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

GUM GUM: Recent Research Produces Rubbery Material to Replace Human Tissue

“GUM GUM BAZOOKA!” (Eiichiro, 1999) the protagonist of hit anime One Piece, Monkey D. Luffy, howls to deliver the finishing blow on his enemy.

As watchers of the acclaimed series know, Luffy’s power is that of the gum-gum fruit, which makes his body act as rubber. This seems like something only to happen in an anime, and while it is likely best that rubber bones stay relegated to that fictional, animated world, recent nanostructures and materials research could provide humans with a multipurpose, synthetic, rubbery substance that works in accordance with the human body. At Chalmers University of Technology in Sweden, researchers in the chemistry, chemical engineering, and applied physics departments have discovered a rubbery substance that has the potential to replace human tissue (Rajasekhara et al., 2019). 

In order to create an synthetic elastomer (material of a solid state but with relatively high amounts of elasticity) that could agree with the human body, scientists rethought the process of making elastomers. Previously, researchers made elastomers by randomly linking polymers - materials created by the linking of macromolecules - together. To create elastomers that are compatible with the human body, they sought a more organized approach. This new elastomer would be used as synthetic tissue, so its creators used a technique called ordered structuring to connect polymers with collagen and elastin, two fibrous proteins prominent in human skin (Rajasekhara et al., 2019).

With the help of state-of-the-art nanostructuring technologies, ordered structuring now makes the creation of elastomeric substances possible. This allows the surface to be lined by a material (namely what would be in contact with organs) with antibacterial peptides, making the elastomer resistant to bacteria so that it will not be damaged by the natural bacteria present in humans. One of the current applications for this elastomer involves catheter tubes. The material is able to carry medicine or blood while remaining decontaminated and also not killing the bacteria. This is helpful because there is an increasing trend of bacteria becoming antibiotic resistant , so it is becoming harder to eliminate them (“Nanostructured rubber-like material…”, 2020). This synthetic elastomer tube does not result in bacteria death, rather bacteria removal.

Beyond bacterial resistance, the elastomer has a variety of unique properties. Its soft and elastic nature means that it can be injected into the body by a cannula or 3D printed into a specific shape, and its nanopores can be filled with medicine to allow the synthetic tissue to cater to patients’ specific needs (“Nanostructured rubber-like material…”, 2020).

In theory, these biological elastomeric tissues could be used to create a being with rubbery bones. But, let's leave the gum-gum fruit abilities to Luffy and appreciate the material for its potential to revolutionize medicine.

References:

Eiichiro, O. (Oda), & Konosuke, U. (Uda). One Piece. Toei Animation.

Nanostructured rubber-like material with optimal properties could replace human tissue. (n.d.). ScienceDaily. https://www.sciencedaily.com/releases/2020/03/200316090334.html 
Rajasekharan, A. K., Gyllensten, C., Blomstrand, E., Liebi, M., & Andersson, M. (2019). Tough Ordered Mesoporous Elastomeric Biomaterials Formed at Ambient Conditions. ACS Nano, 14(1), 241–254. https://doi.org/10.1021/acsnano.9b01924

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/

Turning Waste into Wellness: The Power of Fecal Matter in Medicine

It is not the most pleasant substance. Its notorious smell and inextricable connection to potty humor make it an unappealing subject for many. However, its healing abilities offer a promising treatment for Autism Spectrum Disorder symptoms. What is this mysterious substance? Human fecal matter - also known as poop. 

In a procedure known as fecal microbiota transplantation (FMT), human stool from healthy donors is introduced into a patient’s gut through a colonoscopy or a pill (Gupta et al., 2016). The healthy bacteria from the donor’s stool can positively impact the patient’s imbalanced intestinal microbiome. The intestinal microbiome is a collection of countless microorganisms such as bacteria, archaea, and viruses found in the gastrointestinal tract (Gupta et al., 2016). These microorganisms support various bodily processes, but they can be impaired by environmental factors and infectious diseases. FMT is highly effective in treating some of these infectious diseases. For example, it is up to 90% effective in curing recurrent infections of Clostridium difficile bacteria (Wang et al., 2019). 

Recent research has extended the potential applications of FMT to address the symptoms of Autism Spectrum Disorders (ASDs). This diverse group of neurodevelopmental disorders typically leads to distinct patterns of behavior (difficulty in deviating from routines, repetitive movements, and fixations on specific objects or activities) and other social communication issues that impair one’s ability to hold a conversation or detect various social cues (“Autism Spectrum Disorder,” 2018). ASDs affect approximately one in fifty-nine individuals in the United States (Sharon et al., 2019). Many studies indicate a link between abnormal gut microbiota and ASD (Kang et al., 2019). Children with ASD who experience food sensory issues are more likely to face gastrointestinal problems due to deficits in calcium and protein intake. There are not many medical treatments available for these symptoms of ASD (Kang et al., 2019). Behavioral therapy can help improve social skills and issues with communication, but it does not address physical problems in the body. This is where FMT comes into play. 

A study conducted by researchers at Arizona State University found promising results when combining FMT with bowel cleanses and antibiotics to treat children with ASD. After an eighteen-week trial, they observed an 80% reduction in gastrointestinal symptoms of ASD. When they re-evaluated participants two years later they found significant improvements in gastrointestinal and behavioral symptoms (Kang et al., 2019). These findings found support in subsequent studies that investigated the impacts of FMT on gastrointestinal symptoms and metabolic profiles of people with ASD (Martínez-González & Andreo-Martínez, 2020). However, further research is needed to validate this link between FMT and the improved health of patients with ASD. These additional studies should consider the diverse spectrum of ASD severity and the differences in methodologies used to measure ASD behaviors (Martínez-González & Andreo-Martínez, 2020).

These results are not only exciting because they can help such a large number of people, but also because they highlight the potential of treatments derived from readily available materials. The world is in an exciting era of medical innovation and amazingly complex medical technology, but FMT serves as a reminder that we don't always need highly specialized tools to start helping patients in need. Sometimes, using what we already have – in this case, an abundance of human fecal matter – can lead to significant medical breakthroughs.

References

Gupta, S., Allen-Vercoe, E., & Petrof, E. O. (2016). Fecal microbiota transplantation: in perspective. Therapeutic Advances in Gastroenterology, 9(2), 229–239. https://doi.org/10.1177/1756283X15607414

Kang, D. W., Adams, J. B., Coleman, D. M., Pollard, E. L., Maldonado, J., McDonough-Means, S., Caporaso, J. G., & Krajmalnik-Brown, R. (2019). Long-term benefit of Microbiota Transfer Therapy on autism symptoms and gut microbiota. Scientific Reports, 9(1), 5821. https://doi.org/10.1038/s41598-019-42183-0

Martínez-González, A. E., & Andreo-Martínez, P. (2020). Prebiotics, probiotics and fecal microbiota transplantation in autism: A systematic review. Revista de psiquiatria y salud mental, 13(3), 150–164. https://doi.org/10.1016/j.rpsm.2020.06.002 

Autism Spectrum Disorder. (2018, January 6). Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/autism-spectrum-disorder/symptoms-causes/syc-20352928

Sharon, G., Cruz, N. J., Kang, D. W., Gandal, M. J., Wang, B., Kim, Y. M., Zink, E. M., Casey, C. P., Taylor, B. C., Lane, C. J., Bramer, L. M., Isern, N. G., Hoyt, D. W., Noecker, C., Sweredoski, M. J., Moradian, A., Borenstein, E., Jansson, J. K., Knight, R., Metz, T. O., … Mazmanian, S. K. (2019). Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice. Cell, 177(6), 1600–1618.e17. https://doi.org/10.1016/j.cell.2019.05.004

Wang, J. W., Kuo, C. H., Kuo, F. C., Wang, Y. K., Hsu, W. H., Yu, F. J., Hu, H. M., Hsu, P. I., Wang, J. Y., & Wu, D. C. (2019). Fecal microbiota transplantation: Review and update. Journal of the Formosan Medical Association, 118 Suppl 1, S23–S31. https://doi.org/10.1016/j.jfma.2018.08.011