Influenza Marches On

Its winter here in Calcutta, India. The sombre wintry wind and the overcast skies bring a pall of melancholy in their wake. To add to it, the bird flu wave this part of India is experiencing, leaves us all sad in the stomach.

While this epidemic of avian influenza (bird flu) is affecting large parts of Asia, Europe and extending its grip towards other continents, the earliest known documentation of human influenza was given by Hippocrates (the famous Greek physician, known as the Father of Medicine) about 2,400 years ago.

It is known that the disease caused by orthomyxovirus ( an RNA virus) occurs more commonly during the cold winter season. In fact, the word influenza comes from the Italian word Influenza di freddo meaning 'influence of the cold'. But why this season is specially chosen by the virus is not known for sure. Many different explanations have been put forward. Some say that in winter people remain indoors, they huddle together thus facilitating the spread of infection. People also go on holidays during this period and may thus help in disseminating the infection. Others argue that in winter the immunity is low due to fall in vitamin D level (staying indoors will mean less exposure in the sun, causing decline in vitamin D levels.) Some researchers even postulated that air currents in the upper atmosphere during winter was to blame.

Peter Palese, a flu researcher of the microbiology dept. of Mount Sinai school of medicine in New York, now suggests that it is the winter's influence on the virus that may be responsible and not the other way around. During winter, the humidity in the air is less. The droplets containing the virus get dried up faster and thus suspend in the air longer. Moreover, the cold air is more conducive for the virus. The virus is more 'stable' during winter.

Compared to common cold (caused mostly by rhinovirus and spread mainly via droplet infection or direct touch or with fomites such as door-knobs, handkerchiefs etc.), influenza is a much more severe disease. It spreads via droplet infection. When we sneeze, for example, droplets of mucus are thrown out at high speeds of about 150 kph (as is shown in the figure). Thus influenza differs from colds. It should also be differentiated from Haemophilus influenzae, which is a bacteria that produces pneumonia, meningitis and other diseases.

In influenza, the patient suffers from cough and cold, myalgia or muscle weakness, headache and other symptoms. Apart from giving symptomatic relief and antiviral drugs [Tamiflu (oseltamivir) Relenza (Zanamivir): both are neuraminidase inhibitors and interfere with the budding out off the host cells], we must also vaccinate persons by giving 'flu shots' for prevention. Typically, a trivalent vaccine is used to offer immunity. The virus contains two important antigens- hemagglutinin and neuraminidase. The genes that are responsible for the antigens, H and N, mutate rapidly thus evolve into new strains easily. The avian flu virus (H5N1) is usually restricted to the birds. But they are changing patterns and are out to get us. This will be fatal!

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The Scent of a Pathogen

Our immune system, the defense ministry of our bodies, tackles extraneous foreign molecules in a variety of ways. It may produce highly specific antibodies which fight against specific pathogens, as an example of 'adaptive immunity'. Or it may act then and there by virtue of 'innate immunity'.

Adaptive immunity takes some time to develop : due to the processing and presentation of antigen and the subsequent production of antibodies. Innate immunity, on the other hand, is inborn: encoded in the genome. They have broad specificity, meaning that one soldier (receptor) can kill a variety of organisms only if they fitted a certain criterion.

This is exactly how innate immunity handles pathogens. The soldiers (cells) in charge of innate immunity first detects the telltale signature trail of the pathogen: PAMPs or Pathogen Associated Molecular Pattern. Some of the examples of this molecular pattern are LPS (lipopolysaccharide of Gram negative bacteria which serves as endotoxin), peptidoglycans of Gram positive bacteria and flagellin of bacterial flagella. These soldiers seek the scent (motif) of the pathogens and sniff them out.

Frequently, these molecules have some mannose (a carbohydrate) residues in them and they are promptly recognized by pathogen recognition receptors. These receptors may be found in the circulation, in soluble form; may be PAMP receptors in macrophage cells, cells in charge of killing and engulfing invaders or may be Toll like receptors, present in macrophages and dendritic cells. Wherever they are located they just look for the signature thumb prints, latch onto them to give them the death kiss. These patterns are shared by more than one pathogen, it will identify and kill 'em all as per its recognition algorithm.

I can't help but mention Lavasoft's adware software in this regard. This antispyware software program looks for unwanted cookies in your hard disk in much the same way. It uses a protocol called code sequence identification to recognize telltale patterns based on its database of past records. You may download the program for free (if you click the link) but how about the physiological program we inherited from our ancestors, more importantly who programmed it?

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A Giant Leap For The Mankind?

It was Har Gobind Khorana who carried Watson and Cricks' legacy so elegantly. He was the first to synthesize oligonulceotides (short sequences of nucleotides: RNA or DNA) and the first to isolate DNA Ligase (an enzyme that 'stitches' pieces of DNA together). Now maverick Venter is poised to give the finishing touch to it.

Craig Venter, the bald and bearded American biologist, who has the habit of hitting newspaper headlines, is 'back in black'. He has now synthesized a piece of chromosome, in his laboratory. His team, headed by Nobel laureate Hamilton Smith, is now on the verge of creating the first artificial life form, christened Mycoplasma laboratorium. This 'organism', containing 381 genes, is capable of behaving as an infecting organism, when it enters a living cell.

What does it mean? A lot. For example, this could herald a new era in drug delivery systems. They can also be manipulated to manufacture weapons of bioterrorism. Even a highly infectious organism may emerge from a research misadventure.

Prion proteins (proteinaceous infective organism) are proteins, which are normally present in cells such as nerve cells. When the shape of these proteins are altered, they may behave as infecting organisms too. These 'misfolded' proteins have the ability to distort other proteins too, thus giving them abnormal shapes. These abnormally folded proteins do not work properly, and diseases such as mad cow disease (bovine spongiform encephalopathy: it makes so many holes in the brain that it resembles a sponge), Creutzfeldt Jakob disease (CJD), and many others.

So what is life? Protein molecules consisting of simple amino acids; or simple nucleotide sequences comprising of nitrogenous bases and pentose sugars? You can well imagine a strand of molecule, the physical part, but where is this abstract part called life? And more importantly, what next?

Crazy Little Thing Called Life

Scientists have recently discovered a body of evidence regarding the existence of water on the red planet and has, for obvious reasons, gone gaga over it. They are conjuring up all the possibilities of existence of life on it.

Well, what are the basic ingredients of life? Are carbon, hydrogen, nitrogen and similar molecules extremely essential (mandatory) for life? What constitutes life and above all, how is life defined? If prions, (which are nothing but misfolded proteins, the cause of a myriad of illnesses like mad cow disease, kuru, scrapie and various other diseases) can be counted as living organisms, then perhaps any complex molecule or even radioactive elements like Polonium 210, which disintegrates on its own, to form many other elements, which in turn disintegrates (reminds me of Iron Maiden's 'Seventh son of a Seventh son' song), may be said to have life too, for they undergo an automatic activity. If you pore into the inside of an atom, you can see interactions in the nucleus: mesons; orbiting electrons around them, dutifully obeying Pauli's principle and many such activities that mimic life. Or are they living things themselves?

( En passant: Polonium 210 is found in tobacco in minute quantities; it was used to poison the famous Russian political dissident Alexander Litvinenko).

Life on earth perhaps needed the carbon skeleton, or it may even have been due to a chance occurrence. Microorganisms have been discovered in conditions in places, hitherto considered inviable for life (Bacillus stearothermophilus, B subtilis, Thermus aquaticus for example). The constituent of life could be molecules other than the conventional ones, even anti-matter! If we zoom in, we find tissues, cells, microtubules, mitrochondria, nucleus, the DNA and various other things which themselves are teeming with life. Zooming further still, we enter the constituent molecules to find the hadrons and the leptons, deeper still, quarks and gluons etc etc. They all seem full of life to me.

Look at the celestial objects. The sun is said to be a middle-aged star. So? Heavenly objects sometimes die a violent death: in supernova, or turn into neutron stars or black holes or some 'dwarf's. And the universe is said to have been born in the form of a major birth pang called the Big Bang. Are they living things then?

We know that there is a very small probability of finding two exactly similar humans, having all identical attributes. Likewise, no two electrons orbiting the nucleus can have the same quantum state, as per Pauli's exclusion principle (teleportation using entanglement/twiddling is an exception, for here two particles at a distance have the same properties) . This only shows that like unique human minds, the not-so-living things can also have their own uniqueness. Can they be said to have a life too, for they too move, have mass and energy. What about a cellphone or a computer or anything having AI(Artificial intelligence).

Let's be introspective. You are as much life as I am and we are made up of molecules arranged in a particular configuration: just matter; but where is the life? It may be here, in the entity called consciousness. Consciousness may be explained in terms of interactions among material elements. When we are dead, what exactly is missing? We may be brain dead, but the transplant surgeon may take out the kidney or cornea to transplant on others. Thus even after we die, we still continue to live in some of our tissues: they remain alive!

The question of life has to be addressed holistically, if we want to arrive at a sane and unanimous conclusion. Till then controversy will rage.