from the International Rice Research Institute (IRRI, Philippines), farmers here have learned to cut down on pesticides by almost 80% through the practice of Integrated Pest Management Program. Planthoppers (Nilaparvata lugens) is the biggest enemy of rice crop  and bees and wasps are its predators. Now  along the field dividers, farmers grow a variety of plants including flowering plants.  The flowers attract bees and wasps  which   feast on the planthopper larvae on the rice plants then settle on the flowers for the dessert of nectar. 

We may not be able to say NO to pesticides altogether but we can definitely reduce and even eliminate  their ill effects by judicious usage. 

Reference 

1. Silent Spring : Rachel Carson,  Penguin Classics ISBN:9780141184944 
2.Science  16 August 2013 special section on Pesticides

Tales of Adaptation

"The reasonable man adapts himself to the world, but the unreasonable one persists in trying to adapt the world to himself. Therefore, all progress depends on the unreasonable man."- 

So spake George Bernard Shaw.  Biologically  we are   hard  wired to  adapt, but mentally we are determined  to resist and conquer   Adaptation   is not an accident, but an  intentional evolutionary trick, in other words a  time tested  route to survival.  Recent  research papers highlight this unique trait  the  quintessential characteristic of evolution,  instances when adaptation becomes  the best form of resistance. Here are a few such tales. 

We don't consider cockroaches intelligent, even when told that in the event of a nuclear war, they will be the sole survivors. We  lay all kinds of traps for them, to wipe them from the surface of the earth.  However, the tiny cockroach is smart enough to see through all such  tricks and in turn develops its own defense strategy. Sugar   is the key  additive in  the bait recipes to lure cockroaches  and  would you believe it, German cockroaches (blattella germanica) have evolved a clever way of saying "NO" to these sweet poisons.   Wada-Katsumata and his team carried out a  comparative study of two populations of cockroaches over several years.   The test group,  was consistently and continuously exposed to  glucose containing insecticide and the control group   was reared free of  restrictions. The lifespan of these insects could be as long as  9 months. After several years,  using glucose and caffeine for sweet and bitter taste the team monitored the responses of both populations of   cockroaches. That is, they monitored the responses of four specific GRNs, ( Gustatory Receptor Neurons, or simply the  taste buds) of cockroaches. GRNs are the quality control lab for edibility and taste.   In normal unbiased cockroaches  GRN1 responds exclusively  to sweet taste, and GRN2   exclusively to bitter , while GRN3 and 4 could be titillated by both sweet  and bitter taste.  Analyzing the  resultant neuronal signals generated at these GRNs,   the  investigators  found that years of continued exposure to  sweet poison,  triggered glucose aversion in the test  population. Their  GRNs had undergone modifications with the result that sugar   tasted  bitter and they consciously avoided the baits.   And this   information was built into their genetic make-up and passed on to  successive generations. 

Just as,  thousands of years ago,  natural selection favored a deliberate mutation in the hemoglobin gene of the sub Saharan Africans faced with a deadly form of malaria. This mutation  turned the nice spongy disc like hemoglobin into a sickly looking sickle shape  but bestowed resistance to the disease and thus  ensured survival. It is  suggested  that  sickle cell hemoglobin molecules don't confront the  malaria parasites at all, they simply raise the tolerance factor of  human blood to these parasites (2). This heritable trait is passed onto the offspring.  However there is a catch. We carry  two copies of every gene.  A combination of normal plus  mutated gene works as a protective armor, but if  both are mutated  then  other lethal complications set in.

So what is the dynamics of adaptation?  A rather elaborate study on evolving yeast populations has yielded at least  some of the answers.  Lang et al who pioneered this study found that when faced with challenges, the organisms split into groups and  try several pathways all at once  and the best one survives. (3). 

Rats, in a similar fashion can rewire their metabolic capabilities when the need arises. Stylopoulos and his team  were studying rats which underwent GBP. GBP in more explicit terms is gastric bypass procedures. GBP, (and there are several types)  is a medical procedure to down size stomach.  It is  being recommended  as a treatment for weight reduction for  obesity and possibly obesity related diabetes.    Surgically,   top portion  of the stomach    is sliced off and then  directly connected to   the small intestine (jejunum), thus bypassing almost 90% of the stomach pouch. Smaller the stomach, lesser the food intake, that is the logic.  But then stomach is not just a passive receptacle for food, it  plays a crucial  functional  role in human machinery. So what happens when the major portion of stomach is eliminated and   undigested food is  tipped into the small intestine ? Stylopoulos and his team  observed that the gut almost immediately  adapts to improve glucose homeostasis, by slightly enlarging itself and enhancing glucose expenditure. 

But alas the benefits of the GBP stops  with the individual, their offspring  still retain the risk of obesity and diabetes(4).  Being inclusive of next generations, doesn't make business sense either, does it? 

1. Changes in taste neurons support the emergence of an adaptive behaviour in 
    cockroaches. Wada-Katsumata etal Science p. 972- 975 24 May 2013,
2.Sickle Haemoglobin confers tolerance to Palsmodium infection.Marguti et al.Cell           
   145(3)398-409    
3. Pervasive genetic hitchhiking and clonal interference in forty evolving yeast populations 
    Lang et al Nature 29 August, 2013, pages 571-574
4. Reprogramming of intestinal glucose metabolisk and glycemic control in rats after   
    gastric bypass. Seidi et al Science page 406-410, 26 July 2013
5. Heavy toll of stomach surgery :Nature 29 August 2013 page 504

Stockholm archipelago: view from the ship

Time for the return of the Prodigal Child.

For Albert Hofmann, chemistry was his  hobby as well as his  profession. Employee of  the drug company Sandoz, in Basel, Switzerland,  Hofmann's toys were organic molecules. In 1938, while playing with a rather unstable chemical,  lysergic acid,    he made   a series of its derivatives,    with the hope that at least  one among these  might prove to be a potential cardiovascular drug. None proved satisfactory, except that the  25th compound in the series, a colorless tasteless solid,  made the guinea pigs  unusually restless. Hofmann labeled the compound   LSD25 in his notebook and soon forgot about it.  But in 1943, on a hunch  he synthesized the molecule, LSD25,   lysergic acid diethylamide,   again. Here is what happened in his own words 

"I was forced to interrupt my  work in the laboratory in the middle of the afternoon and proceed home being affected by a remarkable restlessness combined with a slight dizziness. At home I lay down and sank into a not unpleasant intoxicated like condition characterized by an extremely stimulated imagination. In a dreamlike state with eyes closed (I found the daylight to be unpleasantly glaring), I perceived an uninterrupted stream of fantastic pictures, extraordinary shapes with intense, kaleidoscopic play of colors. After two hours this condition faded away." 
(Albert Hofmann, LSD : My Problem Child)


Hofmann was bothered, he had  to clear the nagging doubt in his mind, so  three days later he carried out a self experiment. The mystic chemist  intentionally dissolved what he then considered a very small  amount,  250 microgram in water and consumed it. A very precise scientist, he wrote down the time and observation:  19th April 1943, 16.20 hrs: "Tasteless". Forty minutes later is the next entry in the note book:   dizziness, anxiety , visual distortions, unable to move limbs and an uncontrollable desire to laugh. He had to be escorted home by his colleague. The news spread like wild fire, and before long  Hofmann realized that his Problem Child was born. Labelled as hallucinogen and psychedelic drug  LSD fell into wrong hands  was misused, abused and  finally   disgraced, denigrated and shunted out of public view. 
                                        
It is now 75 years since LSD was first synthesized. The medical curiosity didn't die down completely. Of late  there is a renewed, though  subdued interest in LSD  as an anxiety alleviator  and some of the credit for this should go to Serotonin, a neurotransmitter. Serotonin is a tiny organic molecule, an amine,  originally isolated from  human  blood serum and hence the name.   Much later serotonin received a more scholarly and chemically precise name, 5-hydroxytryptamine, which soon  became  just 5-HT, short and sweet.  5-HT proved to be  very mischievous and got  implicated in several diverse and contradictory physiological and psychological functions. For example it could induce migraine or a  general sense of well being, it could induce appetite or nausea.  Intrigued, scientists    prodded on; once released what does it do and where  does it go and sit?   It  was soon found out  that there are,   at least 15 sites along the central and peripheral nervous system, where 5-HT can dock.  These docking stations  are referred to as 5-HT receptors. It is now known that LSD has a preference to the receptor 5-HT2A. Detailed structural information about  5-HT2A receptor and   how  LSD binds to it will unravel most of the mysteries.  

Hofmann died at the age of 102,  to the very end he believed in the therapeutic value of LSD. 

Reference 
1.  LSD: My     Problem Child  by Albert Hofmann. 
2. Structural Basis for Molecular recognition of Serotonin receptors 
    Wang et al Science 3rd     May vol. 340, pages 610-614,  2013 
3. Structural features for functional selectivity at serotonin receptors.
    Wacker etal Science 3rd May Vol. 340, pages 615-618.  2013

Have we Murder'd Sleep ?

Still it cried "Sleep no more!" to all the house 

"Glamis hath murder'd sleep and therefore Cawdor 

Shall sleep no more, Macbeth shall sleep no more!"

(Macbeth Act 2, Scene 2)

Greed and ambition robbed  Macbeth  ( and his Lady too) of his sleep. Among other things it played havoc with his  decision making capability and drove him to commit heinous crimes. Once mental peace is lost, sleep is hard to come and vice verse. ,  Then the vicious cycle starts and soon it is hard to say what was lost first, the sleep or the mental peace?  And so we use a general term Stress . Sleep deprivation doesn't add up as in simple arithmetic, we need to resort to complex mathematics to see the cumulative effect.  Recent issue of Nature (1)  has a special section on Sleep. 

Life evolved on earth with Sun the energy source as the sole reference point. Under nature's supervision work-life balance also evolved,  day light hours for work  and  night for sleep and rest.  The circadian clock was embedded in the suprachiasmatic nucleus (SCN), which took orders from the retina in the morning and  responded to the melatonin level build up after sunset. Melatonin is secreted by the pineal gland which preferentially works during the night shift.  Everything must have  gone on well, till Prometheus stole fire from the heaven and man realized that fire could be used not only to cook delicious food and keep warm but also to light up the dark night. From then on we have been trying to extend daylight hours, literally burning the midnight oil to make the night as bright as the day could be and the advent of electricity was the greatest triumph of all.  But that upset the carefully built in circadian clock within the human body.   

The circadian clock is delicately balanced by the interplay of  neurotransmitters such as acetylcholine,  , orexin, noradrenalin, serotonin, histamine, dopamine  etc during the " Arise awake" phase. When pineal gland senses no more light is coming through the retina,  it starts secreting melatonin which in turn gives the signal for the build up of a simple molecule gamma amino butyric acid or GABA for short. GABA  lulls us to sleep. But mind you,  all these neurotransmitters hold several other  jobs too.  Professor Charles Cziesler is convinced that artificial lighting has interfered with this delicate balance. Retina perhaps never experiences total darkness and that impairs the build up of melatonin. and hence GABA. But can we go back in time to be cave men, hunting by the day and sleeping by the night?  Of course not. Especially when we have learned to cross continents and time zones. So what is the quickfix? Sleep inducing pills? But they are not without side effects. 

Macbeth couldn't do much to get back his sleep, but we could and should. Can we be coached and coaxed into better sleep behavior?   Prof. Espie  is exploring the possibility of putting Cognitive Behavioral Therapy (CBT) to use.  He has developed an online program called the Sleepio which aims to do exactly the same.  A  good night's sleep  could do wonders and could be a simple remedy for several ailments. That is why the crucial question of sleep hygiene is doing the rounds. To begin with, have you removed those audiovisual distractions  from your bedside?

Reference 

1. Sleep: Nature  23rd May 2013 vo. 497 pages S1-S20