The Double-Edged Nature of Prions

One of the most gut-wrenching yet addictingly intriguing games I played growing up was Mafia. Sitting around a circle, discussing and debating the culprit…only for it to be the one person you thought was the healer!

The stealth and deception involved across the game reflect much more. Within our bodies, we see this play at a much larger scale across the immune system, manifesting as fevers, allergies, and other diseases. One prominent disease that often slips past our immune defenders, however, is prions. Our most secretive yet deadly macromolecules, prions, have the potential for immense harm but also surprising benefit.

But what exactly are they? Prions are a series of proteins that have become misfolded in a way that allows them to self-replicate, becoming independent of the cells in which they reside. They can be classified into three forms: prion proteins, responsible for forming prions, transcellular prionoids, misfolded proteins that aggregate through cell-cell interactions, and quasi-prions, anomalies in between prions and transcellular prionoids¹. Unlike viruses, bacteria, or even cells, prions are devoid of genetic material within their structure, with a mechanism of replication that varies based on how they have been misfolded. For instance, research on prions within the brain has shown that changes in electric charge may cause prion fibril elongation, leading the proteins to propagate and aggregate².

This aggregation mechanism often goes unnoticed by the immune system. As a biologically derived molecule, the prions are not viewed as foreign or antigenic by most immune cells. The most deadly is the neurodegenerative Creutzfeldt-Jakob disease (CJD), caused by overproduction of the prion protein, encompassing 85% of prion-disease forms in humans³. Variants of CJD spread dramatically due to mutation heritability and exposure to diseased tissue. In 1986, mad cow disease, a CJD that originated in cattle, spread to humans that ingested the meat, and was only controlled once infected herds were no longer consumed⁴. At a molecular level, it appeared that the abnormal prions in cattle were somehow modifying human prion development, indicating conserved mechanisms across species.

Prion disease manifestation can vary from person to person. CJD, for example, exhibits symptoms similar to many prevalent neurodegenerative diseases, making it hard to trace. Causing severe symptoms from confusion and dementia or hallucinations, the severe ailments that follow CJD still have very few treatment options⁵. Recent efforts have utilized a biotechnological approach to treating the disease, using tools such as gene editing with CRISPR-based tools, synthetic molecules and antibodies, and disinfectants⁶.

Like all biological phenomena, prions may have evolved to have unexpected positive effects. Due to their heritable nature, prions have the potential to pass on beneficial traits. A 2016 study at Stanford University found 46 prions in yeast cells that could improve the cell’s resistance to antifungals and heat⁷. With looser formations than their disease-causing counterparts, as well as a better affinity to DNA, these prions are more adaptable, ensuring better fitness of the cells containing these prions. Others like the CPEB prion-like proteins in the common fruit fly, Drosophila, have also shown potential to improve memory⁸.

For now, the legacy of prions in humans remains bleak. But could there be benefits to their existence? And, if we understand more prion-growth mechanisms, we might just alter our fundamental understanding of biology. This game of Mafia has just begun!

References

1. Harbi D, Harrison PM. ­Classifying prion and prion-like phenomena. Prion. 2014;8(2):161-165. doi:10.4161/pri.27960

2. UCL. Study reveals new detail on how prions replicate in neuronal cells. Brain Sciences. December 20, 2023. Accessed March 3, 2025. https://www.ucl.ac.uk/brain-sciences/news/2023/dec/study-reveals-new-detail-how-prions-replicate-neuronal-cells

3. Ritchie DL, Peden AH, Barria MA. Variant CJD: Reflections a Quarter of a Century on. Pathogens. 2021;10(11):1413. doi:10.3390/pathogens10111413

4. CDC. Bovine Spongiform Encephalopathy (BSE). Bovine Spongiform Encephalopathy (BSE). May 10, 2024. Accessed March 3, 2025. https://www.cdc.gov/mad-cow/php/animal-health/index.html

5. Prion Diseases. February 28, 2025. Accessed March 3, 2025. https://www.hopkinsmedicine.org/health/conditions-and-diseases/prion-diseases

6. Therapeutic Approaches for Prion Diseases | NIAID: National Institute of Allergy and Infectious Diseases. October 21, 2019. Accessed March 3, 2025. https://www.niaid.nih.gov/diseases-conditions/prion-therapeutic-approaches

7. Prions can pass on beneficial traits, study finds. News Center. Accessed March 3, 2025. https://med.stanford.edu/news/all-news/2016/10/prions-can-pass-on-beneficial-traits-study-finds.html

8.Prions: What Are They Good For? | Annual Reviews. Accessed March 3, 2025. https://www-annualreviews-org.ezproxy.rice.edu/content/journals/10.1146/annurev-cellbio-100913-013409#right-ref-B101

From Lizards to Mammals: Unraveling the Science Behind Cell Regeneration

Have you ever seen a lizard regrow its tail? What if people had this ability to regrow a lost limb or organ? In the animal kingdom, anamniotes—fish and amphibians that lay eggs in aquatic environments—such as salamanders and zebrafish, have extensive regenerative properties. The axolotl is the first model for regenerative studies and has been studied since the 1860s for its ability to restore limbs, tails, eyes, and hearts [1]. Zebrafish are even capable of regenerating their brains. Lizards, on the other hand, are part of a vertebrate group known as amniotes. Amniotes include reptiles, birds, and mammals that reproduce on dryland. Surprisingly, lizards are the only amniotes capable of cell regeneration and are the closest relatives of humans that can regrow tissue [5]. They regrow their tails through autonomy, an anti-predation strategy that utilizes cell regeneration to restore damaged and lost tissue [2]. Understanding this regenerative process could be essential for regenerative medicine and treating neurological disorders.

How is regeneration possible? Neurogenesis is a process integral to tail regeneration. Neurons are generated from neural stem cells in the adult brain to add to or replace neurons in pre-existing circuits [3]. It occurs in the telencephalon, the part of the brain responsible for higher-level functions such as thinking, memory, and processing sensory information. Adult neurogenesis occurs in all vertebrate groups, including humans, but has more extensive effects in non-mammalian groups [3]. For example, neurogenesis in lizards produces more neurons and impacts more parts of the brain. In mammals, it is restricted to olfactory bulbs and the hippocampal dentate gyrus, the regions of the brain responsible for sense of smell and processing sensory information. This limitation means that while neurons are replaced in these areas, other parts of the brain are still susceptible to damage and deterioration.

Current hypotheses suggest that regeneration is a trait that occurred early in evolution, as it is most commonly found in lower-level organisms. Higher-level organisms, like humans and other mammals, evolved to have more robust immune systems with defensive macrophages— white blood cells responsible for detecting and breaking down viruses and bacteria—at the expense of regenerative capabilities [1]. These strong immune systems dispose of viral and bacterial tissue, whereas lizards and anamniotes rely on non-immune mechanisms to avoid infection [5]. Baffling to researchers, although macrophages regulate the regeneration process, macrophage depletion in salamanders and zebrafish leads to delayed or altogether halted regeneration [5].

Harnessing this ability in humans would revolutionize research and healthcare. Researchers are working to leverage the unique regenerative capabilities of lizards as a model to transform the field of regenerative medicine. They use the lizard model to reprogram somatic cells—cells found in mammals that repair or replace damaged or aging tissue—toward a multipotent state, in which they become specialized for various tissues and functions [1]. This would mean that, on a small scale, humans could restore damaged or lost tissue. Advancements in studying neurogenesis could significantly impact regenerative medicine, neuroscience, and the treatment of neurological disorders. This progress would revolutionize the future of medicine, changing the landscape for disease and disorder treatment.

References

Daponte, V., Tylzanowski, P., & Forlino, A. (2021). Appendage Regeneration in Vertebrates: What Makes This Possible? Cells, 10(2), 242. https://doi.org/10.3390/cells10020242. Most helpful connection to biomedicine.

Donato, S. V., & Vickaryous, M. K. (2022). Radial Glia and Neuronal-like Ependymal Cells Are Present within the Spinal Cord of the Trunk (Body) in the Leopard Gecko (Eublepharis macularius). Journal of Developmental Biology, 10(2), 21. https://doi.org/10.3390/jdb10020021

González-Granero, S., Font, E., Desfilis, E., Herranz-Pérez, V., & José Manuel García‐Verdugo. (2023). Adult neurogenesis in the telencephalon of the lizard Podarcis liolepis. Frontiers in Neuroscience, 17. https://doi.org/10.3389/fnins.2023.1125999

Hye Ryeong Kim, Choi, H., Soon Yong Park, Song, Y., Kim, J.-H., Shim, S.-I., Jun, W., Kim, K., Han, J., Chi, S., Sun‐Hee Leem, & Jin Woong Chung. (2022). Endoplasmin regulates differentiation of tonsil-derived mesenchymal stem cells into chondrocytes through ERK signaling. Journal of Biochemistry and Molecular Biology, 55(5), 226–231. https://doi.org/10.5483/bmbrep.2022.55.5.173

Londono, R., Tighe, S., Milnes, B., DeMoya, C., Quijano, L. M., Hudnall, M. L., Nguyen, J., Tran, E., Badylak, S., & Lozito, T. P. (2020). Single cell sequencing analysis of lizard phagocytic cell populations and their role in tail regeneration. Journal of Immunology and Regenerative Medicine, 8, 100029. https://doi.org/10.1016/j.regen.2020.100029

Epigenetics: The Hidden Key To Development

Have you ever wondered why your parents have different colored eyes than you, or why you and your sibling don’t look alike? The answer may lie in one simple yet complicated term: epigenetics. Epigenetics is defined as the “study of heritable changes in gene expression that do not involve modification to the underlying DNA sequence” [1]. To put it in simpler terms, it’s how certain molecular modifications alter the way genes, such as those determining eye color, are expressed. There are a multitude of factors that determine how certain genes are expressed, but these epigenetic patterns begin in fetuses during pregnancy. 

To understand the factors that affect a fetus, we need to first understand the mechanism behind epigenetics. Firstly, gene expression is regulated by the modification of nucleosomes. A nucleosome is essentially elongated and uncoiled DNA that is wrapped around a set of proteins called histones [2]. While DNA carries a negative charge, histones generally carry a positive charge; like magnets, the negatively charged DNA molecules are attracted to the positively charged histones, and the degree of attraction regulates gene expressions. Modifications often affect how tight the DNA is wrapped around the histones [2]. One common modification is DNA methylation, in which a special molecule called methyl is added to the histones, which affects how tightly DNA is wrapped around the histones [2]. The increased attraction causes DNA to tightly coil around the histones, creating heterochromatin – tightly packed DNA — which prevents gene expression [2].   

Now, let's take a look at how these molecular processes apply to pregnancy. According to a study by Andrawus and peers, the patterns for DNA methylation in a fetus are established during pregnancy [3]. Furthermore, environmental factors during a pregnancy also play a role in epigenetics [3]. Two notable environmental factors that affect gene expression are pollution and nutrition. Pregnant mothers living in areas with increased air pollution “have been reported to show decreased DNA methylation” in a gene called LINE-1 [4]. Studies have shown that decreased methylation of LINE-1 is a common contributor to cancer and its development [5]. Furthermore, changes to maternal nutrition can lead to physical and mental changes in development [1]. According to Zuccarello and peers, vitamin B12 intake during pregnancy affects the methylation of DNA, and“high levels of vitamin B12 in maternal blood was correlated with the reduction” of DNA methylation of the fetus [1]. Such high levels of vitamin B12, and the corresponding decrease in DNA methylation levels, can result in potential intrauterine growth, which means that the fetus does not grow to a healthy weight as expected [1].

Overall, epigenetic expression during pregnancy plays an important role in our physical traits, as well as our overall well being. Both pollution and nutrition play a role in affecting DNA methylation patterns throughout development, which can affect the health of the child. Ensuring that pregnant women are in clean environments with access to correct nutrition allows them to sustain a healthy pregnancy and birth a healthy child.

References:

Zuccarello, D., Sorrentino, U., Brasson, V., Marin, L., Piccolo, C., Capalbo, A., Andrisani, A., & Cassina, M. (2022). Epigenetics of pregnancy: Looking beyond the DNA code. Journal of Assisted Reproduction and Genetics, 39(4), 801–816. https://doi.org/10.1007/s10815-022-02451-x

Al Aboud, N. M., Tupper, C., & Jialal, I. (2023). Genetics, Epigenetic Mechanism. In StatPearls. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK532999/

Andrawus, M., Sharvit, L., & Atzmon, G. (2022). Epigenetics and Pregnancy: Conditional Snapshot or Rolling Event. International Journal of Molecular Sciences, 23(20), 12698. https://doi.org/10.3390/ijms232012698

Li, S., Chen, M., Li, Y., & Tollefsbol, T. O. (2019). Prenatal epigenetics diets play protective roles against environmental pollution. Clinical Epigenetics, 11(1), 82. https://doi.org/10.1186/s13148-019-0659-4

Phokaew, C., Kowudtitham, S., Subbalekha, K., Shuangshoti, S., & Mutirangura, A. (2008). LINE-1 methylation patterns of different loci in normal and cancerous cells. Nucleic Acids Research, 36(17), 5704–5712. https://doi.org/10.1093/nar/gkn571

A deep dive into the Ashwagandha frenzy – is it really worth it?

For those of us that have been chronically online in the last several months and are prone to adopting the newest ‘hacks’ for how to improve our health and lifestyle with every headline we see, the name of one substance is easily recognized - Ashwagandha. This medicinal plant, scientifically known as Withania somnifera, is a staple in Ayurvedic and indigenous medicine and is known by herbalists to have antioxidant, anti-inflammatory, and immunomodulatory effects (Bharti et al., 2016). Recently, there have been claims from users of ashwagandha that they experience immense stress relief, boosted confidence, and increased drive and motivation – seemingly raising the herb to a magical pedestal (Pelc, 2023). 

But, how true are these claims, and is ashwagandha really worth the hype?

Scientifically speaking, several studies affirm that ashwagandha can stimulate cell-mediated immunity, such as killing microorganisms, repairing DNA of an inflamed cell, and increasing the amount of beneficial gut microbiota in the body – thereby working well towards managing immune-suppressed diseases, with the most recent study coupling ashwagandha with COVID-19 immune-boosting (Panda et al., 2021). As an Indian ayurvedic medicinal plant, ashwagandha has also been used to alleviate the symptoms of neurodegenerative disorders and is grown on a commercial scale in several Indian states (Murthy et al., 2010). In fact, somnifera - the formal name for ashwagandha itself - in Latin is an ode to a “sleep-inducer”, which is yet another prominent effect of ashwagandha as a stress reliever (Murthy et al., 2010). 

Where, one might ask, is the doubt here? The biggest difference between the ashwagandha used in herbal care versus Western commercial products is that, based on Ayurveda, herbal preparation, known as “rasayana”, is a long process of creating an elixir that nonspecifically increases human health. In the case of ashwagandha, this most commonly includes boiling the fresh roots of Ashwgandha in milk to extract undesirable minerals (Murthy et al., 2010). However, there aren’t any direct signs that this methodology is used when creating American commercial products, which leads to the question of the efficacy of ashwagandha sold commercially in the United States. 

Recent research does support that ashwagandha use was associated with a decrease in stress and anxiety levels, but it cannot be considered a long-term solution for deeper physical, psychological, or physiological issues (Pelc, 2023). For example, according to nutritionist Brittany Craig at the Mount Sinai Hospital Cancer Center, ashwagandha only has mild to moderate effects on hormone levels, which impact libido, strength, and stress. She notes that claims on social media that place ashwagandha use at a high pedestal can be “misleading”, since their effects are often limited (Pelc, 2023). In addition, studies that show ashwagandha’s positive impacts have only been conducted with small populations and limited durations of under 12 weeks, which may explain why its use as a supplement may not be as commonly accepted as their results suggest (Pelc, 2023). Craig, as well as other researchers, note several studies claiming that while ashwagandha stimulates immune activity, it can have the adverse effect of exacerbating autoimmune diseases. 

Ashwagandha, meaning “smell of the horse” in Sanskrit, may seem to imply that the herb provides the strength and stamina of a horse to those who use it (Thompson, n.d.). However,  giving it the title of a magical pill may be taking it too far. More information should be publicized on the proper uses and expectations of ashwagandha so that its users (both current and potential) experience the most accurate benefits to their health.

References

Bharti, V. K., Malik, J. K., & Gupta, R. C. (2016, February 19). Ashwagandha: Multiple health benefits. Nutraceuticals. https://www.sciencedirect.com/science/article/abs/pii/B9780128021477000528 

Murthy, M. R. V., Ranjekar, P. K., Ramassamy, C., & Deshpande, M. (1970, January 1). Scientific basis for the use of Indian Ayurvedic medicinal plants in the treatment of neurodegenerative disorders: 1. ashwagandha. Latest TOC RSS. https://www.ingentaconnect.com/content/ben/cnsamc/2010/00000010/00000003/art00004 

Panda, A. K., & Kar, S. (2021). Ayurvedic immuno booster: Is it myth or reality in COVID-19 pandemic. International Journal of Current Research and Review, 13(01), 134–140. https://doi.org/10.31782/ijcrr.2021.13140 

Pelc, C. (2023, October 24). Ashwagandha: Does it really lower stress and benefit health?. Medical News Today. https://www.medicalnewstoday.com/articles/how-accurate-are-the-claims-about-ashwagandhas-benefits 

Thompson, K. (n.d.). Ashwagandha monograph. HerbRally. https://www.herbrally.com/monographs/ashwagandha#:~:text=The%20common%20name%20comes%20from,who%20take%20it%20(5).

Bio-Art: The Cross Between Science and Art

When thinking about works of art, science may be the complete opposite of what comes to mind. But bio-art, a genre of art categorized by its avant-garde methods of displaying life, is bridging the gap between these two seemingly unrelated areas. Often, these artists collaborate with scientists and labs to express beauty or provoke thought through biotechnology, using techniques such as cell culturing and genomic editing to create art.

One of the earlier and most impactful pieces of bio-art was Eduardo Kac’s GFP Bunny, which was a rabbit by the name of Alba who glowed green through the use of genetic engineering. In order for Alba to be created, Kac worked with a biological research laboratory. This prompted questions about where the credit was due and how the life forms used are treated, not only for GFP Bunny but also for other major works of bio-art that require collaboration between different fields. This work has sparked much dialogue on the ethics and moral implications of bio-art and has been referenced in shows such as Big Bang Theory, the Simpsons, and Sherlock. 

Another prominent bio-art piece is a work titled Victimless Leather, created by artists and researchers Oron Catts and Ionat Zurr. Both artists were research fellows at Harvard Medical School before turning their attention to bio-art. In this piece, cell lines are used to culture tissue on a jacket shaped polymer matrix, a process very similar to the way that artificial organs are grown. The work is meant to explore the potential consequences of using biotechnology for commercial purposes and prompt reflection on the sources of the clothes we wear. Among Catts and Zurr’s other innovative bio-art pieces are Semi-living Worry Dolls, Better Dead Than Dying, and Stir Fly: Nutrient Bug 1.0. 

With many works of bio-art comes discussion about its ethics. Should any form of life be used in art? Where do we draw the line when it comes to using life in art? Is bio-art taking away from resources that could be used to further biomedical research? Certainly an argument can be made in favor of bio-art because it can draw attention to existing biological controversies like animal testing, genomic editing, and cell culturing (although, on the other hand, this could be done through other mediums.) Bio-art may have the capability to increase public awareness of what goes on in biological research laboratories, but some may believe that this form of art often feeds into what its artists are supposedly fighting against.

While the ethics of bio-art remain a big question, this relatively new form of art has been connecting society with research laboratories through the creation of what could be considered emotional, shocking, and even disgusting projects. At its most basic level, bio-art is about not only aesthetics, but also provoking discussion and thought surrounding difficult but important topics.

References

GFP bunny. (n.d.). https://www.ekac.org/gfpbunny.html 

Victimless Leather. The Tissue Culture & Art Project. (n.d.). https://tcaproject.net/portfolio/victimless-leather/ 

What is Bio Art?. ARTDEX. (n.d.). https://www.artdex.com/what-is-bio-art/