In a poignant passage in the book A Short History of Nearly Everything (2003), Bill Bryson juxtaposes two events that occurred at almost the same time in the late 17th century: the publication of the Principia Mathematica by Isaac Newton in England and the killing of the last dodo by some unknown sailor far away in Mauritius. As testimony to the boundless capacity of human beings for both fantastic brilliance and inanity, it is indeed a telling example. We have come a long way since then, the hundred-fold or higher rate of extinction of various species (compared to the natural rates of extinction) on Earth can directly be linked to human activity.
Of course the last 50 years has seen a change: we now realise that we are responsible and take paltry and almost pathetically ineffective steps to prevent it. Simultaneously we accelerate this extinction process by the rapacious use of natural resources in the name of growth and development. We have truly become the masters of this earth. No wonder then that we now turn this newfound mastery to develop methods to destroy ourselves.
Take the present coronavirus pandemic. Scientists have repeatedly warned that the practices of industrial farming tremendously heighten the probabilities of diseases jumping from farm animals to human beings. We are indeed lucky that the present strain of coronavirus is not as lethal as the earlier SARS and less infectious than the common cold. My virologist friends tell me that usually lethality and infectivity do not go hand in hand. Otherwise things could have become really dangerous. Still, we need to pause and think whether our exponential growth in knowledge and power is going to be used for the betterment or destruction of humankind.
However, just as the blame for the dodo’s extinction is often attributed to its own stupidity, the blame for the ongoing pandemic must lie with someone else. Naming is the first step to stigmatising. It is therefore no surprise that Donald Trump keeps calling the new coronavirus the Chinese virus, to underscore the fact that it originated in China. One wonders why the swine flu was not called the US virus – after all, though the virus was first observed in Mexico, it contained a combination of genes mainly from pigs bred in North America. The lethal Ebola virus is named after a river in Africa though it does not even flow near the village where it was first discovered. Fortunately the river has not lodged any complaints.
In India, too, specific communities are blamed for the spread of this virus. The poor who cannot practice social distancing are also easy targets and blamed for the spread when they gather in long queues for food or at bus and railway stations in a desperate bid to reach home. Maybe they should turn around and call it the ‘airport virus’ or the ‘foreign-returned virus’ because it is such people who brought the virus into the country in the first place. The blame-game has reached such ludicrous proportions, courtesy the media, that today our country has a pandemic of fear, bigotry and prejudice – things which might be more difficult to eradicate than the virus itself.
The nature of the pandemic
Consider the facts more dispassionately. The new coronavirus has infected more than 2.3 million people worldwide and caused 0.16 million deaths, by the latest reckoning. These are huge numbers frightening to the First World, which has never experienced death and disease of this magnitude for the past hundred years. But in India, tuberculosis alone infects twice as many and kills thrice as many every year. And that’s just one disease. Add all the diseases that attack and kill the poor disproportionately and you get a number towering over the COVID-19 pandemic. And do we ever react in this fashion? And then there are hunger and malnutrition – how many lives they claim directly or indirectly?
The percentage play for the poor, if ever they had the choice, would be to go on with their lives and maintain their precarious earnings, to hell with COVID-19. That is what self-centred rationality would dictate because that would maximise their chances of survival. Yet they are supposed to make sacrifices to prevent the spread of this virus – which is difficult when you see your child going hungry to bed, day after day, and the promised handouts either never materialise or are impossible to access.
However, if we and the world wish to privilege this disease over others, then that is a policy decision. After all if left unchecked, this disease has the ability to grow to frightening proportions very quickly and that is surely a matter of grave concern. Blocking it at a nascent stage might give respite and be beneficial in the long run. It may even help humanity better understand the tragedy of death and disease, which has until now been ignored primarily because it is a constant companion only of the underprivileged.
But this job has to be carried out with sensitivity and rationality. Victim-blaming has no place in this enterprise. Food needs to be delivered to the hungry and needy, an exercise of such mammoth proportions that it cannot be done without a spirit of volunteerism from society at large. Food queues are long because there are not enough food distribution outlets to serve the millions who are starving. Gurudwaras have been selflessly running langars for ages. Why can’t this model be replicated in every locality? The real tragedy is large quantities of fresh produce rotting in villages while the urban poor go hungry. Many mandis have been shut because they are potential hotspots. As a critical source for food, the rational approach would be to regulate the crowd in the mandi rather than shut it down. This is surely a case of the cure being worse than the disease but it’s possible the people who take such decisions have never faced hunger themselves.
We have a food economy that is essentially informal and hugely decentralised, and it is time we realised that social distancing is about maintaining physical distance, not about shutting down all possible forms of social cooperation. This cooperation will surely be needed for a very long time. Thus even if the lockdown were to be lifted, families of those quarantined will need food, medicines and other necessities. How will we get it to them?
The potential of the scientific community
Not everyone has the ability or the proclivity to reach food to the poor but every person has strengths and skills. Consider the scientific community (if only because it is the one I know best). India has one of the largest scientific communities in the world, and today, it is essentially sitting idle at home. Can we not leverage their skills and knowledge? Knowledge is power and we are hamstrung in our fight against this virus because of lack of knowledge. We know about it only in terms of what we know of other coronaviruses, not the specifics. Fortunately the Council of Scientific and Industrial Research has now taken the initiative to sequence the virus and hopefully we will soon know better.
India has undertaken huge genome-sequencing projects in the past, including of humans, rice, potatoes and many farm animals; compared to them, this task should be a walk in the park. Maybe we will have multiple viral sequences to look for variability in this population. We have highly skilled immunologists to work on understanding how this virus works. To be sure, the epidemic in India and in some other countries is playing out differently than it is in, say, Europe or the US: here, for as yet unknown reasons, its doubling time in the population is very low. Thus, in India, the virus emerged fairly early and has since been spreading at a relatively slower but steady pace.
In the first week of March, India had around 30 cases while for example Turkey had one. Then the epidemic exploded in Turkey in mid-March, and the case load doubled almost every day crossed the 10,000-mark before the month was over. The doubling rate then started slowing, to a still high rate of once every seven or eight, days resulting in a fairly large infected population of 86,000 individuals. In contrast, the doubling in India has been uniformly low, leading to a tenfold increase in 15-16 days even when the lockdown was not in effect.
Contrast this with the US, where it increased tenfold every eight days, thereby increasing 100-fold in the same 15-16 day period. In Russia, the tenfold increase happened over around 10-12 days (somewhere between India and the US). But Russia also shares the problem with India, which is that the rate is stubbornly refusing to decline, as has happened in other countries. On the site Worldometers.info, when you plot the time course of the cases as a logarithmic plot, the slope of the plot becomes a measure of the doubling time. And this slope for most countries begins to angle downward after a time. Why this happens is not yet clear.
While social distancing surely helps, there are other factors at play as well. One of the exceptions is India (and Russia and a few other countries) where the most frightening thing is the unbending nature of this straight line that you observe when you plot the logarithm of total cases v. time. The slow rise may be a blessing but its inexorable nature is truly alarming. Some hopeful statisticians have tried to locate a small change in the slope of this straight line after April 6 and connected it with the lockdown. See for yourself whether you can locate this small bending downwards visually, which is admittedly difficult given the natural fluctuations in any real data. I can’t, but then I would reserve judgment and wait because statistical analysis is after all a more rigorous method.
On the other extreme, some modellers in the US have predicted large case loads in India, running into tens of crores after two months, though how they arrived at these numbers with such a scarcity of information is a mystery to me. Maybe they extended the straight line of the logarithm plot right into July, though such extrapolation is clearly as unwarranted as those who would predict the line bending downwards.
The issue of low testing rates
One serious problem is the paucity of testing, and the very real fear that we don’t know with confidence the exact number of infected patients. Which means all our predictions are going to be faulty. On the one hand, India has opened up many more testing centres and the number of tests compare favourably with the number of positive cases. The fact that as of today 4 lakh tests have been done to detect the 17,000 positive cases is an indicator that if more COVID-19-positive patients had been actually out there, most probably the tests would have identified them. Thus France has only conducted slightly higher number of tests, 4.6 lakh, but detected a larger number of people with the virus, 1.5 lakh. So we can be reasonably sure that the Indian numbers are not a gross underestimate.
On the other hand, our population is much larger and the number of tests are very small with respect to the total. It can therefore be argued that if the virus has spread far and wide, these test numbers are woefully inadequate. One argument used to defend the low number of tests is the non-availability of test kits that supposedly come from China, and their high cost. This is an amazing proposition. Our scientists routinely carry out PCR1 experiments in their labs and the number of PCR machines in biology labs in institutes and universities is very high. Maybe some detail is required here.
The coronavirus is an RNA virus, which means its genetic material is RNA and not DNA. To detect it, RNA is isolated from patient samples and converted to DNA using an enzyme called reverse transcriptase. As an interesting aside, this enzyme is also present in humans as is used by the virus to replicate itself inside the human host. Why it is present in humans is a mystery, since it is known to serve no useful purpose. One fashionable theory is that nature put it inside so that if human beings became too cocky, their hubris could be pulled down a notch or two by ensuring a visit by RNA viruses like AIDS and the new coronavirus! This theory is clearly part of the loony fringe and no respectable scientist would subscribe to it, though I must admit that I do have a grudging admiration for its basic premise.
Once this DNA is made, it is amplified using a PCR machine and gene specific primers, which are simply short stretches of DNA that bind specifically to the target DNA. The amplified DNA is detected by the release of fluorescent dyes as the amplification proceeds inside the machine – giving rise to the name ‘real-time PCR’. But – and this is important – the amplified DNA can also be detected at the end of the amplification process by simply running the samples on a gel. As a matter of fact this was and still remains the traditional practice.
The presence of amplified DNA implies a presence of the original RNA, and hence the sample is marked as COVID-19-positive. This traditional method of detection is well established and routinely conducted in every research lab. It is not a jugaad method (a term I dislike because of its connotations with poor quality and compromised safety standards). Why can’t our numerous research labs volunteer to undertake large-scale testing, since most of the material required is either already present in the lab or easily purchased. It simply precludes the need for kits. If I were to be permitted to introduce my own little bias and prejudice, I would say that our research staff and students are as good as certified labs at running these experiments, especially if one were to include private labs. Another interesting detail is that we can pool samples to reduce the number of tests and hence costs.
For those who are interested, here is a simple trick I learnt during the days when PCR materials used to be expensive and large number of samples needed to be processed. It leverages the power of PCR to amplify even trace amounts of DNA making it a very sensitive tool for detection.
Suppose we have hundred samples. Arrange them in a square grid of 10 x 10, labelling them as follows: A1, A2, A3 … to A10 (first row); B1, B2, B3 … to B10 (second row); and so on until J1, J2, J3 … J10 (tenth row). Now pool the first row samples A1 to A10 (called sample A) and second row (sample B) till the tenth row (sample J). Now similarly pool the column samples i.e. samples A1, B1, C1 … J1 (sample 1) samples A2, B2, C2 … J2 (sample 2) and so on until sample 10. Now run these 20 pooled samples on a PCR. Now for example if sample C and sample 5 turns out to be positive, the conclusion is that sample C5 was the original positive sample. This grid can be made much larger, say 24 x 24, allowing us to process much larger number of samples with no significant loss of sensitivity.
To give you a sense of the numbers, let me choose a small subset of biology labs present in the JNU-NII ICGEB cluster in Southwest Delhi. By a conservative estimate, they have more than a hundred PCR machines and trained manpower to run them. In a single day, each PCR can run a thousand tests using the pooled technique. This translates to a lakh tests per day – clearly enough to resolve the whole problem of low testing rates. And the cost per sample would also reduce drastically to a couple of hundred rupees. One argument that can be made is that these are not certified labs, and the tests are therefore somehow not acceptable. Fine, we can treat this as a screening protocol. The positives can be tested again in certified labs, and one can easily estimate the huge reduction in the workload of these labs in identifying COVID-19-positive cases.
There is another method of testing, being popularised as fast and convenient since it depends on directly locating the presence of antibodies against the new coronavirus in patients. However, this is an insensitive procedure since people at the early stage of infection don’t make significant amounts of antibodies, and by some estimates 50% of early positive cases could escape detection by this method.
The work doesn’t end there. Research labs have also got real-time PCR machines and fluorescent dyes. These can be run on positive samples not to simply confirm the test results but also answer the more intriguing question of the viral load in the original sample. This is done by calculating backwards, and given that each PCR cycle results in doubling the DNA, we can estimate the copies of DNA in the original sample. Does this viral load vary between patients? And how does it compare with patients from European countries, where the virus virtually exploded in their population? Will these results give insights to the epidemiology of the virus and its variability across nations? We do not know – but we do know that more sophisticated models rather than simple exponential growth with varying exponents is required.
Scientists are curious people and they love solving puzzles. This is a happy and rare confluence, where their curiosity matches social needs and an improved understanding of the virus could possibly save millions of lives.
But let us be honest. Implementing these ideas requires a sea-change in the attitudes of not only the people but also the government and bureaucracy. Samples have to be collected from patients far and wide and transported to these labs, a huge logistic exercise. Scientists and research staff have to be permitted access to their labs and we need to trust their common sense to ensure physical distancing. We need a larger perspective, where good citizenship doesn’t simply mean sitting cozily in our homes like obedient schoolboys in a classroom. It means reaching out with whatever strengths we have at our disposal for the good of society. In the immortal words of John Milton
“I cannot praise a fugitive and cloistered virtue, unexercised and unbreathed, that never sallies out and sees her adversary, but slinks out of the race…”
It requires that bureaucrats implement the spirit and not just the letter of the guidelines issued to them. It requires that policemen stop raining lathis on hapless individuals and extend a hand of courtesy. It requires that the media promote the spirit of volunteerism by bringing into the limelight the stories of countless individuals whose selfless courage and sacrifice in the face of this adversity illuminates these dark times. It requires them to enter the households of people throwing stones at health workers and understand the reasons for this supposedly irrational and self-destructive behaviour, rather than vilify them. It requires that educators join in large numbers to counter the poisonous half-truths and the downright lies being spread in social media. It requires empathy for the underprivileged and the dispossessed. And it requires the unleashing of the vibrant and creative force of a hundred million people doing a million different things.
Only then can we say that we are a nation united in our fight against COVID-19, and not a bunch of squabbling, self-serving individuals. I have great hopes that things will ultimately change for the better and we will emerge as better human beings after this crisis blows over. But then, to quote Commissioner Gordon in the Batman movie: “I have been known to be wrong before”.
K.J. Mukherjee is a retired professor and former dean of the school of biotechnology, Jawaharlal Nehru University, New Delhi.
Polymerase chain reaction↩