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Pandemic and emergence of variants

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By Prof Kirthi Tennakone

The behaviour of the coronavirus bears resemblance to a high-speed magnified video of Darwinian evolution. The virus changes in front of our eyes and variants emerge as the fittest that survive. Genome surveillance has succeeded in reading the genetic changes accurately and sees how the genotype expresses as phenotype. Genotype being the chemical-genetic constitution and phenotype, characters as manifested in the environmental background.

Humans have sinisterly arrested the natural evolution of animals and plants; but despite scientific advancements, find it difficult to deal with a fast-evolving virus, science alone cannot resolve a social calamity. Containment of the pandemic would be difficult if our actions lag in relation to the pace of virus evolution.

Mutations: cause of biological evolution

According to Charles Darwin’s theory of evolution, life on earth continues by descent, inheriting parental characters subject to infrequent variations or mutations. After the discovery of DNA, the mechanism of inheritance and mutations was understood.

The genetic material DNA, present in all living cells, is a double-stranded structure composed of bead-like moieties pairs, known as nucleotide bases, denoted by symbols A, T, G and C. The sequence of these entities in a strand encodes genetic information analogous to a four-letter alphabet. Some viruses contain one strand referred to as RNA and encode information in the same way. When the cell or the virus replicate, most of the time, the sequence of nucleotides is copied exactly giving birth to a genetically identical cell or a virus. Rarely, copying errors creep in during replication. For example, the sequence AAGCT may be miscopied as AAGCG. This is a minor change in comparison to the entire genome, nevertheless a genetic change or a mutation. Most mutations will not lead to overriding alterations in the character of an organism. Mutations are often deleterious. Very infrequently, a change in character, owing to a mutation, turns out to be beneficial for the species to survive and procreate.

Mutants fitting the environment survive and proliferate. Paleontological findings provide ample evidence of the evolutionary process, when noticeable changes in living species manifest during, more or less, millennia. In most cellular organisms a mutation, fit to get established, takes place once in a million generations. For that reason, we do not see sporadic changes in the progenies of animals and plants. In the past there had not been significant alterations in genetically transferred characters of wild animals. The leopards we see today are not different from ones that lived during the Anuradhapura period, their hunting capabilities are similar.

The situation is different if a virus invades a population devoid of immunity. Their intrinsically fast mutation and replication rates and sheer numbers, invariably bring forth more adaptable strains in very short periods. Certainly, the same phenomenon occurred during previous epidemics and pandemics. Today it is happening at an escalated level because of high human population density, mobility and unrestrained interference in the environment.

Viruses live on cellular life, constantly interacting and following their evolution, while they themselves evolve.

Unicellular and multicellular and viruses

The first living cells or unicellular microbes seemed to have originated 3.5 billion years ago. A giant step in the advancement of life on earth has been the appearance of multicellular organisms, living systems made of assemblies of cells. A mutation in a unicellular agent around 1.5 billion years ago is believed to have cleared the way for the development of multicellular life. These individual cells, sharing similar DNA, formed colonies. Later colonies subdivided, each expressing genetic instructions differently to create complex animals, with organs performing varying functions. The above developmental pathways, leading to advanced forms of life existing today, took more than one billion years.

Viruses are distinct from cellular forms of life. The latter possesses the capacity to grow and reproduce, deriving energy and essence of structural materials from non-living substances; whereas the former needs to enter a living cell to reproduce. All cellular creatures and viruses replicate, mutate and interact with each other and the external environment and evolve.

The pandemic is just one episode of this universal phenomenon, progressing fast and tracked by humans, the concern now is the threat posed by variants.

Variants of Coronavirus (SARS-CoV-2)

A variant means a mutated version of an organism, distinct from the original in a noticeable deviation of an observable trait. For example, king coconut is a variant of coconut, the distinguishing attribute being the colour of the nut. Apart from the shade of the nut, this particular mutation had turned the tree into a dwarf, very disadvantageous for harvesting sunlight. Unable to compete with other trees, the king coconut would not survive in the wild. Attracted by the colour, humans (in Sri Lanka) have taken care of the variety and propagated it.

In the case of the Coronavirus, the important qualities distinguishing variants are higher infectivity, degree of virulence and resistance to vaccines.

The Coronavirus and other RNA viruses mutate faster than DNA based organisms. Here the probability of a viable mutation per generation (replication) exceeds 10,000 times that of a cellular life form. Furthermore, the generation time of the Coronavirus is a few hours compared to years and months in the case of animals and the total population of viruses in bodies of infected persons, during the time of the pandemics, is many billions times larger than an animal population. Consequently, Coronavirus variants popped up in durations as short as a few months, after the aggravation of the pandemic in late 2020. The longer the pandemic lasts and the greater the intensity, the more variants we encounter.

Since the emergence of COVID-19 in Wuhan, China in December 2019 and its global spread, many variants have appeared in geographically distinct regions and crossed borders. The original version of the virus which triggered the epidemic in Wuhan underwent the mutation D614G altering the spike proteins, making it more contagious. Soon the strain D614G surfaced almost everywhere initiating the pandemic. It is the common ancestor of almost all variants seen today. The World Health Organization and Center for Disease Control, United States, have classified Coronavirus variants into three categories.

Variants of Concern

: They have increased transmissibility, detrimental alteration in epidemiology, enhanced virulence, decrease effectiveness in public health measures or available vaccines and diagnostics. The Alpha variant detected in the United Kingdom, September 2020; Beta in South Africa, May 2020; Gamma in Brazil November 2020; Delta in India October 2020 falls into this category.

Variants of Interest

: These are strains of the Coronavirus genetically distinguished by sequencing with potentialities of higher transmissibility, disease severity, and immunity resistance. They could pose threats in the future and need to be watched. Variants; Eta, Iota, Kappa, Lambda and Mu recently detected in Colombia are classified as variants of interest.

Variants of high consequence

: These are variants that would largely escape known control measures. Fortunately, at the moment, no candidates come under this category.

How Coronavirus variants originate

A variant begins as a mutation of one single virus in an infected person somewhere. It is very unlikely it would enter someone else and cause the disease. The variant requires to breed sufficiently in the individual in whom it was created. Again, in order to procreate and proliferate, it will have to compete with the parent strain, initially dominant in the patient. The variant will succeed in competing if it replicates faster and more effectively invades cells. As expected, all variants of concern possess the above qualities. Similarly, if the mutant had acquired the trait of evading host immunity, it could overshoot the parent strain.

Variants possibly originate and breed in immunosuppressed persons chronically infected with COVID-19. They carry large viral loads for prolonged durations, a pathology conducive to the birth and growth of variants. A wide range of mutants have been detected in such patients.

Characteristics of variants

Variants of concern spread faster in contrast to the parent strain. A pertinent question is, what changes in the virus provide this facility? For the virus to invade the human system, it must attach to a cell in the respiratory tract and transfer genetic material to the interior of the cell. The virus does this with a special protein in the spikes, binding selectively to a receptor in human cells named ACE2. In variants, the chemistry and architecture of the spikes are redesigned to enhance attachment. Thereafter, the migration of the replicating viruses to adjacent cells is also facilitated by the same process. The host antibodies drive the immune response by attacking spikes to suppress their bondage to the receptors. Mutagenic alterations in the spikes also help the variants to escape host immunity.

Most contagious Delta variant

The delta variant first identified in India, October 2020, resulted in an aggressive epidemic there and rapidly diffused. Several mutations in the spike proteins facilitated its fast spread. While retaining the common ancestral mutation D614G, the Delta carries three other mutations named P681R, L452R and D950N. The mutation D614G increases the number of spikes on the viral envelope. Production of higher viral loads in Delta-infected patients is believed to be a character manifested by the P681R mutation. Their respiratory tracts carry 1000 times more virus particles. The L452R mutation seems to protect spikes from antibodies helping immunity evasion. An ability of the Delta variant to attack a wider group of cells probably originates from a trait induced by D950N mutation. Mainly because of the changes in the spike proteins, the Delta variant reproduces faster by cell-to-cell invasion. Consequently, once this brand of Coronavirus enters a susceptible person, the symptoms appear in a shorter period of four to five days, compared to about a week for the alpha variant.

The Delta variant is 60 percent more transmissible than the alpha which stands 50 percent higher than the ancestral strain. A parameter defining the transmissibility of an infectious disease is the average number of cases reproduced by one carrier of the pathogen, the basic reproduction number (R0). An infection reaches epidemic proportions if R0 exceeds unity. When the pandemic originated in China, the value of R0 was about 2.5. The estimated value of R0 for the delta variant is somewhere between six and nine, an enormous increase in transmissibility relative to the previous strains.

Virus variants compete, whenever the Delta entered new territory, it out-competed other strains.

Vaccinations and Delta Variant

Except for a partial immunity evasion of the Delta variant, vaccines are effective against both variants. Vaccines lower the probability of catching the infection, more importantly greatly reduce serious complications and death. Some statistical assessments conclude that breakthrough infections (re-infections) are higher for the Delta variant compared to Alpha.

The discrepancies reported could also be indications of the fact that the Delta variant is far more contagious than previous strains. Here, the statistically meaningful epidemiological parameters are the number of different categories of infected persons (vaccinated, the severity of infection as determined by hospitalizations and mortality) as a percentage of the total number of infected individuals, recorded temporally. It is extremely difficult to keep track of these quantities when the disease spreads fast. Even the total number of people infected cannot be ascertained reliably. Under such circumstances, the anomalies reported as lesser effectiveness of vaccines in the case of the Delta variant, could also entail errors in data interpretation, arising from the fact that the Delta variant spreads fast.

There are also reports to the effect that more unvaccinated younger adults and children are hospitalized after the arrival of the Delta variant, reflecting the severity of symptoms. Theories have been put forward to explain the apparent anomaly. However, because of faster transmission of the Delta variant, proportionately younger patients may seek hospitalization.

As the dominant strain infecting a large proportion of people; the Delta variant will continue to mutate and evolve. Few mutational changes have already been noticed and named Delta pluses, but there is no evidence to conclude they are more dangerous.

Doomsday variant

News spreads like viruses. Just as mutations, inadvertent or deliberate distortions and exaggerations happen in reproducing news. Versions with more sensational twists disseminate faster.

In May 2021 a new variant carrying mutations suggestive of fast transmission and immunity resistance was identified in South Africa. Months later a reputed epidemiologist tweeted that the variant could be an imminent danger, prompting media to name it a doomsday variant. The ensuing panic was the result of premature unconfirmed assertion. The World Health Organization announced that this variant is not propagating as fast as the Delta.

Stories of pathogens spreading exceedingly fast, evading immunity, are common in science fiction. There is no evidence for such, even at times when preventive measures were completely unknown. Attributes encoded in different mutations do not add arithmetically. If one virus has a trait that allows it to spread fast and another to evade immunity, these two qualities will not necessarily be pronounced, to the same extent, in a third virus endowed with both mutations. Fear-mongering concerning doomsday viruses is most unlikely to persist.

Herd immunity and Delta variant

When the percentage of subjects acquiring immunity (either by vaccination or contracting the illness) exceeds a threshold, epidemics wane and disappear. The point at which this transpires depends on the value of the basic reproduction number R0; determined on the assumption there were no immune individuals, at the time the pathogen initiated the epidemic. As the immunity of the community increases, the reproduction number decreases proportionate to the fraction of people remaining susceptible and the rate of transmission is determined by an effective reproduction number RE. If N is the total population and M the number among them immune, the fraction susceptible is 1- M/N. Therefore the reproduction number reduces to the effective value RE = R0 (1 – M/N). Once RE reaches a value less than unity, the epidemic ceases to continue and the threshold corresponding to RE = 1, occurs when M/N = 1 -1/R0. At the beginning of the pandemic, the value of R0 was approximately 2.5 and the above formula yields M/N = 0.6, so that herd immunity threshold is 60 percent. For the highly transmissible Delta variant, a mean value of R0 is 7.5 and the same formula gives a herd immunity threshold of 87 percent. As vaccinated persons sometimes get re-infected, the actual threshold may exceed the above number, suggesting herd immunity is virtually beyond reach. Fortunately, R0 can be reduced by preventive measures such as social distancing, wearing masks and hand sanitization, thereby lowering the threshold.

Are we sufficiently disciplined to follow preventive measures stringently? The virus will continue to evolve via random mutations and their selection may be influenced by our behaviour. Will it turn more deadly or less deadly? These questions are too complex and unpredictable.

Fortunately, vaccines answer satisfactorily and redesigning and improvements are within reach. Preventive measures dampen transmission significantly. Every individual needs to follow these two strategies confidently, without resorting to unproven practices and myth.



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Features

Why Small Farms will be the backbone of food security

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The ecological axiom that: ‘Energy flow through a system tends to organise and simplify that system’, is abundantly clear in agriculture. As farms moved from small interdependent units, bounded by fences and hedgerows, to large cropping fields to accommodate machine management, we lose the biodiversity that once existed on that landscape and the biomass that provided the Ecosystem Services. This sacrifice was rationalised through the invocation of economic profit. The economic ‘profit’ gained by subsidies on fossil fuel and uncontrolled extraction from the Global Commons. The ‘development’ of agriculture has become a race to control the commodity market. The farmer ceased to be a feature of the farm. In a telling statement, the farmers of Sri Lanka sent the following statement to the CGIAR in 1998 :

‘We, the farmers of Sri Lanka would like to further thank the CGIAR, for taking an interest in us. We believe that we speak for all of our brothers and sisters the world over when we identify ourselves as a community who are integrally tied to the success of ensuring global food security. In fact it is our community who have contributed to the possibility of food security in every country since mankind evolved from a hunter-gather existence. We have watched for many years, as the progression of experts, scientists and development agents passed through our communities with some or another facet of the modern scientific world. We confess that at the start we were unsophisticated in matters of the outside world and welcomed this input. We followed advice and we planted as we were instructed. The result was a loss of the varieties of seeds that we carried with us through history, often spanning three or more millennia. The result was the complete dependence of high input crops that robbed us of crop independence. In addition, we farmers producers of food, respected for our ability to feed populations, were turned into the poisoners of land and living things, including fellow human beings. The result in Sri Lanka is that we suffer from social and cultural dislocation and suffer the highest pesticide- related death toll on the planet. Was this the legacy that you the agricultural scientists wanted to bring to us ? We think not. We think that you had good motives and intentions, but left things in the hands of narrowly educated, insensitive people.’

The diverse farm had to yield to production monoculture, which was made possible through the burning of fossil fuels. Ironically the burning of fossil fuels is the major reason for the current destabilised climate and threat to agriculture. One consequence of climate change is the predicted rise in global temperatures. If ambient temperatures exceed 40 degrees , which has become the reality in many places even today, food production will be compromised. All the food we eat originates with plants and plants produce using photosynthesis. Photosynthesis, or the capture of solar energy by plants, is done with chlorophyll, the thing that makes plants green and chlorophyll begins to break down after 40 degrees. Landscapes whose summer temperatures go beyond this limit will have smaller and smaller crops as the temperatures increase. The only solution to this oncoming crisis, is to begin introducing trees at strategic points on the landscape.

Trees and all other forms of vegetation cool the environment around them through the transpiration process, which takes place in the leaves. The water absorbed by the roots is sent up to the leaves which release it as vapor, cooling the air around it. Measurements on trees done by research institutions worldwide, indicate that an average large tree produces the cooling equivalent of eight room sized air conditioners running for 10 hours, a cooling yield 0f 1,250,000 Bthu per day. Plantations of trees have been recoded to have daytime temperatures at least 3 degrees below the ambient. This is an important aspect of Ecosystem Services that needs to be considered for adaptive agriculture.

Small farms which produce food with low external energy and maintain high biomass and biodiversity, are the models of food production that can face the climate compromised future before us. Capital, resource and energy expensive agricultural systems could fail in a high temperature future and threaten global food security, we need options. One would be to encourage a consumption and distribution system that facilitates small farmers to enter the market. Another would be to realise the value of the ecosystem services of a farm and develop systems to measure and reward. We are all aware of the future before us. Now is not the time to stand blinking like a deer facing the headlights.

But placing trees in and around cropping areas becomes a problem in large cropping fields designed to accommodate machine management. The management of such trees and hedgerows requires needs that cannot be provided without human management. Agricultural landscapes will need management that will be adaptive to the changing climate. An example would be; small interdependent units bounded by fences and that increase biodiversity and the biomass while providing Ecosystem Services.

Investment in food security, should take climate change seriously. All new agricultural projects should address the heat thresholds of the planned crops. The Sri Lankan country statement at COP 21 stated that :

“We are aware that the optimum operating temperature of chlorophyll is at 37 deg C. In a warming world where temperatures will soar well above that, food production will be severely impacted.”

And that :

“We are aware that the critical Ecosystem services such as; production of Oxygen, sequestering of Carbon, water cycling and ambient cooling is carried out by the photosynthetic component of biomass. This is being lost at an exponential rate, due to the fact that these Ecosystem Services have not been valued, nor economically recognised.”

These statements cry out for the recognition of the role that small farms will have to play in the future. In a temperature compromised future, small farms with high standing biomass, through their cooler temperatures will continue to produce food in heat stressed periods. If such Ecosystem Services can be given a value, it will strengthen the economy of small farms and ensure local, sustainable food production into the future.

Small farms which produce food with low external energy and maintain high biomass and biodiversity, are the models of food production that can face the climate compromised future before us. Capital, resource and energy expensive agricultural systems could fail in a high temperature future and threaten global food security, we need options. One would be to encourage a consumption and distribution system that facilitates small farmers to enter the market. Another would be to realize the value of the ecosystem services of a farm and develop systems to measure and reward. We are all aware of the future before us. Now is not the time to stand blinking like a deer in sheadlights.

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Encouraging signs, indeed!

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Derek and Manilal

Local entertainers can now breathe a sigh of relief…as the showbiz scene is showing signs of improving

Yes, it’s good to see Manilal Perera, the legendary singer, and Derek Wikramanayake, teaming up, as a duo, to oblige music lovers…during this pandemic era.

They will be seen in action, every Friday, at the Irish Pub, and on Sundays at the Cinnamon Grand Lobby.

The Irish Pub scene will be from 7.00 pm onwards, while at the Cinnamon Grand Lobby, action will also be from 7.00 pm onwards.

On November 1st, they are scheduled to do the roof top (25th floor) of the Movenpik hotel, in Colpetty, and, thereafter, at the same venue, every Saturday evening.

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Constructive dialogue beyond international community

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by Jehan Perera

Even as the country appears to be getting embroiled in more and more conflict, internally, where dialogue has broken down or not taken place at all, there has been the appearance of success, internationally. President Gotabaya Rajapaksa will be leading a delegation this week to Scotland to attend the UN Climate Change Conference (COP26). Both the President, at the UN General Assembly in New York, and Foreign Minister Prof G L Peiris, at the UN Human Rights Council, in Geneva seem to have made positive impacts on their audiences and, especially amongst the diplomatic community, with speeches that gave importance to national reconciliation, based on dialogue and international norms.

In a recent interview to the media Prof Peiris affirmed the value of dialogue in rebuilding international relations that have soured. He said, “The core message is that we believe in engagement at all times. There may be areas of disagreement from time to time. That is natural in bilateral relations, but our effort should always be to ascertain the areas of consensus and agreement. There are always areas where we could collaborate to the mutual advantage of both countries. And even if there are reservations with regard to particular methods, there are still abundant opportunities that are available for the enhancement of trade relations for investment opportunities, tourism, all of this. And I think this is succeeding because we are establishing a rapport and there is reciprocity. Countries are reaching out to us.”

Prof Peiris also said that upon his return from London, the President would engage in talks locally with opposition parties, the TNA and NGOs. He spoke positively about this dialogue, saying “The NGOs can certainly make a contribution. We like to benefit from their ideas. We will speak to opposition political parties. President Gotabaya Rajapaksa is going to meet the Tamil National Alliance on his return from COP26, which we will attend at the invitation of the British Prime Minister. So be it the NGO community or the foreign diaspora or the parliamentary opposition in Sri Lanka. We want to engage with all of them and that is very much the way forward”

INTERNAL FRAGMENTATION

The concept of a whole-of-government approach is indicative of a more cohesive approach to governance by government ministries, the public administration and state apparatus in general to deal with problems. It suggests that the government should not be acting in one way with the international community and another way with the national community when it seeks to resolve problems. It is consistency that builds trust and the international community will trust the government to the extent that the national community trusts it. Dialogue may slow down decision making at a time when the country is facing major problems and is in a hurry to overcome them. However, the failure to engage in dialogue can cause further delays due to misunderstanding and a refusal to cooperate by those who are being sidelined.

There are signs of fragmentation within the government as a result of failure to dialogue within it. A senior minister, Susil Premajayantha, has been openly critical of the ongoing constitutional reform process. He has compared it to the past process undertaken by the previous government in which there was consultations at multiple levels. There is a need to change the present constitutional framework which is overly centralised and unsuitable to a multi ethnic, multi religious and plural society. More than four decades have passed since the present constitution was enacted. But the two major attempts that were made in the period 1997-2000 and again in 2016-2019 failed.

President Rajapaksa, who has confidence in his ability to stick to his goals despite all obstacles, has announced that a new constitution will be in place next year. The President is well situated to obtain success in his endeavours but he needs to be take the rest of his government along with him. Apart from being determined to achieve his goals, the President has won the trust of most people, and continues to have it, though it is getting eroded by the multiple problems that are facing the country and not seeing a resolution. The teachers’ strike, which is affecting hundreds of thousands of schoolchildren, is now in its fourth month, with no sign of resolution. The crisis over the halting of the import of chemical fertiliser is undermining the position of farmers and consumers at the present time.

EARLY WARNING

An immediate cause for the complaints against the government is the lack of dialogue and consultation on all the burning issues that confront the country. This problem is accentuated by the appointment of persons with military experience to decision-making positions. The ethos of the military is to take decisions fast and to issue orders which have to be carried out by subordinates. The President’s early assertion that his spoken words should be taken as written circulars reflects this ethos. However, democratic governance is about getting the views of the people who are not subordinates but equals. When Minister Premajayantha lamented that he did not know about the direction of constitutional change, he was not alone as neither does the general public or academicians which is evidenced by the complete absence of discussion on the subject in the mass media.

The past two attempts at constitutional reform focused on the resolution of the ethnic conflict and assuaging the discontent of the ethnic and religious minorities. The constitutional change of 1997-2000 was for the purpose of providing a political solution that could end the war. The constitutional change of 2016-19 was to ensure that a war should not happen again. Constitutional reform is important to people as they believe that it will impact on how they are governed, their place within society and their equality as citizens. The ethnic and religious minorities will tend to prefer decentralised government as it will give them more power in those parts of the country in which they are predominant. On the other hand, that very fact can cause apprehension in the minds of the ethnic and religious majority that their place in the country will be undermined.

Unless the general public is brought aboard on the issue of constitutional change, it is unlikely they will support it. We all need to know what the main purpose of the proposed constitutional reform is. If the confidence of the different ethnic and religious communities is not obtained, the political support for constitutional change will also not be forthcoming as politicians tend to stand for causes that win them votes. Minister Premajayantha has usefully lit an early warning light when he said that politicians are not like lamp posts to agree to anything that the government puts before them. Even though the government has a 2/3 majority, this cannot be taken for granted. There needs to be buy in for constitutional reform from elected politicians and the general public, both from the majority community and minorities, if President Rajapaksa is to succeed where previous leaders failed.

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