The Overlord

LET’S GET THIS out of the way first: What, exactly, is a ‘microbe’? Quite simply: any life form that can only be seen under a powerful lens or microscope. And how many microbes exist in the world? If you were to say a trillion to the power of trillion, chances are you will still be well short of the actual number which is likely to be inestimable, perhaps even unimaginable. Consider this: the ongoing COVID-19 pandemic (short for coronavirus disease 2019) started out as a tiny speck in the airway of a wild animal before it passed through hundreds of millions of human lungs, trailing havoc in its path. At the time of writing this, there have been nearly 122 million recorded cases of COVID-19 in the world.

A British mathematician has, however, estimated that all of the world’s circulating SARS-CoV-2 (short for ‘severe acute respiratory syndrome coronavirus 2’, the causative agent of COVID-19) virus could easily fit inside the confines of a single can of cola! From what we know, only an infinitesimally small fraction of microbes makes us sick, even fewer have the power to kill us. Most simply pass through us, and a few use us as a suitable substrate to make more of their kind. They usually don’t bother us in the least and some, in fact, many, actually do us good.

In every pinch of undisturbed soil, in every drop of water, there live a billion bacteria and ten times that number of viruses. Every lungful of breath we take contains about a thousand microbes. Most of them are unknown to us. Into this mysterious universe of microbes, come the scientists diving deep, like Captain Nemo, stooped over modern microscopes. They sit gazing at a wondrous world to explore the lives of predators and prey, producers and parasites. Some of the microbes are solitary, a few are in conjugal bliss or are colonisers; many are barely minutes old, the rest are mature, dying or already dead. Each speck of life you see under a microscope has a well-defined role, and in their plurality, they make up habitats no less complex than that of a multi-storeyed tropical forest. The crucial difference is that life in the microbial world plays out several times faster. Microbes come in tantalizing forms and often in geometry-defying shapes. They can be translucent and iridescent, twitching or fleeting as one watches them; a plethora of awesome diversity in just a thimbleful of pond water or in soil taken from under leaf litter.

There is no singular world of microbes. Every ecosystem has its own set of curious microbial communities—from the freezing ice of Antarctica to the hot sands of the Sahara, in the placid pond in your neighbourhood to deep-sea volcanic vents. They are everywhere. The surface of a pond teems with numerous photosynthetic organisms. Delve just a foot deeper and the character of organisms changes, while the benthic bottom of the pond and its sediments may have nothing in common with what is on top. A change of seasons or even the time of day can alter the proportions and number of microbes present. Microbial diversity shifts across the surface of the Earth as a consequence of the same three forces that Charles Darwin highlighted to explain the diversity of plants and animals— environment, dispersal and diversification. Microbes mirror the same geographic patterns of diversity as those found in larger organisms, with the variety of microbes (or bacterial species richness) twice as large in the warmer tropics than it is at the frigid Poles.

Microbes come in bewildering shapes, are deeply complex, and in terms of sheer numbers are unmatched by any other life form. Try this for size—it is estimated that there are 100 million times as many bacteria in the oceans (1.3 x 10 to the power 29) as there are stars in the known universe. There are more microbes in natural water than in the soil around it, or in the air above. Even on dry land, their numbers are immense and surpass the imagination. The average number of microbes in a single teaspoon of soil (10 to the power 9) is as large as the human population of Africa. The human jowl alone, on average, has more than 6 billion microbes that can be made up of more than 600 separate species. A single gram of the stale-smelling yellow grimy film on our teeth, good old plaque, has approximately 1011 bacteria, which is about the same number as that of all the humans that have ever lived.

VIRUSES ARE BLIND, and they are not driven towards any goal and, as far as we know, work in a completely random fashion, driving evolution in no specific direction. These replicators take every opportunity to absorb and affix information in the form of genes from their hosts. A bit like bots or the machine learning algorithms of your search engine or social media, which store all your data and use it to constantly feed you with information, some useful, much of it junk. This exchange of genes between viruses and the cells they infect occurs both ways and both amalgamate each other’s genes. This is what the arms race is all about in nature. Just a few genes decide which species will die out and which ones will survive. This ability of the viruses makes them one of the most persistent and potent forces of evolution.

THE INFLUENTIAL BRITISH biologist and science writer, Sir Peter Medawar, called the virus ‘a piece of bad news wrapped in protein’. Scientists, too, can often be faulted for looking at viruses through the narrow lens of the infections and diseases they cause. But as the world’s most abundant ‘life forms’, the ambit and influence of viruses is a whole lot broader. Viruses are everywhere, infecting all forms of life, and this ability to shuttle and shuffle genes is another reason that makes viruses one of the most persistent and potent forces of evolution. Everything about viruses is extreme, including perhaps, the reactions they evoke. But for every truism about viruses, the opposite is also often true. Take for example, the speed with which they multiply within a host. While a single bacterial cell divides every few minutes or hours, viruses, too, can take just a few minutes or hours, like the viruses that bring about conjunctivitis or the common cold; or they can take several days, like the dengue virus; and a small minority can even do a Rip Van Winkle, lying dormant for years, like HIV does; or even for decades, as in the case of shingles.

Whether we see viruses as dead or alive, as life-threatening or life-affirming, there is an ineluctable beauty and even a certain elegance in the way viruses go about their lives. Each virus, under different conditions, adopts a unique strategy to multiply. Outside a host’s body, a virus is inert. To spring back to life, it needs to inject its tiny package of genes into the right kind of cell, and in order to do that, it first needs to overcome a maze of complex defences of a host, locate the right cell inside the host, inject its genes into this cell, and only then is it able to make copies of itself, and hopefully, thrive. Whether it is their cunning in dodging a host’s immune system, their craftiness in dismantling a host’s DNA or their brilliance in making new copies of themselves—there is a majesty in the entire process which begins when the host cell starts to die until the emergence of several tens or hundreds of viruses.

Every virus has a rhapsodic cycle of its own, and if you were to watch the viral invasion of cells under an advanced optical instrument, you might even hear in your mind’s eye a march by Strauss, the brass band of Grieg or a Sibelius drama with drums rolling!

IT’S NOT EASY being tiny and a total parasite. Viruses spend a lifetime out of sight and virtually out of mind—blending into the air, buried in the soil, afloat in water or hitch-hiking on a host. But the self-effacing virus plays a disproportionately vital role on Earth by making all life possible. The complex network of life is driven by the action of microbes who simultaneously create, consume, break down, synthesise and fix organic matter. They also produce energy with relentless and tireless efficiency. At the heart of every critical process in the biosphere—from creating the atmosphere to decomposing waste—lie microbes, and maintaining control over these are ultimately, what else? Viruses!

After the Sun and plate tectonics (gargantuan geological processes by which the continents and oceans, landscapes and rocks are created or destroyed), viruses are the most significant force to shape the course of evolution on Earth. Viruses have the power to cause billions of infections every second and to reproduce within their hosts quickly. In doing so, they create opportunities to cause mutations which, in turn, create new varieties of themselves and that of the host they infect. It is in this sense that viruses are a powerful unseen force that keeps the planet and its complex systems in order or throws it into chaos. Geological processes for the most part take place at a very slow—geological—pace. Every day, the Sun’s radiation and UV rays pour unlimited energy on the surface of the Earth. It is solar energy that powers wind patterns and ocean currents, shapes the seasons and determines climate. Viruses, on the other hand, work much faster, but their actions, like viruses themselves, are covert and little known.

WHEN WE ARE born—and even before we are born—our bodies are exposed to a variety of bacteria and viruses and we are colonised by a number of them. By the time we enter school, we become infected or passively acquire multiple viruses, most of them, fortunately, ‘benign’ ones. We are also endowed with endoretroviruses that are embedded in our genome, that we pass on to our children, and they to theirs. In fact, it is these very viruses that make our gestation and birth possible. Then there are viruses that lie dormant in our cells, blood and body fluids, and only emerge when instigated. Unlike the genome-embedded endoretroviruses, these viruses turn pathogenic at some point of time in their lives (and that of their host) in order to reproduce. Infecting and causing disease, therefore, is necessary for their survival.

INCREASINGLY, IMMUNOLOGISTS are beginning to appreciate that these free-ranging viruses may be more beneficial than harmful to us. Because of their widespread yet largely dormant existence, they are an excellent indicator of our immune status and can be used to predict individual health. A few long-term immunological studies have found early evidence of some resident viruses offering mild protection and the ability to signal the possible presence of viruses and emerging medical conditions. Like spooks, some viruses like JCV spot vulnerable cell receptors that can be open to attack, alert our immune system to repair these and thus avert serious diseases. They can be used as indicators of the onset of early manageable but later irreversible conditions like cancers, diabetes and obesity. Another lurker, the hepatitis G virus, decelerates disease progression in immune-compromised patients like those with HIV. Some viruses may be key to building our innate immunity, the one that we are born with. Very few of us, apart from some isolated ethnic groups and communities, remain herpes virus-free. Since the discovery of these silent and hidden viruses, the idea that viruses are all agents of disease is giving way to the notion that they can exert positive and even protective effects.

We still don’t know if there is any trade-off in those who are infected versus those who are not. And we don’t quite know whether the presence of these freewheeling viruses continues to influence the evolution of our genome, shape our immunity or affect the functioning of specific cells. What we do know is that there is much we still need to find out and explore about these tiny residents in our bodies, and we need to delve deep to begin to unravel the secrets they hold.

MICROBES, AS WE have seen, are everywhere—outside our bodies, of course, but also inside. And within our bodies they are found in numbers that defy the imagination. The food we consume has a direct impact on the bacteria that live within us. The interplay of bacteria, phages and immune cells in the gut (and elsewhere) could provide key information on how to manage future health and disease, and how we can harness the microbiota in our pursuit for personalised medicine and treatment. With so much happening in our guts, and also lungs, vagina and skin, microorganisms are constantly at work, helping themselves and you, right inside you, whether you are aware of it or not. So, don’t reach for the antacid, that cigarette you are craving or the disinfectant you have been using compulsively. These may be counterproductive for your microbiome and therefore to you. The answer may be to gradually change our lifestyles and not resort to quick fixes like supplements. For example, although there is a lot of research that talks of the benefits of probiotics, their long-term effects are yet to be studied. Off-the-shelf probiotics may be good when you are recovering from an episode of diarrhoea, but in general, they are medically underwhelming. Probiotic products contain proprietary strains of bacteria that have been heavily domesticated. They are present in these products in very low numbers and the species are chosen for the ease with which they can be manufactured, stored and for their shelf life, and not necessarily because they are the best for our bodies. Research is ongoing and there are no clear right or wrong answers yet. Although, as one review put it, ‘It may be plausible that consuming more fermented foods improves the health of the gut microbiome and may stimulate the vagal afferents and functions of the brain.’ For now, reaching for the sauerkraut, miso or kimchi may be a safer bet than that probiotic product on the supermarket shelf.

A MORE CRITICAL POINT to remember is that microorganisms, or any small life form for that matter, are not ‘bugs’. Or critters, or germs. Nothing is a ‘bug’ when seen in the context of its role in nature and evolution. These minuscule organisms that share our bodies are not random stowaways or hitchhikers. Some of them are critically important to our lives. We have been looking at ourselves, our existence, our biology and our relationship through a keyhole and from our perspective alone. Thankfully, new, more accessible research has thrown the door wide open to appreciate a grander view of life and processes which tie us intimately to the microbial world. Any assault on them is to turn the gun towards ourselves. The next time you follow your ‘gut instinct’, remember that it is not just you but a teeming multitude of organisms that may be behind it—all cheering for you! And keeping a tight control over the numbers, the spread, and the actions of all microbes is that overlord of every microbiome—the virus.

(This is an edited excerpt from Invisible Empire: The Natural History of Viruses by Pranay Lal | Viking | 500 pages | ₹ 799)

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