Rabies as weaponry

Rabies as weaponry

Primarily we think about rabies and other lethal viruses as the subject of sad tales, of people who have become infected and inexorably die.  However, as I’ve written about in earlier blogs, rabies could become the basis for horrific weapons – not the painful, but fairly rapid death from sarin nerve gas, but horrific in the psychological and physical damage induced.  They will not be produced by rabies itself; for the virus to be an effective weapon it would have to be introduced directly into the nervous system, likely requiring some means of penetration the bony skull or spinal column.  Even then it would probably take some days for the effects to manifest, with certain death after a week or more.  Thankfully, we don’t have any direct information on exactly how quickly the symptoms and death would occur in humans given the rabies virus directly into the central nervous system… and hopefully we won’t!  The real threat will come from chemical compounds that act on the rabies receptor.  From these we could well expect to produce the rage, and attacks on other people, that rabies can produce as well as the muscle weakness.  Whether such compounds would kill is unclear since it is still unknown exactly how rabies results in death.

It is interesting that the use of the rabies  virus has been contemplated by a number of authors.  Below I copy an accounting of this.

“Rabies arrived in Greece in the fifth century BC. The ancient temple of Athena at Rhocca (Crete) was notorious for rabid dogs. Athena of Rhocca was invoked to cure human victims of rabies. In about AD 200, the natural historian Aelian described an experiment to cure some young boys who had been bitten by rabid dogs near Rhocca, whose ruins are found south of Methymna, Crete. A doctor administered the toxic stomach acid of seahorses to his patients in an attempt to counteract the mad dog “venom.” This early attempt to fight poison/venom with another poison/venom (anticipating the principles of vaccines, chemotherapy, and venomics) failed and the stricken boys died.
Aelian remarked that a piece of cloth bitten by a rabid dog could imbue the fabric with deadly saliva, causing second-hand infection of anyone who came into intimate contact with it. The virus can indeed infect via an open wound. Aelian’s ominous comment insinuates that mad-dog “venom” could have weapon potential.
Sure enough, historical detective work uncovers two intriguing formulas for creating biological weapons in an ancient Indian manual of warfare. The Arthashastra by Kautilya (fourth century BC) tells how to make many different types of poison arrows.
One recipe calls for mixing various toxins with the blood of a musk rat. “Anyone pierced with this arrow,” wrote Kautylia, “will be compelled to bite ten companions, who will each in turn bite ten more people.” The implication is that musk rats were a vector of rabies in India.
The other poison arrow recipe calls for “the blood of a man and a goat to induce biting madness,” which sounds suspiciously like rabies. Perhaps goats were susceptible to rabid animal bites.
Two thousand years later, in about 1500, the idea of “weaponizing” rabies occurred to Leonardo da Vinci, who envisioned a terror-bomb created from sulphur, arsenic, tarantula venom, toxic toads, and the saliva of mad dogs.

In 1650, the Polish general Casimir Siemenowicz entertained a similar notion. He suggested placing “the slobber from rabid dogs” in hollow glass or clay balls and catapulting them on the enemy to cause “epidemics” of rabies. The effectiveness of such weapons is dubious, but the diabolical intentions are chilling.

About the author: Adrienne Mayor is a Research Scholar in Classics and History of Science, Stanford University. She is the author of “Greek Fire, Poison Arrows, & Scorpion Bombs: Biological and Chemical Warfare in the Ancient World” (2009); and “The Poison King: The Life and Legend of Mithradates, Rome’s Deadliest Enemy,” a nonfiction finalist for the 2009 National Book Award.

This article originally appeared at Wonders and Marvels.”

None of the methods mentioned would be very effective, at least immediately, because they still require the highly variable time from exposure to actual infection.  In present times, this would almost always be sufficient for prevention of rabies’ effects by treatment with the prophylactic vaccine.

Still, someday, the rabies receptor will be discovered, and the fearfulness of rabidity will become real.

Lyssants – it may be defensive, but it’s aggressive as hell

Lyssants – it may be defensive, but it’s aggressive as hell

The rage of lyssants, natural or rabies-induced, appears to be a defensive act.  It is trying to fend off an unspecified (emotional, subconscious) threat.  Lyssantic rage is not a passive defense; it is no submissive behavior.  Lyssantic rage is an all-out, full-scale, no-holds barred attack meant to subdue whatever is felt to be hurting/frustrating the victim – physically and/or psychically.  I emphasize ‘feel’ because the rage attack is not a rational, conscious, social act, but simply the worst the lyssant can muster in response to an unspecified attacker.

An example of this is the attack this month by a rabid fox on a boy in North Carolina.  Given the circumstances of the attack, medical personnel did not have to think before immediately beginning treatment with the anti-rabies vaccine; the boy will not become infected!  Yes, the fox was euthanized, its brain tested, and yes, it was positively infected by rabies.

"I was trying to walk home and I guess he was running, but I didn't see him…, and out of nowhere, I felt something grabbing my pants.”  The fox continued to harry the boy, following him as he tried to escape, even going into the boy's apartment and jumping up on a couch before actually being able to sink its teeth into him.

Wild animals and humans are not typically aggressive unless aggravated or stalking prey.  Wild animals generally stay/run away from humans.  To be found ambling along in the open, like the beaver in Belarus, is very unusual behavior and a good indication that something’s wrong “in their head”.  If they do approach and try to attack a human, or if they look like they're drunk, in a fog and stumbling along, that's a great warning sign that the human should back away.

Of course, when it appears “out of nowhere”, as the rage of human lyssants generally does, then about all one can do is to escape.  One can try to appeal to the lyssant’s positive emotions and try to elicit rational thought, but it is critical to understand that it is not happy emotions nor conscious, intellectual thought that is driving the lyssant.  And you can’t presume the attack will just stop.  YOU aren’t the target; you’re just in the way or are some avatar of a threat.  The rage-induced attack will run its course; until it has given all that it has to give.  If you know a lyssant, have an escape plan because they can’t help themselves, and you can’t help them while they are a lyssant.  If you’ve ever been chased by someone with lyssant road rage, you know what it means.  I had one person tell me that during a fit of road rage, they followed, honked at, and tried to harass their ‘target’ for miles!

Of course, we shouldn’t have to deal more than twice with someone’s lyssant behavior.  Like so many other ills of social behavior, the person prone to being a lyssant needs to take responsibility for their actions and seek help.  Ah, there’s the rub, what help can they seek?  Psychodynamic therapy is largely ineffective, at best it can point out some initial issue that now triggers lyssantic behavior.  To assume that such conscious “insight” can control non-/sub-conscious behavioral repertoires is foolishly presumptuous.  Cognitive-behavioral therapy is equally inappropriate to deal with autonomic nervous system dysfunctions that are neither cognitive nor, at base, open to learning/conditioning.  One avenue is to teach the lyssant to be mindful of themselves in social situations.  To become aware of signs in their own behavior that are omens that their inner lyssant is being activated, and to extract themselves from those situations.  This is much, much, much easier said than done.

Pharmacological options simply don’t exist because we don’t know the target receptor for 
rabies.  Without that neuronal communication receptor being identified and studied, we stand 
no chance of helping human lyssants, vampires, and werewolves.

Clinical vampirism – something in the blood of youngin’s

Clinical vampirism – something in the blood of youngin’s

It’s not rage, but it is related.  Clinical vampirism is the obsession with drinking blood. The first formal psychoanalytic report was published in 1964 by RL VandenBergh and JF Kelley (Archives of General Psychiatry, 1964, 2: 543–547).  Earlier reports of blood-drinking, especially associated with sexual pleasure, can be found, for example, in the writings of R von Krafft-Ebing in the 1890s. The drinking of a victim’s blood is one feature of some unusually violent murders (e.g., Bulletin of the American Academy of Psychiatry and Law, 1994, 22: 533–544).  Despite its existence, this disorder seems to be very rare and is not specifically noted in the Diagnostic and Statistical Manual of Mental Disorders.

Within our current focus on lyssantic behavior, it is interesting, and not surprising, that it can be associated with sexual frenzy.  We’ve already noted that rabies can lead to increased libido, and also that love bites are a not uncommon aspect of particularly excited sexual congress.  Although humans are not well-designed to break skin with our teeth, it certainly does occur and the blood of one’s partner happily tasted.

And then, there are the recent studies showing that the blood of young animals, mice, can reverse some signs of aging, specifically cognitive impairment and cardiac hypertrophy.  A Wagers, R Lee and colleagues (Cell, DOI: 10.1016/j.cell.2013.04.015) joined the circulatory systems of mice, one young and another an old mouse with signs of thickening (hypertrophy) of cardiac muscle.  By the end of the study, the muscle of the old mouse’s heart had returned to normal size!

I think I’ll just leave all this with a “wowser” and hope I can sleep tonight.

Rage disorders – DSM-5, psychopharmacology, & rabies

I congratulate all those who put together the newest version of the Diagnostic & Statistical Manual of Mental Disorders, DSM-5.  It must be an overwhelming task.  I am particularly pleased to see a unified chapter on “Disruptive, Impulse-Control, and Conduct Disorders”.  It is a step forward in putting into one place a number of conditions in which rage is prominent.  And it is recognition that explosive disorders are fairly common. 

Then one notices a new disorder, “Disruptive Mood Dysregulation Disorder”, which is defined by frequent outbursts of rage.  Of course that goes into this new chapter, right?  Wrong!  This rage, disruptive, impulse-control, and conduct disorder, that is, lyssantic disorder is placed in with Depressive Disorders!  That’s really lame, and casts serious doubt on the DSM as a whole.

This brings to the fore that clinical psychiatric disorders are the sum of all the symptoms seen in people with behavioral disorders.  These disorders don’t fit into neat little boxes that can be defined at the didactic level.  Comorbidity is the rule for psychiatric disorders rather than the exception.  The DSM is important for giving therapists and researchers a common set of symptoms to describe what they are hearing.  And it is critical to aid in determine the symptoms most interfering with a person’s life and livelihood in order to prioritize therapy.  Therapies, be they pharmacological, cognitive-behavioral, or even psychodynamic or humanistic must focus on one aspect at a time, however much the therapist wishes to treat the ‘whole patient’.

Yet it is evident that psychiatric categories are grounded in theoretical constructs conceived by individual therapists and the schools of thought in which they were taught.  The whole point of the DSM in the first place was to find commonality in the behaviors/problems patients described and did not depend upon theoretical constructs.  This was a huge advance over the way psychiatry was carried out previous to 1950 when each therapist could uniquely define, without much regard to the thoughts of others, each patient they encountered.  However, the DSM still clumps various disorders (collections of symptoms) into categories that reflect psychoanalytic systems; systems that cannot be directly tied to testable biological events.

This must change!  One criticism of the newest DSM is the intrusion of pharmaceutical interests into its construction.  I cannot comment on this directly.  However, pharmacology must inform psychiatry!  Psychoactive drugs, to the extent that we can define their mechanism of action, act as a kind of experimental psychiatry, a way of testing schemas.  The effects of psychoactive drugs on human behavior and disorders must become a manual of its own, to be an adjunct to the DSM.  If SSRI’s, for example, reduce symptoms X, Y, & Z, then we know there is a neural circuit mediated (in some measure) by serotonergic synapses that can modulate those symptoms, those behaviors.  It may be that such an analysis of each drug’s effect on various patients will, in the short term, confuse psychiatric terms even more.  However, in the long run it will lead to strong underpinnings for categorizing disorders and lead to more selective therapies.

Beyond that, the study of the brain itself, when and how various behaviors and concepts are produced and modulated, is critical to our understanding of human beings.  I am obviously keen to explicate where rage is constructed and carried out.  But, we know that our nervous systems are built up of many layers carrying out different types of analyses on the world around us.  Rage will reveal itself in many ways in many people based on their genetics and the environment they grew up in, and the environment they operate in today.  Defensive rage is a synchronized group of behaviors designed to protect us from a threat that cannot be fully analyzed – no time to analyze it, perhaps it is just beyond comprehension (or just too immense to see how to defend against it), or presently unseen.  But even in its most basic form, it is triggered, and held at bay, by analyses of numerous parts of the nervous system.  Still, we can only understand its complexity if we know its source.  And while that source might be, for some, feelings of inferiority with regard to superhuman parental figures, it still has a specific place in the nervous system.  Together, and only together, these three analyses can write the story of human beings.

I have invented the term lyssant for someone who exhibits rage, be it normal or abnormal.  That term and its underlying neurobiology have been specifically enslaved by the rabies virus for its own purposes.  In having done so, rabies can light the way to understanding this important part of our behavior.  More important than some other aspects because it is a part of our non-conscious/subconscious nervous system that we cannot directly access by language or bring under control by learning or conditioning. 

The DSM should be seen as one aspect of the way we look at human beings.  Psychopharmacology and neurobiology form the other parts, and the intersection of all three will be the final understanding of what it means to become human.

Rabid about rabies – why me?

Rabid about rabies – why me?

As a neurobiologist, I’ve been interested and intrigued about rage, emotions, & rabies for many years.  But without a clear model to work on, there’s never been an experimental approach to use to study rage.  As I mentioned earlier, the most promising model, septal rage, disappears after a short time leaving us with nothing to interrogate.  In terms of treating rabies, there is a very good prophylactic and post-exposure (but pre-infection) vaccine that vastly reduces the chance of infection.  So, there isn’t a huge (in comparison to, say, Alzheimer’s disease) patient population demanding the time and resources of academic or pharmaceutical researchers.  So, I’ve worked on many other projects and neuropsychiatric disorders.

For me, that all came to a crashing halt in 2005 when a boy, Zachary Jones, died from rabies just a few miles from where I live!  He was bitten in his sleep by a rabid bat.  To him, it was just a dead bat on the floor and he may not even have noticed the bite; certainly nothing to tell his parents about.  When the symptoms of rabies infection appeared, it was too late to save him.  Even though the best treatment, the Milwaukee protocol, was used, there really is nothing we can do to treat rabies infection.  Zachary died. 

That made me mad!  How could we have let this happen with all the modern tools and treatments that medicine and neurobiology have to offer?  Of course, at the time I was engaged in more immediate projects and still had no idea of how to engage rabies.  But, I began to re-read and read more about the rabies virus.  I found that its unique properties do make it amenable to understanding.  There is a straight-forward series of studies that will identify the rabies receptor.  I tried to garner interest within Pharma, but no one was interested enough to listen.  Neuroscience research groups, often made up of younger investigators who have never read about how the Papez circuit was discovered, if they’ve even heard of the Papez circuit at all, said that rabies is an infectious disease, so I needed to talk with the infectious disease or immunology department.  And the infectious disease/immunology departments said, that rabies only kills about 50,000 people a year, while HIV, etc., kill many, many more, and we don’t have the resources to work on all the viral diseases.  As a lone pharmaceutical researcher, without academic ties, I don’t have much access to government grants either. 

New treatments for rabies infection are important, and treatments that would block the effects of the virus after infection are critical.  But, in addition, and in some ways more critical is to understand and find treatments for human lyssants, for outbursts of rage that disable so many victims and hurt so many others.  Rage attacks come through many neuropsychiatric disorders as I’ve noted in earlier blogs.  But, as we have no central, biological understanding of rage, they are shoved into a vast array of disorders where they are a secondary, comorbid condition without any hope of treatment.  And then there’s simply the fact that lyssantic behavior is a normal part of being human and control of it a vital part of becoming an adult member of social society.  As long as we don’t know where rage comes from, we will continue to depict it as supernatural vampires and werewolves; creatures, feelings, and behaviors apparently beyond our control.  As long as we use that excuse, we won’t really become the humans that we actually are.

For all these reasons, I am rabid about discovering the target, the receptor, by which the rabies virus releases our inner lyssant, and why I’m determined that we better understand ourselves, and better protect ourselves from the virus and from ourselves when necessary.  We have the tools and reagents to discover the rabies receptor.  The path forward is straight-forward, but it is not inexpensive.  Help me!

Lyssants need help – we need understanding

 Lyssants need help – we need understanding

Leila Fowler’s 12-year old brother needs help.  I can hope that his inner rage, his self-defense mechanisms, didn’t kill his sister, but I don’t give that hope much chance.  I believe it will turn out that some stressful events triggered him to do the unthinkable, likely unthinking as it happened.  Rage, lyssantic behavior, is in all of us, but for some and sometimes for any of us it escapes our social inhibitions and becomes reality. 

Werewolf, vampire, monster, lyssant; they all reflect a natural part of our behavior, but one that we still can’t even talk about straight.  I’ve given it a name, lyssant, and a probe, the rabies virus.  Now we need to put that into action, discover the receptor that the virus disrupts our own defensive behaviors to attack others.  The virus needs us to turn victims, to survive.  The behavior is self-defense in its most extreme form that doesn’t really recognize its victim; it just feels there is a threat and attacks wherever (whatever, whoever) that threat appears to be coming from.

Psychiatrists will parade out their useless terms; sociopath, psychopath, antisocial personality disorder, ADHD and autism with conduct disorder, intermittent explosive behavior.  All these prove is that we know there’s a problem, but we have no clear way of defining it.  Dr. Tom Insel, head of the National Institute of Mental Health (NIMH), recently brought this basic issue out into the light (where vampires are supposed to burn up) again saying that even the new version of the DSM, the Diagnostic and Statistical Manual of Mental Disorders, was irrelevant unless its definitions were grounded in neurobiology.  I couldn’t agree more.  Of course, the onus is then on neurobiology and the NIMH to identify those underlying biological mechanisms. 

So, once again I state that the effects of rabies, especially furious rabies, produces all the behaviors that have been ascribed to the daimona Lyssa, to werewolves, to vampires, and to all the other aspects and avatars of rage.  We’ve written about rabies for 4,000 years.  Isn’t it about time we actually discover what the virus understands so well about us, our nervous system, and our behavior?  It’s time to quit pretending rage is some supernatural invasion and recognize it is a natural part of what it means to becoming human.  And to recognize that some of us can’t always keep it under wraps and may need help in controlling it.                  Lyssants need help!

Transneuronal tracing – rabies virus excels!

Transneuronal tracing – rabies virus excels!

The National Institutes of Health has made it a major goal to define the connectome, that is, how all the parts of the central nervous system (CNS) are connected to, communicate with, each other.  This is critical information if we are to understand ourselves, our mental processes and how the CNS mediates the expression of those processes.  And, it is critical if we are to understand how those processes can go awry or, like rage, perilously surprise us.  The rabies virus can be a very important tool in defining the circuitry of the CNS because of its unique ability to infect, without damaging, almost all the regions.

A number of neuroanatomists, scientists working to understand how the parts of the CNS communicate with each other, have found the rabies virus to be a nearly perfect tool for identifying connections.  They have taken on the risks of working with the deadly virus because it is such a unique and powerful tool.  People working in these labs must be vaccinated against rabies, and the strength of their immunity against the virus rechecked frequently.  It is an enormous commitment to better our understanding of ourselves.  Below is an excerpt from a review by just one of these intrepid investigators.

“Powerful transneuronal tracing technologies exploit the ability of some neurotropic viruses to travel across neuronal pathways and to function as self-amplifying markers. …rabies virus is the ideal tool for studying motor innervation, since its peripheral uptake occurs exclusively at motor endplates. Rabies virus is the only viral tracer that is entirely specific, as it moves exclusively across chemical synapses by strictly unidirectional (retrograde) transneuronal transfer without altering neuronal metabolism, allowing for the stepwise, time-dependent, identification of neuronal networks across an unlimited number of synapses.” [Advances in viral transneuronal tracing. Ugolini G., J Neurosci Methods. 2010;194:2-20. PMID:20004688]

As I’ve written before, rabies is very unique in that it specifically infects neurons (nerve cells) of the CNS.  It does not infect sensory neurons or neurons of the peripheral autonomic nervous system, and, it does not infect any other cell that we know of.  It is, in a way, a perfect storm.  Moreover, infection of neurons by rabies does not lead to damage of those neurons.  It uses the neurons to replicate/to multiply and to move along, but without evidence of damage to them.  To do its job, to turn new victims, it must maintain the basic operation of the CNS, only redirecting it to become a lyssant, a rage machine.  The rabies virus does not burst out of the neurons as many viruses do from the cells they infect.  Amazingly, when newly synthesized viral particles do leave a neuron they have infected, they do so only at the neuron’s normal communication sites, called synapses. 

At these synapses, specifically chemical synapses, two neurons come very, very close to one another.  The two communicating neurons create specializations that allow the ‘first’ neuron to release chemicals, neurotransmitters, which will attach to receptor molecules on the ‘second’ neuron.  The second neuron will use the attachment/binding of those chemicals as a means to detect and transmit the signal on to additional neurons.  The synapses also use various means, such as trophic factors and adhesion molecules, to maintain the specializations and to keep them located directly across from one another so that communication is optimal.  Rabies uses these communication ports to move from neuron to neuron, disrupting the normal flow of information to direct its host to go out and turn additional victims – all so that the virus can survive. 

I believe, but am speculating, that the receptor that the rabies virus uses to initially infect skeletal motor neurons is exactly the same as the one that it will use to be taken up into, infect, each new neuron.  I can’t imagine that the extreme selectivity that limits the virus to only infecting the presynaptic endings of skeletal motor neurons will not be maintained at each synapse that the virus crosses.  Therefore, it is this receptor and the brain circuits it controls that are the key to us understanding lyssantic behavior, be it intermittent explosive behavior or a human werewolf.  And, once again we come back to wonder why this receptor has not been discovered.

playing 'possum, for the better

playing 'possum, for the better

The rabies virus is particularly insidious.  Many potentially lethal viruses appear to become less virulent, less rapidly lethal, as they spread through a population of victims.  Or perhaps it is more correct to say that variants that do not immediately kill victims become more prevalent.  Many deadly viruses require close, social contact for transmission from the infected host to another victim.  If the original host dies too quickly, before interacting closely with others, the virus dies with it.  No transmission and no survival of the viral species.  Rabies has not had to weaken itself at all because it forces its victims to actively seek out and actively infect additional hosts, actively turns new victims.  Therefore the former host can die relatively quickly and still complete its deadly mission.  The rabies virus uses the propensity of all mammals to bite to secure its own survival! 

But, biting comes in several varieties, with differing intents.  Biting can be aggressive and predatory used to kill a victim for food.  It can also rend foodstuffs in order to make them small enough to swallow.  And then there’s defensive biting used to damage and drive away foes and predators.  Finally there’s biting, nipping, that is at the height of emotional pleasure.  Our search involves the latter two forms.

The behaviors expressed as furious rabies make it clear that the rabies receptor is in a position within neuronal circuits to control rage and other emotional outburst behaviors.  The level of expression of this receptor in various people and various mammalian species may help explain their personalities.  And with tools to modulate its activity we can help those who find it nearly impossible to avoid the negative consequences of rage.  In this regard, I find it interesting that the opossum is known to be much less susceptible to rabies infection than other mammals.  Opossums do exhibit defensive rage, hissing and baring their teeth, but this is relatively short-lived, and when push comes to shove they quickly “play possum”.  That is, they play dead rather than attacking and biting their foe.  The opossum’s behavior is particularly amazing because the opossum is an omnivore, that is, it kills and eats other animals (although it tends to prefer carrion) as a routine part of its diet.  Clearly, aggressive, predatory behavior is not lacking in opossums, it’s only defensive rage that appears cut short. 

Is it possible that opossums express less of the receptor that rabies needs, that our brains need, to express rage behavior?   It will be very interesting to determine whether the rabies receptor protein is expressed at lower levels in opossums.  More speculation, but another testable hypothesis, at least once we identify the rabies receptor.

Rabies – infection, furious vs. paralytic forms, bats vs. wolves, motorneurons

Rabies – infection, furious vs. paralytic forms, bats vs. wolves, motorneurons

Rabies first infects a motorneuron, a neuron whose function is to tell skeletal muscles to contract to make our bodies move.  Inside the axon of the neuron it travels back (formally: in a retrograde manner) to the main cell body of the motorneuron that is situated inside the central nervous system (CNS) proper.  The cell body is where the protein- and the RNA-making machinery are located.  It is here that the virus finally begins to multiply and then spreads out to other neurons. 

Axons of motorneurons heading back into the CNS are clustered together in bundles.  These bundles are known as nerves.  Thus, once taken up by the presynaptic ending of a motor neuron, the virus travels inside nerves, that is, inside axons, to the CNS.  Because the viral particle is inside a neuron it is fully protected (unfortunately) from any antibodies the immune system might have made that could capture the viral particles.  This trip to the CNS takes some time, and that time will depend on the length of the axon/nerve that has been infected.  Infection that began in the toe will take longer to enter the CNS proper than a bite on the neck.  However, this length of time only accounts for a small part of the time between infection and symptoms, and does not at all account for the wide variability in time from exposure to symptoms.  That variability – up to a couple of years at least – is completely a function of the time it takes a viral particle to find and be internalized by the receptor that will take it into the CNS.  In the meantime, the virus is simply floating around in the body.  To emphasize again, if this were not true, Pasteur’s vaccine would be useless.

Yet, infection does occur more rapidly following some bites than others.  Moreover, some infections result in furious rabies while others produce paralytic rabies.  Both of these differences need to be explained. 

Bat bites, or possibly bat rabies, are more frequently associated with the paralytic form of rabies, while dog and wolf bites are more often associated with induction of furious rabies.  It is possible that this is due to differences in the virus itself, yet bat bites clearly can induce furious rabies in dogs and other animals.  It is certainly true that one can determine which animal a particular rabies viral particle came from.  However, this is a result of the virus using cellular components from the particular animal it has infected in order to make its outer shell, e.g., Hardy plank vs. aluminum siding.  It is not the result of any known difference in the viral RNA or the receptor recognition motif.  There are not different types of rabies virus that could possibly account for differences in the time to infection nor in inducing furious versus paralytic rabies.

A more plausible explanation might be because a bat’s bite is likely to introduce less virus-laden saliva into the victim than most dog or wolf bites.  It seems very reasonable that being exposed to more viral particles would shorten the time before one find its way into the central nervous system, that is, shortens the period between exposure and infection.  Perhaps the difference between furious and paralytic rabies is also largely a function of the amount of viral particles the victim is exposed to, leading to a greater number of axons, of neurons, infected.  But, infected at the same time?  That strains credulity. 

The site of initial exposure does appear to play a role, at least in the period of time between exposure and infection.  “Closer to the CNS” is often used to describe this observation.  As the time from initial infection to the onset of symptoms is not hugely different when traversing the axons from the toes or the neck, I propose that it is something else, something about the density and/or location of the rabies receptor that accounts for the difference.  A bat bite penetrates the skin, but probably does not often enter muscles directly, certainly not very deeply into them.  On the other hand, a wolf’s bite will almost certainly penetrate and gore muscle, breaking the various membranes that cover muscle tissue.  The dog’s bite has a much greater chance of directly exposing neuromuscular junctions to the virus.  This seems reasonable to explain why wolf bites might induce rabies infection more quickly, but still doesn't explain the two types of rabies, nor that wolf bites seem more likely to result in furious rabies.

It is possible that the rabies virus can enter the axons of both types of skeletal motorneurons, alpha and gamma, although I’m not aware of data on this point.  And, perhaps gamma-motorneurons have more, or stronger affinity, receptors for rabies than alpha-motorneurons.  Muscles of the neck, for example, have a high density of gamma-motorneurons and therefore infection via gamma-motorneurons could occur more rapidly.  Being closer to the CNS may simply mean a muscle being responsible for more types of controlled movements -- those required to let our eyes, ears, and nose have the best chance of picking up information about the world around us -- and therefore having more gamma-motorneurons.  Gamma-motorneuron endings are encased in an additional membrane, a joint capsule, which would also have to be penetrated in order to access the gamma-motorneuron terminals.  In this way, as well, a wolf’s bite, designed to rip and tear flesh, that is, muscle, would be more likely to rip open those joint capsules, exposing the nerve terminals to the virus.  Moreover, as the neuronal pathways from alpha- and gamma-motorneurons into the brain are different, at least for the first few steps, I further propose that infection of gamma-motorneurons primarily leads to furious rabies, while infection via alpha-motorneurons primarily induces paralytic rabies.  This is speculation, but testable.

Rabies – selectivity unequaled

Rabies – selectivity unequalied

Before continuing, it is important to note a number of implications regarding this extreme selectivity of the target for rabies infection.  First, it is the scarcity of the rabies receptor outside the CNS that accounts for the long, often extremely long, time period between exposure and infection.  The virus must chance across one of these rare receptors to gain access to the CNS. 

On the other hand, it is known that neurons within the CNS express the rabies receptor in very great numbers.  So, once the virus does infect the CNS it is rapidly transported to almost all areas of the spinal cord and brain.  Even here, however, infection of additional neurons only takes place at specialized connections between neurons.  These specialized junctions are known as synapses.  Just like the neuromuscular junction (synapse) where the rabies virus first enters the CNS, synapses are where neurons communicate with each other.  Binding to these communication sites, these receptors, the rabies virus can alter, most likely inhibits, certain avenues of communication in the brain.  Importantly, rabies does not exit from the host cell at any point except via synapses (the communications portals).  Nor does rabies induce the host neuron to burst – thus releasing a large number of viral particles, but killing the host – as many viruses do.  Rabies does not appear to structurally damage the CNS at all, only altering it functionally.  There are some reports of damage associated with injection of rabies virus.  Given the extensive use of rabies as a neuroanatomical tracer without reports of damage, I believe that reports of damage are the result of additional material contained in a preparation from an infected animal that has been injected along with the virus.

Some authors have suggested that the rabies virus infects some, particularly skeletal muscle cells, during the time between exposure and infection.  I have not seen a direct demonstration that this occurs, and certainly there is no evidence of replication in, or release of new viral particles from, these hypothetical cells. What has been observed is a high concentration of virus within skeletal muscle tissue; not necessarily within muscle cells themselves. Of course, the neuromuscular junctions are located in muscles and these contain the receptor by which rabies normally first infects the CNS.

 In reality, rabies virus is just pushed along around through the body until by chance it encounters the appropriate receptor, or, if the victim is extremely lucky, it may be excreted before producing infection.  It is certainly possible that the areas near the appropriate receptor may have special properties that make them reservoirs for the virus.  It may even be that the virus becomes attached to the receptor, but the conditions needed to internalize the receptor have not yet occurred.  In either scenario, this indicates the virus is sitting outside of all cells waiting for whatever stimulus induces its internalization into skeletal motorneurons.  If this were not the case Pasteur’s world-changing vaccine would be of little value.  The antibodies evoked by the vaccine are themselves too large to enter the CNS.  Their only chance of stopping rabies infection is to capture it, all of it, before any viral particles enter the CNS.  The vaccine does this very, very well, fully confirming that the virus remains outside of cells, most certainly outside of the nervous system, for a fairly long time.  We know this because the vaccine can be administered post-exposure (but pre-infection) and be completely effective.

In the laboratory, one can get rabies to infect a number of cells.  This does not imply any lack of specificity by the rabies virus.  Cells internalize (by a process called endocytosis) many external substances and membrane components (e.g. receptors) via large vesicles (sacs).  Given a high enough concentration of rabies virus in the solution cells are living in, it is highly likely virus will be accidently internalized.  There may also be receptors with very low affinity for the virus that, coupled with the high laboratory concentrations of virus, may allow internalization.  In the body however, the specific neuronal receptor is critical.  

A report of infection via inhalation of aerosolized virus has been made.  The conditions for this – millions of bats within a small cave – were certainly extreme.  This, possibly single, report does not imply a lack of specificity either; some neurons of our smell (olfactory) system, part of the CNS, are directly apposed to the external world.  In this case, infection most likely occurred via the unique neuronal rabies receptor that is well-known to be highly expressed within the CNS. 

Given that laboratory infection of cells is probably mainly non-physiological – does not represent natural infection – why don’t investigators use cultured neurons to study rabies infection in the laboratory?  Unfortunately, it is difficult to grow neurons in the laboratory.  While numerous reports and examples exist, these neurons were overwhelmingly gathered from embryonic tissue, long before the nervous system fully grew and developed.  Even when harvested from (early) post-birth tissue, the neurons are immature and do not express many of the receptors seen in adult neurons, at least not in their adult form, and also do not have many of the between-cell attachments standard in the native CNS.  Our understanding of how the rabies virus moves through the nervous system strongly suggests that specialized connections between neurons must be in place in order for it to infect most areas of the brain.  The study of rabies infection of neurons in vitro is difficult and simply has not been carried out very often.  And, it is actually the receptor, whose activity is changed by viral attachment and not the virus per se, that holds the promise for us understanding lyssants.  The virus is just there to survive and reproduce itself.  The virus is, in its characteristically horrifying way, goading us to find the receptor.

Rabies, a virus, but oh what a virus

Rabies, a virus, but oh what a virus

The specific ways that rabies affects the nervous system, its sole target, can tell us volumes about human behavior, normal and abnormal, and human development, from infant to the fully socialized, highly civilized beings we are expected to become as adults.  It can show us the extent to which humans act as vampires and werewolves, and the meaning of such behavior.  Yet, the rabies virus has not given up its knowledge, although it has been part of our written history since writing began. 

So what is this rabies, this lyssavirus that I am rabid to understand?  Briefly, it is a virus, meaning it contains a long string of RNA (ribonucleic acid) molecules whose.  The specific order of these different RNS molecule makes a code on how to make various proteins. The RNA is packaged inside a protective shell that also contains a specific chemical motif that will provide attachment to the cell it will infect.  Viruses do not have the machinery to gather the necessary material – amino acids – nor the assembly lines to actually construct proteins or RNA.  Therefore, replication of viruses is dependent on the virus’s ability to enter and take over the machinery of a cell that is self-replicating.  Entry must be made into a host cell, that is, a cell whose protein-making capabilities can be manipulated by the viral RNA.  This entry primarily occurs via attachment of the virus to a receptor molecule on the outside surface of the host cell.  Once anchored to the outside of a host cell, the virus may have its own machinery for injecting its RNA through the cell’s membrane (its ‘skin’).  More often, the receptor is internalized into the host cell as part of the normal replacement of that receptor.  In this case, the virus just hitches a ride into the cell.  Lyssavirus uses this method, hitchhiking, to enter its host cells.

The receptors used by many viruses are fairly common across many types of cells or the cells having the necessary receptor are fairly frequent.  The rabies virus is unique in the level of specificity of its target.  Rabies can only infect (enter and take over) neurons.  And, it can only infect neurons of the brain and spinal cord, that is, the central nervous system (CNS).  Neurons wholly outside of the CNS, in the peripheral or autonomic nervous systems or sensory neurons, apparently do not have the appropriate receptor molecule.  Nor does any other cell in our body!  Among other things this means that just because one is bitten by a rabid animal, even having virus-laden saliva in the bloodstream, does not mean that one is infected.  At this stage the victim is simply exposed.  While this is true of any virus, for most viruses the time from exposure to infection is very short.

The CNS is well-protected from many kinds of unwanted material, be it bacteria, toxins, even the body’s own immune cells.  This is a result of the blood-brain barrier.  This consists of very tight junctions – very tiny spaces -- between cells of the blood vessels in the CNS.  The CNS maintains a stringent regulation over what is allowed to enter, or leave, the CNS.  Rabies viral particles are too large to slip between the cells of the cerebral blood vessels.  The virus also cannot infect the cells of the blood vessel walls and thus cannot enter the CNS in that way. 

There are a few CNS neurons that extend out of the CNS.  One type is the neuron that controls skeletal muscle movement, called skeletal motorneurons.  Almost without exception it is the endings, nerve terminals, of these CNS neurons, which are located in our skeletal muscles that are the target for rabies infection. 

Rabies is the only tool for understanding lyssants

Rabies is the only tool for understanding lyssants

We glibly talk about the brain regions and circuits of the rage circuit as givens, but they cannot be effectively studied at the present time.  The risks of working with rabies-infected animals as well as the cruelty of forcing experimental subjects to experience the lethal effects of rabies infection render this approach unacceptable.  We must, instead, be able to work with the native target for the virus, able to turn on, and off, the effects that the virus would produce, without the fear of actual infection and death. 

Early on in the study of animal psychology investigators stimulated various regions of the brain to see what would result.  In some cases they induced behaviors, in cats especially, that had characteristics of attack or of defensive rage.  However, without an object to fully express these behaviors upon, it was difficult to say what was being produced; aggression, defense, rage, or simply a collection of muscle movements.  In light of the uncertainty of what these collections of behaviors meant, they were termed “sham rage” and investigation of them stopped. 

Another tool that held promise was a result of damaging a brain region known as the septal nucleus, an area in the heart of the rage circuit.  Damage to this area sometimes produced a syndrome very much like furious rabies where sudden noises or movements would result in a sudden, full-blown attack on whatever happened to be near.  I can personally vouch that the attack rabbit from Monty Python and the Holy Grail is no fiction!  The speed and ferocity of a raging rabbit flying out of its cage and aiming itself directly at one’s throat is terrifying.  Unfortunately, for our understanding of the basis of rage, this syndrome disappears fairly quickly after the septal area is damaged and is therefore not useful for study. 

Some instances of human rage, like that of Charles Whitman’s murder spree from the University of Texas Tower, can be traced to specific trauma to the brain; in his case a tumor pushing on another structure in the rage circuit called the amygdala.  However, most lyssants, like animals infected with rabies, show no signs of structural damage in the brain.  We know that the amygdala is activated during very stressful events, like those that result in PTSD (post-traumatic stress disorder).  This activation appears to be necessary for making the emotional memories so strong.  We can presume that this type of activation of the amygdala is important for the amazing feats of strength, etc. that can occur in emotional situations.  On the other hand the amygdala is largely absent in some people.  These people do not feel fear.  The understand that certain situations are dangerous, but they do not express fear in the situation.  They don’t exhibit lyssantic behaviors.  We can expect that pharmacological manipulation of the amygdala or brain regions connected with it will allow us to induce rage.  However, this hasn’t occurred yet, strongly suggesting that the critical neuronal circuits, the critical neurotransmitter receptors, are not known.  But we do know that rabies virus, its targeting motif, can produce rage behaviors, so we can presume that it is affecting the critical receptors. 

Experimental neurobiologists have also studied aggressive behavior, but aggression by itself overlaps only partially with rage.  Even the studies of aggressive behavior have had limited success, in large part because we did not/do not have pharmacological tools to selectively stimulate and block all the subtypes of serotonin receptors that appear to be the most promising underlying mechanisms.  Even when these tools do become available, it is already clear that aggressive behavior is quite different from rabidity.  Aggressive behavior, bullying is one aspect, has a large component of voluntary control with positive reinforcement of past occurrences that lead an individual to continue to use these behaviors.  On the other hand one of the hallmarks of lyssantic behavior is that it does not appear to care whether it is likely to result in a win or a loss, it just rages.  Of course, we presume that lyssantic behavior has been successful in keeping individuals alive and therefore has been kept as an important part of our genetic heritage.  I expect it is possible for people to learn the triggers that can release a lyssant’s rage, but there is still a large difference from aggressive pushiness and impulsive aggression.  Reports about the changes in demeanor of people like Al Capone going beyond their being aggressive to becoming a ‘monster’ with a baseball bat are probably good examples of lyssantic behavior in action.

Our most promising avenue to pursue understanding lyssants and their behavior is still the rabies virus.  However, as long as we have only the lethal virus itself, we will be unable to fulfill our need to understand rage.  We must, and we have the tools to do this, discover the target of the rabies virus; the only psychologically important part of the virus.  Being a virus has largely distracted us from learning the secrets it holds to our own inner selves.  The behaviors it unlocks in its victims are not the result of it being a virus, only its targeting motif is necessary to produce these behaviors.  So, we need to discover the target.  And, as a major added bonus, discovering the target, the CNS receptor, will also provide us the means to discover post-infection treatments for rabies itself.  It’s a win-win-WIN BIG situation.

Lyssants – incidence & prevalence – anyone willing to be census-takers?

Lyssants – incidence & prevalence – anyone willing to be census-takers?

Just how prevalent are lyssants?  At some time we have all been lyssants even if only when we were toddlers and having a temper tantrum.  It is a natural part of our behavioral repertoire.  It plays a critical role when it occurs as defensive rage and allows us to overcome or frighten away an assailant.  And the playful frenzy during sexual relations can serve to strengthen interpersonal attraction, and can help overcome external pressures.  But, for teens and adults, becoming a lyssant often produces more trouble than it solves.  Lyssant behavior is not tolerated in most societies and is quickly punished.  An exception occurs to some regulated degrees in various sports.  Even here, there is increasing recognition of progressive neural damage from multiple physical traumas.  This suggests these outlets for our innate lyssantic behaviors need continual monitoring and improvement in safety equipment and health surveillance. There is no chance, certainly no wish by this author, to try to curtail these means of ‘letting off steam’.  I fully believe this would be disastrous to us as a species and would just move such behaviors further into underground fight clubs and the like.

Given the lack of a specific accepted definition or test, calculating the prevalence of uncontrolled lyssant behavior is presently impossible.  However, some insights into its prevalence may be gained from comorbidity studies.  For example, the occurrence of oppositional defiant disorder and/or conduct disorder in people with ADHD is commonly reported to be 30-50%. Certainly not all are lyssant, but some are.  The rage cycle in people with an autism spectrum disorder is well-recognized.  Some of this behavior is surely lyssantic. The prevalence of Intermittent Explosive Behavior has been estimated to be from 3-7% of the population.  What is crystal clear is that rage that “comes out of nowhere” is common, and more so among people with other conditions that make generating accepted social behavior difficult.  It is also clear that ADHD, autism disorders, bipolar disorder, and others are not synonymous with lyssantic behavior.  Lyssants need to be uniquely defined and specific treatments found for when their behavior interferes with the conduct of their lives.  Specific means to draw it out, like sodium lactate for panic disorder, must be found.  And, as much as I admire the accomplishments of cognitive-behavioral therapy (CBT), I simply do not believe that overt reinforcements or ‘mindfulness’ can address the true measure of lyssantic behavior.  I know a number of people that can recognize they are heading toward having a migraine headache, but they still need pharmacological treatments to blunt or block the migraine headache itself.  Lyssantic behavior is much, much more powerful than that.

there be monsters… actually, they’re lyssants

there be monsters… actually, they’re lyssants

If, as I proclaim, rabidity is a natural part of human behavior that emerges in a number of situations, then we need a single, general term to refer to a person or animal affected in this way.  I introduce a new word, lyssant, to refer to a person or animal exhibiting rabid behavior, however it is induced.  The word derives from the Greek word, lyssa, which refers to rabies, certain kinds of madness, and is the goddess (daimona, i.e. spirit or demon) of rage, fury, and rabies (ref).  Indeed, the formal name for the rabies virus is Lyssavirus.  The Roman equivalent of Lyssa was variously called Ira, Furor, and Rabies.  Although this narrative will continue to use terms such as rabid, vampire, werewolf, intermittent explosive behavior, road rage and others, all refer to a lyssant, a person or animal exhibiting these behaviors.  This term also allows us to dissociate temporarily our discussion from a second set of symptoms of rabies, the so-called dumb or paralytic form.  Lyssa clearly refers to the rage aspect, i.e., furious rabies, and for now, lyssant does also.

Lyssantic behavior is found throughout psychiatry and clinical psychology.  However, its appearance is fragmented, inserted piecemeal into a wide array of behavioral disorders.  Behaviors that include rage are clustered with Impulse Control Disorders where they are uselessly clumped together with kleptomania and compulsive gambling.  Lyssantic behavior is couched in a variety of terms including Impulse Control Disorder, Intermittent Explosive Disorder, Conduct Disorder, Emotional Dysregulation, Impulsive Aggression, and others.  Lyssants and their behaviors are listed among the myriad of symptoms of broader diseases including Attention Deficit/Hyperactivity Disorder (ADHD), for example ADHD with Conduct Disorder, and in various subclasses of autism spectrum disorders.  Disorders such as road rage and domestic violence are shunted into corners of Personality Disorders that have no meaningful therapeutic approaches. 

This jumble is clearly the result of a lack of a specific physiological or pharmacological means of categorizing lyssants and their specific set of neuropsychiatric characteristics.  At best it is likened to the temper tantrums of toddlers.  While temper tantrums are surely lyssantic behavior, psychoanalytic analysis of regression to some unconscious psychological trauma is of no use in describing or in treating lyssants.  Given the lack of a specific definition, lyssants are bombarded with anxiolytics, antipsychotics, and antidepressants.  Essentially the full range of psychotherapeutics is thrown at them simply hoping the lyssant will obtain some relief or be controlled.  Maybe also a full dose of sunlight or a stake through the heart for good measure.

By defining a specific term, lyssant, and the behaviors it encompasses, we have the opportunity to untangle this mess.  We can apply the full weight of neuroscience research tools to discover and study the pathways and actions of rabies.  Most usefully, we can discover and study its native target in the central nervous system.  We can already expect this to be successful because our knowledge of the emotional centers of the brain, exemplified by the Papez circuit, are exactly the result of Dr. Papez’s work in determining the avidity of the rabies virus for various regions of the brain.  These regions and their connections are sometimes referred to as the Rage Circuit, and it is in modulating this circuit that we will be able to treat lyssantic behavior gone awry (psychological disorders as well as the actions of mad-men) and to come to understand our own inner vampires and werewolves, that is, come to understand what it means to be a complete human.

Human vampiric virus…. no, it’s much scarier

Human vampiric virus….  no, it’s much scarier

We are, in a revolting sense, lucky that rabies-infected, rabid, victims do not survive long.  Death comes quickly, though not at all mercifully.  One can wonder what would happen if humans could survive infection by rabies, or, if not rabies itself, then a closely related virus.  Even more, perhaps this related virus is what produces real vampires and werewolves!  Thanks to our extraordinary imaginative capacity, a Human Vampiric Virus (HVV to make it sound like a real medical term) has been dreamed up.  The reader can see and hear about it on Animal Planet’s website in its section on Freak Encounters.  This imaginary virus might have been first written about in 1616 in a Treatise on Vampires, written by an Italian scientist Ludovico Fatinelli.  He could have speculated on the role of an invisible pathogen to induce vampirism.  Of course, this is a modern hoax -- thanks to an Amateur Vampirologist for seeing through it [http://doaav.blogspot.com/2011/09/ludovico-fatinelli-exposed.html].  Still, it makes good starting material for a blog.

In order to produce true vampires and werewolves, the virus would have to induce the rapid and reversible growth of our canine teeth and other such bodily transformations as are beyond any biology that we can even conceive.  The painful changes that Prof. Lupin [thanks to J.K. Rowling] and other movie and TV werewolves go through are easily indicative of the utter impossibility.  [And yet, these painful, difficult movements do resonate with the difficult movements of the paralytic (dumb) form of rabies.]  No, we are stuck with rabies itself, producing all the behaviors of our avatars of rage, but without the bodily transformation.

Potentially more likely is that some people may be able to survive rabies infection and then be in a constant state of bloodthirsty, biting behavior.  Although not outside the realm of possibility, this wouldn’t be very useful for the survival of the rabies virus itself.  And, we’ve already noted that humans are poorly designed to pass the virus on to other victims, however much biting is a natural, prepotent behavior for us.  We just can’t sink our teeth into it.  The virus would likely simply die off as its human carrier dies.  Perhaps this is more plausible to occur in carnivores, like wolves.  Still, my guess is that the incessant attempt to bite other members of the pack would result in the, in this case, timely death of the infected victim.  And yet...

What would a living rabid person be like?  They would be the embodiment of several psychological disorders including intermittent explosive behavior, impulsive aggression, extremely prone to road rage, having hair-trigger tempers.  The primary danger wouldn’t be whether one is turned and could pass on the virus.  It is enough that they would maim, mutilate, and murder.  Imagine the ability to produce true ‘dog soldiers’, a movie I still have nightmares about.  The greatest threat probably wouldn’t be an attack by a force of dog soldiers – like Tolkien’s orcs they would probably kill as many of their own kind as any enemy.  The real threat is spreading the rabidity among our own friends and neighbors and the havoc it would wreak on our own people turned and caught up in the madness that is rabies infection.  But this wouldn’t happen by using the rabies virus itself; we’ve seen that it takes weeks or longer to infect its victim.  Not a very efficient weapon.

Could rabies virus be changed to get into the central nervous system (CNS) more quickly?  Possibly, but not likely.  As we will see, it is the targeting vector in the rabies virus that produces its effects.  It does not produce its deadly effects as do most viruses, by multiplying and then destroying the cells it has infected.  We really must stop focusing on the virus aspect of rabies.  It is a virus, obviously, but that’s neither the menace, nor the hope that it represents.  Rabies is cleverer, more insidious than that.  The behaviors it releases are the result of it binding to, presumably blocking (but that also awaits the discovery of its target), the activity of specific types of neuronal receptors – selectively modulating lines of neuronal communication and control.    It takes advantage of what we already are – closet vampires and werewolves – and uses our own behavioral repertoire to get us to pass the virus on to new victims.  In the long run, the multiplication of these receptor ‘blockers’ does overwhelm essential functions of the nervous system resulting in the death of the victim.  But, as it initially infects the CNS, it selectively ratchets up our rage defense attack system, by enhancing it or dampening our social inhibitions, or both.  Luckily for us humans, we generally become exposed to it from short-toothed, clean wounding animals resulting in the paralytic, muscle-weakening effects rather than furious rabies, or perhaps the ataxia and paralysis just limit the victim from being able to actively engage potential new victims.

Getting the rabies virus into the CNS faster would require changing its targeting motif so that it attaches to something more common, something found on many types of neurons or cells in general.  But, that would destroy its specificity, its ability to induce a unique and frightening set of behaviors; it would just kill us.  No, dog soldiers and bioterror weapons will be the result of a pharmacological agent that modulates the receptors that are targeted by rabies.  It may be good theater to continue to have a virus be the means of producing werewolves and vampires, even zombies, but it will be straight-forward chemistry that makes these horrific visions come alive.  Civilized people and nations need to ensure that we understand how to defend against this before someone does turn it loose.  Is anybody listening?!

it's rabies, plain as the claws on your paws

Authors before me have hypothesized that rabies is at the root of werewolves and vampires.  Certainly many of the modern tales at least allude to a viral infection.  Specifically, Dr. Gomez-Alonso published a report (Neurology, 1998, 51:856-9.) drawing the link between rabies infection and the vampire legends.  He proposed “that rabies may have played a key role in the development of the vampire legend, given the coincident time of the phenomena and the striking similarities between them.”

Ian Woodward in his comprehensive analysis The Werewolf Delusion states “But I have no doubt that, because of the shared symptoms, a vast proportion of history’s dreaded “werewolves” were in fact either rabid wolves or their rabid human victims.  The facts seem to speak for themselves” (p. 168).

Yet, some authors discount this connection, although still noting the similarity over and over.  Most recently the book Rabid sought to sever the link.  Rabid is a wonderful compilation of information about rabies and other zoonotic diseases.  The authors give a number of reasons why rabies does not produce vampires and werewolves.  One possible anomaly is that vampires and werewolves can give long accounts of their behavior, seemingly in contrast to the short lifespan of the infected individual.  Yet, only a few pages earlier they note the case of Charles Lennox, governor-general of Canada in 1819.  He was bitten by a fox and contracted rabies.  He became lucid at various times during his madness, in one case dictating “a lengthy letter to his eldest daughter” (p.10).  And later, discussing the possibility that Edgar Allen Poe died from rabies, they again state “Rabies sufferers, by contrast, are prone to just these sorts of swings between delirium and lucidity” (p.108). As these authors note, this cycling is a notable, and perhaps one of the most heart-wrenching, aspects of rabies infection.  A person with rabies will have periods when they are fully aware of what’s been happening to them, and fully aware of what’s to become of them! 

It also seems to the authors of Rabid and many other investigators that the fact that victims of rabies infection die quickly once symptoms appear is at odds with the longevity of some imprisoned self-confessed vampires and werewolves.  However, not one of those self-confessed monsters turned into a vampire or werewolf while in the presence of authorities.  These people were certainly mentally ill, but they were not true vampires or werewolves, and they did not have rabies.  Moreover, especially in times before hospitals patients would have been treated at home.  As noted, many victims of rabies do, at times, understand what their fate will be and the danger they pose to family and friends.  This knowledge, coupled with rabies’s urges for the victim to escape any confines (real or apparent) and to roam resulted in many victims running away, into the forest, from which they might never be seen again.  Who’s to say they died… although almost certainly they did die from the rabies itself or from a foolish encounter with another predator.

Tuberculosis and porphyria are two other disorders often tried to be linked with vampires (but not werewolves).  In the case of tuberculosis the link is really to revenants with their sickly, ghostly appearance.  There is no room for werewolves, nor vampires, in this scenario. 

Nor does porphyria explain the primary behaviors of vampires and werewolves, that is, rage and blood-lust.  Porphyria produces a hypersensitivity to sunburn and therefore a healthy avoidance of direct sunlight.  This simply doesn’t compare with the active startle and apparent fearfulness of bright light, and sounds, associated with vampires and werewolves, and very prominent in people infected with rabies.  Porphyria may have provided people with the hope of a defense against vampires - that they would burn up in sunlight - but the message certainly didn’t get across to rabid bats and wolves (and beavers) that are notable for being seen openly during the daylight that they normally avoid.

There really is no doubt that rabies infection is the model for the behavior of vampires and werewolves.  Whether true vampires and werewolves exist may be another story, but it is clear that their behavior closely mimics that of rabies infection as well.  More intriguing, more frightening, and truly more hopeful, is that rabies infection allows us to understand that this behavior is a normal aspect of every human being – we each carry our own vampire and werewolf inside our own brains, and in some of us, they come out to romp at times of their own choosing.  This realization gives us hope to understand, and when necessary to treat our inner monsters.  That rabies infection is linked to our legends is very satisfying, but it is the fact that rabies draws out, in a consistent and predictable way, the set of rage behaviors that otherwise seem to be the work of some supernatural, at least subconscious, power over which we have no control.  We need to understand the workings of the rabies virus because then we will be able to obtain control, and understanding, of all that it means to be completely human.

Which came first, rabies or rabid creatures?

Which came first, rabies or rabid creatures?

In terms of when they first appeared, rabies is at least as old as vampires and werewolves.  Of course, this only means that they both appear in the earliest of human writings.  Rabies makes its way into our earliest books of law, not long after the advent of writing.  Rabies may be referred to in the Codex Eshnunna of ancient Mesopotamia (1930 B.C.E.).  A more definitive reference, specifically noting a mad dog, is found in the code of Hammurabi (1750 B.C.E.), still nearly 4,000 years ago.  To be specifically mentioned when writing was considered an essentially mystical creation meant only for demigod-like royalty strongly indicates that rabies infection was already a very prominent fear and a fairly common occurrence!

Rabies is well-documented within the pantheon of gods and goddesses of the earliest written European cosmologies.  Lyssa, the Greek goddess of rage - who has a rabid dog crowning her head - certainly dates from earliest Olympian cosmology.  The Romans had their own counterparts -- Ira, Furor, and Rabies.  Lyssa is perhaps best known for driving Hercules (Heracles) to madness during which he murdered his wife and child.  Many cosmologies have wolf gods, Fenrir in Norse mythology and Wepwawet in Egyptian, but their raging characters are a given rather than a unique excess that might be due to rabies infection. Of course, with wolves it’s best to presume they are rabid.

We have already noted that a werewolf, King Lycaon, is mentioned in Ovid’s Metamorphoses from around 1 C.E.   This story almost certainly followed the lead of earlier oral traditions.  Humans living and behaving like animals are fairly common in Greek tales – Circe certainly did a number on Odysseus’s crew.  But this jumbles lycanthropy into the mix.  Tales of werewolves exist, but are generally just added in to tales of shape-shifting in general.  Still, as King Lycaon’s tale attests, transformation into a werewolf has a specific character, and a specific implication, that is, the loss of social, civilized behavior, and of killing or turning new victims

Vampires, in their earliest form as revenants, are clearly noted in folktales from earliest times.  For historical purposes, these folktales were perhaps best kept alive in Eastern Europe where pantheistic, pre-Christian beliefs were still common at the same time the printing press was invented making preservation of oral traditions a reality.  As the modern (since the Americas were discovered) view of vampires did not coalesce until Europeans observed vampire bats (1600’s), it is difficult to directly or simply trace the early conceptions of vampires.  Many of the words from which vampire has been derived may originally have referred to witches.  Witches could turn people mad, or drove themselves into madness in search of mystical knowledge.  A deeper analysis of the origin may not be fruitful since vampires as we understand them almost certainly required the discovery of vampire bats to take on their distinctive, singular persona.

In summary, rabies, werewolves, and vampires have coexisted as far back as we can trace.  This doesn’t prove they are one and the same, but it is definitely consistent with that notion.  In concert with the similarity of behaviors and the commonality of how they are passed from one victim to another, it is almost impossible to deny their unity.