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Introduction

Pulmonary Cryptococcosis is an uncommon lung infection [1] caused by the pathogenic species complex of Cryptococcus neoformans. All 11 sub-species of the complex are yeast-like encapsulated saprophytic basidiomycetes [2&3].

Cryptococcus neoformans is an occasional opportunistic fungal so although it’s relatively inactive in immunocompetent patients, it can cause very serious complications in immunosuppressed patients, including fatal meningitis - meningoencephalitis (mortality rate is 10-30% [5]), as well as severe pneumonia which is one of the leading mycological causes of morbidity/ mortality among HIV patients worldwide [1&6].

However, as previously said, immunocompetent hosts usually do not experience any symptoms and if they do, those symptoms are relatively mild. Also, the study of sign and symptoms of the disease is at a relatively early stage. Those 2 factors are detrimental to the fact that a great percentage of such cases are misdiagnosed as other diseases, such as lung cancer [6].

The reason lung cancer is one of the main misdiagnoses clinicians make, is because the radiography of the chest indicates the presence of nodular or mass-like lesions in the lungs. It is therefore easy yet obviously wrong to assume those lesions as malignant [1&6].

The proper diagnosis of this infection employs chest X-rays and computed tomographic (CT) scans to detect the the nodular or mass-like lesions in combination with tissue biopsy and culture to identify the specific type of microorganism, before jumping to conclusions on the nature of the cells inside the lesion [5&6]

Alternatively, in order to properly explain the presence of such lesions, we have to also utilize histopathological methods. This is because just by analyzing the radiography, we cannot differentiate whether the presence of the lesions is due to malignancy or not. Also, even if we somehow knew that the cells of the lesions were not cancerous, we still couldn’t specify the infections and thus, we wouldn’t proceed with the optimal disease management plans [5&6].

On a more general scale, histopathology enables experts to explore changes in cells that can clarify the real cause of the patient’s illness. Pathologists are able to reach a conclusion for their diagnosis, just by examining a little piece of tissue from various organs [7].

Therefore, histopathology is extremely important because it broadens and advances the treatment options [7].

Materials and Methods

Patient’s Clinical History

The patient is a 59 year-old male which currently travels through his post-orthotopic-liver-transplant (due to HCV) period. Patient resides in Pennsylvania, where the general climate is temporal. Patient is also a light smoker. After the liver transplant, patient appeared with an overall increase in the values of the liver function tests, as well as a decrease in his body weight. He was then admitted to the hospital where the following conclusions were deduced: stable vital signs, afebrile, ordinary lung function (auscultation), great overall abdominal image and no signs of adenopathy. Clinicians proceeded with a routine CT scan of his chest, in which four nodular lesions were observed, within the peripheral aspect of the left upper lobe. Again, no signs of adenopathy were noted in any of the examining regions.

Methodology

[After the radiographic scans, CT-guided fine needle aspiration of the left upper lobe mass was performed]

Through a careful and thorough observation and examination of the panel images on the Figure 2 and Figure 3, we came in the following conclusion regarding the methods and the techniques used to acquire those panel images:

The images were captured by a light microscope with the help of histochemistry. We can clearly observe the colouring of the tissue and thus we can assume tissue staining. Specifically, the staining materials ranged from PAS to possibly H&E and ultimately, mucicarmine which is widely for the detection of C. neoformans fungi.

From the fact that the above techniques were used to find out the presence of malignancy or fungi, we can rationally assume that the procedure that was executed to obtain the corresponding samples was CT-guided fine needle aspiration.

CT-guided FNA is a type of biopsy procedure, in which a very thin needle is inserted into the “abnormal” area -in this case the lobe mass- and a tissue sample is extracted and placed into smear aspirator and from there, it is sent to the laboratory for further analysis. It’s most usually used to rule out conditions such as cancer.

The diagnostic yield of FNA in these cases has been shown to be higher than that of bronchoscopy with biopsy and many other techniques, and that’s why we can assume that the images were obtained using with this method.

Finally, note that histological sections are almost transparent, and stains are used to utilized to recognize individual components of cells. However, Immunohistochemistry uses antibodies labelled coloured dyes, which are then used as specific test modes, to locate specific protein molecules to individual cells in tissue sections, and this study is irrelevant at our case.

Results

Computed tomography scan of his chest demonstrated four nodular lesions within the peripheral aspect of the left upper lobe, the largest measuring 3x3cm. A small left pleural effusion was also noted, however, no adenopathy was identified within the axillary regions, mediastinum, or hilar regions.

Computed tomography guided FNA of the left upper lobe mass was performed.

Cytologic examination of direct smears of FNA material obtained from the left upper lobe mass revealed a slightly mucoid background, moderate cellularity, polymorphonuclear leukocytes, lymphocytes, and epithelioid histiocytes (figure 2).

Also, a significant number of spherical to ovoid yeast forms were seen which appeared to have a capsule. Several of the organisms exhibited narrow-based budding. Mucicarmine stain highlighted the capsular material (figure 3).

Figures

Figure 1: The figure represents the CT scan of the patient’s chest. We can clearly observe the presence of relatively big nodular lesion on the (upper) left lobe. However, there are another 3 nodular lesions which are not clearly captured in this image

Figure 2: This figure represents histological tissue samples obtained from the lobe mass (both panels are PAS stained). (A) Deep red colour (magenta) demonstrates the presence of mucus. (B) The bluish colour in the 2nd panel demonstrates yeasts morphology.

Figure 3: This figure represents histological tissue samples obtained from the lobe mass (1st panel is PAS stained but the 2nd can be both PAS and H&E stained). (A) Green circles clearly indicate the presence of narrow-based budding yeasts (B) The toned purple border in the 1st panel indicates the presence of capsular material (C) The 2nd panel is also stained with mucicarmine, in order to emphasize the characteristic gelatinous capsule with a bright pink.

Discussion

Diagnosis

“Cytologic examination of direct smears of FNA material obtained from the left upper lobe mass revealed a slightly mucoid background, moderate cellularity, polymorphonuclear leukocytes, lymphocytes, and epithelioid histiocytes (Figure 2).”

The presence of high amount of immune cells (leukocytes , lymphocytes, histiocytes) in the specific are (left upper lobe), indicate the presence of an infection or injury for which the immune cells are getting concentrated.

Looking at the clinical image of the patient and the above information, we can exclude the presence of an injury (non-mentioned). We can then exclude a number of infections which cause inflammation because the patient was afebrile (ex. pneumonia bronchitis). We can also semi-exclude a number of infections which usually have an effect on the heart, because the patient showed regular rate and rhythm (ex. Influenza virus). Finally, we can semi-exclude adenopathy related diseases as we assume no abnormal lymph nodes were palpated during the physical examination of the patient.

“Also, a significant number of spherical to ovoid yeast forms were seen which appeared to have a capsule. Several of the organisms exhibited narrow-based budding. Mucicarmine stain highlighted the capsular material (Figure 3).”

The presence of encapsulated spherical/ ovoid shaped yeasts combined of the observation of narrow-based budding, clearly narrows down the potential infectious agent to a complex of species: Cryptococcus neoformans.

That is because out of the kingdom of fungi the complex of C. neoformans have the distinct following characteristics, polysaccharide capsule and replication via narrow-based budding.

Finally, the histological findings in are quite specific to this disease, yet they cannot identify which one of the species was the infectious agent, because both C neoformans species complex and C gattii exhibit a similar morphology. However, pulmonary infection is rarely caused by C gattii, and only a few cases were reported [6].

Pulmonary Cryptococcosis

Cryptococcosis is a common opportunistic infection in acquired immunodeficiency syndrome (AIDS) patients and in other immunosuppressed patients and significantly more uncommon to those with no apparent immunocompromise. Most infections with C. neoformans occur in the lungs. However, meningitis and encephalitis are often caused by C. neoformans, making it a particularly dangerous fungus [6].

Most of the cases are caused by the ubiquitous encapsulated yeast, C. neoformans, whereas, as mentioned, C. gatti accounts for a smaller proportion of cases, often in immunocompetent patients. It is an intracellular pathogen that can utilize phagocytes of the host to spread within the body [8].

In the human lungs, C. neoformans cells are phagocytosed by local macrophages. Those macrophages produce toxic agents, in order to create a hostile environment, to kill the invading pathogens. However, some C. neoformans cells can survive intracellularly in macrophages, with the help of their capsule. "Intracellular survivors” appears to be the fundamental brick for latency, disseminated disease, and resistance to eradication by antifungal agents [9].

In our case, the patient is currently traveling a time period after which he had a liver transplant due to sever hepatitis C and thus, he receives immunosuppressant drugs on a weekly basis, in order for his body to accept the donor’s liver [6].

That’s exactly why our patient falls under the “immunocompromised” category of patients and is susceptible to opportunistic infections such as (pulmonary) cryptococcus [7].

Pulmonary Cryptococcosis Management

Factors predisposing to cryptococcal infection include corticosteroid administration, lymphoreticular malignancies (especially Hodgkin's disease), sarcoidosis and HIV infection (80-90%); however, 50% of cases have no recognized predisposing condition [manual].

Temperate climates, exactly like Pennsylvania which our patient lives in, are the primary location for Cryptococcus neoformans var. neoformans [manual]. Thus, we not only identify a potential cause of the disease, but we can conclude that the disease was caused by this very specific variety of the complex.

“Initial therapy of pulmonary disease should be amphotericin B alone or in combination with flucytosine. Amphothotercin B can be administered alone for 6-10 weeks or in conjunction with flucytosine for 2 weeks, followed by fluconazole for a minimum of 10 weeks.” [11]

References

1. Kanet Kanjanapradit,1 Zdravko Kosjerina,2 Wiwatana Tanomkiat,3 Warangkana Keeratichananont,4 and Siripen Panthuwong, 2017, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5546643/

2. [FerryHagenabKantaraweeKhayhanacBartTheelenaAnnaKoleckaaItzhackPolacheckdEdwardSionovdeRamaFalkdfSittipornParnmeng ThorstenLumbschhTeunBoekhout](https://www.sciencedirect.com/science/article/pii/S1087184515000328?via%3Dihub#!), 2009, https://www.sciencedirect.com/science/article/pii/S1087184515000328?via%3Dihub#s0145

3. Gustavo de Sousa Arantes Ferreira, Andre Luis Conde Watanabe, Natalia de Carvalho Trevizoli, Fernando Marcus Felippe Jorge, Carolina de Fatima Couto, Priscila Brizolla de Campos, and Gabriel Oliveira Nunes Caja, 2016, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280860/

4. Joel Schop, 2007, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2323542/

5. Unknown author, 2012, https://en.wikipedia.org/wiki/Cryptococcus_neoformans

6. Kanet Kanjanapradit,Zdravko Kosjerina, Wiwatana Tanomkiat, Warangkana Keeratichananont, and Siripen Panthuwong2007, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5546643/

7. Unknown author, 2009, https://anapath.ch/things-to-know-about-histopathology/

8. Assoc Prof Patrick Emanuel, 2017, https://dermnetnz.org/topics/cryptococcosis-pathology

9. Unknown author, 2006, https://webpath.med.utah.edu/LUNGHTML/LUNG503.html

10. Findra Setianingrum, Riina Rautemaa-Richardson, David W Denning, 2003, https://academic.oup.com/mmy/article/57/2/133/5133472

11. Unknown author, unknow date, https://www.medscape.com/register?client=205502&scode=msp&action=complete&lang=en&register=true&form=about&urlCache=aHR0cHM6Ly9lbWVkaWNpbmUubWVkc2NhcGUuY29tL2FydGljbGUvMjE1MzU0LXRyZWF0bWVudA

Introduction

I have always being quite skeptical about vegans. I’ve always had my opinions on the matter but I never invested the time to dig a little deeper. Not because I didn’t want to, simply because it hasn’t been my priority.

Nobody in my close circle of friends ever suddenly came up to me and said: “I’m thinking about converting to a vegan diet”. Not only that but I haven’t had any serious, in-depth, intellectual discussion -consisting solid and rational arguments-with an individual who supports this narrative.

The only usage of the word "vegan" between my close group of friends is the same as words that describe activities that are not seen as particularly masculine. I believe this “phenomenon” is quite common in traditional, male-dominated groups, and it is not unhealthy. However, I understand how it could be seen as offensive to some people, so I’d like to clarify my stance; My friends and I recognise that certain adjectives are considered offensive in certain contexts, as they can lead to stereotypical behaviours and discrimination. We would never use them with malicious intent, we wouldn’t even use them outside the group. I can confidently say that we are kind and polite people. Of course you could say that I’m biased, but it's impossible to effectively demonstrate the contrary. The only way for you to make an accurate judgement, is to experience it yourself, and the only way to do that is by meeting us in person.

Carrying from my previous point, I haven’t had a discussion with an individual who supports this narrative. To my understanding, that by itself does not indicate that my network is small or that “I haven’t tried enough” (as such a assumption would be naive); it indicates that the people supporting this endeavour are either not so capable of such a discussion (something I am unwilling to accept), or they don’t have a strong argumentative foundation on why they are doing, what they are doing.

The most common arguments I have encountered are as follows:

• “It prevents the slaughtering and exploitation of animals”

• “I have emotional attachment with animals, and thus I cannot eat them”

• “It’s more healthy”

• Rarely: “It’s better for the environment”

Although I thought about each and every one of them quite extensively, I decided to find additional discussions and arguments online, before presenting my finalized opinions.

Concerns

I firmly believe that when conducting research, scientific or not, one should strive to be as objective as possible while being exposed to potential influence. To that end, I have decided to implement the following principles in my research: I will invest my time as fairly as possible in researching the differing opinions on veganism, and I will strive to pursue and extrapolate the truth, even if it is personally unfavourable. Simply put, I will try to dedicate approximately the same time when expanding on the opposing sides of an argument and I will try to be as open-minded as possible in embracing the truth, even if it is inconvenient to do so (e.g. if it comes out to be “better” to be vegan, I shall not only present this as the truth, but seriously contemplating becoming one).

Another concern I would like to raise is the amount of information that is inaccessible to the general public, myself included, when conducting research. This could potentially affect the results of a research. For example, many people, myself included, admitted that during the Covid-19 pandemic, it was difficult to make an unbiased and absolute conclusion, or even conduct proper research, regarding the validity of some medical news. It is not my intention to discuss strange conspiracy theories; I merely want to point out that each topic has a number of facts that are not available to the public for whatever reason, which can compromise the accuracy of my presented results.

Discussion

Whether it's based on scientific research or not, I firmly believe Reddit is the best place to start your research. You can hear the unfiltered, unbiased opinion of people from all sorts of backgrounds and experiences. You can find out what the general consensus is on a particular topic, and you can also gain insight into what the general public thinks and feels about a certain subject.

I quickly found out that most people tend to separate the discussion into the following broad categories: nutrition, ethics, philosophy and environment; so I decided to do the same.

Nutrition

I'll be brief on this point, as it was not something that initially sparked my interest to research veganism.

I'm generally quite fond of the idea of having an optimal way of eating, especially when it takes into consideration one's personal goals. However, I assume that if the vegan diet had particularly great health benefits, we would be hearing more from it (both from the general public and from the medical community). Perhaps this assumption is naive, perhaps is not. Nevertheless, despite its “unpopularity”, I won't completely disregard it. I just won't be spending as much time on it as on the others. When it comes to nutrition, I'm mainly interested in whether the nutritional benefits of an omnivorous diet can be adequately replaced by a vegan diet, or even surpassed.

Despite saying Reddit is the best place to begin research, I decided to approach this topic from an academic perspective, given its close relation to medicine and general well-being, both in which I’m well-versed. The most cited article I could find was an article published by the “The American Journal of Clinical Nutrition” with the title “Health effects of vegan diets” [1]. I get that research can only be considered thorough when it encompasses a great variety of sources, something that I’m evidently not doing, but as I already stated, I will not be investing as much time as in the other sections, so I chose to make my conclusions solely based on the most popular and presumably trustworthy article available.

The article summarised the up-to-the-point literature (2009) related to health effects of vegan diets. It contained lots of exhaustingly specific data (ex. high tomato consumption protects against prostate cancer), but I managed to extrapolate and present the most solid, yet interesting conclusions (note that in a highly regarded article such as this one, you won't typically find many bold statements or groundbreaking theories).

The first half of the article examines the impact of a vegan diet on cardiovascular health, cancer, and bone health. Cardiovascular health appears to be the most positively affected by a vegan diet, likely due to vegans having on average lower BMI (which is associated with a lower risk of heart disease) or due to the cardioprotective effects of fruits and vegetables. Evidence for cancer being positively impacted by a vegan diet is not as convincing. Bone health is more complex; it’s indicated that as long as calcium and vitamin D levels are monitored, it is unlikely to be an issue.

The other half of the article focuses on "nutrients of concern" that may be lacking in a vegan diet and how to replenish them to avoid deficiencies. Ultimately, it is concluded that, with appropriate food choices, vegans can generally avoid nutritional problems. Although my goal in this article is to take an idealistic approach to veganism, it's important to remember that only a small percentage of vegans actually adhere to their supplement guidelines (10-50% [2]).

I have come to the realization that it is more than feasible to substitute the nutritional value of an omnivore diet with a vegan diet while experiencing some positive health effects. Yet, it is essential to make smart food selections in order to get the most out of a vegan diet. This means carefully considering the content of the food that is being consumed while being aware of any dietary restrictions that may be present. With a little diligence and care, it is absolutely possible to enjoy the benefits of a vegan diet while still maintaining a healthy lifestyle.

Ethics

Ethics, is when it gets quite tricky for me.

I was truly astonished when I stumbled across the most highly upvoted posts in the related subreddits. I’m talking about in-depth, semi-scientific articles, containing innumerable arguments that can -at least- either strengthen the doubts of the most ardent vegan, or come really close to converting non-vegans. I couldn't help but wonder why someone would take the time to research and write something like that. Is there some kind of financial incentive involved? Or maybe they just feel a need to contribute to the conversation and receive personal gratification from their efforts? Nevertheless, these are all questions to be pondered at another time, as they are not the main focus of this article. I went through these articles several times, and I used some of the points made within to support some of my arguments. Despite this, I wish to make it abundantly clear that I do acknowledge the lack of objectivity of the articles, as it’s quite clear they were composed with a pre-existing narrative in mind.

The anti-vegan community (AVC) are quite fierce and “extremely creative” when it comes to the ethical discussion. I’ve taken almost the entirety of my anti-vegan arguments from the most upvoted post in the r/Antivegan subreddit. I admit I’ve read the most captivating stories ever. From “cheese replacements are usually made with cashews, which burn the fingers of the women who have to remove the shells” to “25 times more sentient beings die to produce a kilo of protein from wheat than a kilo of protein from beef”, to even “a kilogram of flour probably has 15g of animal product in it, from rodent excreta to weevils to cockroach legs”.

The vegan community (VC) isn’t lacking creativity either. Similarly, I used most of the pro-vegan arguments, from the most upvoted posts in the r/DebateAVegan subreddit (before you get mad at me for not taking them from in r/vegan, know that I went there and I couldn’t find anything more than memes, let alone in-depth articles). These contained -to my surprise- equally wild claims, ranging from “global hunger would be eradicated if we stopped breeding 80 billion animals into life.” to “due to overfishing, the oceans are expected to be depleted” and “veganism is the only known diet that can fully cure…diabetes”.

After carefully reading not only these two posts, but also several other related articles, live debates and even book sections, I formed my own opinions on the differing aspects of ethical veganism. I condensed my final conclusions in the following paragraphs, in a way for them to be concise and easy to understand. These paragraphs demonstrate a continuous alternation between anti-vegan and pro-vegan stances. Enjoy.

Human Suffering

The framework of an ethical veganist, which promotes actions or inactions that reduce animal suffering, can be occasionally problematic, if strictly and recklessly applied [6].

For instance, some vaccines contain animal or animal-derived products [3][4]. Even if they don’t, essentially all vaccines are tested on animals [5]. It's also important to note that the side effects and the proper vaccine dosage, in early pre-clinical stages, are broadly-speaking, unknown. You can see where I’m going with this. For anyone not getting it though, I want to make it clear that I am definitely not suggesting to avoid vaccinations. Instead, I'm suggesting that individuals should have reasonable exceptions in their moral code, whatever that is. Additionally, research involving animal testing has led to numerous breakthroughs in the fields of medicine, not only development of vaccines, but also cancer treatments, and other life-saving drugs. These innovations would not have been possible without the use of animal testing [4][5].

At the same time, ethical arguments provided by anti-vegans can be accordingly problematic. For instance, "Why should we care about animals when there is so much human suffering in the world?" This is a false dilemma as it fails to recognize that veganism is an individual choice and is not an either/or proposition. How can it not be possible to fight against human suffering and -at the same time- reject the exploitation of animals, by not consuming animal products? There is virtually nothing stopping us from doing both. It is entirely possible to care about both animals; and human suffering, and indeed, many vegans are actively engaged in charitable works and other causes that alleviate human suffering. Note that helping animals does not require complex solutions that many of our other most pressing social issues do. It can be as simple as providing food, shelter and a safe space to animals who may otherwise be neglected or mistreated.

The most common ethical argument made by vegans is regarding the emotional toll slaughterhouse workers face, the psychological strain of having to kill animals on a daily basis [8][9]. I have to admit that I'm not a fan of this line of argument, either in this debate or generally. I understand that some people may have no other choice than to work in places they don't want to do. I also get that not having a choice to work in a coffee shop and not having a choice to work in a slaughterhouse are two completely different things. Nevertheless, nobody is forced to work in those places at gunpoint; it's completely voluntary. Some jobs carry risk and this is the nature of the capitalistic system we live in. I believe we can all agree there are countless examples of jobs with significantly higher emotional and physical risk. If these are the only jobs available for someone, who are we to deny them from choosing, solely on the basis of "saving them from -potential- emotional damage"?

“Anything you buy from a capitalistic system reinforces exploitation of animals...The consumption of commodities, even if the production method of these commodities is unethical, it is done in a way that it alienates us from the ethical consequence of being deemed immoral” Vaush

The correlation between vegan diets and human suffering is yet to be examined; no one should assume that veganism, or any other food diet, is entirely benevolent. Personally, after taking the time to explore the issue further and to consider the various perspectives, I could not come to a solid conclusion as to which diet has the worst human-oriented effects. Such a conclusion can only be drawn upon a thorough analysis of many different sources, something that constitutes a research of its own.

Animal Suffering

Veganism is a philosophy that raises awareness for animal suffering and exploitation. The concept has been around for centuries, but only recently it has gained unprecedented recognition. Some say it's simply because people can now be more flexible with their dietary choices. Others attribute it to "post-modernism", a 21st century movement characterized by skepticism of the grand narratives of the modern world. No matter the cause, it's clear that this issue is here to stay; and that's probably for the best.

One of the main motivators for people to become vegan is exactly to steer away from animal suffering [15]. Unfortunately, our society is still far from ensuring that animals are treated with respect and kindness. Reports of animal cruelty and violence in slaughterhouses around the world are plentiful and well-established, making this a major cause for concern. Taking action to protect animals and end their mistreatment is essential.

While taking action is essential, being able to formulate and associate these actions with a net positive animal-related effect is of uttermost importance. I’m mainly referring to the relationship between dietary choices and their impact on animal suffering. When it comes to this, things are more complex than one may expect. Let me explain:

Vegan activists have been generally unable to effectively demonstrate that their dietary practices are scientifically associated with fewer animal deaths (not reduced suffering, simply deaths) [6]. I most definitely agree with the idea that vegans often overlook the intricate connections between -seemingly- straightforward food choices.

An article written by a former chef [7] demonstrates several mind-boggling examples of sentient animals killed to protect the cultivation of plant-based foods (admittedly, lack of citations and use of empirical examples attenuate the trustworthiness of the article). Animals, ranging from rodents to deer-like species, are presented in the article as “collateral damage”, a necessary evil in the process of cultivating crops and producing plant-based foods. Smaller species can harm crops by residing on them, while larger species can ruin them by trespassing crop fences.

The article also notes a quite interesting paradox: Vegans generally don't eat honey due to its domestication and extraction, which is correlated with the exploitation and death of bees. However, bees are essential for pollinating crops, with one-third of all crops relying on them. Without them, some crops would fail, and others would become more expensive. Thus, not consuming honey can have a negative, or more precisely a “boomerang” effect on the availability of plant-based foods. It’s either one or the other, you can’t have both.

The main overall takeaway is that the effects of our diet, whatever that is, are highly unpredictable and quite complex. It's a nuanced issue that can't be easily boiled down to a black-and-white answer.

“Vegans are right to point out the consequences of meat consumption, but they should not be intolerant to other views. Eating less meat probably translates into less suffering, but veganism isn't free of harm either.” [8]

Philosophy

Before reading this section, please bear in mind that prior to writing this, I’ve had the same friction with the science of philosophy as I have had with videos of how to put on makeup on; none. Before doing this, I didn't even know how philosophy and ethics were separated. Don’t get your hopes up, I still don’t.

I have always assumed philosophy to be a publicly inaccessible subject, something only those with the highest levels of intellect could grasp. However, as I began researching more, I realized that philosophy can indeed be an intriguing and thought-provoking field, but at the same time, somewhat accessible.

Unfortunately, my citation frequency has been drastically reduced since I was writing based on the overall picture I formulated. Nevertheless, I made an honest attempt to tackle the topic as professionally as I could.

"Veganism is a philosophy and way of living which seeks to exclude—as far as is possible and practicable—all forms of exploitation of, and cruelty to, animals for food, clothing or any other purpose; and by extension, promotes the development and use of animal-free alternatives for the benefit of animals, humans and the environment. In dietary terms it denotes the practice of dispensing with all products derived wholly or partly from animals." The Definition of Veganism, The Vegan Society.

“As far as is possible and practicable” has been the greatest point of controversy between the communities. It’s a big part of the core philosophy of vegans, which is widely characterised as “negative utilitarian”, meaning one should strive to minimize the total amount of -animal- suffering.

The AVC proposes that this statement is so loosely defined that it basically implies anyone can or cannot be called a vegan [6]. You could be called a vegan as long as you ever did something that is not directly contributing to animal suffering. This “something” could be virtually anything, even killing an animal, since there is always room to cause more harm to the animal or even harm multiple animals at once. At the same time, you could be called a non-vegan solely because you have not made the maximal attempt to reduce animal suffering at all times.

The VC claims that they (AVC) are deliberately ignoring the bigger picture of their philosophy, which is to reduce animal suffering, and instead they are preoccupied with unimportant details, such as this one. They believe that although one may stumble in this paradox, the purpose of this conversation is not to set a highly accurate and definitive limit for what is morally acceptable, but rather to generally encourage abstinence from activities that are clearly linked with animal suffering.

Responding, the AVC argues that the reason they focus on this detail is because many radical vegans tend to exploit its ambiguity, to aggressively promote their agenda, rather than respectfully and holistically advocate for it. Evidently, there are numerous incidences where vegan activists tend to criticise people for not completely and invariably sticking to their agenda [10][11][12]2. This, it is argued, is in direct contrast to a more healthy and balanced approach that allows for individual autonomy, freedom of choice, and more importantly, long-term diet viability. Not only is this criticism understandable, but it’s also a reminder for all of us that promoting a message of inclusivity and understanding is more important than coercing and by extension alienating those who do not support our narrative.

“The goal here shouldn’t be to frame people as being immoral for participating in these systems, the goal should be to help them understand that finding alternatives in participating in those systems would be better” Vaush

The two communities largely agree on this point of criticism; promoting a humane message is preferable to a coercive one. However, the VC tend to highlight that in the 21st century, it is unforgivably easy to abstain from animal products. They argue that access to vegan options is now more convenient than ever, with vegan-friendly restaurants, grocery stores, and even convenience stores stocking plant-based products [12]. Therefore, while they respect people making their own partial contributions, they argue that this may not be enough.

As you may understand, you could easily find yourself down the rabbit hole of watching them keep debating about this: Is there a threshold of what one can do to be considered a vegan? If so, where is it? Can it be followed in practice? The discussion goes on and on.

Another greatly discussed issue is the whether “animal suffering” and “animal death” should be used interchangeably. This comes down to the following; If animals are -generally- killed instantly and painlessly, how can it be said they are actually suffering? [13]

Some people believe that animals should not suffer any pain whatsoever, even if it is for a brief period of time. These people often use the counter-argument, “so you’re ok with another human dying instantly...”. Others dispute that this brief time period is actually brief by arguing that slaughterhouses adopt killing methods solely on the basis of maximizing profit rather than reducing suffering. They argue that businessmen do care about conditions in which animals live and die, as long as their wallet is intact. Without trying to make stereotypes, I noticed that these people often express opinions surrounding a more left-wing outlook, a more anti-capitalistic one. Others even say that it is impossible to know for sure whether an animal is actually suffering, even if it is killed quickly and painlessly. Additionally, they argue that it is impossible to determine whether an animal is actually suffering from the death itself, or from the conditions leading up to the death.

“The death they suffer in our hands commonly is, and always may be, a speedier, and by that means a less painful one, than that which would await them in the inevitable course of nature[...]We should be the worse for their living, and they are never the worse for being dead.” Jeremy Bentham, modern utilitarian philosopher.

Environment

Given the size of the article at this point, I was tempted to exclude this segment entirely. This temptation intensified after I came across several statistics, like the one below: “...45% had originally become vegetarian for ethical reasons, 27% for health reasons, 1% for environment reasons...” [15]. However, while researching for the aforementioned topics, I was repeatedly exposed to arguments regarding the ecological/ environmental impact of diets. This left me no choice but to include some of the ideas I encountered.

1. “...a 100% plant-based diet (e.g., vegan) has the least environmental impact...Still, it is important to note that, in order for a 100% plant-based diet to be sustainable, local products that minimize the environmental impact of transport should be preferred.” [14]

2. “While veganism can reduce the environmental impact of animal agriculture, it is not a guarantee that a vegan lifestyle will result in a more sustainable and environmentally friendly existence, as other factors such as transportation, food processing, and energy use must also be considered.” [7]

As we can see from the aforementioned segments, there is a recurring theme that veganism is the least harmful diet for the environment, provided that certain factors are taken into careful consideration. What's particularly noteworthy is that these segments are sourced from two different articles, which were repeatedly cited by opposing sides, namely the left by the VC and the right by the AVC, to support their respective arguments.

This highlights the need for critical analysis and objectivity when it comes to interpreting scientific literature. It's not uncommon for individuals with different agendas to “cherry-pick” data that aligns with their pre-existing beliefs and ideologies.

Moreover, we can clearly extract that while veganism may have certain advantages over other diets in terms of environmental impact, it's important to recognise that the issue is complex and multifaceted. There are numerous factors that contribute to the overall ecological footprint of food production, including land use, water consumption, transportation, greenhouse gas emissions, food processing and waste management, to name a few. Therefore, a holistic approach that takes into account all of these factors is necessary to arrive at a comprehensive understanding of the environmental impact of different diets.

Closing, I acknowledge that my understanding is limited in the face of the vast amount of literature available on this topic. In fact, I may be repeating myself here, but the relationship between enviroment and dietary choices genuinely requires its own dedicated research. However, I believe to have made an honest attempt to grasp the general scientific consensus.

Conclusion

As I conclude this project, two months in the making, I am humbled by the magnitude and complexity of the topic of veganism. My perfectionism, once a source of pride, has now become a fundamental cause for concern. What started as a one-week endeavor has turned into a two-month journey of self-discovery and growth.

As I reflect on the countless hours of research, writing, and editing, I cannot help but feel a sense of unease. Have I done justice to this important topic? Have I been objective in my analysis, or have my biases and personal preferences clouded my judgment? These are questions that torment me as I present this article to the world.

Despite my doubts and shortcomings, I am proud of this work, and I hope that it contributes to the ongoing dialogue surrounding veganism. I acknowledge that my journey is far from over, and that seeking truth is my true lifelong pursuit.

As for veganism, I am now more convinced than ever of its complexity. I used to be frustrated by articles that did not take a clear stance. Now I can understand more than ever the importance of avoiding premature conclusions and pushing personal agendas. Instead, we should focus on promoting inclusivity and understanding when exploring a topic as controversial as veganism. It would be naive and foolish for me to dictate what you should do or believe. Therefore, the only confident conclusion I can make is that it is essential to engage in respectful and open-minded conversations without alienating those who do not support our particular narrative.

References

1. Craig, W.J. (2009). Health effects of vegan diets. The American Journal of Clinical Nutrition, 89(5), pp.1627S1633S. URL: https://doi.org/10.3945/ajcn.2009.26736n

2. Federal Commission for Nutrition (2018). Vegan diets: review of nutritional and health benefits and risks. URL: https://www.blv.admin.ch/blv/en/home/das-blv/organisation/kommissionen/eek/vor-und-nachteile-vegane-ernaehrung.html

3. Animal Aid. (n.d.). COVID-19 Vaccines and Veganism. URL: https://www.animalaid.org.uk/the-issues/our-campaigns/animal-experiments/covid-19-vaccines-and-veganism/

4. GOV.UK. (2021). Guide to the use of human and animal products in vaccines. URL: https://www.gov.uk/government/publications/use-of-human-and-animal-products-in-vaccines/guide-to-the-use-of-human-and-animal-products-in-vaccines#animal-products-used-to-make-vaccines

5. Stanford Medicine (2019). Why Animal Research? Animal Research at Stanford. URL: https://med.stanford.edu/animalresearch/why-animal-research.html

6. [Reddit Article] r/AntiVegan (2020). I made an evidence-based anti-vegan copypasta. Is there anything important missing?. DOI: https://www.reddit.com/r/AntiVegan/comments/e3c2om/i_made_an_evidencebased_antivegan_copypasta_is/

7. Sott.net. (2020). So you’re a vegan ... but are you, really? -- Sott.net. URL: https://www.sott.net/article/416231-So-you-re-a-vegan-but-are-you-really

8. [Reddit Article] r/DebateAVegan (2021) CMV: There isn't really an excuse to not be vegan. Please feel free to comment why you aren't vegan, and I will respond with everything I got. URL: https://www.reddit.com/r/DebateAVegan/comments/n0t199/cmv_there_isnt_really_an_excuse_to_not_be_vegan/

9. [Reddit Article] r/DebateAVegan (2019) People dislike veganism because it shows how flawed their own morals are. URL: https://www.reddit.com/r/DebateAVegan/comments/g2x04z/people_dislike_veganism_because_it_shows_how/

10. [Youtube] Debate AskYourself Vs Vaush, I Wrecked Vaush So Badly He Had Me Silenced! URL: https://www.youtube.com/watch?v=AQ-AD95jGK8&ab_channel=AskYourself

11. [Youtube] Debate AskYourself Vs Blaire White, Discussing veganism with Blaire White. URL: https://www.youtube.com/watch?v=Zv5SFCGLXxY&t=2401s&ab_channel=AskYourself

12. Says, E. (2014). Fanatic Vegans not caring about humans. [online] Vegan Rebuttals. URL: https://veganrebuttals.wordpress.com/vegans-are-fanatic-and-dont-care-about-humans/

13. Gary Lawrence Francione and Garner, R. (2010). The Animal Rights Debate. Columbia University Press.

14. Chai, B.C., van der Voort, J.R., Grofelnik, K., Eliasdottir, H.G., Klöss, I. and Perez-Cueto, F.J.A. (2019). Which Diet Has the Least Environmental Impact on Our Planet? A Systematic Review of Vegan, Vegetarian and Omnivorous Diets. [online] 11(15), p.4110. URL: https://www.mdpi.com/2071-1050/11/15/4110

15. Hopwood, C.J., Bleidorn, W., Schwaba, T. and Chen, S. (2020). Health, environmental, and animal rights motives for vegetarian eating. PLOS ONE, 15(4), p.e0230609. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7117663/

Introduction

Lactose intolerance is one of the most, if not the most, researched food intolerances in the world. It occurs when the body is unable to digest lactose, a sugar found in milk and other dairy products, leading to uncomfortable symptoms such as bloating, gas, and diarrhea.

Lactose intolerance has played a vital role in the evolution of human populations, shaping their dietary habits, cultural practices, and genetic makeup. In this article, we explore among other things, lactose intolerance from an evolutionary standpoint, diving into the mechanisms that have influenced its frequency and distribution across populations, and examining its impact on human evolution.

Before doing that, it is of great importance to explain and simplify some basic concepts surrounding the topic. These include: (a) what exactly is lactose and how our body absorbs it, (b) the pathophysiology of lactose intolerance, the mechanisms behind uncomfortable symptoms and (c) the genetic factors that determine intolerance, including the related genetic mutations.

It's important to note that the information presented on this article are not based on proper, rigorous, acaedemic research. Rather, they are intended to provide a general overview of the topic and shall not be taken either as a citation source or a substitute for professional advice.

Lactose

Lactose makes up approximately 6% of the milk, and it’s one of the main ingredients in dairy products [1]. It is a relatively large sugar (disaccharide – double sugar) and cannot be absorbed by our body. In order to be absorbed, mammals developed a mechanism, in which they break it to smaller sugars (monosaccharides – single sugars), galactose and glucose; sugars that can be then absorbed and used as an energy source from the cells of our body. This “breaking process” is a consequence of the action of a certain enzyme-protein, lactase, which is encoded-produced by the lactase gene (LCT) [2].

Lactose Intolerance Pathophysiology

In the majority of humans (2/3), the activity of lactase declines rapidly right after the end of the weaning phase, a trait known as lactase non-persistence (LNP). On the contrary, the remaining 1/3 maintains the ability to produce lactase, a trait known as lactose persistence (LP). [2]

Individuals with the trait LNP experience the following pathophysiological process: Most of the lactose passing through the GI, cannot be broken down to its monosaccharides due to insufficient lactase present. Thus, it continues down the GI tract and enters the colon [3]. Inside the colon, where the presence of bacteria is most notable, the following processes happen: (a) Bacteria ferment-process the excess lactose, creating a mixture of gases including hydrogen, carbon dioxide and methane, all resulting in various abdominal symptoms such as gas and bloating. (b) The fermentation products (ex. acetate, butyrate, propionate) along with the unabsorbed lactose decrease water absorption (osmotic pressure), resulting in symptoms such as diarrhea. [3]

Note that the individuals with the trait LNP vary in the amounts of lactose they can tolerate before symptoms develop; this being one of the main reasons the number of individuals actually being diagnosed is significantly lower than the 2/3 of the population. [1]

Lactose Intolerance Genetics

This segment may prove challenging for individuals who lack a foundational understanding of genetics. Therefore, to ensure catholic comprehension, an attempt was made to concisely demonstrate some core concepts. If you are already familiar with these, feel free to skip the following four paragraphs.

Genes are segments of DNA that control the production-expression of proteins, which in turn perform various functions in our bodies. Usually, the produced proteins of a specific gene are inter-related and control certain traits in our body. For instance, eye colour is determined by a set of proteins, only expressed by certain genes.

Humans have two copies of each gene, called alleles, one from each parent. These copies-alleles can be the same, or they can be different. If the alleles are different, the individual is termed hetero-zygous for the specific gene and if they are the same, the individual is termed homo-zygous. Let's consider a simplified example of the gene controlling eye color. You can inherit two black-eye alleles from your parents (homozygous), or you can inherit one black-eye allele from your mother and one brown-eye allele from your father (heterozygous). As you may have imagined, in case of inheriting two black alleles (homozygous), you'll end up having black eyes. However, things get a little more complicated in heterozygous inheritance. In that case, you'll end up having brown eyes. That is because the brown allele is stronger and dominates the expression, and that's why we cal it the dominant allele. The black allele is completely silenced and that's why we call it the recessive allele.

In a more generalized fashion, heterozygous inheritance consists of one dominant and one recessive allele. However, there can be cases of intermediate inheritance (incomplete dominance). In intermediate inheritance, the alleles are not expressed as dominant or recessive; rather, the dominant allele is expressed in a reduced ratio. To help you understand this, let's imagine that the gene for eye color was following intermediate inheritance. In this case, you could have dark brown or light black eyes, or anything in-between black and brown.

Another important term you should know is single nucleotide polymorphism (SNP). SNPs are frequently occurring DNA variations (variation and mutation are used somewhat interchangeably). SNPs are like typos in a book, small changes in the letters that can alter the meaning of a word or sentence. In the case of DNA, these small changes can impact genomic function and alter the end-result, protein formation. SNPs are often used as genetic markers in research studies to track the inheritance of genes or to identify genetic variations associated with specific traits or diseases.

In the case of lactose intolerance, several SNPs had been found on the LCT gene. However, none of them consistently correlated with the production of lactase. That is to say, scientists could not calculate whether an individual’s trait was LP or LNP, simply by looking at the behavior of those SNPs [3]. In a recent study however, two relevant SNPs have been found. One SNP in particular, known as SNP -13910C/T, has been found to be strongly linked to an individual's ability to digest lactose. This SNP describes the presence of two alleles on a certain gene, termed "T" and "C", which influence how much lactase an individual's body can produce at any moment. This directly translates into whether the individual is lactose intolerant or not [4].

As you can observe from the above table, if the individual is homozygous for the "C" allele (C/C), the production of lactase will be at a minimum and thus the individual will most probably be lactose intolerant (LNP). On the contrary, if the individual is homozygous for the "T" allele (T/T), the production of lactase will be sufficient enough for the individual to be deemed lactose tolerant (LP). However, when an individual is heterozygous for the specific gene, a bizarre phenomenon is observed (incomplete dominance). It seems that if the individual inherits both "T" and "C" alleles (T/C), the production of lactase is moderate. And not just moderate, but moderate enough for the individual to probably be considered lactose tolerant (LP). Concluding, lactose intolerance in cases of heterozygosity has an intermediate character, in which no clearly dominant or recessive allele is obvious. Nevertheless, a weak pattern of dominance is observed by the "T" allele [4].

It's worth noting that the existence of two different alleles ("C" and "T") is solely due to the presence of the SNP in question. Without this SNP, there would only be one allele present, resulting in either universal homozygosity for the "T" allele or the "C" allele. This directly translates into humanity being either universally lactose tolerant or intolerant. And to determine that, one should note that humans are the only species that consume milk from other species. This being the case, we can deduce that almost certainly, if the SNP didn't exist, the prevailing scenario would have been universal homozygosity for the "C" allele, resulting in total human lactose intolerance.

Evolutionary Genetics of Lactase Persistence

As stated, the T allele of the specific SNP tilts towards domination. It has been shown that in cases of heterozygosity, the T allele prevails and causes the production of moderate amounts of lactase. The result is an individual with minimal-to-none signs of lactose intolerance. Several questions arise here. Why is this the case? Why nature facilitated the prevalence of lactose tolerant individuals?

Apparently, it has been elicited that the "T" allele originating from specific SNP, has a positive natural selection [2]. That means that individuals who inherit at least one "T", have a greater likelihood of surviving and reproducing, leading to an increase in the frequency of the allele within the population over time. As a matter of fact, some authors have estimated that the specific selection has been shown to exist as far as twenty thousand years ago. Its strength is also estimated to be extremely high, even surpassing the powerful selection mechanism for malaria resistance [2][4]. Strong positive natural selection means that the advantage conferred by LP is strong enough, to generate a rapid increase in the frequency of lactose tolerant individuals within the population. Nevertheless, the question remains: Why has nature facilitated this phenomenon?

The most widely accepted theory is that the LP trait provided an evolutionary advantage by allowing lifetime access to nutrient-rich milk in societies that traditionally practiced cattle domestication. While this theory serves as the best explanation for the majority of scenarios, there are regions and cultures where it simply does not apply. For example, some cultures in the Middle East, although heavily relying on pastoralism, exhibit low frequencies of LP. This, along with other discrepancies, have puzzled evolutionary biologists. However, some counter-explanations have been proposed [2]:

One theory proposes that a variety of factors influence the willingness and the ability of a said population to process and ferment milk in order to produce dairy products [2]. Note that the fermentation of milk results in the breakdown of lactose. For instance, a population that prefers dairy products, over consuming milk by itself, would have been less exposed to lactose, leading to an increase in lactose intolerant individuals, over time.

Another theory proposes that the mixing of pastoral and non-pastoral populations may have reduced the effectiveness of natural selection [2]. This can be explained as follows: hat has relied on domesticated cattle as their primary food source for generations. Now, imagine this population moving to a new region where people have other sources of food and do not depend on cattle. After several years and interbreeding between these populations, a mixture of genes may result in the formation of traits that do not correspond to the new environment.

In conclusion, the fact that the specific SNP(s) underwent strong positive natural selection, shaped the evolution of human populations. However, while LP provided an evolutionary advantage in societies that practiced cattle domestication, there are exceptions and they can be challenging to our understanding.

Conclusion

Diving into the complex world of lactose intolerance has been nothing short of amazing. From examining its pathophysiological mechanisms, to studying cultural and genetic factors that contributed to its occurrence and distribution. I hope this article provided a clear and manageable picture as my goal has always been to make scientific concepts accessible and understandable to everyone.

While there is still much to learn and explore, our understanding of this condition highlights the importance of genetic and cultural diversity in human evolution. Ultimately, further research on the evolutionary aspects of lactose intolerance can provide valuable insights into the complex interplay between genetic, cultural, and environmental factors that shape our understanding of human health.

References

1. Gerrit M. Westhoff, Ben F.M. Kuster, Michiel C. Heslinga, Hendrik Pluim, Marinus Verhage (2014). ‘Lactose and Derivatives.’Ullmann's Encyclopedia of Industrial Chemistry. Wiley-VCH. pp. 1-9 DOI: 1002/14356007.a15_107.pub2

2. Augusto Anguita-Ruiz, Concepción M. Aguilera, and Ángel Gil (2020). ‘Genetics of Lactose Intolerance: An Updated Review and Online Interactive World Maps of Phenotype and Genotype Frequencies’ Nutrients DOI: 3390/nu12092689

3. Praveen K Roy, Sarah D Komanapall, Homayoun Shojamanesh (2019) ‘Lactose Intolerance’ Gastroenterology< Drug & Diseases, Medscape. URL: https://emedicine.medscape.com/article/187249-overview

4. Nabil Sabri Enattah, Tine G.K. Jensen, Mette Nielsen, Rikke Lewinski, Mikko Kuokkanen, Heli Rasinpera, Hatem El-Shanti, Jeong Kee Seo, Michael Alifrangis, Insaf F. Khalil, Abdrazak Natah, Ahmed Ali, Sirajedin Natah, David Comas, S. Qasim Mehdi, Leif Groop, Else Marie Vestergaard, Faiqa Imtiaz, Mohamed S. Rashed, Brian Meyer, Jesper Troelsen, and Leena Peltoneo (2008). ‘Independent Introduction of Two Lactase-Persistence Alleles into Human Populations Reflects Different History of Adaptation to Milk Culture’ American Journal of Human Genetics 1 to 109; 1949 to 2022 DOI: 10.1016/j.ajhg.2007.09.012

5. Rejane Mattar, Maria do Socorro Monteiro, Cibele Aparecida Villares, Aníbal Ferreira dos Santos, Flair José Carrilho (2008). ‘Single nucleotide polymorphism C/T(-13910), located upstream of the lactase gene, associated with adult-type hypolactasia: validation for clinical practice’ Clinical Biochemistry DOI: 1016/j.clinbiochem.2008.01.006