Bowdoin Science Journal

Science

Look to What You Know: Making Environmental Change Using What We Already Have

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Despite being conscious of the current global climate crisis, many people today feel they lack the knowledge, solutions, time, or energy to implement major environmental change. But they may be more powerful than  they think– they truly do have the power to make small-scale change in the world, if they get creative. Small groups like Glass Half Full and Swahili Modern, as well as individuals like Aviva Rahmani, use their normal daily actions and hobbies to their advantage in order to create healthy and sustainable change. 

Glass Half Full Nola was founded in 2020 by Franziska Trautmann and Max Steitz, two Tulane students who wanted to build stronger infrastructure for glass recycling in New Orleans. According to the EPA, the United States produced 12.3 million tons of glass in 2018, and 7.6 million tons of glass entered landfills. Only 3.1 million tons of glass were recycled that year (EPA). In light of this issue, Trautmann and Steitz used the resources they already had and started their project in their backyard. They hand-crushed the glass that they and their friends used in their day-to-day lives. As their community learned of their project and sent in more donations, their project expanded to a small business operating out of a glass processing facility. The company established drop-off sites and collection services all over New Orleans to increase accessibility for their new method of environmental stewardship. The donated glass gets crushed into sand and gravel for coastline restoration, disaster relief, flooring, and new glass products. With just an idea, a backyard, and some everyday tools, Trautmann and Steitz made a positive environmental impact. Though their initial plan grew into a more ambitious project, the humble beginnings of Glass Half Full Nola prove that anyone can use what they have to make meaningful small-scale change for the Earth.

Founders Franziska Trautmann and Max Steitz

 

Students in New Orleans aren’t the only ones putting their trash to good use: Swahili Modern, a fair trade company based in Portland, Oregon, distributes artisanal, handmade, African products to consumers in the United States. The business which now consists of twenty employees began with only its founder, Leslie Mittelberg. Mittelberg aimed to supply African artisans with more options for work, to give struggling artisans a stable and steady income, and to empower female artisans working from home. Swahili Modern currently distributes recycled art, and the pieces’ descriptions inform consumers of who made them and how. For example, the lion sculpture shown above was built from upcycled flip-flops. The sculptors, who work for a company called Ocean Sole, are based in a workshop in Nairobi, Kenya, and they make a living by collecting the several tons of flip-flops that wash up on the Kenyan coast each year. By working with this company, and many others, Mittelberg’s network of small businesses prove that it is possible to incorporate environmentally conscious products into a company’s regular inventory– something every small business is capable of doing.

Kenyan Artisans sculpt lion from discarded flip-flops
Artisans in Nairobi, Kenya, working against climate change and pollution

 

While artists in Africa create dazzling forms from discarded flip-flops, the artist Aviva Rahmani makes local change from right here in Maine. In her art, she embraces the idea of intersecting art and environmentalism. In 2002, Rahmani started the Blue Rocks Project to spread awareness about an obstructed causeway on Pleasant River in Vinalhaven, a town on an island in Maine. The Army Corps of Engineers had just finished construction on the causeway, leaving it narrower than before, and the construction prevented tidal flow between the saltwater and freshwater. Wetlands are vital to the health of the environment, and according to the World Wildlife Fund, the world lost about 35 percent of wetlands between 1970 and 2015 (WWF). Aviva Rahmani painted forty boulders around the causeway with complex blue designs using non toxic paint to draw attention to this serious issue. When the town subpoenaed her to wash off the rocks, she staged a “wash-in” to educate people in passing cars about the importance of maintaining healthy estuaries as she washed. The attention she brought to estuarine health helped convince the USDA to commit $500,000 to restoring twenty-six acres of vital wetlands. Rahmani wanted to make change, so she used what she had and what she knew to spread awareness for important causes. While not everyone can procure thousands of dollars from the USDA, Rahmani’s willingness to incorporate parts of her daily life into the world of environmental activism proves that anyone else can do the same.

Aviva Rahmani paints rocks with blue paint to draw attention to wetland safety.

All of these individuals and small companies making environmental change began as the rest of us are now– just people with an idea and a rudimentary set of tools to implement their plan: hammers and large containers of glass in someone’s backyard; old pieces of footwear and tools from the workshop; a bucket of paint and a rock. These simple beginnings prove to the world that anyone who wants to can make a difference in the environment. Anyone at all. On your daily walk, pick up the trash you see along the way. See how creative you can get with the soda bottles you throw away– maybe they’d make a cool plant pot. No matter what it is, the next time you have an idea that could help save the environment but don’t know where to start, just look to what you know.

 

Learn more about Glass Half Full Nola here.

Learn more about Swahili Modern’s recycled art here.

Learn more about Aviva Rahmani’s work here.

 

Works Cited

Facts and Figures about Materials, Waste, and Recycling– Glass: Material-Specific Data. EPA. Retrieved December 3, 2023, from https://www.epa.gov/facts-and-figures-about-materials-waste-and-recycling/glass-material-specific-data. 

Glass Half Full Nola— Glass recycling, coastal restoration. Glass Half Full. Retrieved October 15, 2023, from https://glasshalffull.co/. 

Kiri Technologies. (n.d.). Founders: Franziska Trautmann and Max Steitz. Kiri News. Retrieved October 15, 2023, from https://kiri.news/from-waste-to-resource-the-innovative-story-of-glass-half-full-nola/.

Our Impact. Ocean Sole. Retrieved December 3, 2023, from https://oceansole.com/pages/our-impact. 

Rahmani, A. (n.d.). Blue Sea Lavender detail on Echoes of the Islands. Aviva Rahmani. Retrieved November 10, 2023, from https://www.avivarahmani.com/endangered-species-ecoart.

Recycled Handcrafted Sculptures from Kenya. Swahili Modern. Retrieved October 15, 2023, from https://www.swahilimodern.com/collections/recycled-art. 

Swahili Modern. (n.d.). Extra Large Flip Flop Lion Sculpture. Swahili Modern. Retrieved October 15, 2023, from https://www.swahilimodern.com/collections/recycled-art/products/extra-large-flip-flop-lion-sculpture-1.

Swahili Modern. (n.d.). Kenyan artisans that build sculptures from recycled materials. Swahili Modern. Retrieved October 15, 2023, from https://www.swahilimodern.com/collections/recycled-art/products/extra-large-flip-flop-lion-sculpture-1.

Water Ecosystems Preservation — Aviva Rahmani. Aviva Rahmani. Retrieved November 10, 2023, from https://www.avivarahmani.com/water-ecosystem-preservation-ecoart. 

WWF. World’s wetlands disappearing three times faster than forests: Global Wetlands Outlook paints alarming picture of decline in world’s most valuable ecosystems. World Wildlife Fund. Retrieved December 3, 2023 from https://wwf.panda.org/wwf_news/?335575/Worlds-wetlands-disappearing-three-times-faster-than-forests.

Unpacking the Ethical Implications of Human Germline Editing

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On December 30th, 2019, biophysicist Dr. He Jiankui was sentenced to three years in prison for forging ethical review documents and misleading doctors into unknowingly implanting gene-edited embryos into two women in China (Normile 2019). One of these women had a set of twins and the other had a single child. These children are now the first genetically modified humans in history to be resistant to HIV. They can pass this modification to the next generation, and their whereabouts are still unknown (Greely 2019). Jiankui used CRISPR/Cas9, a gene editing tool, to modify their germlines and edit the CCR5 gene, a contributor to broad immune responses (his focus was its importance to HIV viruses).

Based on the National Natural Science Foundation of China, there has been a total of 3.7 billion yuan (roughly $576 million) government spending on embryonic stem cell research from 1997 to 2019 (Lou 2021). Germline gene editing research is allowed, but establishing a pregnancy with genetically modified embryos has been outlawed by multiple regulations (Xinqing 2014). Similarly to China, the National Institutes of Health within the US estimates that human embryonic stem cell research has received $1.48 billion in government funding since 2009. There are no current laws or regulations that ban germline gene editing conducted through private funding within the US, but it would have to be approved by the FDA for marketing and clinical studies. No proposals have been submitted (​​Genetic Literacy Project 2019). Dr. Jiankui has since been disgraced by the scientific community around the world for his actions. Some scientists believe that germline gene editing is not only an unethical practice but a potentially dangerous one that could lead to a new era of eugenics with irreversible harm (Genetic Literacy Project 2019). Little is known about the intricate details of Dr. Jiankui’s experiment, but what has been revealed poses several hard-hitting ethical questions. Should we manipulate the next generation of humans? What are the ethical dilemmas in the advancement of this technology? To create an informed opinion on the matter, it is helpful to first understand the intricacies of Dr. Jiankui’s experiment, and how exactly he made the first genetically modified children.

Dr. Jiankui conducted human germline genome editing, which refers to the technique of modifying not only the genetic information of a subject but also what can be passed down to the next generation (Normile 2019). Germ cells can create a new generation (ex. sperm and eggs). So germ cells, and cells that produce germ cells, are known as the germline. These are different from somatic cells, which are body cells that continuously divide throughout a person’s lifetime and play a minimal role in gene inheritance (Greely 2019). Certain alleles or alterations to CCR5 within the human genome can provide resistance to HIV. Thus, Jiankui used CRISPR to alter CCR5 in HIV-susceptible patients to make them resistant to the disease.

CRISPR, which stands for clustered regularly interspaced short palindromic repeats, is a technique originally found in bacteria as a defense system to render inserted viral DNA ineffective. It also allows for the modification of DNA (Rapini 2023). The enzyme Cas-9 can cut pieces of DNA and is guided to its location based on an attached strand of RNA (called the guide RNA strand). By cutting a targeted sequence of DNA, it can render protein-coding genes inactive or disfunctional. After Cas-9 has cut the target DNA, researchers can choose to place a modified DNA sequence in the vacant space (Fig 1).

Figure 1. The editing technique of CRISPR involves the guide RNA strand, guide RNA sequence, Cas-9 enzyme, and target DNA (Roach 2015).

While little is known about Dr. Jiankui’s specific technique in using the CRISPR/Cas-9 system, we know that he modified the gene CCR5 (Greely 2019). CCR5 is a gene on chromosome 3 that encodes for a protein called C-C chemokine receptor type 5 (also shortened to CCR5) (Normile 2019). CCR5, along with another receptor called CD4, is utilized by the HIV virus to bind to bacteria-detecting/destruction cells called macrophages (white blood cells) and infect them. The HIV virus protein envelope binds to the primary receptor CD4 on the macrophage with the gp120 protein, which are exterior “protective” protein around the HIV cell. If the CCR5 coreceptor is present as well, it can successfully enter the macrophage, release viral RNA and enzymes, and infect the macrophage. This infection alters the function of the macrophage, causing it to assemble and release viruses. Eventually, the gene that codes for the gp120 receptor is altered by a mutation and can now bind to a different co-receptor called CXCR4 which is found on the CD4 plus T-cells. (Prakash 2019). The same process of virus construction occurs within T-cells, but as the viruses leave the T-cell it ruptures the plasma membrane. This kills the T-cells, causing a weakened immune response and eventually resulting in the onset of AIDS.

Figure 2. The mechanism by which the HIV viral envelope infects the macrophage creates mutated viral cells with different gp120 receptors and destroys T-cells. (Prakash 2019) 

It is believed that Dr. Jiankui used the CRISPR/Cas-9 system to delete 32 base pairs of the CCR5 gene, therefore making it produce non-functional copies of the CCR5 protein. This was done in the hope that HIV would be unable to infect the white blood cells of the babies born from the embryos (Normile 2019). If Jiankui only modified somatic cells using this technique, the children may or may not have gained protection against HIV and could not pass it down to the next generation.

In 2015 (before He’s experiment was released) Jennifer Doudna, one of two researchers who published their findings on CRISPR, convened with the U.C Berkeley’s Institute for Genome Innovation, which was composed of Nobel laureates and esteemed professors of bioethics. They concluded that conducting germline editing would be irresponsible until matters such as balancing the potential risks and benefits have been concluded and that there is a broad societal consensus about the appropriate use of proposed applications of this technology (Cohan, 2018). Jennifer Doudna and Emmanuelle Charpentier created this technology to find ways to edit out faulty genes and cure diseases at the source—within our genetic code (Doudna 2019). However, after the release of He’s experiment, Doudna publicly stated her evolving concerns relating to this application of her discovery. During her national press tour in 2019, she shared a frightening dream she had in which a colleague of her’s asked about CRISPR but later turned out to be Hitler (Than 2019). This likely stems from the horrifying history of Nazis and the eugenics movement, which stemmed from the idea of improving the genetic quality of humans and sterilizing and or eliminating those with unfavorable traits. She also voiced that her opinion on germline genome editing has been evolving from an outright ban to warranting it in certain circumstances. However, her underlying opinion remains that it would have to be under transparent and safe circumstances and concern a medical need that was unmet by any technology. In addition to Doudna, countless other scientists have come out in disagreement with He Jianku’s work including researchers from Stanford University, Harvard Medical School, and the NIH (Cohen 2018). Specifically, a journalist from Science magazine states that representatives from eight countries who attended the International Summit on Human Genome Editing in Hong Kong came to a consensus that his actions were irresponsible, violated international norms, lacked transparency, and did not have sufficient medical justification (Cohen 2018).

Jennifer Doudna stated that her goal was to edit out faulty genes, but that definition leaves a lot to interpretation. How can we as a society come together to define the parameters of a faulty gene? From treating HIV to Down Syndrome, these conditions hold more than just health implications, but social ones as well. If the scientific community deems it accessible to prevent Down syndrome using human germline genome editing, are they stating that humans that currently possess this condition are “wrong” and have “faulty genes” in need of correction? Whoever holds the power to manipulate this technology essentially has the power to decide what the next generation of humans will be capable of and what genes are deemed “faulty” within our society. Jianku’s reckless use of technology was majorly deemed wrong for its lack of transparency, safety, and following set regulations upheld by currency bioethical standards. However, in situations like parents wanting their children to be healthy, it is completely understandable that human germline editing sounds like an intriguing way to protect their children. For these reasons, it is imperative to familiarize ourselves with the development of this technology, and its continued push for regulations across the world to maintain ethical standards. Further, it is also important to ask ourselves hard-hitting questions such as: should one person, scientist, or government have the power to determine what the next generation will possess, look like, or become? We as members of society must continue to stay informed in a world with the capacity to genetically modify human beings.

References:

  1. Bhanu Prakash. “How the HIV Infection Cycle Works.” Proceum Pvt. Ltd. January 2019. https://www.youtube.com/watch?v=GyofqO1TRjU
  2. Brianna Rapini, Sarina Peterson, “Genetic Engineering.” September 2023. https://www.youtube.com/watch?v=CDw4WPng2iE
  3. Dennis Normile. “Chinese scientist who produced genetically altered babies sentenced to 3 years in jail.” Science. December 2019.https://www.science.org/content/article/chinese- scientist-who-produced-genetically-altered-babies-sentenced-3-years-jail
  4. Deng Luo, Zihui Xu, Zhongjing Wang, Wenzhuo Ran. “China’s Stem Cell Research and Knowledge Levels of Medical Practitioners and Students.” Stem Cells International. 2021. https://doi.org/10.1155/2021/6667743.
  5. Doudna J. 2019. Faculty Research Page. Department of Molecular & Cell Biology. http://mcb.berkeley.edu/faculty/BMB/doudnaj.html.
  6. Dylan Roach, Tanya Lewis. “CRISPR, the gene-editing tech that’s making headlines, explained in one graphic.” Insider. December 2015. https://www.businessinsider.com /crispr-gene-editing-explained-2015-12
  7. Genetic Literacy Project. 2019 July 23. United States: Germline / Embryonic. Global Gene Editing Regulation Tracker. https://crispr-gene-editing-regs-tracker.geneticliteracy project.org/united-states-embryonic-germline-gene-editing/.
  8. Henry T Greely. “CRISPR’d babies: human germline genome editing in the ‘He Jiankui affair.’” Journal of Law and the Biosciences. Volume 6, Issue 1. October 2019, Pages 111–183, https://doi.org/10.1093/jlb/lsz010
  9. Indra Mani. “CRISPR-Cas9 for treating hereditary diseases.” Progress in molecular biology and translational science. Volume 181. February 2017. https://pubmed.ncbi.nlm.nih.gov/34127193/
  10. John Cohen. “After last week’s shock, scientists scramble to prevent more gene-edited babies.” Science. December 2018.https://www.science.org/content/article/after-last- weeks-shock-scientists-scramble-prevet-more-gene-edited-babies
    Join David Ignatius. “Walter Isaacson & Jennifer Doudna join Washington Post Live to discuss CRISPR.” Washington Post. March 2021. https://www.youtube.com/ watch?v=cKHuuALENZk
  11. Than K. 2019 Nov 12. AI and gene-editing pioneers to discuss ethics. Stanford News. [accessed 2023 Dec 3]. https://news.stanford.edu/2019/11/12/ai-gene-editing-pioneers- discuss-ethics/#:~:text=Doudna%20decried%20the%20act%20but.
  12. Yi Zheng et al. “Structure of CC Chemokine Receptor 5 with a Potent Chemokine Antagonist Reveals Mechanisms of Chemokine Recognition and Molecular Mimicry by HIV.” Immunity. Volume 46, Issue 6. June 2017. https://www.cell.com/immunity /pdf/S1074-7613(17)30218-2.pdf
  13. ‌Zhang Xinqing, Zhang Wenxia, Zhao Yandong. “The Chinese Ethical Review System and its Compliance Mechanisms.” TRUST. September 2014. https://trust-project.eu/ wp-content/uploads/2016/03/Chinese-Ethics-Review-System.pdf

The Creation of a Universal Flu Vaccine

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Figure 1. Influenza Remains a Threat to the US population (Adapted from CDC, 2022)

 

Influenza, also known as the common flu, infects approximately 8% of the United States population annually, leading to 140,000-710,000 hospitalizations and 12,000-52,000 deaths from 2010 to 2020  (CDC, 2023) (CDC, 2022). Influenza is becoming more prevalent, causing more infections, hospitalizations, and deaths (see Figure 1). Those most at risk include the very young, the elderly, and those with chronic medical conditions (Schmidt & Lapuente, 2021). Common symptoms of influenza include fever, cough, sore throat, runny nose, and fatigue (CDC, 2023). An annual vaccine offers the best protection against influenza, however, this vaccine has drawbacks. A universal vaccine, while still under development, would largely alleviate these issues. For example, a universal vaccine would teach the immune system to protect against all strains of influenza, not just the strain that happens to be circulating during the flu season. 

There are 4 distinct types of influenza genera that circulate: A (IAV), B (IBV), C (ICV), and D (IDV). IAV and IBV are most prevalent in human infections. IBV has a limited host range and strain diversity whereas IAV is constantly creating new lineages and subtypes. IAV alters through genetic drift, the exchange of gene segments among different IAV strands, and because its viral polymerase lacks proofreading activity, causing a backup of mutations. Therefore, IAV poses a greater risk for causing a pandemic. Influenza strains can  be further classified by their glycoproteins: hemagglutinin (HA), which has 3 types– 1 (H1), 2 (H2), and 3 (H3) – and neuraminidase (NA) which has 2 types– 1 (N1) and 2 (N2). These antigens are highly variable among strains and no single vaccine offers full protection against them. The most devastating influenza outbreak in 1918, often dubbed the Spanish Flu, was caused by the H1N1 IAV that led to fifty million deaths worldwide (CDC, 2022). Most recently, in 2009, the H1N1 IAV, known as swine flu, swept the globe at an unprecedented rate due to airline travel. Additional influenza pandemics caused by IAV have appeared more and more frequently as our world becomes increasingly connected. Further, the coronavirus pandemic demonstrated the impact a pandemic may have on nearly every aspect of daily life. IAV remains a constant threat as it has the potential to become a pandemic once more.

Figure 2. History of Influenza A Virus Outbreaks (Adapted from Al Hajjar & McIntosh, 2010)

 

Vaccines are the best protection against influenza, however, current vaccines have many drawbacks. To develop the annual vaccine, scientists must first predict and identify which strain will dominate the flu season. Even if their predictions are correct, the vaccine efficacy (VE) will still be less than 70%. However, if their predictions are incorrect, the VE will be close to 0%. This process is also slow; it takes six months after an influenza outbreak to make a vaccine commercially available to the public. Existing influenza vaccines are imperfect and depend on strain-specific neutralizing antibodies, leaving them vulnerable to new strain mutations.

Figure 3. Varying Types of Influenza Vaccines (Adapted from Al Hajjar & McIntosh, 2010)

 

A universal influenza vaccine would alleviate many of these issues and offer broad immunity. While the annual vaccine’s VE depends largely on how the virus mutates over the duration of the flu season, a universal vaccine would develop protection against conserved parts of the influenza virion. To create a universal vaccine, scientists study the similarities across flu strains to isolate identical segments and then train the immune system to make protective antibodies. As early as 1965, Jerome Schulman and Edwin Kilbourne noticed that mice recovered from a prior H1N1 infection were partially protected against virus replication, mortality, and lung tissue damage after an H2N2 infection. Immune cells called T cells are crucial to this protection. In mice and humans, T cell responses are centered on internal virus proteins such as nucleoproteins, polymerases, and more. Other types of T cells are more diverse and can recognize surface proteins HA and NA. One study found IAV-specific T cell responses at a baseline of 43% in the study population and discovered that the presence of viral nucleoprotein-specific T cells significantly decreased the chance of developing a symptomatic IAV infection. Other studies have confirmed that T cells show a strong inverse correlation to symptom scores. Many of these studies with T cells have done well with animal models but not many have progressed to human clinical trials.

While a universal vaccine is still being developed, it will be extremely beneficial. Recent vaccines are not sufficient to protect the community against seasonal and pandemic influenza flu strains. A universal flu vaccine would solve many of the issues current vaccines present and would offer a higher VE. While they are still a work in progress, these vaccines have great potential and importance.

 

Works Cited

Al Hajjar, S., & McIntosh, K. (2010). The first influenza pandemic of the 21st century. Annals of Saudi Medicine, 30(1), 1–10. https://doi.org/10.4103/0256-4947.59365

CDC. (2022, October 4). Burden of Influenza. Centers for Disease Control and Prevention. https://www.cdc.gov/flu/about/burden/index.html

CDC. (2023, May 2). Key Facts About Influenza (Flu). Centers for Disease Control and Prevention. https://www.cdc.gov/flu/about/keyfacts.htm

Schmidt, A., & Lapuente, D. (2021). T Cell Immunity against Influenza: The Long Way from Animal Models Towards a Real-Life Universal Flu Vaccine. Viruses, 13(2), Article 2. https://doi.org/10.3390/v13020199

Inverse Vaccines: A New Way to Treat Autoimmune Disorders

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Williams, 2023

Of the 8.1 billion people in the world, 1 in 10 have an autoimmune disorder. There are 8.1 billion people in the world, and 810 million of these people, or 1 in 10, have an autoimmune disorder (“1 in 10 people”, 2023). Autoimmune disorders are a category of conditions in which the body attacks itself. Although management systems for most of these types of conditions have been developed, autoimmune diseases still cannot be cured (“Autoimmune disorders”). In fact, even with management of their symptoms, up to 50% of patients with autoimmune disorders still experience impairment in their health-related quality of life (Pryce and Fontana, 2017). The development of so-called “inverse vaccines” may provide the much needed mechanism to help find a cure for this class of conditions by teaching the body not to attack itself. 

A traditional vaccine works because it helps the body learn to recognize parts of foreign pathogens and builds up the body’s immune response against these pathogens so that the response is stronger and happens more quickly after recognition. In people with autoimmune diseases, the body also forms an immune response against self molecules because it mistakenly identifies them as foreign antigens, or pathogenic molecules (usually proteins or sugars) that induce an immune response. The idea behind “inverse vaccines” is that instead of building up the immune system’s response to foreign antigens, they could suppress the response to self-antigens by helping to teach the body to recognize these misidentified molecules as self. 

A study led by Andrew Tremain at the University of Chicago’s Pritzker School of Medicine is one of the groups who are involved in this novel inverse vaccine research. The inverse vaccines they developed contain modified copies of the self-antigens that are targeted by the immune system which are attached to long chains of sugars called polysaccharides (Tremain et al., 2023). These polysaccharide chains guide the self-antigens to the liver, which plays an important role in the establishment of tolerance to these molecules. Once these modified self-antigens arrive at the liver, specialized immune cells pick them up and then inhibit the action of T cells against them through T cell uptake (Leslie, 2023). T cells are a type of immune cell that carry out part of the typical response against molecules identified as foreign or invaders through either cytotoxic or signaling based immune responses. The inhibition of the T cell response against misidentified self-antigens reduces or prevents the autoimmune response that causes the body to attack itself, thereby acting as a kind of “inverse vaccine”. 

Once Tremain et al. developed their inverse vaccine, they conducted testing to determine its efficacy and viability as a method for increasing tolerance to self-antigens in those with autoimmune disorders. First, they wanted to ascertain whether inverse vaccines could truly provide inhibition of an immune response. To do this, they injected an egg white protein into mice as an experimental foreign antigen to trigger a strong immune response. Then an inverse vaccine against the egg white protein was injected to suppress the response to the original dose of the protein. In their analysis, they found that the T cells that would’ve responded to the egg white protein were not present. These results suggested that the inverse vaccine blocked the typical immune response, demonstrating viability as a treatment method against stimulated immune responses (Tremain et al. 2023).

However, Tremain and his colleagues still had to demonstrate the efficacy of inverse vaccines in inhibiting an autoimmune response rather than one caused by a foreign antigen. To do this, they induced an autoimmune disease called experimental autoimmune encephalomyelitis (EAE) in mice. In EAE, the immune system attacks myelin, the substance responsible for forming insulation around nerve cell axons. EAE is a particularly informative experimental model in mice because it mimics multiple sclerosis (MS), a human autoimmune disorder. Once they induced EAE, Tremain et al. injected an inverse vaccine made up of a polysaccharide carrying part of a myelin protein. Physiological analysis after injection suggested that this treatment had stopped mice from developing EAE. Furthermore, injection of a different inverse vaccine targeting an alternate form of EAE showed prevention of symptom relapse. This means that Tremain et al. were able to demonstrate inhibition of autoimmune responses against two types of EAE in mice, representing two different types of MS, providing a heartening outlook on this research (Tremain et al., 2023). 

In summary, inverse vaccines had the ability to turn off immune responses to particular antigens in mice. These results are a promising sign for the ability of inverse vaccines to combat autoimmune diseases. Additionally, initial clinical trials testing the safety and efficacy of inverse vaccine strategy to increase tolerance to self-antigens in humans have had positive results so far for immune disorders such as multiple sclerosis and celiac disease where the misidentified self-antigens are known (Leslie, 2023). However research into tolerance-increasing strategies tends to stall both because we do not know which self-antigens are attacked in several autoimmune disorders, and because the mechanisms that produce tolerance after antigens are brought to the liver are not well understood (“Immune Tolerance”). This means that even if autoimmune vaccines prove to be a viable form of treatment for autoimmune disorders, they will only be able to treat diseases with known self-antigens until further research into the antigen and tolerance mechanisms is conducted. Nevertheless, inverse vaccine research is incredibly promising and has the potential to help hundreds of millions of people worldwide.

Works Cited

Pryce, CR., and Fontana, A. (2017). Depression in autoimmune diseases. Current Topics in Behavioral Neurosciences, 31. https://doi.org/10.1007/7854_2016_7 

1 in 10 people suffer from autoimmune diseases. (2023). Neuroscience News.  https://neurosciencenews.com/population-autoimmune-disease-23198/ 

Autoimmune disorders. (n.d.). Retrieved November 5, 2023, from  http://www.betterhealth.vic.gov.au/health/conditionsandtreatments/autoimmune-disorders

Tremain, A.C., Wallace, R.P., Lorentz, K.M. et al. Synthetically glycosylated antigens for the antigen-specific suppression of established immune responses. Nat. Biomed. Eng 7, 1142–1155 (2023). https://doi.org/10.1038/s41551-023-01086-2 

Leslie, M. (2023). ‘Inverse vaccine’ could help tame autoimmune diseases, Science. https://www.science.org/content/article/inverse-vaccine-could-help-tame-autoimmune-diseases 

Immune Tolerance in Autoimmune Disease, Immune Tolerance Network. (n.d). Retrieved November 5, 2023, from https://www.immunetolerance.org/researchers/clinical-trials/autoimmune-disease 

Understanding Multiple Sclerosis, Oregon Health and Science University. Retrieved November 5, 2023, from  https://www.ohsu.edu/brain-institute/understanding-multiple-sclerosis 

Williams, S. (2023). “Inverse vaccine” shows potential to treat multiple sclerosis and other autoimmune diseases. Pritzker School of Molecular Engineering,  The University of Chicago. https://pme.uchicago.edu/news/inverse-vaccine-shows-potential-treat-multiple-sclerosis-and-other-autoimmune-diseases

Pupil Mimicry Strengthens Infant-Parent Bonding

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Sometimes, it is a wonder how something so small can connect human beings on a deeper level, but that is what pupil mimicry does. Pupil mimicry describes the changes in pupil size that occur in both participants during eye contact, which can help with social bonding. It also reflects the different cognitive and emotional processes that occur during eye contact and socialization, such as showing social interest (Aktar et al., 2020). When pupil size synchronously dilates, meaning the pupil expands when eye contact is made, there is a promotion of trust and bonding between the two responders. The opposite is true for synchronous pupil constriction, which diminishes a positive social bond between the two responders.  

Pupil mimicry is an old, robust phenomenon (Prochazkova et al., 2018) that is modulated by oxytocin. This evolutionarily conserved neuropeptide acts as a hormone and neurotransmitter and facilitates social bonding (Aktar et al., 2020). Pupil mimicry has been observed in monkeys and chimpanzees, where it also increases trust and social familiarity (Kret et al., 2014). This effect occurs in infants as well, which suggests that pupil mimicry may help facilitate bonding between infants and their parents. But how can scientists measure that? 

It has been shown that young infants can differentiate between their own-race faces and other-race faces. Therefore, scientists hypothesized that infants would have quicker pupillary responses to pupils belonging to the same race as their parents when compared to other races. Researchers Aktar, Raijmakers, and Kret conducted a study with three aims to test this hypothesis: 

  1.  Do infants’ pupils react to dynamic videos of eyes with pupil sizes that change realistically? 
  2. Do parents and infants have the same speed in matching pupil size? 
  3. Do both the parents’ and infants’ pupils have differing rates of pupil mimicry between own-race faces and other-race faces

For the first aim, infants and parents watched black-and-white dynamic videos of same-race models (Dutch male and female) that had constricting, static, or dilating pupils while their pupillary reactions were tracked (Figure 1; Aktar et al., 2020). For the second and third aims, infants and parents watched black-and-white dynamic videos with two races: Dutch for the same-race category and Japanese for the other-race category (Aktar et al., 2020). The researchers compared the parents’ pupil mimicry speed to the infants’. 

Figure 1: Experimental set-up of infants and parents as they observe the stimuli (Aktar et al., 2020).

The researchers confirmed that both infants and parents were able to perform pupil mimicry. They also found that parents had quicker pupil response to dilated or constricted pupils than infants, possibly due to adults being more cognitively advanced than infants. Finally, they concluded that there was no significant difference in pupil mimicry response between own race and other races, but there were slight pupil mimicry delays. The researchers have several explanations for the slight delays. For instance, the infants’ pupils tend to stay dilated when they see a dilated pupil, regardless of race, since infants are still developing their pupil mimicry control. For adults, pupil mimicry tends to take about 2.5 milliseconds longer when given other-race stimuli. This may be from greater cognitive effort used to process other-race faces than own-race faces (Aktar et al., 2020). 

The key finding of the research is race does not affect the participants’ rate of pupil mimicry during emotionally neutral interactions (Aktar et al., 2020). So, though pupil mimicry helps strengthen parent-infant relationships, infants also have the skills to establish trust and awareness with strangers regardless of race. However, when infants are not in a neutral setting, meaning an environment where they feel unsafe and discontent, they are more likely to seek out their parents and less likely to make eye contact (Aktar et al., 2020). That is why, if the infants felt fussy or frightened, the researchers sat the parents right next to them to provide a feeling of safety (Figure 1). Eye contact conveys a great deal of information. Maybe the next time you make eye contact with someone, stare at them to see how their pupil responds to you!

References

Aktar, E., Raijmakers, M. E. J., & Kret, M. E. (2020). Pupil mimicry in infants and parents. Cognition and Emotion, 34(6), 1160–1170. https://doi.org/10.1080/02699931.2020.1732875

Kret, M. E., Tomonaga, M., & Matsuzawa, T. (2014). Chimpanzees and humans mimic pupil-size of conspecifics. PloS one, 9(8), e104886. https://doi.org/10.1371/journal.pone.0104886

Prochazkova, E., Prochazkova, L., Giffin, M. R., Scholte, H. S., De Dreu, C. K. W., & Kret, M. E. (2018, July 16). Pupil mimicry promotes trust through the theory-of-mind network – PNAS. Proceedings of the National Academy of Sciences. https://www.pnas.org/doi/10.1073/pnas.1803916115

Aspartame Exposure May Lead to Learning and Memory Defects

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If you’re reading this article, you have probably had aspartame today. Aspartame, an artificial sweetener commonly found in diet sodas and other sugar-free products, is consumed by millions of people each day. Yet, there is still doubt about the safety of aspartame—even at levels well below the FDA’s recommended maximum daily intake. 

As the correlation between aspartame consumption and risk for metabolic diseases and cancers becomes more widely recognized (WHO Advises Not to Use Non-Sugar Sweeteners for Weight Control in Newly Released Guideline, 2023), it is equally important to evaluate the possible effects of aspartame on cognitive abilities. When aspartame is digested, it is broken down into phenylalanine, aspartic acid, and methanol. Phenylalanine can cross the blood-brain barrier and is a precursor of the monoamine neurotransmitters dopamine, epinephrine, and serotonin. These three neurotransmitters control memory, mood, motivation, and motor function, which may explain how aspartame affects the central nervous system (CNS).  

A study published this year in Nature sought to clarify how aspartame affects cognitive skills, specifically learning and memory abilities, and if the effects of aspartame are inheritable (Jones et al., 2023).The researchers chose to solely study male mice because there is less research concerning the heritability of cognitive defects from males.  

The researchers used three groups of mice, each with a different level of aspartame in their water: 0.015% aspartame, 0.03% aspartame, and no aspartame (the control group). These levels are equivalent to 7-15% of the FDA’s daily limit, and thus reflect the amount of aspartame many people consume per day (about 2-4 small diet soda drinks). The mice were treated for 16 weeks to evaluate the effect of long-term aspartame exposure.  

The first generation (F0) were tested for spatial working memory defects in weeks 4, 8, and 12 using a Y-Maze test. Mice have an innate curiosity to visit new arms of the maze instead of returning to ones previously visited. Hence, Y- Maze tests demonstrate the intact working memory of mice by seeing how well they remember the arms of the maze they already visited (Kraeuter et al., 2019). While there were no significant cognitive differences in the defects shown between mice of the 0.03% treatment group and the 0.015% treatment group, there were significant cognitive defects recorded for both groups of aspartame mice compared to the control group. The mice treated with aspartame were less likely to remember which parts of the Y-Maze they had already explored. However, no defects were found in relearning tasks or in learned helplessness evaluations between the groups.  

Next, the researchers tested to see if the spatial working memory defect could be paternally passed down to the next generation of mice. The mice from each of the three groups (0.015% aspartame, 0.03% aspartame, and the no aspartame group) were bred with females who had been living of off plain drinking water. However, if they mated with an aspartame-treated mouse, the females unavoidably received the same aspartame water for 1-5 days during exposure. The researchers do not believe this was enough exposure to produce aspartame defects from maternal inheritability because there was no exposure during pregnancy or lactation. When the Y- Maze test was conducted for this next generation, the spatial working memory defect found in the F0 generation was passed down.  

A third generation (F2) was also studied for possible transgenerational heritability. For this generation, the F1 mice from the 0.03% aspartame lineage and the control lineage were bred with female mice drinking only plain (non-aspartame) water. The 0.03% group was selected because it was the group with the largest exposure to aspartame, so any transgenerational effects would have been the most apparent. Nevertheless, the spatial working memory defect was not passed down across two generations.  

Because spatial learning and working memory defects were seen in the F0 and F1 generations, the researchers believe the daily aspartame consumption impacted the mice’s amygdala. The amygdala regulates emotional functions, learning, and memory (Hermans et al., 2014), and thus is one region that could explain the observed effects. However, other brain regions are involved in spatial working memory, so more research needs to be done to conclusively establish the mechanism underlying the aspartame-induced behavioral changes. 

While these results leave a lot of questions unanswered, they rightfully raise awareness concerning aspartame’s possible adverse effects. If the defects caused by aspartame are inheritable, the amount of people potentially affected by aspartame is far greater than currently recognized. The results of this study call for more research, especially on the long-term effects of aspartame at the levels people consume it. 

So, maybe be a bit more cautious the next time you reach for a diet coke! 

Literature Cited

Hermans, E. J., Battaglia, F. P., Atsak, P., de Voogd, L. D., Fernández, G., & Roozendaal, B. (2014). How the amygdala affects emotional memory by altering brain network properties. Neurobiology of Learning and Memory, 112, 2–16. https://doi.org/10.1016/j.nlm.2014.02.005 

Jones, S. K., McCarthy, D. M., Stanwood, G. D., Schatschneider, C., & Bhide, P. G. (2023). Learning and memory deficits produced by aspartame are heritable via the paternal lineage. Scientific Reports, 13(1), Article 1. https://doi.org/10.1038/s41598-023-41213-2 

Kraeuter, A.-K., Guest, P. C., & Sarnyai, Z. (2019). The Y-Maze for Assessment of Spatial Working and Reference Memory in Mice. Methods in Molecular Biology (Clifton, N.J.), 1916, 105–111. https://doi.org/10.1007/978-1-4939-8994-2_10 

WHO advises not to use non-sugar sweeteners for weight control in newly released guideline. (n.d.). Retrieved November 17, 2023, from https://www.who.int/news/item/15-05-2023-who-advises-not-to-use-non-sugar-sweeteners-for-weight-control-in-newly-released-guideline 

Are Kids Innately Helpful? The Bystander Effect in Children

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Many of us reflect on our childhoods as a time of blissful lack of social inhibition. As kids, we are often unaffected by the sense of embarrassment and self-consciousness which can hold us back as adults. This lack of social inhibition could explain why kids — even those as young as one year old — seem to have an inherent inclination to be helpful towards others (Plötner et al., 2015, p. 500). In fact, psychological forces which lead adults to resist offering their help can have a very different effect on kids. One such example is the bystander effect, which suggests that people are less likely to jump in and help someone in need when other onlookers are present. A previous study showed that the presence of bystanders can actually make children more likely to help (Plötner et al., 2015, p. 500). Researchers have identified three forces which may contribute to the bystander effect: social referencing, diffusion of responsibility, and shyness to act in front of others. Maria Plötner and colleagues recently conducted a study on the impact of diffusion of responsibility — the feeling of decreased sense of duty to help when more people are around — on children’s willingness to help an adult in need. The study calls into question our previous conceptions of kids as innately helpful, suggesting that children as young as five may be less likely to engage in helping behavior in the presence of other bystanders.

The researchers recruited sixty five-year-old participants to be assigned randomly to one of three conditions. In all conditions, the experimenter told the children that they were going to color a picture while she painted a cardboard wall. The test of helping came in after about thirty seconds, when the experimenter spilled her cup of dirty paint water all over her table. At regular intervals, she recited scripted dialogue (“oops,” “my cup has fallen over,” etc.) to let the children know she needed their help getting paper towels, which she had used to clean something up at the start of the experiment but were now out of her reach (Plötner et al., 2015, p. 501–502).

Figure 1. The alone (a), bystander (b), and bystander-unavailable (c) conditions.

For each of the three conditions, the researchers recorded whether or not children helped the experimenter by bringing her a paper towel. The first was the “alone” condition, which was identical to the other two except for the fact that, as you might guess, there were no other children present. When they were alone, the subjects helped the experimenter about ninety five percent of the time (Plötner et al., 2015, p. 503). On the other hand, in the “bystander” condition, two “confederates” — other children in on the study — were present when the experimenter spilled her water and did nothing to help her. Here only about fifty five percent of subjects helped (Plötner et al., 2015, p. 503). Some might account for this difference using the concept of social referencing, our tendency to look to others when an emergency or accident takes place. When those around us seem not to notice or care about what’s happening, we use their behavior to inform our own. It’s easy to see how this could make the five-year-old subjects much less likely to bring the experimenter a paper towel, considering that the confederates had seen what happened but were completely indifferent to the experimenter’s distress.

Figure 2. The percentage of children who helped in each of the three conditions.

But this study’s third condition, termed “bystander-unavailable,” put the social referencing explanation to the test. In this condition, while two other children were present, they were seated in such a way that they were physically unable to get up and help the experimenter (see Figure 1). Lo and behold, the children were much more likely to help when the other bystanders were “unavailable” than when they were also able to help. In fact, subjects helped just as often in the bystander-unavailable condition as when they were alone (Figure 2) (Plötner et al., 2015, p. 503). So social referencing really couldn’t explain why bystanders made the children less likely to help, since they were able to observe others’ indifference toward the experimenter in both bystander conditions. And if shyness to act in front of others had made the difference, we would have seen a low likelihood to help whenever others were present, not just in the regular bystander condition. So the researchers concluded that the diffusion of responsibility was the key force limiting these five-year-olds’ tendency to help while in the presence of others.

This study presents a novel discovery of the ability of even young children to dismiss their own sense of duty when they know they are not the only ones able to help. More broadly, it highlights the important role of taking responsibility for helping others in motivating us to actually step in. Meta-analyses of other studies on the subject have emphasized this, showing that people are less likely to take responsibility for helping when more bystanders are present and when “the need for help is ambiguous” (Plötner et al., 2015, p. 500). While it may not be possible to overcome the seemingly innate phenomenon of the bystander effect, being aware of it may allow us to take responsibility and offer our help in moments of need.

References

Plötner, M., Over, H., Carpenter, M., & Tomasello, M. (2015). Young Children Show the Bystander Effect in Helping Situations. Psychological Science, 26(4), 499-506. https://doi.org/10.1177/0956797615569579

Caution in STEM: Inhibition, Intuition, and Counterintuitive Reasoning

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Imagine you’re on a 1950s game show. The host presents three doors and lays out the rules: Behind one door is a car, and behind the other two are goats. After you choose a door, the host, knowing what’s behind each door, opens one of the remaining two doors, revealing a goat. You have the opportunity to switch. Do you?

This is, of course, the infamous Monty Hall problem. Assuming you prefer the car over the goat, the answer is to always switch, since it will give you double the probability—⅔ rather than ⅓—of winning the car. Here’s an explanation that goes through each possible case (Table 1):

Table 1: Possible outcomes for staying and switching in the Monty Hall problem (Saenen et al., 2018)

If you got it wrong, you’re not alone—between 79% and 87% of adults get it wrong, too (Saenen et al., 2018). But what is behind this phenomenon? Solving unintuitive problems like the Monty Hall problem is thought to require the inhibition of misleading information, such as from prior knowledge or false cues (Dumontheil et al., 2022; Saenen et al., 2018). However, a 2018 study by Brookman-Byrne et al. and a 2022 study by Dumontheil et al. shine a new, more nuanced light on the connection between inhibitory control and (counter)intuition.

Both studies had British schoolchildren aged 11-15 undergo a volley of tests assessing their response inhibition (the ability to manage and filter out conflicting information), semantic inhibition (the ability to suppress responses driven by impulse ), vocabulary, reasoning, and working memory. Researchers then had participants complete a set of intuitive (control) and counterintuitive math and science problems. Dumontheil et al. (2022) measured neural activity using fMRI (functional Magnetic Resonance Imaging, an imaging technique which measures blood-oxygen levels to determine which parts of the brain are active) throughout.

Unsurprisingly, researchers consistently found that participants were more accurate and faster in solving intuitive problems than counterintuitive problems. Furthermore, in counterintuitive reasoning, response inhibition predicted response times, whereas semantic inhibition predicted accuracy. Interestingly, however, the only predictors of counterintuitive reasoning ability found in both studies were a more extensive vocabulary and increased age, both of which also predicted response inhibition (Brookman-Byrne et al., 2018; Dumontheil et al., 2022). Given these unexpected findings, neuroimaging results by Dumontheil et al. (2022) were necessary to provide some insight into what goes on in participants’ brains. 

Figure 1: Brain regions showing greater activation for (A) counterintuitive versus control (intuitive) problems, (C) response inhibition versus no response inhibition, and (D) semantic inhibition versus no semantic inhibition (Dumontheil et al., 2022). 

Figure 2: A comparison between areas showing increased activation during counterintuitive reasoning and (A) complex inhibition behavior, and (B) interference control behavior (Dumontheil et al., 2022). 

Since the overlap is limited in Figure 2, researchers concluded that the relationship between inhibitory control and counterintuitive problem solving was not direct (Dumontheil et al., 2022). They posit that the role of inhibition in counterintuitive reasoning may be limited to specific types of inhibition. In particular, semantic inhibition might be a better explanation than just response inhibition (Dumontheil et al., 2022). 

Neurosynth (an fMRI image database) also associates areas activated during counterintuitive reasoning with “working memory,” “calculation,” “symbolic,” “attention,” “visually,” and “spatial,” suggesting that inhibition is not the only factor at play (Dumontheil et al., 2022). They highlight that two areas known as the intraparietal sulcus (IPS) and Brodmann area 7 (BA 7)—which together are responsible for visuo-spatial attention—show increased activation during counterintuitive reasoning, response inhibition, and semantic inhibition (Dumontheil et al., 2022). Hence, they also suggest that visuo-spatial attention may be another factor in counterintuitive reasoning (Dumontheil et al., 2022). 

So what does this mean, practically? For educators, it seems that curriculum design in STEM should not be done in isolation. Given the impact of semantic reasoning, it would be prudent to balance training in purely symbolic reasoning with training in semantic reasoning (e.g., by requiring humanities classes be taken with STEM classes). For cognitive neuroscientists, this research suggests that there may be another dimension to understanding counterintuitive reasoning: the complex causal relationships between visuo-spatial attention, inhibitory control, and counterintuitive reasoning. Indeed, this is a cautionary tale about the importance of inhibition in science itself—causation is difficult to establish, and the most intuitive models in science may not always be right, either.

 

References

Brookman-Byrne, A., Mareschal, D., Tolmie, A. K., & Dumontheil, I. (2018, June 21). Inhibitory control and counterintuitive science and maths reasoning in adolescence. PLoS ONE, 13(6), 1-19. https://doi.org/10.1371/journal.pone.0198973

Dumontheil, I., Brookman-Byrne, A., Tolmie, A. K., & Mareschal, D. (2022). Neural and Cognitive Underpinnings of Counterintuitive Science and Math Reasoning in Adolescence. Journal of Cognitive Neuroscience, 34(7), 1205. https://doi.org/10.1162/jocn_a_01854

Saenen, L., Heyvaert, M., Van Dooren, W., Schaeken, W., & Onghena, P. (2018). Why Humans Fail in Solving the Monty Hall Dilemma: A Systematic Review. Psychologica Belgica, 58(1), 128-158. https://doi.org/10.5334/pb.274

 

ChatGPT Beats Humans in Emotional Awareness Test: What’s Next?

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In recent times, it can seem like everything revolves around artificial intelligence (AI). From AI-powered robots performing surgery to facial recognition on smartphones, AI has become an integral part of modern life. While AI has affected nearly every industry, most have been slowly adapting AI into their field while trying to minimize the risks involved with AI. One such field with particularly great potential is the mental health care industry. Indeed, some studies have already begun to study the uses of AI to assist mental health work. For instance, one study used AI to predict the probability of suicide through users’ health insurance records (Choi et al., 2018), while another showed that AI could identify people with depression based on their social media posts (Aldarwish & Ahmed, 2017). 

Perhaps the most wide-spread AI technology is ChatGPT, a public natural language processor chatbot that can help you with a plethora of tasks, from writing an essay to playing chess. Much discussion has been done about the potential of such chatbots in mental health care and therapy, but few studies have been published on the matter. However, a study by Zohar Elyoseph has started the conversation of chatbots’ potential, specifically ChatGPT, in therapy. In this study, Elyoseph and his team gave ChatGPT the Levels of Emotional Awareness Scale (LEAS) to measure ChatGPT’s capability for emotional awareness (EA), a core part of empathy and an essential skill of therapists (Elyoseph et al., 2023). The LEAS gives you 20 scenarios, in which someone experiences an event that supposedly elicits a response in the person in the scenario, and the test-taker must describe what emotions the person is likely feeling. Two examinations of the LEAS, one month apart, were done on ChatGPT to test two different versions of ChatGPT. This was done to see if updates during that month would improve its ability on the LEAS. On both examinations, two licensed psychologists scored the responses from ChatGPT to ensure reliability of its score. On the first examination in January 2023, ChatGPT achieved a score of 85 out of 100, compared to the French men’s and female’s averages of 56.21 and 58.94 respectively. On the second examination in February 2023, ChatGPT achieved a score of 98: nearly a perfect score, a significant improvement from the already high score of 85 a month prior, and a score that is higher than most licensed psychologists (Elyoseph et al., 2023).

This study shows that, not only is ChatGPT more capable than humans at EA, but it is also rapidly improving at it. This has massive implications for in-person therapy. While there is more to being a good therapist than just emotional awareness, it is a major part of it. Therefore, based on this study, there is potential for chatbots like ChatGPT to rival, or possibly even replace, therapists if developers are able to develop the other interpersonal traits of good therapists. 

However, ChatGPT and AI needs more work to be done before it can really be implemented into the mental health field in this manner. To start, while AI is capable of the technical aspects of therapy, such as giving sound advice and validating a client’s emotions, ChatGPT and other chatbots sometimes give “illusory responses”, or fake responses that it claims are legitimate (Hagendorff et al., 2023). For example, ChatGPT will sometimes say “5 + 5 = 11” if you ask what 5 + 5 is, even though the answer is clearly wrong. While this is a very obvious example of an illusory response, harm can be done if the user is not able to distinguish between the real and illusory responses for more complex subjects. These responses can be extremely harmful in situations such as therapy, as clients rely on a therapist for guidance, and if such guidance were fake, it could harm rather than help the client. Furthermore, there are concerns regarding the dehumanization of therapy, the loss of jobs for therapists, and the breach of a client’s privacy if AI was to replace therapists (Abrams, 2023). ​​

Fig 1. Sample conversation with Woebot, which provides basic therapy to users. Adapted from Darcy et al., 2021. 

However, rudimentary AI programs are already sprouting that try to bolster the mental health infrastructure. Replika, for instance, is an avatar-based chatbot that offers therapeutic conversation with the user, and saves previous conversations to remember them in the future. Woebot provides a similar service (Figure 1), providing cognitive-behavioral therapy (CBT) for anxiety and depression to users (Pham et al., 2022). While some are scared about applications such as these, these technologies should be embraced since, as they become more refined, they could provide a low-commitment, accessible source of mental health care for those who are unable to reach out to a therapist, such as those who are nervous about reaching out to a real therapist, those who live in rural environments without convenient access to a therapist, or those who lack the financial means for mental health support. AI can also be used as a tool for therapists in the office. For example, an natural language processing application, Eleos, can take notes and highlight themes and risks for therapists to review after the session (Abrams, 2023). 

There are certainly some drawbacks of AI in therapy, such as the dehumanization of therapy, that may not have a solution and could therefore limit AI’s influence in the field. There is certainly a chance that some people would never trust AI to give them empathetic advice. However, people said the same when robotic surgeries began being used in clinical settings, but most people seem to have embraced that due to its superb success rate. Regardless of whether these problems are resolved, AI in the mental health industry has massive potential, and we must make sure to ensure that the risks and drawbacks of such technology are addressed and refined so that we can make the most of this potential in the future and bring better options to those who need it. 

 

Citations

Abrams, Z. (2023, July 1). AI is changing every aspect of psychology. Here’s what to watch for. Monitor on Psychology, 54(5). https://www.apa.org/monitor/2023/07/psychology-embracing-ai

 

Aldarwish MM, Ahmad HF. Predicting Depression Levels Using Social Media Posts. Proc – 2017 IEEE 13th Int Symp Auton Decentralized Syst ISADS 2017 2017;277–80.

 

Choi SB, Lee W, Yoon JH, Won JU, Kim DW. Ten-year prediction of suicide death using Cox regression and machine learning in a nationwide retrospective cohort study in South Korea. J Affect Disord. 2018;231(January):8–14.

 

Darcy, Alison & Daniels, Jade & Salinger, David & Wicks, Paul & Robinson, Athena. (2021). Evidence of Human-Level Bonds Established With a Digital Conversational Agent: Cross-sectional, Retrospective Observational Study. JMIR Formative Research. 5. e27868. 10.2196/27868. 

 

Elyoseph, Z., Hadar-Shoval, D., Asraf, K., & Lvovsky, M. (2023). ChatGPT outperforms humans in emotional awareness evaluations. Frontiers in psychology, 14, 1199058. 

 

Hagendorff, T., Fabi, S. & Kosinski, M. Human-like intuitive behavior and reasoning biases emerged in large language models but disappeared in ChatGPT. Nat Comput Sci 3, 833–838.

 

Pham K. T., Nabizadeh A., Selek S. (2022). Artificial intelligence and chatbots in psychiatry. Psychiatry Q. 93, 249–253.



PedPRM Unveils Promising Treatment for Insomnia in Children with Autism Spectrum Disorder

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Getting enough sleep is widely considered crucial to our well-being. However, for some individuals with Autism, getting enough quality sleep is not as easy as it sounds. Autism Spectrum Disorder (ASD) is a developmental disorder that widely affects the U.S. population, as 1 in 36 children aged eight has been diagnosed with autism (CDC, 2023). The kind and severity of the symptoms that individuals with ASD may exhibit can vary along the ASD spectrum.  Sleeping, in particular, is a common challenge for those with ASD, as many suffer from problems related to the REM (Rapid Eye Movement) sleep phase, a phase critical for memory consolidation (Devnani & Hedge, 2015). This can quickly become a vicious cycle for some, as lack of sleep can increase the severity of other Autism-related symptoms but also affect both the individual and the quality of life of their family or caretakers. 

To investigate possible treatments, a recent study by Malow et al. focuses on the pharmacological approach of using melatonin to treat sleep disorders. Melatonin is a hormone produced by the body’s pineal gland to regulate circadian rhythm, allowing the body to relax according to the appropriate light-darkness cycles of the day. This study uses a small, long-release tablet (PedPRM) used to mimic endogenous melatonin secretion. It focused mainly on a younger population, from children to adolescents, who met two criteria. The first was that they had confirmed diagnoses of either Autism or Smith-Magenis syndrome and had also experienced sleep abnormalities. Smith-Magenis syndrome is also a developmental disorder that involves symptoms similar to those of ASD, affecting behavior, cognition, and sleep. They also had to have not previously seen improvements when using sleep hygiene treatments to be included in the study, such as establishing a strict bedtime routine and taking steps to provide a calm and comfortable sleep environment (CHOC, 2023).

With the study sample set, the study was conducted over 108 weeks and divided into four phases (Graph I). Throughout the four phases, participants’ caregivers would document sleep quality and total sleep time in a sleep and nap diary to record the efficacy of treatment. The study participants started the first stage with a 2-week period in which they were given placebos. If participants showed improvement while receiving a placebo, they would be removed from the study to reduce the possibility of external factors affecting the results (Scott et al., 2021). After clearing Phase 1, participants entered the second phase, which consisted of a double-blinded 13-week period in which they were randomly placed into either a placebo or treatment group (PedPRM). After this, Phase 3 comprised a longer 91-week open-label period in which both groups were combined. For the final phase of the study, participants were placed again in a 2-week single-blind placebo period to ensure that the drug had been completely removed from the participants with no adverse effects after stopping treatment.

Upon concluding the experimental period, the results to be considered for this study could be divided into three groups: participants’ sleep quality, caregivers’ well-being, and the participants’ growth development. With this data, the researchers found a significant

 decrease in sleep disturbance (Graph II-A) and an increase in caregiver satisfaction (II-B) and quality of life (II-C). These were most pronounced during the first half of the treatment. In the latter half of treatment, sleep disturbance continued to decrease but at a slower pace than the initial treatment phase. Fortunately, there were no reported deaths, and most adverse reactions included daytime fatigue and mood swings. However, the severity and extent of these were not detailed in the results of the study and offer the potential to be analyzed further.  

The study shows compelling initial evidence that PedPRM is an effective treatment for sleep disorders in individuals with ASD. However, as noted by the researchers, it also shows that constant active treatment is required as most sleep quality improvements are removed upon halting treatment. Since medications for children are generally more strictly controlled, PedPRM consistently demonstrates a possibility for effective pediatric treatment, even if for long-term medication. In particular, these findings are essential as it has been found that rapid-release melatonin is not helpful with maintaining sleep a couple of hours after administration, and it had long been considered a challenge to find small, swallowable prolonged-release tablets for children (Fliesler, 2022). As sleep interruption is something that mainly affects those with neurodevelopmental disorders, this is a significant step towards adequate treatment. However, it is essential to note that this pharmacological alternative should only be considered if behavioral interventions and sleep hygiene modifications have been attempted but have been found unsuccessful. 

 

 

Sources 

CDC. (2022, December 9). Centers for Disease Control and Prevention. https://www.cdc.gov/ncbddd/autism/facts.html 

CDC Newsroom. (2016, January 1). CDC. https://www.cdc.gov/media/releases/2023/p0323-autism.html 

CHOC – Children’s Hospital of Orange County. (2023, March 2). Autism and Sleep Hygiene – Children’s Hospital of Orange County. Children’s Hospital of Orange County. https://www.choc.org/programs-services/autism-neurodevelopmental/co-occurring-conditions-program/autism-and-sleep/ 

Devnani, P., & Hegde, A. U. (2015). Autism and sleep disorders. Journal of Pediatric Neurosciences, 10(4), 304. https://doi.org/10.4103/1817-1745.174438 

Fliesler, N. (2022, June 13). Melatonin for kids: Is it effective? Is it safe? – Boston Children’s Answers. Boston Children’s Answers. https://answers.childrenshospital.org/melatonin-for-children/#:~:text=There%20is%20some%20evidence%20to,the%20ability%20to%20swallow%20capsules. 

Furfaro, H. (2023, March 10). Sleep problems in autism explained. Spectrum | Autism Research News. https://www.spectrumnews.org/news/sleep-problems-autism-explained/ 

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