Understanding the Monsters of Myth Through a Rare Genetic Disorder

by Paige Hauke
figures by Daniel Utter

Myths play a fundamental role in explaining the seemingly unexplainable. From Greek and Egyptian gods to Bigfoot and Nessie, we search for meaning in the world and find it in stories. As our scientific understanding of the world grows, though, we take less and less meaning from these grandiose tales. However, we can use science alongside storytelling to enhance our understanding of myths and bring them into our modern reality. An example of this: vampires. Made popular by 19th century horror writer Bram Stoker, the bloodsucking monsters of legend have become a fantasy icon. Yet hiding behind the fantasy is a real, explainable blood disorder, erythropoietic protoporphyria (EPP), that very likely inspired the Dracula we know today.

What is EPP?

EPP is a genetic blood disorder. With an estimated incidence of between 2-5 people in 1,000,000, it is classified as a rare condition. For patients who suffer from EPP, however, the disorder wreaks havoc on their blood.

Healthy blood systems depend on red blood cells to transport oxygen from the lungs to the rest of the body. This capacity to transport oxygen is delegated to a molecule called hemoglobin, which picks up oxygen in the lungs, carries it throughout the body, and deposits it in various tissues along the way. Because of the importance of oxygen to many biological processes, any problems with hemoglobin production can translate to large complications throughout the body.

Normally, hemoglobin synthesis begins with “building block” compounds called porphyrins (Figure 1). Porphyrins react with iron and other, smaller compounds to create a larger intermediate compound, heme. Many hemes then group together to scaffold the foundation of hemoglobin. In the case of EPP, though, there is a malfunction in proper hemoglobin synthesis. This malfunction stops production of heme intermediates and, instead, causes the direct incorporation of porphyrins into the final hemoglobin product. Just as buildings rely on specific scaffolding to keep them standing, hemoglobin relies on heme groups for proper function. While porphyrin components can still aid in oxygen transfer, they provide less structural integrity to hemoglobin and thus can incite complications throughout the body.

Figure 1: Hemoglobin production in health and EPP. A) Hemoglobin synthesis begins with porphyrin compounds and builds up to hemoglobin through a heme compound intermediate. B) In cases of EPP, this synthesis pathway is disrupted at the intermediate step, stopping production of heme groups and incorrectly incorporating porphyrins throughout hemoglobin.

A Taste for Blood

So how does vampirism come into the mix? When looking more closely at EPP’s specific complications, the parallels speak largely for themselves.

Vampires are, of course, most credited for their unquenchable thirst for blood. While EPP does not turn people into bloodthirsty monsters, more outdated EPP treatments may explain this portion of vampire myth. In the current day, blood infusions have become commonplace procedures to inject blood from healthy human donors directly into the veins of compatible patients. For treating EPP in particular, pharmacologists have developed a way to isolate heme from donated red blood cells and inject the compound directly into the blood of EPP patients. This injection gives the body materials to incorporate fully formed heme into hemoglobin synthesis, slowing the accumulation of porphyrin-incorporated hemoglobin. The number of unstable red blood cells decreases, and oxygen transfer occurs as it should.

Before medical advancements introduced heme infusion, however, patients would have needed to take a different measure to relieve symptoms: drink blood. While drinking blood does not inject healthy heme immediately into the bloodstream, heme compounds from the hemoglobin are robust enough to survive digestion. In the intestine, heme is absorbed through the tissue and into the bloodstream, where it can work similarly to a direct infusion. Considering this, it is likely that patients, prior to the infusion era, had to constantly ingest animal blood. For them, this was a necessity, but for any uninformed onlookers, such an action could easily come off as a terrifying ritual. And so a vampire myth was born.

Living in Darkness

It turns out that blood deficiency is not the only correlation between vampires and EPP patients. Both groups also share acute light sensitivity.

Light is a form of energy that has a lot of power in chemical reactions. For example, in order for plants to make food through photosynthesis, they use the energy in light to drive chemical reactions that convert carbon dioxide and water into sugars. In this case, the energy from the sun’s rays helps plants survive. However, in EPP patients, exposure to the sun and other intense light sources initiates an undesirable chemical reaction. When exposed to light through the skin’s surface, the misincorporated porphyrins in red blood cells produce a toxic compound that affects surrounding cells. Even on cloudy days or through tinted windows, the sun’s rays are fierce enough that EPP patients can find themselves plagued by rashes, swelling, and blisters over exposed arms, hands, and faces. Protection from the sun, then, is crucial for these patients.

Prolonged time shrouded in darkness inevitably leads to a lighter complexion, meaning sun protection can also account for paler skin in EPP patients. While the pallid physique and dramatic sensitivity to sunlight accredited to vampires initially seem like fabricated traits, the symptoms of EPP suddenly paint them in a different light. In eighteenth century Transylvania, pre-light protective technology, it would make sense to live in a darkened house and only venture out at night. Instead of stalking victims or waking the dead, the original Transylvanian “vampires” more likely, and quite literally, were protecting their own skin.

 Long Life

 Another prominent character trait, immortality, permeates vampire lore. But this one must be a lie, right; no one can live forever? Of course, EPP doesn’t magically give people unlimited life expectancies, but its genetic component may link this condition to the tell-tale longevity of vampirism.

EPP is programmed into the human body through genetics, or a set of instructions written into our DNA. When we have children, much of our own genetic code transfers to them. The EPP gene is recessive, meaning its code must come from both parents for their children to also suffer from it. The recessive nature contributes to the scarcity of known EPP patients in a modern day setting, but this wasn’t always the case.

In the past, inbreeding between distant family members occurred at higher rates, especially in smaller, isolated communities like Transylvania. Because of increased instances of inbreeding, communities would have been more likely to share overlapping gene pools. In the context of EPP, this means that patients’ otherwise rare genetic disorder had a higher chance of being inherited by their children (Figure 2). So, while patients themselves were not gifted with immortality, the condition they suffered from could potentially live on in their families for decades, even centuries.

Figure 2: Inheritance of EPP. EPP is a recessive gene, that, when passed on by two carrying parents, will inevitably show up in their children.

Beyond EPP

Do EPP patients turn invisible in mirrors? Do they scream in the presence of holy water? While some of the myths and mysteries behind vampires can be explained away, others are the product of thousands of years of a mythical game of telephone. It is most likely that, as the unexplainable observations of patients travelled over time and space, the details morphed drastically. This is where EPP most greatly branches away from its fantasy counterpart.

It is important to remember that, although vampire myths are most likely based in observable, scientific phenomenon, the original misunderstandings that spurred the creation of these fictitious monsters inevitably gave rise to details that are less than factual as well.

That being said, trying to understand where the two overlap can lead to a greater appreciation of the truth in the fiction. Extending beyond vampires to the larger world of fact and fiction, there can be no doubt that science serves an intriguing, informative role in tracking the progression of myths. No one story will ever match reality perfectly, but scientific analyses can give us a glimpse into how we create fantastical narratives to grasp at the unknown.

Paige Hauke received undergraduate degrees in Chemistry and English from Wellesley College. She currently works as a research technician at Dana-Farber Cancer Institute.

Daniel Utter is a 5th year Ph.D. student in Organismic and Evolutionary Biology at Harvard.

For more information:

The post Understanding the Monsters of Myth Through a Rare Genetic Disorder appeared first on Science in the News.