These poems often speak of love and lust, Words gushing from the pens of Romeos. The desperate hearts of poets beat and bust Out of their chests, and like their words, blood flows,
Fast from their aching heart’s aortic arch The largest coronary artery From there the blood begins its coursing march It rushes on like nimble Mercury.
When blood’s arterial adventure ends, The veinous system beckons it back home. The vena cavas let the blood transcend Back to the body’s heart-shaped hippodrome.
The poet’s inner workings do impart That life is often similar to art.
Artificial flavors aren’t always as scary as they’re made out to be
Forget the autumnal equinox; Americans have come to associate the beginning of fall with the annual roll-out of all things pumpkin spice. Even if you’re like me and find Starbucks’ famous PSLs too cloying for your taste, you probably enjoy the aroma of pumpkin spice in some other form, whether that be in a homemade baked good, mulled wine, or a scented candle. Pumpkin spice’s popularity is inextricably linked to the holiday-time nostalgia that many people, particularly Westerners, associate with the aroma of a freshly baked pumpkin pie. Our perception of flavor is heavily influenced by memories of past experiences involving that flavor, such as where we consumed it, what we were doing, who we were with, even the color and appearance of the food. When that flavor is then isolated and mixed into your Starbucks latte, all of those warm fuzzy feelings associated with the pumpkin spice flavor come rushing back, resulting in a positive reaction to the taste of the drink. The psychology of pumpkin spice’s popularity is more broadly understood than the actual chemistry that goes into creating pumpkin spice flavoring. What exactly is in pumpkin spice flavoring that makes it taste so much like the real thing?
Secret (Pumpkin) Sauce: Volatile Compounds
Despite the negative connotations associated with PSLs for being “artificial”, they taste so much like the real thing because chemically, they pretty much are the real thing. The main flavor notes in a pumpkin pie, as well as many other autumnal treats, are cinnamon, nutmeg, clove, and allspice. These four spices are the same main flavor notes incorporated in industrially produced pumpkin spice flavor packets. Rather than use spices in their ground form, food industry-grade pumpkin spice flavor is created using nature-identical flavor molecules. “Nature-identical” molecules are compounds that are chemically identical to an ingredient found in nature, but are produced synthetically in a laboratory1.
In their natural form, ingredients that create flavors and aromas aren’t just one compound; they’re composed of hundreds of chemicals. For example, take cinnamon. The cinnamon plant, like any other plant, is a conglomeration of hundreds of chemical compounds. Even hydrodistilled cinnamon bark oil isn’t just “cinnamon”; it’s composed of over 17 chemicals. But when we think of “cinnamon”, we don’t think of bark oil, or even the cinnamon plant as a whole. We think of the warm, rich flavor of cinnamon. In order to replicate that flavor, not all 17 chemical compounds of cinnamon bark oil are essential. Of the many chemicals found in the natural ingredient, only a couple contribute to the overall flavor or aroma of the ingredient2. In the case of cinnamon, cinnamic aldehydes are the chemical compounds that give cinnamon its characteristic flavor and smell.
An original drawing by yours truly…currently accepting volunteers to sketch my horrible puns
Similarly, just a small handful of compounds make up the major flavor notes that we associate with the natural ingredients of nutmeg, cloves, and allspice. The cute little chemical structures of eugenol and sabinene (pictured below) are mainly responsible for the big flavors we know as nutmeg and cloves, respectively3.
Eugenol
Sabinene
How can these little chemicals pack such a big punch when it comes to flavor? One thing that many flavor-contributing compounds have in common is that they are volatile compounds. Volatile compounds are compounds that vaporize easily4.
When we describe a person as “volatile”, we mean to say that they are unstable, or have a quality that rapidly and unpredictably changes. Volatile chemicals can be described in the same way; they have a characteristic that is unstable, which contributes to their ability to rapidly change from liquid to gaseous form. Take another look at the chemical structures of cinnamaldehyde, eugenol, and sabinene. The configuration of atoms and chemical bonds in a structure informs us of the chemical’s intermolecular forces, or forces holding a molecule together. Bonds between two hydrogen molecules are particularly strong.
What does hydrogen have to do with your PSL, you say? Bonds between hydrogen bonds are attractive forces that hold a molecule together. The fewer potential hydrogen bonds that a chemical can form, the less energy it takes to break those bonds and allow the molecule to vaporize. Chemicals that are easily vaporized, or emitted from a food matrix, in turn easily contribute to the major aroma notes of a food product.
Cooking is an Art, Baking is a Science
If pumpkin spice is a combination of cinnamon, nutmeg, cloves, and allspice, then why is it so difficult to create that specific PSL flavor at home? That’s because pumpkin spice flavor mimics the aroma of a baked pumpkin pie. A pumpkin pie doesn’t smell or taste nearly as good when it’s just uncooked batter sitting in a pan, as opposed to when it’s fresh out of the oven. Baking a pie is a chemical reaction that manipulates the chemical structure of food ingredients, releasing aromatic products in the process. Your kitchen is basically just one big science lab. Any type of heat-based cooking process, such as frying, baking, or broiling, physically changes the chemical composition of the ingredients being subjected to said cooking process. This increase in temperature alone is enough to vaporize volatile compounds found in food, and release the aroma of the heated ingredient. Additionally, baking a pumpkin pie is a chemical reaction that releases flavor notes that can’t be extracted from the raw ingredient as it’s found in nature. Baking a pie is a heat-facilitated reaction between the sugars and proteins of the pie ingredients. This reaction, known as a Maillard reaction5 in the chemistry world, releases products that give off aromas associated with caramelization or freshly baked bread.
The Maillard reaction is essentially the chemical process of caramelization. As an example, in order to create the flavor and smells associated with brown butter, butter and brown sugar need to be heated for a given amount of time as opposed to just being added in with the rest of the ingredients. Similarly, in order to truly capture the aroma of a freshly baked pumpkin pie, Maillard reaction products are just as critical to include in the pumpkin spice flavor packet as the core ingredients of cinnamon, nutmeg, and cloves.
Maillard reaction products can be synthesized in a lab and are added alongside cinnamon, nutmeg, cloves, and allspice, to food industry-grade pumpkin spice flavoring. In order to recreate a natural flavor in synthetic form, flavor chemists need to consider the high-level essence of the flavor. The incredibly nuanced profession of flavor chemist is just as creatively complex as it is technical.
Gas Chromatography
Flavor chemistry as we know it today is possible because of the 1952 invention of the gas chromatograph6, an instrument that separates compounds that can be vaporized without decomposing.
Chromatography is a general term that refers to the process of separating parts of a mixture. Specifically, gas chromatography is the process of converting a mixture into gaseous form, and then separating the components of that gaseous mixture. Because so many flavors and aromas come from volatile compounds (compounds that easily vaporize), gas chromatography is a great analytical tool to apply to the study and production of flavors and fragrances.
Chromatographs (machines that perform chromatographic separation) separate mixtures by forcing the mixture to move through a medium in which the components move at different speeds, due to different components binding more or less strongly to the medium. All types of chromatography have two types of phases, or parts that aid in separating mixtures; stationary phases and mobile phases. Stationary phases are materials, often resins or packed beads inside of a column, that attract different components at different rates. Mobile phases are gasses or liquids that flow through the instrument at the same time as the sample, and help carry the sample through the stationary phase. The balance between the stationary and mobile phases causes certain components to bind more strongly to, or move more slowly through, the stationary phase, which ultimately separates the components by causing components to come out of the column at different times.
In the case of gas chromatography, a mixture is injected into a hot sampler port. The high temperature of the port vaporizes any samples that aren’t already in gaseous form.
The mobile phase is an inactive carrier gas, like helium or nitrogen, that transports the gaseous sample into a column.
Inside the column is the stationary phase, usually coated with an adsorbant solid. As the carrier gas pushes the sample molecules through the column, different components of the mixture adsorb onto the stationary phase at different rates, eventually reaching the end of the column at different times.
At the end of the column is a detector which records the time and relative amount of each component after it is separated.
The detector creates a picture of the relative separation of components in a mixture. Is it an ugly picture that looks like a four year old just scribbled a bunch of lines on a paper? Yes, but properly resolved chromatograms (think “Instagram”; chromatograms are pictures of chromatographic data) can give us lots of valuable information. Below is a gas chromatogram of cinnamon essential oil. Each peak is a different component or molecule inside the larger mixture that is cinnamon essential oil. This is why flavor chemists focus on the handful of molecules that contribute to a food’s flavor, as opposed to recreating the entire thing; can you imagine synthesizing all 26 compounds in this chromatogram7?
However, at the end of the day, chromatograms are just pictures. From images alone, there’s no way to know exactly what each peak and line represents. Once a mixture is separated, flavor chemists (as well as scientists in the many other fields that utilize gas chromatography) identify each separated component, most often through a mass spectrometer detector. Mass spectrometry is an incredibly powerful tool with mechanisms that would be incredibly difficult to describe without putting all of you readers to sleep. It also isn’t necessary to understand the physics of the inner workings of mass spectrometry in order to understand how mass spectrometer detectors work on a high level (fine print: physics is not the author’s strong suit).
After gas chromatography separates a mixture into its individual components, a connected mass spectrometer ionizes and fragments these separated components. The fragments can then be identified by their mass-to-charge ratio. Large mass spectral libraries containing mass-to-charge ratios of known compounds are used as references to identify the components in the analyzed mixture. (If you’re interested in learning more about the basics of mass spectrometry, Explain that Stuff has a great article to get you started: https://www.explainthatstuff.com/how-mass-spectrometers-work.html ).
The Nose Knows
There is one more detector that is commonly used for industry-grade identification of aroma-inducing compounds. The olfactory detector, when coupled with gas chromatography, forms the highly sophisticated analytical assay known as GC-O (gas chromatography-olfactory)8. Some say that the olfactory detector is even more sensitive and valuable than the strongest mass spectrometers.
The olfactory detector is literally just a human nose.
Sometimes the molecules that contribute to an appear in trace amounts that are below a GC-MS’s level of detection. This is when olfactory detectors, or professionally trained sniff-testers, use their super-smell to identify aroma components. In GC-O, a chamber with a sniffing port is connected between the output line of the gas chromatograph and a signal generator. The scientist stands at the sniffing port and puts their nose to work.
Once the trained flavorist identifies the aroma-attributing compound, that compound is diluted in incremental amounts and re-sniffed until the flavorist can no longer detect the smell9. The dilution at which the flavorist can no longer detect the aroma of the compound is valuable information that is used to determine the level at which to formulate that aroma-attributing compound into a product.
Synthetic Flavors Are the Spice of Life
This is just a high-level overview of the complexities of flavor chemistry. If it takes years of education and training to learn how to properly synthesize artificial flavors, is it worth all of that effort?
The short answer is yes, absolutely. Compared with their natural ingredient counterparts, synthetic flavors are significantly cheaper, easier, and more sustainable10 to formulate in large-scale productions.
If every time someone wanted a pumpkin spice latte, they went out and used naturally extracted cinnamon and vanilla, there would be a lot less of those ingredients left in the world, and therefore a lot less pumpkin spice flavored things for all of us to enjoy. Sourcing natural ingredients in this way is inefficient, expensive, and often unethical. It’s much cheaper and ecologically sustainable to chemically synthesize the top flavor notes of those natural spices.
Synthetically produced flavors are also much more soluble in water than their ground spice counterparts (cinnamon or nutmeg sprinkled atop your coffee often tends to sink to the bottom of the cup). This makes synthetic flavors easy to incorporate into a variety of food products. Ease of formulation combined with a highly regulated and quantitative synthesis allows for more consistent flavoring from batch to batch.
The next time you swing by Starbucks for your daily dose of seasonal caffeinated goodness, do so shamelessly, knowing that you’re supporting a marvel of modern and sustainable chemistry. The only shame in indulging in a PSL is knowing that a bunch of chemistry nerds can make a better cup of coffee than you.
Once again, a prescription drug has become a household name in the United States. Easy to pronounce and even easier to obtain from your local pharmacy (or livestock store), the antiparasitic ivermectin has recently undergone an astronomical increase in usage. Ivermectin’s pre-pandemic prescription rate of about 3,600 prescriptions per week spiked to over 88,000 prescriptions per week by mid-August 20211. However, this surge in usage is not associated with the treatment of parasitic diseases, but rather with attempts to treat the COVID-19 virus.
A handful of legitimate in vitro studies investigating ivermectin’s anti-viral properties have been largely overshadowed by the vast number of fraudulent or poorly conducted in vivo studies, causing public confusion over whether ivermectin can be considered a legitimate treatment for COVID-19. In the public eye, the debate was never a scientific one, but rather a giant log thrown onto the already blazing fire of contention in the American political system. Parties on either side of the COVID-19/ivermectin debate are equally passionate, but neither group seems to be backed by the scientific community. What exactly is ivermectin, and how did it rise to the forefront of the COVID-19 pandemic?
Ivermectin’s Origin Story
Discovered in 1975 by two scientists who were eventually awarded the 2015 Nobel Prize for their work, ivermectin is an internationally recognized and robust antiparasitic drug. Specifically, ivermectin is a highly efficacious broad-spectrum antinematode that damages nervous and muscular cells in parasitic worms. Ivermectin is formulated and dosed to treat parasitic infections in both humans and animals. If you have a four-legged friend at home, you are probably familiar with Heartgard; this is ivermectin for dogs, most commonly used to target roundworms and hookworms. In humans, ivermectin is prescribed to treat internal parasites that cause diseases such as river blindness and strongyloidiasis, two neglected tropical diseases that have infected hundreds of millions of people worldwide2. Ivermectin is also used topically to treat infections caused by the parasites associated with lice and scabies.
Additionally, ivermectin is commonly used to treat parasitic infections in livestock. Ivermectin is an incredibly efficacious and safe drug (when dosed properly, as is the case with most drugs) that has saved countless lives and immeasurably elevated the state of global public health. Those who tout ivermectin as mere “horse paste” would be remiss to not recognize ivermectin’s life-saving global impact.
However, the lives saved by ivermectin are those that were given the drug at proper doses, to treat parasitic infections. You wouldn’t use a broad-spectrum antibiotic to treat a broken bone, and administering overdose-level quantities of antibiotic won’t magically cause your bone to heal. In a broader sense, just because a drug successfully treats one indication does not necessarily mean that it can treat other indications. While some drugs certainly can be successfully repurposed to treat indications other than the original target, repurposing a drug requires careful scientific experimentation and deliberation.
How Ivermectin Works
When new diseases arise, scientists look to see if existing drugs can be repurposed, because it’s easier, faster, and cheaper to repurpose an existing drug than it is to develop a new one. An existing drug’s known physiological and chemical properties are used as starting points for assessing if the drug could be used for other indications. In the case of ivermectin, scientists have a general understanding of its method of action against parasites. This knowledge can be leveraged to hypothesize if ivermectin could possibly treat non-parasitic targets.
In order to damage and ultimately kill parasitic worms, ivermectin targets cellular features that are specific to parasitic worms. While all cells have membranes with ion channels, there are types of ion channels that are present only in particular species. Parasitic worms are classified as “proteasome invertebrates”, a small taxonomic group that includes species such as jellyfish, sea urchins, crustaceans, and snails. These species are known to have cells that contain glutamate-gated chloride channels. This means that when glutamate, a naturally occurring amino acid, binds to such an ion channel, the ion channel opens and allows the passage of chloride ions over the cell membrane. The proper flow of ions over cell membranes is essential to physiological processes imperative to the survival of the cell and health of the overall organism.
While vertebrate cells have chloride channels that are gated by other ions, such as acetylcholine or glycine, glutamate-gated chloride channels have yet to be identified in vertebrates. This feature, that only invertebrates possess, can be exploited as a target in cases when invertebrate parasites infect vertebrates (i.e. when parasitic worms with glutamate-gated chloride channels infect humans without glutamate-gated chloride channels). When ivermectin is administered to an afflicted human or animal, ivermectin binds to the glutamate-gated chloride channels in the parasite’s cell membranes. This pushes open chloride channels, increasing the flow of chloride ions across the cell membrane, which ultimately paralyzes and kills the cell due to hyperpolarization of the cell membrane.
How could this method of action be applied to a viral target? Viruses don’t have cells, so ivermectin would not be able to directly “kill” a virus in the same way that it kills parasites. However, viruses cause disease in living organisms by infecting their cells. If ivermectin can bind to and block cellular receptors during viral infection in a mechanism similar to how ivermectin pushes open glutamate-gated chloride channels in parasitic cells, it certainly is possible from a physiological standpoint that ivermectin could have anti-viral properties.
In Vitro Triumphs
A 2012 study published in Biochemical Journal3 outlines a series of experiments that demonstrate ivermectin’s anti-viral properties. The experiments described in the paper (authored by Kylie Wagstaff and colleagues at Monash University in Victoria, Australia) are follow-up experiments to a preliminary high-throughput screen4 used to identify molecules that inhibit viruses from entering the cell nucleus. In this preliminary screen, ivermectin was identified as one such viral protein nuclear import inhibitor (basically a long-winded way of saying that ivermectin successfully blocks viruses from entering the cell nucleus. This is important because when viruses enter cell nuclei, they override the nucleus’s machinery and force it to create more virus). The experiments detailed in the 2012 paper focus on ivermectin’s specificity towards nuclear import pathways, and the degree to which ivermectin can inhibit viral infection of cells grown in a lab.
The results of the 2012 study showed that ivermectin is a broad-spectrum inhibitor of a particular nuclear transport factor known as the importin alpha/beta1 heterodimer. The name of the transport factor isn’t important; what is important here is that “importins” (pun intended) are proteins that help move large molecules into the cell nucleus. The specific importin that ivermectin inhibits (importin alpha/beta1) is known to facilitate viral infection of cells. In order to assess how strongly ivermectin blocks viral infection via the importin alpha/beta1 heterodimer, cells were infected with both HIV-1 and dengue virus (in separate experiments). The infected cells were then divided into three groups: one treated with ivermectin, one treated another antiviral called mifepristone, and a “blank” control (the “blank” is used to measure levels of viral infection in untreated cells).
The results of these simple cell culture experiments were objectively clear: ivermectin significantly reduces viral replication in vitro. In the scientific industry, one experiment commonly used to measure viral infectivity is the plaque titer assay. In this experiment, cells are infected with virus and incubated for a defined length of time. Infectious viral particles eventually infect nearby cells and produce a visible blob, or a plaque, of infected cells. The more visible plaques, the more virus produced.
The scientists involved with this particular study used the plaque assay to assess how effective ivermectin was in inhibiting viral replication in cells. The cells that were infected with dengue virus and then treated with ivermectin showed almost no plaques, which means that ivermectin successfully blocked viral replication at the level of infection used in the study. The paper includes some great graphs showing the scientists’ work; you can check out their data here: Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus.
Dr. Wagstaff’spaper was a great first step in researching and establishing the potential of ivermectin’s antiviral properties. Since then, other cell culture experiments focused on ivermectin’s inhibition of viral activity have been performed. One such famous study is the Caly study5, authored by Leon Caly and colleagues at the Doherty Institute in Melbourne, Australia.
Ivermectin and COVID-19
The Caly study is a well-documented and clearly written paper that chronicles Dr. Caly’s experiments on ivermectin’s anti-viral properties. The paper validates the results described in the 2012 Biochemical Journal paper and dives further into trying to understand ivermectin’s antiviral method of action. What makes the Caly study special is that its objective was to directly assess ivermectin’s efficacy in inhibiting the replication of SARS-CoV-2, the virus that causes COVID-19.
The experiments outlined in the Caly study are similar in nature to those described in the 2012 Biochemical Journal article. Cells were infected with SARS-CoV-2 and treated with ivermectin. Cells treated with ivermectin were shown to have 5000 times less viral RNA compared to a “blank” control. Viral titer assays produce valuable data, but because things like counting plaques can be fairly subjective, the Caly study took the extra step to add a more quantitative piece of orthogonal data to support their findings: RT-PCR.
RNA was extracted from the COVID-infected/ivermectin-treated cells and then amplified and detected on RT-PCR, probing specifically for sequences found only in SARS-CoV-2 RNA. The PCR results showed anywhere from 93% to 99.8% reduction of viral RNA in samples collected from ivermectin-treated cells compared to the untreated control. These exciting results confirm that ivermectin is a potent inhibitor of the importin alpha/beta1 heterodimer, by which SARS-CoV-2 also seems to use in order to infect cells with virus.
A quick skim of Dr. Caly’s study, or an uninformed retelling of the study results, may suggest that ivermectin is an efficacious treatment to administer to COVID-19 patients. Scientific experiments were conducted by experts that show that ivermectin has potent antiviral effects, and the virus that causes COVID-19 was even tested directly.
So what’s the catch? Out of all of these studies, not a single one was performed in humans. When these studies talk about ivermectin’s antiviral properties, they are referencing observations and scientific data generated from cells grown in a lab. This is an excellent starting point for scientific discovery, but just because something works in cells doesn’t mean that it will work in animals, let alone the complex machine that is the human body.
In Vivo Failures
To the layreader, it can be difficult to discern if an experiment described in a scientific paper was conducted in vitro or in vivo. And how could the average layreader know such terminology when experimental methodology is hidden in the fine print of scientific papers? The ivermectin-COVID-19 debate is a great example of how poor scientific communication can lead to mass confusion and unnecessary conflict.
In vitro experiments are performed in cells. The literal translation of the Latin term is “in the glass”. Studies performed in vitro are performed in an artificial environment, like a test tube or cell culture plate. In vitro studies are performed outside of a living organism.
In contrast, in vivo experiments are performed inside a living organism. Preliminary studies performed on mice, toxicology studies performed on non-human primates, and clinical trials performed on human subjects all fall under the in vivo umbrella.
In order to be tested in humans, drugs must first prove to be efficacious in cells in vitro, and then efficacious and safe in animals that are less risky to dose than humans. Once a drug clears these hurdles and has sufficient data to suggest that it will be more helpful than harmful, only then is it tested in humans in clinical trials. Clinical trials themselves are thorough, multi-tiered investigations of a drug’s potency, efficacy, and safety that take years to see to completion.
In other words, the results of one study performed on cells grown in a tissue culture plate are not indicative of how humans will respond to such a treatment.
To muddy the waters even further, there have been several fraudulent and entirely fabricated “studies” on the human in vivo effects of ivermectin administered as an antiviral drug. To date, there are about 26 major in vivo clinical trials studying ivermectin as a COVID-19 therapeutic. About a third of these studies have been proven to be fraudulent or outright falsified. The remaining studies have yielded no data that suggests that ivermectin has any effect, let alone positive effect, on patients with COVID-19.
Perhaps one of the most well-circulated fraudulent studies is the Elgazzar paper6 out of Benha University in Egypt. The pre-print paper first came under scrutiny when Jack Lawrence, a masters student in the UK, read it and noticed several instances of plagiarism. When he reported his suspicions to researchers who assess fraud in scientific publications, even more fraudulent discoveries came to light. Patient data appeared to be fabricated, raw experimental data didn’t match up with conclusive remarks, and much of the experimental data was so mathematically unsound that it is likely it was generated falsely. There were even records of patient data stating that patients enrolled in the study actually died before the study’s start date. Among the most humorous pieces of misinformation was a patient leaving the hospital on June 31, 2020. Perhaps such a date exists in the equally fictitious world in which the study took place.
Despite such blatant transgressions on good science, the paper was viewed over 150,000 times and cited more than 30 times before it was withdrawn from the preprint platform.
The Elgazzar paper is far from the only “study” to report fraudulent in vivo ivermectin data. The authors of a study conducted in Iran7 claim that half of all patients involved in the trial tested negative for COVID-19 upon beginning the study, completely negating the intended objective of studying the effects of ivermectin on COVID-19 at all. Other details in the paper’s methodology indicate that the poor randomization of results is likely due to fabrication of said results.
Desparate Times, Desparate Measures, and the Rise of Horsepaste
Once misinformation, like the “findings” reported in the aforementioned fraudulent studies, is shared by the scientific community, it’s even easier for the truth to be skewed by those with no scientific background, like many American politicians. This misinformation is more easily accessible to the public, and when the public is also desperate for a safe treatment to a deadly virus, a pandemic quickly becomes a pandemonium. To those looking for an alternative to the COVID-19 vaccines, an existing drug with seemingly reputable in vivo data becomes an attractive choice. This is what causes people to self-dose ivermectin for COVID-19.
When dosed properly (“properly” being a loose term, since ivermectin is nowhere near close to FDA approved for the treatment of COVID-19), administering ivermectin as a treatment for COVID-19 will likely not cause any harm, but it won’t treat or alleviate symptoms caused by COVID. This is based on what we know of ivermectin’s biochemical method of action as well as results from legitimate in vivo clinical trials of ivermectin as a COVID-19 therapeutic (such as the ongoing study at McMaster University8). However, this is under the generous assumption that those who are self-dosing ivermectin are adhering to appropriate human ivermectin doses. There is a large overlap between those desperate and misinformed enough to use ivermectin as a COVID-19 treatment and those who obtain ivermectin by means other than a pharmacy. This is more of a failing of the American health care and health insurance system than it is a reflection on those who choose to circumvent it.
Oftentimes veterinary ivermectin can be more easily obtained than human ivermectin, especially at places like livestock stores. This is where the real danger lies; livestock ivermectin is much more concentrated than human ivermectin. This makes it very easy to overdose on ivermectin and cause some pretty unpleasant and potentially lethal side effects. This is where ivermectin has gotten its notorious “horse paste” nickname. Ivermectin intended for horses is often packaged in a large syringe, with one full syringe containing enough drug product to dose a 1250 lb animal9. Each little line on the syringe indicates a dose for 250 lb of bodyweight. The difference in scale combined with the immense risk of inaccuracy of administering a horse drug to a human is the cause for a recent increase in calls to poison control. This year, the National Poison Data System reports a 163% increase10 in cases related to ivermectin alone. With more and more hospital beds being filled with unvaccinated COVID-19 patients, and less time that health-care workers have to spend on non-COVID-related cases, is OD-ing on an ineffective COVID treatment really something worth wasting one’s own time (and potentially life) on?
Impatience, the Most Deadly Side Effect of Good Science
Although in vivo clinical trials assessing ivermectin’s effects on COVID-19 still have a long way to go, the data generated so far concludes that ivermectin has no effect on treating the virus in humans. Despite tremendous in vitro success, ivermectin does not demonstrate the same antiviral efficacy inside the human body. However, these disappointing in vivo results don’t invalidate ivermectin’s antiviral in vitro triumphs; the experiments described in the Wagstaff and Caly papers discuss exciting discoveries that have led the scientific community closer to fully understanding the complicated world of viruses and how they work. Even more disappointing than ivermectin’s lackluster performance in the COVID clinic is how careless the global scientific community was to allow so many fraudulent in vivo studies to be publicly circulated. While political manipulation of scientific information is almost inevitable, the scientific community must take seriously its responsibility to publish high-quality and transparent peer-reviewed data.
The COVID-19 pandemic has skewed everyone’s sense of drug development timelines; multiple vaccines were developed and rolled out in less than one year. The secret sauce to developing a novel vaccine in no time at all is a tremendous amount of funding, huge public interest to boost clinical trial participation, and reductions in administrative red tape to speed up timelines. Not every scientific endeavor can, or should, have the same super-accelerated emergency timeline as the COVID-19 vaccines. Good science is methodical, deliberate, and oftentimes doesn’t yield the results you were hoping for. Good science isn’t always exciting or fun, but then again, neither is suffering damage done to your body and ego after self-administering medicine intended for an animal five times your size.
