Author: grinn124

That is a mouthful.

This week I will be delivering a full helping of information on the monoclonal antibody treatment Adalimumab, a drug that has more information than you can imagine on its FDA page. Adalimumab, under the manufacturer’s name Humira, is a Tumor necrosis factor (TNF) inhibitor used for a variety of different autoimmune disorders where the individual’s TNF naturally has gone a little haywire. As a means of introductions, monoclonal antibody treatments are drugs that consist primarily of an antibody that binds very specifically to a single epitope of an antigen. They are used for blocking and inactivating a variety of different self and non-self things as a means of stopping a certain pathogen or problematic self something-or-another to protect the person.

Humira is one such monoclonal antibody treatment that is used for a small set of different autoimmune disorders where TNF, a cytokine produced by a variety of leukocytes, is implicated as part of the problem. Humira is actually something I am very familiar with as a good friend of mine takes it as treatment for rheumatoid arthritis, a condition where TNF has a problem recognizing tissue in the joints and signals for inflammation and attack of the tissues, causing severe pain and eventual breakdown of the joints if untreated. The antibody in Humira binds to the body’s circulating TNF and inactivates it, preventing it from signaling for inflammation in the joints.

Obviously this is not a perfect solution. If TNF didn’t have any function in the body, it probably would not be produced. TNF functions to induce inflammation, as well as apoptosis in certain situations, such as with cancer cells and infected macrophages. Since it is produced by a variety of leukocytes, macrophages, and T-cells included, this diminishes the capabilities of both the innate and acquired immune systems to respond to infections. The side effects of using Humira are generally things that happen because TNF is not around to prevent them, with a few exceptions. Here is a list so you know what I am talking about:

• Increased risk for systemic infections
• Increased chance for certain malignant cancers
• Increased risk for activation of latent infections such as TB
• Possible Anaphylaxis
• Possible Heart Failure

Now, these are pretty bad, but also very rare, and are monitor-able and treatable for the most part. The individual would be much worse off if they chose not to use this treatment and avoid those risks, as the auto-immune disorders that Humira treats are not self-limiting and are basically guranteed to cause great pain and disability for the individual. Now one thing in particular to keep in mind when starting Humira is that point about activation of latent infections. Humira is contraindicated for individuals with latent TB, as it can cause the infection to become active once TNF is taken out of the picture. The reasoning for this is a bit convoluted, but if you can digest the information in this article, it discusses the fact that TNF helps to induce apoptosis in infected macrophages, which is where TB likes to hide. Without TNF to kill off TB’s breeding grounds, the infection can get out of control. This is why individuals who are about to start taking Humira must get some serious TB testing to make sure they don’t have a latent infection, though it seems to have very little link to arthritis.

These are trying times. What started as news in the microbiology world has erupted into the one word that has at least temporarily changed and reshaped the lives of just about everyone around the globe. Many are sick, and many more are scared, not just for themselves but for the role they could play in its transmission and the balance they discovered they must strike between public and personal interest. Those hunkered down in their homes are surely wondering if there is more being done than just waiting it out. Surely there must be more being done to stop it than just hiding from it right? Allow me to shed some light on the subject.

As I’m sure many who have spent their time glued to the news have noticed, it seems every day a new potential cure is being touted. A drug that was used for this, a treatment that was used for that, why don’t we just have a vaccine already, etc. Many who don’t have a great understanding of how vaccines and vaccine development works are likely frustrated at the lack of a magic shot that shields us from the virus. What they don’t understand is that scientists need months of data and work to even determine what is effective at stopping the virus, and even more time to figure out how to make and use it safely. Right now, we are still in a stage where we are trying to more accurately determine numbers of cases and trace the body’s response to the virus. As this John Hopkins Public Health school article points out, the name of the game in testing and tracking exposure lies in antibodies. We have identified the antibodies that indicate exposure to COVID-19, and blood tests that show that these antibodies are present in the blood means that they have been produced in response to the virus being present in the body.

However, we can get even more specific than that. By measuring the type of antibody present in the blood, we can get actually get a sense of how long it has been since the individual was exposed. IgM is generally the first antibody type that is produced during an infection, and is slowly replaced by a much higher scale production of IgG as the infection continues. IgG also has a longer half-life than IgM, so after the infection has run its course, IgG is the primary antibody left in the bloodstream. As this Medicinenet article points out, this method as well as testing for viral RNA in the blood sample are the primary lab based methods of testing for the virus. Though we still have a ways to go in terms of testing before we can start to get some real answers, this does provide real hope that shows the real progress being made. What this means for us is that we have developed the tools that can give us a better map of the transmission of the virus, and hopefully move faster to stop it than it can move.

You get a CAR! and you get a CAR, and you get a CAR!!

T-cell therapy has slowly emerged over the last decade or so as a novel immunotherapy for several forms of cancer, primarily blood cancers such as lymphoma. It involves taking T-cells from the patient, genetically modifying them with what’s called a chimeric antigen receptor or CAR, which binds specifically to the tumor cells of the patient, then placing them back into the patient with the idea that it would boost immune system recognition of the tumor, according to this article from a cancer news site. It seems simple enough. Give your t-cells a receptor that binds to your cancer, and the only change that should happen is it now has the ability to attack your tumor. Easy. This concept bridges fundamental immune system understanding with high level genetic engineering (maybe I’m just saying that because I have very little understanding of genetic engineering in the first place).

When you get into the logistics of it however, T-cell therapy goes big in all aspects of a cancer treatment. Not only is it seriously effective, but it also can have serious side effects and is seriously expensive. We’re talking nearly $500,000. Some of the side effects include severe cytokine responses, and several neurological problems such as speech problems and seizures. Not quite the miracle cure it sounded like it was before, but, they never are. Fortunately, the ever-moving flow of research promises methods of maintaining efficacy of the treatment while reducing rates of complications. According to this cancer.gov article, trials are underway testing new and different patterns for the CAR receptor to make it more specific to the tumor, with less of the unwanted reactions with other host cells.

This is all good and dandy, and maybe this is a lack of cancer treatment exposure on my part, but how did this treatment get through without dealing with these complications in the first place? Were researchers simply not equipped with the tools necessary to test for unwanted binding with other host cells? Were they acknowledged but deemed a much better outcome for the patient than likely death? Or is it a matter of the CAR being developed specifically for each person, and so it is difficult to predict an unwanted reaction, making it a risk associated with personalized medicine? These are difficult questions to answer, but hopefully ones that will become obsolete with the passing of time and research.

The age of Covid-19 has meant many things to many people. I managed to find myself in what is likely one of the few years in my life that I really would not have preferred a global pandemic to occur and shut everything down. Not only am I a college student who was just really starting to find their groove and accomplish all they wanted to accomplish in college, but I managed to find myself at that point in my senior year of college, meaning all of these things that had started to come to fruition were chopped at the stem and left to never have the opportunity to grow again. Too many events left cancelled, goodbyes left unsaid, memories left unmade, and lasts that I couldn’t expected to be lasts. No more sport club practices, intramurals, or lenoir (yes I had a meal plan as a senior, and I was proud of it) left to go back to.

Now maybe this sounds dark and depressing, and seeing it in writing myself is a little bit unsettling, but surprisingly, I don’t feel much more than nostalgia. Maybe I have already come to terms with all that has past, maybe Micro prepared me for it, or maybe its yet to hit me, who knows. Only time will tell. I am currently staying with a friend out in a rural community in western NC, as I did not have an opportunity to schedule a flight home before everything went downhill and don’t feel like now is a time to be taking flights. I realized I am likely in one of the safest communities possible right now, as people are spread few and far in between already, and don’t travel much at all, so social distancing hardly takes much effort here to enact. Mostly, what I struggle with most right now besides making sure I am correctly juggling the due dates for all my new online assignments, is the always looming BOREDOM.

Keeping myself entertained outside of class time has been quite an underdog in terms of what I expected to face during this time. When faced with long periods of free time, I am not someone who is content with sitting down for long Netflix sessions. I have a strong need to feel productive, to use my time to get something done. My capabilities for that have been somewhat diminished but not nearly as much as other things, because the internet is a wonderful place. I can’t go out and build a shed, go rock climbing with my friends, but I can still further myself. I have been doing copious amounts of home workouts, running, and research into how to train with minimal supplies for different physical feats such as handstands, front-levers and the like. I tried a few different things to fill the time, and this has brought me the most feeling of fulfillment while loosely under house arrest. I also have just been looking into various intellectual interests, and have found solace also in the UNC meme page on Facebook in particular, a page filled with people in similar situations, using humor as a coping mechanisms. I was especially comforted by the meme pictured below, which gives me hope that my musings will eventually lead to something greater coming out of these wild times.

Recent years have brought about an unexpected resurgence of STIs, with syphilis one of the major ones jumping on board with this trend, even though it was widely thought to be essentially a disease of the past. How could this be the case in an age of increased education about safe sexual practices? The answer, to the dismay of many of the younger population may be dating apps. Maybe this is exactly what defensive parents trying to get their children off of those apps and to meet people the ‘good old fashioned way’ want to hear, but it is still a worrisome trend that must be corrected. Whether it is less thoughtless usage or more education, the actions that the app developers and users take may play a significant impact on rates of transmission of these diseases.

To me, this news is not surprising. Even without having been a user of one, I know enough people that are users to know that many of the interactions set up by users of these apps are made very quickly, which is often the appeal and point of the apps in my opinion. This Politico article discusses the idea that individuals on these apps are often looking for brief relationships, and managing risk of STI transmission is put on the backburner when their thoughts are on quickly moving forward towards a sexual interaction. The apps involved also are hesitant to include information about syphilis and other STIs because they don’t want their app being associated with disease, as it hurts their image. Luckily, as of recently, some apps such as Grindr have moved in the direction of cooperation with organizations that promote STI prevention, taking measures to allow free ads for clinics offering STI screenings and pushing users to disclose any STIs they may have with a potential partner.

This is a particularly smart move, one that I wish more apps would take part in, and stop perpetuating the stigmatization of individuals with these diseases, as a measure of stopping disability and mortality associated with them. This is especially important with syphilis, as it is a potentially lethal disease when not treated. Luckily, it is often easily treatable with antibiotics, that is, assuming it doesn’t become resistant, but that is another conversation. While this is encouraging, one concern to keep in mind as brought up by an information sheet addressing rising syphilis rates in Nevada, that as with many STIs, individual with a long term syphilis infection carry a risk of passing it on congenitally, creating a deadly disease in children. All of this goes to say that even when it comes to relationships either short or long term, think about the health of you and your partner first.

Most people know the story by now; antibiotic overuse is causing superbugs to run rampant and risk making this vital disease defense useless. Doctors are over-prescribing, patients are misusing, slewing antibiotics everywhere causing a whole big mess of… 30% of total antibiotic use. What? Yes. Human usage accounts for only about 30% of all used antibiotics, with the large remaining majority of antibiotic products being used in farm animals. The agriculture industry, like many industries, is quite imperfect in its operations, and vast quantities of antibiotics are used one as a preventative measure of disease for animals, but also in sub-therapeutic doses as a means of promoting growth. The mechanism for this is not largely understood, but likely has to do with killing off bacteria that could steal even a morsel of food from the animal, allowing them to fatten up faster than their microbiota-infused counterparts. No, it doesn’t directly impact humans as quickly as misuse in humans, but it is still a big problem.

This Wired article meanders a bit before getting to the point, but it does do a good job of summarizing the threat caused by this practice. Besides the obvious point of diseases that can affect both animals and humans quickly becoming resistant when faced with constant high levels of antibiotic use, these resistant bacteria can also pass along these resistance genes to other bacteria that may not impact the animal, but does impact humans. This use has created resistance to antibiotics that were not even previously on the radar as ones that were being resisted, with the source being resistant bacteria in livestock transferring genes. This means that even though we are very much part of the problem in our own consumption, we are pushing the metaphorical snowball of antibiotic resistance along much faster by using them recklessly on animals.

While the obvious solution seems to be make antibiotic use in animals illegal, that creates an unsurprising messy web of problems that must be dealt with. First of all, resistance is popping up the fastest in places where use is highest, which seems like the obvious place to start. However, these are most often areas where the use is high because the demand is high. These are areas that desperately need the food, and likely would prioritize immediate needs over global public health. Second, it doesn’t seem like there are currently many good alternatives. If antibiotic use were to stop cold turkey, disease and reduced growth would cut a sizable hole in productivity. This c&en article discusses some alternatives in the process of development, but given the language of the article that in order to meet the current effectiveness of antibiotics in production, there would be a much higher cost associated with the remedies involved, among them being probiotic promotion and new vaccines. This is obvious, as antibiotic overuse wouldn’t be a problem if there was an easy solution sitting on our lap. More research needs to be done before these solutions can be rolled out, so cold turkey doesn’t seem like a viable option. For now, I think cooling the turkey as much as each producer can within their means is the best we can do, while diligently keeping an ear out for developing research.

Vaccines seem to be all the rage these days. And by rage, I mean rage in the typical usage of that colloquial phrase, and rage as in rage. The concept of vaccination has managed to become the divisive topic that few would expect could even be divisive. So called anti-vaxers have emerged seemingly from nowhere in an era that is supposedly more trusting of science more so than other sources than any generation up to this point, to the lamentation of the scientific community. As an individual who is free of measles, mumps, chickenpox, polio, tetanus and many more preventable diseases, due to the diligence of my parents and the parents of countless others in vaccinating their children, it is a question I am greatly curious about. So I took this opportunity to educate myself on the movement and how it has managed to spread ironically at a similar rate to some of the diseases they choose to let their children be susceptible to.

Some searching yielded some surprisingly satisfying results. This New York Times article actually did a good job of getting to the point and delivering on the title of the article. It discussed numerous factors that could contribute to the rise of vaccine apprehension, without claiming that any were the sole cause of the movement. Among the reasons cited, there was one quote that stood out to me: “Vaccines are a victim of their own success”. This is actually a quote from a doctor quoted in the article, who went on to explain that widespread vaccination has led to a severe decline in the diseases they were made to prevent (big surprise), so many individuals today do not know of anyone who has faced these diseases, and therefore see vaccines only as shots that are made by big pharma and required by the government. Conspiracy theorists would likely be skeptical of vaccines on this reason alone but I can see how it would play a role in diminishing the trust of vaccines in the eyes of someone who has little other knowledge to go by, given the fact that big pharma and the government are often seen these days as giant suspicious institutions.

This trend is inherently dangerous to public health, with a prime example being polio, a debilitating disease thought to be on the verge of eradication. The vaccine for this comes in two flavors; the intravenous IPV, and the oral OPV, with the OPV in recent history generally being the method of choice for vaccination in areas with civil unrest or lack of resources due to its ease of access and use. However, as shown in an article from the disease prevention news site Healio, the OPV vaccine has recently recreated a strain of polio, leading to numerous cases in these areas. The article listed the cause as the weakened virus making its way from a vaccinated child to the GI tract of multiple other unvaccinated children, which gave it time to mutate back into a virulent form. Given the low vaccination rates in these areas, the cases of polio have managed to rise again, and now threaten more developed areas where polio was eliminated from due to pockets of non-vaccination forming. On top of that, other pockets of wild type polio have also reemerged at the same time in more developed areas that never fully eliminated the disease, allowing it to take hold again. If you’re going to be an anti-vaxer, at least wait until the disease is actually eradicated before putting people in danger.

Unless your gut is telling you to avoid reading this blog post and go do something else. If that’s the case, then ignore it. Research is giving us more and more reason to give credit to our gut for so many different aspects of our health. If you’re into more of the science behind it, take a look at this article that gives a great overview on how the bacteria of your gut are essential to how you function. In brief, many of these bacteria are able to digest things that we can’t, and make products that we can use, prevent harmful bacteria from damaging us, trigger necessary homeostatic reactions, and so much more.

Ok, so what? Yeah our microbiome is essential to our function, meaning the reverse is also true if it gets messed with. While it isn’t necessarily intuitive, anyone who thinks about it enough could realize that if everyone has bacteria in their gut, then there must be some sort of beneficial reason for its presence or it wouldn’t be so prevalent. Is there anything more interesting than just an important role in survival? What else does our microbiome do for us? When it comes to questions like these, we often need to look no further than research. As an endurance athlete, I wanted to know if our microbiome had any role in endurance sport performance, like whether some people had some bacteria in their gut that provides some sort of product that increases performance, or something along those lines. After I short search, I was not disappointed. An article from a team at Harvard studying Boston marathoners found that a certain bacteria that was normally a small part of the microbiome was extremely active in a vast majority of the marathoners following activity. It was found that this bacteria processes lactate and produces free fatty acids that we can then use in beta oxidation during long duration activities.

To me, this adds not only a new layer of depth to the study of the roles of the microbiome, but also another layer to the ethics of performance maximization of sport. If there are bacteria found to increase performance when in the guts of athletes, would it be ethical to artificially increase your numbers of this bacteria? In my mind it would be on the same level as blood doping, but it will be interesting to see what comes from this.

Every few years, it seems there is a new up and coming disease to test its mettle against humanity. Right now that disease seems to be the coronavirus. News articles are dropping by the day with new reports on death tolls, infection rates, quarantines, new areas of infection, etc., building it up to be a scary enough bug to make you double check that you lock your doors at night. But is it truly something that the general American public needs to concern themselves with? Many are quick to remind us that the flu is what we should really be worried about, pointing towards stats from the CDC reporting that there’s been an estimated 18 million cases and 10,000 deaths in the US this flu season.

So which threat should the average layperson actually direct their efforts towards avoiding? The known killer with a firm historical grip or the newcomer surrounded by unknowns? One would think the easiest way is to simply look at infection vs mortality rates. So first, the flu: looking just at the US, 10,000 deaths out of 18 million cases would put the odds of dying from a case of this year’s flu strain at .005%. On the other hand, using data from an article by the Scientific American, there have been about 20,000 reported cases, and 427 deaths. Looking purely at the numbers, 10,000 is a whole lot more than 427, but the odds of dying from the currently are around 2%. In that case, then it’s obviously coronavirus that needs to be avoided then?

I just don’t think its so simple to be comparing these two diseases. There are too many changed variables between the two diseases that its an apples and oranges discussion. Obviously there are going to be a lot more flu cases than cases of the coronavirus because the flu is present around the entire country, and coronavirus has just emerged in China, so transmission rates are hard to compare. The rate of death is higher for the coronavirus, but there’s also not a vaccine of any kind for it, and it is hard to compare all the environmental factors that differ between Wuhan, China where the virus is most prevalent, and the vast array of different areas in America. Coupled with the fact that there is so much we still don’t know about the mechanisms of the disease, and it makes a mess of a comparison. There is little reason to be watching out more for one over the other, especially considering that it is believed that the coronavirus spreads by small droplet transmission, similar to the flu. So, at the end of the day, wash your hands and cover your mouth when sneezing, coughing, or when you feel like you are about to say something about whether the flu or the coronavirus is more worrisome.

This is the first post of my blog for my microbiology class. My name is Greg and I am a student at UNC with an exercise and sports science major. Outside of my microbiology class, you will rarely find me more than a couple of feet away from a rock climbing wall. I am an avid member of the rock climbing club on campus, and you can find more information about that here. Stay tuned here for more microbiology related posts and likely some desperate attempts to relate it to rock climbing.