CAR T-cell therapy and its uses

While reading ahead in our textbook, many of the immune therapies impressed me with their clinical applications. However, one in particular stood out to me. Chimeric Antigen Receptor T Cell Therapy (CAR T), discussed in chapter 17.3 of our textbook, is a form of T cell tranfer therapy in which cells are removed from the patients body and augmented with a receptor for a specific kind of cancer, according to The American Cancer Society. This therapy is still relatively new, and research is being constantly conducted concerning its potential applications (NIH National Cancer Institute). Currently, it is only used to treat leukemia, lymphoma, and multiple myeloma (The American Cancer Society).

(NIH National Cancer Institute)

To dive further in depth on the actual treatment process, one must understand how the aforementioned cancers function. Leukemia and Lymphoma are both cancers that target the blood and the lymphatic system, respectively (NIH National Cancer Institute). As a result, they are able to spread throughout the body rapidly, and treating the disease can be hard to do without killing things like healthy red blood cells. CAR T therapy is invaluable in this respect. Blood is harvested from the patient, their white blood cells are extracted from the sample, and then the rest of the blood is returned (The American Cancer Society). The T cells are then grown in a laboratory where they are fitted with an antigen-specific receptor that correlates to a certain kind of cancer such as Hodgkin’s Lymphoma (The American Cancer Society).

The patient is then treated with a low-dose of chemotherapy to suppress immune function (The American Cancer Society). The augmented T cells are reintroduced, where they then kill cancerous cells by latching on to the antigen presented on the surface of the malignant cell (The American Cancer Society). Just as a key fits into a lock, so does the cancerous antigen fit into the antigen-specific receptor on the augmented T cell. Currently, research is being conducted on the effectiveness of CAR T cell therapy against solid tumors such as ovarian cancer (Medscape). According to Medscape, CAR T cell therapy is being combined with an mRNA vaccine and is delivered intravenously. These therapies, while still in early stages, are showing promising results that suggest they may be able to be employed in the coming years (Medscape).

The current state of Tuberculosis

Prior to taking this class, I always regarded Tuberculosis as a thing of the past. You hear the name and automatically think of the 19th century, with its large, open air houses constructed to mitigate spread of the disease. You don’t, however, think of it as one of the leading causes of global death and sickness (ScienceDirect). While in the United States, our incidences of Tuberculosis remain low, an estimated 10 million people contracted Tuberculosis in 2019, according to a 2021 report on the state of Tuberculosis (ScienceDirect). Moreover, a very high majority of these cases are located in Southeast Asia, with even more of them being concentrated in India, which accounts for 26 percent of all cases worldwide (ScienceDirect).

A BCG vaccine is administered to a baby in 1949 (The Scientist).

In 2021, the world celebrated the one hundred year anniversary of the development of the Bacille Calmette-Guérin (BCG) Tuberculosis vaccine (The Scientist). The vaccine, however, is largely ineffective at preventing contraction of the disease (The Scientist). Its main usage is in infants born to families with active tuberculosis infections (The Scientist). The BCG vaccine is effective in reducing the development of a specific, virulent form of tuberculosis that often results in death (The Scientist). So, while the infant most likely will contract thte disease and prevent with the typical symptoms such as coughing and difficulty breathing, they will be easier to treat and have a better chance at surviving (The Scientist). Recent research developments regarding the BCG vaccine have shown that it may in fact rely on an antibody-mediated immune response to protect its host, and not a humoral response (Nature).

These findings provide an opportunity to better understand the mechanisms behind the effectiveness of the BCG vaccine and how to improve its protectiveness. While the global Covid-19 pandemic replaced tuberculosis as the infectious disease with the highest mortality rate in 2020, its persistence is still very worrisome (ScienceDirect). Global health experts desired to reduce tuberculosis cases by twenty percent by the end of 2020; however, they were only able to do so by nine percent (ScienceDirect). Better health education and access to healthcare will be one of the main routes toward reducing tuberculosis globally (ScienceDirect). If affected individuals can receive consistent treatment and be made aware of the risks regarding the disease, incidence should be drastically reduced (ScienceDirect).

Going mediterranean

Growing up in the United States, I’m definitely accustomed to a diet chock-full of processed sugars and grains, pumped full of GMOs and pesticides. While this hasn’t really bothered me, learning about the importance of the gut biome this year has really affected my thoughts regarding the subject. According to an article by Harvard, the gut microbiome is directly fed by what we eat; more complex starches and fibers are digested in the small intestine by microbiota which supplies the body with important nutrients it can’t get elsewhere. As a result, they recommend a high fiber diet, as it triggers chemical reactions in bacteria which lower the pH of the stomach and stunt the growth of certain pathogens Harvard). Sugars and lactose feed microbiota in the stomach, but if you feed them too much sugar, unhealthy levels of unnecessary microbiota can grow Harvard). The list of ways your diet can affect your gut health go on and on, and a poor gut microbiome can lead to things such as poor digestive health Harvard).

A recipe from the mediterranean diet that I’d like to try is the infamous “tik tok pasta. (The Washington Post)” It combines a block of feta cheese, fresh grape tomatoes, whole grain pasta, garlic, basil, and olive oil to make a creamy, unforgettable dish (The Washington Post). It went viral last year for being so quick, easy, and delicious. Not only is this dish rich, but it provides the stomach with complex grains from the pasta, good fats such as olive oil, and nutrients from the grape tomatoes (The Washington Post). Detailed on The Washington Post, there are many potential variations to this recipe, but this one stands out to me the most (The Washington Post).

I am so excited for the national championship game tomorrow! I am leaving for New Orleans immediately after I finish this. I’m not entirely sure where I’m staying tonight … whether that be in my car or in a hostel, but I’m just planning on figuring it out when we get there! I think the matchup between UNC and Dook last night was win they will NEVER be able to top. I am so proud to be a Tar Heel! Enjoy this picture of Hubert Davis below.

https://clutchpoints.com/unc-news-hubert-davis-emotional-reaction-to-north-carolina-reaching-final-four/

The potential for a Norovirus Vaccine

Norovirus is practically the modern-day form of the plague. When I was in high school, a norovirus outbreak sent three hundred students home in just two days. A miserable cause of acute gastroenteritis, no vaccine has been developed due to its high genetic variability. However, a promising cadidate developed by Takeda Pharmaceutical Company Limited is currently progressing along clinical trial phases (Frontiers). The vaccine is a viral-like particle vaccine, meaning it imitates pieces of parts of the virus in question and uses this to prompt an immune response (Frontiers). Moreover, it is an intramuscular, two dose vaccine (Frontiers).

Above is a graphic depicting the signs and symptoms of Norovirus. Graphic courtesy of Medical News Today.

The phases of vaccine research are lengthy and can take many years to progress through in order to make sure that the vaccine is safe. In a YouTube video published by Johns Hopkins Medicine, these phases are explained. Phase 1 is the first human trials allowed, and has very few participants that are studied for one to two years to ensure safety (Johns Hopkins Medicine). Phase 2 is also smaller, with hundreds of people, and can take two to five years to study safety and dosage (Johns Hopkins Medicine). Phase 3 increases in size to thousands of people, which primarily investigates the immune response produced by the vaccine (Johns Hopkins Medicine). Organizations can apply for licensure upon completion of this phase (Johns Hopkins Medicine). Finally Phase 4 has hundreds of thousands of people, and studies participants longitudinally to determine longevity (Johns Hopkins Medicine).

The norovirus vaccine in development by Takeda Pharmaceutical Company Limited is currently in Phase 2 of clinical trials (Takeda). The VLP vaccine is currently being tested in humans in a double blind study that includes the usage of placebo (Takeda). Participants in this study are both men and women. Currently, Takeda’s vaccine is the only norovirus vaccine being tested in humans (Takeda). This phase of clinical testing was launched in 2016 and is currently in continuation (Takeda). Promising data from phase one suggests that the VLP vaccine produces a high immune response upon reception of two doses of the vaccine (Takeda).

Investigating the link between Autism Spectrum Disorder and vaccines

This blog is one that I have been looking forward to. Having grown up in the post-autism-vaccination-scare era of the United States, it was incredibly interesting and informative to learn about the bias and error behind the original study conducted by Andrew Wakefield in 1998 (Behavior.org). Dr. Thomas Zane, in his article “The Vaccine and Autism Connection: The Wakefield Study Once Again Discredited,” discusses the background behind the Wakefield study. He revealed that Wakefield recruited his 12 participants from a group that was known for their anti-vaccination agenda. More over, he was paid by attorneys who were constructing an anti-vaccination lawsuit to conduct the study. Wakefield was incapable of reproducing his results, and he started the initial study with his conlclusion already predetermined. He had no legitimate control group, and the children he studied were subjected to unethical and intrusive tests. As a result, his study was and still is dripping with bias.

Conversely, the Madsen paper , which was an attempt to debunk the Wakefield study once and for all, boasted more than half a million participants from Denmark that they longitudinally studied for 10 years. About 10,000 particpants were excluded from the study due to diagnosis of autism spectrum disorder or other realted conditions, immigration, death, or extreme illness. Unvaccinated children were the controls in this experiment. There is no clear bias in this paper. One could argue that the researchers entered into this study with the desire to disprove Wakefield; however, throughout their paper, they remain open to the possibility of its validity and merely examine the data to determine truth. In regards to the results of this study, it can be argued that the relative risk of autism spectrum disorder in kids injected with the MMR vaccine is equitable to those who are unvaccinated. As defined by the CDC, it could be said that the relative risk ratio of autism in vaccinated versus unvaccinated children is close to one.

https://covid19.ncdhhs.gov/vaccines

Personally I have no problem with vaccines. In fact, it upsets me when people do. Especially with the recent events of the COVID-19 pandemic, it is incredibly frustrating to know that life-saving injections exist, yet privileged people turn them down, selfishly endangering those who are not so fortunate as to be able to avoid exposure to diseases like the mumps. I am so thankful that my parents dilligently followed immunization recommendations, and that I was able to stay up to date on all my vaccines as a child. I can only hope that, moving forward, the anti-vaccination movement would lose steam and die out. If so, we can eradicate so many deathly illnesses from not only our country, but the whole world too.

Cholera flares up in Nigeria, Cameroon

When we studied Cholera in class, I was really interested by the disease, as I had always regarded it as a disease of the past. This assignment, however, opened my eyes to Cholera’s continued presence in the world. The first outbreak I examined occured in Nigeria in 2021 (US News and World Report). Cholera has an environmental resevoir, so northern Nigeria, where flooding is prominent and sanitation is poor, was hit very hard by this specific outbreak. Cholera organisms living in biofilms in the water was able to infect many and kill more than 2,300 people.

Photo credit: US News and World Report

The second outbreak I examined is a more recent one. Cameroon has counted more than 1,300 cases of Cholera as of February 10th, according to VOA News. This outbreak was driven by water as well, as water shortages led to community spread of Cholera around public water spouts and toilets. In addition, Cameroonian officials warned of eating contaminaed food and keeping latrines, where people use the restroom, dirty. Limited access to sanitized water means that Cameroonians are having to drink water infected with Cholera biofilms, leading to at least 13 deaths. The Public Health Ministry of Cameroon is tracking the cases through local hospitals; however, they believe their tallies are likely off as a lot of Cameroonians visit traditional healers and try not to visit modern doctors if possible.

This outbreak does not appear to have any association with antibiotic resistance. The driving factor behind both is most definitely a lack of access to clean drinking water and poor public sanitary measures. No specific strain of Cholera was identified as the culprit behind either outbreak. The public health officials of both Nigeria and Cameroon warned the public against dehydration and stressed the importance of replenishing liquids and electrolytes. Consequently, one can infer that children are at the greatest risk of passing away from Cholera, as they do not know when to rehydrate themselves and can suffer from complications.

Antibiotic resistance, examined

I never fully understood the gravity of antibiotic resistance until recently. Growing up, my family and I didn’t use many antibiotics – only when we were sick with a legitimate bacterial infection did we ever occasionally take pencillin when it was prescribed to us. My parents made sure to stress that we should always finish our antibiotics, never leaving any left. As a result, I didn’t know that so many people were so careless or misinformed as to not finish their prescriptions; I thought that was something people only joked about. Now, after reading an article published by The Institute for Health Metrics and Evaluation, discussing The Lancet report on antimicrobial resistance, I see that misuse and overprescription of antibiotics is a very scary thing (The Institute for Health Metrics and Evaluation).

The article summarizes the scary findings of the antimicrobial resistance study. It mentions that antimicrobial resistance has become the leading cause of death world wide (The Institute for Health Metrics and Evaluation). They estimated that in 2019, more than one million people passed away as a result of antimicrobial resistance (The Institute for Health Metrics and Evaluation). I couldn’t believe this, as I’m so used to considering cancer, heart disease, and COVID as the leading causes of death. I’ve never thought that, cross-sectionally, something like antibiotic resistance could be the leading cause of global death (The Institute for Health Metrics and Evaluation). While we might not feel its effects as much in the United States, its causing great pain in less developed nations (The Institute for Health Metrics and Evaluation).

Image courtesy of Nature.

Something that The Institute for Health Metrics and Evaluation mentioned stood out to me. They said that the diseases most assisted by antibiotic resistance were “lower respiratory and bloodstream” infections like pneumonas (The Institute for Health Metrics and Evaluation). I decided to do a bit more research on this, and I found an article by Nature, published in 2022 that listed the diseases that are the most deadly when it comes to deaths related to antibiotic resistance (Nature). Much to my surprise, they were almost all diseases we have studied in class. They go on to list E. coli, S. aureus, Klebsiella pneumoniae, and Streptococcous pneumoniae as the top four responsible for the greatest percentages of antibiotic-death (Nature). This definitely worried me, as in class we have discussed the great prevalence and high transmissability of these diseases. I can only hope that as we go forward, we will recognize how great a threat antimicrobial resistance poses to our society and work to combat it in some way.

An in-depth look into Mrs. Meyer’s Multisurface Cleaner

Mrs. Meyer’s Clean Day Multipurpose cleaner has been a STAPLE in my house for the last five years. Its impeccable scent, plus its seemingly magical ability to relieve every surface of stickiness and grime, has earned it a permanent place in our cleaning supply closet. Not only that, but we regularly purchase her hand soaps, candles, wipes, and more. One bottle costs $4.29 straight from her website, and their main selling point is that they use non-toxic, family friendly ingredients. The back of the bottle states that their products are made without “parabens & phthalates, glycol solvents, formaldehyde, and artificial colors.” Upon further investigation, I could not find any reputable sources elaborating on the toxicity of Mrs. Meyer’s Clean Day Multipurpose Cleaner, but instead, found it cited on numerous articles as one of the “Top 10” non-toxic products to try.

Photos: Sarah Lindsay

Not only could I not find any negative news on Mrs. Meyer’s, but the bottle also states that it is a USDA Certified BioBased Product. Truthfully, I am not entirely certain what this means, but it’s definitely used as a selling point for their products. When using this cleaner, I have definitely been just sanitizing, and not disinfecting, my counters. I think disinfecting something is honestly not realistic or necessary in a household setting. Sanitizing my counters is enough for me! Moreover, the cleaner does not SAY it is a disinfectanct, so I doubt it even has the capacity to disinfect. In fact, upon close examination of the bottle, it mentions nothing about killing microbes at all and simply states that it is “tough on dirt and grime.” Essentially, this multisurface cleaner mainly exists to eliminate tangible dirt from your counters and nothing more.

For the “How To” portion of this blog post, I visited a site called “The Thrifty Couple.” Their article called “Homemade Natural Antibacterial Spray Cleaner (For Cleaning And Personal Use)” gave recipe on how to make your own antibacterial wipes (The Thrifty Couple). The author goes on to talk about how she loves essential oils, which was an immediate red flag to me (The Thrifty Couple)! The recipe for antimicrobial wipes consisted of only water, tea tree oil, lavender oil, lemon oil, and oregano oil (The Thrifty Couple). After examining this list of ingredients, I am quite confident that this spray and its wipes will have virtually no effect on bacteria. None of the ingredients listed would ever be able to eradicate the cell wall of a microbe or penetrate its envelope.

The Variants, Explained

Throughout the course of the recent pandemic, I feel as though I have recevied more education in the greek alphabet than ever before! Titles such as gamma, alpha, omicron, and delta were thrown around incessantly, yet I never truly understood what they meant until I studied them more closely. I knew that viruses tended to mutate thanks to the four times I’ve watched the movie Contagion, but I didn’t know how this applied to our current SARS-CoV-2 pandemic. An article by The New York Times was able to shed some light on the topic for me. It explained that viruses are constantly mutating, and a variant is deemed a variant when a collection of viruses all boast the same group of mutations.

In the case of the coronavirus, the mutations of concern occur in regards to the spike proteins (The New York Times). Through our studies in microbiology, I have learned that RNA viruses such as COVID-19 are much more prone to mutations than DNA viruses due to replicating errors. According to the World Health Organization, these errors effect the order of amino acids in a viruses’ RNA, triggering the development of different proteins. Scientists have been able to identify specific amino acid sequences of concern and watch them (World Health Organization). In class, we learned that this is the reason why being an RNA virus is considered a virulence factor, as changes in the proteins a virus produces can lead to it becoming more infectious or deadly.

The above graphic highlights important “clusters” of mutations in the Omicron coronavirus variant. Graphic courtesy of The New York Times.

As explained in The New York Times article, the Omicron variant has a unique combination of 50 mutations, 30 of which pertain to the spike proteins which “the coronavrius uses to attach to human cells” and infect them (The New York Times). In comparison to Omicron’s 50, the Delta variant was home to at least 12 mutattions that also modified the viruse’s spike proteins (The New York Times). These mutations contributed to the viruse’s abiltiy to dock onto a human cell as well (The New York Times). In increasing the virus’ abiltiy to attach to a human cell, the infection rate of the virus is increased, as it can more easily begin to replicate and take up residence in a human, causing illness (The New York Times). It is for this reason that the Delta variant and the Omicron variant became more prominent than the original strain of SARS-CoV-2, because these mutations enabled them to more rapidly spread and had a much lower infectious dose.

The gut microbiome and depression

We’ve all heard it before. Some foods are “brain foods,” others are “junk foods,” but before investigating the many effects of microbes in the gut, I brushed this off as merely a platitude. However, upon reading two articles from The New York Times and Science, I now know that there is strong evidence the microbiome is directly linked to depression and mental health (The New York Times, Science). While this evidence is not causal, it opens up a world of opportunities for investigation into potential new treatments for depression (Science). Additionally, these treatments provide hope of greater accessibility, as diets such as the “Mediterranean Diet” provide healthier options at an affordable price (The New York Times).

Graphic courtesy of Rocio Egio via The New York Times

The microbiota in the human gut may play a role in depression through the production of neurotransmitters, specifically catecholamines such as dopamine and biogenic amines like serotonin (The New York Times). These neurotransmitters play a large role in the development of depression, as deficiencies in both are often attributed to be a major cause of the disorder. Recent research has supported the plausablity of a brain-to-gut link via the vagus nerve that enables these microbiota to provide mental health benefits (Science). Additionally, research reported in Science has documented similar missing microbiota in people with depression and repeated these results within three different people groups (Science). Evidence such as this bolsters the hypothesis that differences in microbiota may contribute to the development of depression.

One stipulation of this research is that there is little to no understanding of whether microbiota are responsible for depression or merely a product of it (The New York Times). People with depression are may simply eat foods with higher fat content, leading to consistencies in their gut microbiomes (The New York Times). Moreover, a study conducted in which two groups of participants with depression were given equal amounts of counseling and support, but only one group was placed on the “Mediterranean Diet” in which they ate more seafoods, nuts, and vegetables found that participants who ate according to the diet reported higher levels of improvement than those in the control group (The New York Times). This evidence gives support to the theory that differences in microbiota precede depression and not the other way around (The New York Times). I am excited to learn more as research drives forward and hopefully produces new treatments for mental health disorders like depression.