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.