SOLUTIONS
How do we fix things? Should all problems be solved? Problem solving consists of using specific or common methods in a systematic or untidy way to find solutions to problems. Approaches to problem solving strategies may be discipline-specific or interdisciplinary. Areas that have attracted significant attention in recent decades include managerial problem solving, lawyers' reasoning, electronics troubleshooting, personal problem solving (such as personal financial decision making, lifehacks, self-help), invention and innovation, and crowdsourcing. Common crises that demand solutions may involve economics, disasters, lifestyle choices, relationships and family, chronic illness and injury, workplace conflicts and career pressures, social justice and wealth distribution, mobility, and mental health, often in combination.
Reading and Mental Health
Camilla Brown
I was taught to read at a young age due to homeschooling. It became my infatuation and my escape from reality. As technology became more prevalent, my interest in reading waned. I became more addicted to my cell phone and social media. I have noticed a significant change in my mental state since I stopped reading. I find myself feeling more anxious and unfulfilled. The positive feedback loop from social media and notifications on my phone is both addicting and damaging. I will never stop feeling unfulfilled. Recently, I have found that making deliberate efforts to read more brings me a sense of calm and fulfillment not found in social media.
Studies have shown that reading has numerous mental health benefits, including improved mood, reduced stress and anxiety, and even assistance against symptoms of depression. The evidence is strong. A survey conducted by the UK charity The Reading Agency in 2018 found that reading can positively impact mental well-being. Three-quarters of respondents reported that reading improves their mood and more than half reported that it helps them relax. The survey also found that reading can be particularly helpful for people experiencing stress or anxiety. Almost three quarters of respondents reported that reading helps them cope with difficult times.
Another study published in the Journal of Psychiatric Research in 2015 found that reading can be an effective form of self-help for people experiencing symptoms of depression. The study found that participants who read self-help books as part of their treatment experienced significant reductions in depression symptoms compared to a control group. Research has also found that reading can help improve cognitive function and may even help to reduce the risk of developing cognitive decline and dementia. A study published in the journal Neurology in 2013 found that people who engaged in mentally stimulating activities such as reading throughout their lifetime experienced less cognitive decline in later life compared to those who did not engage in such activities.
With the increasing prevalence of digital media and distractions like social media and smartphones, it can be challenging to find dedicated reading time and maintain focus while reading. Some evidence suggests that our decreased attention span may affect our reading capacity. As our attention span decreases, we may find it more difficult to focus on and engage with longer texts, such as books or articles, which require sustained attention and concentration. It's important to note that reading itself can be a great way to exercise and improve our attention span. Engaging in deep reading practices that require sustained attention and focus helps counteract the distraction and improves our ability to concentrate over time.
Making Theatre Safer: How Sequential Disassembly Can Prevent Injuries
Alyx Strong
Behind the magic of live theatre, concerts, and circus shows is a hidden world of engineering called rigging. This intricate system of cables, motors, and metal beams—known as trusses—makes it possible to suspend lights, sound equipment, props, and even performers. For touring productions that move between cities quickly, these systems must be set up and torn down promptly, often in just a few hours. But when mistakes happen during teardown, the results can be dangerous. This is where sequential disassembly comes in, offering a safer and more efficient way to handle rigging systems by making it impossible to disassemble them incorrectly.
Rigging systems are complex and similar to puzzles in that every piece is connected to build a bigger picture. The problem arises when one must have intricate knowledge on the order to remove the pieces to do so safely. Much like with Jenga, if you remove the wrong piece, the entire thing can come crashing down in an instant. If the wrong cable is unhooked, or a beam is unbolted out of sequence, the whole system becomes unstable and dangerous to both the crew and equipment.
These risks are not purely theoretical; theatre technicians often hear first-hand accounts from coworkers about how a rushed teardown and improper training or supervision can go wrong. During the Army’s Soldier Show in 1996, a new worker removed the bolts securing the trusses to their anchor points in the ground without first hinging the trusses and safely lowering them to the ground. This caused the truss to violently come crashing down, damaging the truss and the stage, and nearly flattening several crew members with the force of the fall. Thankfully, no one was severely injured, but that truss fell with such speed and force that it could have easily killed someone. This accident is one of many, and provides a stark reminder of how susceptible traditional rigging systems can be to human error especially with new personnel and high turnover. This dilemma underscores the need to eliminate human error through design.
The safest way to address this issue is with practical or technological sequential disassembly systems to ensure that parts can only be removed in a predetermined order, otherwise activating safety features. There are various ways to implement design that prioritizes safety through enforcing a step-by-step process. For example, mechanisms can be as straightforward as physically blocking the next bolt or connection point until the previous one has been safely removed, preserving the sequence without the need for complex tools or electronics. Alternatively, sequential disassembly systems can include more technologically advanced components like automatic locks, and visual or audible signals which can alert the crew and prevent unsafe disassembly.
Sequential disassembly systems enhance safety, protect equipment and crew, and streamline rigging for timely assembly and disassembly. They prevent accidents, demonstrate commitment to safety standards, reduce crew injuries, and safeguard live performances, making them essential for fostering creativity and building a safer future for productions.
The Ethics of AI
Jackson Greer
In a time where many are worried about their jobs being replaced by technology, it may be comforting to hear that people have shared identical worries for centuries. Textile and agricultural workers were the first to see their jobs transformed. When Ford introduced the assembly line, it became more common for workers to do a specialized, repetitive task, rather than the whole process, like a craftsman shoemaker being replaced by a group who can mass produce with the assistance of machines. Throughout technological advancement, people have always been replaced, but they have always found adjacent things to do. One could say that modern advancement is no different and we will all settle into new jobs, but the comfort this provides may be superficial.
Bring Back the Hutchins Commission
Lily Perry
“When you think about news today, what do you think about?”
I polled a group of 25 college students, and the top three answers to this question were “entertaining,” “anxiety-provoking,” and “lies.” News, especially on television, is about entertainment and emotion, rather than informativeness and objectivity. Companies will do or say anything to profit, even if that means misinforming the masses and spreading lies.
The news was not always like this. In the 1940s Henry Luce and Robert Hutchins created a commission on social reasonability and ethics for journalists. This “Hutchins Commission” decided that the press has a responsibility to give voice to the public and to society generally. In other words, the media has a responsibility to inform.
The Commission outlined five requirements for a responsible press:
(1) the media should provide a truthful, comprehensive, and intelligent account of the day’s events in a context that gives them meaning
(2) the media should serve as a forum for the exchange of comment and criticism (that is, the press should present the full range of thought and criticism)
(3) the media should project a representative picture of the constituent groups within the society
(4) the media should present and clarify the goals and values of the society
(5) and the media should provide full access to the day’s news.
Today’s media neglects most of these requirements. We struggle as Americans against an irresponsible press. Most media outlets now promote misinformation and disinformation. They spread falsehoods. Media has also become more polarized. Outlets allow only certain ideas to be promoted. They are platforms for sharing one-sided viewpoints. We watch, read, or listen to Fox News for a right-wing perspective and CNN for a left-wing perspective. There are very few middle-of-the-road sources, or sources that will cover the multiple perspectives. The ones that do are not very popular since they do not prioritize entertainment over informativeness.
So how do we hold the press accountable and to the standards of the Hutchins Commission? There is no clear answer, but I believe to combat disinformation, misinformation, and polarization we need to create a new non-profit or government organization that funds news that is free and fair. We need a media outlet that is focused more on informing than capital profit. We must learn about different perspectives and acquire truths that will help us start conversations that promote change.
mRNA Vaccines: Our Magic Bullet for Seasonal Influenza?
Simon Anderson
Nearing the end of 2020, many Americans began to hear an unfamiliar term: "mRNA," particularly alongside the word "vaccine." Two years into the COVID-19 pandemic, such a term is commonplace. Looking beyond the current infectious threat to future outbreaks, could mRNA vaccines be the magic bullet that allows us to protect the citizens of the world from a multitude of flu strains, or even be the platform upon which we craft a universal influenza vaccine?
Below is a roadmap of this article. As shown, all of the advantages of mRNA influenza vaccines are rooted in the vaccine’s structural simplicity. In this article, I will demonstrate that mRNA vaccines are easier to produce, faster to produce, and cheaper to produce than whole-virus vaccines. They can provide increased protection against influenza by targeting multiple antigens, and those antigens are more likely to resemble those on circulating virus than antigens found in whole-virus vaccines. Finally, mRNA influenza vaccines can be freeze-dried for easy storage, enabling health workers to get the vaccines to areas without cryo-temperature freezers.
Compared to traditional influenza vaccines, mRNA vaccines may be simpler and easier to produce
Seasonal influenza vaccines contain whole viral particles that have been inactivated through heat or chemicals, or live attenuated influenza virus (LAIV) grown in eggs (or cell cultures for those with egg allergies) (CDC, 2021). There are several drawbacks of these vaccines, the foremost being that the viruses that make up the vaccine must be propagated through cell cultures. Not only is this time-consuming, requiring that vaccine production begin eight months before flu season, but every replication of a virus yields mutations. Given that a new generation of influenza viruses can be produced from a single infected cell in just six hours (WHO, 2022), the vaccine’s viruses will go through almost 1000 generations over the eight months of production. The mutations accrued during this time may cause the vaccine virus to antigenically drift away from the viral strains the vaccine is designed to target. By the same process (where humans serve as the cell cultures), the seasonal influenza virus may also antigenically drift or shift away from the virus being cultured. Because of the long production times and whole-virus production methods currently used, the influenza vaccine we administer to the population generally does not look immunologically identical to the seasonal influenza virus. The result is a vaccine that is generally only 40-60%, and sometimes as low as 10%, effective (Zimmer, 2021).
An intuitive way to avoid antigenic drift is to produce vaccines faster, giving the seasonal flu virus less time to mutate. However, with current methods, the plausibility of speeding up vaccine production is limited. Whole-virus vaccine production requires large amounts of space, machinery, and manpower to culture and purify virus to be used in the vaccine. RNA vaccines are structurally much simpler than whole-virus vaccine; as such, RNA vaccine manufacturers only need the capability to produce in vitro-transcribed (IVT) RNA. “In vitro” means that whole cells are not necessary for production of the RNA, the RNA can be produced solely through biochemical synthesis using cell-free enzymes (Guevara et al., 2020). In vitro transcription uses the same synthetic DNA template for every copy of RNA (Guevara et al., 2020), as opposed to whole-virus vaccines, where every new generation of virus is actually a copy of a copy of a copy, hundreds of times over. By merit of every RNA being a copy of one parent nucleic acid, RNA vaccines technically only have to be propagated one generation. The use of IVT RNA reduces the number of mutations found in vaccine-derived antigens to near zero. This could allow seasonal influenza vaccines to be 80% or more effective consistently (Zimmer, 2021); as an example, the Pfizer-BioNTech COVID vaccine is 95% effective (Zimmer, 2021; Blakney et al., 2021). In 2017, the National Institute of Allergy and Infectious Diseases (NIAID) published that one of their goals for a universal influenza vaccine is that it be 75% effective (Chen et al., 2020); an mRNA vaccine seems more likely to meet this standard than a killed or LAIV vaccine.
IVT RNA vaccine technology has been in development for the better part of three decades, though initial setbacks due to adverse immune reactions delayed their entry into mainstream use until the 2010s (Zimmer, 2021). During these decades of extra research, new methods of synthesizing and delivering IVT RNAs emerged that have made mRNA vaccines viable alternatives to whole-virus vaccines. The figure below shows the components and assembly scheme of a lipid nanoparticle (LNP), the vehicle that has been devised to deliver IVT RNA to cells, along with a brief discussion of the mRNA itself. Each molecule in the figure represents advances in the field of IVT RNA and mRNA-LNPs. These advances make the mRNAs and LNPs longer-lasting, more productive, and less adversely immunogenic (the body does not recognize the vaccine itself as an invader), enhancing the protective nature of the vaccination. The relative simplicity of constructing mRNA-LNPs is key to understanding why mRNA vaccines can be produced so much faster than LAIV vaccines.
Components and assembly of mRNA-containing lipid nanoparticles
IVT mRNAs go through several modifications before they are ready to be used in vaccines. Without these modifications, the mRNA is recognized by cells as foreign, and is destroyed before it can make any viral proteins. If the body deems the mRNA is not human enough, it is treated like a virus and destroyed, making the vaccine not protective. I do not include any analysis of self-amplifying mRNA (saRNA) in this article; Blakney et al. (2021) have discussed the production and merits of saRNA vaccines in the journal Vaccines.
The major lipids shown here make up most of the LNP, with the additional classes of lipids added to increase stability, prevent premature destruction of the nanoparticle, aid in localization to certain parts of the body or certain cell types, and help the LNPs enter cells. The lipids can be mass-produced through chemical synthesis and purchased by mRNA vaccine manufacturers, as opposed to the production of whole-virus vaccine, which requires the vaccine makers purchase living cell cultures and all the consumables that are required to maintain them. Combination of the lipids in certain ratios will facilitate self-assembly of the lipids around mRNA molecules to form LNPs, with the LNPs’ properties varying with the exact ratios of the lipids used (Lindgren et al., 2017). Figure elements adapted from Guevara et al. (2020).
Instead of producing viral proteins in a factory, which is what is needed to produce whole-virus or viral subunit vaccines, mRNA vaccines allow the human body to become the factory. A gene encoded within the mRNA (“transgene” in the figure above) is delivered to your cells by the LNP, and your cells produce the viral subunits the gene encodes. For influenza, this subunit could be the hemagglutinin spike, neuraminidase spike, M2 ion
Instead of producing viral proteins in a factory, which is what is needed to produce whole-virus or viral subunit vaccines, mRNA vaccines allow the human body to become the factory. A gene encoded within the mRNA (“transgene” in the figure above) is delivered to your cells by the LNP, and your cells produce the viral subunits the gene encodes. For influenza, this subunit could be the hemagglutinin spike, neuraminidase spike, M2 ion channel, or nucleoprotein (Chen et al., 2020). In some cases, it may be possible to make combination vaccines, where more than one kind of mRNA can be included in the vaccine, or even more than one protein can be encoded in a single mRNA. It may also be possible to encode whole viral particles, using our own bodies to produce whole-virus “vaccines” without the need for egg-based vaccine factories (Guevara et al. 2020). Vaccines that are currently being pursued are combination flu-COVID-RSV (respiratory syncytial virus) vaccines, pentavalent (five strains; seasonal influenza vaccines are quadrivalent, targeting only four strains) influenza vaccines, and combination hemagglutinin-neuraminidase vaccines (Zimmer, 2021; CDC, 2021; Dolgin, 2021). Some studies are also looking into encoding monoclonal antibodies against infectious diseases and cancer in mRNA vaccines (Guevara et al., 2020). Most interestingly, and perhaps most ambitiously, the ease of production of mRNA vaccines has prompted NIAID to work on a universal mRNA influenza vaccine, which is currently undergoing preclinical testing (Dolgin, 2021).
All of the above shows that mRNA vaccines present several advantages over current seasonal influenza vaccines. They avoid the risks of incomplete inactivation of killed vaccines or reversion of attenuated vaccines (Wong & Webby, 2012), while also having the potential to target more than one subunit of the virus. Their structural simplicity makes them easier to produce than LAIV vaccines. mRNA vaccines’ greatest advantage over LAIV vaccines, however, is that they have the potential to be consistently more effective than LAIV vaccines.
Compared to traditional influenza vaccines, mRNA vaccines may be faster to produce
Whole-virus vaccines must be propagated through biological means, requiring about eight months of production before vaccines can be administered. mRNA vaccines can be manufactured in vitro, requiring significantly less time. Because it takes so long to produce the seasonal influenza vaccine, selection of strains to be targeted happens a long time before flu season, resulting in the accumulation of mutations and decreased vaccine efficacy discussed above. Any successor to LAIV vaccines must be able to be manufactured in fewer than eight months to address this shortcoming. mRNA vaccines can be produced in six months, or even in a matter of weeks.
Production schedule of egg-based influenza vaccines versus projected schedule of mRNA-LNP vaccines
Given a flu season that starts in November, strain selection for an egg-based vaccine occurs in March. In the period from March to June, the engineered attenuated virus is propagated. The virus starts to be purified from egg cultures in July, and the first widespread vaccinations occur in October. The impending seasonal influenza virus and the virus used in vaccine production may antigenically drift and shift away from each other during this time, ultimately reducing the protective effects of the vaccine.
An mRNA-LNP vaccine can start production two to three months later than egg-based vaccines and does not require generation of new viral particles. This eliminates much of the opportunity for difference to appear between the circulating influenza virus’s antigens and the antigens contained in the vaccine.
The graphic outlined in red, illustrating an accelerated vaccine production timeline, shows that mRNA-LNP vaccines can be designed, produced, and tested in approximately two months in times of public health emergency. Not only does this virtually eliminate accumulation of mutations, but it also shows that mRNA vaccines will always be more feasible than egg-grown vaccines in the event of health crises, such as pandemics. Figure elements adapted from Chen et al. (2020), Blakney et al. (2021), and Moderna (2020).
The figure above compares three production schedules: the egg-based LAIV timeline (Chen et al., 2020), a projection for yearly mRNA vaccine production (Blakney et al., 2021) (which is longer than the emergency schedule because yearly campaigns will not receive the immense government support that emergency production does (Zimmer, 2021)), and an accelerated timeline, using Moderna’s COVID vaccine as an example (Moderna, 2020). All three are roughly aligned such that vaccination starts around the beginning of October. Thanks to simpler production methods for mRNA-LNP vaccines, selection of which influenza strains will be targeted by the seasonal vaccine can be delayed until May or June, versus March, as is the case with egg-based LAIV vaccines. Moderna has projected that it may be possible to get mRNA-LNP vaccines into clinical trials just 63 days after neutralizable antigens are identified, providing an extraordinary advantage over LAIV vaccines (Moderna, 2020).
Compared to traditional influenza vaccines, mRNA vaccines may be cheaper to produce
Starting in 2007, the WHO started to give grants to help establish new influenza vaccine manufacturing facilities in developing countries. Friede et al. (2011) studied the initial investment of 10 of the 11 companies chosen by the WHO to receive grants. Their findings are in the figure below.
Initial investment, per dose, to establish an influenza vaccine production facility
The investment a company is required to make, split across all doses of vaccines they manufacture, is dependent on how many doses the company can make annually and the method of vaccine production used. All prices are adjusted from Feb. 2011 USD to Feb. 2022 USD using the inflation calculator maintained by the US Bureau of Labor Statistics; these prices do not account for any adjustment of the actual cost, just decreases in the purchasing power of the dollar. Adapted from Friede et al. (2011).
The most striking feature of the graph above is that it requires the least investment per dose of vaccine to establish an egg-based LAIV production facility. However, we have discussed above that this is at the cost of longer production times, lower-fidelity coding sequences, and ultimately compromised vaccine efficacy. To estimate the cost per dose of an mRNA vaccine, which does not have those same weaknesses, we have to, admittedly, squint a little. Pharmaceutical companies are notorious for the obfuscation of their costs, though some independent groups have made some conjectures (“Vaccine monopolies...”, 2021).
It has been estimated that Moderna can produce their COVID vaccine at a cost of $2.85 per dose, and that Pfizer can manufacture theirs at $1.18 per dose (“Vaccine monopolies...”, 2021). Moderna puts 100 μg of mRNA in each dose of their COVID vaccine; Pfizer uses 30 μg in theirs (Kis et al., 2020). Evaluations by Kis et al. (2020) show that, as time goes on and the scale of mRNA vaccine production increases, costs will decrease and stabilize at $2.08 for a single dose of a 100 μg mRNA vaccine, or $0.60 per dose of a 30 μg mRNA vaccine.
Current costs, projected costs, and projected production output of 100 μg mRNA/dose and 30 μg mRNA/dose vaccines as a function of bioreactor volume
The estimates of how much money per dose is required to manufacture each company’s vaccine is marked in red (“Vaccine monopolies...”, 2021). As total bioreactor volume increases (i.e. as a company becomes able to produce more vaccine), the price of manufacturing a single dose of vaccine drops.
Kis et al. (2020) identify a 30-liter bioreactor as the most “technologically feasible and economically viable... working volume.” The cost to produce a single dose of a Moderna-like mRNA vaccine at this scale is approximately $2.08 per dose, and the cost of a Pfizer-like vaccine is $0.60 per dose. Adapted from Kis et al. (2020).
The above graphs reveal that, in theory, a new mRNA vaccine production facility could be established for less than $2.25 per dose. Not only is this less than the average historical investment calculated by Friede et al. (2011), but it is also less than every method of vaccine manufacture Freide and colleagues examined excluding egg-based LAIV. As I have demonstrated, the mRNA vaccines have immense pragmatic value over egg-based vaccines, and so a difference in cost of less than two dollars per dose should not dissuade us from pursuing the establishment of mRNA vaccine manufacturing facilities.
Despite Moderna and Pfizer theoretically being able to produce their mRNA COVID vaccines for $2.85 and $1.18, respectively, the two companies seem to be charging $19.20-$24.00 and $14.70-$19.50 on average (“Vaccine monopolies...”, 2021; Dyer, 2021). These are, of course, just estimates, but it is clear that even though the cost of producing mRNA vaccines against influenza will be lower than that of other vaccine platforms, future vaccination campaigns will have to be designed such that these savings are passed to those purchasing and distributing the vaccines.
Lyophilization makes mRNA vaccines easy to store
Current COVID-19 mRNA-LNP vaccines must be stored in nuclease (enzyme that degrades nucleic acids)-free water at -80°C (-112°F). The “cold chain system” refers to the series of -80°C freezers that biologics move through between the place of their production and the place of their use. While most biological and biochemical materials can be stored for many months – if not indefinitely – at -80°C, the cold chain that the COVID vaccines rely on does not extend everywhere.
LNPs become structurally altered by ongoing exposure to heat. The longer they are not at -80°C, the more warped they become and the less effectively they deliver their mRNA. The mRNA itself can also undergo chemical degradation, making it untranslatable (Muramatsu et al., 2022). In short, warm vaccines become ineffectual. This temperature constraint greatly limits our ability to distribute vaccines where they are needed most, namely poor and rural areas that are not close to, or cannot afford, -80°C freezers. These areas, which COVID has taught us are already at the highest risk of contracting disease, see the highest morbidity and mortality from disease, and have the fewest resources to evade the ongoing financial and health effects of contracting disease, are not a part of the cold chain. Therefore, the only way to make mRNA vaccine use equitable is to make it less reliant on the cold chain.
A well-established method of preserving mRNA-LNPs is lyophilization (freeze-drying). The method and buffers used to lyophilize an mRNA-LNP are dependent on the exact construction of the LNPs, and efficacy of mRNA-LNP vaccines do not always return to 100% upon reconstitution (rehydration) (Muramatsu et al., 2022). The figure below details work done by Muramatsu et al. (2022), which was conducted with mRNAs that encode influenza hemagglutinin.
Effects of lyophilization on the size of lipid nanoparticles and the stability of the mRNA within them, and on the vaccines' immunogenicity upon reconstitution with nuclease-free water
Lyophilized vaccines can be more easily stored, and thus more easily transported to areas where -80°C freezing is not feasible. This data implies that lyophilization of mRNA-LNPs could allow for wider distribution of vaccines worldwide, without any compromise in the protection they provide.
Top panel. Each column represents a different mRNA that was tested; the right column represents the hemagglutinin gene from an H1N1 influenza virus isolated in Puerto Rico in 1934. Particle size is an important factor in determining whether a LNP will be taken up by cells, thus particle size governs whether the antigen the vaccine protects against will be produced. All methods of storage kept particle sizes stable for 24 weeks. 150 nm, the largest average particle size observed, is "still within the range where LNPs have been reported to elicit robust immune responses in animals, including NHPs [non-human primates]" (Muramatsu et al., 2022). The mRNA contained in these LNPs degraded 10-15% when refrigerated and 30% at room temperature, versus virtually no degradation when kept at sub-zero temperatures and 70-80% degradation when over 100 degrees F. These both provide evidence that mRNA-LNP vaccines are largely structurally preserved by lyophilization and reconstitution.
Bottom panel. The hemagglutinin vaccines were still able to elicit robust hemagglutinin-neutralizing responses after reconstitution. The protective effect of mRNA-LNP vaccines is not significantly compromised by any structural changes that result from lyophilization. Adapted from Muramatsu et al. (2022).
Muramatsu et al. (2022) show here that lyophilization of their hemagglutinin-encoding mRNA-LNP is a viable method of keeping their vaccine stable outside of the cold chain with very little structural change for several months at a time. They also show that the efficacy of their vaccine was not significantly compromised by lyophilization. Lyophilized mRNA-LNP vaccine can be stored in a simple fridge (4°C, 39.2°F), or even at room temperature (25°C, 77°F), for up to six months, and earlier work by Petsch et al. showed that lyophilized vaccine can even be kept at human body temperature (37°C, 98.6°F) for three weeks without significant changes to its stability (Muramatsu et al., 2022; Wong & Webby, 2012). Lyophilization, while not exactly a straightforward process, is a method by which we might decrease the reliance of vaccine distribution on the cold chain and ensure more equitable vaccine distribution.
mRNA vaccines work against influenza
mRNA vaccines are faster and easier to produce and store than traditional influenza vaccines. They require less stuff in their production. The proteins they encode are more likely to resemble those found on natural virus. All of this is meaningless if they don’t work. Luckily for us, mRNA vaccines do show promising results in animal models.
The figure below is adapted from Lindgren et al.’s (2017) study of the protective effects of an mRNA vaccine against influenza hemagglutinin in NHPs. The goal of the experiments the following graphs are drawn from was to observe whether mRNA vaccines are capable of producing levels of anti-influenza antibodies that will protect against infection. These antibodies prevent the molecular actions that allow the virus to attach to and enter respiratory cells, and are thus referred to as “hemagglutinin-neutralizing antibodies.” Lindgren et al.’s (2017) results show that mRNA vaccines are equally – or perhaps more – capable of protecting against influenza versus traditional vaccines, in addition to having various logistic advantages over LAIV vaccines.
Immunogenicity of an mRNA-LNP vaccine encoding the hemagglutinin of a pandemic H10N8 virus
Two injections, four weeks apart, are sufficient to prompt a protective level of hemagglutinin-neutralizing antibodies. Following hemagglutinin-specific, not necessarily hemagglutinin-neutralizing, IgG (the antibody isotype most commonly used by the body to fight infection) shows a similar spike in anti-influenza antibodies, which takes about 19 weeks to return to the level of antibodies produced at the time of the second injection. The avidity (how well/strongly antibodies bind to hemagglutinin once they find it) was found to stay approximately stable after the second immunization, followed by an increase around 11 weeks after the animal was first challenged. What this demonstrates is that, even though the total concentration of anti-influenza antibodies in the blood decreases, the immune system starts to replace those antibodies with ones that bind to hemagglutinin more tightly, and thus neutralize the virus more effectively. This is thought to be indicative of an ongoing immune response against influenza, and is correlated with long-lived antibody-secreting plasma cells in the bone marrow. This data shows that mRNA-LNPs have the potential to be effective vaccines against seasonal flu. Figure elements adapted from Lindgren et al. (2017).
In 2016, a clinical trial by Moderna showed that mRNA vaccines could elicit antibodies against influenza, though this was at the expense of several side effects (Zimmer, 2021). At the time the COVID-19 pandemic struck, three more mRNA vaccines against influenza were in phase I clinical trials (Dolgin, 2021), but the work had to be put on hold as researchers turned their attention to the new threat. Satisfied that mRNA vaccines have done all they can for the COVID-19 pandemic, Pfizer, BioNTech, Moderna, the French company Sanofi, and the English company Seqirus are all conducting or planning to conduct phase I clinical trials on mRNA vaccines against influenza (Zimmer, 2021). If these trials reinforce what has been found in NHPs, and do not carry the side effects observed in the 2016 Moderna trial, we will have taken a huge step towards the eradication of seasonal influenza.
While not without side effects (usually fevers, aches, and fatigue (Dolgin, 2021)) and not without raising questions of equity (artificially inflated costs and difficulties in getting vaccine to where it is needed most), mRNA vaccines represent a new superweapon in the war on influenza. While not always as cheap as egg-based LAIV vaccines, mRNA-LNP vaccines are
- structurally simpler
- easier to produce
- faster to produce
- cheaper to produce than most other influenza vaccines
- less reliant on the cold chain, which negligently leaves poor and rural areas without vaccines
- capable of eliciting protective antibody responses against influenza
- able to target more subunits of influenza virions more easily than current subunit vaccines
- projected to be consistently more effective than egg-based LAIV vaccines
Further investment in influenza vaccines should be directed towards the establishment of mRNA-LNP production facilities, and toward education and trust-building campaigns. Without the latter, the former means nothing.
References
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Why Environmental Problems are Actually Wicked Human Problems
Gabika Watson
Many are familiar with Agatha Christie’s saying that “to every problem, there is a most simple solution." Some people even try to apply it to real life. Unfortunately this ideology is only true theoretically, or in simple problems that exist only in the human mind. When it comes to problems in reality, we can look to H. L. Mencken’s restatement: “For every problem, there is a solution that is simple, neat, and wrong.” Wrong does not necessarily mean that the solution is not fit for the problem posed, but that a real problem has too many agents with many different relationships and outcomes. Attempting to answer the questions only creates more. This is simply because “you can’t just do one thing."
One of the greatest problems faced by our world today comes from the environment. But we cannot think of the challenge of climate change, pollution, or other concerns as environmental problems. They are human caused, making them human problems. The environment has evolved and changed at its natural rate for millions of years. This has been conducive for millions of species. Since humans began living with a mindset to grow and conquer, the environment and other organisms have suffered tremendously. The society which has evolved out of settlement itself is incredibly complex and all of it either directly or indirectly impacts the environment. Unfortunately, our society was built on an unsustainable model and many of our actions have negative effects.
The environmental problem proposes a unique dilemma in which the more we intervene, the more the problem grows, which makes humans want to intervene more so then the problem just keeps redoubling. An example of this is seen in the drilling and use of petroleum oil. We realize that the more gasoline is burned, the more greenhouse gases are produced, thus worsening and speeding up the effects of climate change. More efficient cars are developed that use less gas for more miles, which causes people to buy more cars since it is cheaper to maintain them and then they also want to drive more, which increases the need for more gasoline. So more oil is pumped, more carbon dioxide is released, and then we decide to make a more efficient car so we use less gas. The cycle continues by a power rule growing exponentially until we are pumping more oil than is profitable and the atmosphere is so overrun with greenhouse gases that the climate is bound for a drastic change.
This problem is extraordinarily complex, with each level to the issue having its own sub-levels and so on. Proposed solutions to certain parts of the problem can create new or exacerbate other issues. One action always affects another which affects another, creating a never ending chain of reactions that leads to unknown negative or positive effects. Essentially problems keep evolving, making them not solvable but rather manageable. If we become able to realize the impact of our actions and able to work cohesively as a global community, humanity might stand a chance at managing the wicked environmental problem.
Technology's Emerging Role in Leadership Training and Development
Jonny Morris
One of the more relevant and commonest critiques of leadership development programs, both academic and professional, is that they do not offer enough hands-on application. Knowledge is power. But information without practical application is more like "potential" rather than actual "power."
For example, being able to identify a situation in which a member of your team may be served best through coaching, isn’t nearly as effective as being able to identify the situation and confidently provide coaching. The learning of leadership, like many fields and skills, comes through doing. A potential problem with applying leadership information: The rigorously fast-paced and perfectionist orientation of companies and organizations sometimes does not provide space for the necessary trials that accompany learning and growth.
I view positional-leaders as those who are often expected to produce perfection and perfect productivity. High-risk situations, typically, do not promote the psychological safety that encourages creativity or floating new balloons. Leadership training often includes training on different social dynamics such as conflict management, coaching, and emotional intelligence. As evolved social creatures, we are wired to seek comfort, avoid pain, and maintain a sense of belonging. As leaders, it is our job to grow, improve our resilience, and challenge and assist other people in ways that encourage their growth and resilience.
Above drowning, spiders, and death, public speaking is the most common fear people experience. Leadership training that focuses more on information-intake than hands-on-learning, mixed with the high-pressure situations and expectations that leaders face, is a combustible mix. It would not surprise me that some leaders may be reluctant to step forward an encourage social dynamics that help their teams, communities, and companies grow.
One of the technologies that has been shaking up the world of leadership training and development is virtual reality. Virtual reality training allows users to place themselves in life-like scenarios, where they interact with virtual characters on leadership techniques like conflict management and coaching. Have you ever reflected on an unpleasant conversation and later begun thinking of all the things you could have said that would have been way better than what you did say? VR provides the space for users to practice different conversational pathways and observe the results that those choices promote, allowing leaders to practice new approaches in a space that does not present a social or job-related risk.
Virtual reality training, especially in terms of social-dynamics, is still very new. From a few video demonstrations I’ve seen on VIAR 360’s website there are a limited number of responses that both you, as the user, and the virtual characters that you interact with, can give. As AI and VR develops and begins to intertwine in new and more detail-rich ways, we’ll see that leaders are able to experience situations and interactions that are extraordinarily similar to those we encounter in the real world.
Automation and the Future of Work
Kearney Quillen
One of the biggest threats to the jobs and livelihoods of millions of working class people is not immigration, as some politicians would have you believe, but automation. After making the initial purchase of manufacturing equipment, the cost of upkeep and repairs for machinery is leagues lower than the hourly wages of human labor. Workers, put simply, are being priced out of their own jobs by their own bosses.
But let's examine why this is a bad thing. After all, the jobs technology is rendering obsolete aren’t fulfilling jobs, rarely paid a living wage and something often tolerated if not loathed. When people perform the tasks that the robots who replace them now do, they become little more than more expensive, more fleshy robots themselves. The replacement of such demeaning work with the more efficient, more cost effective alternative is only bad because our society is structured to make unemployment the equivalent of rock bottom. Being unemployed, in the eyes of too many Americans, renders one unworthy of the bare necessities, like food, clothes, shelter, and healthcare. People take more issue with a homeless person being given a home that they don’t feel as if they “deserve” than they do with that person dying on the street. This, despite the fact that simply giving empty homes to the homeless ends up being cheaper for taxpayers than the alternative.
What we learn from this is that this reluctance to provide people the basic necessities of life unless they “earn” it creates problems where they otherwise don’t need to exist. If our citizens and their families were actually properly provided for, the looming threat of automation would not only no longer be a threat, it would be a good thing. Homelessness in America would no longer be a concern if we only gave those half a million people one of the 17 million empty homes currently waiting to be occupied. In fact, if one’s employment status was only disconnected from their access to their basic needs, none of us would need to be working as much as we do now.
This system where jobs provide access to basic necessities fundamentally demands the existence of enough jobs for the amount of people operating within that system. We need jobs, but there’s not actually that much that we need to be doing. Our national productivity has skyrocketed from 9.3% in 1950 (America’s golden age) to 252.9% in 2018, and so has our population. America has gone from 152.3 million people in 1950 to 321.2 million in 2019. In summary, our work is 250% more productive, with 175.9 million more people to do the work. So if we’re getting more done, and have more people to do it, why are we still working the same amount of hours a week, if not more, as people did in the 1950s?
The way our economy is structured relies on the existence of jobs. And not just in that we have things that need to get done, so we need people to do them, but in that things go wrong when our national employment rate is not leveling somewhere around 96%. People who aren’t getting paid can’t feed themselves or their families, can’t spend their money and stimulate the economy, can’t get loans from banks if there’s no way for them to pay the bank back. Capitalism necessitates the existence of as many jobs as it takes to keep employment at that 96%.
So what does that mean when automation swoops in and renders millions of jobs obsolete? What does that mean when there’s more people who need jobs than jobs that need to get done? The phenomenon that seems to have developed out of this need is the rise of “pointless jobs.” Anthropologist David Graeber has sorted what he refers to as “bullshit jobs” in his book of the same name into five categories: flunkies, goons, duct tapers, box tickers, and taskmasters. These jobs, as well as all those lost to automation, aren’t necessary in order to keep our society functioning, they only exist to keep it functioning the way it is now.
But it doesn’t need to keep functioning the way it is now. Even John Mayard Keynes, the father of Keynesian economics, expected that we’d achieve a system of “technological unemployment,” where we’d “work as few as 15 hours a week, and that mostly just to avoid losing our minds from all the leisure” all by 2030. In his writings, this pressure to work until we bleed and generate as much profit as can be squeezed out of us was only supposed to be temporary. A necessary evil to get us to the point that it would no longer be necessary. We are reaching the point that it will no longer be necessary, but we’ve seen no end on the horizon.
There are other ways we can go about getting done the tasks that we need done in order to function as a society. Keynes predicted a society of “technological unemployment,” Dr. Graeber advocates for a universal basic income (UBI), the Industrial workers of the World (IWW) have been suggesting a “four-hour work day, four-day week, and a wage people can live on” since the 1930s. University of London Professor Aaron Bastani has even put forth a theory of “fully automated luxury communism” in his 2019 book of the same name. Clearly, we have no shortage of alternatives. We as a society should absolutely have a system of assigning and completing necessary tasks, no one is arguing otherwise, but the tasks we assign should be necessary ones, not busy work we need only to stave off our economy from crumbling in on itself.
Every Religion Needs Healthcare (and a New Social Science Media Portal)
Simon Anderson
A Pew Research study published in 2014 determined that there were over 5.8 billion religious adults and children in the world in 2010. This represents 84% of the world’s population at that time. It includes not only the major religions like Christianity, Judaism, and Hinduism, but also Shintoists, Jains, Wiccans, and practitioners of Chinese and African folk religions. A Gallup Poll performed in 2009 found that, in all but seven of the territories examined, religion is important to more than 25% of the population. The exceptions were Estonia (the lowest, with 16%, which is still a considerable amount), Sweden, Denmark, the Czech Republic, Norway, Japan, and Hong Kong. In fact, in 55 countries studied by Gallup, more than 90% of the population said religion was important to them, and five countries – Oman, Bangladesh, Somalia, Ethiopia, and Niger – had 100% of correspondents say religion was important to them.
In light of these facts, it can be assured that doctors all over the world will run into people practicing all sorts of beliefs, including ones that might seem exceptionally alien to the doctor. This goes for doctors in the clinic as well as doctors out in the field.
As discussed in one of my previous pieces, Complexities of Healthcare: The Need to Know Something about Everything, pre-medical students don’t always have the best grasp on other sects’ beliefs. The example I gave was the classroom case study of Jehovah’s Witnesses, where students tend to believe that the Witness patient will not accept a transfusion because he or she practices faith healing. I only found out that Jehovah’s Witnesses did not practice faith healing through an interprofessional education class, where I was first exposed to this exact case study. While all of the students enrolled in this class were pre-professional health students, there were only about 20 of us – a miniscule fraction of all the pre-professional health students at JMU.
Later, in a cultural anthropology class (again an unconventional or unique setting for pre-medical students), I found out that the Amish also have a “non-traditional” or “unusual” interaction with healthcare systems. They will pool resources to pay for medical care instead of using strictly personal funds or health insurance agencies. The Amish will accept medical care, but often only when the patient can be assured that treatment will return him or her to full function. These phenomena, especially the latter, may at first strike a less culturally competent medical student as odd. Wouldn’t the patient want to live as long as possible? To watch their children grow up? Or to continue to take in the ever-changing world around them? This Amish belief stems from their belief in service to others and their family. If the patient will not be able to contribute to farm work to feed his or her family and community, the patient becomes something of a parasite to them. A doctor treating an Amish patient should know this when presenting the facts of their case and potential treatments, and should respect the patient’s wishes should they decline. Under no circumstances should a doctor knowingly force their own beliefs about medicine upon a patient.
Just these two religious groups – comprising roughly 1.5 million people in the United States alone – can present cultural boundaries that are easily crossed by the unsuspecting health professional. Even more worrisome is that some pre-medical students may end up not receiving any sort of formal education in social science or other cultures whatsoever, leaving them completely open to making intercultural mistakes. The problem that I suggest an answer to is this: How can the medical community make sure that all patients’ cultural needs are acknowledged and met, even by health professionals that have already completed their schooling without any social science courses? My answer: By harnessing the power of the internet and online chat spaces to communicate intercultural differences within the medical community.
The internet, despite its faults and deliberate misinformation, is fundamentally a place of knowledge. As education and the workplace move more into cyberspace – especially in conjunction with the COVID-19 pandemic – every person in the medical field will have access to the internet. I propose that someone, even if that someone is myself, should start to build an online interactive space for medical professionals to discuss and disseminate cultural information and difficulties they have studied or encountered. Established medical professionals can learn from those who are still in school what might be taboo for one culture. A doctor in California can relay something he did to offend a patient, and a nurse in Pennsylvania can avoid making the same mistake in her practice. Over time, the medical community will build a vast library of cultural "dos and don’ts" for colleagues near and far to learn from. And there’s no reason that only medical professionals should be able to access this new social-science media. Anyone who can verify their expertise should be able to contribute to this new repository, and anyone hungry for knowledge should be able to view it.
Together, every doctor, theologist, and sociologist can make sure that every religion, every ethnicity, and indeed every community, can obtain the effective and compassionate healthcare that it needs and deserves.
Clothing Solutions
Anna Lee