Wednesday, October 14, 2015

Blood --- Not Just For Vampires Anymore

“Nosferatu” was the first film (1922, directed by F.W. Murnau)
made about the blood sucking undead. It followed the Stoker
novel so closely that his estate sued and a court ordered all the
copies destroyed. Only five survived, and were used to restore
the film in 1994. One area where did deviate from the novel
was in the way the vampire dies. Murnau introduced the idea
of sun sensitivity, which caught on and was accepted as part
of the myth.
It may not be surprising, but there’s a lot of pathology in Halloween. Since the holiday is coming up soon, let's take a look at some of the gory details.

Pathology (pathos = disease, and ology = study of) is the study of disease, and being dead is the worst disease - O.K., maybe being undead is worse. Between life and death is where the vampires live, so maybe this is a good place to start.

One prerequisite for being a vampire is that you have a taste for blood, but if that was the only rule, then almost everyone would be a vampire. Hematophagy (hemo = blood, and phagy = eat) is as common as bad Dracula impressions. Almost every culture consumes blood.

Many people eat cooked blood. The Poles eat blood soup (czernina), and the Brits love their blood pudding as much as the Chinese gobble their fried blood tofu. The next time you go to a French restaurant for the coq au vin, remember that the sauce is made with rooster blood!

There are also those cultures that drink blood. The inuit peoples drink fresh seal blood, and the Maasi in Africa rely on a mixture of cow’s milk and cow’s blood as a staple of their diet. And why not, blood is a decent source of nutrition.

Blood has a lot of protein and is a good source of lipids. Of course it is iron rich, and is a source of fluid and salt if you happen to be caught in the desert. If a vampire happens to pick out an uncontrolled diabetic, a drink of blood could also be a good source of carbohydrates.

These are Finnish blood pancakes. You have to wonder about 
a recipe whose first ingredient is 40 ml of blood. But 
the lingonberry jam on top is a nice touch; you would 
hardly remember that you are eating blood.
Many animals practice hematophagy. Female mosquitoes consume blood; both sexes of the Cimicidae family (bed bugs) survive solely on blood, as do arachnids of the Ixodida order (ticks). Some of the 700 species of leeches feed on blood only, but most eat small invertebrates as well. There is even a vampire finch on the Galapagos Islands that bites the rumps of other birds and licks off the blood. And then there are the vampire bats.

As members of the Chiroptera order (chira = hand, and ptera = wing), vampire bats are members of a grand biologic exception. Bats are the only mammals that truly fly. True flying requires lift, being able to sustain a rise in altitude by mechanical means. Closest to this is soaring, which is the use of upwelling air currents to gain altitude. But gliding is the most common type of aerial motion in reptiles, amphibians, mammals. Gliding is really controlled falling; it means moving at less than a 45˚ angle to the ground.

Bats are so finely evolved for flying that they have lost most of their ability to walk, but vampire bats are an exception even in the world of bats. They often approach their victims by walking or running up to them from behind. Vampire bats were quite the biologic discovery.

The vampire bat wasn’t named as such until 1774, but vampire legends (4000 BCE) and the word vampire (circa 1734) had been around much longer. Therefore, the bat was named after the undead, blood-drinking person, not the other way around.

Three species of bat, ranging from Mexico to Chile, subsist exclusively on blood. Each has evolved tricks to help them secure the blood they need. Their noses house special thermoreceptors to help them find areas of flesh where blood vessels lay close to the surface. The way their brain perceives and interprets this information (see this post) is very similar to the way pit viper snakes sense live prey (see this post).

Common vampire bats like to bite and lick blood from around 
the hooves of cattle and such. They are so sneaky, they run 
up to the animals from behind instead of flying. Their wings 
are stronger than most bats, so they can help support their 
body weight when they run or hop.
Two species (Diphylla ecaudata, Diaemus youngi) feed on the blood of birds, while the other (Desmodus rotundus, a.k.a. common vampire bat) feeds on mammals, including humans, but they all feed exclusively at night. This may have helped to link the bats to the monsters, as vampires are supposedly harmed by sunlight.

The common vampire bat will shave away the hair away with its teeth and then plunges its incisors in about 7-8 mm to bring blood, as its incisors are conical and are designed for cutting. Vampire bats are an exception in that they are the only bat species that do not have enamel on their incisors.

Enamel is very strong in compression and wear, but is brittle and rounds off the points of the teeth. Vampire bats need very sharp incisors, so they have forgone the enamel. Broken enamel would blunt their teeth, a lethal problem for a bloodsucker (although they don't suck).

The Swiss Federal Institute for Technology at Lausanne has
developed a drone that can walk and fly, based on the movement
of the vampire bat. When it goes terrestrial, it pulls in the the
middle section of wing and the rotates the wing tips
to propel itself (2015).
Importantly, vampire bat salvia contains anticoagulants to keep the blood flowing and vessel relaxants to keep the local blood vessels from constricting.  A new study has shown that bat saliva may have potential in human medicine. The common vampire bat is the source of a new clot-dissolving compound called desmoteplase; it activates an enzyme called plasminogen, which breaks down early clot formation.

Desmoteplase is structurally similar to a currently used clot buster called tPA (tissue plasminogen activator), but has some differences that make it more selective for fibrin. Importantly, it doesn’t cause nearly as much neuronal apoptosis or breakdown of the blood-brain barrier as does tPA. Desmoteplase is in phase III clinical trials for use in ischemic stroke patients (a brain blood vessel is blocked by clot). I wonder if human vampires have such useful saliva.

Ischemic stroke occurs when a blood vessel in the brain
is occluded so oxygen rich blood can’t reach the brain
tissue beyond the occlusion. The middle cerebral artery is
a common site for these cerebrovascular accidents. 
Desmoteplase appears to be effective against occlusions
caused by blood clots, but there can be other occlusions,
name scar tissue from infection or atherosclerotic plaques.
Vampire bats usually slice open a small vessel with their incisors, and then lick the 20-25 ml of blood that flows out. This is very different from the idea of vampires sucking out all the blood from a human; something not consistent with long life. But could losing blood ever be considered a good thing? You know there has to be an exception.

In certain diseases, removing excess blood is beneficial. We talked earlier about excess iron in hereditary hemochromatosis, for which bloodletting is an appropriate treatment, but there are others.  Polycythemia vera is a genetic disease in which too many red blood cells are produced, leading to high blood volume and pressure, excess bleeding and clotting. To bring the volume closer to normal, a pint of blood may be removed once a week.

Finally, in chronic hepatitis C infection there is damage to the liver, a major storehouse of iron. This releases iron into the blood, and causes a secondary hemochromatosis. Small amounts of blood can be removed to help lessen the iron overload. Maybe old-timey medicine didn’t have everything wrong.

These same old cultures had myths about the undead that would feed on human flesh, but our current vampire myths date from early 1700’s Southern Europe. There are diseases that could be mistaken for some or all of the aspects of vampirism, but are they the chicken or the egg? In many cases, myths and folklore have some basis in fact, but in these cases hindsight is hardly ever 20/20.

Tuberculosis and rabies have a few aspects that are similar to the common tales of vampires. TB leaves its victims emaciated; they end up pale with swollen eyes that make them sensitive to light. They might cough up blood, and the first victim often gave the disease to other members of the house, so it have might appeared that the first was draining the others.

Similarly, people with rabies may exhibit a bloody froth from the mouth because lesions on the throat make it very painful to swallow. They may also be driven to bite people due to the encephalitis (encephalo = brain, and itis = inflammation) that the rabies virus causes. Other behaviors associated with rabies are sleeplessness (night time activity) and fear of looking at one’s own reflection.

Rabies spreads through the nerves, and the brain is the main
organ affected by the infection. Without vaccination or
treatment rabies is 100% fatal. Animals with the infection lose
fear of man, and become very aggressive, and then so do people
who contract the virus. Two cases of human bit rabies have been
confirmed (both in Ethiopia in the 1990’s).
Vampire bats are carriers of rabies, and this may contribute to their use in vampire lore, but recent evidence says bat rabies may not be such a bad thing. A 2012 CDC study shows that many Peruvian natives have a natural immunity to rabies, a disease that kills 55,000 people each year. The vampire bat maybe helping drive this immunity. It’s bite can deliver a sub-pathogenic dose of virus, enough to convey immunity, but not enough to cause disease. A case of vaccination by bite!

Another disease that mimics some vampire characteristics is xeroderma pigmentosum (XP). XP leads to an extreme sensitivity of the skin to the radiation of the sun. XP was first described in the scientific literature in 1874, just a couple of years before the first tales of sun sensitivity in vampires. There are several different types of XP, but all are autosomal recessive genetic diseases. Most involve mutation and inactivation of nuclear excision repair enzymes.

Sunlight contains UV radiation that causes DNA mutation. Excision repair enzymes usually fix the DNA damage. Without them, afflicted individuals manifest hundreds of skin cancers, and acquire others that are lethal (malignant melanoma). The patients’ eyes are very sensitive to light; they sunburn almost instantly, and must be kept out of sunlight. The children from the 2001 film, “The Others” had XP (while they were alive).

Congenital Erythropoietic Porphyria (CEP) is by far the disease most often associated with vampirism. Exceedingly rare, this autosomal recessive genetic disease has only been diagnosed in about 200 people, but there are many variants of porphyria that carry some or most of the same symptomology as CEP.

Porphyria can lead to deposits of porhyrins in the enamel
of developing teeth. The word porphyrin comes from the
Greek word for purple, so the discoloration is often darker
than what is shown here. Interestingly, tetracycline use in
pregnant women and children can lead to a similar
deposition, but for very different reasons.
The mutation common to the porphyrias is in the gene for an enzyme called uroporphyrinogen cosynthetase. Involved in heme synthesis, the loss of this enzyme leads to the buildup of heme intermediates called porphyrins. The porphyrins accumulate in the skin and organs and act as a sun-activated toxin.

The symptoms of the porphyrias do make you think of vampires: sun sensitivity with extreme burning, white skin, bloodshot eyes, sensitive eyes, anemia (low number and therefore a need for red blood cells), reddish tears, reddish urine, red pigment in the enamel of the teeth (erythrodontia).

The red teeth really bring to mind feeding on flesh or blood, and porphyrias also bring increased body and facial hair (hirsutism), so they may contribute to the werewolf legend as well. This is interesting because Medieval Europeans would burn the corpses of people who were thought to be werewolves, so as to prevent them from returning as vampires - better safe than sorry! 

Next week we will continue our look at Halloween by investigating death – how likely is that you might be buried alive?

For more information or classroom activities, see:

Hematophagy –

Vampire bats –

Xeroderma pigmentosum –

Congenital Erythropoietic Porphyria –

Medcalf RL (2012). Desmoteplase: discovery, insights and opportunities for ischaemic stroke. Br J Pharmacol. DOI: 10.1111/j.1476-5381.2011.01514.x

Amy T. Gilbert, Brett W. Petersen, Sergio Recuenco, Michael Niezgoda, Jorge Gómez, V. Alberto Laguna-Torres and Charles Rupprecht (2012). Evidence of Rabies Virus Exposure among Humans in the Peruvian Amazon Am J Trop Med Hyg DOI: 10.4269/ajtmh.2012.11-0689



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