1st Place Essay

We can now sequence the genome of all life forms, from viruses to humans. What could be the point of this?

Elektra Epanomeritakis
The Wallace High School, Lisburn, Northern Ireland, United Kingdom

I propose to sequence the genome of COVID-19 because humanity must win the fight against the pandemic. Genome sequencing is the process of ‘decoding’ an organism’s genetic material. A genome resembles a device’s instruction manual, containing the information required for the device to be manufactured and function.1 Genomes are made of DNA or RNA and consist of variable combinations of four nucleotide base ‘letters’.The identification of the precise order of these ‘letters’ (genomic code) can be done using a number of complex scientific techniques.2 In January 2020, as a response to the SARS-CoV-2 (COVID-19) outbreak, Chinese researchers shared the genomic sequence of the virus with scientists across the world.2 Since then, COVID-19 has claimed the lives of more than 2.7 million people worldwide.3 Genomic sequencing has been the most valuable weapon that humankind possesses in the battle against the deadly virus. While human genetic material is made of double-stranded DNA, consisting of over 3 billion base ‘letters’, COVID-19 has a much shorter, single-stranded RNA genome of just under 30,000 bases long.1 The viral genome contains instructions for the production of the protein responsible for invading the human cells, as well as instructions for the virus’ self-replication.2 The scientific milestones of accurate diagnosis, effective prevention of infection spread and disease epidemiology are dependent on the ‘reading’, or decoding, of the COVID-19 genetic ‘alphabet’.1 Testing: In order to establish the diagnosis of COVID-19 infection, we test samples taken by swabbing the nose and throat or by aspirating bronchial secretions. The presence of the viral genetic sequence in these samples can be identified by Polymerase Chain Reaction (PCR) or antigen tests. The detection of the viral genome in the human airway confirms the diagnosis of infection.1,2 Identification of COVID-19 variants: Viruses are able to alter their genetic material through random changes in the structure of specific genes (mutations). These mutations result in new versions of the virus (variants) with potentially different behavioural properties.1 Knowing the original viral genetic sequencing enables scientists to detect genomic changes and track the emergence of new COVID-19 variants. Identification of variants helps us understand the spread of the disease and establish their association with specific symptoms or severity of illness.1,2 Vaccine production: In the race against the pandemic, researchers and pharmaceutical companies have used two different COVID-19 vaccine manufacture technologies, both relying on knowledge of genomic sequencing for their development.4,5 These include the RNA (e.g., Moderna, Pfizer & BioNTech)4 and the Viral Vector (e.g., Oxford/AstraZeneca, Johnson & Johnson) vaccines.5 COVID-19 penetrates the human cells using its ‘spike protein’. Scientists have identified and isolated the part of viral RNA coding for this protein.4,5 The RNA vaccines contain synthetic RNA which codes for the spike protein. This RNA is encapsulated in lipid nanoparticles so it can be protected from breaking down and can be taken up by human cells.4 The Viral Vector vaccines contain genetically altered (harmless) viruses carrying viral RNA incorporated in their own genetic material.5 Once the RNA is inside human cells (aided by either lipid nanoparticles or viral vectors) it starts the production of the spike protein, triggering an immune response.4,5 Epidemiology: Extensive and rapidly performed genome sequencing of COVID-19 offers us invaluable epidemiological information, determining Public Health policies and governmental decisions.1,6 Understanding the pattern of viral transmission helps evaluate and reshape the interventions we implement. Genome sequencing of new variants can help us determine the number of imported cases and distinguish them from the local transmissions. Similarly, we can also identify transmission chains and clusters of cases. Scientists from all over the world have created international databases of genomic sequences in order to compare COVID-19 variants and accurately record transmission rates and patterns of spread.1,6 In conclusion, the dynamic and constantly evolving process of the COVID-19 genome sequencing is currently the most valuable tool for outbreak management and vaccine generation. Furthermore, the lessons learned during this process will make the world wiser, stronger and better equipped to face any future pathogenic threat.6

1. UK Research and Innovation (2020), “How does virus genome sequencing help the response to COVID-19?”
2. Compound Interest (2021), “Chem vs COVID Timeline”,
3. Johns Hopkins University, Coronavirus Resource Centre (accessed 22/3/2021)
4. Brunning, A. (2021), Chemical & Engineering News, ‘How are RNA vaccines made?’
5. Compound Interest (2020), “What are the viral vector vaccines and how they work?”
6. World Health Organisation (2021), “Genomic sequencing of SARS-CoV-2: a guide to implementation for maximum impact on public health”

2nd Place Essay

I propose to sequence the genome of Rhinolophus ferrumequinum.

Neil Sardesai, Cheryl Buchanan
The Perse School Cambridge, Cambridge, United Kingdom

I propose to sequence the genome of Rhinolophus ferrumequinum (the greater horseshoe bat) because we might be able to reduce the spread of epidemics and even develop a cure for cancer.Bats are the vector for many viruses that have caused epidemics in the last few decades, including Ebola, Marburg, SARS [1] and possibly even, in 2020, COVID-19 [2]. These outbreaks have led to massive problems for the global community, not only tragically leading to the huge loss of life, but also having severe economic impacts on the countries they affect. To take one example, the Ebola epidemic between 2014-2016 not only resulted in the death of 11,325 people [3], but it also led to the economic collapse of countries in West Africa, with 3 countries in this area experiencing a loss in GDP of $2.2 billion. [4] These economic effects only serve to further exacerbate the social problems caused by the disease, as there are fewer funds to spend on key local infrastructure.According to a paper published in 2018, millions of years ago an ancestor of the mouse-eared bat appropriated a genetic sequence (called VP35) from an ancestor of Ebola [5]. This genetic sequence, which is made up of 280 amino acids, remains intact today in the DNA of all 15 modern bat species of the genus Myotis. Viruses like Ebola and Marburg have the VP35 gene to block the immune system of the animals they infect, thus allowing them to be infected with the virus. Meanwhile, lab tests have shown that the version of VP35 found in bats suppresses its own immune system, making it susceptible to infection. While we know that this gene is present in Myotis bats, it is not clear whether they are present in Rhinolophus ferrumequinum. As such, by sequencing its genome, we could find out whether the bat’s genes make it more susceptible to be infected by coronaviruses. Not only is Rhinolophus ferrumequinum one of the most widespread bat species in Europe [6], but it can also be found in other parts of Africa and Asia. Consequently, there is a high likelihood that if the species has the VP35 sequence, it could spread coronaviruses quickly around the continents. This would be catastrophic for these countries as disease would be able to spread quickly even if conventional measures to stop the spread, such as airport screenings, are implemented. Moreover, by conducting research into bat telomeres, we could potentially even cure cancer and increase the health of our ageing population. For our body to grow or repair damage, new cells must be created. This replenishment occurs by mitosis, where the genetic material inside each cell is duplicated before the cell splits (or undergoes cytokinesis). However, the enzymes involved in duplicated the genetic material can’t read the genetic material at the end of the chromosomes. To stop genetic material from being lost, telomeres are placed on the ends of chromosomes. Telomeres are pieces of excess genetic code which cap the ends of chromosomes, protecting them from damage [7]. As the whole telomere is not read by the enzymes during DNA replication, telomeres get shorter every time the cell copies itself. Eventually, these telomeres become too short to protect the chromosomes. When this happens, these cells stop functioning properly. [8] As such, telomeres are often described as the aging clock in each cell.Since telomeres get shorter each time a cell divides, a longer telomere is associated with a longer life span. However, if a telomere is too long, then there is a high likelihood of cancer developing [9]. As such, most mammals attempt to shorten telomeres and repress telomerase in an effort to reduce the likelihood of cancer developing [10]. The greater horseshoe bat has very long telomeres, which helps it have a long lifespan. Despite this, however, cancer is rarely reported in bats [11], suggesting that telomeres in bats have different
properties than human ones. If we can learn these differences, then there is a chance that we could develop medicines to prevent cancer and increase the average human life expectancy. In conclusion, the sequencing of Rhinolophus ferrumequinum would prove exceedingly valuable to our society. Not only does it have to potential to advance our knowledge in telomeres, possibly even to extent that we can cure cancer, but it also could prove vital in combatting disease. Pandemics have the power to cause economic collapse and social problems on an astronomical scale, so it is necessary for us to all we can to prevent this.

Bibliography[1] New Scientist, “Bats spread Ebola because they’ve evolved not to fight viruses,” 2018.[2] K. Andersen, et al., “The proximal origin of SARS-CoV-2,” Nature Medicine, 2020. [3] CDC, “2014-2016 Ebola Outbreak in West Africa,” Accessed 2020.[4] CDC, “https://www.cdc.gov/vhf/ebola/history/2014-2016-outbreak/cost-of-ebola.html,” 8 3 2019, Accessed 2020.[5] University at Buffalo, “Bats harbor a gene swiped from an ancient Ebola-like virus — here’s how they may use it,” 2018.[6] O. Tournayre et al,, “Integrating population genetics to define conservation units from the core to the edge of Rhinolophus ferrumequinum western range,” Ecology and Evolution, vol. 9, 2019.[7] M. A. Shammas, “Telomeres, lifestyle, cancer, and aging,” Current Opinion in Clinical Nutrition and Metabolic Care, 2011 [8] E. DTA, “An evolutionary review of human telomere biology: the thrifty telomere hypothesis and notes on potential adaptive paternal effects.” American Journal of Human Biology, 2011 [9] E. J. McNally, et al., “Long telomeres and cancer risk: the price of cellular immortality,” Journal of Clinical Investigation, 2019. [10] Nuno, O. Ryder, et al., “Comparative biology of mammalian telomeres: hypotheses on ancestral states and the roles of telomeres in longevity determination,” Aging Cell, 2011 [11] L.-F. Wang, et al., “Mass extinctions, biodiversity and mitochondrial function: are bats ‘special’ as reservoirs for emerging viruses?,” Current Opinion in Virology, 2011. [12] C. McGrath, “Highlight—Blind as a Bat? The Genetic Basis of Echolocation in Bats and Whales,” Genome Biology and Evolution, 2020 [13] H. Wang, e al., ” Evolutionary Basis of High-Frequency Hearing in the Cochleae of Echolocators Revealed by Comparative Genomics,” Genome Biology and Evolution, 2020.

3rd Place Essay

Saving the Javan rhino; lessons for conservation

Isabella Ioannidou, Catherine Panayiotou
The English School, Nicosia, Cyprus, Nicosia, Cyprus

I propose to sequence the genome of the Javan rhinoceros (Rhinoceros sondaicus) because this will be an invaluable tool in the efforts to secure the survival of this critically endangered species and contribute to the protection of biodiversity and the wider health of our ecosystems.Javan rhinoceroses (rhinos) are the rarest of the five surviving rhino species, with only about 70 animals remaining in the wild. The decline in their population is mainly due to poaching which is compounded by habitat loss secondary to human activity and the prevalence of plant species that compete with rhino food plants. Infectious diseases transmitted by local cattle also pose a potential threat.In 1998, the roundworm (Caenorhabditis Elegans) became the first animal whose genome was sequenced and 2001 marked the very significant milestone of the sequencing of the human genome; a seminal development in our efforts to promote human health and combat disease. The evolution of massively parallel sequencing technology has made whole genome sequencing much more accessible and efficient and has significantly reduced costs. Scientists apply this technology to access the genomes of an ever increasing number of organisms using a set of criteria to prioritise their targets. These include the insight the sequenced genome could provide into human health and disease, its value to the research community and practical considerations such as sample accessibility. On a much grander scale, the Earth Biogenome Project aims to sequence all eukaryotes on earth (1).A relatively recent application of this technology is the genomic analysis of endangered species in an effort to conserve them; a field known as conservation genomics. This is a critical field as current extinction rates are so high that the current period is considered to be the sixth mass extinction. Genome-scale data, such as the study of single nucleotide polymorphisms, can be used to combat the loss of biodiversity by giving us a broader understanding of the genetic variation of a particular population and help us identify the gene loci that contribute to fitness and susceptibility to disease and the effects of inbreeding (2). The Javan rhino is a sensible sequencing target as it is already genome-enabled with the reference genome of other rhino species already established.Genome sequencing studies and the analysis of allelic frequencies can provide significant insights into changes in population sizes, the structures and movements of populations as well as the role of gene flow which are key concepts in conservation biology (3). These studies can also provide evidence of taxonomic divergence and relevant genetic adaptation and can lead to the identification of alleles that confer either resistance or susceptibility to infectious and other diseases that pose serious threats to the populations, which can inform their management. One such example is the role of genetic variation at the Major Histocompatibility Complex (4).Another important aspect of the conservation effort is our ability to identify how genetic diversity and genetic adaptation have enabled specific populations to thrive in new habitats and adapt to a changing environment as is the case with climate change. Genomic studies also allow the detailed study of hybridisation and introgression, which is the process of gene flow from one species to another. The detailed analysis of the timeline of such events, particularly in relation to evolution and adaptation to new environments, are very valuable to the scientific community.One of the significant challenges to the conservation of endangered species is the emergence of small populations that are isolated from each other as a result of shrinking habitats and other external factors. The small size of these populations enables deleterious alleles to become established through genetic drift and promotes inbreeding, increasing the likelihood of the emergence of recessive traits that compromise the fitness of the population. Genomic information can identify the specific loci involved and support conservation efforts by identifying the carrier status of individual animals.The knowledge gained through deciphering the genome of the Javan rhino can provide new insights into managing threats such as climate change and habitat loss and has potential wider benefits such as supporting the development of novel therapeutic approaches to fight both animal and human disease. Conserving endangered species can have multiple benefits to society, particularly when viewed though the ‘One Health’ perspective (5). The unquestionable interconnectivity between the health of humans, animals, plants and the environment underscores the significance of the conservation of biodiversity in our efforts to secure sustainable food supplies and effectively manage the resources of our planet.

1Lewin HA, Robinson GE, Kress WJ et al (2018) Earth BioGenome Project: Sequencing life for the future of life. Proc Natl Acad Sci 115 (17): 4325-4333 2. Steiner CC, Putnam AS, Hoeck PEA, Ryder OA (2013) Conservation genomics of threatened animal species. Annu Rev Anim Biosci 1:261-281. 3. Frankham R (2005) Genetics and Extinction. Biological Conservation 126 (2): 131-140 4. Savage AE, Zamudio KR (2011) MHC genotypes associate with resistance to a frog-killing fungus. Proc Natl Acad Sci 108: 16705-10 5. Calistri P, Ianetti S, Danzetta ML et al (2013) The Components of ‘One World-One Health’ Approach. Transboundary and Emerging Diseases 60(S2): 4-13

Essays Honourable Mention – Metin Furkan Amarat

Opinions on the Genome Sequencing of E. aspergillum

Metin Furkan Amarat, Nuran Ozkan
Buca Doga Koleji, izmir, Turkey

I propose to sequence the genome of Euplectella aspergillum, otherwise known as Venus’ Flower Basket, because of its ability to produce glass fibres biologically and without the heat necessary in man-made glass production{1], which also form its skeleton in addition to the lack of certainty regarding the species’ lifespan.
Benefits regarding physics: The glass skeleton created by Venus’ Flower Basket is truly marvellous as its unique geometry allows its skeleton to bear the maximum force even though the main component is silica[3], which allows further insights to design for systems supporting high pressure or weight with lightweight fibres. Another reason to focus on the sophisticated silica system of these animals is that the ability of their skeleton to direct light and be used as fibre optics[4]. While the source for their silica and some of the proteins they use to synthesise the structure are known and have been studied, how the structure exactly takes its shape and its fibre optic capabilities are still unknowns, possibly ones that can be illuminated through the sequencing of their genome, allowing us to this species’ intricate fibre structure in architecture and engineering.
Benefits regarding biology and aging: Another major unknown regarding E. aspergillum and all sponges in general is their lifespan. It is estimated that they have a very long one, yet the exact date is currently unknown. Sequencing their genome will help us understand if the theory of aging as telomeres shorten holds true in other animals and possibly other methods they use to keep their cells with multiple nuclei young.
Benefits regarding chemistry and glass production: Yet another reason to sequence the genome of the Venus’ Flower Basket is its ability to produce the silica without the heat we use in the known methods of producing glass, implying that E. aspergillum is using chemical processes we are not aware of to create the material for its skeleton, possibly in a way we can replicate to produce other types of silica compounds.
In conclusion, E. aspergillum has many interesting features which could have many practical applications in today’s world, and the best way to further understand and replicate these features is to sequence its genome to understand the biological and chemical mechanics behind it.

1. Sundar, V. C., Yablon, A. D., Grazul, J. L., Ilan, M., & Aizenberg, J. (2003). Fibre-optical features of a glass sponge. Nature, 424(6951), 899-900. doi:10.1038/424899a
2. Saito, T., Uchida, I., & Takeda, M. (2002). Skeletal growth of the deep-sea hexactinellid sponge Euplectella oweni, and host selection by the symbiotic shrimp Spongicola japonica (Crustacea: Decapoda: Spongicolidae). Journal of Zoology, 258(4), 521-529. doi:10.1017/s0952836902001681
3. Michael A. Monn, James C. Weaver, Tianyang Zhang, Joanna Aizenberg, Haneesh Kesari. New mechanics insights into spicule architecture. Proceedings of the National Academy of Sciences Apr 2015, 112 (16) 4976-4981; DOI: 10.1073/pnas.1415502112
4. Kulchin Y.N. et al. (2009) Optical and Nonlinear Optical Properties of Sea Glass Sponge Spicules. In: Müller W.E.G., Grachev M.A. (eds) Biosilica in Evolution, Morphogenesis, and Nanobiotechnology. Progress in Molecular and Subcellular Biology, vol 47. Springer, Berlin, Heidelberg. doi.org/10.1007/978-3-540-88552-8_14. Accessed April 12, 2021.

Essays Honourable Mention – Sophia C. Froehlich

The genetic origins of longevity

Sophia C. Froehlich
Lycée général Isaac de l’Etoile, Poitiers, France

I propose to sequence the genome of Galapagos giant tortoises because it can provide us with information about the genetic origin of longevity. Since this sequencing has already been done, I will outline its benefits by analysing the study entitled “Giant tortoise genomes provide insights into longevity and age-related disease”, conducted by scientists V. Quesada, S. Freitas-Rodríguez, C. López-Otín, A. Caccone et al., and published on December 3, 2018 on nature.com [1].The genomes of Lonesome George, the last member of the now extinct Galapagos giant tortoise species, were analysed and compared to genes from related species [2]. Ageing consists in the process of progressive deterioration of an organism that is naturally irreversible and accompanied by the accumulation of mutations in the genetic material resulting in the dysfunction of certain cells [3]. Indeed, uncontrolled proliferation of cells can result in cancer, a disease linked to ageing. The Lonesome George genome included many variations of the five genes SMAD4, NF2, PML, PTPN11 and P2RY8, encoding anti-oncogenes that inhibit cell division [1]. These anti-oncogenes exert a negative control on cell division and trigger apoptosis, i.e. the self-destruction of cancer cells [3]. Thus, through their regulatory role, tumour suppressor genes curb the development of potentially fatal cancers and increase the body’s life expectancy [4]. Since the copies of these five genes are much more numerous in the species of turtles Chelonoidis abingdonii and Aldabrachelys gigantea than they are in vertebrates, the authors of this study consider them as one factor of longevity of these species.
Further, selective evolution favoured the functioning of the Galapagos giant tortoises’ immune system as they had many alleles of genes that attack and kill foreign bodies to avoid infections and inflammations. By sequencing the genome of Lonesome George, scientists found twelve copies of the PRF 1 gene, responsible for the production of perforin, as well as more granzymes than the human body provides [1]. Perforin being a cytolytic protein, attacks the cell wall of pathogenic cells by making them porous, before they can finally be killed off by granzymes [5]. In addition, the Lonesome George genome contains twice as many genes from the Major histocompatibility complex encoding immune recognition, than the human genome [6]. Therefore, the Galapagos giant tortoise’s organism was not only able to better detect pathogens due to its high sensitivity, but its genes also rendered the immune response stronger than the human immune system. It can be concluded that the Galapagos giant tortoises lived longer due to the high performing protection against infections and inflammations, triggered by their genetic material.
Finally, the study “Giant tortoise genomes provide insights into longevity and age-related disease” shows that Galapagos giant tortoises have many copies of the TDO2 gene [1], that protects against protein aggregation, i.e. the insoluble accumulation of misfolded proteins that is believed to cause Parkinson’s and Alzheimer’s disease [7]. In addition, the speed of telomere shortening also remains genetically regulated. Since the Lonesome George genome contained the TERF2 and DCLRE1B genes [1], telomere shortening and thus cell division was slowed down, which simply caused the organism to age more slowly and thus live longer.
This study outlines to what extend the genome of the Galapagos giant tortoise could be the key to better health and increased physical resistance for humans, even at an advanced age. This fact would have multiple impacts on both economy and society: Social inequalities could be reduced since physically resistant elderly people were less depending on cost-intensive care. Better public health would also relieve national health care systems and permit to focus the resulting budget surplus on other national purposes such as education. Finally, seniors being able to work longer would be better integrated into community. On the other hand, the bioethical legitimacy of such scientific progress is to be questioned due to the profound interference into human genetic material. Indeed, the artificial prolongation of human life would have complex social, economic and evolutionary consequences that cannot be predicted at the present time.
Thus the sequencing of the Galapagos giant tortoise genome, represented by Lonesome George, gives us essential information about a near-perfect organism that defies age by the destruction of tumours, the inhibition of microbial inflammation, the protection of the organism against self-destruction and the deceleration of biological ageing in a much more efficient way than the human body is able to.

[1] Quesada V., Freitas-Rodríguez S., López-Otín C., Caccone A., i.a. ; ,,Giant tortoise genomes provide insights into longevity and age-related disease“, Nature ecology & evolution, December 3, 2018, www.nature.com/articles/s41559-018-0733-x[2] Wilgar H., i.a. , DNA sequencing, Your genome – Methods and Technology, March 15, 2018, www.yourgenome.org/video/dna-sequencing[3] Géli V. and Gilson É., ,,Pourquoi vieillissons-nous?“, CNRS Le journal, November 18, 2016, lejournal.cnrs.fr/billets/pourquoi-vieillissons-nous[4] Rédaction de Futura, ,,Les secrets de longévité de la tortue George dévoilés par son génome“, Futura Sciences, December 4, 2018, www.futura-sciences.com/planete/breves/tortue-secrets-longevite-tortue-george-devoiles-son-genome-240/[5] Osínska I., Popko K., Demkow U., Perforin: an important player in immune response, National Centre for Biotechnology Information – US National Library of Medicine – National Institutes of Health, April 17, 2014,
www.ncbi.nlm.nih.gov/pmc/articles/PMC4439970/[6] Major Histocompatibility Complex, Britannica Micropædia, Volume 7, p. 715, 15th edition, 1998[7] Bustamante J. G. , Zaidi Syed Rafay H., National Centre for Biotechnology Information – US National Library of Medicine – National Institut of Health, March 16, 2020, www.ncbi.nlm.nih.gov/books/NBK470285/

Essays Honourable Mention – Patrick Humphreys

Sequencing MRSA to Save Lives

Patrick Humphreys, Shona Anderson
Methodist College Belfast, Belfast, United Kingdom

I propose to sequence the genome of all nosocomial methicillin-resistant Staphylococcus Aureus (MRSA) infections, because it would facilitate the implementation of infection control measures within healthcare environments, allow scientists to better monitor the mutational evolution of MRSA and aid in the production of new, more advanced antibiotics. Since it was first identified in 1960 [1], MRSA has become a major healthcare problem globally, a problem which must be urgently addressed. Its resistance to ?-lactam-based antibiotics poses a significant threat to patients worldwide, as it is becoming increasingly difficult to treat.
In 2019/20, Public Health England recorded a total of 814 MRSA cases across all acute Trusts, of which 201 patients died within 30 days of diagnosis [2]. While these numbers indicate a reduction in cases over the past decade, MRSA infection and antimicrobial resistance remain pressing issues, and I believe that whole genome sequencing of all nosocomial MRSA infections could reduce these problems.
Firstly, whole genome sequencing would aid in-depth analysis of MRSA strains which are present in hospital patients. This would allow healthcare providers to more easily determine the origin of such infections, which could prove vital in the implementation of appropriate infection control measures, because if MRSA is known to have been transmitted within a healthcare environment, the necessary measures could be put in place to prevent further spread. This has been proven by a research group studying MRSA transmission in the Cambridge University Hospitals NHS Foundation Trust, which used whole genome sequencing to demonstrate that several MRSA cases on a special care baby unit (SCBU) had originated from the same source [3]. By applying this method to other healthcare environments, it would be possible to gain better insights into the transmission of MRSA and importantly, could reduce the detrimental impact of MRSA outbreaks. A joint research group from the University of Cambridge and the London School of Hygiene and Tropical Medicine also recently established a method by which whole genome sequencing of MRSA could be carried out in under 24 hours; this method could be used to significantly hasten the response of hospitals to MRSA outbreaks [4].
Furthermore, whole genome sequencing of MRSA infections could also prove vital in the production of antibiotics to combat novel strains of MRSA. It has been used previously to aid the development of treatments for pathogenic bacteria, such as tuberculosis (TB). It allowed scientists to identify several factors which contribute to TB’s antimicrobial resistance, including the exact molecular mechanism which is inhibited by bedaquiline, the active substance in some existing TB medications [5]. It is therefore possible that whole genome sequencing could be applied to the production of MRSA antibiotics in a similar manner, providing novel insights into the mechanisms of resistance within different MRSA strains. In addition, there is evidence to suggest that MRSA can impair the function of the lymphatic system, which can lead to long-term immunodeficiency in patients who have recovered from MRSA infection [6]. The development of more effective antibiotics for MRSA could not only result in reduced mortality, but also reduced post-infection morbidity.
Moreover, whole genome sequencing could be used to monitor the inheritance and evolution of genes which are already known to cause methicillin resistance, such as the mecA gene. For example, whole genome sequencing was previously used by a group of Dutch scientists [7] to demonstrate the key role of horizontal transfer in the dissemination of the mecA gene. Horizontal transfer is the movement of genetic material from one bacterium to another via mobile genetic elements (MGEs). This observation has had significant implications for our understanding of the epidemiology of MRSA, as it explains why methicillin resistance is able to spread quickly within populations of methicillin-susceptible S. aureus (MSSA).
In conclusion, whole genome sequencing of novel MRSA strains could have an enormously positive impact on the wider community. It could reduce the number of patients who die from the infection each year, by facilitating both development of new medications and contact tracing of infected individuals. Furthermore, by closely monitoring the transmission of MRSA within healthcare environments, it would be possible to minimise the spread of infection into the community, as patients could be properly treated before discharge. The potential role of whole genome sequencing of MRSA also shows promise for developing nations, as there is a possibility that more affordable antibiotics could be discovered. As a result, the impending threat of MRSA could be significantly reduced, and many lives could be saved in years to come.

[1] Harkins, C. P., Pichon, B., Doumith, M., Parkhill, J., Westh, H., Tomasz, A., et al. (2017) Methicillin-resistant Staphylococcus aureus emerged long before the introduction of methicillin into clinical practice. Available at: www.ncbi.nlm.nih.gov/pmc/articles/PMC5517843/ (Accessed: 19th April 2021).[2] Public Health England (2021) Thirty-day all-cause mortality following MRSA, MSSA and Gram-negative bacteraemia and C. difficile infections: April 2019 to March 2020, Available at: www.gov.uk/government/statistics/mrsa-mssa-and-e-coli-bacteraemia-and-c-difficile-infection-30-day-all-cause-fatality (Accessed: 11th April 2021).[3] Harris, S.R., Cartwright, E.J.P., Török, M.E., Holden, M.T.G., Brown, N.M., Ogilvy-Stuart, A.L., et al. (2012) Whole-genome sequencing for analysis of an outbreak of meticillin-resistant Staphylococcus aureus: a descriptive study, Available at: www.thelancet.com/journals/laninf/article/PIIS1473-3099(12)702682/fulltext (Accessed: 18th April 2021).[4] Raven, K.E., Blane, B., Leek, D., Churcher, C., Kokko-Gonzales, P., Pugazhendhi, D., et al. (2019) Methodology for Whole-Genome Sequencing of Methicillin-Resistant Staphylococcus aureus Isolates in a Routine Hospital Microbiology Laboratory, Available at: jcm.asm.org/content/57/6/e00180-19 (Accessed: 18th April 2021).[5] Zumla, A., Nahid, P., Cole, S. (2013) Advances in the development of new tuberculosis drugs and treatment regimens., Available at: www.nature.com/articles/nrd4001 (Accessed: 19th April 2021).[6] Jones, D., Meijer, E.F.J., Blatter, C., Liao, S., Pereira, E.R., Bouta, E.M. et al. (2018) Methicillin-resistant Staphylococcus aureus causes sustained collecting lymphatic vessel dysfunction, Available at: stm.sciencemag.org/content/10/424/eaam7964 (Accessed: 21st April 2021)[7] Weterings, V., Bosch, T., Witteveen, S., Landman, F., Schouls, L., Kluytmans, J., (2017) Next-generation sequence analysis reveals transfer of methicillin resistance to a methicillin-susceptible Staphylococcus aureus strain that subsequently caused a methicillin-resistant Staphylococcus aureus outbreak: a descriptive study Available at: pubmed.ncbi.nlm.nih.gov/28679522/ (Accessed: 21st April 2021).

Essays Honourable Mention – Nil Isindag

New Vision at Gene Treatment: Check, Treat, Change

Nil Isindag
Özel Emine Örnek Fen Lisesi, Bursa, Turkey

I propose to sequence the genome of all living and extinct organisms because of the perennial urge for carrying out the main goal of Homo Sapiens for good: long-lasting human life. Since we can sequence the genome of all life forms, from viruses to humans, we are now holding the ultimate key to the perennial urge. In our ecosystem, every single biotic or abiotic element has an irreplaceable role in life, at which they are the most successful. And,what viruses do best is copying. In other words, sequencing, to maintain its’ life, is viruses’ perennial urge. Thus, at that point viruses seem our best companion through this noble mission. This explains how we can take benefit from the type of viruses, which don’t make humans sick, to develop further gene therapies and maintain the ecosystem’s balance at the same time, since each creature is still doing what they had been doing for billions of years.
Not to mention, today we can take advantage of the sequenced genomes of some organisms for producing medications such as the production of Insulin hormone with the benefit of recombinant DNA procedure predominantly using E. coli and Saccharomyces cerevisiae bacteria [1], yet these procedures aren’t enough. Moreover, in my perspective, I don’t think that this is the aspect that we should mainly focus on. Instead, we should concentrate on preventing diseases in the first case, rather than trying to treat them with medications or gene therapies. Accordingly, I’d like to introduce my 3 step action plan: “Check-Treat-Change” for degradation of mortality and morbidity, with the help of cutting-edge sequencing systems.
1.CHECK: Unless we know what’s wrong with the patient, we cannot treat. Therefore, with the assistance of current sequencing methods, anomalies may be detected and then the treatment procedure may start. Depending on the variety of these anomalies either gene therapies or conventional way drug-assisted treatments or surgical procedures may be done. More importantly, what to do next is: in case of detection of a specific anomaly, an urgent scan may be done to the patient’s closest family -considering the genetic heritage- so a possible disease will be monitored much priorly and start the treatment immediately. Or even an immediate intervention during pregnancy may be considered. At this point, we may observe the superiority of gene sequencing check-up to conventional way check-up procedures as; in gene sequencing check-up, the whole organism will be scanned through the head to toe, which will monitor the most accurate results and prevent possible overlooked situations.
2.TREAT: For gene-targeted treatments, we can take advantage of the type of viruses -which don’t make humans sick- by their efficiency at nucleic acid delivery to specific cell types.[2] In most genetic diseases, the reason why the anomaly is the lack of a specific protein, consequently here are the steps of a disease, which resulted from lack of a specific protein:
I.The suitable virus should be chosen regarding the occurring anomaly. II.The DNA of the virus should be subtracted. III.Non-working or missing genes should be targeted and the new, working form of that exact gene should put into the DNA subtracted virus. IV.Under normal circumstances, the production of the required protein should be produced with the assistance of a working gene. V.Patients should be under surveillance after the possible treatment for results.
Through these abstract steps, viruses will be used for the transportation of the gene throughout the body for production. The new gene will not become part of the patient’s DNA. [3] But what if we could make that happen?
3.CHANGE: Today we can transport a good gene into cells via viruses, however, we cannot put the virus right into the nucleus of DNA. What I propose is to make that gene “a part of the patient’s body”. If this could happen, the transmission of genes by inheritance possible. Which would help to diminish the vast amount of diseases that have been occurring.
Considering the steps of my plan, these developments should be under the supervision of authorities for society’s concordance. In a nutshell, we can take the utmost benefit of the sequence of all living creatures without any alteration in our ecosystem and society: by making whole-genome sequencing preferable and available, conserving the fact that “primum non nocere”.

1.Johnson, I. S. (1983). Human insulin from recombinant DNA technology. Science, 219(4585), 632-637.
2.Walther, W., & Stein, U. (2000). Viral vectors for gene transfer. Drugs, 60(2), 249-271.
3.Reece, J. Urry, L. Cain, M. , Wasserman, S. ,Minorsky, P. , Jackson, R. (2013). Campbell Biyoloji (9th ed., pp 373-376). Ankara. Turkey: Palme Yay?nlar?. 

Essays Honourable Mention – Zenia Mistry

Killing the Unkillable

Zenia Mistry
NIST International School, Bangkok, Thailand

I propose to sequence the genome of Carbapenem-resistant Enterobacteriaceae (CRE), a specific kind of antibiotic resistant bacteria. It is supposedly one of the most deadly antibiotic resistant bacteria, as most of the time, it is unkillable. As time passes, and it continues to spread, it poses an increasing risk to humankind.
Antibiotic resistance occurs when bacteria develop the ability to survive in spite of being attacked by antibiotics (CDC, 2019). CRE are a specific group of antibiotic resistant bacteria which live in the intestines (Felson, 2021). They are resistant to carbapenems, a very strong type of antibiotic which successfully treats other kinds of superbugs. When CRE bacteria travel outside the intestines, they have the ability to cause life-threatening infections in the bloodstream, urinary tract, and lungs (for example, pneumonia or meningitis), which are nearly impossible to treat – due to the fact that antibiotics do not work on them. Everyone is at risk of an antibiotic resistant infection, though some are more at risk than others – for instance, someone with a chronic illness or weakened immune system (CDC, 2019). According to MayoClinic, 2021, outbreaks of CRE-related infections typically occur in hospitals, which is detrimental since most patients’ immune systems are compromised, making them more prone to developing these infections. Half the patients infected with CRE die (Fox, 2018), making it definitely one of the most urgent health problems.
When antibiotics which are not needed are used, antibiotic resistant bacteria are developed (Felson, 2021). When bacteria replicate through binary fission, mutations occur. Natural selection takes place – most bacteria die, but some, with a mutation which helps them stay alive, survive (CDC, 2019). These reproduce, and even have the ability to transfer genes to other bacteria (through horizontal gene transfer), making them resistant as well. In particular, Carbapenem-resistant Enterobacteriaceae produce an enzyme, called Klebsiella pneumoniae carbapenemase, which allows them to break down antibiotics before they even get a chance to start working (Felson, 2021). Carbapenems are the specific kind of antibiotic these bacteria are resistant to – according to Fox, 2018, carbapenems are a “last-resort” antibiotic, meaning CRE are one of the most dangerous and hard-to-treat superbugs, considering they can defeat a very strong antibiotic. Clearly, it is imperative that a treatment for CRE-related diseases should be developed – the best way to do so is through sequencing its genome.
In order to sequence the genome of Carbapenem-resistant Enterobacteriaceae, its DNA must be extracted and the double helix must be uncoiled (MayoClinic, 2018). According to the same source, samples of this DNA would be inserted into a DNA sequencing instrument. Using high frequency sound waves, this instrument would break the DNA down into small pieces, which are around 600 bases long. These small pieces of DNA would then be attached to a glass slide, and clusters of identical DNA fragments are created. Using different coloured tags for each base, the sequencer reads the DNA. The tags are detected by specialised sensors in the sequencing machine. When this is completed, a computer would put together the sequences of each of the DNA fragments, to complete an overall genome sequence for the CRE (MayoClinic, 2018).
The genome sequence created would be able to allow scientists to create a novel antibiotic which would have the ability to kill the CRE (NIH, 2020). According to Donkor, 2013, knowing the DNA sequence would help researchers identify the protein structures which made the CRE resistant and able to break down the antibiotic. The amino acids which make up the protein can be found through the genome sequence – since this information is found, it can be used to model the protein. This model can be used to screen for new antibiotics which target the specific enzyme that allows Carbapenem-resistant Enterobacteriaceae to break down Carbapenems.
Finding a way to produce a treatment for antibiotic resistant bacteria, specifically Carbapenem-resistant Enterobacteriaceae, would be revolutionary. Countless people die from this bacteria, and its risk is increasing on the daily. The discovery of a cure can also lead to the treatments for other antibiotic resistant superbugs with similar mechanisms to itself. Overall, it is really important to sequence the genome of CRE, since a novel antibiotic would be found from it – therefore killing the unkillable.

CDC. (2019, November 05). CRE. Retrieved April 23, 2021, from www.cdc.gov/hai/organisms/cre/index.htmlFelson, S., MD. (2021, March 9). CRE superbug INFECTIONS: Treatment and Prevention. Retrieved April 23, 2021, from www.webmd.com/a-to-z-guides/cre-superbug-infectionsMayoClinic. (2021, February 24). Superbugs. Retrieved April 23, 2021, from www.mayoclinic.org/diseases-conditions/infectious-diseases/in-depth/cre-bacteria/art-20166387Fox, M. (2018, February 06). What is CRE and Why do people catch it? Retrieved April 23, 2021, from www.nbcnews.com/health/health-news/what-cre-why-do-people-catch-it-n308881MayoClinic. (2018, February 07). What is genomic sequencing? Retrieved April 23, 2021, from www.youtube.com/watch. (2020, August 16). DNA Sequencing Fact Sheet. Retrieved April 23, 2021, from www.genome.gov/about-genomics/fact-sheets/DNA-Sequencing-Fact-SheetDonkor, E. S. (2013, October 14). Sequencing of bacterial genomes: Principles and insights into pathogenesis and development of antibiotics. Retrieved April 23, 2021, from www.ncbi.nlm.nih.gov/pmc/articles/PMC3927574/

Essays Honourable Mention – Francisco Monteiro

The Balaena mysticetus, the owner of our dreams

Francisco Monteiro
Escola Secundária/3 de Alpendorada, Marco de Canaveses, Portugal

I propose to sequence the genome of Balaena mysticetus because it has a long lifetime and is very resistant to some aging-related diseases and also cancer. By identifying the genes and understanding how its DNA works, we could apply that knowledge and try to find techniques to improve the life quality of humans. The Balaena mysticetus, known as Bowhead Whale, is a species of baleen whale belonging to the family Balaenidae that lives all its life in the Arctic. It “has not only been estimated to live over 200 years, making it the longest-lived mammal, but these animals remain disease-free until much more advanced ages than humans can” [1]. The reason why they can live so long and resist age-related diseases, particularly cancer, is not well known by the Scientific community. It’s actually fascinating how such a big and old animal shows such low cases of cancer since cancer is associated with living beings with big quantities of cells. Scientists have been trying to understand the reason for having a long and healthy life. In an article published in 2015 on the NCBI site [2], the researchers analyzed parts of the Balaena mysticetus DNA and Identified proteins related to aging, but the results didn’t give much information. We know these species have genetic and molecular mechanisms associated with longevity. Now we just need to discover which genes are responsible for those proteins, how do they relate, which biochemical factors intervene and try to apply that knowledge in humans. If we knew the genes that allow the Balaena mysticetus to live longer, maybe we could insert those genes into the human genome. We would need better techniques, maybe a better version of CRISPR, but we need to start with the basics, which includes sequencing the Balaena mysticetus DNA. Knowing the Balaena mysticetus DNA sequence not only allows us to find the genes related to longevity, but also the genes that prevent cancer and other diseases. The cases of Bowhead Whales with cancer are extremely rare, which is strange because, due to its long lifetime, “their cells have plenty of opportunities to mutate and become cancerous, but they hardly ever do. Vera Gorbunova of the University of Rochester in New York, US, keeps bowhead whale cells in her lab. So far, she has not found a way to make them cancerous” [3]. If we sequence its DNA maybe we could find a gene responsible for the low number of cancer cases in the species and try to apply that gene in humans. It’s not just cancer, it’s a lot of other diseases related to aging. We could not only cure cancer, but also diseases that prevent us from having a pleasurable end of life. In addition to everything already mentioned, knowing its genetic sequence also increases the DNA sequences available in the genetic sequence databases. Genome comparison is one of the most important areas and if we get more sequences to use as a comparison we will be able to get information more quickly. Genome comparison “helps us to further understand what genes relate to various biological systems, which in turn may translate into innovative approaches for treating human disease and improving human health” and “also provides a powerful tool for studying evolution” [4]. The more sequences we have available the faster knowledge appears. Genome sequencing is one of the important steps to understand life and our evolution. The Balaena mysticetus has a lot of interesting characteristics that if applied to humans would increase our life quality. That way we need to explore beyond its phenotype and understand the genome.

[1] Bowhead whale genome sequencing and analysis. Human Ageing Genomic Resources (HAGR). genomics.senescence.info/sequencing/bowhead_whale.html. Published date not available. Accessed February 10, 2021. [2] Insights into the Evolution of Longevity from the Bowhead Whale Genome. National Center for Biotechnology Information (NCBI). www.ncbi.nlm.nih.gov/pmc/articles/PMC4536333/. Published 2015 January 6. Accessed February 12, 2021. [3] The animal that doesn’t get cancer. British Broadcasting Corporation (BBC). www.bbc.com/earth/story/20151031-the-animal-that-doesnt-get-cancer. Published October 31, 2015. Accesses February 12, 2021. [4] Comparative Genomics Fact Sheet. National Human Genome Research Institute (NHGRI). www.genome.gov/about-genomics/fact-sheets/Comparative-Genomics-Fact-Sheet. Published August 15, 2020. Accessed February 12, 2021.

Essays Honourable Mention – Aikaterini Patrinou

Sequencing the genome of algae: A revolutionary approach with environmental and commercial implications


I propose to sequence the genome of algae because they have a huge potential for commercial applications and environmental protection. In a world where climate change and sea pollution pose a serious threat for humanity, DNA sequencing could provide biotechnology-based solutions as attractive, environmentally-friendly and sustainable alternatives to conventional ones to address and possibly resolve such issues [1,2]. This concept includes both resequencing known algae species for detecting genetic elements of interest, as for example toxicity factors, as well as the identification and de novo sequencing of novel-yet to be identified algae species for classification purposes and also to seek possible products and processes hidden in their genome with practical interest, as happening regularly with other species and taca [3]. Next generation sequencing was first introduced in the early 2000s as the follow up of traditional DNA sequencing independently established as the Maxam-Gilbert and the Sanger methods in the late 1970s [4]. The main difference between traditional and next generation sequencing, which revolutionized molecular genetics and genomic medicine, is the ability of the latter technology to determine massive amounts of nucleotide sequences in a fast, accurate and cost-effective manner by a combination of improved biochemical methods and a robust bioinformatics pipelines. Next-generation sequencing of algae’s genomes is the first step towards understanding their genes’ structure and function in order to exploit their fine-tuned genetic machinery, evolved through millions of years of environmental pressure. The initial objective is to identify species with useful traits and qualities, characterize and culture-grow them, so as to use them as needed when needed. Subsequently, a more refined use would be to employ selected genes, or rather gene and regulatory elements’ complexes to develop engineered (synthetic) algae cells to specifications with improved features or groups and combinations of features attuned to the desired objective, conditions and peculiarities. Indicatively, potential uses could be the production of biofuel, of biological growth or microbicidal factors or of edible biomass for fish and oyster cultures or even for livestock feeding. Another massive and instrumental application would be in the oil degrading sector which is of paramount importance in drilling and sea-transportation accidents regarding crude oil spill incidents that cause sea pollution with detrimental economic and devastating environmental effects. The latter is obvious, but the former, in terms of loss of limited fossil fuel supplies, high insurance costs and increased safety features leads to a rise in energy prices not compatible with the “networked planet” concepts forwarded currently. This biotechnological approach is achievable either by copy-pasting genes of interest in existing cell species, or by fully engineering a novel (over)genome, bearing the desired characteristics into a generic similar (algal, in this case) host cell with a most basic, house-keeping undergenome [5]. This way, one can create a truly synthetic organism, susceptible to export controls, biosafety and environmental regulations and intellectual property clauses that can be used to combat these global sustainability challenges. However, this does not come without any ethical dilemmas. It is well known that any modification of a naturally existing organism is considered to be a moral discernment that can possibly generate unpredictable outcomes possibly detrimental in massive scale. More specifically, this technology bears the potential of creating organisms (or products such as, but not limited to, biotoxins) that can be used as bioterror weapons, or biocrime modalities, including the globally threatening scope of agroterrorism and food source compromization [6], not to speak of genetic pollution [7] which may be curtailed to some point by technological advances such as Xenobiological firewalls [8,9]. Such misuse can pose a threat to public health and security since incorporating synthetic DNA into virulent pathogens is a new source of potential dual-use agents, i.e. benign and weaponized [10]. These ground-breaking advancements need to be brought into perspective and regulated thoroughly before full-blown commercial exploitation. A starting point could be to develop strategies for identifying and weighing the various values at stake in dual-use dilemmas, with first and foremost the need for genetic certification, meaning full genome sequences of engineered organisms submitted for patenting such organisms and random resequencing to marketed samples to show compliance to the submitted genetic blueprints.

References1. [Mishra PK, Mukherji S. Biosorption of diesel and lubricating oil on algal biomass. 3 Biotech 2(4), p. 301, 2012]2. [Picardo S et al. Recent advances in the detection of natural toxins in freshwater environments. Trends in Analytical Chemistry 112 p. 75, 2019]3. [Perfumo A et al. Discovery and Characterization of a New Cold-Active Protease from an Extremophilic Bacterium via Comparative Genome Analysis and in vitro Expression. Frontiers in Microbiology 11, p.881, 2020]4. [Niedringhaus T et al. Landscape of next-generation sequencing technologies Analytical Chemistry 83(12), p. 4327, 2011]5. [Gibson D et al. Creation of a bacterial cell controlled by a chemically synthesized genome. Science 329, p. 52 2010]6. [Kambouris ME et al. Humanome Versus Microbiome: Games of Dominance and Pan-Biosurveillance in the Omics Universe. OMICS-JIB 22(8) p. 528 2018]7. [Grewe PM et al. Preventing Genetic Pollution and the Establishment of Feral Populations: A Molecular Solution. Ecological and Genetic Implications of Aquaculture Activities p. 103 Springer Netherlands 2007]8. [Schmidt M. Xenobiology: A new form of life as the ultimate biosafety tool. Bioassays 32(4), p. 322 2010 ]9. [Schmidt M et al. Xenobiology: State-of-the-art, ethics, and philosophy of new-to-nature organisms. Advances in Biochemical Engineering/Biotechnology 162, p.301 2018]10. [Kambouris ME et al. Rebooting Bioresilience: A Multi-OMICS Approach to Tackle Global Catastrophic Biological Risks and Next-Generation Biothreats. OMICS-JIB 22(1), p.35 2018]

Essays Honourable Mention – Oshadha Perera

Sequencing the Genome of Influenza A and B Viruses

Oshadha Perera, Jessica Cross
Southland Boys’ High School, Invercargill, New Zealand

I propose to sequence the genome of Influenza A and B viruses because it affects people all around the world, resulting in 3-5 million severe cases and 290,000-650,000 deaths worldwide every year.[1] Influenza viruses are categorised into types A, B, C and D, out of which A and B affect humans the most.[1] Genome sequencing shows the order of nucleotides of a gene.[2] Whole Genome Sequencing (WGS) sequences all the DNA in one’s genome. It is easier to identify mutations and rearrangements using the multiple insert sizes of WGS than shorter-scale sequencing methods.[3] WGS can be done through Next-Generation Sequencing (NGS), which sequences many different virus particles in a single sample within a short time with high resolution of information and detail, and is cost-effective.[2] Thus, NGS is an ideal method for sequencing the Influenza viruses’ genome.
Comparing the genome of a currently circulating virus with an older virus or a virus used in a vaccine (called ‘genetic characterisation’) helps us understand the genetic evolution of the virus.[2] This includes deepening our understanding of genetic changes that cause properties of the virus to be changed, such as transmission and spread, antibody resistance and more severe forms of the disease.[2] This is done by comparing the genes of two viruses to understand genetic variation.[2] Influenza viruses are known to rapidly evolve through mutations, challenging the optimal efficacy of vaccines and making the eradication of Influenza harder.[4] While Influenza viruses constantly evolve through drifts and shifts, the danger of antigenic shifts was shown by the 2009 H1N1 outbreak, which caused 50 million deaths worldwide.[5][6] Genome sequencing takes an important place during a pandemic. For example, during the COVID-19 outbreak, genome sequencing provided real-time information about the epidemiology and evolution of the virus, origins of cases, transmission patterns, and effectiveness of disease control measures, which ultimately helped in introducing policies and measures that controlled the disease spread.[7] Studying the Influenza viruses’ genetic changes responsible for the above properties and their evolution would help us identify changes in the virus and possibly have a warning that will allow us to be prepared for sudden outbreaks and pandemics that occur through mutations of the virus. This would give us more time to learn about characteristics such as transmission methods and antibody resistance of the new strains and start developing vaccines for them, increasing the chance of finding a cure faster. With genome sequencing providing epidemiological and transmission data, controlling the spread of the disease would be much easier. These factors could significantly minimise the medical, social, and economic damages caused by a sudden outbreak.
Genome sequencing is an important step in developing new vaccines as it reveals the function, location and evolution of the viruses’ amino acids that code the viruses’ properties.[8] For instance, sequencing the SARS-CoV-2 genome was a major step in developing a vaccine for COVID-19. Genetic characterisation can then be used to determine the efficiency of flu vaccines by comparing the genetic similarity of the currently circulating virus and the one used in the vaccine.[2] This would help constantly update our vaccines and develop them to cater to a broader range of evolving Influenza viruses by accounting for various properties such as different spreading methods and levels of resistance to current vaccines. The current Influenza vaccine covers Influenza A(H1N1), A(H3N2) and B, and has a 40-60% vaccine effectiveness.[9] The World Health Organization updates the Influenza vaccine twice a year, but with the viruses rapidly evolving, the time between identifying a new strain of the virus and distributing the vaccine takes over six months.[1][4] Updating our vaccines with constant genetic surveillance and using genome sequencing to develop new Influenza vaccines with higher effectiveness will assist in preventing sudden outbreaks.
In conclusion, the eradication is hindered due to the Influenza viruses rapidly evolving and changing their properties to increase their spread, resistance to vaccines and severity of the disease. Genome sequencing helps us understand the genetic evolution of the virus and the genes responsible for different properties of the virus. Studying these will help us identify the evolution of viral properties that will increase the severity or spread of the disease and develop vaccines to be better prepared for sudden outbreaks. We will also be able to test our vaccines, update and develop them constantly to keep the morbidity and mortality rates at a minimum. Thus, sequencing the genome of Influenza A and B viruses, ideally using NGS, will be an important step in our way to eradicating Influenza.

[1] World Health Organisation. (2018, November 6). Influenza (Seasonal). www.who.int/news-room/fact-sheets/detail/influenza-(seasonal)[2] Centers for Disease Control and Prevention. (2019, October 15). Influenza Virus Genome Sequencing and Genetic Characterization. www.cdc.gov/flu/about/professionals/genetic-characterization.htm[3] Abel, H., Pfeifer, J., & Duncavage, E. (2015). Translocation Detection Using Next-Generation Sequencing. In S. Kulkarni, & J. Pfeifer (Eds.), Clinical Genomics (pp. 151-164). Academic Press. doi.org/10.1016/B978-0-12-404748-8.00010-1[4] Shao, W., Goraya, M. U., Wang, S., & Cheng, J. L. (2017). Evolution of Influenza A Virus by Mutation and Re-Assortment. International journal of molecular sciences, 18(8), 1650. doi.org/10.3390/ijms18081650[5] Centers for Disease Control and Prevention. (2019, October 15). How the Flu Virus Can Change: “Drift” and “Shift”. www.cdc.gov/flu/about/viruses/change.htm[6] Centers for Disease Control and Prevention. (2019, March 20). 1918 Pandemic (H1N1 virus). www.cdc.gov/flu/pandemic-resources/1918-pandemic-h1n1.html[7] Geoghegan, J., Ren, X., Storey, M., Hadfield, J., Jelley, L., Jefferies, S., . . . Ligt, J. (2020). Genomic epidemiology reveals transmission patterns and dynamics of SARS-CoV-2 in Aotearoa New Zealand. Nature Communications, 11, 6351. doi.org/10.1038/s41467-020-20235-8[8] Bambini, S., & Rappuoli, R. (2009). The use of genomics in microbial vaccine development. Drug discovery today, 14(5-6), 252-260. doi.org/10.1016/j.drudis.2008.12.007[9] Centers for Disease Control and Prevention. (2020, December 16). Vaccine Effectiveness: How Well Do the Flu Vaccines Work? www.cdc.gov/flu/vaccines-work/vaccineeffect.htm

Essays Honourable Mention – Leja Simkute

Opportunities and obstacles of genome sequencing

Leja Simkute, Daiva Puodziukiene
Vilniaus Zirmunu gimnazija, Vilnius, Lithuania

I propose to sequence the genome of all human beings because today medical achievements have reached an incredible high and human life expectancy has soared in the past years. Nevertheless, keeping up the quality and comfort of life until old age is still a puzzle to be solved for humanity. The principal objective of science is not only to aid in relieving the symptoms of a disease but also to help prevent and lower the risk of illnesses that affect us. Moreover, it is certain that the same drugs do not always benefit every individual identically, so it is crucial to take each and everyone’s case into consideration when choosing the medications. In short, the future of medical science is individualized treatment plans, designed according to each person’s needs. One of the solutions to this problem – whole human genome sequencing.
Utilisation of genomic sequencing provides information on genetic variants that can cause disease or increase the risk of disease growth, even in asymptomatic people. Thus, the main advantage of genome sequencing is that it has the potential to improve the ability to intervene preemptively before the development of a disease or to initiate treatment for a disease that has not yet been diagnosed. DNA sequencing can provide a detailed diagnosis for individuals with a health-impacting disease, which may affect the medical management of symptoms, or provide alternatives for treatment.
A further advantage of genome sequencing that I see is that it aids in obtaining the information regarding drug efficacy or adverse effects of drug use. Predicting who will benefit from a drug, who will not respond at all, and who will suffer negative side effects can be challenging. Researchers are now discovering, with the information acquired from the Human Genome Project, how inherited gene variations influence the response of the body to medications. “These genetic variations will be used to determine whether a drug would be beneficial for a specific individual and to help avoid adverse drug reactions”1.
However, even though whole human genome sequencing may sound like a perfect solution to a lot of world’s medical problems, we cannot forget that it is still quite new and inevitably has its own flaws.
How accurately and reliably genome sequencing measures genome variants is termed “analytical validity.” “The more times a particular base is read, the higher the accuracy that it was measured, or “called,” correctly at that particular position”2. The amount and quality of DNA available for sequencing, as well as the computational capabilities of the software chosen to determine the DNA sequence, can affect the coverage depth. “If it is not sufficient, it is possible that a base will be identified that is not actually present in a person’s genome”3. For example, if a mutation leading to a disease is mistaken for a normal gene (a false negative), the individual may assume that a disorder has been successfully tested and found to be “negative” for it, although that may not be the case. On the other hand, a gene may be misread as a mutation that is supposed to lead to an adverse condition, although the individual does not actually carry such a mutation in their genome (a false positive). In summary, the coverage of genome depth varies throughout, and the lower the depth, the lower the likelihood that the base is correctly calculated. Conversely, the higher the coverage, the greater the chance of precise base calling. “The current standard expected is a minimum of 95% of the genome being sequenced with 95% or greater accuracy”4.
Another downside proposed by genome sequencing, is that it can “uncover data that have potential negative psychological consequences to the client and the client’s family”. Some examples of data that suit this definition are: the detection of a pathogenic variant, the receipt of indecisive findings with respect to certain health conditions, the challenge of assimilating data that contradicts previous views, and the information that, as previously assumed, the target of genome sequencing is not biologically linked to family members. If all individuals are not sufficiently prepared, sharing discovered knowledge with other people, especially with family members, may be an additional source of distress.
In conclusion, from my personal standpoint, the previously mentioned advantages of genomic sequencing are undoubtedly essential and can help speeding up the creation of personalized treatments and early prevention of diseases. Nonetheless, we should likewise take into account probable dangers of these methods and discover a way to conciliate science and ethics in order to keep evolving as humans.

1. What is pharmacogenomics? 2020, viewed 31 January 2021
2. Advantages and limitations of genome sequencing, 2016-2020, viewed 30 January 2021
3. Advantages and limitations of genome sequencing, 2016-2020, viewed 30 January 2021
4. Advantages and limitations of genome sequencing, 2016-2020, viewed 30 January 2021
Genome sequencing, 2003, J. Craig Venter Institute, viewed 31 January 2021
The importance of Whole Genome Sequencing, 2019, Genomes.io, viewed 29 January 2021

Essays Honourable Mention – Sian Talbot

How could sequencing the genome of the mosquito benefit science and society?

Sian Talbot
Cheadle Hulme School, Manchester, United Kingdom

I propose to sequence the genome of the mosquito because it is one of the world’s main vectors of disease. Accounting for 17% of the estimated global burden of infectious disease, it kills over 700,000 people per year i and is a carrier of malaria and the zika, dengue and yellow fever viruses. In order to be an effective carrier of these diseases the mosquito has evolved measures to protect against them. By sequencing genomes of mosquito subspecies, I would aim to identify genes offering protection against such diseases; and provide an understanding of the mosquito’s molecular level biological processes ii and vectoral capacity iii. From this, work could be done towards mosquito control and prevention of transmission iv by using the knowledge of its “reproductive processes, immune response, chemosensory mechanisms and insecticide resistance” v. One example would be the malaria mosquito – anopheles gambiae vi. Malaria is the world’s most deadly vector-borne disease, there were an estimated 228 million cases and 405,000 deaths in 2018, 67% of whom were children under the age of five vii. By using knowledge gained about this mosquito’s biological processes and life cycle, female mosquitoes could be engineered to be infertile; or a gender bias towards males could be created. This would reduce the mosquito population, and the occurrence of blood feeding, thereby reducing transmission of the malaria parasite. Alternatively, resistance to the malaria parasite could be spread throughout the mosquito population. For example, mosquitoes have a type of immune cell called haemocytes which shed fragments of plasma membrane (micro vesicles). These activate a cascade of proteins that target and destroy the malaria parasite viii. An example of a protein is SCRBQ2 in the female mosquito mid-gut which has up-regulated gene expression after blood-feeding and infection by malaria ix. By spreading the genes for these proteins, the number of mosquitoes carrying malaria would diminish; hence transmission rate would reduce. These tactics could be achieved with CRISPR gene drives. (CRISPR Gene drives allow a whole species to be genetically modified by changing the DNA of a few individuals. The gene editing tool is inserted as well as the desired gene; it transfers the attached gene and the tool onto both chromosomes meaning there is almost 100% chance of inheritance, all offspring will have the gene which will be copied onto both of their chromosomes and so on)x. These methods could be applicable to other mosquito borne diseases. Sequencing the mosquito genome would further our understanding of mosquitoes from an evolutionary, biological and medical perspective; thereby advancing our ability to combat mosquito borne diseases. This would be extremely beneficial to society as many of the main mosquito-borne diseases, such as malaria and zika, are especially prevalent in the tropics, which tend to be poorer (93% cases of malaria occur in the WHO African region xi). If rate of disease decreases more people would be able to work and receive an education, as the disease would be less prevalent in their lives. Infant mortality would drop, and more people would reach adulthood. This would increase the economic output of these countries, as the workforce increased in size and qualification/education, narrowing the development gap between more and less economically developed countries. Unemployment would decrease and both society and individuals would benefit. There would be lower healthcare costs and a reduced burden on the healthcare system in these countries meaning funds and resources could be targeted at other areas, benefiting the whole population, not just the ones suffering from disease. Also, from an individual’s perspective, they would be spared the trauma of losing their friends and family to disease or suffering it themselves.
However, sequencing the mosquito’s genome would use resources which could otherwise be used in alternative research or treatment with more definite results. Additionally, the use of genome sequencing to enable genetic modification in the whole mosquito population might have adverse ecological impacts. For example, engineering a gender bias towards male mosquitoes would decrease the population and disrupt the food chain. This could have devastating consequences as many species such as fish, dragonflies, bats and birds rely on mosquitoes as a food source. Some species would go extinct, for example the mosquito fish which relies on mosquito larvae as its main food source xii. It may be better not to drastically reduce mosquito numbers, instead focusing on preventing them from transmitting diseases.

i www.isglobal.org/en_GB/-/mosquito-el-animal-mas-letal-del-mundo18/08/2017, IS Global, Barcelona Institute for Global Health
ii www.annualreviews.org/doi/full/10.1146/annurev-ento-120710-100651 2012, David W. Severson and Susanta K. Behura
iii www.sciencedaily.com/releases/2014/11/141127212323.htm27/11/2014, Science Daily, source of story is the University of Notre Dame
iv www.annualreviews.org/doi/full/10.1146/annurev-ento-120710-100651 2012, David W. Severson and Susanta K. Behura
v www.sciencedaily.com/releases/2014/11/141127212323.htm27/11/2014, Science Daily, source of story is the University of Notre Dame
vi journals.plos.org/plospathogens/article, Jonas G. King and Julián F. Hillyer
vii www.who.int/news-room/fact-sheets/detail/malaria14/01/2020, WHO
viii cosmosmagazine.com/biology/why-mosquitoes-don-t-die-from-malaria23/01/2017, Cosmos: the science of everything
ix www.ncbi.nlm.nih.gov/pubmed/19366631, department of cell biology, Centro de Investegación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico
x www.vox.com/science-and-health/2018/5/31/17344406/crispr-mosquito-malaria-gene-drive-editing-target-africa-regulation-gmo26/09/2018, Dylan Matthews
xi www.who.int/news-room/fact-sheets/detail/malaria14/01/2020, WHO
xii mosquitoreviews.com/learn/mosquitoes-purpose/2020, Mosquito Reviews

Essays Honourable Mention – Simona Zelionkaite

We can now sequence the genome of all life forms, from viruses to humans. What could be the point of this?

Simona Zelionkaite, Egle Tauraite
Vilnius Lyceum, Vilnius, Lithuania

I propose to sequence the African genome because of its impressive genetic diversity. Establishing a detailed understanding of the heritable variation in the human genome is one of the key challenges of the post-genome period. Progress in human genome research is currently being observed, but while the importance of genetic data is increasing, the problem is not the availability of sequencing but the lack of diversity in genetic information. Since modern people originated in Africa and have adjusted to assorted conditions [1], African populations have substantially higher levels of genetic and phenotypic diversity. Subsequently, it is fundamental to study genomic diversity of African ethnic groups in order to understand human evolutionary history and how this prompts differential disease risk in all people. Africa is a diverse region in terms of genetics, culture, semantics and phenotypic characteristics. There are over 2000 specific ethnolinguistic groups in Africa, communicating in dialects that make up about almost 33% of the world’s languages. The genetic diversity of Africa is influenced by a variety of factors [2]. To begin, Africans live in a wide range of habitats ranging from deserts and tropical rainforests to savannahs and wetlands. Secondly, different exposures to infectious diseases is also a major factor which determines genetic diversity. And lastly, Africans have diversified subsistence and diet patterns that include pastoralism or hunting-gathering. To summarize, Africa is so diverse because of its size – Africa is about the size of the land masses of China, the United States, India, Japan, and most of Europe combined. It’s a continent consisting of 54 countries which stand out both culturally and geographically. Taking this into account, it can be said that broadening the genetic data with African genomic information could utterly transform the world. There are two potential scenarios – realizing that the African genetic data could possibly change our whole perception of disease prevention and treatment or ignoring this fact and facing stigma. Nowadays most of the ongoing genetic studies rely mostly on European genetic information. Current lack of genetic diversity is one of the main reasons why scientists fail to incorporate genomic research into clinical practice. The purpose of all medicine can be described in three words: diagnose, treat, prevent. Medicine, with all the necessary data and using certain existing genetic markers, could adapt the diagnosis and treatment of the disease according to a person’s unique genetic model. For the time being, however, scientists are conducting research largely based on data from white European populations, distinguishing Africans that have a wide genetic variety. Such a lack of diversity in genomics research is thought to undermine our scientific understanding of the genetic basis of disease in all populations and increase health care bias. Take, for example, a single mutation named ?F508 in CFTR gene which accounts for 70% cystic fibrosis (CF) cases in the world [3,4]. In this case, the disease is caused by a specific variant of one gene, which in one population should be as disease-causing as in other populations, but this does not always correspond to real cases of the disease. This mutation is responsible for more than 70% of CF cases in Europeans, but only for 29% of cases in the African diaspora. Thus, even single gene mutations in
different populations have different consequences for the phenotype, and the lack of diversity of genetic data potentially affects many non-Europeans without adequate diagnostic and treatment possibilities. Limiting oneself to the genome information of Europeans greatly narrows the horizons of scientists and prevents other populations from receiving full-fledged treatment. It is clear that different genetic variations in different populations can affect both disease risk and treatment efficacy. Unfortunately, most research in this area is still concentrated on populations of European ancestry, as approximately 80% of participants in genomics research are of European descent [5], and the results obtained are very limited and not necessarily meaningfully transferable to other populations such as Africans. This trend is reflected in the poor diagnosis of diseases in individuals who are underrepresented in such studies. By placing utmost importance on diversity in genetic and genomic research, we would improve our ability to have a broader understanding of genetic disease architecture, which would ultimately increase the accuracy of medical care.

References:[1] Schmid, R., 2009. Africans have world’s greatest genetic variation. [online] nbcnews.com. Available here [Accessed 24 April 2021].[2] Campbell, M. and Tishkoff, S., 2008. African Genetic Diversity: Implications for Human Demographic History, Modern Human Origins, and Complex Disease Mapping. [online] ncbi.nlm.nih.gov. Available here [Accessed 24 April 2021].[3] Lukacs, G. and Verkman, A., 2011. CFTR: folding, misfolding and correcting the ?F508 conformational defect. [online] ncbi.nlm.nih.gov. Available here [Accessed 24 April 2021].[4] Alfonso-Sánchez, M., Pérez-Miranda, A., García-Obregón, S. and Peña, J., 2011. An evolutionary approach to the high frequency of the Delta F508 CFTR mutation in European populations. [online] NIH. Prieinamas: Available here [Accessed 24 April 2021].[5] Hussein, S., 2020. New genome sequencing sheds light on diversity in Africa. [online] medicalxpress.com. Available here  [Accessed 24 April 2021].