Cover Art Guidelines for The Aggie Transcript’s 2020-2021 Print Edition
Thank you for submitting to The Aggie Transcript! The Editorial Board is excited to view your submission. All received submissions, pending board review, will be featured on our website and our social media. The winning art submission will be featured as the cover of our 2020-2021 print edition journal!
Here are a few guidelines on how to prepare and submit your art:
Size:
The cover dimensions are 8.5’’ x 11.’’ Your design does not need to fill the entire space, but it will be finally printed on a cover of this size, so please keep this in mind when designing your submission.
Requirements:
The Aggie Transcript is only accepting digital art for the 2020-2021 cover. This includes, but is not limited to:
- graphic designs
- vector drawings
- digital/tablet drawings
- digital renderings
- photography
If any non-original sources are used (e.g. vector images, photographs, etc.), they must have a Creative Commons license. Here’s how you can check if your image has a CC license:
- Go to Google Images.
- Click Tools → Usage Rights → Creative Commons licenses.
- Search for your topic (e.g. brain anatomy).
- The resulting images are free to download and reuse, and you can select any of them to include in your work.
Alternatively, you can use Wikimedia, Pixabay, and other free stock image sites to find images. Please see below for additional resources.
The cover art must be connected to science on the SARS-CoV-2 virus or COVID-19 pandemic in some way. We encourage you to be as creative as you’d like and interpret this however you see fit, but please note the following:
We are NOT looking for designs that solely feature renderings of the SARS-CoV-2 virus particle. Submissions like the following two examples will most likely not be selected as the winning cover submission. Your design can certainly include renderings of the virus particle, but it should not be the prominent image or feature of your design unless you have some unique take on it (digital collage, etc.)
Style Suggestions:
The 2020-2021 print edition will be using the following color palette. It is not required that you follow this color palette, but we suggest that you choose colors in your design that will complement our color palette (or use these exact colors):
Resources:
For your convenience, we have provided 2 templates that contain our logo and masthead. If you’d like, you can use these templates while designing your submission, so you can get an idea of how your design will look on the cover should it be selected.
Submitting:
When you are ready to submit, please upload your design sample WITHOUT the cover template provided to this Google form. Again, we should receive only your art, without the logo and masthead pasted on it. Please upload your design in the highest quality you are able to, and be sure to write an author’s note describing your submission. The deadline for submission is April 27th, at 12:00 p.m. PST (noon).
Additional Resources:
For more details on submitting writing, photography, and art (COVID or non-COVID-related), please visit our submissions page.
Strimvelis: An Application of Personalized Medicine
By Aditi Goyal, Genetics & Genomics, Statistics, ‘22
Author’s Note: I heard about this therapy during a freshman seminar, and I presented on this during that class. This article is an adaptation of that presentation.
ADA-SCID is a rare, autosomal recessive disease that cripples one’s immune system. ADA SCID stands for Severe Combined Immunodeficiency due to Adenosine Deaminase Deficiency, which occurs due to a mutation in the ADA gene [1]. This gene normally assists in the production and regulation of lymphocytes, also known as white blood cells [1]. Specifically, ADA (Adenosine Deaminase) breaks down deoxyadenosine, which is toxic to lymphocytes [2]. In the absence of a working ADA gene, this deoxyadenosine collects in the body and continues to degrade lymphocytes. Eventually, the lack of functioning lymphocytes leads to severe combined immunodeficiency (SCID) [2].
ADA-SCID is typically screened for at birth and has a variety of treatment options. The most common treatment is a bone marrow transplant from a sibling. In this process, stem cells are taken from someone with a matching blood type, and transplanted into the patient, with the hope that these cells will proliferate and produce healthy lymphocytes [3]. While this approach is effective approximately 70% of the time, the real challenge is in matching a patient to a donor. Because the patient’s immune system is already so impacted, there is a high possibility of rejection of the transplant. Additionally, for patients who do not have a sibling or someone in the family who is able to donate, finding a match can be incredibly difficult.
For patients unable to have a transplant, enzyme therapy is also a possible form of treatment [3]. Enzyme Replacement Therapy, ERT, is simply providing the patient with a working copy of an enzyme, ADA in this case [4]. The drawback to this form of treatment is that it requires a patient to be dependent on a hospital for their entire lives. They cannot travel too far away from a hospital for too long, because if they miss a delivery of the enzyme, there can be drastic consequences [5]. Additionally, ERT can lose effectiveness over the years [4].
The third, and still experimental, treatment option is a gene therapy known as Strimvelis [6]. Strimvelis is one of the first gene therapy products to be used anywhere in the world. While it has yet to be approved by the FDA in the United States, it marks a milestone in the development of personalized medicine.
Strimvelis treatment has three steps, starting with harvesting hematopoietic stem cells (HCS’s) from the patient. These cells carry the mutated ADA gene and are ineffective at supporting catalyzing deoxyadenosine. Once extracted, the corrected ADA gene is delivered to the HCSs in an ex vivo environment using a gammaretrovirus [7]. Once the cells have been transformed, they are delivered back to the patient using an IV drip, and take hold in the body, subsequent to a dose of Busulfan or Melphalan [8]. These two chemotherapy drugs are intended to kill any remaining damaged HCS’s in the body, allowing for the corrected cells to grow without interference. Once injected, the corrected cells will continue to proliferate, producing a healthy amount of ADA. The reason this therapy works well is that the patient’s own HCS’s are used, so there is little to no risk of rejection by the body’s immune system. Another key advantage to using Strimvelis is that it is a single treatment. Once the corrected HCS’s are delivered to the body, the patient is considered “cured” and is no longer reliant on any medical procedures to maintain their immunity.
The results of Strimvelis trials have been incredibly promising. A clinical trial conducted by the European Medicines Agency (EMA) found Strimvelis to have a 100% success rate, leading to its approval by the European Commission about one month later [9]. However, there have been rare cases of Strimvelis leading to patients developing T-cell leukemia [10]. These cases have led to the parent company of Strimvelis, Orchard Therapeutics, halting all administration of Strimvelis until an investigation on the possibly cancerous effects of Strimvelis has been completed [11].
Another primary drawback of Strimvelis is its cost. Strimvelis costs 594,000 euros per patient, which is equivalent to approximately 650,000 dollars [12]. While Strimvelis is not the most expensive gene therapy on the market, the cost is still incredibly restrictive, as the average middle-class family would not be able to afford this treatment.
The reason the cost for this treatment is so high is that ADA-SCID is considered an orphan disease. Orphan diseases are conditions that affect under 200,000 people worldwide [13], which means that from the perspective of a pharmaceutical company, it is not cost-effective to develop a treatment. ADA-SCID only affects around 350 people worldwide [2]. Therefore, the cost per patient is high, since there are not that many people affected by this disorder and because the therapy cannot be mass-produced.
Strimvelis is not perfect, by any means. There are still thousands of unknowns surrounding gene editing, and the side effects are dramatic. Even with Strimvelis on the market, it is not the number one treatment option for most ADA-SCID patients. Nevertheless, it is a step forward. In a world where we learn more about our genetics every day, Strimvelis is a milestone in the development of personalized medicine.
References
- Adenosine deaminase DEFICIENCY: MedlinePlus Genetics. (2020, August 18). Retrieved March 10, 2021, from https://medlineplus.gov/genetics/condition/adenosine-deaminase-deficiency/
- Hershfield M. Adenosine Deaminase Deficiency. 2006 Oct 3 [Updated 2017 Mar 16]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1483/
- Kohn DB, Hershfield MS, Puck JM, Aiuti A, Blincoe A, Gaspar HB, Notarangelo LD, Grunebaum E. Consensus approach for the management of severe combined immune deficiency caused by adenosine deaminase deficiency. J Allergy Clin Immunol. 2019 Mar;143(3):852-863. doi: 10.1016/j.jaci.2018.08.024. Epub 2018 Sep 5. PMID: 30194989; PMCID: PMC6688493.
- Adenosine deaminase deficiency: Treatment and prognosis. (n.d.). Retrieved March 10, 2021, from https://www.uptodate.com/contents/adenosine-deaminase-deficiency-treatment-and-prognosis#H2288540670
- Scott O, Kim VH, Reid B, Pham-Huy A, Atkinson AR, Aiuti A, Grunebaum E. Long-Term Outcome of Adenosine Deaminase-Deficient Patients-a Single-Center Experience. J Clin Immunol. 2017 Aug;37(6):582-591. doi: 10.1007/s10875-017-0421-7. Epub 2017 Jul 26. PMID: 28748310.
- Aiuti, Alessandro et al. “Gene therapy for ADA-SCID, the first marketing approval of an ex vivo gene therapy in Europe: paving the road for the next generation of advanced therapy medicinal products.” EMBO molecular medicine vol. 9,6 (2017): 737-740. doi:10.15252/emmm.201707573
- Candotti F (April 2014). “Gene transfer into hematopoietic stem cells as treatment for primary immunodeficiency diseases”. International Journal of Hematology. 99 (4): 383–92. doi:10.1007/s12185-014-1524-z. PMID 24488786. S2CID 8356487.
- Touzot F, Hacein-Bey-Abina S, Fischer A, Cavazzana M (June 2014). “Gene therapy for inherited immunodeficiency”. Expert Opinion on Biological Therapy. 14(6): 789–98. doi:10.1517/14712598.2014.895811. PMID 24823313. S2CID 207483238.
- https://www.ema.europa.eu/en/documents/product-information/strimvelis-epar-product-information_en.pdf
- Stirnadel-Farrant, Heide et al. “Gene therapy in rare diseases: the benefits and challenges of developing a patient-centric registry for Strimvelis in ADA-SCID.” Orphanet journal of rare diseases vol. 13,1 49. 6 Apr. 2018, doi:10.1186/s13023-018-0791-9
- Orchard statement on Strimvelis®, a Gammaretroviral Vector-Based gene therapy For ADA-SCID. (n.d.). Retrieved March 10, 2021, from https://ir.orchard-tx.com/index.php/news-releases/news-release-details/orchard-statement-strimvelisr-gammaretroviral-vector-based-gene
- Mullin, E. (2020, April 02). A year after approval, gene-therapy cure gets its first customer. Retrieved March 10, 2021, from https://www.technologyreview.com/2017/05/03/152027/a-year-after-approval-gene-therapy-cure-gets-its-first-customer/#:~:text=Strimvelis%2C%20used%20to%20treat%20an,Money%2DBack%20Guarantee%E2%80%9D).
Combating Malaria: Genetically Modified Mosquitoes Projected to Prevail Over Traditional Methods
By Marian Warner, Biotechnology ‘21
Author’s Note: I chose the subject of gene drives for UWP 104E (writing in science class) because I found it personally interesting and wanted to learn more about its controversy. The more I did research on the subject throughout the quarter the more I realized how much is unknown by the general public. The mechanism is a bit complex, so there are not many sources that attempt to explain it to a generalized audience. I hope this paper does a good job of helping those unfamiliar with gene drives become interested and gain a grasp on the scientific backing behind it. I also hope it aids them in forming an informed opinion on the subject or gives them an idea of what further questions they may want to ask.
Malaria, a mosquito-borne disease, has been a stubborn, unrelenting issue despite the established traditional methods used to combat it. Because the female mosquito in the Anopheles genus is the intermediary host transmitting the infectious agent, Plasmodium parasites, from an infected to a non-infected person, current preventative efforts mainly target the mosquitoes by dispersing insecticide-treated bed nets, insecticide for indoor use, and occasional environmental control by destroying larval habitats [1]. For infected individuals, there are treatment options such as antimalarial drugs that can suppress infections, but these target the Plasmodium parasites instead. Although these efforts have helped slow the spread of malaria, it still affected 229 million people and killed an estimated 409,000 in 2019 [2]. Fortunately, scientists such as Andrea Beaghton from Imperial College London have developed a promising strategy using genetically modified mosquitoes to rapidly spread the male-biased sex determination genes in order to exponentially decrease the amount of breeding in a population, which has proven to be effective in completely wiping out populations of malaria-carrying mosquitos in as little as 30 generations in a laboratory setting [3]. The complete collapse of malaria-carrying mosquito populations due to using this strategy in the wild would efficiently lead to the eradication of malaria.
The Role of Selfish Genetic Elements
The strategy works by utilizing a gene drive, a technique that spreads a gene throughout a population at an abnormally fast rate. Usually, any given copy of a gene has a 50 percent chance of being passed down to one’s offspring. This occurs because each diploid organism, such as a human or an insect, carries two different alleles, or variations, of a given gene. One allele is inherited from each of that organism’s parents.
When it comes to a gene drive, however, the allele in question is almost always inherited. Scientists use a naturally occurring selfish genetic element to propel gene drives. Selfish genetic elements, or selfish genes, are alleles that convert the other inherited allele into a copy of itself. In this scenario, the gene no longer has a 50 percent chance of being passed down, but instead nearly a 100 percent chance [Figure 1].
Figure 1
The Mechanism Behind the Selfish Genetic Element
To convert the other allele inherited into a replica of the selfish gene, the selfish gene exploits a natural process the genome uses to repair itself, known as homology driven repair, allowing harmful genes to bypass the rules of natural selection. The mechanism works by encoding a pair of biological scissors, an endonuclease, that cut DNA at the position of the second allele. Once the endonuclease slices open a segment of DNA, the DNA is more unstable and gets chewed back, resulting in the allele being lost. The cell registers the damage and repairs the region by copying and pasting the DNA sequence of the selfish genetic element into the spot where the naturally occurring allele was previously, resulting in both alleles being that of the selfish gene [4]. The only reason why the mechanism doesn’t work 100 percent of the time in practice is because of occasional issues the endonuclease has with recognizing the target allele [5].
The Anopheles Gambiae Gene Drive
With new powerful genome editing technologies, scientists can choose any gene to be a selfish genetic element. Many have focused on trying to identify and genetically modify an allele that could wipe out the Anopheles gambiae population, the most common mosquito species involved with the spread of malaria. However, this technique is not as simple as it seems at first glance. Trying to spread a deadly allele would not work, because the mosquitoes need to be alive and reproducing to spread it. Spreading an allele that makes mosquitoes weaker would not work either. For example, trying to eradicate their ability to fly could help suppress a population briefly, but the chances of mosquitoes forming resistance to the mechanism of this gene drive due to natural selection is high.
Instead, scientists have decided to target genes that are involved with sex determination, to make the population spread genes that reduce female survivorship. Under this gene drive, females are born with intersex mouth parts that do not allow them to feed, and therefore die relatively quickly. Targeting females is beneficial because they are the only ones capable of transmitting malaria. Additionally, as the population becomes increasingly more male-dominated, chances of reproduction become slimmer, and fewer mosquitos are born. The specific sex-determining genes for this are unlikely to invoke evolved resistance, because any changes to a pathway as specific as the sex determination pathway will most likely result in detrimental effects on the mosquito, preventing the spread of the mutations by natural selection [3]. As the gene drive rapidly spreads throughout the population, the number of malaria cases would rapidly decrease. Compared to traditional methods, the strategy would be incredibly efficient and a low cost, but there is a potential for unknown side effects, leading many to believe that using traditional methods is the best option for now.
Potential Consequences of Traditional Methods and Gene Drives
Despite the efficiency gene drives are thought to have, sceptics often argue that the current methods used to control malaria have a much lower risk of adverse side effects. Experts have approved pyrroles and pyrethroids as insecticides for mosquito bed nets because of their relatively low consequences on human health. However, mosquitos are now evolving resistance to pyrethroids. To reduce the odds of mosquitoes becoming resistant, many bed nets include multiple insecticides. However, there is not yet any evidence that these nets work in regions that already have high levels of pyrethroid resistance [6]. Similarly, Plasmodium parasites have also been found to harbor drug resistance to antimalarial drugs. Partial resistance to the drug artemisinin has already been detected in over five percent of some Plasmodium populations, and several other types of drug resistance have been detected as well. As of now, insecticides and antimalarial drugs can continue to be used effectively, but resistance to them must be closely monitored by collecting data on malarial drug treatment cases and looking for molecular markers of resistance in natural populations to prevent these methods from becoming useless in the future [1].
Many scientists agree that gene drives should be further studied as they currently have potential for more concerning side effects than traditional methods. One example of a significant concern is the unknown effect on the food chain from eliminating the A. gambiae populations [7]. So far, studies show that few animals rely solely on A. gambiae as a food source, so many experts believe the chance of negative environmental impacts are slim although there may always be the potential for side effects that were not studied in a specific sub-population or environmental niche [8]. Another concern is the potential for unethical uses with this new technology [7]. If, for example, someone releases a gene drive before enough research has been done and before it has been approved by a regulatory agency, serious environmental consequences could take place. Therefore, laws should be put in place to prevent such a thing from happening. Jim Thomas, a member of the Action Group on Erosion, Technology and Concentration says, “So far, all the proposals around gene drives are things like voluntary ethics codes and agreements between funders. They’re not binding in any way, so to what extent they can be enforced and who would be liable in the event of a problem — there’s none of that” [7]. Kevin Esvelt, one of the researchers who helped engineer the first gene drive, agrees that gene drive technology development could lead to consequences. “This isn’t just going to be about malaria,” Esvelt said. “This is potentially going to be something any individual who can make a transgenic fruit fly could build to edit all the fruit flies” [9].
The Costs of Traditional Methods and Gene Drives
Despite potential ethical and environmental concerns about the technology, the cost of gene drive research and implementation is overall lower than the cost of traditional methods and would save money in the long run. Comparatively, the cost of producing and dispersing nets, insecticides, and drugs each year is more expensive than developing and releasing a successful gene drive. The World Health Organization estimated that about $6.8 billion in resources for malaria prevention was needed in 2020, and that the cost will continue rising each year by an estimated additional $720 million [2]. As long as there is no complete way to prevent malaria, it is unlikely for the annual cost of these developments to disappear any time soon.
Unlike traditional methods, gene drive research has the potential to eradicate malaria completely and thereby curb all expenses involved in malaria research and malaria equipment dispersal. The Bill and Melinda Gates Foundation contributes a majority of grants going into gene drive research, donating about $7.4 million in grants in 2020. This funding has been going towards furthering promising research on gene drives and studies on the environmental effects of gene drives [10]. Ongoing research in future years may continue to require similar amounts of funding to the amount from current grants. However, this price is relatively small considering how much funding goes into malaria prevention and control annually, as well as the potential for a gene drive to completely curb the need for future funding of any kind. The cost of real life implementation is thought to be negligibly small, due to the process involving the release of only a small population of mosquitoes into the wild.
Efficiency of Traditional Methods and Gene Drives
Although cost is a big factor, the main reason for the huge support of gene drive research is the evidence pointing to a gene drive being a much more effective method than current traditional strategies. Current strategies such as insecticide use and drug use have not led and will unlikely lead to the elimination of malaria. Data suggests an overall trend towards fewer malaria cases likely due to traditional methods currently in place [1]. However, a full eradication of malaria around the world is the ultimate goal. Despite prevalent insecticide use and mosquito population control, there is still always a chance of a deadly mosquito bite in areas hard hit by malaria. Deadliness is especially the case when the issue of drug resistance pertains in Plasmodium. Mutations involved in partial drug resistance have already been detected in Plasmodium, and the more drugs continue to be used, the more likely resistance will continue to develop. Overall, insecticides can only be somewhat effective and cases of treatment failure are on the rise [1].
Gene drives, on the other hand, have been incredibly promising when it comes to efficiency. In the study by Beaghton, when the gene drive allele was released in a caged population and only made up 2.5 percent of the population, the entire population was predicted to crash in at least 30 generations [3]. Some models predict that even less mosquitos would need to be released into the wild in a real life scenario. One predicted that the release of just 500 gene drive mosquitoes could result in the complete collapse of a targeted mosquito species population in the timeframe of eight years [11]. Further mathematical models may be used in the future to calculate the optimal percent of the genetically modified mosquitoes that could be released to wipe out the population in the shortest timeframe feasible. From there, more gene drives targeting the other species of malaria-carrying mosquitos could be released, which would lead to a complete eradication of malaria. For now, scientists must continue to study the safety of gene drives by studying them in the lab, computationally, and perhaps in small contained real life settings. Additionally, further laws and policies will hopefully continue to be developed over gene drives in order to regulate the powerful technology. With enough time and research, affected communities and authorities may approve the gene drive strategy and begin implementing it in the near future.
Bibliography
- World Health Organization. 2019. World malaria report 2019. Geneva, Switzerland: World Health Organization.
- World Health Organization. 2020. World malaria report 2020. Geneva, Switzerland: World Health Organization.
- Simoni, A., Hammond, A. M., Beaghton, A. K., Galizi, R., Taxiarchi, C., Kyrou, K., Meacci, D., Gribble, M., Morselli, G., Burt, A., Nolan, T., & Crisanti, A. (2020). A male-biased sex-distorter gene drive for the human malaria vector Anopheles gambiae. Nature biotechnology, 38(9), 1054–1060. https://doi.org/10.1038/s41587-020-0508-1
- Windbichler, N., Menichelli, M., Papathanos, P. A., Thyme, S. B., Li, H., Ulge, U. Y., Hovde, B. T., Baker, D., Monnat, R. J., Jr, Burt, A., & Crisanti, A. 2011. A synthetic homing endonuclease-based gene drive system in the human malaria mosquito. Nature [Internet]. 473(7346), 212–215. doi:10.1038/nature09937
- Oberhofer, G., Ivy, T., & Hay, B. A. (2018). Behavior of homing endonuclease gene drives targeting genes required for viability or female fertility with multiplexed guide RNAs. Proceedings of the National Academy of Sciences of the United States of America, 115(40), E9343–E9352. https://doi.org/10.1073/pnas.1805278115
- Centers for Disease Control and Prevention. Insecticide-Treated Bed Nets. Accessed July 15, 2020. Available from: www.cdc.gov/malaria/malaria_worldwide/reduction/itn.html.
- Kahn, Jennifer. 2020. The Gene Drive Dilemma: We Can Alter Entire Species, but Should We? The New York Times Magazine.
- Collins, C. M., Bonds, J., Quinlan, M. M., & Mumford, J. D. (2019). Effects of the removal or reduction in density of the malaria mosquito, Anopheles gambiae s.l., on interacting predators and competitors in local ecosystems. Medical and veterinary entomology, 33(1), 1–15. https://doi.org/10.1111/mve.12327
- Scudellari M. (2019). Self-destructing mosquitoes and sterilized rodents: the promise of gene drives. Nature, 571(7764), 160–162. https://doi.org/10.1038/d41586-019-02087-5
- Bill and Melinda Gates Foundation. Awarded Grants. Accessed 15 July 2020. Available from: www.gatesfoundation.org/How-We-Work/Quick-Links/Grants-Database#q/k=gene%20drive
- Eckhoff PA, Wenger EA, Godfray HC, Burt A. 2017. Impact of mosquito gene drive on malaria elimination in a computational model with explicit spatial and temporal dynamics. Proc Natl Acad Sci U S A [Internet]. 114(2):E255-E264. doi: 10.1073/pnas.1611064114.
Loneliness in Young Adults Causes Mental Decline in Covid-19
By Vishwanath Prathikanti, Political Science ‘23
Author’s note: As an undergraduate researcher at UC Davis, I have planned and executed a study in chemistry education and now am in the process of presenting findings. This experience sparked my interest in how students learn and what detriments there are to obtaining education. As a student, I was interested in learning what social isolation does to our brains and how it affects our education.
In the current Covid-19 pandemic, the norm in terms of education has been virtual classes and recorded lectures. In the interest of safety, schools have closed lecture halls, minimized the number of students staying in a single dorm, and generally encouraged students to avoid contact with others. While these steps are all necessary to prevent the spread of Covid-19, they also contribute to student loneliness, which severely hampers learning.
Why do we feel lonely right now?
When discussing social isolation today, we might find ourselves asking if we truly are “isolated.” Schools all across the country use Zoom to facilitate discussions and classes that would normally be in-person. Outside of the learning environment, many try to stay connected with friends and family via virtual meeting spaces to watch TV or play games together. However, being socially isolated isn’t necessarily about the number of interactions, but rather the quality of interactions. Hawkley et al. state that “Perceptions are critical … People can live rather solitary lives and not feel lonely, or they can have many social relationships and nevertheless feel lonely” [1].
This is coupled with the fact that historically, college students have been more prone to feelings of loneliness compared to the general populace. Diehl et al. were some of the first to study loneliness in college with an emphasis on transition-related causes, such as moving out for the first time or the formation of new relationships, and concluded that transitions naturally led to loneliness [2]. And indeed, the transition from in-person learning to online learning has been documented to have caused loneliness as well. Killgore et al. studied over 3,000 adults in the first three months of the Covid-19 pandemic [3]. The loneliness scores were calculated via a set of online questionnaires including the UCLA Loneliness Scale-3, and the Patient Health Questionnaire-9 [3].
Interestingly, even when communities started to reopen and participants noted that their “sheltering-in-place” was decreasing, their loneliness scores increased significantly from April to May 2020 and eventually plateaued in June, which was attributed to participants adjusting to their situations [3]. Diehl et al. speculated that “[refraining] from handshakes, hugs, and pats on the back,” long-held social behaviors to express closeness “have been radically altered,” leading to the continuation of loneliness even as we re-enter communities [3].
Indeed, physical touch has been shown to have an important link to loneliness, and even those who are socializing with others, or wouldn’t categorize themselves as lonely, still suffer if they are not touching others. In a study conducted in May 2020, Tejada et al. tested people to see if human touch would affect their feelings of loneliness despite belonging to a culture described as “individualistic” [4]. Tejada et al. explained that individualistic cultures, such as Anglo-Saxon societies, stress independence and neglect physical contact. They found that participants’ loneliness scores generally decreased when they were given a small oil rub by researchers [4]. They calculated the scores using heart rate, questionnaires, and an emotional recognition test [4]. The study essentially proves that even individuals who may view a lack of touch as normal, or those who normally have limited social interaction with others, still feel lonely without direct human contact.
Cognitive decay linked to loneliness
Now that we have established that social isolation leads to a general increase in loneliness, it is important to illustrate the link between loneliness and cognitive decay, which is negatively impacting students’ ability to learn. Cacioppo and Hawkley documented that, in addition to physical health problems such as increased blood pressure, increased levels of stress, and a decrease in physical activity, loneliness also contributes to various mental problems, such as a decrease in IQ and an increase in the risk of Alzheimer’s disease [5]. While Cacioppo noted that these mental problems were mostly observed in the elderly, there was evidence to suggest that loneliness early on would lead to changes in IQ levels over a lifetime. In young adults specifically, Cacioppo. et al. witnessed in a separate study that lonelier people tend to get more distracted and have a harder time focusing compared to people who did not feel lonely, indicating the lonelier people may have experienced cognitive decay [6].
So how are we supposed to avoid this cognitive and physical decay? According to Dr. Maggie Mulqueen in a PBS interview, we should practice social distancing, but make a more conscious effort to reach out to people and avoid social isolation. “We need to respect social distancing and hand-washing as our best means right now to save ourselves physically. But we need to really shore people up against social isolation,” she said [7]. Dr. Todd Ellerin, director of infectious diseases and vice chairman of the department of medicine at South Shore Hospital in Weymouth, Massachusetts, acknowledged the need for touching one another, and encouraged people to plan demonstrations of affection, even something as simple as a hug, in advance [8]. While it is important to minimize the spread of Covid-19, it is also important to maintain our own mental wellbeing and avoid isolating ourselves socially.
Citations
- Hawkley, et al. “From Social Structural Factors to Perceptions of Relationship Quality and Loneliness: The Chicago Health, Aging, and Social Relations Study.” November 2008. The Journals of Gerontology: Series B, Volume 63, Issue 6: S375–S384137. https://academic.oup.com/psychsocgerontology/article/63/6/S375/519628
- Diehl, et al. “Loneliness at Universities: Determinants of Emotional and Social Loneliness among Students.” September 2018. Int J Environ Res Public Health 15(9): 1865. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163695/
- Killgore et al. “Three months of loneliness during the COVID-19 lockdown.” November 2020. Psychiatry Research 293: 113392. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430289/
- Tejada, et al. “Physical Contact and Loneliness: Being Touched Reduces Perceptions of Loneliness.” 2020. Adaptive Human Behavior and Physiology (6): 292–306. https://link.springer.com/article/10.1007/s40750-020-00138-0
- John T. Cacioppo, Louise C. Hawkley. “Perceived social isolation and cognition.” 2009. Trends in Cognitive Sciences, Vol 13, Issue 10: 447-454. https://www.sciencedirect.com/science/article/pii/S1364661309001478
- J.T. Cacioppo, et al. “Lonely traits and concomitant physiological processes: the MacArthur social neuroscience studies.” 2000. Int. J. Psychophysiol. (35): 143-154 https://www.sciencedirect.com/science/article/pii/S0167876099000495
- Hari Srinivasan. “The impact isolation can have on mental health during the outbreak.” March 22, 2020. https://www.pbs.org/newshour/show/the-impact-isolation-can-have-on-mental-health-during-the-outbreak
- Steve Calechman. “How risky is a hug right now?” June 25, 2020. Harvard Health Blog. https://www.health.harvard.edu/blog/how-risky-is-a-hug-right-now-2020062520329
A Conversation on Bioethics with Linda Sonntag, PhD
By Mari Hoffman, Genetics & Genomics ‘21
Author’s Note: I was interested in interviewing Dr. Linda Sonntag because of her time and dedication spent in the biotechnology field. She has been involved in multiple biotechnology companies as the Chief Executive Officer and participating as a board member. The multitude and diversity of her experiences with different companies and projects have encouraged her to get involved with bioethics. She has been a leader in bioethics and has started many of the bioethical conversations that are still being discussed today. In that capacity, she has formed multiple bioethics committees, including the very first. I was very honored to be able to interview Dr. Sonntag and ask her some of my own questions revolving around bioethics in the past and modern development of biotechnology.
This interview has been lightly edited for clarity and brevity.
Mari Hoffman: To start off, if you would like to give a brief introduction on who you are and your background.
Dr. Linda Sonntag: My name is Linda Sonntag, and I was born, raised, and educated in South Africa. I came to the United States in 1980 and completed my post-doctoral studies at UCSF with Herbert Boyer, the founder of Genentech. I quickly realized that I was not cut out for academia in this country. I come from being a very big fish in a very small pond and now I was a Mino in the ocean. I had to find a different way of using my education and I decided to go into industry, which was right at the beginning of the formation of biotechnology.
MH: Since you entered the field of biotechnology when it was still relatively new, when do you first remember a conversation on bioethics taking place and how has that conversation changed with the increasingly advancing technology and scientific capabilities that we have today?
LS: The very first conversation on bioethics took place before my involvement. I think it took place around 1976 at a seminar that was led by David Baltimore, after recombinant DNA and genetic engineering were first discovered. People were concerned about what could be done with biotechnology (a term only coined in the early 1980’s) and a public conversation on bioethics up until this point had not occurred. The technology was way ahead of any conversations or agreement on how to proceed to use it for the common good and not ill. To address the concerns on the ethical issues related to recombinant DNA, a conference was organized to discuss the ethics at Asilomar, in Northern California. A moratorium was placed on all genetic engineering for academic research until the scientist could agree on what was ethical or not. The moratorium lasted several years. During this time, a number of research areas were declared ethical and others not, and the organizers also played a significant role in establishing rules and regulations as well as the creation of multiple regulatory bodies to govern the use of recombinant DNA. At that time, the scientists were able to restart their research in a robust way.
MH: What was your first direct experience with starting a conversation on bioethics?
LS: The first company I worked with was called Agrigenetics and it was the very first agricultural biotechnology company. At the time, no regulations were in place by any federal agency to regulate genetically modified foods (GMA). The very first conversation that I had around bioethics was around whether or not the agricultural industry should be regulated. I was the lone voice who believed it should be regulated. I was very concerned that if there were no regulations, people would be very frightened by the products we wanted to commercialize if we were successful. They might view us as creating monsters that could escape into the environment. Although I had my concerns, for expediency’s sake, the industry leaders as a whole decided against being regulated because regulation adds significant costs and delays the time to reach the market.
The very first experiment that went into the field was in Davis, CA, associated with a company that was founded by academic scientists at UC Davis. It was for a strawberry plant that had been engineered to have an anti-freezing gene derived from fish inserted into its DNA so that strawberries would not freeze and the crop would not be destroyed when there was frost. When the GMO plants were planted, local citizens in the area protested and rioted by breaking down the greenhouses and destroying the crops. That product never reached the market.
Agricultural biotechnology eventually took off, but in a highly regulated way. You can still see the stigma today that GMO plants and seeds hold; people remain afraid of them and the business models around how they are sold.
MH: How did that experience lead to you making a change in a company’s regulations?
LS: My next involvement was a very interesting one. Around 1985, I joined a startup where we were the first to practice precision medicine and use it to create a preventive medicine program that was designed for a circumscribed group of individuals. Historically, prevention has always been in the domain of government and consequently had been very costly to implement since governments could not be seen to discriminate and therefore all newborns were being tested for those diseases that were preventable, whether they were at risk or not.
I went around the country and licensed many genes that had been identified in academic labs that were linked to preventable diseases. They had the potential to be powerful predictors to identify who was at risk for certain diseases. I eventually licensed about 50 different genetic markers that could be used to identify individuals’ predispositions for developing a disease that was preventable. I was only interested in licensing genetic markers for diseases that had an environmental and/or behavioral component to them and that a patient could do something to change the outcome of the disease. After licensing these technologies, we created the very first artificial intelligence system which allowed us to circumscribe who was at risk. To test out the system we were involved with a large telephone company in Washington, DC who opted to offer our test to their employees. It quickly became very evident that with no rules in place, individuals were not protected from being discriminated against by their employers or insurance companies because they had a genetic profile that identified them as being at risk of developing diseases that could result in considerable healthcare costs or disruption to an individual’s productivity. To think through and address these issues, I created the very first bioethics committee, dedicated exclusively to problem solve and develop systems to protect individuals from discrimination. To overcome these issues, we were successfully able to identify individuals, and only we held the key to their identity and were able to preserve the patient’s anonymity from their employers and insurers. They could now get access to educational programs and support without their identity being exposed. That was the very first time that a bioethics committee was created as an institutional entity that made decisions about how businesses would be run in a more mindful and ethical manner.
MH: That is very interesting. Would you say with ancestry tests like 23andMe where you are provided an option to give your name overrides the anonymity of genetic tests that you discussed?
LS: Absolutely. What we have discovered now is even if that data is anonymized, there are ways to deconstruct and identify individuals.
MH: It is very interesting that this conversation on data privacy that you started years ago is still a prevalent issue today. Are there any set laws that are currently in place today to provide protections?
LS: Laws do exist to protect genetic information from being used prejudicially, but if an individual gets refused insurance it is really hard to find out why they have been refused. If an employer has accessed that data and uses it prejudicially, for one to have any recourse, you have to prove that it was based on their knowledge of that genetic information, which is very difficult to prove.
The one law that is unfortunately currently at risk is the protections that come from the Affordable Care Act (ACA). The ACA forbids insurance companies from using pre-existing conditions to deny an individual any insurance. Due to COVID-19 and the Trump Administration’s attempt to end the ACA, a multitude of individuals who have lost their health insurance this past year due to the pandemic are now at risk of no longer being able to buy insurance that covers pre-existing conditions. All the sequelae and multitudes of long term health consequences of COVID-19 could be excluded from coverage by anyone who has lost their job as a consequence of this pandemic of epic proportions. A genetic predisposition might be included as a pre-existing condition, which might disqualify an individual for insurance. As long as the ACA is the law, nobody can be denied insurance for those reasons. Although there are these laws that exist, there are still issues around them and how to enforce them.
MH: Have there been any other experiences that you have that have led you to build a bioethics committee?
LS: The third time that I got involved in bioethics and formed a committee was when I was running a company called SyStemix, the very first stem cell company. We were using fetal tissue in our experiments which was a topic that has been controversial under Trump and prior to that during the George W. Bush administration. We were one of the first commercial companies that was openly admitting to using fetal tissue in our experiments. We knew that this might be highly controversial, so once again, I assembled a bioethics committee to opine on what we would face and how best to deal with the issues. Our committee actually included a Catholic Bishop to be a part of the conversation and eventually concluded that since we were not in any way women to choose abortion and since we were not paying for the tissue, the abortuses were simply being disposed of with no potential to benefit humankind. Even the Bishop agreed that using fetal tissue for the benefit of humankind was a worthwhile endeavor, as opposed to throwing the embryos away.
Just this last year, Trump dismantled every single research project funded by the United States government that used fetal tissue in any way, thereby squandering hundreds of millions, if not billions of dollars worth of experiments by having all that research come to a screeching halt.
Our company was founded on the use of a SCID-hu mouse model where any tissue from any organisms can be transplanted into the mouse since the mouse did not have an immune system of its own. It could not recognize the donor tissue as foreign and hence would not reject it. Few adult organs are capable of regeneration, whereas virtually every fetal tissue has applicability in these valuable experiments. This mouse model became the gold standard for all research on the etiology of human diseases and the potential ways to treat them.
In our case we were able to use it for AIDS and HIV research. It was the first time that we could actually create a fully functional human immune system in a mouse and infect it with HIV, to determine if different drugs could potentially cure HIV and AIDS. AZT, the very first approved HIV-antiviral drug was discovered to be effective in humans by using the SCID-hu mouse model around 1990. AZT is a pro-drug, and the only other organism that can convert it from a prodrug to an active drug is chimpanzees. By using this mouse model, it was no longer necessary to infect chimpanzees with HIV to study the disease. This year, unfortunately, for political reasons, all experiments that were using this gold standard mouse model for studying many human diseases came to a halt because President Trump decided that fetal tissue could not be used in any circumstance in any government funded research programs, for purely political reasons.
MH: What do you think are some of the most current pressing bioethical issues?
LS: The other discussion that is very current, but I have mixed feelings on is about vaccines for COVID-19. COVID-19 trials are blinded and are conducted by splitting cohorts of individuals in a control arm and a treatment group, without the researchers or participants knowing which group is receiving the vaccine. Now that the experiments are unblinded and we can see that the vaccine is highly efficacious, the question becomes whether or not people in the control arm should be vaccinated. If they get the vaccine, it truncates our ability to see for example the longevity of the protection provided by the vaccine or long-term side effects by no longer being able to track the control group. So, what to do? The way the health care community is leaning is that the control group has to get the vaccine to protect them and then we have to figure out other ways to understand the longevity and side effects of vaccination. This is an ongoing discussion at the FDA and the NIH in order to make these important decisions around how to continue the clinical trials. Also, once the first vaccine is approved, how do you get other vaccines tested if there is already a vaccine available? There are a lot of ethical questions to consider regarding these issues.
MH: There is a lot of stigma about taking vaccines, how do you think the implementation of distributing the vaccine and getting people to take it will play out?
LS: There are weekly conversations regarding how to distribute the vaccine and who should get it first. Clearly, they have to treat frontline workers first as they are the most at risk. Then the conversation is about who is most at risk for the virus aside from the frontline workers. People of color have a higher risk of getting sick from COVID-19 completely disproportionate to the population. The question raised asks if young children should be prioritized in getting the vaccine since they can be reservoirs of the virus and for their emotional and cognitive development must be allowed to return to school as soon as possible? There are still conversations going on around how to allocate the vaccine equally and I don’t think they have reached a complete conclusion other than the frontline workers will get it first. Who gets it next and how it rolls out is still under discussion.
MH: Is there worry that there will not be enough people willing to get the vaccine due to stigma?
LS: Yes, I think that is a very significant concern. I can personally tell you as a scientist that I think that vaccines and antibiotics have extended our lives dramatically. At the beginning of the 1900s, the average life span was about 40 years old due to people dying from common infectious diseases. The advantage of antibiotics and vaccines has extended our lifespan by double. I will not hesitate in getting a vaccine as soon as I can after it has been reviewed and approved by an independent, apolitical group of scientists.
MH: Are there any other major ethical topics that we missed that you would like to discuss?
LS: One critical vast ethical issue that we have not discussed is CRISPR technology. CRISPR technology is one of the most fraught technologies on the planet with the ability to do both good and bad. On the downside, scientists have found ways for example to change genes in entire populations of mice to render them infertile so that they cannot transmit Lyme disease or to eradicate entire populations of mosquitoes to prevent malaria or zika transmission or other mosquito borne diseases, of which there are many. What happens to the global ecosystem if these species are eradicated because they can no longer reproduce? The cat is out of the bag on this line of research, before a discussion on the ethics ever got started.
The first infants to have their genes in their germline modified have already been born in China. This means the germplasm (eggs and sperm) have been permanently altered and so these modifications will be transmittable to future generations. This is something that the scientific and civil community worldwide has historically completely forbidden. There are a lot more conversations surrounding ethics that need to take place in order for this technology to be broadly used. I’m afraid, it is already too late to regulate and control in a meaningful way from being used in ways that could be terribly detrimental to our planet and all its inhabitants, whether fauna, flora, microbes, or humans.
Is it Bad to Be A “Night Owl”? An Investigation into the Association of Preferred Sleep Time with Allergy & Asthma Symptoms in Adolescents
By Reshma Kolala, Microbiology ‘22
Author’s Note: Adolescents are notorious for not getting enough sleep, but can that impact how the cells of our immune system operate? The following study reinforces the significance of maintaining a natural sleep schedule in adolescents and unveils a new area of research where sleep-wake patterns could be used as a diagnostic when screening for respiratory illnesses.
Our circadian rhythm regulates a myriad of biological activity, ranging from metabolism and cell signaling pathways to various psychological and behavioral patterns. The circadian rhythm is defined as endogenous (built-in mechanism) and entrainable (adjusted to external stimuli such as temperature and light) [1]. Together, these factors manifest into a unique chronotype which describe an individual’s propensity to sleep and wake at a particular time [2]. Recent studies have examined this biological pattern in relation to respiratory illness, revealing how disruption in the circadian rhythm plays a critical role in the pathogenesis of airway inflammation and physiology. The following study aims to further elucidate the relationship between an individual’s chronotype and their susceptibility to asthma or allergic diseases, particularly in the adolescent population.
The study conducted by Halder et al. analyzed data from 1684 adolescents, ranging from ages 13-14, from the Prevalence and Risk Factors of Asthma and Allergy-Related Diseases among Adolescents (PERFORMANCE) study. Each individual was administered the International Study of Asthma and Allergy in Childhood (ISAAC) Phase III questionnaire to determine each adolescent’s disposition to respiratory illness, with particular emphasis on wheeze, rhinitis, rhinoconjunctivitis, and asthma. This data was analyzed against responses from the reduced Morningness–Eveningness Questionnaire (rMEQ), which was used to determine each participant’s chronotype. An individual’s chronotype was classified into one of three categories: morning, evening and intermediate types. External factors such as demographics, social characteristics, and neighborhood environment (rural, industrial suburban, nonindustrial suburban and urban) were also considered as potential influences that may enhance asthma/allergy symptoms. Results revealed that an “individual’s chronotype was associated with respiratory symptoms among adolescents”. More specifically, those that were evening types, and intermediate types to a lesser extent, had a higher risk of current wheeze and current or ever rhinitis when compared to morning types. Intermediate types also demonstrated higher levels of Rhinoconjunctivitis when compared to morning types. Overall, individuals that were identified as evening types had a consistently higher prevalence of respiratory symptoms when compared to morning types. Those identified as morning types did not exhibit significant correlation with respiratory symptoms. This association between respiratory symptoms and chronotype was paralleled, though to a lower degree, in individuals identified as intermediate types as well [3].
The wide pathophysiology of asthma and allergy makes it challenging to pinpoint a particular cellular process to explain this finding [4]. Previous studies have shown that asthma/allergy symptoms worsen at night which can be attributed to multiple immunological factors. A study by Christ et al. in 2018 observed the link between mast cell responsiveness, function in allergic diseases, and the circadian rhythm. Mast cells possess a high affinity for IgE antibody, which is produced by the immune system in response to allergen recognition. When activated by bound IgE, mast cells release chemokines, cytokines, and other inflammatory mediators such as histamine, which exhibit diurnal character (are active during the daytime). This study illustrates how mast cell signaling, critically involved in the inflammatory response, operates on a circadian rhythm. This is due to the fact that inflammatory mediators are governed by diurnal (active during the day) behavior. [5]. This study focused on mast cell signaling by Christ et al. may provide some reasoning behind the results observed in the aforementioned study conducted by Halder et al. The Christ et al. study shows how dysregulation of the sleep-wake cycle interferes with how the immune system responds to the presence of allergens, which could potentially aggravate the respiratory symptoms detailed in the Halder et al. study. For example, those identified as “evening-types” are “more easily prone to circadian misalignments that could eventually lead to circadian clock dysfunction which triggers several down-stream mechanisms including altered immune systems in the lungs”.
Melatonin production is also a significant factor in the inflammatory immune response. Evening type individuals are exposed to higher levels of artificial light at night (ALAN) which disrupts daily rhythms and suppresses nocturnal melatonin production [6]. Melatonin, known as the sleep hormone, plays a vital role in immunomodulation. Immunomodulation is responsible for orchestrating the events of cellular and humoral immunity [7]. Recent studies have identified melatonin as a key player in asthma and allergy-related disease when the circadian rhythm is misregulated by abnormal sleep-wake patterns.
This study is the first to find an association between chronotype and respiratory symptoms in adolescents. As this is a cross-sectional study, researchers in this study are unable to make a causal statement that directly links sleeping patterns to respiratory illness. However, results from this study warrant further investigation into the cellular and behavioral effects of individuals who possess “intermediate” and “evening type” chronotypes. This finding uncovers a new outlet of healthcare, where an individual’s unique chronotype is utilized as a tool in patient diagnosis for various metabolic, behavioral, and respiratory illnesses.
References:
- Circadian rhythm. (2020, November 09). Retrieved November 12, 2020, from https://en.wikipedia.org/wiki/Circadian_rhythm
- Chronotype. (2020, November 08). Retrieved November 12, 2020, from https://en.wikipedia.org/wiki/Chronotype
- Haldar, P., Carsin, A., Debnath, S., Maity, S., Annesi-Maesano, I., Garcia-Aymerich, J., . . . Moitra, S. (2020, April 01). Individual circadian preference (chronotype) is associated with asthma and allergic symptoms among adolescents. Retrieved November 12, 2020, from https://openres.ersjournals.com/content/6/2/00226-2020
- Huang, R., E. Callaway, H., Burki, T., RS. Edgar, A., JE. Long, M., D. Montaigne, X., . . . LK. Williams, M. (1970, January 01). The Role of the Body Clock in Asthma and COPD: Implication for Treatment. Retrieved November 12, 2020, from https://link.springer.com/article/10.1007/s41030-018-0058-6
- Christ, P., Sowa, A., Froy, O., & Lorentz, A. (2018, July 6). The Circadian Clock Drives Mast Cell Functions in Allergic Reactions. Retrieved November 12, 2020, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043637/
- Haim, A., & Zubidat, A. (2015, May 5). Artificial light at night: Melatonin as a mediator between the environment and epigenome. Retrieved November 12, 2020, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375362/
- Srinivasan V;Spence DW;Trakht I;Pandi-Perumal SR;Cardinali DP;Maestroni GJ;. (n.d.). Immunomodulation by melatonin: Its significance for seasonally occurring diseases. Retrieved November 12, 2020, from https://pubmed.ncbi.nlm.nih.gov/18679047/
The Pursuit of a SARS-CoV-2 Vaccine: Lessons in Public Trust of Medical Institutions
By Jessica Lee, Biochemistry and Molecular Biology ‘21
Author’s Note: Alarmed by the fact that so many Americans are skeptical of receiving a COVID-19 vaccine, I wanted to write an article delving into the reasons why public trust in medical institutions has waned. I look to previous breaches of trust to propose public health messaging strategies for the rollout of the highly anticipated COVID-19 vaccine.
As of November 2020, approximately 63% of Americans say they would not be willing to immediately receive a COVID-19 vaccine—even if the vaccine was approved by the Food and Drug Administration (FDA) and free of cost [1]. Public willingness to receive a COVID-19 vaccine has rebounded since its all time low of 50% in September of 2020. The fluctuation in willingness to be vaccinated reflects how the public perceives undue influence on the vaccine development and regulation process. A successful vaccine distribution process will require broad public support to control the ongoing global pandemic.
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The human and economic consequences of the COVID-19 pandemic are staggering: over 350,000 people in the U.S. have died from COVID-19 and the unemployment rate remains high at 6.7% as compared to 3.5% in February 2020 [2, 3]. Given the devastating impacts of COVID-19 on Americans’ health and well-being, why are so many Americans skeptical of a vaccine with the potential to restore normalcy?
The history of American public and private biomedical institutions may provide useful context for Americans’ skepticism of a potential COVID-19 vaccine. The anti-vaccination movements, opioid crisis, and bumpy introduction of COVID-19 therapeutics have all contributed to waning trust in public health institutions. With the approval of Pfizer/BioNTech and Moderna vaccine candidates for the prevention of COVID-19, the biomedical community needs to foster trust by delivering correct and consistent messaging to the public as vaccines become available to the American public.
Trust in Biomedical Institutions
The modern anti-vaccination, or “anti-vax,” movement in the U.S. was sparked by Andrew Wakefield’s infamous paper published in The Lancet and perpetuated by outspoken celebrities, politicians, and social media groups [4]. Even though Wakefield’s claims about a causal relationship between the childhood measles, mumps, and rubella (MMR) vaccine and autism have since been thoroughly debunked by a scientific majority, the damage caused by his falsified research is evident as measles outbreaks continue to impact the U.S. Characterized by fantastical and conspiratorial thinking, the modern anti-vax movement has evolved to include a range of beliefs about vaccines. On social media platforms, misinformation about vaccines can include false safety concerns to conspiracies about social control.
However, there are also legitimate reasons to be skeptical of the pharmaceutical industry and its regulators. Mistakes driven by commercial interests have resulted in horrific public health crises. Motivated by profit, pharmaceutical companies misled the public about the safety of opioids, such as oxycontin, resulting in the liberal prescription of highly addictive and dangerous drugs. Opioid overdose is now one of the most common causes of preventable death in the U.S. [5]. Financial incentives can corrupt the scientific process, even corrupting leading medical experts.
Dr. Russell Portenoy, a pain specialist, received millions of dollars from the manufacturers of opioids while assuring the public that addiction risks were low [5]. When the addictive nature of opioids became evident, Portenoy defended his actions.
“My viewpoint is that I can have these relationships [and] they would benefit my research mission and to some extent, they can benefit my own pocketbook, without producing in me any tendency to engage in undue influence or misinformation,” said Portenoy [5].
In light of the unethical—and often illegal—behavior of pharmaceutical companies, the reaction of the American public is not entirely unreasonable. However, the waning trust in biomedical institutions is nonetheless a public health problem with clear consequences. In 2019, there were several outbreaks of measles among communities with low vaccination rates [6]. Over 1,200 cases were reported by the Center for Disease Control (CDC), which is the highest number of measles cases since 1992 [6]. It is important to highlight that overall measles vaccination rates are high throughout the country. However, outbreaks of deadly diseases can still occur when vaccination rates within a community dip below those needed for herd immunity. To eradicate a disease, outreach to fringe communities is necessary to ensure they buy into the vaccination process. Furthermore, vaccines must be made accessible to traditionally underserved communities. Within the context of the COVID-19 pandemic, this means that public health officials must reach out to those with anti-vaccination tendencies, ethnic minorities, and immigrant populations. Furthermore, the vaccine must be made widely accessible for the poorest citizens of all countries. Only then can COVID-19 be completely eradicated.
Number of Measles cases reported by year
Data from CDC.gov as of October 15, 2020
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The consequences of eroded trust in biomedical institutions are even more tangible as authorities in the U.S. attempt to control the COVID-19 pandemic. Confusing, conflicting messaging and policies on cloth mask usage has resulted in a partisan gap of 16 points between Republicans and Democrats on regular mask usage [7]. Even though current data and modeling demonstrate that masks reduce infections, some Americans continue to refuse to participate in this common-sense risk reduction practice [8].
The Credibility of the Food and Drug Administration (FDA)
There has also been widespread confusion on the development of COVID-19 therapeutics. The FDA has the authority to allow the use of unapproved drugs and medical products during national emergencies under an emergency use authorization (EUA). Many COVID-19 therapeutics such as Remdesivir, hydroxychloroquine, and convalescent plasma have been granted EUAs for use in specific populations, such as hospitalized patients [9]. Importantly, medical products that are granted EUAs are not granted full FDA approval. To obtain an EUA, it must be determined that the product meets three criteria: the product may be effective in diagnosing, treating, or preventing a serious disease or condition, the known and potential benefits outweigh the risks, and there are no available alternatives [9]. Many of the EUAs granted for COVID-19 treatment have stirred controversy within the biomedical community. For instance, the FDA’s decision to grant an EUA for the use of convalescent plasma in August resulted in dissent among biomedical institutions.
A National Institutes of Health (NIH) panel rebutted the FDA’s claims by issuing this statement: “There are insufficient data for the COVID-19 Treatment Guidelines Panel to recommend either for or against the use of COVID-19 convalescent plasma for the treatment of COVID-19” [10].
Other figures in the biomedical community such as Dr. Eric Topol, the director of the Scripps Research Translational Institute, criticized the head of the FDA, Dr. Stephen Hahn, for making hyperbolic statements on the safety and efficacy of convalescent plasma and for presenting misleading data to the public [11].
“So in order to get this straight, Dr. Hahn needs to also talk to the public and say that he erred and that there is no established evidence for survival advantage of convalescent plasma. That has to be determined through randomized trials that are ongoing,” said Topol on NPR’s All Things Considered [11].
The FDA also has played a controversial part in the development of hydroxychloroquine. The agency issued an EUA for hydroxychloroquine in March only to revoke the EUA in June after adverse cardiac events were reported [12]. Whether the FDA’s actions were influenced by political pressure, corporate pressure, or a desire to save lives, the controversy around COVID-19 therapeutics degrades public trust in the FDA as an institution.
Emergency Use Authorization for Vaccines to Prevent COVID-19
The discussion on therapeutic EUAs is important since the two currently approved COVID-19 vaccines were first approved through the intermediate step of an EUA. At time of publication, Moderna and Pfizer/BioNTech have successfully completed their phase three clinical trials for COVID-19 vaccines and received EUAs from the FDA [13]. Globally, approximately twenty other vaccine candidates are also in phase three clinical trials [13]. Each clinical trial has enrolled between 30,000 and 60,000 volunteers, half of which will receive the vaccine candidate and half of which will receive a placebo [13]. Approximately 160 infections of SARS-CoV-2 will be necessary to statistically determine the efficacy of each vaccine candidate. While only 160 infections might seem small in a clinical trial of 60,000, this number allows the FDA to determine if there is a statistical significance between the two arms of the clinical trial. Interim analyses may also be conducted at fewer infections by external data safety monitoring boards [14, 15]. Such data safety monitoring boards are independent of sponsors, regulators, and the scientists conducting the clinical trials. If the external board finds statistically significant results at an interim point, then the sponsors of the clinical trial may ask the FDA to review the vaccine for an EUA [14].
Published in a non-binding guidance document, the FDA outlines the criteria for potentially obtaining an EUA for a COVID-19 vaccine. Since this guidance document is non-binding, the FDA may modify the EUA process moving forward. If a sponsor seeks an EUA at an interim analysis of a phase three clinical trial, then they must demonstrate at least 50% efficacy, have a median follow-up duration of at least two months after the administration of the last dose, and safety data that would allow the FDA to make a favorable risk-benefit analysis [16]. Furthermore, the sponsor must provide sufficient data demonstrating the ability to consistently manufacture the vaccine [16]. If the FDA believes the criteria are met for an EUA, then the vaccine candidate may be administered to certain at-risk populations while the full-approval process continues. At the time of publication, both Pfizer and Moderna have produced data from their phase three clinical trials indicating their vaccines may be over 90% effective—far surpassing the 50% efficacy threshold set by the FDA [13].
Developing and Maintaining Public Trust
The COVID-19 vaccine trials are safeguarded in many ways. The scientists at the FDA have approved the phase three clinical trial protocols and monitored phase one and two clinical trials for safety and efficacy. The oversight safety boards have watched for unexplained adverse events and paused the AstraZeneca trial when unexplained neurological symptoms presented in one participant [14]. Peer reviewers have analyzed and criticized the data and conclusions generated from phase one and two clinical trials. Furthermore, influential members of the biomedical community have spoken out when they believe mistakes have been made. Evidently, there are safety measures in place to protect the public from a dangerous or ineffective vaccine. However, safety measures are not perfect. When the FDA allowed the use of hydroxychloroquine and then revoked its EUA, the FDA weakened its authority with the general public. Even the appearance of political and commercial influence on the scientific process may elicit skepticism from the public.
How can the biomedical community increase the public’s willingness to get the COVID-19 vaccine? Certainly, consistent messaging from figures of authority is important. Furthermore, the biomedical community must continue to hold regulatory agencies, corporations, and politicians responsible for their rhetoric. There must be political, legal, or economic consequences for misleading the public and degrading trust in medical institutions. Economic consequences—for example—might range from lawsuits to executives being debarred from working in the pharmaceutical industry.
Biomedical professionals have advocated for widespread outreach to many different types of communities [15]. Social media campaigns can be effective in rapidly disseminating information by engaging users to add their own input. However, social media may also hinder outreach as demonstrated by the uncontrolled spread of misinformation by anti-vaccination groups on platforms such as Facebook [17]. Viral posts containing misinformation can seed public distrust in medical institutions. Still, polling indicates that Americans overwhelmingly trust medical professionals over industry leaders or politicians for information about vaccines [18].
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Utilizing this trust would mean elevating medical scientists as the voice communicating the state of a COVID-19 vaccine rather than relying on politicians, the news media, or industry leaders. However, it is important to communicate scientific consensus rather than relying on the voices of individual biomedical professionals. Individuals can make genuine mistakes, have differing opinions, or be corrupted; thus, it is essential that public health messaging is centered around scientific consensus.
The effectiveness of a COVID-19 vaccine on a population scale will depend on the percent of people willing to get the vaccine. To end the COVID-19 pandemic, it’s likely that most people will need to be vaccinated. To accomplish this, the biomedical community will need to work with the public to foster open and honest communication, understanding the public has relevant concerns about the influence of politics and commerce on the scientific process. By learning from previous anti-vax movements, public health professionals must counter the spread of misinformation with compelling, fact-based messaging. Ultimately, the public health community must regain the trust of the American public and appeal to Americans’ civic duty. The act of taking a vaccine is a social contract; as Dr. Topol says, “I take the vaccine to help you, not just me” [15]. The COVID-19 pandemic is one of the largest public health crises in modern times and it will require good science and good communication to solve.
References
[1] Brenan M. “Willingness to Get COVID-19 Vaccine Ticks Up to 63% in U.S.” Gallup, December, 2020.
[2] “CDC COVID Data Tracker.” Centers for Disease Control and Prevention, January 6, 2021.
[3] “Employment Situation Summary.” U.S. Bureau of Labor Statistics, December, 4, 2020.
[4] Hussain A, Ali S, Ahmed M, Hussain S. “The Anti-vaccination Movement: A Regression in Modern Medicine.” Cureus, July 2018. doi: 10.7759/cureus.2919.
[5] Gale AH. “Drug Company Compensated Physicians Role in Causing America’s Deadly Opioid Epidemic: When Will We Learn?” Mo Med, July 2016.
[6] “Measles Cases and Outbreaks.” Center for Disease Control, November 2020.
[7] Kramer S. “More Americans say they are regularly wearing masks in stores and other businesses.” Pew Research Center, August 2020.
[8] Zhang K, Vliches TN, Tariq M, Galvani AP, Moghadas SM. “The impact of mask-wearing and shelter-in-place on COVID-19 outbreaks in the United States.” International Journal of Infectious Diseases, December 2020. doi: 10.1016/j.ijid.2020.10.002.
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A Dive into a Key Player of Learning and Memory: An Interview with Dr. Karen Zito
Image by MethoxyRoxy – Own work, CC BY-SA 2.5
By: Neha Madugala, Neurology, Physiology, and Behavior, ‘21
Author’s Note: After writing a paper for the Aggie Transcript on the basics of dendritic spines, I wanted to take a more in-depth look at current research in this field by interviewing the UC Davis professor Karen Zito, who is actively involved in dendritic spine research. While there are still a lot of questions that remain unanswered within this field, I was interested in learning more about current theories and hypotheses that address some of these questions. Special thanks to Professor Zito for talking to us about her research. It was an honor to talk to her about her passion and knowledge for this exciting and complex field.
Preface: This interview is a follow-up to an original literature review on dendritic spines. For a more in-depth look at general information on dendritic spines, check out this article.
Neha Madugala (NM): Can you briefly describe some of the research that your lab does?
Dr. Karen Zito (KZ): My lab is interested in learning and memory. Specifically, we want to understand the molecular and cellular changes that occur in the brain as we learn. Our brain consists of circuits, connecting groups of neurons, and the function of these circuits allows us to learn new skills and form new memories. Notably, the strength of connections between specific neurons in these circuits can change during learning, or neurons can form new connections with other neurons to support learning. We have been mainly focusing on structural changes in the brain. This includes questions such as the following: How do neurons change in structure during learning? How do new circuit connections get made? What are the molecular signaling pathways that are activated to allow these changes to happen while learning? How is the plasticity of neural circuits altered with age or due to disease?
NM: What are dendritic spines?
KZ: Dendritic spines are microscopic protrusions from dendrites of neurons and are often the site of change associated with learning. Axons of one neuron will synapse onto the dendritic spine of another neuron. Spines will grow and retract during development and synapses between a spine and axon will form during learning, forming complex circuits that allow us to do intricate tasks such as playing the piano.
NM: Transient spines only last a couple of days. What role do they play in learning?
KZ: One hypothesis for the function of transient spines is that they exist to sample the environment, allowing the brain to speed up its ability to find the right connections required for learning. Thus, the rapid growth and retraction of transient spines in the brain helps our neurons find the right connections required to form the new neural circuits by sampling many more connections and narrowing in on the right ones. For instance, in a past study on songbirds, researchers found that baby songbirds with faster moving transient spines were able to learn songs quicker than baby songbirds with slower moving transient spines. Once these transient spines find the right connection, they will transition from transient to a permanent spine to partake in a circuit that supports a new behavior, such as the songbird learning a new song.
NM: Can presynaptic neurons directly synapse onto a dendrite or only a dendritic spine?
KZ: Many neurons do not have spines at all. Spines are predominantly present on neurons in the higher order areas of the brain involved in learning, memory, perception and cognition. Spiny neurons are present in areas of the brain where neural connections are changing over time, or plastic — allowing the brain to learn, adjust, and change. Certain areas of the brain do not require a lot of change and, in some cases, circuit change may be detrimental to function. For example, we may not want to change connections established for movement of specific muscles.
NM: What is the difference between synapses that occur directly on a dendrite versus onto a dendritic spine?
KZ: Importantly, the molecular composition at synapses can vary widely between synapses, regardless of whether this connection occurs at a shaft or a spine. Therefore, it is difficult to name specific compositional elements always found at a spine versus a shaft. Inhibitory synapses, formed by GABAergic neurons, tend to be found directly on the shaft of dendrites. Glutamatergic neurons, which are excitatory, in the cerebral cortex tend to synapse on dendritic spines, but can also connect directly with the dendrite.
NM: All dendritic spines have excitatory synapses that require NMDA and AMPA receptors [1]. Are these receptors necessary for these spines to exist?
KZ: To my knowledge, we do not know the answer to this question. It is possible to remove these receptors a few at a time, and spines do not disappear. However, it is really hard to remove a receptor from a single spine and, if the receptors are removed from the entire neuron, it is often replaced with another receptor in a process called compensation. In order to test if this is possible, someone would have to knock out all genes encoding AMPA receptors and NMDA receptors, which is over seven genes, to see if spines still formed. Notably, if AMPA receptors are internalized, the spine typically shrinks, and if more AMPA receptors are brought to the surface, the spine typically grows. Indeed, the number of AMPA receptors at the synapse is directly proportional to the size of the spine.
NM: What drives spine formation and elimination when creating and refining neural circuits?
KZ: There really is no definitive answer to this question currently, and many of those performing dendritic spine research are interested in answering these questions. Let’s first look at formation. One theory suggests that there are factors coming from neighboring neurons, such as glutamate or BDNF [2], which promote spine formation. However, it is unclear which of these are acting in vivo, in the animal. Also, spine formation is much greater in younger animals compared to older animals. That can suggest that the cells are in a different state when younger versus older. The cell can be a less plastic state where all the spines are moving slowly, seen in older animals, or more plastic states where all the spines are moving more quickly, seen in younger animals. Thus, there appears to be a combination of intrinsic state, or how plastic the cell is, and extracellular factors such as the presence of glutamate that dictates spine formation. Elimination is similar in that we do not really know the entire molecular signaling sequence that is driving it. It is a fascinating question for so many reasons. For example, when we are young we overproduce spines, and as we grow the spine density declines as our nervous system selectively chooses which connections to keep. Then, as adults, our spine density remains relatively stable. However, we obviously keep learning as adults, even though our spine density remains constant. One hypothesis is that, as a spine grows while learning, a nearby spine with no activity shrinks and eventually becomes eliminated. In fact, we have observed this phenomenon in our studies. Therefore, there may be some local competition between these spines for space. This keeps the density the same across most of the adult life span.
NM: Does learning drive the formation of synaptic spines or does synaptic spine formation drive learning?
KZ: This may depend on the type of learning. Both have been observed. Studies have been done imaging the brain during learning. Some people have found an increase in new spine growth suggesting that learning drives new spine formation. Other people say they found the same number of new spine growth, but a greater amount of new spine stabilization, suggesting that learning drives new spine stabilization.
NM: It has been observed that some intellectual disabilities and neuropsychiatric disorders are associated with an abnormal number of dendritic spines when compared to a neurotypical individual. Is this related to the insufficient production of dendritic spines at birth or deficits in pruning?
KZ: Indeed autism spectrum disorders have been associated with an increase in spines. This could potentially be associated with an overproduction of spines or reduced spine elimination. Notably, the majority of neurological disorders resulting in cognitive deficits, such as Alzheimer’s disease, are associated with decreased spine densities. It is unclear if the spine numbers or brain function diminishes first, but much of the current research seems to suggest that the spines go away first, leading to the cognitive problems observed. In many disorders with too few spines, there is a normal formation of spines but excessive elimination. This is seen as Alzheimer and schizophrenic patients’ spine density is relatively normal prior to disease onset. For Alzheimer’s specifically, some researchers suggest that the molecular release of the pathogenic amyloid beta peptide binds to molecules on the surface of the dendritic spine that drive spine loss.
NM: How might dendritic spine research help in treating neuropsychiatric and neurodegenerative disorders?
KZ: Current research is looking at how to stabilize and destabilize dendritic spines. If we were able to manipulate the stability of these spines, we could potentially help rescue the stability of spines in patients with neuropsychiatric disorders, which could potentially lead to better therapies and outcomes. Understanding the pathways that control the stability of these spines will allow researchers to find targets for future therapeutic treatments.
Footnotes
- Receptors that are permeable to cations. They are usually associated with the depolarization of neurons.
- Brain-derived neurotrophic factor (BDNF): Plays a role in the growth and development of neurons.
The Technological Impact on Coffee Growing in the Face of Climate Change
By Anushka Gupta, Genetics & Genomics, ‘20
Author’s Note: Climate change is an important topic and must be discussed in order to mitigate the severe consequences. Unbeknownst to most people, however, coffee is also heavily impacted by climate change due to the sensitive conditions necessary for proper cultivation. I hope I can bring to light some of the less serious impacts of climate change and how something normal, like coffee, may become extinct without interference.
Over fifty percent of Americans enjoy a daily cup of coffee, with over 500 million cups of coffee served everyday. Unfortunately, with the increasing temperatures due to climate change, coffee is at high risk of extinction. However, with new advances in technology, coffee can now be grown in a wider range of environmental conditions. Specifically, the integration of modern technology to pre-existing growing practices and the use of artificial intelligence have both contributed to making a future with coffee a possibility.
To understand the new developing technologies, it is crucial to understand the severity of climate change and how it specifically affects the coffee production business. Given the rapidly increasing rate of global temperatures, coffee will likely be much more expensive and be of a much lower level of quality within just 30 years. On top of this, the amount of land that is available for coffee growing will be cut in half by 2050, according to Climate Institute, a company in Australia. Coffee is grown mostly in tropical regions, like Honduras and Brazil, which also happen to be the regions hardest hit by climate change. In fact, the top countries that are most affected by climate change are the same countries where the majority of the world’s coffee beans are grown.
This becomes problematic as coffee beans are also extremely sensitive to temperatures outside of their ideal growing temperature. Most coffee beans will only grow in the range of 18°C to 21°C at high altitudes. They also require a perfect amount of rain, as anything outside of these optimal conditions will damage or even kill the plants. Climate change has already had its effects on coffee production around the world. Heavy rains in Columbia, droughts in Indonesia, and coffee leaf rust (a fungus that attacks coffee bean leaves) in Central and South America have significantly decreased the coffee yield in the past few years. These are only a few of the many examples of how coffee growers are struggling to maintain their crop yield each year [1].
One way coffee growers are preparing for climate change is by engineering a new resistant strain of coffee beans. Currently, only one type of coffee bean, Arabica, dominates the entire industry. Arabica is known for its high quality flavor and aroma, but lacks genetic diversity, commonly leaving it susceptible to coffee leaf rust [2]. The coffee leaf rust fungus preys on the leaves of coffee plants, and eats away at the leaf until an orange-brown color is left instead of the previous green leaf, thus destroying the plant’s ability to make its own energy [3]. The lack of genetic diversity allows for this fungus to spread rampantly across coffee bean farms. For instance, if one strain of the fungus affects a particular variety of Arabica, it is also extremely likely that other Arabica plants will also be afflicted [2]. With increasing temperatures already posing a greater threat to plants, the leaf rust fungus is expected to have an even more apparent impact on coffee yield. In addition, the availability of farmable land is decreasing, as coffee plants only grow in a narrow range, a range that is shrinking due to increasing global temperatures. However, creating a hybrid coffee bean can resolve this problem by choosing strains in hopes of achieving a desired quality, such as coffee leaf rust resistance [2].
Coffee breeder William Solano works at the tropical agricultural research and higher education center (CATIE) in Costa Rica doing just that. He works on creating coffee hybrids by combining genetically distant yet complementary coffee strains in hopes to achieve a product that takes in characteristics from each parent coffee strain [3]. At CATIE, he created the Centroamericano coffee bean, a cross between the Ethiopian landrace variety Rume Sudan and another coffee bean called T5296, which is known for its coffee leaf rust resistance [2]. On its own, the Centroamericano has proven to be twenty percent more productive than other coffee beans and is tolerant to coffee leaf rust. However, it soon became clear that it fares better against the effects of climate change as well, as it can survive temperatures below freezing. This was an especially surprising find as the plant was originally designed with only disease resistance in mind [3].
On top of changing the coffee bean, scientists are also finding a way to use new technologies to make coffee farming more efficient. The most promising example seen so far has been the implementation of artificial intelligence (AI) to the coffee growing business. AI technology now allows farmers to accurately analyze soil fertility properties and compute an estimation of coffee yields [4]. The American technology company IBM has developed an AI-powered device that does just that. The device, called the AgroPad, is portable and about the size of a business card. This device has the capability to quickly analyze the soil to check for chemical composition, allowing coffee farmers to make educated decisions on how to manage their crops. Coffee growers can improve sustainability of their crops as well as save money since they know the amount of water and fertilizer that would be most beneficial to the crop to maximize yield.
To activate the device, only a small sample size is needed. The sample can either be a drop of water or a liquid soil extract that is produced from a pea-sized clump of dirt, depending on the type of analysis needed. Within about 10 seconds, the device will generate a report using a microfluidics chip inside that performs data analysis. The device can give accurate information on the pH, and amount of various chemicals, such as nitrite, aluminum, magnesium, and chloride. This information is given in the form of circles that correlate to the soil composition. These circles give colorimetric test results, where each circle will represent the amount of a specific chemical that is in the sample [6]. The figure below shows what a sample report may look like. Once this output is given out by the AgroPad, the farmer can use an app to take a picture of the output where the app will read the data. The implementation of this device could allow coffee to be grown in more parts of the world as it will be evident what specifically must be done to ensure the productive growing of coffee in these fields [5].
Dedicated mobile app scanning of a sample report created by AgroPad
Fig. 1. Peskett, Matt. “IBM’s Instant AI Soil Analysis – the AgroPad.” Food and Farming Technology, 28 Jan. 2020, www.foodandfarmingtechnology.com/news/soil-management/ibms-instant-ai-soil-analysis-the-agropad.html.
Technology has the potential to save some of these coffee plants in the face of climate change, however, at the current rate of climate change, it is difficult to say how the world will look like thirty or even fifty years in the future, and if coffee will be a part of that world. Hopefully, more technological advances will continue to rise over the years giving hope to both coffee growers and coffee drinkers alike around the globe.
Sources
- Campoy, Ana. “Another Species Threatened by Climate Change: Your Morning Cup of Coffee.” Quartz, Quartz, 3 Sept. 2016, qz.com/773015/climate-change-will-kill-coffee-by-2100/. Accessed 1 Jun. 2020.
- Mu, Alejandra, and Hernandez. “Coffee Varieties: What Are F1 Hybrids & Why Are They Good News?” Perfect Daily Grind, Perfect Daily Grind, 20 Apr. 2020, perfectdailygrind.com/2017/06/coffee-varieties-what-are-f1-hybrids-why-are-they-good-news/#:~:text=Centroamericano%20is%20a%20cross%20between,high%20yielding%20and%20rust%2Dresistant.&text=SEE%20ALSO%3A%20Bourbon%20vs%20Caturra,Variety%20%26%20Why%20Should%20I%20Care%3F. Accessed 1 Jun. 2020.
- Ortiz, Arguedas. “The Accident That Led to the Discovery of Climate-Change-Proof Coffee.” MIT Technology Review, MIT Technology Review, 2 Apr. 2020, www.technologyreview.com/2019/04/24/135937/the-accident-that-led-to-the-discovery-of-climate-change-proof-coffee/. Accessed 1 Jun. 2020.
- “The Future of Coffee: 3 Technologies to Be on the Lookout for in 2019.” Royal Cup Coffee, 28 Dec. 2018, www.royalcupcoffee.com/blog/articles/future-coffee-3-technologies-be-lookout-2019. Accessed 1 Jun. 2020.
- “Enveritas Pilots IBM’s AI-Powered AgroPad to Help Coffee Farmers.” IBM Research Blog, 10 Dec. 2019, www.ibm.com/blogs/research/2019/12/enveritas-pilots-ibms-ai-powered-agropad-to-help-coffee-farmers/. Accessed 1 Jun. 2020.
- “No Farms, No Food.” IBM Research Blog, 7 Mar. 2019, www.ibm.com/blogs/research/2018/09/agropad/.
- “IBM’s Instant AI Soil Analysis – the AgroPad.” Food and Farming Technology, 28 Jan. 2020, www.foodandfarmingtechnology.com/news/soil-management/ibms-instant-ai-soil-analysis-the-agropad.html.
The Neck Raising Behavior of Branta canadensis
By Cristina Angelica Bilbao, Biological Sciences ‘22
Author’s Note: I performed this ethological research study for my Zoology class at Las Positas College. I love animals and was excited to have the opportunity to conduct research on an animal of my choice. I chose to research Canada Geese because I grew up around them and was initially scared of them. I wanted this project to be something that would help me understand the complex behavior of geese and provide knowledge to my community. I chose to go to Shadow Cliffs Lake in Pleasanton California because that is where a large population of Canada Geese live year round.
Above all, I hope this paper can convey that Canada Geese are not as aggressive as we may think. I hope that this paper can provide the knowledge that geese are actually a lot humans. With an understanding of their emotional displays, we can begin to understand them in ways similar to how we understand and interact with one another.
ABSTRACT
For centuries, biologists have tried to understand the mechanics of animal behavior. In 1963, Niko Tinbergen published four questions that allowed zoologists to focus on animal behavior in a scientifically rigorous manner. Tinbergen’s Four Questions center around four different concepts that could be related to animal behavior: Causation, Development, Adaptation, and Evolution.
In this ethological study, I aimed to explain if the neck raising behavior of Canada Geese was due to causation or adaptation. An adaptive behavior is a behavior that has been shaped by an environment over a long period of time, while causative behaviors can be linked to physiological responses to stimuli. I hypothesized that the neck raising behavior done by Canada Geese is an adaptation and not a causative behavior in response to a negative stimulus.
In order to understand this behavior, I observed a population of Canada Geese residing at Shadow Cliffs Lake in Pleasanton, California. Previous studies proposed that Canada Geese raise their necks due to an adaptation and not solely as a reaction to a negative stimulus. This study was done over a period of ten days with a close study and a distant observation study. If the distance was minimal, the geese were indifferent and only raised their necks out of curiosity. If the distance was further away with no external stimulus, the geese would still raise their necks at the same frequency. The results of this experiment was confirmed by concluding that the neck raising behavior of Canada Geese is an adaptation rather than just a reaction to a stimulus. I was also able to conclude that my observations were able to support the null hypothesis because the geese raised their necks at the same frequency during the close and distant studies.
INTRODUCTION
In the book Geese, Swans and Ducks [1], Canada Geese are described to be sociable and family oriented birds that show their emotions through a variety of displays.
Emotional responses can be the key to understanding Canada Geese behavior. It has been observed that dominance and aggression tend to be expressed simultaneously among Canada Geese. Bernd Heinrich, a professor of biology at University of Vermont, conducted an observational study on a breeding pair of Canada Geese. He made many personal accounts of how the breeding pair had a high intensity of aggression towards him while guarding their eggs. When Heinrich came back once their young had hatched, the pair was not aggressive and seemed to adjust to the researchers presence [2].
The prominent neck of the Canada Goose is an important indicator of emotional responses. Emotional displays characterized by head pumping, withdrawn necks, and vocalizations have been designated as situational and related to attacking or fleeing action [3]. The threat postures were categorized as having a variety of neck movements accompanied by vocalized hissing noises [4]. Another study was able to observe specific members of Canada Geese families taking up ‘guard positions’, which involved various sets of alert and alarm postures [3]. The alert and alarm postures were characterized with similar behaviors relating to threat postures. If the geese were in an alert posture, they would raise their necks high and freeze. If they were in alarm postures, the geese would more than likely begin to display similar threat behaviors of wing flapping and vocalization to warn the rest of the group. This behavior was seen equally between the male and female geese, especially at the time when they are protecting their nests from predators [3].
While it seemed that aggression was the only explanation for this reaction, I began to question if that was the sole conclusion that could be made. The Shadow Cliffs lake population usually could be seen on the beach, in the lake, or on the grass with minimal worry about threats. I observed that the geese lived mutually with the other waterfowl in the area and they seemed to have grown comfortable around humans due to constant contact. This could be one of the reasons that the group chose to stay in this area for prolonged periods of time.
Before I performed my observational study, I conducted two preliminary observations over two days and was able to notice an unusual behavior. At specific times of the day when the geese fed, members of the group would raise their necks at random. The neck extension would occur for about a minute before they went back to eating again. I believe that this may have been a form of communication, until I noticed another behavior that proved my initial hypothesis to be incorrect. While feeding, the geese would form a tactical perimeter around those who were eating in the center. The geese acting as guards on the outside would raise their necks for the longest periods of time and remain alert.
As I performed my preliminary research, I aimed to learn more about the population of Canada Geese residing at the lake. I interviewed Mark Berser, one of the Shadow Cliffs Park Rangers who has been working at the park for over 10 years. He confirmed the geese were usually around the lake throughout the year. He stated the tall grass by the water edge close to the picnic benches was a place the geese went to both eat and sleep. He had not observed the frequency of the geese’s neck raising behavior, but he was aware of the fact that they all seemed watchful in their close groups regardless of the threat.
I expanded my research to online scholarly journals, and I found more information regarding threat postures instead of the specific behavior I aimed to observe. These studies provided a generalized explanation on threat postures, which included neck raising [4]. I was able to find foraging studies that mentioned neck raising behavior as well, but it did not provide details about why the behavior occurred [4]. I was able to deduce that most researchers thought of this behavior as a biological reaction to a stimuli, also known as the attack-flee response [4]. The attack-flee response is a neurological response to a threat that prepares an animal to make the decision fight or to flee. I aim to challenge this idea by hypothesizing that the neck raising behavior done by Canada Geese is an adaptation and not a causative behavior in response to a negative stimulus.
MATERIALS AND METHODS
Before I began my study, I gathered binoculars for observations and a field notebook to keep records of my observations. Next, I developed a detailed schedule relating to how and when I would observe the geese. I planned to conduct a ten day study on the population of Canada Geese in their habitat at Shadow Cliffs Lake. My observation days were on Mondays and Fridays before noon, in order to reduce the possibility of outside interference. If there was a situation that prevented me from not attending on Monday or Friday, I was able to make observations on another day at the same time in order to prevent discrepancies in the results.
During the first five days of the experiment, I positioned myself ten feet away from the geese. I casually sat at one of the tables in order not to disturb them in their normal routines. I then focused my observations on the frequency of the neck raising behavior over the course of one hour. Through these five days, I made sure to make note of the frequency of the behavior in my field notebook. Once the first five observation days were complete, the second portion of the experiment began. I made sure to arrive unnoticed as I positioned myself at a further distance away from the population. By keeping distance, I eliminated the possibility of the geese raising their necks as a reaction to my presence. During this time, I watched the geese with binoculars and took note of their neck raising behavior for one hour. I continued to take notes on the frequency of the behavior and I began to transfer the data to a table in order to properly visualize the results.
RESULTS
The target population of Canada Geese typically remained in a large group. On random occasions, smaller groups would split off from the rest of the family to either get an early start on bathing in the lake or to find food elsewhere. While they did split, they would eventually come back together in one location.
In large and small groups, there was a known presence of ‘guard’ geese. These geese would take position around the perimeter of the large or smaller groups. When the guard geese noticed me, they raised their necks more frequently and held the position for the longest period of time. The geese observed me before leaning down to eat and switch roles with another member.
During the first five days of observation, the geese were observed in close proximity. The geese were aware of my presence but they did not spread their wings or pump their necks in a threatened manner. Instead, they appeared to be indifferent towards me, raising their necks at a very low frequency as they waited to see if I had food. However, the geese would raise their necks more frequently if they felt that I was too close.
The second half of the observational study was performed at a further distance. The geese were unbothered as they continued with their usual daily routine. The guards and the others in the population raised their necks at low frequency, similar to what was observed in the first part of the study.
CONCLUSION AND DISCUSSION
In this ethological study, I aimed to observe the neck raising behavior of Canada Geese over the course of 10 days. During this observation period, I intended to explain whether or not the behavior was due to causation or an adaptation, as it relates to Tinbergen’s Four questions. Causation would describe the behavior as physiological while adaptation would describe the behavior as a reaction to stimuli developed over time. Through this study I was able to compare whether or not this behavior was more physiological or adaptive by taking certain factors such as visual stimuli and general environment into account. Initially, I hypothesized that the neck raising behavior done by Canada Geese is an adaptation and not solely a physiological response to a negative stimulus.
To successfully observe this behavior in the chosen target population, a variety of variables were taken into account. The Canada Geese were set to be observed without an external stimuli, which meant that time, presence of food and distance were all important variables. There was no food present and the population was observed at a time with minimal external stimuli exposure. The geese were observed from a far and close proximity in order to prove that neck raising behavior was an adaptation.
To support my hypothesis, observational data was collected over the course of ten days. Chart 1 presents the behavior observations from a short distance. The geese were aware of my presence because they raised their necks frequently, but they seemed indifferent towards me. More specifically, the perimeter guard geese seemed to be raising their necks the most and for the longest period of time. When the designated guards vocalized, the group of geese raised their necks collectively. I kept note of these results as I moved into the next phase of the study. Chart 2 depicts the behavioral observations made from a distance. Similarly, the geese raised their necks at the same frequency to look at their surroundings as they went about their daily routine.
The similarity in the results prove that the behavior of neck raising is not just linked to the presence of a stimulus. In relation to the work done by Blurton-Jones, neck raising and held erect posture could be perceived as a threat posture to drive away predators [8]. At a closer distance, the geese would raise their necks. While this could be seen as a threatened reaction, the behavior seemed to be more of an awareness of my presence rather than aggression. This was confirmed when the geese did not flex their wings or alert the group of a threat. The geese raised their necks and did not give any further reaction unless I got significantly closer. This allowed me to conclude that neck raising behavior is linked to threatening external stimuli.
With these results in mind, my hypothesis was confirmed. This experiment proves that neck raising behavior seems to be an adaptation developed through time as a method of protection rather than just a reaction to a stimulus. Through the act of raising their necks, the Canada geese make it known that they are aware of threats and are watching out for members of their family.
In the future, I would hope to perform more in-depth studies. Within my study, I was limited by the population of Canada Geese that I studied. The population of geese was the only significantly large population in Pleasanton, which ultimately limited my results. There was also a limiting factor relating to human contact; the group of geese that I observed had grown used to human contact instead of perceiving them as threats. While the group of geese displayed the behavior I aimed to observe, the results could be different in situations with limited human contact.
In future research, populations of Canada geese that have not experienced human influence should be observed. This would be able to prove whether or not the environment is a factor contributing to the neck raising behavior. Further research should include sexing the geese in order to rule out sex being a possible factor contributing to the frequency of neck raising behavior.
References
- Kear J. 2005. Canada goose (Branta canadensis).Ducks, geese and swans: general chapters, species accounts (Anhima to Salvadorina). New York (NY): Oxford University Press. P.306-316.
- Blurton-Jones NG.1960. Experiments on the causation of the threat postures of Canada geese. Wildfowl. 11(11): 46-52.
- Klopman RB. 1968. The agonistic behavior of the Canada goose (Branta canadensis canadensis): I. attack behavior. Behaviour. 30 (4): 287-319.
- Raveling DG. 1970. Dominance relationships and agonistic behavior of Canada geese in winter. Behaviour. 37(3/4):291-319.
- Hanson HC. 1953. Inter-family dominance in Canada geese. The Auk. 70(1):11-16.
- Herrmann D. 2016. Canada geese. Avian cognition: exploring the intelligence, behavior, and individuality of birds. Boca Raton (FL):CRC Press. P.72-143.
- Akesson TR, Raveling DG. 1982. Behaviors associated with season reproduction and long-term monogamy in Canada geese. The Condor. 84(2): 188-196.
- Heinrich B. 2010. Parenting in pairs. The nesting season: cuckoos, cuckolds, and the invention of monogamy. Cambridge (MA): Harvard University Press.p. 210-213.
Appendix
Chart 1: Field Notes Observation Table Results for Close Study
| Date | Day/Description | Summary of Behavior |
| 9/30/19 | Day 1- 1:30-2:30 p.m.
The weather at the time was comfortably warm. The sun was out and there was a light breeze. While it did seem like the perfect day to go out to the lake, there actually weren’t a lot of people in the area. This made it easier to reduce any interference. |
–In the large family of geese and even in the smaller sub groups, there were designated ‘guards’. These rotating guards seemed to have a strategy of holding the perimeter. They were the members of the group that actually raised their necks the longest and most frequently. They would hold their necks up for about 10-20 seconds.
-When it comes to noticing me or if I was too close, the guard geese signaled a call to the rest of the group. The call would get the rest of the group to raise their necks. Overall though, they didn’t seem threatened but instead either somewhere in between indifferent or curious about if I had food. |
| 10/4/19 | Day 2- 11:30-12:32 p.m.
The weather at the time was a little colder than the first observational day. The sun was out but it was all around a little colder with a slight breeze. There were not many people at the lake. |
–The entire family of geese would raise their necks at random points. It became clear that the ‘guards’ were in a position where the ones that had the most power to alert the group of any potential problems.
-The guards raised their necks the most frequently. -In an area with no remote threats, the geese still seemed to be very clearly aware of their surroundings. |
| 10/8/19 | Day 3-12:30-1:30 p.m.
The weather today easily symbolized that fall was near. The sun was out but it was cloudy and there was a strong wind. This ultimately made it a cold day. There were people but not many near the geese. |
–Similarly to the other two observation days, the geese were still mostly indifferent to my presence.
-If I got too close, the guard geese would make sure others knew about me, but they weren’t even close to being threatened. -The neck raising behavior occurred frequently when I was in the presence of the population. |
| 10/11/19 | Day 4-11:27-12:30 p.m.
The weather today was cold. I could still see the sun but there were more clouds than most of the other days. There also was a slight breeze. Once again there were not many people at the park. |
–The geese retained the same indifferent behavior towards me.
-Most of the time I could justify that they raised their necks simply because they wanted to be aware of me and maybe were hoping that I had food. -The guards at the same time still were the ones that raised their necks the most frequently. |
| 10/16/19 | Day 5-6:40-7:40 p.m.
Mainly because it was the evening, the sun was actually setting. The weather itself started to get windy and cold as the darkness approached. There were still a few people at the lake but they weren’t providing interference to the geese. |
–The geese were raising their necks every few minutes like usual and holding the position before they went back to eating.
-It was interesting to see that there were actually more guards around vocalizing and raising their necks quite frequently. -The guards were also still raising their necks quite frequently when it came to watching out for the small groups flying to the water to sleep. |
Chart 2: Field Notes Observation Table Results for Distance Study:
| Date | Day and Description | Summary of Behavior |
| 10/19/19 | Day 1- 1:20-2:20 p.m.
The weather at the time was sunny and warm. There weren’t too many people at the lake at this time, which minimized experimental interference. |
–The geese still seemed to display the same alert behavior through the action of neck raising.
-The perimeter guard geese still seemed to be the particular members of the family that raised their necks the most often and longest. The longest neck raised posture that the geese held was about 10 seconds. -The neck raising behavior would occur at random points of time to be alert of the surroundings and what the other members of the population were doing. |
| 10/22/19 | Day 2- 2:13-3:30 p.m.
The weather was sunny and warm, but there was a stronger breeze than the previous observation day. There were a bit more people at the lake today, but they weren’t anywhere near the geese population |
–The guard geese were still on alert both on the beach and in the park area.
– It is important to note that while the guards were the ones still raising their necks the most and the longest, the rest of the family was also doing the action. -When the guards seemed to vocalize, they had the power to get the whole group to stop eating and raise their necks to attention. The behavior also seemed to occur if two groups were calling to each other from two different locations. |
| 10/25/19 | Day 3- 1:13:2-13 p.m.
The sun was out but it was a bit colder, hinting at the arrival of the fall season. There were people fishing but since the geese took particular interest in feeding within an enclosed area, observation was not affected. |
–The geese in the parking lot and picnic area actually seemed to have similar frequencies of neck raising behavior.
-In the picnic area, the geese seemed extremely indifferent to the people in the distance and actually laid down. It was interesting to see the guards lay down as well, yet still raise their necks in the same frequency. -In regards to the group in the parking lot, it seemed that the neck raising behavior still occurred at the same frequency. The difference was more observable in how long the posture was held, which came out to be about 30 seconds. |
| 11/8/19 | Day 4- 11:30 a.m. -12:30 p.m.
There were a bit more clouds and a stronger breeze, but I could still clearly see the sun. The observations were carried out with no interference. |
– The guard geese prominently were still the usual members of the population raising their necks the longest and most frequently compared to the rest of the population.
-The geese that took up the roles as the guards happened to be the most alert and aware of the surroundings and other members of the family. – The neck raising behavior almost seemed summed as both a reaction to family calls and a general adaptation to watch the surroundings for any threats to the population. |
| 11/15/19 | Day 5- 12:40-1:40 p.m.
The sun was out but the overall weather was cold, mainly due to the strong breeze. Once again there weren’t many people around, which allowed for the geese to not get distracted. |
–On the final day of observation, the geese were in a much larger group feeding in the park area. There was also a small group on the beach.
-It was clear that there were designated guards, which told me that these roles were not just temporary. -The whole family would raise their necks, but it was the guards that raised their necks most frequently. -It seemed that the neck raising behavior was occuring quite randomly. Realistically this could mean that the geese raising their necks could be an adaptation to be aware of what the family is doing. It could also be an adaptation to avoid predators. |
Field Note Photos and Supplementary Images:
- The first set of images are entries from my field journal. Though they may be difficult to see, the data has been summarized in the tables above.
- The second set of images depicts two instances where the geese were displaying neck raising action. They also show the guard geese in place.
Image 1: This image was taken at the time the close distance observations were being conducted. In this image, a group of geese can be seen eating on the grass of the park hill. On the far corners of the image, two guard geese can be seen taking up perimeter positions around the rest of the group.
Image 2: This image was taken at the time close observations were being conducted for the experiment. In this image, two Canada Geese, possibly a mating pair, were foraging in the grass. The current acting guard can be seen on the left.