ZKEA

Biological Warfare : Biological Terrorism : Emerging Diseases

The Ecology of Flu

Influenza (the "flu") is an ancient disease. It is likely that it has been with mankind since the dawn of civilization. Untold millions have died from this virus through the centuries. However, by the standards of other more virulent pathogens (such as smallpox, rabies and anthrax ) influenza is usually not very lethal. Normally it kills less than 1% of its victims. This is sad comfort if you happen to be one of the unlucky 1%, of course, but as a statistical matter the disease is not particularly deadly.

The influenza attack rate is high in children, ranging from 15% to 40% yearly. However, it can even be higher among the elderly. Rates in nursing homes have sometimes approached 100%.

The disease is transmitted via small droplets generated as people talk, sneeze or cough. The virus has a short incubation period (1-2 days) before full onset of symptoms. The afflicted person is contagious at this point and for 5-7 days after the onset of symptoms.

Influenza is a wide-ranging virus that infects many species. Birds, in particular, are prone to influenza infections. This is partly due to their flocking behavior; influenza needs a certain critical population threshold and density in order to maintain an epidemic. Large bird flocks are therefore perfect incubators for virus transmission.

However the virus also affects mammals - particularly those, like birds, that are sociable and tend to congregate in large numbers. In this respect people are the perfect targets. Like birds we enjoy the proximity of our kind and in very large numbers. This allows the virus to move quickly and efficiently through human populations. Because it is an ancient organism that has had a long time to get it right, influenza is perfectly adapted to exploiting such populations. The influenza virus ensures that at least one additional person gets infected before it departs (either through death or immunity) the original host. This behavior keeps the chain of infection alive. This contrasts with younger and more virulent viruses, such as ebola, which are so "hot" that they tend to kill their host before he can infect another human. These types of epidemics tend therefore to be self-limiting; the infected person usually dies quickly before infecting anyone else.

Prior to the founding of cities humanity probably never maintained social groups large enough to provide a habitat for influenza. Therefore influenza - like a number of other diseases, such as smallpox - is really a disease associated with civilization. Ancient hunting and gathering tribes may have lacked civilization's myriad benefits, such as canned spinach and the automatic garage opener, but they also lacked much of the modern world's disease burden.

Influenza is a seasonal disease. It is much more transmissible and infectious in a cooler or wetter climate. Therefore each year the disease tends to oscillate between the southern and northern hemisphere. And each year there is always a flu epidemic. Influenza is very reliable in this way. Every season it can be counted on to inflict damage somewhere on the planet.

Given the wide reservoir of species it infects, influenza is a good example of a zoonotic disease, that is, a pathogen which can exist in an animal reservoir independent of Homo sapiens. For this reason influenza is basically impossible to eradicate in the wild. Even if influenza were eliminated in every human on the planet, the virus would lie latent in any of innumerable other organisms. From this base it could then easily spring back into human populations.

Influenza viruses are divided into three types; A, B and C. Types A and B are responsible for the damage. Together they account for all the epidemics and mortality. Type C, in contrast, is a mild beast that has never been associated with any epidemics or deaths.

Type A viruses are divided into subtypes based on differences in two viral proteins. These proteins are known by the tongue-twisting names of hemagglutinin and neuradminidase. We'll just call them H and N for short. H and N are important, for these are the substrates on which viral change takes place.

Influenza viruses undergo two kinds of changes. One is a series of mutations that occur over time and cause a gradual alteration of the virus. This is called antigenic drift. The other kind of change is an abrupt mutation in the hemagglutinin and/or the neuraminidase proteins. This is called antigenic shift. In this case a brand new subtype of the virus suddenly emerges. Type A viruses undergo both types of changes whereas type B viruses change only through antigenic drift. Together these two types of mutations drive much of influenza's constant evolution. This evolution enables the virus to evade the immune system of its host, thus enabling the virus to re-infect a person who is immune to the previous generation of the virus.

Influenza makes up for its comparative lack of lethality by being extremely infectious. In some extreme epidemics it has infected the majority of a population. Thus, if you do the math, influenza can kill large numbers of people, even if the odds are pretty good for a given patient. Because of this basic arithmetic the disease kills millions of people around the world each year.

There are two additional key points about influenza's relative lethality.

First, this lethality is only relevant for populations that have been consistently exposed to the virus in the past. By necessity such populations have evolved a certain degree of immunity to influenza. Nowadays "such populations" includes everyone in the world, given that influenza has ranged everywhere at one time or another. However, in historical times there were isolated groups which were never exposed to the virus. These groups were biologically naive and thus their immune systems were not primed to defend against it. Thus when influenza was introduced to such people the results were usually apocalyptic. A good example of such an event was the Columbian Exchange.

The second point to remember is that influenza evolves very quickly. Every year - either through antigenic drift or antigenic shift - it presents one or more new variants to the world (thus necessitating a yearly change in vaccines). Some of these variants have been much more lethal than others. When this happens the usual influenza season can turn into a global epidemic. Such global events are called pandemics. During the last 100 years influenza pandemics have happened three times:

• 1918-10 Spanish Flu A(H1N1): 40 million dead.
  
• 1957 "Asian Flu" A(H2N2): 1 million dead
  
• 1969 "Hong-Kong flu" A(H3N2): 200,000 dead.
  

It is these lethal pandemics that keep health authorities awake at night. The classic question: what would happen if the viral version that caused the Spanish Flu were to reappear? Given today's higher populations and the greater degree of travel and overall interconnection, such a virus would cause planetary havoc. For this reason, the World Health Organization (WHO) and other governmental health organizations mantain a global surveillance network. This network acts as an early-warning system, so that when a new virus does appear there will be sufficient time to develop a vaccine and take other preemptive health measures. In this fashion a devastating pandemic can be averted.

That, at least, is the theory. Theories are amusing things but no one should ever mistake them with reality. As the SARS epidemic in 2003 demonstrated, reality can not only be different but far more deadly. In the case of SARS, governmental ineptitude and outright cover-ups almost allowed the virus to explode into a very frightening pandemic indeed.

Over the past few years, influenza has been demonstrating a strangely increased rate of evolution. New and "hotter" variants keep cropping up, usually in Asian bird populations. Asian duck and chicken farms are particularly fertile ecologies in this regard (hence the great medical interest in the influenza H5N1, otherwise known as Avian flu).

H5N1 first arose in the late 1990s, much to the woe of anything sporting feathers. Indeed, for birds at least, the new virus proved quick and deadly. Chickens universally expired within a few days of getting the virus. Infected pigeons literally dropped dead from the sky. More alarmingly, this virus seems to be in an evolutionary hurry. Between 1998 and 2002 it underwent no fewer than 17 genetic reassortments. Improvment was rapid.

In January 2003 the "Z" variant of H5N1 evolved, which proved capable of dealing with a broader range of environments. By 2005 this virus (now dubbed "Z+") became supervirulent and quite capable of killing a diverse range of species, including cats, rodents, pigs and people. This virus was now spectacularly agile and dangerous. For instance, mice are typically unaffected by influenza, but Z+ causes 100% mortality in every mouse population tested. And the virus continued to intrude into species that normally are not affected. Among other things, it began to kill migratory birds - which normally are relatively immune. It even began to kill tigers - wiping out 30% of the tigers in Thailand zoos in a single ferocious epidemic.

From the standpoint of the virus, tigers and people are virtually interchangeable. And the speed at which H5N1 has adapted and increased in power has raised more than a few eyebrows. Some influential epidemiologists (such as Dr. Keiji Fukuda, the head of the CDC's flu branch), have labled these developments "spooky".

Another concern is biological terrorism and warfare. The genetic basis for pathogenic organisms is increasingly understood, as are the techniques for amplifying the effects of these genes. Nor are the ingredients - and even the recipes - for biological mayhem difficult to find. To cite a recent celebrated example, in 2005 the U.S. Department of Health and Human Services published the genome of the 1918 influenza virus on the internet. How much more public can one get? Interestingly, this genome demonstrates that the 1918 virus arose from birds, just as H5N1 has done. But, more to the point, publications such as these made independent "research" all the more likely. After all, it was now possible for anyone on the planet to download the exact code for this organism. All it took was an interest, a computer and a reasonably fast network connection ...

The basic knowledge and techniques necessary to harness and exploit such databases are widely dispersed and easily applied. Any reasonably competent postgrad, combined with a modest laboratory, can translate this information into deadly weapons. Reconstructing the 1918 virus would be an obvious little project, but in truth that's just a warmup exercise. Why not tweak H5N1 itself? Give it a little boost to enable human-to-human transmission? And why stop there? Why not enhance "common" influenza (an already-proven agent) into greater lethality? Why not combine the best genes from multiple viruses, breeding a super-killer that the world has never seen? These are not theoretical concerns. A number of states have demonstrated a deep interest in such weapons. In addition, there is perhaps even greater interest from rogue entities or terrorist groups. As 9/11 demonstrated, religiously-oriented terrorists in particular have few moral qualms about using any weapon at their disposal. The looming intersection of biotechnology and global terrorism will be one of the defining moments of this century.