Chapter 1: When to Worry


This is the first installment of what was a book project of mine. It is written for a general scientifically interested audience and the style reflects that. Feedback on my ideas is always welcome.

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“You’ll tell us when you’re worried, right?” This was a question I was frequently asked by reporters, colleagues, and even my barista during the height of the 2014 West African Ebola outbreak — the deadliest in history — when, drawing on my work in infectious diseases and pandemic preparedness, I was called upon to serve as a media expert.

Throughout the hysteria and the 24-hour news cycle, I repeated one statement: “Ebola is a deadly scary disease, but it is not that contagious and will not find the United States (or other industrialized nations) to be a hospitable environment.” In the end, this was borne out, increasing my credibility with those who had heard my predictions.

But my predictions were not based on some overly rosy outlook on the landscape of infectious disease. How could I have a rosy outlook on infectious disease with serial killers such as HIV, malaria, and tuberculosis presently threatening the human race, and diseases such as MERS and SARS emerging as deadly threats? We had just experienced a pandemic of a novel influenza virus that took the world by storm and surprise. Meanwhile, its highly lethal avian cousins, including to this day, seem to be waiting for the right opportunity to pounce. In 2014, abetted by the primal scream of the anti-vaccine movement, the US had a record number of measles cases (in the post-vaccine era) and just 4 years later the Americas lost their measles elimination status and the US broke measles records. Perpetually lurking in the background of all these explosive outbreaks, antibiotic resistant bacteria threatened to collapse the entire structure of modern medicine.

 In short, I know just how deadly and disruptive infectious diseases have been, both historically and presently, as well as what it takes for an infectious disease to be included in the pantheon of pandemic causing pathogens.

Despite almost no chance of contracting Ebola, ordinary people in industrialized nations took extreme, unwarranted measures – such as buying spacesuit-like apparatuses for what they believed was the coming apocalypse – that would not make them any safer from the disease. Though many people truly feared the world was poised to become a dead zone inhabited by Ebola-stricken zombies, their fears have not come true.

 Indeed, in the midst of the unprecedented Zika outbreak in 2016, I echoed a similar message to dampen fear. Drawing on historical examples such as rubella – which caused similar devastating fetal anomalies – I tried to explain that Zika, notwithstanding its considerable public health impact, doesn’t measure up to a widespread pandemic threat.

 What some actually fear, with each outbreak of emerging infectious disease, is the arrival of an extinction event. Hypothetically, such an event would cause such a large proportion of the human race to succumb to infection, leaving few or no survivors, that the population would cross a critical threshold, beyond which the species cannot be sustained. The extinction event concept activates the human imagination like nothing else: our minds fill with dinosaur images, science fiction narratives, and post-apocalyptic scenarios.

This focus on extinction or existential level infectious disease threats may be intellectually stimulating, has synergy with ordinary pandemic preparedness, catches the eye of prominent philanthropists such as those involved in the Effective Altruism movement, but is often hyperbolic and distracts away from actual infectious disease and public health tasks that are tractable and merit attention. As we have learned through COVID-19, hyperbolic pronouncements sow mistrust between public health authorities and the public and often create false alternatives for policymakers.

 The most famous extinction event is, of course, that of the dinosaurs 66 million years ago. Though we tend to associate it exclusively with dinosaurs, the truth is that three quarters of animal and plant species perished during this period, formally known as the Cretaceous-Paleogene extinction event. The leading hypothesis, which has amassed enough supportive evidence to reach the level of a theory, points to an asteroid impact. It is important to note that the impact alone, rather than cause mass extinctions in itself, created changes in planetary conditions that made life impossible for those species unable to adapt and ill-equipped to a markedly different habitat.

 Such a cataclysmic result is not surprising, since many species would not have developed resiliency mechanisms to cope with a major habitat change. Natural selection would not have produced superfluous traits (in the absence of an asteroid strike) on a large scale. In essence, the Cretaceous-Paleogene extinction event was a great culling, the survivors of whom possessed, by chance mutations, the characteristics that allowed them to survive.

 An interesting footnote to this event is the idea that drastic reductions in the amount of sunlight killed those plants that relied on photosynthesis for life, resulting in the proliferation of non-photosynthetic organisms such as fungi. If, like me, you try to find an infectious cause in every event, you may wonder if the increase of fungi led to widespread fungal infections, magnifying the devastation posed by the loss of nutritious vegetation relied upon by most species. Today, fungal infections are responsible for annihilating species of reptiles and amphibians.

 Whatever the mechanics, the Cretaceous-Paleogene extinction event is the most widely known of its kind, but it is decidedly not akin to something an infectious disease pathogen could do. I mention this event only to draw a distinction between an actual mass extinction event and what a severe human pandemic is capable of doing.

For many species – unequipped by evolution for changes in habitat, predator-prey relationship variations, and myriad other factors – micro-extinction events occur continuously.

Amongst these micro-extinction events, there has been only one semi well-established infectious disease extinction event—that of the Christmas Island rat by Trypanosoma lewisii, a mosquito-borne protozoan (related to the causes of the human infectious diseases African Sleeping Sickness and Chagas Disease). In this instance, the poor rodent, stuck on an island and unequipped to leave it, had nowhere to run. Incidentally, there is an effort to de-extinct this rat using modern technology.

However, between a fleeting infectious disease outbreak and an extinction level event there is a lot of room for disaster. I agree with most experts who do not think an extinction event is possible. However, there is a concern for what are termed global catastrophic biological events (GCBRs). These events, which are caused by infectious disease outbreaks, have the capacity to lead to dire consequences for modern industrial society as the resources needed to contain them outstrip national governments and the private sector.

The COVID-19 pandemic, with its relatively low mortality ratio of <1%, has proved to be such a case. The early failures to see it as the looming threat it was — and eventually became — reflect either a degree of evasion or a failure to understand the threat matrix of infectious diseases. The events of this pandemic exposed major vulnerabilities in what were deemed the world’s most prepared nations. There have been several times that I have been baffled and frustrated by the response. This was especially true in the early stages where inaction followed by wrong actions could not have been more perfectly calibrated to orchestrate disaster if they were planned. For example, ineffectual travel bans, flawed testing criteria, the lack of testing capacity, the lack of personal protective equipment (PPE), the failure to fortify nursing homes, and the general reactive evasive nature of the response set the stage for the million plus deaths that followed in the U.S.

 

When it comes to infectious diseases, it is events such as these that induce people to worry about the future of the species, societal collapse, and economic ruin.

The human species, for the vast majority of its existence, has struggled against infectious diseases of one sort or another. And the explosive increase in our average life span, a very recent occurrence, can be directly attributed to the control of infectious diseases through sanitation, vaccination, and antimicrobial therapies. So, for most of mankind’s history, infectious diseases were the existential threat. And time after time, they have proven their success at killing humans and impacting civilizations. The emotion of fear, given this context, is quite understandable. The luxury of death from cancer, heart disease, or stroke in our eighth decade of life has only emerged in the modern era, when industrialized societies learned to mitigate many infectious diseases. Idyllic childhoods – free from watching siblings and friends die from outbreaks of typhoid, scarlet fever, smallpox, or measles – were not the norm for most of our ancestors. Even today, some parts of the world still face such threats.

 

Extinction Event is the result of my daily engagement in this field which ranges from treating patients, to speaking to the media, to thinking deeply about the role of infectious diseases and human societies. My aim is to provide you, the reader, with an important context by which to gauge any infectious disease outbreak by providing you a grounding in the key factors that govern an infectious disease’s trajectory, grasping the significance of certain facets of historical outbreaks, understanding other variables that set boundaries for infectious disease outbreaks, and recognizing the key tasks of pandemic and emerging infectious disease preparedness.

 

In what follows, I will alternate between discussing outbreaks, epidemics and pandemics, because much can be gleaned from looking at extreme and varied cases to elucidate, and set limit conditions, of what will be most likely to occur. Also, and crucially, preparations for the mitigation of these events are similar, utilize the same infrastructure, and engender expertise in outbreak response fundamentals. By executing the right actions for the most minute threat such as a limited salmonella outbreak or the occurrence of a single case of a high consequence pathogen, the threat of larger occurrences is lessened.

           

It is important to emphasize that when it comes to humans and infectious disease outbreaks, we cannot evolve our way out of them. Whether it is influenza, COVID-19, or plague, the key question to ask is how to diminish the societal disruption that will be engendered. This can only be accomplished by knowing the key questions to ask, acquiring knowledge iteratively, and ultimately taking the right actions.

 

Though I will argue against an infectious disease being able to cause an extinction or even a global catastrophic biological event for humans it should not be construed as minimizing the impact and importance of extreme resiliency against infectious disease threats. What my discussion does provide is a framework to better focus preparedness on the most crucial elements. How can we minimize the chance that infectious disease threats cause disarray? If a low lethality pandemic like COVID-19 can wreak such havoc, what would happen if something far more dangerous took hold.

 

As part of my argument, I will introduce several themes or principles that will provide a framework that I, personally, rely on as a lens to understand past infectious disease events, gauge the impact of current threats, and try and predict those that lie in the future. Whether or not they are exhaustive, at minimum this framework provides an integrated and principled way of thinking about this field. I consider the below points my primaries, first principles, or starting points:

 

1.    For an extinction level event to occur, an infectious disease will have to possess certain attributes that allow it to first cause a pandemic. Not every infectious disease has pandemic potential.

 

2.    By its very nature a pandemic pathogen must be capable of transmitting efficiently between humans, putting bounds on which of the myriad members of the microbial world are capable of this feat.

 

3.    The human immune system, which evolved in the midst of our microbial planet, is a major constraining factor on the impact of infectious disease threats because of how it operates.

 

4.     The human mind’s ability to develop new tools to attenuate the impact of infectious disease threats — in increasingly more rapid fashion — has grown increasingly formidable through our species’ existence.

 

Any human pathogen — whether pandemic, epidemic, or outbreak worthy — will have to overcome these factors.

 

So, here again is the crucial question I began with, but reformulated: why couldn’t an infectious disease constitute an existential level threat to humans?