Viruses, DNA Cages, and Tigers, Oh My! A Review of Tiger Tiger

In a world in which daily headlines announce breathtaking advances in genetic engineering and synthetic biology that have the promise to eradicate disease and lengthen lifespans, it is not surprising -- and actually prudent -- that there efforts to understand how such technology could be misused. So called, dual use research of concern, is not something that is specific to biologic advances it applies to literally everything. Any technology can be misused from a drone to a fishing rod. However, it is the threat of bioterrorism coupled to rapid advances in biology that have motivated much concern and debate. Naturally, this debate has spilled into popular culture with a planned television show centered on the gene editing technology CRISPR in the works and several books, including a fiction thriller I just finished.

Tiger Tiger, the second novel in author Joann Mead's Underlying Crimes series of bio-thrillers, is the story of a biological attack on the United States and efforts to stop it. This attack is not accomplished using the usual suspects of anthrax, smallpox, plague, or botulism. It is accomplished using engineered influenza viruses -- inspired by the controversial influenza gain-of-function experiments -- for which there is no vaccine readily available. The perpetrator of the attack, an overtly nihilist philosophy professor, seeks out unscrupulous and disturbed scientist from whom to purchase these tiger influenza viruses which are derived from strains that had caused an outbreak in zoo tigers (something that has really happened). The delivery system for these viruses is no crop-duster by DNA molecular cages -- a major advance in nanomedicine.

The plot oscillates between the nefarious actors attempting to initiate their attack and the efforts of a secret group of government agents and other experts (the Partners)  to discover what is occurring after the first test infections are "successful". As they race to unravel the etiologies of these infections in order to stop them before a bigger wave of infection occurs, Mead emphasizes how open source intelligence gathering from social media, for example, can be harnessed in such endeavors as her namesake character run down various clues.

I enjoyed reading the book, less for its literary value (and multiple unusual sex scenes), than for its presentation of how a bioterrorism attack might look in the world of nanotechnology, CRISPR and synthetic biology. When it comes to these technologies, I view them as pathbreaking technologies with enormous value that far eclipses any potential downside from improper use -- which isn't as easy as it might seem in a novel, a movie, or a government report. I also enjoyed a science-driven plot that was not completely fantastical and well-informed by the actual issues, the science, and the technology of the day.

The theme of Tiger Tiger may be the relative ease with which a bioterrorist attack can be executed and the increasing realization of that fact by those who would seek to do harm -- something which almost everyone in my field would agree is true.

Cats Beware: Eating Tweety Bird May Be Hazardous to Your Health

Though buried among Christmas season headlines, the report of a veterinarian contracting an avian flu strain from a cat is, to me, highly significant. When people speak of avian influenza viruses it is the highly lethal H5N1 or H7N9 that are being discussed as these two viruses are high on many threat lists. 

In this incident, a New York City veterinarian caring for sick cats contracted the H7N2 virus which had not been known to infect cats before this event. It has been speculated the cat may have contracted it from a pigeon. It had been diagnosed in humans at least twice since 2002: once from someone involved in a Virginia avian outbreak and once before, interestingly, from a person in New York City without an unknown exposure. The veterinarian, like the two other human cases, recovered uneventfully and no secondary spread of this virus to other humans was detected via a robust surveillance operation conducted by the New York City Department of Health. 

This event, to those who track influenza, transcends the minor illness that results as it is an important example of how zoonotic flu viruses could take hold. These types of incursions into new species are important to study and the viral characteristics and changes that made such a jump possible should be compared to wild-type viruses that circulate in avian species. 

Influenza possesses many capacities that bestow it with the the capacity to cause cataclysmic (no pun intended) pandemics. Among these capacities, its ability to infect a variety of different types of animal species and shuffle viral genes inside them is probably the most valuable. Moving from birds to cats to humans is one such example. Indeed, the pandemic H1N1 virus has a complex genealogical origin that is a triple-reassortant virus that reassorted again. When a virus has a wide host range, it can take all sorts of turns and jumps some of which may lead to a human pandemic. These types of events can be predicted but the precision may not be perfect as our last pandemic emerged, not from China, but from Mexico.

While there has been a much needed focus on H5N1, we also know that H7 (H7N2, H7N3, H7N7, H7N9) flu viruses have an ability to jump into humans and, in the case of H7N9 cause severe disease. I wonder if the fact that multiple H7's have been making incursions into humans is a sign of what our next pandemic flu virus may be. Thus far, it appears the most prolific of these H7's, H7N9, has not changed substantially through its 4 waves of infection. 

While it appears that, fortunately, H7N2 does not lead to severe disease in humans this event should remind people of the prowess of flu viruses and the eternal vigilance needed to protect the human race from this extremely successful virus.

A Key to the Realm: My thoughts on the Anthropology of Infectious Disase

One of the reasons why infectious disease as a medical speciality has so much more allure, to me, than all other aspects of Medicine is that it is explicitly connected to many facets of the world. A person's social history -- what they do for a living, who they do it with, where they travel, their habits, their pets, where they live, and their hobbies -- all condition what microbe they encounter and whether that microbe can damage them. 

In short, the anthropology of infectious disease is a crucial, intellectually stimulating, and fascinating aspect of infectious disease. University of Connecticut Professor Merrill Singer's recent book on the topic, simply entitled Anthropology of Infectious Disease, provides a comprehensive tour of this topic, providing an important grounding for anyone who has an interest in understanding infectious disease.

Why did botulism surge in the republic of Georgia after the fall of the Soviet Union? Why did kuru proliferate and then vanish? Why do certain prisoners traffic in tuberculous sputum? All of these questions can be answered through the lens of anthropology.

As Singer notes, 

Infectious diseases are never only biological in their nature, course, or impact. What they are and what they do are deeply entwined with human sociocultural systems, including the ways humans understand, organize, and treat each other.

The anthropology of infectious disease is the arena of applied and basic anthropological research that focuses on the interaction among sociocultural, biological, political, economic, and ecological variables involved in the etiology, prevalence, experience, impact, cultural understanding, prevention, and treatment of infectious diseases.

This book concretizes, through myriad examples, the many ways in which an infectious disease's proximate causes are, in an anthropological context, secondary to distal causes in, as Singer puts it, an "ecological web of causation." 

While I may take issue with many of Singer's political leanings and assumptions, especially his conflation of political equality (which I champion) with economic "equality" and poverty and his de-emphasis of biosecurity, the book does provide a comprehensive overview that provides the reader with a fuller context, or an essential key, for understanding the realm of infectious disease.

Zombie Spiders, The Emotion of Disgust, & Parasite Stress: My Thoughts on This is Your Brain on Parasites

in what is a trend in my list of books I read, I just completed another which deals with the host-parasite interaction from the angle of how parasites influence behavior: This is Your Brain on Parasites: How Tiny Creatures Manipulate Behavior and Shape Society by Kathleen McAuliffe. 

The aim of this extraordinary book is to explore the many ways in which parasites, with a view to their own reproductive success, change behavior in the species they infect. This ranges from very subtle perturbations to seismic shifts. McAuliffe expertly provides multiple examples from varied species including zombified spiders to sexually-charged rabid dogs to insights into human psychiatric disease. Her discussion of the emotion of disgust and its potential origin and usefulness when it comes to parasitical infection is enlightening as is her discussion of the origins of vampire myths.

Another fascinating aspect of this book is its probing of the characteristics of high parasite-burden human societies. While causation is difficult to establish -- nor maybe even valid in such a context -- the correlations produced are extremely interesting. The "parasite stress" a country, community, a village, a people, or region faces has a high correlation to their view of immigrants, their views on gender issues, and a tendency to dictatorial-style governments. This last is an extremely important finding and something I think deserves further exploration. Parasite stress, the way I conceptualize it, not only may have subtle direct behavioral consequences but also will tend to create a poverty trap for the infected, stifling opportunities for economic activities necessary for flourishing and ripening the prospects for dictatorship to rise in an environment in which challenges are not feasible as people stick to their clans and deal with the onslaught of infectious disease.

The lines of inquiry in this book are very intellectually stimulating and do not undermine human volition. Human free will is axiomatic however alterations in cognition can occur for a variety of reasons, some of which may be parasitic in origin. For example, the prevalence of toxoplasmosis in certain psychiatric conditions cannot, based on its pathophysiologic characteristics, be purely coincidental.

The book is highly recommended. 

Ushering in a New Paradigm: My Thoughts on The Human Super-Organism

One of the things that irks me about people's obsession with compulsive sterility and the over-reliance on antibiotics, hand sanitizers, and the like is that it completely runs contra to facts and science. Microbes are essential to human life as we know it and to eradicate them would be catastrophic. A new book by Cornell University immunologist Rodney Dietert provides an excellent overview to this topic that is well-worth reading. Many books have been written about the microbiome in the past few years each with its own specific focus. In this book, Professor Dietert's focus is apparent from the title: The Human Superorganism: How the Microbiome is Revolutionizing the Pursuit of a Health Life.

The proposition that humans are best understood as superorganisms -- an intricate combination of human and microbial genes and cells -- is the theme of the book and Professor Dietert concretizes this theme with with a plethora of examples of how dysbiosis impairs health. One of the most intriguing, to me, lines of thought advanced in this book is "The Completed Self Hypothesis." According to this hypothesis, mammals can not flourish with just the mammalian genes they inherit alone and require the addition of a 2nd genome of microbial genes for optimal life. So those who have deficits in this 2nd genome -- via antibiotic use or birth via caesarean section, for example -- are missing a key component required for health and suffer the consequences in immunity that play roles not only in staving off infections but in the development of non-communicable diseases such as obesity, diabetes, and heart disease (among many others). The challenge in the future will be to prevent dysbiosis from occuring and correcting it when it does. 

The book is full of evidence outlining the case for this "hypothesis" (which I believe to be essentially true and a full-fledged theory of disease) as well as many interesting anecdotes including the overall genetic contribution Henry VIII made to his daughter Queen Elizabeth I.

I once attended a very important lecture in which the infectious disease doctor of the future was described as a "microbiome specialist". It will be books such as Professor Dietert that will pave the way in redefining the specialty of infectious disease medicine in a manner that is completely consonant with the new science.