The Human Microbiome: A look into our microscopic world

Did you know the number of microorganisms in the human body is in the trillions, outnumbering our own cells by a ratio of at least 10 to 1, or that the estimated weight of microorganisms in the human body is 2 to 6 pounds or nearly the same as the weight of the brain? Well if you're like me you had no idea how significant and essential the human microbiome is to our lives, many operations throughout our body that keep us alive can not occur without the help of the human microbiome, let's dive deeper into this small and exciting world to learn the wonders of the human microbiome and their essential roles in digestion, immunity, and overall health!

The Human Microbiome 

What is the Human Microbiome?

The term "human microbiome" describes the assortment of microbes that live in different regions of the human body, such as bacteria, viruses, fungi, and other microbes. Our skin, mouth, gut, reproductive organs, and other mucosal surfaces are home to these microbes. The dynamic and intricate ecosystem known as the human microbiome is essential to preserving our health and well-being. I think it is so important to learn about the human microbiome because of how intricate it is and how vital it is to our lives. The human microbiome has a very diverse composition that differs from person to person. It is affected by things like heredity, age, diet, hygiene standards, environment, and even the way we were born. Even though bacteria in the human microbiome are the microbes that have been studied the most, new research has broadened our understanding to encompass other microbial communities as well.

Composition of the Human Microbiome

The human microbiome is composed of many different microscopic organisms like bacteria, fungi, archaea, and other microbes. Let's take a deeper look at a few very common and very interesting microorganisms found in the human microbiome:

Bacteria

Bacteria under microscope

The microbes that make up the majority of the human microbiome and have received the most research are bacteria. They are essential for several body processes, including vitamin production, immune system control, and digestion. Particularly in the human gut, a wide variety of bacterial species, including Bacteroides, Firmicutes, Actinobacteria, and Proteobacteria, can be found. Hopefully, you can now understand that bacteria are not always harmful to our bodies, many strains of bacteria are very beneficial.

Viruses

COVID-19 Virus up close

When I say the word virus what is the first thing that comes to your mind? I would assume you think of COVID-19 because of how prominent the virus has been for the past few years but there are soooo many other viruses that reside on or in our body at all times, isn't that crazy?! The most prevalent viruses in the microbiome are bacteriophages, which infect and multiply inside bacteria. In the gut and other settings, bacteriophages are extremely prevalent and have the ability to affect the makeup and activity of bacterial communities. Viruses can also directly harm a person's health, for instance by interfering with their immune system. Viruses have many key jobs in the microbiome like viral diversity, bacterial regulation, horizontal gene transfer, and stabilizing human health.

Fungus

C. albicans italicize

The human microbiome includes fungi, which can be found in numerous species on the skin, gut, mouth, and other mucosal surfaces. The microbiome frequently contains the fungi Candida, Malassezia, and Aspergillus. While certain fungi are helpful and support a balanced microbiome, others can cause diseases in specific circumstances. Although fungi are not as major a part of the human microbiome as bacteria or viruses, their existence and interactions within the body nevertheless have substantial effects on human health, including the regulation of the immune system and the metabolism of nutrients. The greater function of fungi in the human microbiome is still being studied by many scientists.

Roles of the Human Microbiome

The human microbiome is responsible for many jobs inside and outside the body including digestion, immunity, and overall human health. Let's take a look at these different roles and see why they must be done correctly for the human body to function properly!

Digestion

Drawing of the gut microbiome

In the human body, digestion is greatly influenced by the microbiome, especially the gut microbiome. Complex carbohydrates, such as dietary fiber, are broken down into smaller, more digestible molecules by the billions of microbes that live in the gut. The breakdown of carbohydrates, proteins, and lipids is accelerated by these microorganisms because they create enzymes that humans lack. The gut microbiome ferments indigestible substances into useful byproducts like short-chain fatty acids, which fuel the cells lining the colon and promote colon health as a whole. Additionally, the microbiome assists in the synthesis of necessary vitamins and nutrients that the human body cannot generate, such as vitamin K and several types of B vitamins. The microbiome works with the immune system to maintain a balanced and healthy gut environment, reinforces the gut barrier to keep infections out, and helps the body detoxify toxic substances.

Immune system and immunity

The human immune system

In the human body, immunity is greatly influenced by the microbiome. The trillions of microorganisms that live inside and on top of our bodies have a strong relationship with the immune system, influencing how it develops, works, and reacts. The microbiome serves as an instructor, teaching the immune system to identify pathogens and react correctly while retaining tolerance to safe chemicals. This interaction lowers the risk of allergies, autoimmune illnesses, and other immune-related diseases by ensuring that immune cells mature properly and that immune tolerance is established. By fighting for resources and space, the microbiome also serves as a barrier against infections, driving them out and preventing their colonization. Additionally, the microbiome affects the generation and distribution of regulatory and T cells, two types of immune cells that help regulate immune responses.

How to keep your microbiome healthy

Now that you know what the human microbiome is and why it is so important for the well-being of all humans here as some great tips and tricks to keep your microbiome healthy and operating at peak performance! 

Fix your diet

Average balanced diet

Choose a variety of fresh produce, healthy grains, legumes, and other plant-based foods to include in your diet. These offer vital minerals and dietary fiber that feed the good bacteria in the gut. To encourage a diverse microbiome, strive for a varied diet. The microbiome's balance can be disturbed by eating a lot of highly processed food and sugar. Reduce your intake of sugary beverages, refined cereals, and processed foods because they can have a negative effect on microbial diversity and encourage the development of dangerous germs. Include fermented foods in your diet, such as yogurt, kefir, sauerkraut, kimchi, and kombucha. Live beneficial bacteria found in these foods can help replenish and diversify the microbiome.

Manage your physical health

Man running

Exercise frequently since it has been demonstrated to have a good impact on the microbiome's makeup. Exercise increases intestinal motility, which helps with waste removal and fosters microbial variety. To stay hydrated and support healthy digestion and microbial function, drink plenty of water. Water aids in the movement of nutrients, the elimination of waste, and the maintenance of the microbiome's healthy habitat. The general health of the microbiome is influenced by maintaining a healthy lifestyle, which includes regular sleep schedules, abstaining from tobacco use, and limiting alcohol intake.

Are You Smarter Than a Slime Mold?

Have you ever found yourself sitting on a subway train in New York City marveling at the subway system's astonishing efficiency? You ask yourself, "Who came up with all of this? This must have taken them forever!" With just a quick Google search, your curious thoughts would be proven true, as it did in fact take engineers years to create the subway system that shuttles millions of people around New York City today. While, yes, this is an impressive feat by engineers, what if you were told that a unicellular organism could map out the same route in just a small fraction of the time it took humans? Well, the species of slime mold, Physarum polycephalum , can do just that, and it's absolutely marvelous! 

The Experiment 

Through countless explorations of different ecosystems, scientists began to notice just how good this species of mold was at navigating through its environment to the nearest food source in the most efficient way possible. In an effort to investigate just how capable this slime mold was, Japanese scientists proposed an experiment. The slime mold was placed in the middle of an agar plate with oats placed throughout, arranged in the pattern of Japanese cities around Tokyo. 

Slime Mold Experiment

When presented with this scenario, the slime mold slowly began to create the most efficient route to each of its nutrient sources. When scientists took a closer look at what exactly the mold had done, they noticed the mold's route looked awfully similar to the current Japanese subway system route. When they compared the two, the scientists found the routes to be almost identical! Fascinating, right!? But how exactly was this unicellular organism able to carry out such a complex function?   

While the mere fact that this unicellular organism is able to carry out this function is quite impressive, once you begin to understand what exactly the mold is doing on a molecular level, the feat becomes even more remarkable. 

Slime Mold: What is it? 

The slime mold Physarum polycephalum is a eukaryotic , single-celled, soil-dwelling amoeba . That's right! It is NOT a fungus! Although it is commonly mistaken for one considering its ideal environment tends to be more damp and dark like many fungi. This species of amoeba follows a growth cycle that is far different from the one that we learned about in AP Bio this year. Instead of the growth of this organism being driven by cytoplasmic divisions and increased cell numbers, a cellular life cycle, it follows an acellular life cycle, as the organism continues to stay single-celled throughout its entire life regardless of how large it may grow. While the cell itself does not divide or multiply, the nuclei inside of the cell do. The cell is still undergoing the process of mitosis, however, it is skipping cytokinesis , allowing the cell to maintain its single-celled structure while still having the same amount of genetic material a multicellular organism would have. Ultimately, this species of slime mold grows to be a giant blob of a cell with many nuclei dispersed throughout. Although it may be surprising, the process of mitosis without cytokinesis happens in humans as well! Certain cell types in humans including osteoclasts (cells that break down bone tissue) and skeletal muscle fibers actually aren't very far off from this species of slime mold, as all three cell types undergo mitosis without cytoplasmic divisions.  

With this unique blob-like structure of the organism also comes quite a valuable function. After all, which I'm sure we all have ingrained in our heads by now (thanks Ms. Eckert!!), a change in structure equals a change in function! Since there aren't any barriers or walls separating any one part of the cell from another, fluids can very easily flow throughout the organism. This may be why the species is so good at navigating through complex environments, as important signaling molecules that signal the retraction or protraction of the organism are easily able to flow throughout the entirety of the cell. 

How Does It Move? 

While this species of slime mold may be good at maneuvering throughout its environment, it does not navigate the way many may believe it to. When told that an organism is good at navigation, many may make the assumption that the organism "knows" where it's going and where to turn in order to reach its end destination as efficiently as possible. While intuitive, this assumption is false! This particular organism does not have a brain to think like us humans. It is unable to make the conscious decision to turn left or turn right. Instead, the mold simply grows wherever it pleases, or at least initially it does. 

The mold first begins to grow throughout its entire environment, sending tendrils of itself out into its surrounding territory. Essentially, these tendrils help the mold to scope out where exactly the nutrient-rich spots may reside in its environment. Once the organism has found all of the nutrient-rich spots, it begins to retract the tendrils of itself that are connected to spots in the environment that do not contain as many nutrients, as this part of its territory is no longer of use to the mold. Slowly, the slime mold retracts all parts of itself that aren't necessary for survival, leaving behind the most efficient pathways to the most nutrient-dense spots in its environment. Isn't that just fascinating??! 

Where Can I Find It? 

Although the concept of a slime mold may seem foreign to many, it's actually quite likely that any Montclair resident would be able to find it in their own town! Hemitrichia serpula , Ceratiomyxa fructiculosa, and Lycogala epidendrum are just three of the many species of slime mold that can be found in New Jersey. One species, in particular, may even be mistaken for dog vomit! Yuck!! 

Dog Vomit Slime Mold

Although it may look like a dog has thrown up on the side of a tree, that foamy yellow goop is, thankfully, just a harmless species of slime mold!  This species of slime mold, Fuligo septica, can be found all throughout the world, usually congregating on bark mulch after significant rainfall or over-watering. Kinda gross, but pretty darn cool if I do say so myself! 

Sourdough Starter: The Living Fermented Dough Behind Sourdough Bread

Have you ever bitten into a warm, fresh piece of bread and wondered why it had a sweet and tangy taste? The answer is sourdough starter! This interesting fermented dough differs greatly from normal yeast that you buy at the grocery store, and has been a coveted baking ingredient for centuries. Sourdough starter was even brought to North America on the Mayflower! 

Sourdough bread has become largely popular in the last few years, especially with the large amount of time spent at home during lockdown, due to the Covid-19 pandemic. Many people have created their own sourdough starters, and even given them names! Although I do not have a name for my starter, I enjoy sharing my sourdough creations with my family. After all, food it a great way to socialize with others! 

As a baker myself, I have found sourdough starter to be a very unique way to spice up different yeasty recipes. I use my sourdough starter for much more than just bread---sourdough discard adds an incredibly fluffy texture to pancakes, and can even add a delectably tangy taste to pizza dough! Also, sourdough starter exhibits the incredibly intriguing process of fermentation, but not the type of fermentation that occurs when you workout. 

Sourdough Starter and Sourdough Bread

What is sourdough starter?

Sourdough starter is synthesized from a combination of flour and water, which ferments over time. Flour contains wild yeast, so when the flour is combined with water, the mixture captures the yeast and brings it to life.  In order to keep the yeast alive and thriving, the starter is fed everyday by creating a levain. A levain is a mixture of flour and water with a little bit of the sourdough starter. It is important to not add too much starter to the levain. This ensures that the yeast all have enough to eat, and are not competing for food. 

Although sourdough starter contains wild yeast, there are many different types of yeast sold in commercial stores, such as instant yeast, active dry yeast, and fresh yeast. Each type of yeast is marketed for a different purpose. For example, active dry yeast is composed of dehydrated yeast granules, which are dormant, similar to a seed produced by a plant! On the contrary, instant yeast is composed of smaller dehydrated yeast granules, which means that each granule has a larger surface area, and therefore blooms faster. Fresh yeast is most similar to sourdough starter because it has not been dehydrated, and is rather a dried mixture of flour, water, and yeast, which are the exact ingredients of sourdough starter. 

Sourdough Starter

What are the benefits of eating sourdough bread?

Unlike many other types of bread, the natural yeast in sourdough starter makes it a healthier option. The probiotics in the starter promote gut health, which means that the bread promotes better digestion. According to EatingWell.com, sourdough bread promotes a better digestion of gluten, due to the process of fermentation in sourdough starter, which contains specific enzymes that aid in the process of breaking down gluten. Sourdough bread is also a good source of vitamin B12, along with folate, which is an important vitamin for pregnant women. 

How does sourdough starter work?

Fermentation is a form of anaerobic respiration, which means that it occurs in the absence of oxygen, therefore differing itself form aerobic respiration. The yeast within the starter feeds on flour by using enzymes that convert the flour into sugars. During cellular respiration, the sugars go through glycolysis, which produces some ATP and pyruvate. The pyruvate then goes through oxidative phosphorylation, where it is converted into Acetyl-CoA. The Acetyl-CoA then moves to the Krebs Cycle, where some ATP is produced, and then goes on to the final stage, the electron transport chain. This metabolic process produces molecules of carbon dioxide, which are held within the gluten strands of the dough, and cause the dough to rise. This carbon dioxide production is the reason for the holes and bubbles in bread. 

The tangy taste behind sourdough bread is a result of fermentation. Yeast goes through alcoholic fermentation, which largely contributes to the taste of the final product. Fermentation occurs when pyruvate, the product of glycolysis, releases carbon dioxide, which then produces acetaldehyde. The acetaldehyde is then phosphorylated from the hydrogen ions from NADH, creating ethanol.

Although yeast uses alcoholic fermentation, a different type of fermentation is greatly utilized by humans. This process is known as lactic acid fermentation. Lactic acid fermentation differs from alcoholic fermentation in that it produces lactate from glucose and other six-carbon sugars. Lactic acid fermentation occurs when cells run out of stored energy, such as ATP or glucose. The body begins lactic acid fermentation in glycolysis, where glucose is converted into pyruvate. The pyruvate then goes through lactic acid fermentation, where NADH is phosphorylated to produce lactic acid, which is then used as an energy source. 

 

The metabolic process of yeast fermentation

When making sourdough bread, it is important to not overproof the bread (let it rise for too long). Over proofing will cause the bread to collapse in the oven because the yeast has eaten through the gluten strands that give structure to the bread. Over proofing will also lead to a stronger fermented taste because more ethanol has been produced. An over fermented dough has a very sour taste, which is not very appetizing. 

Once the sourdough bread has been put in the oven, the yeast increases its metabolic process, which produces more carbon dioxide and causes the bread to rise even more. Once the bread becomes too hot, the yeast dies off, leaving behind large pockets of carbon dioxide. 

Unlike other breads, it is recommended to allow sourdough bread to completely cool before digging in. The high water content within the dough greatly contributes to the cooking of the bread, which creates an airy bread. When the bread is cut into while hot, the cooking process is cut short, resulting in a gummy texture. 

Bats: Reservoir Hosts and Zoonotic Viruses

A grey headed flying fox in flight

Traditionally viewed as harbingers of death or vampires in disguise, the true capabilities of bats are commonly overlooked. Personally, I've never viewed them as scary, in fact, I'd say that they are my favorite animals. Growing up, I'd always see bats flying around during warm summer nights, which is where my interest in bats began. The few characteristics that are generally recognized as common knowledge about bats—being the only flying mammals, sleeping upside down, and using echolocation—do not accurately showcase the role of bats in the ecosystem. In actuality, I believe that their most fascinating trait revolves around one thing: their ability to carry and transmit viruses. 

Background

Bats are a keystone species in their ecosystems. They are responsible for controlling insect populations, seed dispersal, and pollination. They are also extremely diverse--there are more than 1,400 species of bats and they span across many geographical regions. Bats live in large groups called colonies. These colonies can consist of around 30 to thousands of bats of the same species. Due to the the density of their living situations, many deadly viruses are often transmitted among the colony. However, unlike humans, bats rarely show clinical symptoms. 

What is a Zoonotic Disease?

Zoonotic diseases are defined as infectious diseases that are transmitted between species (from animals to humans or vice versa). Well known zoonotic diseases include rabies, encephalitis, monkeypox, or salmonella. In epidemiology, a reservoir is the habitat where the virus is sustained and is able to multiply. Two common types of reservoirs are human reservoirs and animal reservoirs. Bats are an animal (obviously) reservoir—and a very common one at that. In fact, bats carry more zoonotic pathogens than any other animal reservoir. 

A diagram of epidemiological relationships

The Role of Bats as Reservoirs

Why are bats able to tolerate viruses that decimate human populations? This can be explained by a few major differences.

In all immune responses, the first step, or the innate immune response, refers to the expression of pattern recognition receptors. Once these receptors identify a foreign pathogen, they signal for the expression of antiviral cytokines, which will lead to the expression of genes that induce apoptosis—programmed cell death—in infected cells. Among these cytokines are interferons, also known as IFNs. In many bat species, IFN regulatory sites have evolved to enhance the innate immune response. This includes being expressed in more tissues or enhancing the expression of the final antiviral cytokine response. 

Additionally, when humans become infected with a viral pathogen, their immune system activates an immune response in an attempt to combat it. However, when bats are faced with a similar situation, many times, their immune responses are less effective and much weaker than a human's. This may seem like a completely contradictory statement, but it actually gives bats an advantage. The validity behind this paradoxical statement actually relies on a bat's response to inflammation. IFN-α is protein that leads to inflammation. Unlike other mammals, bats express IFN-α at a constant rate. Bats have evolved to counteract the inflammation caused by this protein. Humans cannot do this, which is why our immune systems rapidly produce immune responses to combat infection. This approach may lead to widespread inflammation that can eventually lead to death. 

The unique gene expression of a bat

All of this information leads us to one main question. Why have bats evolved this way?

In the introduction of this post, I mentioned how bats are the only flying mammal. This is where one the answers to this question lies. The ability to fly requires very different metabolic activity than the normal mammal. If bats retained a similar immune system to humans, everytime they tried to fly, the spike in activity and rise in temperature would cause widespread, debilitating inflammation. Part of the immune system of bats evolved to develop alongside their ability to fly. 

Another answer to this question is quite simple. Since bats live in large colonies and usually inhabit enclosed spaces, the spread of infection and disease among bat populations is very high. Bat's immune systems evolved as a response to their constant exposure to widespread disease. 

Conclusion

After discovering all of this information, you may not be surprised to learn that bats have an extremely high body size to lifespan ratio. Their ratio is even larger than that of a human. Their unique immune systems benefit them as a collection of species, however, they also benefit the entirety of the human race. Scientists can analyze their adaptations and their evolutionary pathway to attempt to strengthen the human immune system or even to try and increase human lifespans. Next time you spot a bat (they are all over Montclair) in the wild, remember that while they may not have the powers of Dracula, they have their own pretty cool version of a superpower. 

Salem Witch Trials: Black Magic or Bad Bread?

As described by my history teacher, the Salem Witch Trials were a low point in our country's history, an example of intolerance and injustice which specifically targeted women. Having visited Salem, Massachusetts as a kid, I became engrossed in the history of the trials, wondering not only how these people could have been prosecuted with so little evidence, but what caused their symptoms of "bewitchment"? The belief that Salem's residents' afflictions were due to supernatural causes did not make sense to me, as an association with the devil seemed to be something that only happened in The Conjuring, not in colonial Massachusetts. Never having believed the "devil's magic" as causing such violent madness of the people of Salem, I searched for a more reasonable explanation. 

The Witch Trials

In the late 17th century, the people of the Puritan village of Salem were plagued by a multitude of worries. In addition to the harsh reality of life in colonial New England, they feared an attack by the neighboring Native Americans. They also suffered the effects of the war between Britain and France fought in the colonies, and experienced tumultuous times in politics as a new royally-appointed governor sought to create changes that the Puritans opposed. Colonial New Englanders were inclined to blame everything they perceived as strange or unpleasant on some aspect of their religion - they always had a Bible verse as an explanation. 

As early as the 14th century, the belief in the supernatural, and the ability of witches to cause harm emerged in Europe and soon became widespread in colonial New England. The second capital crime of the colonists' legal code was witchcraft, which detailed that any person suspected of witchcraft could be sentenced to death. 

In the winter of 1692, the 9-year-old daughter and 11-year-old niece of Samuel Parris, minister of Salem Village, began having "fits." They barked like dogs, complained of invisible hands pinching and biting their skin, had wild outbursts of screaming, fell into trances, and had violent reactions to prayers or religious sentiments, with one of them once hurling a Bible across the room. The local physician could not find any physical cause for their condition, and pronounced that the girls must be suffering from "the evil hand." Friends of the girls soon began to exhibit similar symptoms, and neither prayer nor medicine seemed to help them. The only other explanation the villagers could come up with was that their suffering was caused by witchcraft, and people of the village were accused of bewitching the girls. Hysteria spread throughout the colony, many people were accused and a special court was established to hear the cases of witchcraft. In the end, 200 people were accused, 30 of them found guilty, and 19 people were hanged for their practice of witchcraft. 

Illustration of a courtroom during the Salem Witch Trials

Alternative Explanation

In 1976, Linnda Caporael, now a behavioral psychologist, offered an alternative hypothesis to explain the afflictions of the "bewitched" girls of Salem. Her work claimed that the hallucinations the "bewitched" suffered from were actually caused by a case of ergot poisoning. 

source

Ergot is a plant disease caused by the fungus Claviceps purpurea which can affect rye, wheat, and other types of grain. When a plant is first infected, it will spew out a sweet mucus called "honey-dew" that contains spores and attracts insects, so that the spores can be transmitted to other plants. As the fungus grows, it replaces kernels of the infected grain with sclerotium which contain chemicals of ergot alkaloids such as lysergic acid, which is used to make LSD, and ergotamine, which is now used to treat migraines. Eating grain contaminated with ergot can lead to many symptoms recorded during the Salem Witch trials: muscle spasms, hallucinations, and feelings of things crawling on the skin. 

Grain containing a claviceps purpurea sclerotia

Lysergic acid diethylamide, also known as LSD, is a potent psychedelic drug which can produce changes in perception, mood and thought, and can cause a user to experience hallucinations. LSD is made from the lysergic acid found in the sclerotium of grains infected with ergot.

LSD works by binding to proteins on brain cells called serotonin receptors. Serotonin is a chemical messenger that carries messages between cells in the brain and throughout the body. It helps the brain send messages to control mood, emotions, and digestion. By binding to these receptors, LSD alters the neural pathways, which can cause the hallucinations and "trips" of people who have taken it. Part of the serotonin 2B receptor acts as a lid, trapping the LSD molecule to the receptor, which is why "trips" under the influence of LSD can last so long.

 

Molecule of LSD bound to a serotonin receptor

Ergot thrives after warm and rainy springs and summers, exactly the conditions reported in the diaries of Salem villagers from 1691. Most of the afflicted people of Salem lived in the western section of Salem Village, which consisted of swampy meadows, ideal for the growth of ergot. Rye was a main crop of Salem Village, widely consumed, mostly in bread. Farmers may have ignored the dark kernels of the infected rye as being due to sun damage, and sent the poisonous grain to the mills to be processed and consumed. The villagers in the western section of Salem were at greater risk of consuming the poisonous grain, as confirmed by the higher percentage of afflicted people in that section. 

Map of the distribution of the bewitched/accusers (A), witches (circled W), and the defenders (D)

Linnda Caporael concluded that the "bewitched" girls had been poisoned with ergot. The symptoms of ergot poisoning, including convulsions, hallucinations, and muscle spasms, are consistent with those observed in Salem. However, there are likely other factors unrelated to ergot that contributed to the events in Salem. The villagers of Salem likely also suffered from mass hysteria, and as a result, went along with the accusations and added their own. 

Prions! What are these dangerous little things?

 

The cover of the science fiction novel Aurora, by Kim Stanley Robinson. It includes a plot line about prions rendering a planet uninhabitable to humans.

I first heard about prions when I read the science fiction novel Aurora by Kim Stanley Robinson, which details the journey of a spaceship that successfully reaches another planet (yay!) where (spoiler alert!) there are prions that infect and kill the would-be settlers, rendering the new planet inhospitable. At first, the settlers are unable to figure out what is causing the illness. People seem to be getting sick and dying without any clear cause. Eventually, though, they figure out that a "prion-like organism" is the culprit. So, what exactly are prions? And how could they pose such a great threat to living things?

To start with, prions are generally understood to be misfolded proteins with the ability to transfer their misfolded shape to other proteins of a similar kind. The mechanisms of this shape transfer are not exactly clear, but there are studies being conducted to uncover the process by which proteins can be corrupted. Proteins are the very basic building blocks of living things, and their shape directly determines the functions they will have in a living thing. This shape is determined by the DNA of the organism, and the amino acid sequence that forms the different structures of the protein. All this is a bit complicated, and involves a lot of moving parts! The important takeaway is that proteins need to be functioning correctly for an organism to continue living without complications. When proteins are unable to respond to signals, catalyze reactions, or provide structure and support to the body, things begin to break down. 

A beautiful cow, which appears to be grass-fed, and has probably not ingested any dangerous prions. 

When there is a problem with the shape of a protein, and especially if that problem is spreading to more prion proteins throughout a part of the organism, the effects can be devastating. One disease you may have heard of is mad cow disease, also known as bovine spongiform encephalopathy (BSE). When cows consume feed that contains parts from another cow that was infected, the prion proteins can be taken into the body, where they slowly affect the brain tissue of the cow, causing it to take on a sponge-like texture. It takes several years for the disease to spread enough that it is noticeable in the behavior of the cow, but by the time they are having trouble walking or showing a change in demeanor, they are likely to die in the next few weeks or months. A concern for humans involved with managing and caring for these animals is that there is currently no way to test for BSE while the animal is alive. Luckily, it seems that prions cannot be transferred through bodily fluids or aerosols, like other kinds of diseases. 

Research so far has shown that prions appear to mostly cause neurological diseases in mammals, both humans and others. The diseases tend to have long incubation periods, sometimes several years, and result in degeneration of brain tissues and function, and eventually death. In this way, real-life prions are very different from those described in Aurora, which killed people within months. But before you get too worried, let me remind you that prion diseases, although almost certainly fatal, are extremely rare in humans. The most well-known and well-researched, Creutzfeldt-Jakob disease, occurs in only about one in a million people each year worldwide. Although unrelated to BSE, Creutzfeldt-Jakob causes a similar degeneration of the brain, including the characterization of a sponge-like texture in the brain tissue of those affected. 

A human brain with Creutzfeldt-Jakob has a sponge-like texture (image courtesy of the Centers for Disease Control and prevention)

A cow brain with BSE, also known as mad cow disease, which also exhibits sponge-like lesions (image courtesy of the Food and Drug Administration) 

Prion diseases, like the aforementioned Creutzfeldt-Jakob disease, the creatively named Variant Creutzfeldt-Jakob disease (vCJD), and others such as fatal insomnia, are divided into three subcategories: sporadic, genetic, and acquired.

Sporadic cases of the disease, also sometimes referred to as "classic" cases, do not have an identifiable cause, and the people affected do not have any known risk factors. This is the most common form of CJD, and it usually affects those over 60. Fatal insomnia is another sporadic prion disease, whose symptoms include insomnia and difficulty waking--it eventually leads to loss of consciousness and death. 

Genetic prion diseases are less common and occur either when a new mutation happens or when the gene for the malformed protein is passed down from the parents. In addition to familial CJD and familial fatal insomnia, this category includes Gerstman-Sträussler-Scheinker syndrome, an autosomal dominant change in a prion gene that usually exhibits itself in people aged 35-55. The disease progresses from lack of muscle coordination to more serious symptoms like dementia, blindness, deafness, and ultimately death. GSS syndrome is extremely rare and occurs in less than thirty families worldwide.

The final category, acquired prion diseases, describes diseases that occur when the person suffering from the illness acquired it through contaminated medical procedures, or from consuming meat that was contaminated. A variant of CJD in humans is thought to be caused by eating meat from a cow that had mad cow disease. An outbreak of this variant occurred in the United Kingdom in the 1980s and 90s and is thought to be caused by the use of animal remains in cattle feed, allowing prions to spread from the remains of an affected animal to a living cow, and then potentially to humans who ate the meat from that cow. 178 people died from eating the infected beef, and over four million cattle were subsequently slaughtered in an effort to control the outbreak. In the United States, the importation of British cattle was banned, and many recently imported cattle were slaughtered. Finally, the acquired prion disease Kuru reached an epidemic level in a tribe in Papua New Guinea that partook in cannibalistic rituals for the dead that involved eating their brain. The outbreak persisted until they ceased to perform those rituals. Acquired prion diseases are extremely rare in the global population, and the risk has drastically decreased as regulations are instituted and medical procedures are done in a more sanitary way. 

An image of some members of the Fore tribe, where the Kuru disease affected many people.

With all this information about how dangerous prion diseases can be, and how little we really know about them, it's easy to be disturbed or worried. Fear not! The risk of these diseases in humans is very low, and the likeliest thing is that you won't even know someone with one of these diseases in your lifetime. Additionally, there is some interesting new information from a research study by Stanford that suggests prions may also play a role in the inheritance of beneficial traits, and in evolution. Due to their ability to pass down traits to other proteins, prions can contribute to genetic variation, which is an essential part of evolution and the survival of a species. This study, in particular, focused on protein-based inheritance in yeast, but the information learned could be applicable to humans as well and could help further the ability of medical professionals to identify diseases and treat those who are ill. 

Bacteriophages: The Future of Infection Treatment?

Let me first set the stage for you by talking about two of my least favorite things on the entire planet: mosquitoes and viruses.

Female Culiseta longiareolata (via Wikipedia)

Coronavirus illustration (via FDA.gov)

Doesn't just looking at them give you the heebie-jeebies!? The mosquito's creepy proboscis (its "straw") and the ominous feeling that even just staring at a virus gives you are bad enough, but what if I told you that there was a biological entity that combined these two oh-so-wonderful things? Allow me to introduce to you: the bacteriophage!

Bacteriophage structure (via istockphoto)

 

 

 

Measuring in at a whopping 24 - 200 nm (that's about 1/500th the width of a human hair), the bacteriophage is a special type of virus composed of genetic information (either DNA or RNA) encased by a protein shell, complete with a rather eerie-looking tailpiece, and some even have filaments! Bacteriophages, or as I like to call them "the phage" (it is true, though, that they are often referred to simply as "phages"), are some of the most abundant biological entities to exist on the planet, with there being roughly ten phages to exist per host cell (give or take). There’s about five million trillion trillion bacteria on our planet (that’s 5 ✕10³⁰, or 5 and thirty zeroes -- approximately 667 billion times more than the number of grains of sand on Earth); take that number and multiply it by ten, and that’s how many phages we’ve got hanging all around us!

Scientific animation of a T4 bacteriophage (via XVIVO)

 

 

 

 

 

 

Now, before I get too carried away talking about these creepy little phages, I think we should take a moment to analyze what the word “bacteriophage” actually means. As you can probably guess, “bacterio” stems from the word “bacteria” (you know, those little prokaryotic organisms that are just about everywhere and are honestly pretty darn cool?), but “phage”, which might be a little more foreign to you, originates from the Greek word “phagein”, which means “to eat”; that means that bacteriophages “eat” bacteria! (If you’re interested in reading a bit more about the etymology of the bacteriophage, have a little looksie here!) Now, all this to say that bacteriophages are harmless to people and do NOT affect us! This means that you can keep on reading this blog post without the lingering worry in the back of your mind that phages are going to take over the world one day! With that thought out of your mind (as I’m sure it was), let’s get into some of the nitty-gritty science of these impressive little viruses: 

 

 

 

 

Bacteriophages infecting a cell (via shutterstock)

As I mentioned earlier, bacteriophages are a specific type of virus. To reproduce and infect more hosts, as viruses do, the phage inject their genetic information into their target cells (which are all bacteria), and undergo either a lytic or lysogenic reproductive cycle. While I won’t go into too much detail about these two processes (although you’re welcome to read about them here), the gist of it is that a lytic cycle results in the violent death (via explosion) of the bacterial host cell, while the lysogenic cycle allows for a more silent reproductive path that enables the proliferation of the virus without impacting the host cell too much; this is accomplished through integration of the virus’ DNA into the host cell’s genome (though, after a certain point a lysogenic cycle often turns into a lytic cycle and the bacterium bursts). The purpose of these reproductive cycles is to force the bacterium to synthesize parts of the virus that can later assemble into new, full-fledged bacteriophages that can then go on to infect more cells. This happens because the most basic goal of all life on Earth (and life-akin entities such as viruses) is to reproduce. Since viruses can’t reproduce on their own, they need other cells to produce the proper components of a virus so that they can continue infecting other cells. The phage accomplish this task through the passage of their genetic information stored in either DNA or RNA to a host bacterium, which then undergoes translation (or transcription and translation if the phage contained DNA), and finally the host cell produces a protein. Once enough proteins are made, they accumulate at the cell membrane and assemble into new bacteriophages, then exit the bacterium once the cell bursts. 

Transduction (via springernature.com)

This hijacking of bacterial machinery often results in a form of horizontal gene transfer called transduction. Normally when we think about the passage of genetic information, we think of vertical gene transfer -- that’s the normal (and rather boring) story of how genes are passed down “when a mommy loves a daddy”, but there’s actually a completely different and fairly common method of gene transfer that accounts for up to one-third of a bacterium’s genome. This is what is known as horizontal gene transfer. Horizontal gene transfer occurs in four primary ways, but I’m only going to focus on transduction in this post (although, if you’re just super interested in horizontal gene transfer and want a quick overview, this Khan Academy article is for you!). At its most basic level, horizontal gene transfer is defined as “the non-sexual movement of genetic information between genomes”, meaning that the forced uptake of DNA by bacteria can, in fact, be a form of gene transfer even though the genetic material did not come from parent cells. In transduction, genetic information from one bacterium is transferred to another bacterium by a virus. Oftentimes, this transfer is accidental and happens when a bacteriophage contains some genes from a host cell that got packaged into its capsid head by mistake. These genes are then implanted into the phage’s next victim after it injects its virulent genetic information into a new host. When the foreign DNA is integrated into the host cell’s genome, the DNA from the first bacterium becomes part of the new host cell’s genome, and thus the host’s genome is different than it was before. It’s kind of crazy to think that these little alien-looking viruses are a huge source of genetic variation in our world, especially by accident, but they are!

Antibiotics (via flickr)

 

 

Now, as interesting as I think bacteriophages are, I’ve recently been informed that most people don’t find learning about viruses, and their structures, and their purposes, and their methods of gene transfer to be the most enthralling thing ever. So, I figure it’s about time I talk about why these little suckers are so important to us as people. Prior to the discovery of the first antibiotic in 1910, and the later groundbreaking discovery of penicillin in 1928, humans were subjected to bacterial infections that could render us very dead, very quickly. Many of these same infections, however, are now easily treatable with antibiotics -- or at least they were. As overuse of antibiotics for minor infections has become more prominent, and as bacteria evolve to resist our antibiotic treatments, superbugs (which are bacteria “resistant to most of the antibiotics … commonly used to treat the infections they cause”) and the onset of an antimicrobial resistance crisis have become of great concern to our society. One solution that scientists have turned to in order to combat the growing issue of widespread antibiotic resistance is phage therapy. In phage therapy, specially engineered bacteriophages target specific bacterial cells and obliterate them, thus clearing them from the human body. This is beneficial for many reasons, namely that the phage do not target human cells, they do not need to be constantly injected into patients, all bacteria are known to lyse from some sort of phage, and, since they’re naturally occurring, bacteriophages can evolve right alongside the ever-changing bacteria, allowing them to remain effective for longer periods of time. Aside from the biological pluses of phage therapy, this treatment has also been shown to reduce the cost that patients must pay for life-saving treatments. (If you’re interested in learning about phage therapy a bit more in-depth, I HIGHLY recommend watching the above video!)

 

Two scientists in a bacteria phages lab. Photograph: Aimee Obidzinski. https://www.theguardian.com/science/2022/may/13/phage-therapy-fight-against-drug-resistant-infections-antibiotics

There are, unfortunately, some barriers that make phage therapy a less viable treatment option than, say, antibiotics. Many of the issues with phage therapy arise from the fact that it has not been studied in depth by most countries, so its long-term effects and practicality are largely unknown. Here’s what we know so far, though: while phages being specific to bacteria is a benefit since they protect human cells from unnecessary damage, this also means that it’s harder to find bacteriophages that fight specific infections since they have to be able to perfectly match with a given bacteria. This causes a delay in phage selection, and can make it more difficult to target a specific type of bacteria. The issue that's been most concerning during the course of phage therapy research is that, since they are viruses and do possess many characteristics of life, bacteriophages can evolve and change during the time they are being studied, administered, or even while they’re inside a person, posing possible risks to the study that could jeopardize the future of phage therapy. There are, however, numerous studies being conducted that seek to investigate the best way to further pursue phage therapy and determine the safest, most effective way to administer the phages to humans. A series of experiments conducted in Paris earlier this year explored many of the lesser-understood factors of phage therapy, including the impact of how the viruses are put into patients, as well as details about the viruses themselves (ie: how quickly they infect bacteria, grow, and complete the lytic cycle). The findings of the study are promising, and open the door to quicker, more in-depth, and less expensive research into phage therapy.

So, to recap: bacteriophages are viruses; phages increase genetic variation among bacteria; the phage do not harm humans, and can instead help us combat antibiotic resistance.

Now, that was a whoollllleeee lot of reading, so, as a reward, I’m now going to grace you with a couple of my favorite bacteriophage memes that I found over the course of my research (and before you ask: yes, phage memes constituted approximately 25% of the time I spent writing this blog post!).

Phage meme (via Facebook)

(Nicolas) Cage on the Phage (via ASAP Science)

My final wish for you, my dear reader, is that you’re leaving this little biology rambling of mine with a love for bacteriophages just as strong as mine. I adore these strange, alien-esque, non-living entities so much so that I have set out to crochet one of my own. I’m not very far into it, but I’ve got the capsid head done, which I’ve attached here for your viewing pleasure. I bid you a final farewell, my fellow science lover!

Crochet capsid head