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The future of fevers

Author and biochemist Pranay Lal argues that the next pathogen waiting in the wings will be all of our making

‘Untitled II’, by P. S. Jalaja, from Space118 Fundraiser 2020.

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How did a virus, something we label as a non-living obligate parasite, bring the world to a grinding halt? News from China suggests that the threat is looming again. Was the world’s collective sigh of relief in September, when the World Health Organisation (WHO) announced that the end of the pandemic may be in sight, premature? Should we begin to panic again? I don’t think so but I cannot be certain. Nor, I suspect, can anybody with one hundred per cent accuracy. What I am certain about, though, is that the pathogen waiting in the wings is all of our making, a result of our transgressions with nature.

In his Nobel Prize acceptance speech in 1945, Sir Alexander Fleming, discoverer of penicillin, had presciently warned about the dangers of its misuse. But we began to use antibiotics indiscriminately—in hospitals and outside—often without a prescription. We used it to speed up the growth of our livestock and unscrupulous pharmaceutical companies sold antibiotics to unsuspecting poultry farmers, promising their efficacy in averting potential disease outbreaks. We looked unbeatable with our arsenal of antibiotics, and we got cocky.

Just 20 years after an Oxford policeman was first administered penicillin in 1941, reports of “resistance” to penicillin trickled in from hospitals around the world but Western pharmaceutical companies were convinced that with their growing arsenal of antibiotics, the end of the age of infectious diseases was in sight. The US surgeon general, William Stewart, declared in 1967 that it was time to “close the book on infectious disease”. In this age of ebullient optimism, a popular medical textbook, considered a classic in its day, went so far as to claim that all infectious diseases would be eradicated by the year 2000. Cadres of young medical students and practitioners were made to believe they had to focus on more pressing emerging challenges.

It was only in 1969 that the WHO and the UN’s Food and Agriculture Organization prescribed standards of permissible limits for antibiotics and other chemicals in food and water, thereby tacitly conceding that their pernicious overuse was not acceptable. But we had faltered at the start and we kept fumbling even as new antibiotics were being added, and what had seemed like a 100m dash against disease has become a gruelling, uphill marathon.

Over 50% of life-threatening bacterial infections are becoming resistant to treatment, a recent WHO report reveals. Over 1.27 million deaths result from drug-resistant infections. These human-armed microbes kill more people than the diseases themselves (example: HIV/AIDS, 864,000 deaths; malaria, 643,000 deaths). We have created monsters from the irrational use of medicines. We have weaponised microbes to become deadlier while unleashing new ones.

With new advancements and more individualised treatments, new hierarchies emerged in medicine. Life sciences like bacteriology, which laid the foundation for modern medicine, began to play a supporting, rather than an integral, role in the cure of diseases. Microbiologists and biochemists of the 18th to early 20th centuries—Jenner, Koch, Pasteur, Ross and others, on whose discoveries the principles of modern medicine rested—still had their portraits hanging in medical school corridors but their contributions became inconsequential miscellany, mere footnotes in medical textbook chapters.

From once being part of a vibrant, inspiring and networked community of scientists, medicine became insular, with narrow specialisations. The study of disease outbreaks, new pathogenic agents, and the conditions in which they emerged took a back seat. Year after year, investments and political commitments to fight infectious disease began to dry up and fewer new drugs aimed at diseases that affected the poorest of the poor made it to the market. As globalisation and the exploitation of new resources occurred, new infectious agents appeared, but these were treated as exotic fevers, titillating researchers and journalists who wanted to claim these as their discoveries, with no serious plans being made to counter any potential threat. Unfortunately, even post-covid, the WHO, the UN and the specialised agencies of almost every nation are still caught up in the same mindset.

Globalisation has made it easier for pathogens to circulate through the movement of people and goods. Even when the world shut down, SARS-CoV2 found ways to cross over from human handlers into big cats in zoos, domestic animals in homes, and animals farmed for fur. So we created new opportunities for a virus that was lying dormant in a small mammal, brought it to a wet market, caused a human pandemic, and also found ways for it to enter new animal hosts. We haven’t done much to stop future pandemics. For a start, a global ban on animal and plant trade should have been in order but this was quickly forgotten. The cries of exotic creatures in wet markets in South-East Asia and Africa have not subsided.

What are future waves of fevers likely to be like? I had written in my recent book, Invisible Empire: The Natural History Of Viruses (2019), that m-pox (monkeypox) was waiting to emerge. There may be other poxes too that could capture the missing niches left vacant by smallpox. So what is in store for us? Scientists, who study chaos, develop models and use predictive sciences, generally agree that it is easier to explain intergalactic phenomena, predict weather and future climate scenarios than it is to predict pandemics. Anything that involves human factors is not easily predictable. The number of reliable data sets available is particularly small in relation to the number of variables that need to be considered in the construction of model pandemic scenarios. There are currently no reliable disease forecasting models which can be used to underpin a health policy or an economic allocation. They can, at best, help shape hypotheses and scenarios.

To make matters worse, pathogens are fickle and unpredictable by nature. When a pathogen passes through diverse human populations, it finds the possibility of mutating. Viruses are particularly crafty. The first to get infected by the virus is a naïve population. In them, the virus encounters little or no “selection pressure” because it faces little resistance. There is no evolutionary advantage for the virus to mutate.

As the virus passes on within and across populations, it gets opportunities to mutate. Losing or gaining a few genes makes it less or more virulent. Each variant thus produced has a different impact on that population. Every time they emerge, viruses gain more variability (which we know as an antigenic variation).  

For vaccine makers and health professionals, this is a nightmare. To overcome this, early during the emergence of SARS-CoV-2, networks of virologists began collaborating to understand how and when mutations could occur. Alongside virologists, immunologists probed antibodies in populations in painstaking detail. Together, these helped predict the mutations in the “variant soup” and the population’s response to it. This complementation has helped some countries stay a step ahead of the virus’ wild evolution.

How, and how quickly, these variations occur needs very careful analysis. Only when data is shared openly and analysed to predict what path the pathogen will take can the global community prepare better. In the period when covid-19 devastated the world order, every country felt the impact of the pandemic. But only a handful of countries have made their data available and have since made an assessment of the aftermath. We don’t have any figures for some of the largest countries in the world, including Brazil, India and China, and therefore there can be no robust assessment or plans to control future outbreaks or mitigate epidemics.

We need answers to many more questions before we can lay out even a framework to predict the next outbreak or address ongoing and future pandemics. We need to share openly on what and how much we have learnt from the novel physiologic evolution of pathogens, and what the limits and uncertainties of our current understanding are. Until then, every lifeless minutiae wafting in the air that passes through our lungs and guts has the potential to give us a rude reminder of our place in nature.

Pranay Lal is the author of  Indica: A Deep Natural History Of The Subcontinent and Invisible Empire: The Natural History Of Viruses. He is a biochemist who works at the intersections of environment, climate change and health.

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