Eleventh Grade Finalists Jennifer Zhong, Smithtown High School East Sophia Augier, Smithtown High School East

ly these scientists meant no harm, but if someone who does mean harm learns how they did it, the results could be catastrophic. In response to this, the United States government has been taking steps to prevent information and technology from getting to people who may have malicious intentions by putting new measures in place. These include assessing how potentially dangerous new projects are, more heavily regulating who can access highrisk infectious agents, and keeping more papers classified (1, 6). Despite these concerns, there have been no legitimate biosecurity threats reported yet, making synthetic biology’s safety record very good (6). Its clean record combined with the many new safety measures being implemented helps ease some of the concerns about the field. In summary, synthetic biology is incredibly useful in the medical field and will have a positive impact on the development of vaccines and future medical research. This is proven by the number of accomplishments that have already taken place in the field’s short lifetime. These include, but are certainly not limited to, the improvement of the method for developing vaccines through the use of engineered virus-like particles that are enhanced with the use of synthetic biology and the creation of a synthetic gene network that can test anti-cancer drugs. Although, despite all the good synthetic biology can do, there are plenty of hypothetical dangers that come with the breakthroughs such as the threat of biological weapons. However, there are regulations in place to prevent these possibilities from becoming realities. As has already been shown, synthetic biology is capable of allowing many significant advances in the development of vaccines and in future medical research if we embrace it.

References

1. Staff, Synthetic biology. National Human Genome Research Institute, (2019). 2. F. Meng and T. Ellis, The second decade of synthetic biology: 2010–2020. Nature Communications 11, 1-4 (2020). doi: 10.1038/s41467-020-19092-2. 3. H. Charlton Hume, et al., Synthetic biology for bioengineering virus-like particle vaccines. Biotechnology and Bioengineering 116, 919-935 (2019). doi: 10.1002/bit.26890. 4. J. Rosenthal, et al., Pathogen-like particles: biomimetic vaccine carriers engineered at the nanoscale . Current Opinion in Biotechnology 28, 51-58 (2014). doi: 10.1016/j.copbio.2013.11.005. 5. Z. Kis, et al., Mammalian synthetic biology: emerging medical applications. Journal of the Royal Society Interface 12, 1-18 (2014). doi: 10.1098/rsif.2014.1000. 6. G. Gronvall, Safety, security, and serving the public interest in synthetic biology. Biotechnology Methods 45, 463-366 (2018). doi: 10.1007/s10295-018-2026-4.

Graphics illustrated by Komal Grewal `23

THE SAFETY BEHIND SYNTHETIC BIOLOGY VACCINES

By Jennifer Zhong, Smithtown High School East

As COVID-19 deaths and cases rise, rapid vaccine safety, development, and distribution become extremely important to potentially solve this world crisis. A myriad of people, over 105 million, have been infected with COVID-19 and well over 2 million have passed away as of February 2021 (7). The numbers continue to climb. During a global pandemic such as the current COVID-19 pandemic, vaccines need to be manufactured in large quantities and at a low cost in order to fulfill the availability of vaccines needed for herd immunity (10). Synthetic biology is a field that has been utilized to speed the development of COVID-19 vaccines using synthetically engineered organic molecules (2). DNA and RNA vaccines contain synthetic nucleotide transcripts delivered into the patient to produce translated proteins in the cells. There is an immune response triggered by these proteins that can protect the body from the virus (2,5). Synthetic biology has the potential to make a safe, quicker option for vaccine development compared to traditional vaccines and advance medical research worldwide. There are various benefits to using DNA and RNA vaccines compared to traditional vaccines. Non-viral vaccines provide a less costly, faster option for vaccine development. Previous development has taken an exceptionally long time to develop and manufacture, anywhere between 10 to 15 years, while it has taken less than one year for the COVID-19 vaccines (3). After viral genome sequencing, Moderna started human tests for the development of their current mRNA vaccine after only 66 days (10). Although live vaccines produce a very strong immune response, the dead or weakened pathogen may revert (6). There is a chance a live vaccine can become pathogenic if it recombines with a wild strain in nature, which coronaviruses such as SARS-CoV-2 have done in the past (6). On the other hand, RNA vaccines are considered to be safe because the spike protein is unable to reactivate and become dangerous. Despite many concerns, there is also no risk of integration of RNA into the patient’s genome (10). However, there are a few drawbacks to non-viral vaccines. They require multiple vaccinations to achieve immunity. Pfizer, BioNTech, and Moderna have each produced mRNA vaccines that are currently approved by the Food & Drug Association for emergency use (1). Both Moderna and Pfizer, frontrunners for COVID-19 vaccines, require two doses to be fully vaccinated due to the

first dose only resulting in a weak immune response (6). Pfizer also requires storage at -70 degrees Celsius which can pose a major issue during the transportation and storage of these vaccines at such low temperatures due to necessary special equipment (3). We do not have the industrial capacity needed to produce amounts of doses in the hundreds of millions for future vaccine development yet (12). Safety is considerably important while developing vaccines for rapid mass immunization such as the case of the COVID-19 pandemic, and potential safety risks must be weighed against benefits. Safety is a necessity for public use and lack of trust can create hesitancy and can fuel the anti-vaccination movement, making it extremely difficult to reach herd immunity during times when it is needed (6). Researchers have used the published SARS-CoV-2 sequence in order to synthesize the virus using synthetic biology which can benefit the development of a vaccine as well as drug research. Unfortunately, this may cause increased leakage of the virus and other safety hazards (11). There is also a large safety risk concerning DNA and RNA vaccines in that they have a higher chance of causing an adverse event after vaccination compared to a live attenuated vaccine (7). There have been major adverse events shown in patients during the development of the COVID-19 vaccine, including those that suspended the vaccine trials for review of such events (11). During the Pfizer Phase II trials, it was shown that 27% of people who had the vaccine reported an adverse event compared to 12% in the placebo group (9). Both mRNA vaccines can cause an allergic reaction such as anaphylaxis, preventing patients with allergies to the ingredients from having the vaccine administered (1). The development of RNA vaccines has had many obstacles and limitations in the past due to the result of inflammatory responses and also to the instability of RNA, which we need to be cautious of during synthetic vaccine development as well (8). Due to the scarcity of vaccines and other resources during the pandemic, the distribution of COVID-19 vaccines has differences for different populations and socioeconomic levels. More people lower in social class have been severely affected by COVID-19. Even if vaccines were funded publicly, those with a lower income have previously had lower vaccination rates (4). The distribution of vaccines can deepen disparities between socioeconomic status by further separating those who have the availability to be vaccinated and those who don’t. However, with the quick development of synthetic vaccines, doses may become widely available for the public despite socioeconomic level. As well as in vaccine development, synthetic biology can be incredibly useful in many other cases in medical advancement and research. Cells engineered by synthetic biology can be used for medical diagnosis and treatments. Viruses have been synthetically engineered to kill bacteria that are now resistant to most antibiotics and to attack and prevent the growth of tumor cells for cancer treatment (11). Unfortunately with the advantages of synthetic biology techniques, come detriments. Because of the rapid growth of synthetic biology research, there have been patient deaths and serious side effects due to research rushed without biosafety considerations. Synthetic biology can be used in developing immunogenic vaccines and furthering medical research beyond vaccinology. DNA and RNA synthetic vaccines can be extremely beneficial, especially during a pandemic. They ensure a quicker development and distribution of vaccines for the public to create immunity (10). Synthetic biology can help the world become more prepared for future health crises, but we still need to be wary of the potential biosafety risks and be considerate of other factors, including socioeconomic disparities.

Synthetic biology is a field that has been utilized to speed the development of COVID-19 vaccines using synthetically engineered organic molecules.

References

1. A. Banerji, et al., mRNA vaccines to prevent COVID-19 disease and reported allergic reactions: current evidence and suggested approach . J Allergy Clin Immunol Pract 9, 1423-1437 (2021). doi: 10.1016/j.jaip.2020.12.047. 2. K. Bruynseels, Responsible innovation in synthetic biology in response to COVID-19: the role of data positionality. Ethics Inf Technol 1, 1-9 (2020). doi: 0.1007/s10676-020-09565-9. 3. R. Burgos, et al., The race to a COVID-19 vaccine: opportunities and challenges in development and distribution. Drugs Context 10, 1-10 (2021). doi: 10.7573/dic.2020-12-2. 4. S. Ismail, et al., Navigating inequities: a roadmap out of the pandemic. BMJ Global Health 6, 1-9 (2020). doi: 10.1136/bmjgh-2020-004087. 5. N. Jackson, et al., The promise of mRNA vaccines: a biotech and industrial perspective. npj Vaccines 5, 1-6 (2020). 6. M. Jeyanathan, et al., Immunological considerations for COVID-19 vaccine strategies. Nature Reviews Immunology 20, 615-632 (2020). 7. S. Kashte, et al., COVID-19 vaccines: rapid development, implications, challenges and future prospects . Hum Cell 34, 711-733 (2021). doi: 10.1007/s13577-021-00512-4. 8. N. Pardi, M. Hogan, and D. Weissman, Recent advances in mRNA vaccine technology. Current Opinion In Immunology 65, 14-20 (2020). doi: 10.1016/j.coi.2020.01.008. 9. F. Polack, et al., Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine. The New England Journal of Medicine 383, 2603-2615 (2020). doi: 10.1056/NEJMoa2034577. 10. J. Sandbrink and R. Shattock, RNA vaccines: a suitable platform for tackling emerging pandemics?. Frontiers in Immunology 11, 1-9 (2020). 11. J. Li, et al., Advances in synthetic biology and biosafety governance. Frontiers in Bioengineering and Biotechnology 9, 1-14 (2020). 12. R. Rappuoli, et al., Vaccinology in the post−COVID-19 era. PNAS 118, 1-7 (2021). doi: 10.1073/pnas.2020368118.

WHAT WE OWE TO OURSELVES AND THE FUTURE GENERATION

By Sophia Augier, Smithtown High School East

There is an entire universe of endless possibilities just waiting for humankind to uncover. However, as a nation we struggle to recognize the benefits space research has on human life. Neither the broadening of earthbound scientific research, or the advancement of space research and exploration are mutually exclusive investments. Each is achievable and vital to sustaining human life, and should be simultaneously pursued. Unfortunately, space research, and the benefits these programs yield, lack saliency across the public sphere, and therefore lack the necessary funding and support (1). In contrast, the globally competitive space programs of the 1960’s inspired our nation which subsequently garnered the financial backing of the U.S. government (2). Today, public support can be established with clear correlations drawn between space research and its benefits to life on earth. This type of public understanding is paramount in securing the necessary funding for space research. Space research leads to discoveries and innovations that ultimately feed two overarching workstreams; improving life on earth and sustaining human life beyond our planet’s atmosphere. This is seen in the life science research data NASA recently shared regarding the effects of long term isolation and confinement on genes, neural circuits, physiological systems, and behavior (3). This data provides great value to researchers focussing on future space travel, exploration, or habitation. Such findings also provide actionable value here on earth, in that they fuel the development of innovative and efficient health screening tools, diagnostic systems, and treatments to mitigate health risks associated with isolation and confinement (3). These timely inputs provide healthcare opportunities for those deeply impacted by isolation during the COVID-19 global pandemic. In space, astronauts remain in the same place, with the same people, doing the same thing day in and day out.

The commonality observed between social isolation during the pandemic and the isolation of space travel, helps us understand and prepare for life post-pandemic (3). Climate change is another global crisis where we continue to do battle. Space re- search has provided us with solutions to monitoring, managing, and mitigat- ing the harsh effects of climate change.

Rising tem -

It is our job as human beings to create a better life not just for today, but also for generations to come. Without space research today, there will be no hope for a safe and secure tomorrow when Earth can no longer be called home.

of safely extinguishing the fires in time to minimize loss of lives and damage to forests and property (5). Without putting astronauts and resources in space, the world would never have been able to reap the benefits of this unique perspective and technology. The NASA budget is less than 1% of the U.S. federal budget. At only $23 billion, NASA spending is significantly less than it was at its peak at the the start of the Apollo missions in 1966. Since that time the NASA budget shrank from 4.5% of the federal budget to .5% today. Comparatively, NASA receives a fraction of the funding seen in other areas of the federal budget; 26% for healthcare or 17% for defense (6). Government funding is driven by interest and need, which explains why the NASA budget decreased by about $40 billion following the cold war (6). When space exploration was driven by competition and political interests it received more support. As a result, NASA was able to achieve and innovate on many fronts. When public interest faded and political winds shifted, funding and support slowly shrank over the course of the next 40 years (6). However, space research continued to provide knowledge that benefited life on earth, be it at a lesser rate. Consequently when funding slows down, so does space exploration. The commercialization of space travel allows NASA to better collaborate with global research partners by focusing it’s funding and resources on space research, leaving private companies to compete for contracts to handle the routine shuttling of cargo and humans to the International Space Station (ISS) (1). Companies such as SpaceX saw an industry that was lacking in the resources, but had the reputation of discovering and producing great things. Private companies that understand the profit potential surrounding space exploration were eager to invest their time, money, and resources (7). These private enterprises help offset the impact of decreased government funding (1). Space exploration takes a toll on the human body. The effects of microgravity cause serious disruption within the body, especially to the cardiovascular and musculoskeletal systems (8)(9). Once astronauts escape the Earth’s gravitational pull, they put their bones and muscles at risk for atrophy that can lead to increased kidney stone formation and bone fractures, as well as harden the intervertebral discs leading to disc disease and pain (8). Without gravity the cardiovascular system also experiences great changes since blood isn’t being pulled toward the feet, it instead pools up in the torso and head and in response the body decreases the blood pumping rate and red blood cell production, negatively impacting other body systems (9). This may seem like reasons not to continue space research, but the opposite is true (8). Just as firefighters put their lives at stake to save civilians, or soldiers risking their lives at war, astronauts are putting their lives at risk for the future generation. It is our job as human beings to create a better life not just for today, but also for generations to come. Without space research today, there will be no hope for a safe and secure tomorrow when Earth can no longer be called home.

peratures and abnormal precipitation rates have made countries like the United States, Australia, Russia, and Spain increasingly susceptible to extreme and prolonged wildfires and wildfire seasons (4). Astronauts on the International Space Station (ISS) utilize their unique perspective and specialized instruments to provide monitoring and managing services for fighting wildfires. NASA engineers were able to create one of the most effective fire detection systems using tools originally developed for space research (5). Their artificial geostationary satellites are able to quickly detect thermal heat and almost immediately notify field officials back on earth using wireless technology. Being the first to be able to detect and notify officials about early fires burning in distant regions, gives firefighters a much better chance References

1. Nasa, Benefits stemming from space exploration. NASA, (2013). 2. A. Rinaldi, Research in space: in search of meaning. EMBO Reports 17, 1098-1102 (2016). doi: 10.15252/embr.201642858. 3. A. Chouker and A. Stahn, COVID-19 - the largest isolation study in history: the value of shared learnings from spaceflight analogs. npj microgravity 6, 1-7 (2020). doi: 10.1038/s41526-02000122-8. 4. M. Goss, et al., Climate change is increasing the likelihood of extreme autumn wildfire conditions across california. Environmental Research Letters 15, 1-14 (2020). 5. R. Petrescu, et al., NASA satellites help us to quickly detect forest fires. American Journal of Engineering and Applied Sciences 11, 288-296 (2018). doi: 10.3844/ajeassp.2018.288.296 . 6. The Planetary Society, Your guide to NASA’s budget. The Planetary Society, (2021). 7. C. Iacomino and S. Ciccarelli, Potential contributions of commercial actors to space exploration. Adv. Astronaut. Sci. Technol. 1, 141-151 (2018). 8. K. Kandarpa, V. Schneider, and K. Ganapathy, Human health during space travel: an overview. Neurology India 67, 176-181 (2019). doi: 10.4103/0028-3886.259123. 9. B. Dunbar, Cardiovascular health in microgravity. NASA, (2020).

Graphics illustrated by Komal Grewal `23