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Midweek Review

Vaccines. Vaccines?

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by Dr F E Dias

“To vaccinate or not to vaccinate, that is the question”, soliloquised Piglet, “since all vaccines are equal, but some vaccines are more equal than others” – poetic licence applied with apologies to William Shakespeare and George Orwell.

Introduction

Smallpox is a virulent infectious vesicular disease. Vesicular and pox in that it causes eruptions on the skin which develop into pustules or pox, and eventually leaves one covered with pitted pockmarks; and designated “small” since the 16th century, to distinguish it from the “great pox” syphilis. It is caused by the virus variola major, variola being a term introduced in circa 570 AD by Marius of Aventicum, now Avenches, then the capital of Roman Switzerland, and meaning pustule. It was a dreaded pestilence in Europe particularly during the 17th and 18th centuries and killed nearly a third of its victims, most of whom were children. The pathogen was spread mostly during the early rash stage from sores in the tongue and mouth through droplets emitted into the air.

When Francis Xavier arrived in Mannar in 1548, smallpox was raging in Ceylon, and in 1697 the royal city of Kandy was deserted on account of it – with the sufferers, believed to be possessed by demons, abandoned to die on roads and in the jungle by their kith and kin. Joseph Vaz and his nephew Joseph Carvalho tended the sick and buried the dead and astonished the King Vimaladharmasurya II on his return once the epidemic had ceased by declining reward. This disease was introduced into the Americas by Europeans and decimated populations of native Red Indians of the northern plains, the Aztecs of Mexico, and the Incas and Araucanians in the south. It was declared eradicated in 1979, and today exists as a bioterrorist threat, precedent reportedly been set by the British Army in 18th century America by their donation of intentionally infected blankets and handkerchiefs to the enemy camp.

It was a phenomenon of great interest that survivors of smallpox, albeit disfigured and sometimes blinded, become immune to a second infection. Apropos in Asia it had been known since the 10th century that introducing into healthy persons the ground scabs or the pus from sores of those infected could also induce immunity. The latter means was popularised in England by the survivor, her “beauty fled” as expressed in her own poetry, Lady Mary Montagu, the wife of the British ambassador to the Court of the Ottoman Empire, who learned of it during her stint in Constantinople in the early 1700s. Through Lady Montagu’s advocacy and consequent acceptance by several royal houses in western Europe, it became standard practice in that part of the continent during the eighteenth century. This inoculation of variola or variolation usually produced localised and less severe symptoms than naturally acquired infection, did have a fatality rate of circa 2% which was an order of magnitude less than that during an epidemic, and carried the additional risk of triggering one.

Chickenpox is caused by the varicella-zoster virus which is a herpesvirus, and the measles virus is a paramyxovirus. Horsepox and cowpox viruses however, together with inter alia those that cause camelpox, rabbitpox and monkeypox have been classified together with the smallpox virus into the family of poxviruses, and specifically into the genus Orthopox. The disease horsepox – variola equine, and the causative virus is now supposed to be extinct, unless it still exists in unknown wild rodents who constitute its reservoir in nature. There were observations in the military that cavalrymen fared better than infantrymen during the smallpox outbreaks; and that farmers working with cattle tended also to be spared. It was remarkable also that milkmaids – whose hands had been infected with the zoonotic cowpox virus from pustules in the udder and teats of cows and had themselves contracted the relatively milder cowpox disease and subsequently recovered, showed resilience against smallpox. Legend has it of a Bristol milkmaid, Gloucestershire and the western counties being a region where cowpox was prevalent, who boasted that she will never have “an ugly pockmarked face” due to smallpox – variola, because she had already had cowpox – variola vaccinae, the pox of the cow.

Vaccination

Through the acts and observations of Benjamin Jesty, John Fewster and others in the late 1700s and the published clinical observations and methodical investigations of Edward Jenner the effectiveness of building immunity to smallpox safely through the inoculation with the genetically and immunologically similar but pathologically milder virus that causes cowpox was established. The story of the hand of Sarah Nelms the milkmaid, the udder of Blossom the cow and the arm of James Phipps the gardener’s son is a story for another day, and yet the achievement was a marvelous demonstration of ingenuity and enlightened emipiricism – a century before modern concepts of virology were established and the role of microbes in the causation of disease was understood. The term vaccinae, is derived from the Latin vacca meaning cow which is perhaps related to the Sanskrit vassa, and its adjective vaccinus, led to the coining of the word “vaccination”, and likewise “equination” when the horsepox pus was used similarly. However, Louis Pasteur in 1881 proposed to generalise the term vaccination to include all protective immunisation procedures against any infectious disease in honour of Jenner, using this term to describe his own work on anthrax, cholera and rabies.

Vaccination until recently was commonly understood to be a prophylactic treatment effected via inoculation of an antigen – a portmanteau of antibody generator, to elicit an immunological response that could protect against future infections by a pathogenic organism associated with that antigen. The antigenic suspension would contain dead or inactivated, or if alive attenuated pathogen, its fragments or subunits, or purified surface proteins or toxoids – inactivated endotoxins of the pathogen that retain immunogenicity. Vaccination can be justified considering the risks of exposure to the pathogen, contagiousness, vulnerability of subject, consequences of the disease, availability of treatment and the efficacy, including tolerability, of the vaccine. Against these factors and the pertaining facts, vaccination against smallpox was justified.

Genenic Medicine

The spike protein is a key factor in infection and a major surface antigen in coronaviruses, although not the only one. Using the identified DNA sequence of the Wuhan virus SARS-CoV-2’s spike protein, Pfizer-BioNTech and Moderna have in vitro transcribed synthetic spike protein mRNA. Subsequently nucleoside-modified, this now modRNA is encapsulated in lipid nanoparticles to create their investigational products BNT162b2 and mRNA1273 respectively. The modRNA of both organisations are similar but their proprietary lipid nanoparticles which enable merging with human phospholipid cell membranes via endocytosis differ. Once intramuscularly injected, the modRNA enters our cells’ cytosol and our ribosomes translate them into viral spike proteins. The Sputnik, Oxford-AstraZeneca, and J&J products incorporate spike protein DNA into an adenovirus vector that enables antigen expression in the host cells. Through these means, we are programmed to generate trillions of viral antigens without becoming infected with the virus itself – consequent to which immunological response may occur. Such intentional gene transfer as novel means of attempting to effect humoral and cell-mediated immunity is associated with gene therapy, genetic medicine being a nascent science in itself, and is distinct from conventional antigen inoculation – although in retrospect, attenuated virus vaccines with RNA genome viruses do in part operate similarly.

Some Implications

These products received emergency use authorisation in some countries, in that such authorisation becomes null if the situation ceases to be decreed a public health emergency – since the products are unapproved, and by implication their use constituting human trials. Animal trials enable potential immunopathological phenomena to be discovered especially intrinsic antibody dependent enhancement and vaccine hypersensitivity when the vaccinated subject is subsequently exposed to a wild virus – which sometimes result in fatal outcomes, these deaths often incorrectly being reported as due to new and more deadly variants. Such pathogenic priming was a cause for failure of vaccines developed for the first SARS-CoV virus, and for half a century of active research providing no safe dengue virus vaccine to date. Infants may also have ADE caused by maternally acquired SARS-CoV-2 antibodies bound to mast cells.

The spike protein on which the viral infection is reliant for binding on to the angiotensin-converting enzyme 2 in host cells such as those of the pulmonary vascular endothelium, and triggering the clinical symptoms and lung damage, by itself could behave as a pathogen and have effects on the respiratory system more severe than the virus in toto due to stronger binding of the protein alone as compared to it when associated with a whole virus and present on its surface. Further it is not clear how long the RNA in its modified and stabilised form and its proprietary synthetic lipid nanoparticles designed for prolonged antigen expression or the stabilised spike protein variant produced may prevail in vivo.

The blood brain barrier was originally observed in 1885 by Paul Ehrlich, better renowned for discovering the cure for syphilis in 1909. It is a biological phenomenon constituted of blood capillaries with tightly packed endothelial cells that separate the brain tissue from the blood circulatory system and forms a defence against pathogens and toxins that may be present in blood and maintains a controlled environment within the central nervous system. Its structure was understood only after scanning electron microscopy became available and even glucose cannot pass through it except via special ports known as transporter proteins. It has been shown in male mice that the spike protein does pass the blood-brain barrier that holds whole viruses back, when introduced intravenously and intranasally, potentially causing inflammation in the brain, thrombosis and delayed neurodegeneration.

Syncytin-1 is a protein essential in our trophoblast development and for placentation when in the earliest days of our life our syncytiotrophoblast implants us into the maternal uterine decidual epithelium and also produces human chorionic gonadotrophin which among a multitude of wonderful functions suppresses maternal immune response against the foreign organism growing within her – her child. Similarity has been reported between several sequence motifs of the genetic code for the Wuhan virus spike protein and syncytin-1 both of which are fusion proteins. It needs to be ruled out that immune response to the spike protein does not trigger immune reaction against syncytin-1 since if it did that would imply abortifacient immune reaction and infertility over as long as the immunity persisted.

Conclusions

There are situations in which artificial induction of immunisation of the healthy against infectious disease, even amid an epidemic, is just. The means by which immunological response is achieved requires due diligence to ensure that the consequences due to the means is not more tragic than that of the disease. Further, due attention needs to be rendered towards achieving cure via treatment – even if the effective anti-viral drugs are cheap, known, ubiquitous and their patents have long expired.



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Midweek Review

NADAGAMKARAYO

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By Capt Elmo Jayawardena
elmojay1@gmail.com

Some days ago, a fellow Captain dropped in to see us at home. He was accompanied by his wife. Amidst a light conversation and pleasant chatter, they mentioned NADAGAMKARAYO.  He swore it was a great teledrama and that we should give it a go. I had never watched teledramas because I could not allocate a fixed time for sitting in front of the television. The same goes for my wife, who is ultra-busy with our own dramas in life. Somehow the following day we got a break from a tight schedule and went to YouTube and watched Episode 1 of Nadagamkarayo.

Then we watched Episode 2 and then 3 and 4 and 5.Now after two weeks we are at Episode 184 and well set on Nadagamkarayo to light-up our evenings. I called a dear friend. I know his taste. By profession he is the Head Honcho of a prominent bank.  But he’s still got grass-root vernacular taste, yes, from Spielberg masterpieces to Indika Ferdinando’s ‘Ho Gaana Pokuna’.  The bank boss has not been a tele-drama man. The next day he texted me, “Thank you for the gift my friend, the programme is great, I am hooked on Nadagamkarayo.” A few days later, he emailed me that he was on Episode 58. I called another friend, a leading corporate lawyer married to an ultra-busy surgeon. They have three young children, and the lawyer is a multi-tasker from the ‘A’ Team. She too has taken the Nadagamkarayo drug and was watching the teledrama at 8.00 in the morning, the only interval in her roller-coaster daily road map.   So, what is all this hype about Nadagamkarayo? It certainly is no quick fix for lockdown blues. It is much more. Pure Sri Lankan simple story with excellent creativity.

The cast bar none is acting at Sarasavi or Sumathi level.  Kawadiya, who has traces of Dustin Hoffman, gets the Oscar nomination, and Kukul Bada, the young domestic, deserves an honourable mention purely for his varying facial expressions. The totality created by director Sivagurunathan is amazingly watchable.  The insatiable appetite of the TV audience to watch Nadagamkarayo stems from the clever way the drama rolls on, keeping all characters alive and active. If this is watched by anyone as a ‘Daily Bread’ at 9.30 in the night, that is fine, so long as you have that half-hour free to sit in front of your TV. But like us, if you are a late starter and going through the episodes to catch up with the current stage, then you are in trouble. Watch one and then go to the next and the next and the next in an unstoppable frenzy and the wake-up call comes when you hear the clock striking midnight. That is how strong the addiction could be. I do not know who the scriptwriter is or the brilliant cinematographer who is responsible for depicting rural scenery of high pastoral quality.

There will be so many others who added their smidgen to make this a first-class entertainment to all and sundry.  They say cocaine, LSD and pure Kerala ganja are addictive?

Try Nadagamkarayo, you get bewildered from episode to episode which is hard to switch off until you watch the entire story.  Kukula Mudalali seems a veteran from either stage or screen. As bald as a doorknob and with a ‘Taras Bulba’ moustache he is the perfect all-round villain for the drama. Not only is he a thug selling moonshine but a failed Romeo with any skirt that swings in the wind. Manamalan driving his red imitation Ferrari is difficult to define from the audience point of view. He is brash and bawdy and is always the ultimate liar. That is his role, and he sure brings a different dimension to the bucolic village setting with his patch-work denims and action-filled behaviour which has the unique distinction of being pleasing and annoying at the same time. This is what we traded for Netflix and HBO.

At the start it was curiosity, but in no time Nadagamkarayo became an addiction. We have not seen the evening television news for weeks. No, we missed nothing. We do not want to know who stole the garlic and created the Sudulunu scandal or who runs the rice mafia and hides the harvest. Pandora’s Box and how Uhuru Kenyatta and Vladimir Putin looked for reliable laundries to clean their money is way above what we need to know. The same goes for those who bid for a Cypriot passport at 1.3 million dollars.

We do not want to know how 600 plus items were blacklisted for importing and then in a flash a new magician came on stage like Gorgiya Pasha and swung his multi-coloured wand and Ooppss – the restrictions vanished into thin air. No more dollar-saving cutbacks. We can be clad in St Michael’s underwear and feast on Cadbury chocolates stocked in a brand new two-door refrigerator imported from Germany. No, I certainly do not need all that twisted jargon camouflaged as current head-lines to crowd my evening by watching local television channels. Maybe, it is not the fault of these stations but the politically- dominated mundane news that is available or ‘has to be’ shown by order.

I will gladly trade all that to see Loku Hamuduruwo on Nadagamkarayo screen with his serene behaviour and exemplary attitude to life which soothes our very souls. At all times the soft words of Loku Hamuduruwo are always a simple wisdom-filled lesson in life to all of us. Cap it up with the daily occurrences at the tea kiosk by the paddy field where the shop owner, manager, and tea-maker Mudalali and his golaya Gajaman colour the show.  His customers are the banana-eating and kahata-drinking clan who spice the story with palatable ‘Gamey Talk’.

The champion of this mini-stage is Sirisena the erudite goat-milk-seller who has his own interpretations and anecdotes to anything and everything political that happens in the country.Sudu Chooti comes to the story as a village Juliet. She is the daughter of the Music Master and his comely wife Kusumalatha who is ‘all perfect’ in her role as a village mother. Here the village damsel Sudu Chooti falls in love with the Kassippu-selling Sara, the scourge of the village.  No doubt, Sara carries the show wrapped in a rugged flamboyance which is nothing but raw talent. He sure is the ultimate ‘Village Hampden’ from Gray’s Elegy, a rebel against constant village tyranny. He and his Kassippu boys, Kawadiya, Suddha and Kiri Putha depict clearly to the audience the sadness of the youth of today.

The poverty that plagues their young lives with no answers visible to make a decent living is an unchangeable tragedy. They are outcasts in the village and are branded for life with no avenue for redemption.  That part of Nadagamkarayo is a lesson to us all. The underlying message is clear; It is not the core of the man that is rotting, it is the system that denies him the opportunity. Where and when is the brighter day that would give him a chance to wake up and make attempts to be a decent human being?Rasika is poor, her husband has left her and run off with another woman. Rasika is a single parent taking care of an innocent little daughter. They live in a hovel that is called home. Her father is sick, a heart patient, and the mother is unemployed.

The day that dawns for them is always a struggle.A stranger is kind to her. Gives Rasika a lift to visit her father in hospital and brings her home. She invites him for a cup of tea. He is reluctant and hesitates. Even though we are poor we can afford to give you a cup of tea,” she tells the stranger. That line says it all. It defines the soul of Sri Lanka and what is Sri Lankan.Where would we be without it?

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Midweek Review

Is Buddhism pessimistic teaching?

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By Dr. JUSTICE
CHANDRADASA NANAYAKKARA

Buddhism is a non-theistic religion. Unlike many other religions it does not believe in a god or a creator. It is not only a religion but also a philosophy with a moral discipline. It originated in northern eastern India and was founded by Gautama Buddha. Today, Buddhism has become one of the major religions in the world, with more than 500 million adherents. Prince Siddhartha Gautama, who later became Gautama Buddha, having realised the immense human suffering looked for a way of easing their pain and suffering. He pursued strict spiritual disciplines to become an enlightened being. Having achieved enlightenment he preached a path of salvation to his followers, so that they could escape the samsaric cycle of suffering, rebirth and death. In brief, the entire teaching of the Buddha can be summed up in one stanza from the Dhammapada. “Sabba papassa akaranam kusalassa upasampada sacitta pariyodapanam etan buddhana sasanam” (not to do evil, to cultivate merit, to purify one’s mind, this is the teaching of the Buddhas}.

Criticism of Buddhism has taken many forms. Some incline to the view that Buddhism is overly pessimistic in outlook, and always takes a gloomy and melancholic view of life. While others were of the opinion that Buddhism was unscientific, idealistic and impractical. These misconceptions have prevailed from the time of the Buddha to this day. It should be stated that these beliefs are fallacious and misleading, as Buddhism is neither pessimistic or optimistic. If anything at all, it is realistic as it takes a realistic and dispassionate view of life and of the world, and teaches us to look at things as they really are. Buddhism promotes rational and empirical investigation, and invites people to put the teachings of the Buddha to test before accepting it. Buddha does not stop at analysing suffering [dukka], but proceeds to show us the practical way out of it, which is the Noble Eightfold Path.

The erroneous view that Buddhism is pessimistic has come about as a result of many scholars giving a restricted meaning to the word dukkha (Suffering) in the First Noble Truth. They have interpreted dukka (suffering) as nothing but suffering and pain. This has led many to regard Buddhism as a pessimistic religion. But viewed from a Buddhist perspective the word dukkha (suffering) has a deeper and wider connotation and dimension.

It should be noted that other than the ordinary meaning of dukkha (suffering), the word dukkha in the First Noble Truth also connotes such things as ‘’imperfection “, “impermanence” and “insubstantiality”.

Dr. Walpola Rahula Thero in his book “What the Buddha Taught” has stated thus: “First of all, Buddhism is neither pessimistic or optimistic. If anything at all, it is realistic, for it takes a realistic view of life and world. It looks at things objectively (yathabhutam). It does not falsely lull you into living in a fool’s paradise, nor does it frighten and agonise you with all kinds of imaginary fears and sins. It tells you exactly and objectively what you are and what the world around you is, and shows you the way to perfect freedom, peace, tranquility and happiness”.

Pessimism is a philosophy of suffering, while Buddhism is a philosophy of the relief of suffering. Had the Buddha in his discourse proclaimed that there was nothing but misery in life, and there was no happiness to be found anywhere, without showing us the way out of it, we would have been justified in characterising Buddhism as pessimistic.

It is true that the Buddha exposed the unhappy part of life. However, while doing so he explained the way to come out of it.

Buddhism does not countenance a melancholic, sorrowful, gloomy attitude to life, and it does not foster an attitude of hopelessness to life. The Buddha didn’t ask his adherents to contemplate only on the gloomy side of life. He did not expect them to brood over misery only, but wanted them to know that both the happy and sad sides of life are equally fleeting and impermanent.

No one can deny the reality of suffering associated with birth, decay, old age, death, association with the unpleasant and disassociation from the pleasant. In reality there is none in the whole world other than the Buddha, who can be described as a preacher of happiness or sukhavadi. A true Buddhist is the happiest of all beings.

Buddhism is a religion of salvation. It is an ethical philosophy which preaches the unsatisfactory nature of the world. Unlike other religions in the world, which talk about an almighty god on whom people depend for salvation. According to Buddhism, one is indeed one’s own lord {attahi attano natho}.

The entire teaching of the Buddha when summed up, amounts simply to insights into “impermanence” [annicca] suffering or unsatisfactoriness” [dukka] and “non-selfhood” [annitta]. These three characteristics were the aspects of teaching, which the Buddhas stressed more than any other. The three characteristics annicca, dukkha and anatta which facts of life can be realized and grasped by everyone. Even the most placid person would admit that dukka is omnipresent and universal. This truth can be easily realized by anyone who can think soberly and dispassionately. It can be seen everywhere around us. Infatuation with transient pleasures prevents us from seeing things as they truly are.

Walpola Rahula Thero in his book states the Buddha does not deny happiness in life when he says there is suffering. On the contrary he admits different forms of happiness, both material and spiritual, for laymen as well as for monks. In the Anguttara-Nikaya, one of the five original collections in Pali containing the Buddha’s discourses, there is a list of happiness (sukhani), such as the happiness of family life and the happiness of the life of a recluse, the happiness of sense pleasures and the happiness of renunciation, the happiness of attachment and the happiness of detachment, physical happiness and mental happiness etc.

Misery arises because of craving and aversion, which in turn arise from tanha. If these causes are eradicated the root cause of misery is eradicated. The Buddha said pain is followed by pleasure, and pleasure is followed by pain. In other words, pleasure and pain follow each other as day follows night.

If you observe the reality around us it is evident it consists of birth, sickness, old age, sorrow, pain, distress, decay, grief, death, lamentation, etc. Empirical observation of human existence makes it clear. Buddha laid emphasis on knowing things as they really are [yatha bhuta nana] if you take a critical look at life and all its concomitants, it is clear to everyone everything is in a state of flux. Life is a succession of fleeting moments of arising and dissolution. And every cell in the body of a being would die and be replaced by a new cell which in turn would die to be replaced by another. From conception to death the process goes on uninterrupted. Buddha’s definition of suffering is clear and empirical to anyone.

The Buddha has preached that the following come into being and pass away. Release from them is bliss—Annicca vata sankara Uppada vaya dhammino Uuppajjitva nirujjhanti Tesam vupa samo sukho).

He also preached “he who sees dukkha sees also the arising of dukkha, sees also cessation of dukkha, and sees also the path leading to the cessation of dukkha“. This does not make the life of a Buddhist melancholy or sorrowful at all.

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Midweek Review

The Runaway Rash

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By Lynn Ockersz

Drained of its nutritional sap,

Thanks to a runaway rash of scams,

The fabled isle sees red on multiple fronts;

On the one hand, it faces an economic slump,

On the other, it’s being greedily milked dry,

By a political class answerable to none,

And on top of it all, people who most matter,

In revered bodies that help build the land,

Are thrusting aside the Voice of their Conscience,

And vitalizing the gangrenous growth of corruption.

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